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  POISONS:
  THEIR EFFECTS AND DETECTION.




BY THE SAME AUTHOR.

_Fourth Edition. At Press._

  FOODS:
  THEIR COMPOSITION AND ANALYSIS.

_With numerous Tables and Illustrations._


=General Contents.=

  History of Adulteration--Legislation, Past and Present--Apparatus
  useful to the Food Analyst--“Ash”--Sugar--Confectionery--Honey--
  Treacle--Jams and Preserved Fruits--Starches--Wheaten-Flour--Bread--
  Oats--Barley--Rye--Rice--Maize--Millet--Potato--Peas--Chinese Peas--
  Lentils--Beans--MILK--Cream--Butter--Cheese--Tea--Coffee--Cocoa and
  Chocolate--Alcohol--Brandy--Rum--Whisky--Gin--Arrack--Liqueurs--Beer--
  Wine--Vinegar--Lemon and Lime Juice--Mustard--Pepper--Sweet and Bitter
  Almond--Annatto--Olive Oil--Water. _Appendix_: Text of English and
  American Adulteration Acts.

    “Will be used by every Analyst.”--_Lancet._

    “STANDS UNRIVALLED for completeness of information. . . . A really
    ‘practical’ work for the guidance of practical men.”--_Sanitary
    Record._

    “An ADMIRABLE DIGEST of the most recent state of knowledge. . . .
    Interesting even to lay-readers.”--_Chemical News._


_In Large 8vo, Handsome Cloth._ 21_s._

  FORENSIC MEDICINE
  AND
  TOXICOLOGY.

BY J. DIXON MANN, M.D., F.R.C.P.,

Professor of Medical Jurisprudence and Toxicology in Owens College,
Manchester; Examiner in Forensic Medicine in the University of London,
and in the Victoria University; Physician to the Salford Royal Hospital.

PART I.--Forensic Medicine. PART II.--Insanity in its Medico-legal
Bearings. PART III.--Toxicology.

    “By far the MOST RELIABLE, MOST SCIENTIFIC, and MOST MODERN book on
    Medical Jurisprudence with which we are acquainted.”--_Dublin
    Medical Journal_.

    “A MOST USEFUL work of reference. . . . Of value to all those who,
    as medical men or lawyers, are engaged in cases where the testimony
    of medical experts forms a part of the evidence.”--_The Law
    Journal._


LONDON: CHARLES GRIFFIN & CO., LTD., EXETER ST., STRAND.




  POISONS:
  THEIR EFFECTS AND DETECTION.

  A MANUAL FOR THE USE OF ANALYTICAL
  CHEMISTS AND EXPERTS.

  _WITH AN INTRODUCTORY ESSAY ON THE GROWTH OF
  MODERN TOXICOLOGY._


  BY
  ALEXANDER WYNTER BLYTH,
  M.R.C.S., F.I.C., F.C.S., &c.,
  BARRISTER-AT-LAW; PUBLIC ANALYST FOR THE COUNTY OF DEVON; AND MEDICAL
  OFFICER OF HEALTH AND PUBLIC ANALYST FOR ST. MARYLEBONE.


  THIRD EDITION, REVISED AND ENLARGED.

  With Tables and Illustrations.


  LONDON:
  CHARLES GRIFFIN AND COMPANY, LIMITED,
  EXETER STREET, STRAND.
  1895.

  (_All Rights Reserved._)

  D. VAN NOSTRAND COMPANY,
  NEW YORK.




PREFACE TO THE THIRD EDITION.


The present edition, which appears on the same general plan as before,
will yet be found to have been in great part re-written, enlarged, and
corrected.

Analytical methods which experience has shown to be faulty have been
omitted, and replaced by newer and more accurate processes.

The intimate connection which recent research has shown to exist between
the arrangement of the constituent parts of an organic molecule and
physiological action, has been considered at some length in a separate
chapter.

The cadaveric alkaloids or ptomaines, bodies playing so great a part in
food-poisoning and in the manifestations of disease, are in this edition
treated of as fully as the limits of the book will allow.

The author, therefore, trusts that these various improvements,
modifications, and corrections will enable “POISONS” to maintain the
position which it has for so many years held in the esteem of
toxicologists and of the medical profession generally.

  THE COURT HOUSE, ST. MARYLEBONE, W.
  _June, 1895_.




CONTENTS.


  PART I.--INTRODUCTORY.


  I. THE OLD POISON-LORE.

  Section                                                           Page

    1. The History of the _Poison-lehre_--The Origin of Arrow-Poison--
       Greek Myths,                                                    1
    2. Knowledge of the Egyptians relative to Poisons--Distillation of
       Peach-Water,                                                    2
    3. Roman and Greek Knowledge of Poison--Sanction of Suicide among
       the Ancients--The Classification of Poisons adopted by
       Dioscorides,                                                  2-4
    4. Poisoning among Eastern Nations--Slow Poisons,               4, 5
    5. Hebrew Knowledge of Poisons,                                    5
    6. The part which Poison has played in History--Statira--Locusta--
       Britannicus--The Rise of Anatomy--The Death of Alexander the
       Great--of Pope Alexander VI.--The Commission of Murder given by
       Charles le Mauvais--Royal Poisoners--Charles IX.--King John--A
       Female Poisoner boiled alive,                                 5-9
    7. The Seventeenth Century Italian Schools of Criminal Poisoning--
       The Council of Ten--John of Ragubo--The Professional Poisoner--
       J. B. Porta’s Treatise on _Natural Magic_--Toffana and the
       “_Acquetta di Napoli_”--Organic Arsenical Compounds--St. Croix
       and Madame de Brinvilliers--Extraordinary Precautions for the
       Preservation from Poison of the Infant Son of Henry VIII.,   9-13


  II. GROWTH AND DEVELOPMENT OF THE MODERN METHODS OF CHEMICALLY
  DETECTING POISONS.

    8. Phases through which the Art of Detecting Poisons has passed,  13
    9. Treatise of Barthélémy d’Anglais--Hon. Robert Boyle--Nicolas
       l’Emery’s _Cours de Chimie_--Mead’s _Mechanical Theory of
       Poisons_--Rise of Modern Chemistry--Scheele’s Discoveries, 13, 14
   10. History of Marsh’s Test,                                   14, 15
   11. Orfila and his _Traité de Toxicologie_--Orfila’s Method of
       Experiment,                                                    15
   12. The Discovery of the Alkaloids--Separation of Narcotine,
       Morphine, Strychnine, Delphinine, Coniine, Codeine, Atropine,
       Aconitine, and Hyoscyamine,                                15, 16
   13. Bibliography of the Chief Works on Toxicology of the Nineteenth
       Century,                                                    16-19


  PART II.


  I. DEFINITION OF POISON.

   14. The Legal Definition of Poison--English Law as to Poison,  20, 21
   15. German Law as to Poisoning--French Law as to Poisoning,    21, 22
   16. Scientific Definition of a Poison--The Author’s
       Definition,                                                22, 23


  II. CLASSIFICATION OF POISONS.

   17. Foderé’s, Orfila’s, Casper’s, Taylor’s, and Guy’s Definition of
       Poisons--Poisons arranged according to their Prominent
       Effects,                                                   23, 24
   18. Kobert’s Classification,                                   24, 25
   19. The Author’s Arrangement,                                   25-28


  III. STATISTICS.

   20. Statistics of Poisoning in England and Wales during the Ten
       Years 1883-92--Various Tables,                              28-31
   21. German Statistics of Poisoning,                             31-33
   22. Criminal Poisoning in France,                              33, 34


  IV. THE CONNECTION BETWEEN TOXIC ACTION AND CHEMICAL COMPOSITION.

   23. The Influence of Hydroxyl--The Replacement of Hydrogen by a
       Halogen--Bamberger’s Acylic and Aromatic Bases,            35, 36
   24. The Replacement of Hydrogen by Alkyls in Aromatic Bodies,   36-38
   25. The Influence of Carbonyl Groups,                              39
   26. Oscar Loew’s Theory as to the Action of Poisons,            39-41
   27. Michet’s Experiments on the relative Toxicity of Metals,   41, 42


  V. LIFE TESTS: OR THE IDENTIFICATION OF POISON BY EXPERIMENTS
  ON ANIMALS.

   28. The Action of Poisons on Infusoria, Cephalopoda, Insects,   42-44
   29. Effect of Poisons on the Heart of Cold-blooded Animals,    44, 45
   30. The Effect of Poisons on the Iris,                         45, 46


  VI. GENERAL METHOD OF PROCEDURE IN SEARCHING FOR POISON.

   31. Concentration in a Vacuum--Drying the Substance--Solvents--
       Destruction of Organic Matter,                              46-50
   32. Autenrieth’s General Process--Distillation--Shaking up with
       Solvents--Isolation of Metals--Investigation of Sulphides
       Soluble in Ammonium Sulphide--of Sulphides Insoluble in Ammonium
       Sulphide--Search for Zinc and Chromium--Search for Lead, Silver,
       and Barium,                                                 50-53


  VII. THE SPECTROSCOPE AS AN AID TO THE IDENTIFICATION OF
  CERTAIN POISONS.

   33. The Micro-Spectroscope--Oscar Brasch’s Researches of the Spectra
       of Colour Reactions--Wave Lengths,                          54-56


  _Examination of Blood or of Blood-Stains._

   34. Naked-eye Appearance of Blood-Stains--Dragendorff’s Process for
       Dissolving Blood,                                          56, 57
   35. Spectroscopic Appearances of Blood--Spectrum of Hydric Sulphide
       Blood--of Carbon Oxide Hæmoglobin--Methæmoglobin--of Acid
       Hæmatin--Tests for CO Blood--Piotrowski’s Experiments on CO
       Blood--Preparation of Hæmatin Crystals--The Guaiacum Test for
       Blood,                                                      57-62
   36. Distinction between the Blood of Animals and Men--The Alkalies
       in various Species of Blood,                               62, 63


  PART III.--POISONOUS GASES: CARBON MONOXIDE--CHLORINE--HYDRIC
  SULPHIDE.


  I. CARBON MONOXIDE.

   37. Properties of Carbon Monoxide,                                 64
   38. Symptoms--Acute Form--Chronic Form,                         64-66
   39. Poisonous Action on the Blood--Action on the Nervous
       System,                                                    66, 67
   40. _Post-mortem_ Appearances,                                     67
   41. Mass Poisonings by Carbon Monoxide--The Leeds Case--The
       Darlaston Cases,                                            67-70
   42. Detection of Carbon Monoxide--The Cuprous Chloride Method--
       Wanklyn’s Method--Hempel’s Method,                         70, 71


  II. CHLORINE.

   43. Chlorine; its Properties--The Weldon Process of manufacturing
       “Bleaching Powder,”                                        71, 72
   44. Effects of Chlorine,                                           72
   45. _Post-mortem_ Appearances,                                     72
   46. Detection of Free Chlorine,                                    72


  III. HYDRIC SULPHIDE (SULPHURETTED HYDROGEN).

   47. Properties of Hydric Sulphide,                             72, 73
   48. Effects of breathing Hydric Sulphide--Action on the Blood--The
       Cleator Moor Case,                                         73, 74
   49. _Post-mortem_ Appearances,                                     74
   50. Detection,                                                     74


  PART IV.--ACIDS AND ALKALIES.

  SULPHURIC ACID--HYDROCHLORIC ACID--NITRIC ACID--ACETIC ACID--AMMONIA
  --POTASH--SODA--NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM SALTS.


  I. SULPHURIC ACID.

   51. Varieties and Strength of the Sulphuric Acids of Commerce--
       Properties of the Acid--Nordhausen Sulphuric Acid,         75, 76
   52. Properties of Sulphuric Anhydride,                             76
   53. Occurrence of Free Sulphuric Acid in Nature,                   76
   54. Statistics--Comparative Statistics of different Countries, 76, 77
   55. Accidental, Suicidal, and Criminal Poisoning--Sulphuric Acid in
       Clysters and Injections,                                   77, 78
   56. Fatal Dose,                                                78, 79
   57. Local Action of Sulphuric Acid--Effects on Mucous Membrane, on
       the Skin, on Blood,                                        79, 80
   58. Action of Sulphuric Acid on Earth, Grass, Wood, Paper, Carpet,
       Clothing, Iron--Caution necessary in judging of Spots--
       Illustrative Case,                                         80, 81
   59. Symptoms--(1) External Effects--(2) Internal Effects in the
       Gullet and Stomach--Intercostal Neuralgia,                  81-83
   60. Treatment of Acute Poisoning by the Mineral Acids,             83
   61. _Post-mortem_ Appearances--Rapid and Slow Poisoning--
       Illustrative Cases,                                         83-85
   62. Pathological Preparations in the different London Hospital
       Museums,                                                   85, 86
   63. Chronic Poisoning,                                             86


  _Detection and Estimation of Free Sulphuric Acid._

   64. General Method of Separating the Free Mineral Acids--The Quinine
       Process--The Old Process of Extraction by Alcohol--Hilger’s Test
       for Mineral Acid,                                          87, 88
   65. The Urine--Excretion of Sulphates in Health and Disease--The
       Characters of the Urine after taking Sulphuric Acid,        88-90
   66. The Blood in Sulphuric Acid Poisoning,                         90
   67. The Question of the Introduction of Sulphates by the Food--
       Largest possible Amount of Sulphates introduced by this Means--
       Sulphur of the Bile--Medicinal Sulphates,                  90, 91


  II. HYDROCHLORIC ACID.

   68. General Properties of Hydrochloric Acid--Discovery--Uses--
       Tests,                                                     91, 92
   69. Statistics,                                                92, 93
   70. Fatal Dose,                                                    93
   71. Amount of Free Acid in the Gastric Juice,                  93, 94
   72. Influence of Hydrochloric Acid on Vegetation--Present Law on the
       Subject of Acid Emanations from Works--The Resistant Powers of
       various Plants,                                                94
   73. Action on Cloth and Manufactured Articles,                     95
   74. Poisonous Effects of Hydrochloric Acid Gas--Eulenberg’s
       Experiments on Rabbits and Pigeons,                        95, 96
   75. Effects of the Liquid Acid--Absence of Corrosion of the Skin--
       Pathological Appearances--Illustrative Cases,              96, 97
   76. _Post-mortem_ Appearances--Preparations in the different London
       Museums,                                                   97, 98
   77. (1) Detection of Free Hydrochloric Acid--Günzburg’s Test--A.
       Villiers’s and M. Favolle’s Test--(2) Quantitative Estimation,
       Sjokvist’s Method--Braun’s Method,                         98-101
   78. Method of Investigating Hydrochloric Acid Stains on Cloth,
       &c.,                                                     101, 102


  III. NITRIC ACID.

   79. Properties of Nitric Acid,                               102, 103
   80. Use in the Arts,                                              103
   81. Statistics,                                                   103
   82. Fatal Dose,                                                   104
   83. Action on Vegetation,                                         104
   84. Effects of Nitric Acid Vapour--Experiments of Eulenberg and O.
       Lassar--Fatal Effect on Man,                             104, 105
   85. Effects of Liquid Nitric Acid--Suicidal, Homicidal, and
       Accidental Deaths from the Acid,                         105, 106
   86. Local Action,                                                 106
   87. Symptoms--The Constant Development of Gas--Illustrative
       Cases,                                                   106, 107
   88. _Post-mortem_ Appearances--Preparations in various Anatomical
       Museums,                                                  107-109
   89. Detection and Estimation of Nitric Acid,                 109, 110


  IV. ACETIC ACID.

   90. Symptoms and Detection,                                       110


  V. AMMONIA.

   91. Properties of Ammonia,                                        111
   92. Uses--Officinal and other Preparations,                  111, 112
   93. Statistics of Poisoning by Ammonia,                           112
   94. Poisoning by Ammonia Vapour,                                  112
   95. Symptoms--Illustrative Case,                             112, 113
   96. Chronic Effects of the Gas,                                   113
   97. Ammonia in Solution--Action on Plants,                        113
   98. Action on Human Beings and Animal Life--Local Action on Skin--
       Action on the Blood--Time of Death,                       113-115
   99. _Post-mortem_ Appearances,                                    115
  100. Separation of Ammonia--Tests,                            115, 116
  101. Estimation of Ammonia,                                        116


  VI. CAUSTIC POTASH AND SODA.

  102. Properties of Potassium Hydrate,                         116, 117
  103. Pharmaceutical Preparations,                                  117
  104. Carbonate of Potash,                                          117
  105. Bicarbonate of Potash,                                        117
  106. Caustic Soda--Sodium Hydrate,                            117, 118
  107. Carbonate of Soda,                                            118
  108. Bicarbonate of Soda,                                          118
  109. Statistics,                                                   118
  110. Effects on Animal and Vegetable Life,                    118, 119
  111. Local Effects,                                                119
  112. Symptoms,                                                     119
  113. _Post-mortem_ Appearances,                                119-121
  114. Chemical Analysis,                                            121
  115. Estimation of the Fixed Alkalies,                        121, 122


  VII. NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM SALTS.

  116. Relative Toxicity of Sodium, Potassium, and Ammonium Salts,   122
  117. Sodium Salts,                                                 122
  118. Potassium Salts--Potassic Sulphate--Hydropotassic Tartrate--
       Statistics,                                                   122
  119. Action on the Frog’s Heart,                                   122
  120. Action on Warm-Blooded Animals,                          122, 123
  121. Elimination,                                                  123
  122. Nitrate of Potash,                                            123
  123. Statistics,                                                   123
  124. Uses in the Arts,                                             123
  125. Action of Nitrates of Sodium and Potassium--Sodic
       Nitrite,                                                 123, 124
  126. _Post-mortem_ Appearances from Poisoning by Potassic Nitrate, 124
  127. Potassic Chlorate,                                            124
  128. Uses,                                                         124
  129. Poisonous Properties,                                         124
  130. Experiments on Animals,                                  124, 125
  131. Effects on Man--Illustrative Cases of the Poisoning of Children
       by Potassic Chlorate,                                         125
  132. Effects on Adults--Least Fatal Dose,                          126
  133. Elimination,                                                  126
  134. Essential Action of Potassic Chlorate on the Blood and
       Tissues,                                                      126
  135. Detection and Estimation of Potassic Chlorate,           126, 127


  _Toxicological Detection of Alkali Salts._

  136. Natural occurrence of Potassium and Sodium Salts in the Blood
       and Tissues--Tests for Potassic and Sodic Salts--Tests for
       Potassic Nitrate--Tests for Chlorates--Ammonium Salts,   127, 128


  PART V.--MORE OR LESS VOLATILE POISONOUS SUBSTANCES CAPABLE OF BEING
  SEPARATED BY DISTILLATION FROM NEUTRAL OR ACID LIQUIDS.

  HYDROCARBONS--CAMPHOR--ALCOHOL--AMYL NITRITE--ETHER--CHLOROFORM
  AND OTHER ANÆSTHETICS--CHLORAL--CARBON BISULPHIDE--CARBOLIC
  ACID--NITRO-BENZENE--PRUSSIC ACID--PHOSPHORUS.


  I. HYDROCARBONS.


  1.  _Petroleum._

  137. Petroleum,                                                    129
  138. Cymogene,                                                     129
  139. Rhigolene,                                                    129
  140. Gasolene,                                                     129
  141. Benzoline--Distinction between Petroleum-Naphtha, Shale-Naphtha,
       and Coal-Tar Naphtha,                                    129, 130
  142. Paraffin Oil,                                                 130
  143. Effects of Petroleum--Experiments on Rabbits, &c.,       130, 131
  144. Poisoning by Petroleum--Illustrative Cases,                   131
  145. Separation and Tests for Petroleum,                           131


  2. _Coal-Tar Naphtha--Benzene._

  146. Composition of Commercial Coal-Tar Naphtha,                   131
  147. Symptoms observed after Swallowing Coal-Tar Naphtha,          132
  148. Effects of the Vapour of Benzene,                             132


  _Detection and Separation of Benzene._

  149.  Separation of Benzene--(1) Purification; (2) Conversion into
        Nitro-Benzene; (3) Conversion into Aniline,             132, 133


  3. _Terpenes--Essential Oils--Oil of Turpentine._

  150. Properties of the Terpenes, Cedrenes, and Colophenes,         133


  4. _Oil of Turpentine--Spirits of Turpentine._

  151. Terebenthene--Distinction between French and English
       Turpentine,                                              133, 134
  152. Effects of the Administration of Turpentine,                  134


  II. CAMPHOR.

  153. Properties of Camphor,                                        135
  154. Pharmaceutical Preparations,                                  135
  155. Symptoms of Poisoning by Camphor,                             135
  156. _Post-mortem_ Appearances,                                    136
  157. Separation from the Contents of the Stomach,                  136


  III. ALCOHOLS.


  1. _Ethylic Alcohol._

  158. Chemical Properties of Alcohol--Statistics of Poisoning by
       Alcohol,                                                      136
  159. Criminal or Accidental Alcoholic Poisoning,                   137
  160. Fatal Dose,                                                   137
  161. Symptoms of Acute Poisoning by Alcohol,                  137, 138
  162. _Post-mortem_ Appearances,                               138, 139
  163. Excretion of Alcohol,                                    139, 140
  164. Toxicological Detection,                                      140


  2. _Amylic Alcohol._

  165. Properties of Amylic Alcohol,                                 140
  166. Experiments as to the Effect on Animals of Amylic
       Alcohol,                                                 140, 141
  167. Detection and Estimation of Amylic Alcohol,                   141
  168. Amyl Nitrite--Properties--Symptoms--_Post-mortem_
       Appearances,                                                  141


  IV. ETHER.

  169. Properties of Ethylic Ether,                             141, 142
  170. Ether as a Poison,                                            142
  171. Fatal Dose,                                                   142
  172. Ether as an Anæsthetic,                                  142, 143
  173. Separation of Ether from Organic Fluids, &c.,                 143


  V. CHLOROFORM.

  174. Discovery of Chloroform--Properties, Adulterations, and Methods
  for Detecting them,                                            143-145
  175. Methods of Manufacturing Chloroform,                     145, 146


  _Poisonous Effects of Chloroform._


  1. _As a Liquid._

  176. Statistics,                                                   146
  177. Local Action,                                                 146
  178. Action on Blood, Muscle, and Nerve-Tissue,                    146
  179. General Effects of Liquid Chloroform--Illustrative
       Cases,                                                   146, 147
  180. Fatal Dose,                                                   147
  181. Symptoms,                                                     148
  182. _Post-mortem_ Appearances,                               148


  2. _The Vapour of Chloroform._

  183. Statistics of Deaths through Chloroform--Anæsthesia,     148, 149
  184. Suicidal and Criminal Poisoning--Illustrative Cases,     149, 150
  185. Physiological Effects,                                        150
  186. Symptoms witnessed in Death from Chloroform Vapour,      150, 151
  187. Chronic Chloroform Poisoning--Mental Effects from Use of
       Chloroform,                                              151, 152
  188. _Post-mortem_ Appearances,                                    152
  189. The Detection and Estimation of Chloroform--Various
       Tests,                                                   152, 153
  190. Quantitative Estimation,                                      153


  VI. OTHER ANÆSTHETICS.

  191. Methyl Chloride--Methene Dichloride, &c.,                     154
  192. Pentane,                                                      154
  193. Aldehyde,                                                     154
  194. Paraldehyde,                                                  154


  VII. CHLORAL.

  195. Chloral Hydrate; its Composition and Properties,         154, 155
  196. Detection,                                                    155
  197. Quantitative Estimation of Chloral Hydrate,              155, 156
  198. Effects of Chloral Hydrate on Animals--Depression of Temperature
       --Influence on the Secretion of Milk, &c.,               156, 157
  199. Action upon the Blood,                                        157
  200. Effects on Man,                                          157, 158
  201. Fatal Dose,                                              158, 159
  202. Symptoms,                                                     159
  203. Action of Chloral upon the Brain,                             159
  204. Treatment of Acute Chloral Poisoning,                         160
  205. Chronic Poisoning by Chloral Hydrate,                    160, 161
  206. Manner in which Chloral is Decomposed in, and Excreted from, the
       Body,                                                    161, 162
  207. Separation from Organic Matters--Tests for Chloral,      162, 163


  VIII. BISULPHIDE OF CARBON.

  208. Properties of Bisulphide of Carbon,                           163
  209. Poisoning by Bisulphide of Carbon,                            163
  210. Action on Animals,                                       163, 164
  211. Chronic Poisoning by Bisulphide of Carbon--Effects on the Brain,
       &c.,                                                     164, 165
  212. _Post-mortem_ Appearances,                                    165
  213. Separation and Detection of Carbon Bisulphide--Tests,         165
  214. Xanthogenic Acid,                                             165
  215. Potassic Xanthogenate,                                        165


  IX. THE TAR ACIDS--PHENOL--CRESOL.

  216. Properties and Sources of Carbolic Acid,                 165, 166
  217. Different Forms of Carbolic Acid--Calvert’s Carbolic Acid Powder
       --Carbolic Acid Soaps,                                   166, 167
  218. Uses of Carbolic Acid,                                        167
  219. Statistics Relative to Poisoning by Carbolic Acid,        167-169
  220. Fatal Dose,                                                   169
  221. Effects on Animals--Infusoria--Fish--Frogs,              169, 170
  222. Effects on Warm-Blooded Animals,                              170
  223. Symptoms Produced in Man--External Application--Action on the
       Skin--Effects of the Vapour--Use of Carbolic Acid Lotions--
       Injections, &c.--Illustrative Cases,                      170-172
  224. Internal Administration--Illustrative Cases,                  173
  225. General Review of the Symptoms induced by Carbolic Acid, 173, 174
  226. Changes Produced in the Urine by Carbolic Acid,          174, 175
  227. The Action of Carbolic Acid considered Physiologically,  175, 176
  228. Forms under which Carbolic Acid is Excreted,                  176
  229. _Post-mortem_ Appearances,                               176, 177


  _Tests for Carbolic Acid._

  230. (1) The Pine-Wood Test--(2) Ammonia and Hypochlorite Test--(3)
       Ferric Chloride--(4) Bromine,                            177, 178
  231. Quantitative Estimation of Carbolic Acid,                178, 179
  232. Properties of Cresol, and Tests for Distinguishing Cresol and
       Carbolic Acid,                                                179
  233. Properties of Creasote--Tests,                           179, 180
  234. Separation of Carbolic Acid from Organic Fluids or
       Tissues,                                                 180, 181
  235. Examination of the Urine for Phenol or Cresol,                181
  236. Assay of Disinfectants, Carbolic Acid Powders--E. Waller’s
       Process--Koppeschaar’s Volumetric Method--Colorimetric Method of
       Estimation,                                               181-183
  237. Carbolic Acid Powders,                                        183
  238. Carbolic Acid Soaps,                                          183


  X. NITRO-BENZENE.

  239. Properties and Varieties,                                183, 184
  240. Effects of Poisoning by Nitro-Benzene,                        184
  241. Illustrative Cases of Poisoning by Nitro-Benzene Vapour, 184, 185
  242. Effects Produced by taking Liquid Nitro-Benzene,         185, 186
  243. Fatal Dose,                                              186, 187
  244. Pathological Appearances,                                     187
  245. The Essential Action of Nitro-Benzene,                   187, 188
  246. Detection and Separation from the Animal Tissues,             188


  XI. DINITRO-BENZOL.

  247. Properties of Ortho-, Meta-, and Para-Dinitro-Benzol,         189
  248. Effects of Dinitro-Benzol,                               189, 190
  249. The Blood in Nitro-Benzol Poisoning,                          191
  250. Detection of Dinitro-Benzol,                                  192


  XII. HYDROCYANIC ACID.

  251. Properties of Hydrocyanic Acid,                               192
  252. Medicinal Preparations of Prussic Acid--Various Strengths of the
       Commercial Acid,                                         192, 193
  253. Poisoning by Prussic Acid--Uses in the Arts--Distribution in the
       Vegetable Kingdom,                                        193-195
  254. Composition and Varieties of Amygdalin,                       195
  255. Statistics of Poisoning by Prussic Acid,                  195-197
  256. Accidental and Criminal Poisoning,                       197, 198
  257. Fatal Dose,                                                   198
  258. Action of Hydric and Potassic Cyanides on Living
       Organisms,                                               198, 199
  259. Symptoms observed in Animals,                            199, 200
  260. Length of Interval between taking the Poison and Death in
       Animals,                                                 200, 201
  261. Symptoms in Man,                                         201, 202
  262. Possible Acts after taking the Poison--Nunneley’s
       Experiments,                                             202, 203
  263. Chronic Poisoning by Hydric Cyanide,                          203
  264. _Post-mortem_ Appearances,                               203, 204
  265. Tests for Hydrocyanic Acid and Cyanide of Potassium--Schönbein’s
       Test--Kobert’s Test,                                      204-206
  266. Separation of Hydric Cyanide or Potassic Cyanide from Organic
       Matters--N. Sokoloff’s Experiments,                       206-208
  267. How long after Death can Hydric or Potassic Cyanide be
       Detected?                                                208, 209
  268. Estimation of Hydrocyanic Acid or Potassic Cyanide,           209
  269. Case of Poisoning by Bitter Almonds,                     209, 210


  _Poisonous Cyanides other than Hydric and Potassic Cyanides._

  270. General Action of the Alkaline Cyanides--Experiments with
       Ammonic Cyanide Vapour,                                       210
  271. The Poisonous Action of several Metallic and Double Cyanides--
       The Effects of Mercuric and Silver Cyanides; of Potassic and
       Hydric Sulphocyanides; of Cyanogen Chloride; of Methyl Cyanide,
       and of Cyanuric Acid,                                    210, 211


  XIII. PHOSPHORUS.

  272. Properties of Phosphorus--Solubility--Effects of Heat on
       Phosphorus,                                              212, 213
  273. Phosphuretted Hydrogen--Phosphine,                            213
  274. The Medicinal Preparations of Phosphorus,                     213
  275. Matches and Vermin Paste,                                 213-215
  276. Statistics of Phosphorus Poisoning,                      215, 216
  277. Fatal Dose,                                                   216
  278. Effects of Phosphorus,                                        217
  279. Different Forms of Phosphorus Poisoning,                 217, 218
  280. Common Form,                                             218, 219
  281. Hæmorrhagic Form,                                             219
  282. Nervous Form,                                                 219
  283. Sequelæ,                                                 219, 220
  284. Period at which the First Symptoms commence,                  220
  285. Period of Death,                                              220
  286. Effects of Phosphorus Vapour--Experiments on Rabbits,    220, 221
  287. Effects of Chronic Phosphorus Poisoning,                 221, 222
  288. Changes in the Urinary Secretion,                             222
  289. Changes in the Blood,                                    222, 223
  290. Antidote--Treatment by Turpentine,                            223
  291. Poisonous Effects of Phosphine,                          223, 224
  292. Coefficient of Solubility of Phosphine in Blood compared with
       Pure Water,                                                   224
  293. _Post-mortem_ Appearances--Effects on the Liver,          224-228
  294. Pathological Changes in the Kidneys, Lungs, and Nervous
       System,                                                       228
  295. Diagnostic Differences between Acute Yellow Atrophy of the Liver
       and Fatty Liver produced by Phosphorus,                  228, 229
  296. Detection of Phosphorus--Mitscherlich’s Process--The Production
       of Phosphine--Tests Dependent on the Combustion of Phosphine,
                                                                 229-232
  297. The Spectrum of Phosphine--Lipowitz’s Sulphur Test--Scherer’s
       Test,                                                    232, 233
  298. Chemical Examination of the Urine,                       233, 234
  299. Quantitative Estimation of Phosphorus,                        234
  300. How long can Phosphorus be recognised after Death?       234, 235


  PART VI.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES
  SEPARATED FOR THE MOST PART BY ALCOHOLIC SOLVENTS.


  DIVISION I.--VEGETABLE ALKALOIDS.


  I. GENERAL METHOD OF TESTING AND EXTRACTING ALKALOIDS.

  301. General Tests for Alkaloids,                                  236
  302. Group-Reagents,                                          236, 237
  303. Phosphomolybdic, Silico-Tungstic, and Phospho-Tungstic Acids as
       Alkaloidal Reagents,                                      237-239
  304. Schulze’s Reagent,                                            239
  305. Dragendorff’s Reagent,                                        239
  306. Colour Tests,                                                 239
  307. Stas’s Process,                                               239


  _Methods of Separation._

  308. Selmi’s Process for Separating Alkaloids,                240, 241
  309. Dragendorff’s Process,                                    241-254
  310. Shorter Process for Separating some of the Alkaloids,    254, 255
  311. Scheibler’s Process for Alkaloids,                            255
  312. Grandval and Lajoux’s Method,                            255, 256
  313. Identification of the Alkaloids,                              256
  314. Sublimation of the Alkaloids,                             256-261
  315. Melting-point,                                                261
  316. Identification by Organic Analysis,                      261, 262
  317. Quantitative Estimation of the Alkaloids--Mayer’s Reagent--
       Compound of the Alkaloids with Chlorides of Gold and Platinum,
                                                                 262-264


  II. LIQUID VOLATILE ALKALOIDS.


  1. _The Alkaloids of Hemlock_ (_Conium_).

  318. Botanical Description of Hemlock,                             264
  319. Properties of Coniine--Tests,                             264-266
  320. Other Coniine Bases,                                          266
  321. Pharmaceutical Preparations of Hemlock,                  266, 267
  322. Statistics of Coniine Poisoning,                              267
  323. Effects of Coniine on Animals,                           267, 268
  324. Effects of Coniine on Man,                                    268
  325. Physiological Action of Coniine,                              268
  326. _Post-mortem_ Appearances--Fatal Dose,                   268, 269
  327. Separation of Coniine from Organic Matters or Tissues,        269


  2. _Tobacco--Nicotine._

  328. General Composition of Tobacco,                          269, 270
  329. Quantitative Estimation of Nicotine in Tobacco,          270, 271
  330. Nicotine; its Properties and Tests,                       271-273
  331. Effects of Nicotine on Animals,                          273, 274
  332. Effects of Nicotine on Man,                              274, 275
  333. Some Instances of Poisoning by Tobacco and Tobacco Juice, 275-277
  334. Physiological Action of Nicotine,                        277, 278
  335. Fatal Dose,                                                   278
  336. _Post-mortem_ Appearances,                                    278
  337. Separation of Nicotine from Organic Matters, &c.,        278, 279


  3. _Piturie._

  338. Properties of Piturie,                                        279


  4. _Sparteine._

  339. Properties of Sparteine,                                 279, 280


  5. _Aniline._

  340. Properties of Aniline,                                        280
  341. Symptoms and Effects,                                    280, 281
  342. Fatal Dose,                                                   281
  343. Detection of Aniline,                                         281


  III. THE OPIUM GROUP OF ALKALOIDS.

  344. General Composition of Opium,                            281, 282
  345. Action of Solvents on Opium,                             282, 283
  346. The Methods of Teschemacher and Smith, of Dott and others for
       the Assay of Opium,                                      283, 284
  347. Medicinal and other Preparations of Opium,                284-288
  348. Statistics of Opiate Poisoning,                          288, 289
  349. Poisoning of Children by Opium,                               289
  350. Doses of Opium and Morphine--Fatal Dose,                 289, 290
  351. General Method for the Detection of Opium,               290, 291
  352. Morphine; its Properties,                                291, 292
  353. Morphine Salts; their Solubility,                        292, 293
  354. Constitution of Morphine,                                293, 294
  355. Tests for Morphine and its Compounds--Production of Morphine
       Hydriodide--Iodic Acid Test and other Reactions--Transformation
       of Morphine into Codeine,                                 294-296
  356. Symptoms of Opium and Morphine Poisoning--Action on Animals,
                                                                 296-298
  357. Physiological Action,                                    298, 299
  358. Physiological Action of Morphine Derivatives,                 299
  359. Action on Man--(_a_) The Sudden Form; (_b_) the Convulsive Form;
       (_c_) a Remittent Form of Opium Poisoning--Illustrative Cases,
                                                                 299-303
  360. Diagnosis of Opium Poisoning,                            303, 304
  361. Opium-Eating,                                             304-306
  362. Treatment of Opium or Morphine Poisoning,                     306
  363. _Post-mortem_ Appearances,                               306, 307
  364. Separation of Morphine from Animal Tissues and Fluids,        307
  365. Extraction of Morphine,                                  308, 309
  366. Narcotine; its Properties and Tests,                     309, 310
  367. Effects of Narcotine,                                         310
  368. Codeine--Properties of Codeine,                          310, 311
  369. Effects of Codeine on Animals--Claude Bernard’s Experiments,  311
  370. Narceine--Properties of Narceine--Tests,                 312, 313
  371. Effects of Narceine,                                     313, 314
  372. Papaverine--Properties of Papaverine--Tests,                  314
  373. Effects of Papaverine,                                        314
  374. Thebaine; its Properties,                                314, 315
  375. Thebaine; its Effects,                                        315
  376. Cryptopine,                                              315, 316
  377. Rhœadine,                                                     316
  378. Pseudomorphine,                                               316
  379. Opianine,                                                     316
  380. Apomorphine,                                             316, 317
  381. Reactions of some of the Rarer Opium Alkaloids,               317
  382. Tritopine,                                                    317
  383. Meconin (Opianyl),                                            317
  384. Meconic Acid--Effects of Meconic Acid--Tests,            318, 319


  IV. THE STRYCHNINE OR TETANUS-PRODUCING GROUP OF ALKALOIDS.


  1. _Nux Vomica Group--Strychnine--Brucine--Igasurine._

  385. Nux Vomica--Characteristics of the Entire and of the Powdered
       Seed,                                                         319
  386. Chemical Composition of Nux Vomica,                           319
  387. Strychnine--Microscopical Appearances--Properties--Medicinal
       Preparations--Strychnine Salts,                           319-322
  388. Pharmaceutical and other Preparations of Nux Vomica, with
       Suggestions for their Valuation--Vermin-Killers,          322-324
  389. Statistics,                                               324-325
  390. Fatal Dose--Falck’s Experiments on Animals as to the Least Fatal
       Dose--Least Fatal Dose for Man,                           325-328
  391. Action on Animals--Frogs,                                328, 329
  392. Effects on Man--Symptoms--Distinction between “Disease Tetanus”
       and “Strychnos Tetanus,”                                  329-331
  393. Diagnosis of Strychnine Poisoning,                       331, 332
  394. Physiological Action--Richet’s Experiments--The Rise of
       Temperature--Effect on the Blood-Pressure,               332, 333
  395. _Post-mortem_ Appearances,                                    333
  396. Treatment,                                                    333
  397. Separation of Strychnine from Organic Matters--Separation from
       the Urine, Blood, and Tissues,                            334-337
  398. Identification of the Alkaloid--Colour Tests--Physiological
       Tests,                                                    337-339
  399. Hypaphorine,                                                  339
  400. Quantitative Estimation of Strychnine,                   339, 340
  401. Brucine; its Properties,                                 340, 341
  402. Physiological Action of Brucine--Experiments of Falck,   341, 342
  403. Tests for Brucine,                                       342, 343
  404. Igasurine,                                                    344
  405. Strychnic Acid,                                               344


  2. _The Quebracho Group of Alkaloids._

  406. The Alkaloids of Quebracho--Aspidospermine--Quebrachine,      344


  3.  _Pereirine._

  407.  Pereirine,                                              344, 345


  4.  _Gelsemine._

  408.  Properties of Gelsemine,                                     345
  409.  Fatal Dose of Gelsemine,                                     345
  410.  Effects on Animals--Physiological Action,                    345
  411.  Effects of Gelsemine on Man,                                 346
  412.  Extraction from Organic Matters, or the Tissues of the Body, 347


  5. _Cocaine._

  413.  Cocaine; its Properties,                                 47, 348
  414.  Cocaine Hydrochlorate,                                       348
  415.  Pharmaceutical Preparations,                                 348
  416.  Separation of Cocaine and Tests,                        348, 349
  417.  Symptoms,                                                    349
  418.  _Post-mortem_ Appearances,                              349, 350
  419.  Fatal Dose,                                                  350


  6. _Corydaline._

  420.  Properties of Corydaline,                                    350


  V. THE ACONITE GROUP OF ALKALOIDS.

  421.  Varieties of Aconite--Description of the Flower, and of the
        Seeds,                                                  350, 351
  422.  Pharmaceutical Preparations of Aconite,                      351
  423.  The Aconite Alkaloids,                                       351
  424.  Aconitine,                                              351, 352
  425.  Tests for Aconitine,                                         352
  426.  Benzoyl-Aconine Properties--Recognition of Benzoic Acid,
                                                                353, 354
  427.  Pyraconitine,                                                354
  428.  Pyraconine,                                                  354
  429.  Aconine,                                                     355
  430.  Commercial Aconitine--English and German Samples of Aconitine--
        Lethal Dose of the Alkaloid and of the Pharmaceutical
        Preparations,                                            355-358
  431.  Effects of Aconitine on Animal Life--Insects, Fish, Reptiles,
        Birds, Mammals,                                          358-360
  432.  Statistics,                                                  361
  433.  Effects on Man,                                              361
  434.  Poisoning by the Root (_Reg. v. M’Conkey_),             361, 362
  435.  Poisoning by the Alkaloid Aconitine--Three Cases of
        Poisoning,                                              363, 364
  436.  Lamson’s Case,                                          364, 365
  437.  Symptoms of Poisoning by the Tincture, &c.,             365, 366
  438.  Physiological Action,                                        366
  439.  _Post-mortem_ Appearances,                              366, 367
  440.  Separation of Aconitine from the Contents of the Stomach or the
        Organs,                                                 367, 368


  VI. THE MYDRIATIC GROUP OF ALKALOIDS--ATROPINE--HYOSCYAMINE--SOLANINE
      --CYTISINE.


  1. _Atropine._

  441.  The _Atropa belladonna_; its Alkaloidal Content,        368, 369
  442.  The _Datura stramonium_--Distinction between Datura and
        Capsicum Seeds,                                         369, 370
  443.  Pharmaceutical Preparations--(a) Belladonna; (b)
        Stramonium,                                             370, 371
  444.  Properties of Atropine,                                 371, 372
  445.  Tests for Atropine, Chemical and Physiological,          372-374
  446.  Statistics of Atropine Poisoning,                            375
  447.  Accidental and Criminal Poisoning by Atropine--Use of
        _Dhatoora_ by the Hindoos,                              375, 376
  448.  Fatal Dose of Atropine,                                 376, 377
  449.  Action on Animals,                                           377
  450.  Action on Man,                                           377-380
  451.  Physiological Action of Atropine,                            380
  452.  Diagnosis of Atropine Poisoning,                             380
  453.  _Post-mortem_ Appearances,                                   380
  454.  Treatment of Cases of Poisoning by Atropine,            380, 381
  455.  Separation of Atropine from Organic Matters, &c.,            381


  2. _Hyoscyamine._

  456.  Distribution of Hyoscyamine--Properties,                 381-383
  457.  Pharmaceutical and other Preparations of Henbane,       383, 384
  458.  Dose and Effects,                                            384
  459.  Separation of Hyoscyamine from Organic Matters,              385


  3.  _Hyoscine._

  460.  Hyoscine,                                                    385


  4.  _Solanine._

  461.  Distribution of Solanine,                               385, 386
  462.  Properties of Solanine,                                      386
  463.  Solanidine,                                             386, 387
  464.  Poisoning from Solanine,                                     387
  465.  Separation from Animal Tissues,                              387


  5.  _Cytisine._

  466.  The _Cytisus laburnum_,                                      387
  467.  Reactions of Cytisine,                                       388
  468.  Effects on Animals,                                          389
  469.  Effects on Man--Illustrative Cases,                     389, 390


  VII. THE ALKALOIDS OF THE VERATRUMS.

  470.  The Alkaloids found in the _Veratrum Viride_ and _Veratrum
        Album_--Yield per Kilogram,                              390-392
  471.  Veratrine--Cevadine,                                         392
  472.  Jervine,                                                     393
  473.  Pseudo-jervine,                                              393
  474.  Protoveratridine,                                            393
  475.  Rubi-jervine,                                                394
  476.  Veratralbine,                                                394
  477.  Veratroidine,                                                394
  478.  Commercial Veratrine,                                   394, 395
  479.  Pharmaceutical Preparations,                                 395
  480.  Fatal Dose,                                                  395
  481.  Effects on Animals--Physiological Action,               395, 396
  482.  Effects on Man--Illustrative Cases,                          396
  483.  Symptoms of Acute and Chronic Poisoning,                396, 397
  484.  _Post-mortem_ Signs,                                         397
  485.  Separation of the Veratrum Alkaloids from Organic Matters,   397


  VIII. PHYSOSTIGMINE.

  486.  The Active Principle of the Calabar Bean,               397, 398
  487.  Physostigmine or Eserine--Properties,                   398, 399
  488.  Tests,                                                       399
  489.  Pharmaceutical Preparations,                            399, 400
  490.  Effects on Animals--On Man--The Liverpool Cases of Poisoning,
                                                                     400
  491.  Physiological Action,                                        401
  492.  _Post-mortem_ Appearances,                                   401
  493.  Separation of Physostigmine,                            401, 402
  494.  Fatal Dose of Physostigmine,                                 402


  IX. PILOCARPINE.

  495.  Alkaloids from the Jaborandi,                                402
  496.  Pilocarpine,                                            402, 403
  497.  Tests,                                                       403
  498.  Effects of Pilocarpine,                                 403, 404


  X. TAXINE.

  499.  Properties of Taxine,                                        404
  500.  Poisoning by the Common Yew,                                 404
  501.  Effects on Animals--Physiological Action,                    404
  502.  Effects on Man,                                         404, 405
  503.  _Post-mortem_ Appearances,                                   405


  XI. CURARINE.

  504.  Commercial Curarine--Properties,                         405-407
  505.  Physiological Effects,                                       407
  506.  Separation of Curarine,                                 407, 408


  XII. COLCHICINE.

  507.  Contents of Colchicine in Colchicum Seeds,              408, 409
  508.  Colchicine--Method of Extraction--Properties,                409
  509.  Tests,                                                  409, 410
  510.  Pharmaceutical Preparations,                                 410
  511.  Fatal Dose,                                             410, 411
  512.  Effects of Colchicine on Animals,                            411
  513.  Effects of Colchicum on Man--Illustrative Cases,        411, 412
  514.  Symptoms Produced by Colchicum--_Post-mortem_ Appearances,
                                                                412, 413
  515.  Separation of Colchicine from Organic Matters,               413


  XIII. MUSCARINE AND THE ACTIVE PRINCIPLES OF CERTAIN FUNGI.

  516.  Description of the _Amanita Muscaria_--Use of it by the Natives
        of Kamschatka,                                          413, 414
  517.  Cases of Poisoning by the Fungus itself,                414, 415
  518.  Muscarine--Its Properties and Effects,                  415, 416
  519.  Antagonistic Action of Atropine and Muscarine,               416
  520.  Detection of Muscarine,                                 416, 417
  521.  The _Agaricus Phalloides_--_Phallin_,                        417
  522.  _Post-mortem_ Appearances,                              417, 418
  523.  The _Agaricus Pantherinus_--The _Agaricus Ruber_--Ruberine
        --Agarythrine,                                               418
  524.  The _Boletus Satanus_, or _Luridus_,                         418
  525.  Occasional Effects of the Common Morelle,                    418


  Division II.--GLUCOSIDES


  I. DIGITALIS GROUP.

  526.  Description of the _Digitalis Purpurea_, or Foxglove,        419
  527.  Active Principles of the Foxglove--The Digitalins,           419
  528.  Digitalein,                                                  420
  529.  Digitonin--Digitogenin,                                      420
  530.  Digitalin,                                                   420
  531.  Digitaletin,                                                 420
  532.  Digitoxin--Toxiresin,                                   420, 421
  533.  Digitaleretin--Paradigitaletin,                              421
  534.  Other Active Principles in Digitalis; such as Digitin,
        Digitalacrin, Digitalein, &c.,                          421, 422
  535.  Reactions of the Digitalins,                                 422
  536.  Pharmaceutical Preparations of Digitalin,                    422
  537.  Fatal Dose,                                              422-424
  538.  Statistics of Poisoning by Digitalis,                        424
  539.  Effects on Man--Illustrative Cases,                      424-427
  540.  Physiological Action of the Digitalins,                      427
  541.  Local Action of the Digitalins,                         427, 428
  542.  Action on the Heart and Circulation,                    428, 429
  543.  Action of the Digitalins on the Muco-Intestinal Tract and other
        Organs,                                                      429
  544.  Action of Digitalin on the Common Blow-Fly,                  429
  545.  Action of the Digitalins on the Frog’s Heart,           429, 430
  546.  _Post-mortem_ Appearances,                                   430
  547.  Separation of the Digitalins from Animal Tissues, &c.--Tests,
        Chemical and Physiological,                                  431


  II. OTHER POISONOUS GLUCOSIDES ACTING ON THE HEART.


  1. _Crystallisable Glucosides._

  548.  Antiarin--Chemical Properties,                               432
  549.  Effects of Antiarin,                                         432
  550.  Separation of Antiarin,                                      432
  551.  The Active Principles of the Hellebores--Helleborin--
        Helleborein--Helleboretin,                                   433
  552.  Symptoms of Poisoning by Hellebore,                          433
  553.  Euonymin,                                                    433
  554.  Thevetin,                                                    434


  2. _Substances partly Crystallisable, but which are not Glucosides._

  555.  Strophantin,                                                 434
  556.  Apocynin,                                                    434


  3. _Non-Crystallisable Glucosides almost Insoluble in Water._

  557.  Scillain, or Scillitin--Adonidin,                            434
  558.  Oleandrin,                                                   435
  559.  Neriin, or Oleander Digitalin,                               435
  560.  Symptoms of Poisoning by Oleander,                      435, 436
  561.  The Madagascar Ordeal Poison,                                436


  4. _Substances which, with other Toxic Effects, behave like the
  Digitalins._

  562.  Erythrophlein,                                               436


  III. SAPONIN--SAPONIN SUBSTANCES.

  563.  The Varieties of Saponins,                              436, 437
  564.  Properties of Saponin,                                       437
  565. Effects of Saponin,                                      437, 438
  566. Action on Man,                                                438
  567. Separation of Saponin,                                   438, 439
  568. Identification of Saponin,                                    439


  DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS.


  I. SANTONIN.

  569. Properties of Santonin,                                  439, 440
  570. Poisoning by Santonin,                                        440
  571. Fatal Dose,                                                   440
  572. Effects on Animals,                                           440
  573. Effects on Man--Yellow Vision,                           440, 441
  574. _Post-mortem_ Appearances,                                    441
  575. Separation from the Contents of the Stomach,             441, 442


  II.  MEZEREON.

  576. Cases of Poisoning by the Mezereon,                           442


  DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES--NOT ADMITTING OF
  CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS.


  I. ERGOT OF RYE.

  577. Description of the Ergot Fungus,                         442, 443
  578. Chemical Constituents of Ergot--Ergotinine--_Ecboline_--
       _Scleromucin_--Sclerotic Acid--Sclererythrin--Scleroidin--
       Sclerocrystallin--Sphacelic Acid--Cornutin,               443-445
  579. Detection of Ergot in Flour,                                  445
  580. Pharmaceutical Preparations,                                  445
  581. Dose,                                                         446
  582. Ergotism--Historical Notice of Various Outbreaks,        446, 447
  583. Convulsive Form of Ergotism,                                  447
  584. Gangrenous Form of Ergotism--The Wattisham Cases,        447, 448
  585. Symptoms of Acute Poisoning by Ergot,                         448
  586. Physiological Action, as shown by Experiments on Animals, 448-450
  587. Separation of the Active Principles of Ergot,                 450


  II. PICROTOXIN, THE ACTIVE PRINCIPLE OF THE _COCCULUS INDICUS_.

  588. Enumeration of the Active Principles contained in the
       _Menispermum Cocculus_,                                       451
  589. Picrotoxin; its Chemical Reactions and Properties,       451, 452
  590. Fatal Dose,                                                   452
  591. Effects on Animals,                                      452, 453
  592. Effects on Man,                                               453
  593. Physiological Action,                                         453
  594. Separation from Organic Matters,                         453, 454


  III. THE POISON OF _ILLICIUM RELIGIOSUM_.

  595. Dr. Langaard’s Researches,                                    454


  IV. PICRIC ACID AND PICRATES.

  596. Properties of Picric Acid,                                    454
  597. Effects of Picric Acid,                                  454, 455
  598. Tests,                                                        455


  V. CICUTOXIN.

  599. Description of the _Cicuta Virosa_,                           456
  600. Effects on Animals,                                           456
  601. Effects on Man,                                          456, 457
  602. Separation of Cicutoxin from the Body,                        457


  VI. _ÆTHUSA CYNAPIUM_ (FOOL’S PARSLEY).

  603. Dr. Harley’s Experiments,                                     457


  VII. _ŒNANTHE CROCATA._

  604. The Water Hemlock--Description of the Plant--Cases of
       Poisoning,                                               457, 458
  605. Effects of the Water Hemlock, as shown by the Plymouth Cases, 458
  606. _Post-mortem_ Appearances,                                    459


  VIII. OIL OF SAVIN.

  607. Effects and Properties of Savin Oil,                          459
  608. _Post-mortem_ Appearances,                                    460
  609. Separation and Identification,                                460


  IX. CROTON OIL.

  610. Chemical Properties of Croton Oil,                            461
  611. Dose--Effects--Illustrative Cases,                            461
  612. _Post-mortem_ Appearances,                                    461
  613. Chemical Analysis,                                            462


  X. THE TOXALBUMINS OF CASTOR OIL SEEDS AND ABRUS.

  614. The Toxalbumin of Castor Oil Seeds,                           462
  615. Toxalbumin of Abrus,                                     462, 463


  XI. ICTROGEN.

  616. Ictrogen,                                                     463


  XII. COTTON SEEDS.

  617. Cotton Seeds as a Poison,                                     464


  XIII. _LATHYRUS SATIVUS._

  618. Poisonous Qualities of Vetchlings,                       464, 465


  XIV. ARUM--LOCUST-TREE--BRYONY--MALE FERN.

  619. Arum Maculatum,                                               465
  620. The Black Bryony,                                             465
  621. The Locust Tree,                                              465
  622. Male Fern                                                465, 466


  PART VII.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL
  SUBSTANCES.


  DIVISION I.--POISONS SECRETED BY LIVING ANIMALS.


  I. POISONOUS AMPHIBIA.

  623. Poisonous Properties of the Skin of the _Salamandra Maculosa_
       --Salamandrine, &c.,                                          467
  624. Poison from the Toad,                                         468


  II. THE POISON OF THE SCORPION.

  625. Various Species of Scorpions--Effects of the Scorpion Poison, 468


  III. POISONOUS FISH.

  626. Poisonous Fish--Illustrative Cases,                       468-470


  IV. POISONOUS SPIDERS AND INSECTS.

  627. The Bite of the Tarantula--The Bite of the _Latrodectus
       Malmignatus_,                                                 470
  628. Effects of the Bite of the Katipo,                            471
  629. Ants, &c.,                                                    471
  630. The Poison of Wasps, Bees, and Hornets,                       471
  631. Cantharides,                                                  471
  632. Cantharidin,                                             471, 472
  633. Pharmaceutical Preparations of Cantharides,                   472
  634. Fatal Dose,                                                   472
  635. Effects on Animals--Radecki’s Experiments--Effects on Man--
       Heinrich’s Auto-Experiments,                             472, 473
  636. General Symptoms Produced by Cantharides,                473, 474
  637. _Post-mortem_ Appearances,                                    474
  638. Tests for Cantharidin--Distribution in the Body--Dragendorff’s
       Process,                                                  475-477


  V. SNAKE POISON.

  639. Classes of Poisonous Snakes,                                  477
  640. The Poison of the Cobra,                                      478
  641. Fatal Dose of Cobra Poison,                                   479
  642. Effects on Animals,                                           479
  643. Effects on Man,                                          479, 480
  644. Antidotes and Treatment--Halford’s Treatment by Ammonia--
       Permanganate of Potash,                                  480, 481
  645. Detection of the Cobra Venom,                                 482
  646. Effects of the Bite of the _Duboia Russellii_, or Russell’s
       Viper,                                                        483
  647. The Poison of the Common Viper--The Venom of Naja Haje
       (Cleopatra’s Asp),                                       483, 484


  DIVISION II.--PTOMAINES--TOXINES.

  648. Definition of a Ptomaine,                                     485


  _Isolation of Ptomaines._

  649. Gautier’s Process,                                            485
  650. Brieger’s Process,                                        485-487
  651. Benzoyl Chloride Method,                                 487, 488
  652. The Amines,                                               488-490
  653. Methylamine,                                                  491
  654. Dimethylamine,                                                491
  655. Trimethylamine,                                               491
  656. Ethylamine,                                                   491
  657. Diethylamine,                                                 491
  658. Triethylamine,                                                491
  659. Propylamine,                                                  491
  660. Isoamylamine,                                                 492


  _Diamines._

  661. Rate of Formation of Diamines,                                492
  662. Ethylidenediamine,                                            492
  663. Neuridine,                                               493, 494
  664. Cadaverine,                                               494-496
  665. Putrescine,                                                   496
  666. Metaphenylenediamine,                                         497
  667. Paraphenylenediamine,                                         497
  668. Hexamethylenediamine,                                         497
  669. Diethylenediamine,                                       497, 498
  670. Mydaleine,                                                    498
  671. Guanidine,                                               498, 499
  672. Methylguanidine,                                         499, 500
  673. Saprine,                                                      500
  674. The Choline Group,                                       500, 501
  675. Neurine,                                                      501
  676. Betaine,                                                 501, 502
  677. Peptotoxine,                                                  502
  678. Pyridine-like Alkaloid from the Cuttle-fish,             502, 503
  679. Poisons connected with Tetanus--Tetanine,                     503
  680. Tetanotoxine,                                            503, 504
  681. Mydatoxine,                                                   504
  682. Mytilotoxine,                                                 505
  683. Tyrotoxicon,                                             504, 505
  684. Toxines connected with Hog Cholera,                      505, 506
  685. Other Ptomaines,                                              506


  DIVISION III.--FOOD POISONING.

  686. The Welbeck--The Oldham--The Bishop Stortford--The
       Wolverhampton--The Carlisle, and other Mass Poisonings by
       changed Food--Statistics of Deaths from Unwholesome Food, 506-508
  687. German Sausage Poisoning,                                     509


  PART VIII.--THE OXALIC ACID GROUP OF POISONS.

  688. Distribution of Oxalic Acid in the Animal and Vegetable
       Kingdoms,                                                     510
  689. Properties and Reactions of Oxalic Acid,                 510, 511
  690. Oxalate of Lime; its Properties,                         511, 512
  691. Use of Oxalic Acid in the Arts,                               512
  692. Properties of Hydropotassic Oxalate (Binoxalate of Potash),   512
  693. Statistics of Oxalic Acid Poisoning,                          512
  694. Fatal Dose of Oxalic Acid,                                    513
  695. Effects of Oxalic Acid and Oxalates on Animals,               513
  696. Researches of Kobert and Küssner on the Effects of Sodic
       Oxalate,                                                 513, 514
  697. Effects of Vaporised Oxalic Acid,                        514, 515
  698. Effects of Oxalic Acid and Hydropotassic Oxalate on Man--
       Illustrative Cases,                                      515, 516
  699. Physiological Action,                                    516, 517
  700. Pathological Changes produced by Oxalic Acid and the Oxalates,
                                                                517, 518
  701. Preparations in Museums Illustrative of the Effects of Oxalic
       Acid,                                                         518
  702. Pathological Changes produced by the Acid Oxalate of Potash,
                                                                518, 519
  703. Separation of Oxalic Acid from Organic Substances, the Tissues
       of the Body, &c.,                                         519-521
  704. Oxalate of Lime in the Urine,                                 521
  705. Estimation of Oxalic Acid,                               521, 522


  _Certain Oxalic Bases--Oxalmethyline--Oxalpropyline._

  706. The Experiments of Schulz and Mayer on Oxalmethyline,
       Chloroxalmethyline, and Oxalpropyline,                   522, 523


  PART IX.--INORGANIC POISONS.


  I. PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC SULPHIDE--
  PRECIPITATE YELLOW OR ORANGE.


  ARSENIC--ANTIMONY--CADMIUM.


  1. _Arsenic._

  707. Metallic Arsenic; its Chemical and Physical Properties,       524
  708. Arsenious Anhydride--Arsenious Acid; its Properties and
       Solubility,                                              524, 525
  709. Arseniuretted Hydrogen (Arsine),                          525-527
  710. Arseniuretted Hydrogen in the Arts, &c,                       527
  711. The Effects of Arseniuretted Hydrogen on Man--Illustrative
       Cases,                                                   527, 528
  712. The Sulphides of Arsenic,                                528, 529
  713. Orpiment, or Arsenic Trisulphide,                             529
  714. Haloid Arsenical Compounds--Chloride of Arsenic--Iodide of
       Arsenic,                                                      529
  715. Arsenic in the Arts,                                     529, 530
  716. Pharmaceutical Preparations of Arsenic--Veterinary Arsenical
       Medicines--Rat and Fly Poisons--Quack Nostrums--Pigments--
       External Application of Arsenic for Sheep--Arsenical Soaps--
       Arsenical Compounds used in Pyrotechny,                   530-534
  717. Statistics of Poisoning by Arsenic,                           534
  718. Law Relative to the Sale of Arsenic,                          535
  719. Dose of Arsenic,                                              535
  720. Effects of Arsenious Acid on Plants,                     535, 536
  721. Effects of Arsenic upon Life--Animalcules--Annelids--Birds--
       Mammals,                                                  536-538
  722. Effects of Arsenious Acid on Man--Arsenic Eaters,        538, 539
  723. Manner of Introduction of Arsenic,                            539
  724. Cases of Poisoning by the External Application of Arsenic,
                                                                 539-541
  725. Arsenic in Wall-Papers,                                  541, 542
  726. Forms of Arsenical Poisoning--Acute Form,                     542
  727. Subacute Form--Case of the Duc de Praslin,                    543
  728. Nervous Form--Brodie’s Experiments on Rabbits--A “Mass”
       Poisoning reported by Dr. Coqueret,                      544, 545
  729. Absence of Symptoms,                                     545, 546
  730. Slow Poisoning,                                               546
  731. The Maybrick Case,                                        546-548
  732. Post-mortem Appearances met with in Animals after Arsenical
       Poisoning--The Researches of Hugo,                       548, 549
  733. Post-mortem Appearances in Man--Illustrative Pathological
  Preparations in Various Museums,                               549-551
  734. Pathological Changes induced in the Gullet and Stomach--Fatty
       Degeneration of the Liver and Kidneys--Glossitis--Retardation of
       Putrefaction,                                            551, 552
  735. Physiological Action of Arsenic,                         552, 553
  736. Elimination of Arsenic--Question of Accumulation of Arsenic,  553
  737. Antidotes and Treatment,                                 553, 554
  738. Detection of Arsenic--Identification of Arsenious Acid in
       Substance--Test of Berzelius--Identification of Arsenites and
       Arseniates--Detection of Arsenious Acid in Solution--
       Distinguishing Marks between the Sulphides of Tin, Cadmium,
       Antimony, and Arsenic--Marsh’s Original Test for Arsenic--
       Blondlot’s Modification of Marsh’s Test--Distinguishing Marks
       between Arsenical and Antimonial Mirrors--Reinsch’s Tests,
                                                                 554-560
  739. Arsenic in Glycerin,                                          560
  740. Arsenic in Organic Matters--Orfila’s Method of Destroying
       Organic Matter--Extraction with Hydrochloric Acid--Modifications
       in the Treatment of Oils--Resinous Matters--Experiments on the
       Distribution of Arsenic by Scolosuboff, Ludwig, and Chittenden--
       The Question of Contamination of a Corpse by Arsenical Earth,
                                                                 560-562
  741. Imbibition of Arsenic after Death--Mason’s Case,          563-565
  742. Analysis of Wall-Paper for Arsenic,                      565, 566
  743. Estimation of Arsenic--Galvanic Process of Bloxam--Colorimetric
       Methods,                                                  566-568
  744. Destruction of the Organic Matter by Nitric Acid, and Subsequent
       Reduction of the Arsenic Acid to Arseniuretted Hydrogen, and
       Final Estimation as Metallic Arsenic,                     568-571
  745. Arsine developed from an Alkaline Solution,                   571
  746. Precipitation as Tersulphide--Methods of Dealing with the
       Sulphides obtained--(_a_) Solution in Ammonia and Estimation by
       Iodine--(_b_) Drying the Purified Precipitate at a High
       Temperature, and then directly weighing--(_c_) Oxidation of the
       Sulphide and Precipitation as Ammonia Magnesian Arseniate, or
       Magnesia Pyro Arseniate--(_d_) Conversion of the Trisulphide of
       Arsenic into the Arseno-Molybdate of Ammonia--Conversion of the
       Sulphide into Metallic Arsenic,                           571-575
  747. Conversion of Arsenic into Arsenious Chloride,           575, 576


  2. _Antimony._

  748. Properties of Metallic Antimony,                              577
  749. Antimonious Sulphides,                                   577, 578
  750. Tartarated Antimony--Tartar Emetic,                      578, 579
  751. Metantimonic Acid,                                            579
  752. Pharmaceutical, Veterinary, and Quack Preparations of Antimony--
       (1)Pharmaceutical Preparations--(2) Patent and Quack Pills--(3)
       Antimonial Medicines, chiefly Veterinary,                 579-582
  753. Alloys,                                                       582
  754. Pigments,                                                     582
  755. Dose,                                                         582
  756. Effects of Tartar Emetic on Animals--Influence on Temperature--
       Dr. Nevin’s Researches on Rabbits,                       582, 583
  757. Effects of Tartar Emetic on Man--Illustrative Cases,     583, 584
  758. Chronic Antimonial Poisoning,                                 585
  759. _Post-mortem_ Appearances--Preparations in Museums--Pathological
       Appearances in Rabbits, according to Nevin,              585, 586
  760. Elimination of Antimony,                                      586
  761. Antidotes for Tartar Emetic,                                  586
  762. Effects of Chloride or Butter of Antimony,                    587
  763. Detection of Antimony in Organic Matters,                 587-589
  764. Quantitative Estimation of Antimony,                     589, 590


  3. _Cadmium._

  765. Properties of the Metal Cadmium,                              590
  766. Cadmium Oxide,                                                590
  767. Cadmium Sulphide,                                             590
  768. Medicinal Preparations of Cadmium--Cadmium Iodide--Cadmium
       Sulphate,                                                     590
  769. Cadmium in the Arts,                                          590
  770. Fatal Dose of Cadmium,                                        590
  771. Separation and Detection of Cadmium,                     590, 591


  II. PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID SOLUTION--
  BLACK.

  LEAD--COPPER--BISMUTH--SILVER--MERCURY.


  1. _Lead._

  772. Lead and its Oxides--Litharge--Minium, or Red Lead,      591, 592
  773. Sulphide of Lead,                                             592
  774. Sulphate of Lead,                                             592
  775. Acetate of Lead,                                              592
  776. Chloride of Lead--Carbonate of Lead,                     592, 593
  777. Preparations of Lead used in Medicine, the Arts, &c.--(1)
       Pharmaceutical--(2) Quack Nostrums--(3) Preparations used in the
       Arts--Pigments--Hair Dyes--Alloys,                       593, 594
  778. Statistics of Lead-Poisoning,                                 594
  779. Lead as a Poison--Means by which Lead may be taken into the
       System,                                                  595, 596
  780. Effects of Lead Compounds on Animals,                    596, 597
  781. Effects of Lead Compounds on Man--Acute Poisoning--Mass
       Poisoning by Lead--Case of Acute Poisoning by the Carbonate of
       Lead,                                                     597-599
  782. Chronic Poisoning by Lead,                               599, 600
  783. Effects of Lead on the Nervous System--Lead as a Factor of
       Insanity                                                 600, 601
  784. Amaurosis Caused by Lead-Poisoning--Influence on the Sexual
       Functions--Caries--Epilepsy,                              601-603
  785. Uric Acid in the Blood after Lead-Poisoning,                  603
  786. Influence of Lead on Pregnant Women and on Fœtal Life--The
       Keighley Case of Poisoning by Water Contaminated by Lead--Case
       of _Reg._ v. _L. J. Taylor_,                              603-605
  787. _Post-mortem_ Appearances,                                    605
  788. Physiological Action of Lead,                            605, 606
  789. Elimination of Lead,                                          606
  790. Fatal Dose,                                              606, 607
  791. Antidotes and Treatment,                                      607
  792. Localisation of Lead,                                    607, 608
  793. Detection and Estimation of Lead,                        608, 609
  794. Detection of Lead in Tartaric Acid, in Lemonade and Aërated
       Waters,                                                  609, 610


  2. _Copper._

  795. Properties of Copper,                                         610
  796. Cupric Oxide,                                                 610
  797. Cupric Sulphide,                                              610
  798. Solubility of Copper in Water and Various Fluids--Experiments of
       Carnelley, W. Thompson, and Lehmann,                      610-612
  799. Copper as a Normal Constituent of Animal, Vegetable, and other
       Matters--Dupré’s Experiments--Bergeron and L. L’Hôte’s
       Researches,                                               612-614
  800. The “Coppering” of Vegetables--Copper in Green Peas--
       Phyllocyanic Acid,                                       614, 615
  801. Preparations of Copper used in Medicine and the Arts--(1)
       Medicinal Preparations--(2) Copper in the Arts,          615, 616
  802. Dose--Medicinal Dose of Copper,                          616, 617
  803. Effects of Soluble Copper Salts on Animals,               617-619
  804. Toxic Dose of Copper Salts,                                   619
  805. Cases of Acute Poisoning,                                619, 620
  806. Effects of Subacetate, Subchloride, and Carbonate of Copper,  620
  807. _Post-mortem_ Appearances seen in Acute Poisoning by Copper,
                                                                620, 621
  808. Chronic Poisoning by Copper,                             621, 622
  809. Detection and Estimation of Copper--General Method--Special
       Method for Copper in Solution in Water and other Liquids--
       Detection of Copper in Animal Matters,                    622-624
  810. Volumetric Processes for the Estimation of Copper,            624


  3. _Bismuth._

  811. Bismuth as a Metal,                                           624
  812. Teroxide of Bismuth,                                          624
  813. The Sulphide of Bismuth,                                      624
  814. Preparations of Bismuth used in Medicine and the Arts--(1)
       Pharmaceutical Preparations--(2) Bismuth in the Arts,    624, 625
  815. Medicinal Doses of Bismuth,                                   625
  816. Toxic Effects of Sub-nitrate of Bismuth,                 625, 626
  817. Extraction and Detection of Bismuth in Animal Matter,    626, 627
  818. Estimation of Bismuth--Volumetric Processes,             627, 628


  4. _Silver._

  819. Properties of Metallic Silver,                           628, 629
  820. Chloride of Silver,                                           629
  821. Sulphide of Silver,                                           629
  822. Preparations of Silver used in Medicine and the Arts--(1)
       Medicinal Preparations--(2) Silver in the Arts,          629, 630
  823. Medicinal Dose of Silver Compounds,                           630
  824. Effects of Nitrate of Silver on Animals--Chronic Poisoning,
                                                                630, 631
  825. Toxic Effects of Silver Nitrate on Man--(1) Acute--(2) Chronic
       Poisoning,                                               631, 632
  826. _Post-mortem_ Appearances,                                    632
  827. Detection and Estimation of Silver,                      632, 633


  5. _Mercury._

  828. The Metal Mercury--Mercurous Chloride, or Calomel,       633, 634
  829. Sulphide of Mercury,                                          634
  830. Medicinal Preparations of Mercury,                        634-638
  831. Mercury in the Arts--The Sulphocyanide of Mercury--Acid Solution
       of Nitrate of Mercury,                                        639
  832. The more common Patent and Quack Medicines containing Mercury,
                                                                639, 640
  833. Mercury in Veterinary Medicine,                               640
  834. Medicinal and Fatal Dose,                                640, 641
  835. Poisoning by Mercury--Statistics,                             641
  836. Effects of Mercurial Vapour and of the Non-Corrosive Compounds
       of Mercury--(_a_) On Vegetable Life--(_b_) On Animal Life,
                                                                641, 642
  837. Effects on Man,                                          642, 643
  838. Absorption of Mercury by the Skin,                            643
  839. Symptoms of Poisoning by Mercury Vapour,                 643, 644
  840. Mercurial Tremor,                                        644, 645
  841. Mercuric Methide--Effects of, as Illustrated by two Cases,
                                                                645, 646
  842. Effects of the Corrosive Salts of Mercury,               646, 647
  843. Death from the External Use of Corrosive Sublimate,           647
  844. Effects of the Nitrates of Mercury,                           647
  845. Case of _Reg._ v. _E. Smith_,                                 648
  846. Mercuric Cyanide,                                             648
  847. White Precipitate,                                            648
  848. Treatment of Acute and Chronic Poisoning,                     648
  849. _Post-mortem_ Appearances--Pathological Preparations in Various
  Anatomical Museums,                                            648-650
  850. Pathological Appearances from the Effects of Nitrate of Mercury,
                                                                     650
  851. Elimination of Mercury,                                  650, 651
  852. Tests for Mercury,                                       651, 652
  853. The Detection of Mercury in Organic Substances and Fluids,
                                                                 652-654
  854. Estimation of Mercury--The Dry Method,                        654
  855. Volumetric Processes for the Estimation of Mercury,      654, 655


  III. PRECIPITATED BY HYDRIC SULPHIDE FROM A NEUTRAL SOLUTION.

  ZINC--NICKEL--COBALT.


  1. _Zinc._

  856. Properties of Metallic Zinc,                             655, 656
  857. Carbonate of Zinc,                                            656
  858. Oxide of Zinc,                                                656
  859. Sulphide of Zinc--Sulphate of Zinc,                           656
  860. Preparation and Uses of Chloride of Zinc,                656, 657
  861. Zinc in the Arts--Zinc Chromate--Zinc Pigments--Action of Fluids
       on Zinc Vessels,                                         657, 658
  862. Effects of Zinc, as shown by Experiments on Animals,          658
  863. Effects of Zinc Compounds on Man--Zinc Oxide,            658, 659
  864. Sulphate of Zinc,                                             659
  865. Zinc Chloride,                                           659, 660
  866. _Post-mortem_ Appearances--Illustrated by Specimens in
       Pathological Museums,                                    660, 661
  867. Detection of Zinc in Organic Liquids or Solids,          661, 662
  868. Identification of Zinc Sulphide,                              662


  2. _Nickel--Cobalt._

  869. Experiments of Anderson Stuart on the Toxic Action of Nickel and
       Cobalt,                                                  662, 663
  870. Symptoms witnessed in various Classes of Animals after taking
       Doses of Nickel or Cobalt,                               663, 664
  871. Effects on the Circulation and Nervous System,                664
  872. Action on Striped Muscle,                                     664
  873. Separation of Nickel or Cobalt from the Organic Matters or
       Tissues,                                                 664, 665
  874. Estimation of Cobalt or Nickel,                               665


  IV. PRECIPITATED BY AMMONIUM SULPHIDE.

  IRON--CHROMIUM--THALLIUM--ALUMINIUM--URANIUM.


  1. _Iron._

  875. Poisonous and Non-Poisonous Salts of Iron,                    665
  876. Ferric Chloride--Pharmaceutical Preparations of Ferric Chloride,
                                                                     666
  877. Effects of Ferric Chloride on Animals,                        666
  878. Effects on Man--Criminal Case at Martinique,             666, 667
  879. Elimination of Ferric Chloride,                          667, 668
  880. _Post-mortem_ Appearances,                                    668
  881. Ferrous Sulphate,                                        668, 669
  882. Search for Iron Salts in the Contents of the Stomach,    669, 670


  2. _Chromium._

  883. Neutral Chromate of Potash,                                   670
  884. Potassic Bichromate,                                          670
  885. Neutral Lead Chromate,                                   670, 671
  886. Use in the Arts,                                              671
  887. Effects of some of the Chromium Compounds on Animal Life,     671
  888. Effects of some of the Chromium Compounds on Man--Bichromate
       Disease,                                                 671, 672
  889. Acute Poisoning by the Chromates--Illustrative Cases,    672, 673
  890. Lethal Effects of Chromate of Lead,                           673
  891. _Post-mortem_ Appearances,                                    674
  892. Detection of the Chromates and Separation of the Salts of
       Chromium from the Contents of the Stomach,               674, 675


  3. _Thallium._

  893. Discovery of Thallium--Its Properties,                   675, 676
  894. Effects of Thallium Salts,                                    676
  895. Separation of Thallium from Organic Fluids or Tissues,        676


  4. _Aluminium._

  896. Aluminium and its Salts,                                 676, 677
  897. Action of Alum Salts--Siem’s Researches--Alum Baking-Powders,
                                                                677, 678
  898. _Post-mortem_ Appearances,                                    678
  899. Detection of Alumina,                                    678, 679


  5. _Uranium._

  900. Poisonous Properties of Uranium Salts,                        679
  901. Detection and Estimation of Uranium,                          679


  V. ALKALINE EARTHS.


  BARIUM.

  902. Salts of Barium in Use in the Arts,                      679, 680
  903. Chloride of Barium,                                           680
  904. Baric Carbonate,                                              680
  905. Sulphate of Barium,                                           680
  906. Effects of the Soluble Salts of Barium on Animals,            681
  907. Effects of the Salts of Barium on Man--Fatal Dose,       681, 682
  908. Symptoms,                                                682, 683
  909. Distribution of Barium in the Body,                           683
  910. _Post-mortem_ Appearances,                               683, 684
  911. Separation of Barium Salts from Organic Solids or Fluids, and
       their Identification,                                         684


  APPENDIX.


  TREATMENT, BY ANTIDOTES OR OTHERWISE, OF CASES OF POISONING.

  912.  Instruments, Emetics, and Antidotes Proper for Furnishing an
        Antidote Bag,                                           685, 686
  913.  Poisons Arranged Alphabetically--Details of Treatment,   687-700


  DOMESTIC READY REMEDIES FOR POISONING.

  914.  The “Antidote Cupboard,” and How to Furnish it,              701


  LIST OF ILLUSTRATIONS.

  Williams’ Apparatus for Investigating Action of Poisons on the Frog’s
  Heart,                                                              44
  Ether Recovery Apparatus,                                           47
  Micro-spectroscope,                                                 48
  Diagram showing Absorption Bands Produced from Colour Reactions,    55
  Hæmatin Crystals,                                                   61
  Tube for Treatment of Liquids by Ethereal Solvents,                156
  Diagram of Visual Field in Dinitro-benzol Poisoning,               190
  Blondlot’s Apparatus for Production of Phosphine,                  231
  Apparatus for Sublimation,                                         258
  Brucine Hydriodide,                                                342
  Bocklisch’s Flask for Distillation in a Vacuum,                    486
  Berzelius’ Tube for Reduction of Arsenic,                          554
  Bent Tube for Assay of Mercury,                                    654

  Folding-Chart (Deaths from Intemperance and Liver Disease), to face
                                                                 p.  136




  POISONS:
  THEIR EFFECTS AND DETECTION.




PART I.--INTRODUCTORY.


I.--The Old Poison-Lore.

§ 1. It is significant that the root “_tox_” of the modern word
_toxicology_ can be traced back to a very ancient word meaning “bow” or
“arrow,” or, in its broadest sense, some “tool” used for slaying: hence
it is no far-fetched supposition that the first poison-knowledge was
that of the septic poisons. Perchance the savage found that weapons
soiled with the blood of former victims made wounds fatal; from this
observation the next step naturally would be that of experiment--the
arrow or spear would be steeped in all manner of offensive pastes, and
smeared with the vegetable juices of those plants which were deemed
noxious; and as the effects were mysterious, they would be ascribed to
the supernatural powers, and covered with a veil of superstition.

The history of the _poison-lehre_, like all history, begins in the
region of the myths: there was a dark saga prevailing in Greece, that in
the far north existed a land ruled by sorcerers--all children of the
sun--and named Aeëtes, Perses, Hecate, Medea, and Circe. Later on, the
enchanted land was localised at Colchis, and Aeëtes and Perses were said
to be brothers. Hecate was the daughter of Perses; she was married to
Aeëtes, and their daughters were Medea and Circe. Hecate was the
discoverer of poisonous herbs, and learned in remedies both evil and
good. Her knowledge passed to Medea, who narcotised the dragon, the
guardian of the golden fleece, and incited Jason to great undertakings.

In the expedition of the Argonauts, the poets loved to describe Hecate’s
garden, with its lofty walls. Thrice-folding doors of ebony barred the
entrance, which was guarded by terrible forms: only the initiated few,
only they who bore the leavened rod of expiation, and the concealed
conciliatory offering of the Medea, could enter into the sanctuary.
Towering above all was the temple of the dread Hecate, whose priestesses
offered to the gods ghastly sacrifices.

§ 2. The oldest Egyptian king, Menes, and Attalus Phylometer, the last
king of Pergamus, were both famous for their knowledge of plants.
Attalus Phylometer was acquainted with hyoscyamus, aconite, conium,
veratrum, and others; he experimented on the preparation of poisons, and
occupied himself in compounding medicines. Mithradetes Eupator stood yet
higher: the receipt for the famous _theriaca_, prepared in later years
at an enormous price, and composed of fifty-four different ingredients,
is ascribed to him. The wonderful skill shown by the Egyptians in
embalming and technical works is sufficient to render it fairly certain
that their chemical knowledge was considerable; and the frequent
operations of one caste upon the dead must have laid the foundations of
a pathological and anatomical culture, of which only traces remain.

The Egyptians knew prussic acid as extracted in a dilute state from
certain plants, among the chief of which was certainly the peach; on a
papyrus preserved at the Louvre, M. Duteil read, “Pronounce not the name
of I. A. O. under the penalty of the peach!” in which dark threat,
without doubt, lurks the meaning that those who revealed the religious
mysteries of the priests were put to death by waters distilled from the
peach. That the priests actually distilled the peach-leaves has been
doubted by those who consider the art of distillation a modern
invention; but this process was well known to adepts of the third and
fourth centuries, and there is no inherent improbability in the
supposition that the Egyptians practised it.

§ 3. From the Egyptians the knowledge of the deadly drink appears to
have passed to the Romans. At the trial of Antipater,[1] Verus brought a
potion derived from Egypt, which had been intended to destroy Herod;
this was essayed on a criminal, he died at once. In the reign of
Tiberius, a Roman knight, accused of high treason, swallowed a poison,
and fell dead at the feet of the senators: in both cases the rapidity of
action appears to point to prussic acid.

[1] Jos. Ant., B. xvii. c. 5.

The use of poison by the Greeks, as a means of capital punishment,
without doubt favoured suicide by the same means; the easy, painless
death of the state prisoner would be often preferred to the sword by one
tired of life. The ancients looked indeed upon suicide, in certain
instances, as something noble, and it was occasionally formally
sanctioned. Thus, Valerius Maximus tells us that he saw a woman of
quality, in the island of Ceos, who, having lived happily for ninety
years, obtained leave to take a poisonous draught, lest, by living
longer, she should happen to have a change in her good fortune; and,
curiously enough, this sanctioning of self-destruction seems to have
been copied in Europe. Mead relates that the people of Marseilles of old
had a poison, kept by the public authorities, in which cicuta was an
ingredient: a dose was allowed to any one who could show why he should
desire death. Whatever use or abuse might be made of a few violent
poisons, Greek and Roman knowledge of poisons, their effects and methods
of detection, was stationary, primitive, and incomplete.

_Nicander of Colophon_ (204-138 B.C.) wrote two treatises, the most
ancient works on this subject extant, the one describing the effects of
snake venom; the other, the properties of opium, henbane, certain fungi,
colchicum, aconite, and conium. He divided poisons into those which kill
quickly, and those which act slowly. As antidotes, those medicines are
recommended which excite vomiting--_e.g._, lukewarm oil, warm water,
mallow, linseed tea, &c.

_Apollodorus_ lived at the commencement of the third century B.C.: he
wrote a work on poisonous animals, and one on deleterious medicines;
these works of Apollodorus were the sources from which Pliny,
Heraclitus, and several of the later writers derived most of their
knowledge of poisons.

_Dioscorides_ (40-90 A.D.) well detailed the effects of cantharides,
sulphate of copper, mercury, lead, and arsenic. By arsenic he would
appear sometimes to mean the sulphides, sometimes the white oxide.
Dioscorides divided poisons, according to their origin, into three
classes, viz.:--

1. =Animal Poisons.=--Under this head were classed cantharides and
allied beetles, toads, salamanders, poisonous snakes, a particular
variety of honey, and the blood of the ox, probably the latter in a
putrid state. He also speaks of the “_sea-hare_.” The sea-hare was
considered by the ancients very poisonous, and Domitian is said to have
murdered Titus with it. It is supposed by naturalists to have been one
of the genus _Aplysia_, among the _gasteropods_. Both Pliny and
Dioscorides depict the animal as something very formidable: it was not
to be looked at, far less touched. The aplysiæ exhale a very nauseous
and fœtid odour when they are approached: the best known of the species
resembles, when in a state of repose, a mass of unformed flesh; when in
motion, it is like a common slug; its colour is reddish-brown; it has
four horns on its head; and the eyes, which are very small, are situated
between the two hinder ones. This aplysia has an ink reservoir, like the
sepia, and ejects it in order to escape from its enemies; it inhabits
the muddy bottom of the water, and lives on small crabs, mollusca, &c.

2. =Poisons from Plants.=--Dioscorides enumerates opium, black and white
hyoscyamus (especially recognising the activity of the seeds),
mandragora, which was probably a mixture of various solanaceæ, conium
(used to poison the condemned by the people of Athens and the dwellers
of ancient Massilia), elaterin, and the juices of a species of euphorbia
and apocyneæ. He also makes a special mention of aconite, the name of
which is derived from _Akon_, a small city in Heraclea. The Greeks were
well aware of the deadly nature of aconite, and gave to it a mythical
origin, from the foam of the dog Cerberus. Colchicum was also known to
Dioscorides: its first use was ascribed to Medea. Veratrum album and
nigrum were famous medicines of the Romans, and a constituent of their
“_rat and mice powders_;” they were also used as insecticides. According
to Pliny, the Gauls dipped their arrows in a preparation of veratrum.[2]
Daphne mezereon, called by the Romans also smilax and taxus, appears to
have been used by Cativolcus, the king of the Eburones, for the purpose
of suicide, or possibly by “taxus” the yew-tree is meant.[3]

[2] Pliny, xxv. 5.

[3] _De Bello Gallico_, vi. 31.

The poisonous properties of certain fungi were also known. Nicander
calls the venomous mushrooms the “evil fermentation of the earth,” and
prescribes the identical antidotes which we would perhaps give at the
present time--viz., vinegar and alkaline carbonates.

3. =Mineral Poisons.=--Arsenic has been already alluded to. The ancients
used it as a caustic and depilatory. Copper was known as sulphate and
oxide; mercury only as cinnabar: lead oxides were used, and milk and
olive-oil prescribed as an antidote for their poisonous properties. The
_poison-lehre_ for many ages was considered as something forbidden.
Galen, in his treatise “On Antidotes,” remarks that the only authors who
dared to treat of poisons were Orpheus, Theologus, Morus, Mendesius the
younger, Heliodorus of Athens, Aratus, and a few others; but none of
these treatises have come down to us. From the close similarity of the
amount of information in the treatises of Nicander, Dioscorides, Pliny,
Galen, and Paulus Ægineta, it is probable that all were derived from a
common source.

§ 4. If we turn our attention to early Asiatic history, a very cursory
glance at the sacred writings of the East will prove how soon the art of
poisoning, especially in India, was used for the purpose of suicide,
revenge, or robbery.

The ancient practice of the Hindoo widow--self-immolation on the burning
pile of her husband--is ascribed to the necessity which the Brahmins
were under of putting a stop to the crime of domestic poisoning. Every
little conjugal quarrel was liable to be settled by this form of secret
assassination, but such a law, as might be expected, checked the
practice.

Poison was not used to remove human beings alone, for there has been
from time immemorial in India much cattle-poisoning. In the Institutes
of Menu, it is ordained that when cattle die the herdsman shall carry to
his master their ears, their hides, their tails, the skin below their
navels, their tendons, and the liquor oozing from their foreheads.
Without doubt these regulations were directed against cattle-poisoners.

The poisons known to the Asiatics were arsenic, aconite, opium, and
various solanaceous plants. There has been a myth floating through the
ages that a poison exists which will slay a long time after its
introduction. All modern authors have treated the matter as an
exaggerated legend, but, for my own part, I see no reason why it should
not, in reality, be founded on fact. There is little doubt that the
Asiatic poisoners were well acquainted with the infectious qualities of
certain fevers and malignant diseases. Now, these very malignant
diseases answer precisely to the description of a poison which has no
immediate effects. Plant small-pox in the body of a man, and for a whole
fortnight he walks about, well and hearty. Clothe a person with a
garment soaked in typhus, and the same thing occurs--for many days there
will be no sign of failure. Again, the gipsies, speaking a tongue which
is essentially a deformed _prakrit_, and therefore Indian in origin,
have long possessed a knowledge of the properties of the curious “_mucor
phycomyces_.” This was considered an alga by Agaron, but Berkeley
referred it to the fungi. The gipsies are said to have administered the
spores of this fungi in warm water. In this way they rapidly attach
themselves to the mucous membrane of the throat, all the symptoms of a
phthisis follow, and death takes place in from two to three weeks. Mr
Berkeley informed me that he has seen specimens growing on broth which
had been rejected from the stomach, and that it develops in enormous
quantities on oil-casks and walls impregnated with grease. The filaments
are long, from 12 to 18 inches, and it is capable of very rapid
development.

There is also a modern poison, which, in certain doses, dooms the
unfortunate individual to a terrible malady, simulating, to a
considerable extent, natural disease,--that is phosphorus. This poison
was, however, unknown until some time in the eleventh century, when
Alchid Becher, blindly experimenting on the distillation of urine and
carbon, obtained his “_escarboucle_,” and passed away without knowing
the importance of his discovery, which, like so many others, had to be
rediscovered at a later period.

§ 5. The Hebrews were acquainted with certain poisons, the exact nature
of which is not quite clear. The words “_rosch_” and “_chema_” seem to
be used occasionally as a generic term for poison, and sometimes to mean
a specific thing; “_rosch_,” especially, is used to signify some
poisonous parasitic plant. They knew yellow arsenic under the name of
“_sam_,” aconite under the name of “_boschka_,” and possibly “_son_”
means _ergot_.[4] In the later period of their history, when they were
dispersed through various nations, they would naturally acquire the
knowledge of those nations, without losing their own.

[4] R. J. Wunderbar, _Biblisch-talmudische Medicin_. Leipzig, 1850-60.

§ 6. The part that poison has played in history is considerable. The
pharmaceutical knowledge of the ancients is more graphically and
terribly shown in the deaths of Socrates, Demosthenes, Hannibal, and
Cleopatra, than in the pages of the older writers on poisons.

In the reign of Artaxerxes II. (Memnon), (B.C. 405-359), Phrysa poisoned
the queen Statira by cutting food with a knife poisoned on one side
only. Although this has been treated as an idle tale, yet two poisons,
aconite and arsenic, were at least well known; either of these could
have been in the way mentioned introduced in sufficient quantity into
food to destroy life.

In the early part of the Christian era professional poisoners arose, and
for a long time exercised their trade with impunity. Poisoning was so
much in use as a political engine that Agrippina (A.D. 26) refused to
eat of some apples offered to her at table by her father-in-law,
Tiberius.

It was at this time that the infamous Locusta flourished. She is said to
have supplied, with suitable directions, the poison by which Agrippina
got rid of Claudius; and the same woman was the principal agent in the
preparation of the poison that was administered to Britannicus, by order
of his brother Nero. The details of this interesting case have been
recorded with some minuteness.

It was the custom of the Romans to drink hot water, a draught nauseous
enough to us, but, from fashion or habit, considered by them a luxury;
and, as no two men’s tastes are alike, great skill was shown by the
slaves in bringing the water to exactly that degree of heat which their
respective masters found agreeable.[5]

[5] Tacitus, lib. xii., xiii. Mentioned also by Juvenal and Suetonius.

The children of the Imperial house, with others of the great Roman
families, sat at the banquets at a smaller side table, while their
parents reclined at the larger. A slave brings hot water to Britannicus;
it is too hot; Britannicus refuses it. The slave adds cold water; and it
is this cold water that is supposed to have been poisoned; in any case,
Britannicus had no sooner drunk of it than he lost voice and
respiration. Agrippina, his mother, was struck with terror, as well as
Octavia, his sister. Nero, the author of the crime, looks coldly on,
saying that such fits often happened to him in infancy without evil
result; and after a few moments’ silence the banquet goes on as before.
If this were not sudden death from heart or brain disease, the poison
must have been either a cyanide or prussic acid.

In those times no autopsy was possible: although the Alexandrian school,
some 300 years before Christ, had dissected both the living and the
dead, the work of Herophilus and Erasistratus had not been pursued, and
the great Roman and Greek writers knew only the rudiments of human
anatomy, while, as to pathological changes and their true
interpretation, their knowledge may be said to have been absolutely
_nil_. It was not, indeed, until the fifteenth century that the Popes,
silencing ancient scruples, authorised dissections; and it was not until
the sixteenth century that Vesalius, the first worthy of being
considered a great anatomist, arose. In default of pathological
knowledge, the ancients attached great importance to mere outward marks
and discolorations. They noted with special attention spots and
lividity, and supposed that poisons singled out the heart for some quite
peculiar action, altering its substance in such a manner that it
resisted the action of the funeral pyre, and remained unconsumed. It
may, then, fairly be presumed that many people must have died from
poison without suspicion, and still more from the sudden effects of
latent disease, ascribed wrongfully to poison. For example, the death of
Alexander was generally at that time ascribed to poison; but Littré has
fairly proved that the great emperor, debilitated by his drinking
habits, caught a malarious fever in the marshes around Babylon, and died
after eleven days’ illness. If, added to sudden death, the body, from
any cause, entered into rapid putrefaction, such signs were considered
by the people absolutely conclusive of poisoning: this belief, indeed,
prevailed up to the middle of the seventeenth century, and lingers still
among the uneducated at the present day. Thus, when Britannicus died, an
extraordinary lividity spread over the face of the corpse, which they
attempted to conceal by painting the face. When Pope Alexander VI. died,
probably enough from poison, his body (according to Guicciardini) became
a frightful spectacle--it was livid, bloated, and deformed; the gorged
tongue entirely filled the mouth; from the nose flowed putrid pus, and
the stench was horrible in the extreme.

All these effects of decomposition, we know, are apt to arise in coarse,
obese bodies, and accompany both natural and unnatural deaths; indeed,
if we look strictly at the matter, putting on one side the preservative
effects of certain metallic poisons, it may be laid down that generally
the corpses of those dying from poison are _less_ apt to decompose
rapidly than those dying from disease--this for the simple reason that a
majority of diseases cause changes in the fluids and tissues, which
render putrefactive changes more active, while, as a rule, those who
take poison are suddenly killed, with their fluids and tissues fairly
healthy.

When the Duke of Burgundy desired to raise a report that John, Dauphin
of France, was poisoned (1457), he described the imaginary event as
follows:--

“One evening our most redoubtable lord and nephew fell so grievously
sick that he died forthwith. His lips, tongue, and face were swollen;
his eyes started out of his head. It was a horrible sight to see--for so
look people that are poisoned.”

The favourite powder of the professional poisoner, arsenic, was known to
crowned heads in the fourteenth century; and there has come down to us a
curious document, drawn out by Charles le Mauvais, King of Navarre. It
is a commission of murder, given to a certain Woudreton, to poison
Charles VI., the Duke of Valois, brother of the king, and his uncles,
the Dukes of Berry, Burgundy, and Bourbon:--

“Go thou to Paris; thou canst do great service if thou wilt: do what I
tell thee; I will reward thee well. Thou shalt do thus: There is a thing
which is called sublimed arsenic; if a man eat a bit the size of a pea
he will never survive. Thou wilt find it in Pampeluna, Bordeaux,
Bayonne, and in all the good towns through which thou wilt pass, at the
apothecaries’ shops. Take it and powder it; and when thou shalt be in
the house of the king, of the Count de Valois, his brother, the Dukes of
Berry, Burgundy, and Bourbon, draw near, and betake thyself to the
kitchen, to the larder, to the cellar, or any other place where thy
point can be best gained, and put the powder in the soups, meats, or
wines, provided that thou canst do it secretly. Otherwise, do it not.”
Woudreton was detected, and executed in 1384.[6]

[6] _Trésor de Chartes._ Charles de Navarre. P. Mortonval, vol. ii. p.
384.

A chapter might be written entitled “royal poisoners.” King Charles IX.
even figures as an experimentalist.[7] An unfortunate cook has stolen
two silver spoons, and, since there was a question whether “_Bezoar_”
was an antidote or not, the king administers to the cook a lethal dose
of corrosive sublimate, and follows it up with the antidote; but the man
dies in seven hours, although Paré also gives him oil. Truly a grim
business!

[7] _Œuvres de Paré_, 2nd ed., liv. xx. _Des Vennes_, chap. xliv. p.
507.

The subtle method of removing troublesome subjects has been more often
practised on the Continent than in England, yet the English throne in
olden time is not quite free from this stain.[8] The use of poison is
wholly opposed to the Anglo-Saxon method of thought. To what anger the
people were wrought on detecting poisoners, is seen in the fact that, in
1542, a young woman was boiled alive in Smithfield for poisoning three
households.[9]

[8] For example, King John is believed to have poisoned Maud Fitzwalter
by “a poisoned egg.”

“In the reign of King John, the White Tower received one of the first
and fairest of a long line of female victims in that Maud Fitzwalter who
was known to the singers of her time as Maud the Fair. The father of
this beautiful girl was Robert, Lord Fitzwalter, of Castle Baynard, on
the Thames, one of John’s greatest barons. Yet the king, during a fit of
violence with the queen, fell madly in love with this young girl. As
neither the lady herself nor her powerful sire would listen to his
disgraceful suit, the king is said to have seized her by force at
Dunmow, and brought her to the Tower. Fitzwalter raised an outcry, on
which the king sent troops into Castle Baynard and his other houses; and
when the baron protested against these wrongs, his master banished him
from the realm. Fitzwalter fled to France with his wife and his other
children, leaving his daughter Maud in the Tower, where she suffered a
daily insult in the king’s unlawful suit. On her proud and scornful
answer to his passion being heard, John carried her up to the roof, and
locked her in the round turret, standing on the north-east angle of the
keep. Maud’s cage was the highest, chilliest den in the Tower; but
neither cold, nor solitude, nor hunger could break her strength. In the
rage of his disappointed love, the king sent one of his minions to her
room with a poisoned egg, of which the brave girl ate and died.”--_Her
Majesty’s Tower_, by Hepworth Dixon. Lond., 1869; i. p. 46.

[9] “This yeare, the 17th of March, was boyled in Smithfield one
Margaret Davie, a mayden, which had pouysoned 3 householdes that she
dwelled in. One being her mistress, which dyed of the same, and one
Darington and his wyfe, which she also dwelled with in Coleman Street,
which dyed of the same, and also one Tinleys, which dyed also of the
same.”--Wriotherley’s _Chronicle_, A.D. 1542.

§ 7. Two great criminal schools arose from the fifteenth to the
seventeenth centuries in Venice and Italy. The Venetian poisoners are of
earlier date than the Italian, and flourished chiefly in the fifteenth
century. Here we have the strange spectacle, not of the depravity of
individuals, but of the government of the State formally recognising
secret assassination by poison, and proposals to remove this or that
prince, duke, or emperor, as a routine part of their deliberations.
Still more curious and unique, the dark communings of “_the council of
ten_” were recorded in writing, and the number of those who voted for
and who voted against the proposed crime, the reason for the
assassination, and the sum to be paid, still exist in shameless black
and white. Those who desire to study this branch of secret history may
be referred to a small work by Carl Hoff, which gives a brief account of
what is known of the proceedings of the council. One example will here
suffice. On the 15th of December 1513 a Franciscan brother, John of
Ragubo, offered a selection of poisons, and declared himself ready to
remove any objectionable person out of the way. For the first successful
case he required a pension of 1500 ducats yearly, which was to be
increased on the execution of future services. The presidents, Girolando
Duoda and Pietro Guiarina, placed the matter before the “ten” on the 4th
of January 1514, and on a division (10 against 5) it was resolved to
accept so patriotic an offer, and to experiment first on the Emperor
Maximilian. The bond laid before the “ten” contained a regular
tariff--for the great Sultan 500 ducats, for the King of Spain 150
ducats, but the journey and other expenses were in each case to be
defrayed; the Duke of Milan was rated at 60, the Marquis of Mantua at
50, the Pope could be removed at 100 ducats. The curious offer thus
concludes:--“The farther the journey, the more eminent the man, the more
it is necessary to reward the toil and hardships undertaken, and the
heavier must be the payment.” The council appear to have quietly
arranged thus to take away the lives of many public men, but their
efforts were only in a few cases successful. When the deed was done, it
was registered by a single marginal note, “_factum_.”

What drugs the Venetian poisoners used is uncertain. The Italians
became notorious in the sixteenth and seventeenth centuries for their
knowledge of poisons, partly from the deeds of Toffana and others, and
partly from the works of J. Baptista Porta, who wrote a very
comprehensive treatise, under the title of _Natural Magic_,[10] and
managed to slide into the text, in the sections on cooking (_De Re
Coquinaria_, lib. xiv.), a mass of knowledge as to the preparation of
poisons. There are prescriptions that little accord with the title,
unless indeed the trades of cook and poisoner were the same. He gives a
method of drugging wine with belladonna root, for the purpose of making
the loaded guest loathe drink; he also gives a list of solanaceous
plants, and makes special mention of nux vomica, aconite, veratrum, and
mezereon. Again, in the section (_De Ancupio_, lib. xv.) he gives a
recipe for a very strong poison which he calls “_venenum lupinum_;” it
is to be made of the powdered leaves of _Aconitum lycoctonum_, _Taxus
baccata_, powdered glass, caustic lime, sulphide of arsenic, and bitter
almonds, the whole to be mixed with honey, and made into pills the size
of a hazel-nut.

[10] J. Bapt. Porta, born 1537, died 1615. _Neapolitani Magiæ
Naturalis._ Neapoli, 1589.

In the section _De Medicis Experimentis_ he gives a process to poison a
sleeping person: the recipe is curious, and would certainly not have the
intended effect. A mixture of hemlock juice, bruised datura, stramonium,
belladonna, and opium is placed in a leaden box with a perfectly fitting
cover, and fermented for several days; it is then opened under the nose
of the sleeper. Possibly Porta had experimented on small animals, and
had found that such matters, when fermented, exhaled enough carbonic
acid gas to kill them, and imagined, therefore, that the same thing
would happen if applied to the human subject. However this may be, the
account which Porta gives of the effects of the solanaceous plants, and
the general tone of the work, amply prove that he was no theorist, but
had studied practically the actions of poisons.

The iniquitous Toffana (or Tophana) made solutions of arsenious acid of
varying strength, and sold these solutions in phials under the name of
“_Acquetta di Napoli_” for many years. She is supposed to have poisoned
more than 600 persons, among whom were two Popes--viz., Pius III. and
Clement XIV. The composition of the Naples water was long a profound
secret, but is said to have been known by the reigning Pope and by the
Emperor Charles VI. The latter told the secret to Dr Garelli, his
physician, who, again, imparted the knowledge to the famous Friedrich
Hoffman in a letter still extant. Toffana was brought to justice in
1709, but, availing herself of the immunity afforded by convents,
escaped punishment, and continued to sell her wares for twenty years
afterwards. When Kepfer[11] was in Italy he found her in a prison at
Naples, and many people visited her, as a sort of lion (1730). With the
_Acqua Toffana_, the “_Acquetta di Perugia_” played at the same time its
part. It is said to have been prepared by killing a hog, disjointing the
same, strewing the pieces with white arsenic, which was well rubbed in,
and then collecting the juice which dropped from the meat; this juice
was considered far more poisonous than an ordinary solution of arsenic.
The researches of Selmi on compounds containing arsenic, produced when
animal bodies decompose in arsenical fluids, lend reason and support to
this view; and probably the juice would not only be very poisonous, but
act in a different manner, and exhibit symptoms different from those of
ordinary arsenical poisoning. Toffana had disciples; she taught the art
to Hieronyma Spara, who formed an association of young married women
during the popedom of Alexander VII.; these were detected on their own
confession.[12]

[11] Kepfer’s _Travels_. Lond., 1758.

[12] Le Bret’s _Magazin zu Gebrauche der Staat u. Kirchen-Geschichte_,
Theil 4. Frankfort and Leipzig, 1774.

Contemporaneously with Toffana, another Italian, Keli, devoted himself
to similar crimes. This man had expended much as an adept searching for
the philosopher’s stone, and sought to indemnify himself by entering
upon what must have been a profitable business. He it was who instructed
M. de St. Croix in the properties of arsenic; and St. Croix, in his
turn, imparted the secret to his paramour, Madame de Brinvilliers. This
woman appears to have been as cold-blooded as Toffana; she is said to
have experimented on the patients at the Hôtel Dieu, in order to
ascertain the strength of her powders, and to have invented “les poudres
de succession.” She poisoned her father, brothers, sister, and others of
her family; but a terrible fate overtook both her and St. Croix. The
latter was suffocated by some poisonous matters he was preparing, and
Madame de Brinvilliers’ practices having become known, she was obliged
to take refuge in a convent. Here she was courted by a police officer
disguised as an abbé, lured out of the convent, and, in this way brought
to justice, was beheaded[13] and burnt near Nôtre Dame, in the middle
of the reign of Louis XIV.[14]

[13] The Marchioness was imprisoned in the Conciergerie and tortured.
Victor Hugo, describing the rack in that prison, says, “The Marchioness
de Brinvilliers was stretched upon it stark naked, fastened down, so to
speak, quartered by four chains attached to the four limbs, and there
suffered the frightful extraordinary torture by water,” which caused her
to ask “How are you going to contrive to put that great barrel of water
in this little body?”--_Things seen by Victor Hugo_, vol. i.

The water torture was this:--a huge funnel-like vessel was fitted on to
the neck, the edge of the funnel coming up to the eyes; on now pouring
water into the funnel so that the fluid rises above the nose and mouth,
the poor wretch is bound to swallow the fluid or die of suffocation; if
indeed the sufferer resolve to be choked, in the first few moments of
unconsciousness the fluid is swallowed automatically, and air again
admitted to the lungs; it is therefore obvious that in this way
prodigious quantities of fluid might be taken.

[14] For the court of poisoners (_chambre ardente_) and the histories of
St. Croix, De Brinvilliers, the priest Le Sage, the women La Voisin, and
La Vigoureux, the reader may be referred to Voltaire’s _Siècle de Louis
XIV._, Madame de Sévigné’s _Lettres_, Martinière’s _Hist. de la Règne de
Louis XIV._, Strutzel, _De Venenis_, &c.

The numerous attempts of the Italian and Venetian poisoners on the lives
of monarchs and eminent persons cast for a long time a cloud over regal
domestic peace. Bullets and daggers were not feared, but in their place
the dish of meat, the savoury pasty, and the red wine were regarded as
possible carriers of death. No better example of this dread can be found
than, at so late a period as the reign of Henry VII.,[15] the
extraordinary precautions thought necessary for preserving the infant
Prince of Wales.

[15] Henry VIII., at one time of his life, was (or pretended to be)
apprehensive of being poisoned; it was, indeed, a common belief of his
court that Anne Boleyn attempted to dose him. “The king, in an interview
with young Prince Henry, burst into tears, saying that he and his sister
(meaning the Princess Mary) might thank God for having escaped from the
hands of that accursed and venomous harlot, who had intended to poison
them.”--_A Chronicle of England during the Reign of the Tudors_, by W.
J. Hamilton. Introduction, p. xxi.

“No person, of whatsoever rank, except the regular attendants in the
nursery, should approach the cradle, except with an order from the
king’s hand. The food supplied to the child was to be largely
‘_assayed_,’ and his clothes were to be washed by his own servants, and
no other hand might touch them. The material was to be submitted to all
tests. The chamberlain and vice-chamberlain must be present, morning and
evening, when the prince was washed and dressed, and nothing of any kind
bought for the use of the nursery might be introduced until it was
washed and perfumed. No person, not even the domestics of the palace,
might have access to the prince’s rooms except those who were specially
appointed to them, nor might any member of the household approach
London, for fear of their catching and conveying infection.”[16]

[16] Froude’s _History of England_, vol. iii. p. 262.

However brief and imperfect the foregoing historical sketch of the part
that poison has played may be, it is useful in showing the absolute
necessity of a toxicological science--a science embracing many branches
of knowledge. If it is impossible now for Toffanas, Locustas, and other
specimens of a depraved humanity to carry on their crimes without
detection; if poison is the very last form of death feared by eminent
political persons; it is not so much owing to a different state of
society, as to the more exact scientific knowledge which is applied
during life to the discrimination of symptoms, distinguishing between
those resulting from disease and those due to injurious substances, and
after death to a highly developed pathology, which has learned, by
multiplied observations, all the normal and abnormal signs in tissues
and organs; and, finally, to an ever-advancing chemistry, which is able
in many instances to separate and detect the hurtful and noxious thing,
although hid for months deep in the ground.


II.--Growth and Development of the Modern Methods of Chemically
Detecting Poisons.

§ 8. The history of the detection of poisons has gone through several
phases. The first phase has already been incidentally touched
upon--_i.e._, detection by antecedent and surrounding circumstances,
aided sometimes by experiments on animals. If the death was sudden, if
the post-mortem decomposition was rapid, poison was indicated: sometimes
a portion of the food last eaten, or the suspected thing, would be given
to an animal; if the animal also died, such accumulation of proof would
render the matter beyond doubt. The modern toxicologists are more
sceptical, for even the last test is not of itself satisfactory. It is
now known that meat may become filled with bacilli and produce rapid
death, and yet no poison, as such, has been added.

In the next phase, the doctors were permitted to dissect, and to
familiarise themselves with pathological appearances. This was a great
step gained: the apoplexies, heart diseases, perforations of the
stomach, and fatal internal hæmorrhages could no longer be ascribed to
poison. If popular clamour made a false accusation, there was more
chance of a correct judgment. It was not until the end of the eighteenth
and the beginning of the present century, however, that chemistry was
far enough advanced to test for the more common mineral poisons; the
modern phase was then entered on, and toxicology took a new departure.

§ 9. From the treatise of Barthélémy d’Anglais[17] in the thirteenth
century (in which he noticed the poisonous properties of quicksilver
vapour), up to the end of the fifteenth century, there are numerous
treatises upon poison, most of which are mere learned compilations, and
scarcely repay perusal. In the sixteenth century, there are a few works,
such, for example, as Porta, which partook of the general advancement of
science, and left behind the stereotyped doctrine of the old classical
schools.[18]

[17] _De Rerum Proprietaribus._

[18] In the sixteenth century it was not considered proper to write upon
poisons. Jerome Cardan declared a poisoner worse than a brigand, “and
that is why I have refused not only to teach or experiment on such
things, but even to know them.”--_J. Cardan: De Subtilitate_. Basel,
1558.

In the seventeenth century the Honourable Robert Boyle made some shrewd
observations, bearing on toxicology, in his work on “The usefulness of
Natural Philosophy,” &c.: Oxford, 1664. Nicolas L’Emery also wrote a
_Cours de Chimie_,--quite an epitome of the chemical science of the
time.[19]

[19] _Cours de Chimie, contenant la manière de faire les opérations qui
sont en usage dans la Médecine._ Paris, 1675.

In the eighteenth century still further advances were made. Richard Mead
published his ingenious _Mechanical Theory of Poisons_. Great chemists
arose--Stahl, Marggraf, Brandt, Bergmann, Scheele, Berthollet,
Priestley, and lastly, Lavoisier--and chemistry, as a science, was born.
Of the chemists quoted, Scheele, in relation to toxicology, stands
chief. It was Scheele who discovered prussic acid,[20] without, however,
noting its poisonous properties; the same chemist separated oxalic acid
from sorrel,[21] and made the important discovery that arsenic united
with hydrogen, forming a fœtid gas, and, moreover, that this gas could
be decomposed by heat.[22] From this observation, a delicate test for
arsenic was afterwards elaborated, which for the first time rendered the
most tasteless and easily administered poison in the whole world at once
the easiest of detection. The further history of what is now called
“Marsh’s Test” is as follows:--

[20] _Opuscula Chemica_, vol. ii. pp. 148-174.

[21] _De Terra Rhubarbi et Acido Acetosellæ._ _Nova Acta Acad. Veg.
Sued. Anni_, 1784. _Opuscula Chemica_, vol. ii. pp. 187-195.

Bergmann first described oxalic acid as obtained by the oxidation of
saccharine bodies; but Scheele recognised its identity with the acid
contained in sorrel.

[22] _Mémoires de Scheele_, t. i., 1775.

§ 10. Proust[23] observed that a very fœtid hydrogen gas was disengaged
when arsenical tin was dissolved in hydrochloric acid, and that arsenic
was deposited from the inflamed gas on cold surfaces which the flame
touched. Trommsdorff next announced, in 1803, that when arsenical zinc
was introduced into an ordinary flask with water and sulphuric acid, an
arsenical hydrogen was disengaged; and if the tube was sufficiently
long, arsenic was deposited on its walls.[24] Stromeyer, Gay-Lussac,
Thénard, Gehlen, and Davy later studied this gas, and Serullas in 1821
proposed this reaction as a toxicological test. Lastly, in 1836, Marsh
published his Memoir.[25] He elaborated a special apparatus of great
simplicity, developed hydrogen by means of zinc and sulphuric acid,
inflamed the issuing gas, and obtained any arsenic present as a metal,
which could be afterwards converted into arsenious acid, &c.

[23] Proust, _Annales de Chimie_, t. xxviii., 1798.

[24] _Nicholson’s Journal_, vol. vi.

[25] “Description of a New Process of Separating Small Quantities of
Arsenic from Substances with which it is mixed.” _Ed. New. Phil.
Journal_, 1836.

This brief history of the so-called “Marsh’s Test” amply shows that
Marsh was not the discoverer of the test. Like many other useful
processes, it seems to have been evolved by a combination of many minds.
It may, however, be truly said that Marsh was the first who perfected
the test and brought it prominently forward.

§ 11. Matthieu Joseph Bonaventura Orfila must be considered the father
of modern toxicology. His great work, _Traité de Toxicologie_, was first
published in 1814, and went through many editions. Orfila’s chief merit
was the discovery that poisons were absorbed and accumulated in certain
tissues--a discovery which bore immediate fruit, and greatly extended
the means of seeking poisons. Before the time of Orfila, a chemist not
finding anything in the stomach would not have troubled to examine the
liver, the kidney, the brain, or the blood. The immense number of
experiments which Orfila undertook is simply marvellous. Some are of
little value, and teach nothing accurately as to the action of
poisons--as, for example, many of those in which he tied the gullet in
order to prevent vomiting, for such are experiments under entirely
unnatural conditions; but there are still a large number which form the
very basis of our pathological knowledge.

Orfila’s method of experiment was usually to take weighed or measured
quantities of poison, to administer them to animals, and then after
death--first carefully noting the changes in the tissues and organs--to
attempt to recover by chemical means the poison administered. In this
way he detected and recovered nearly all the organic and inorganic
poisons then known; and most of his processes are, with modifications
and improvements, in use at the present time.[26]

[26] Orfila’s chief works are as follows:--

_Traité de Toxicologie._ 2 vols. 8vo. Paris, 1814.

_Leçons de Chimie, appliquées à la Méd. Pratique._ 16mo. Brussels, 1836.

_Mémoire sur la Nicotine et la Conicine._ Paris, 1851.

_Leçons de la Méd. Légale._ 8vo. Paris, 1821.

_Traité des Exhumations Juridiques, et Considérations sur les Changemens
Physiques que les Cadavres éprouvent en se pourrissant._ 2 tom. Paris,
1831.

§ 12. The discovery of the alkaloids at the commencement of this century
certainly gave the poisoner new weapons; yet the same processes
(slightly modified) which separated the alkaloids from plants also
served to separate them from the human body. In 1803 Derosne discovered
narcotine and morphine, but he neither recognised the difference between
these two substances, nor their basic properties. Sertürner from 1805
devoted himself to the study of opium, and made a series of discoveries.
Robiquet, in 1807, recognised the basic characters of narcotine. In 1818
Pelletier and Caventou separated strychnine; in 1819 brucine; and in the
same year delphinine was discovered simultaneously by Brande, Lassaigne,
and Feneuille. Coniine was recognised by Giesecke in 1827, and in the
following year, 1828, nicotine was separated by Reimann and Posselt. In
1832 Robiquet discovered codeine; and in 1833 atropine, aconitine, and
hyoscyamine were distinguished by Geiger and Hesse. Since then, every
year has been marked by the separation of some new alkaloid, from either
animal or vegetable substances. So many workers in different countries
now began to study and improve toxicology, that it would exceed the
limits and be foreign to the scope of this treatise to give even a brief
_résumé_ of their labours. It may, notwithstanding, be useful to append
a short bibliography of the chief works on toxicology of the present
century.

§ 13.--BIBLIOGRAPHY OF THE CHIEF WORKS ON TOXICOLOGY (NINETEENTH
CENTURY).

    ANGLADA, JOS.--“Traité de Toxicologie Générale, &c.” Montpellier et
    Paris, 1835.

    AUTENRIETH.--“Kurze Anleitung zur Auffindung der Gifte.” Freiburg,
    1892.

    BANDLIN, O.--“Die Gifte.” Basel, 1869-1873.

    BAUMERT, G.--“Lehrbuch der gerichtl. Chemie.” Braunschweig, 1889-92.

    BAYARD, HENRI.--“Manuel Pratique de Médecine Légale.” Paris, 1843.

    BELLINI, RANIERI.--“Manuel de Tossicologia.” Pisa, 1878.

    BERLIN, N. J.--“Nachricht, die gewöhnlichen Gifte chemisch zu
    entdecken.” Stockholm, 1845.

    BERNARD, C.--“Leçons sur les Effets des Substances Toxiques et
    Médicamenteuses.” Paris, 1857.

    BERTRAND, C. A. R. A.--“Manuel Médico-Légale des Poisons introduits
    dans l’Estomac, et les Moyens Thérapeutiques qui leur conviennent:
    suivi d’un Plan d’Organisation Médico-Judiciaire, et d’un Tableau de
    la Classification Générale des Empoisonnemens.” Paris, 1818.

    BINZ, C.--“Intoxicationen” in Gerhardt’s “Handbuch der
    Kinderkrankheiten.” iii. Heft. Tübingen, 1878.

    BLYTH, A. WYNTER.--“A Manual of Practical Chemistry: The Analysis of
    Foods and the Detection of Poisons.” London, 1879.

    BOCKER, FRIEDER. WILHELM.--“Die Vergiftungen in forensischer u.
    klinischer Beziehung.” Iserlohn, 1857.

    BÖHM, R., NAUNYN, B., und VON BOECK, H.--“Handbuch der
    Intoxicationen.” (Bd. 15 of the German edition of Ziemssen’s
    Cyclopædia.)

    BRANDT, PHÖBUS, und RATZEBURG.--“Deutschlands Giftgewächse.” Berlin,
    1834-38 (2 vols. with 56 coloured plates).

    BRIAND, J., et CHAUDE, ERN.--“Manuel Complet de Médecine Légale.”
    (The latest edition, 1879.) The chemical portion is by J. Bouis.

    BUCHNER, E.--“Lehrbuch der gerichtlichen Medicin für Aerzte u.
    Juristen.” 3rd ed. München, 1872.

    CASPER, J. L.--“Handbuch der gerichtlichen Medicin.” 7th ed. Berlin,
    1881.

    CHEVALLIER, A.--“Traité de Toxicologie et de Chimie Judiciaire.”
    Paris, 1868.

    CHIAJE, STEF.--“Enchiridis di Tossicologia teorico-pratica.” 3rd ed.
    Napoli, 1858.

    CHRISTISON, ROBERT.--“A Treatise on Poisons.” Edinburgh, 1830. (A
    third edition appeared in 1836.)

    CORNEVIN, C.--“Des Plantes Vénéneuses.” Paris, 1887.

    DEVERGIE, ALPHONSE.--“Médecine Légale, Théorique, et Pratique.” 3rd
    ed. Paris, 1852.

    DRAGENDORFF, JEAN GEORGES.--“Die gerichtlich-chemische Ermittelung
    von Giften in Nahrungsmitteln, Luftgemischen, Speiseresten,
    Körpertheilen.” &c. St. Petersburg, 1868. 3rd ed. Göttingen, 1888.

    ---- “Untersuchungen aus dem Pharmaceutischen Institute in Dorpat.
    Beiträge zur gerichtlichen Chemie einzelner organischer Gifte.”
    Erstes Heft. St. Petersburg, 1871.

    ---- “Jahresbericht über die Fortschritte der Pharmacognosie,
    Pharmacie, und Toxicologie.” Herausgegeben von Dr. Dragendorff.
    1876.

    DUFLOS, A.--“Handbuch der angewandten gerichtlich-chemischen Analyse
    der chemischen Gifte, ihre Erkennung in reinem Zustande u. in
    Gemengen betreffend.” Breslau u. Leipzig, 1873.

    EULENBERG, DR. HERMANN.--“Handbuch der Gewerbe-Hygiene.” Berlin,
    1876.

    FALCK, C. PH.--“Die Klinischwichtigen Intoxicationen.” (Handbuch der
    spec. Pathologie u. Therapie red. von R. Virchow, Bd. 2.) Erlangen,
    1854.

    FALCK, FERD. AUG.--“Lehrbuch der praktischen Toxicologie.”
    Stuttgart, 1880.

    FLANDIN, C.--“Traité des Poisons, ou Toxicologie appliquée à la
    Médecine Légale, à la Physiologie, et à la Thérapeutique.” Paris,
    1847, 1853.

    FRÖHNER, EUG.--“Lehrbuch der Toxicologie für Thierärzte.” Stuttgart,
    1890.

    GALTIER, C. P.--“Traité de Toxicologie Médico-Légale et de la
    Falsification des Aliments,” &c. Paris, 1845.

    ---- “Traité de Toxicologie Médicale, Chimique et Légale,” &c.
    Paris, 1855. A later edition of the same work.

    GREENE, WILL. H.--“A Practical Handbook of Medical Chemistry,
    applied to Clinical Research and the Detection of Poisons.”
    Philadelphia, 1880.

    GUÉRIN, G.--“Traité Pratique d’Analyse Chimique et de Recherches
    Toxicologiques.” Paris, 1893.

    GUY, W. A., and FERRIER, DAVID.--“Principles of Forensic Medicine.”
    London, 1874.

    HARNACK, ERICH.--“Lehrbuch der Arzneimittellehre,” &c. Hamburg,
    1883.

    HASSELT, VAN, A. W. M.--“Handbuch der Giftlehre für Chemiker,
    Aerzte, Apotheker, u. Richtspersonen.” (A German translation of the
    original Dutch edition, edited by J. B. Henkel. Braunschweig, 1862.
    Supplemental vol. by N. Husemann, Berlin, 1867.)

    HELWIG, A.--“Das Mikroskop in der Toxicologie.” 64 photographs, roy.
    8vo, Mainz, 1865.

    HEMMING, W. D.--“Aids to Forensic Medicine and Toxicology.” London,
    1877.

    HERMANN, L.--“Lehrbuch der experimentellen Toxicologie.” 8vo.
    Berlin, 1874.

    HOFFMANN, E. R.--“Lehrbuch der gerichtlichen Medicin.” 5th ed. Wien,
    1890-91.

    HUSEMANN and A. HILGER.--“Die Pflanzenstoffe in chemischer,
    pharmakologischer, u. toxicologischer Hinsicht.” 2nd ed. Berlin,
    1882.

    HUSEMANN, TH., and HUSEMANN, A.--“Handbuch der Toxicologie.” Berlin,
    1862. (Suppl. Berlin, 1867.)

    KOBERT, RUD.--“Lehrbuch der Intoxicationen.” Stuttgart, 1893.

    KOEHLER, R.--“Handbuch der speciellen Therapie, einschliesslich der
    Behandlung der Vergiftungen.” 3rd ed. 2 vols. roy. 8vo. Tübingen,
    1869.

    LESSER, ADOLF.--“Atlas der gerichtlichen Medicin.” Berlin, 1883.

    LOEW, OSCAR.--“Ein natürliches System der Gift-Wirkungen.” München,
    1893.

    LUDWIG, E.--“Medicinische Chemie in Anwendung auf gerichtliche
    Untersuchungen.”

    MAHON, A.--“Médecine Légale et Police Médicale.” Paris, 1807.

    MARX, K. F. H.--“Die Lehre von den Giften.” Göttingen, 1827-29.

    MASCHKA, J.--“Handbuch der gerichtlichen Medicin.” Tübingen,
    1881-82. This work is under the editorship of Dr. Maschka, and
    contains separate articles on medico-legal and toxicological
    questions by various eminent toxicologists, somewhat after the
    manner of Ziemssen’s Cyclopædia.

    MENDE, LUD. JUL. CASP.--“Ausführliches Handbuch der gerichtlichen
    Medicin.” 1819-32.

    MOHR, FRIED.--“Chemische Toxicologie.” Braunschweig, 1874.

    MONTGARNY, H. DE.--“Essai de Toxicologie, et spécialement avec la
    Jurisprudence Médicale.” Paris, 1878.

    MONTMAHON, E. S. DE.--“Manuel Médico-Légale des Poisons,” &c. Paris,
    1824.

    MUTEL, D. PH.--“Des Poisons, considérés sous le rapport de la
    Médecine Pratique,” &c. Montpellier et Paris, 1835.

    NACQUET, A.--“Legal Chemistry: A guide to the detection of Poisons,
    Examination of Stains, &c., as applied to Chemical Jurisprudence.”
    New York, 1876.

    A translation from the French; see “Foods, their Composition and
    Analysis,” page 43.

    NICOLAI, JOH. ANT. HEINR.--“Handbuch der gerichtlichen Medicin.”
    Berlin, 1841.

    The chemical portion is by F. R. Simon.

    OGSTON, F.--“Lectures on Medical Jurisprudence.” London, 1878.

    ORFILA, MATTHIEU JOS. BONAVENTURA.--“Traité des Poisons, ou
    Toxicologie Générale.” Paris, 1st ed., 1814; 5th ed., 1852.

    ORFILA et LESUEUR.--“Traité de Médecine légale.” Paris, 1821; 4th
    ed., Paris, 1848.

    OTTO, F. G.--“Anleitung zur Ausmittelung der Gifte.” Braunschweig,
    1856; 5th ed., 1875. 6th ed. by Robert Otto, Braunschweig, 1884.

    PRAAG VAN, LEONIDES, u. OPWYRDA, R. J.--“Leerboek voor practische
    giftleer.” In Zwei Theilen. Utrecht, 1871.

    RABUTEAU, A.--“Élémens de Toxicologie et de Médecine Légale,
    appliquées à l’Empoisonnement.” Paris, 1873. 2nd ed. by Ed.
    Bourgoing. Paris, 1888.

    REESE, JOHN J.--“Manual of Toxicology, including the consideration
    of the Nature, Properties, Effects, and Means of Detection of
    Poisons, more especially in their Medico-legal relations.”
    Philadelphia, 1874.

    REMER, W. H. G.--“Lehrbuch der polizeilich-gerichtlichen Chemie.”
    Bd. 1 u. 2. 3. Auflage, Helmstadt, 1824.

    SCHNEIDER, F. C.--“Die gerichtliche Chemie für Gerichtsärzte u.
    Juristen.” Wien, 1852.

    SCHNEIDER, P. J.--“Ueber die Gifte in medicinisch-gerichtlicher u.
    gerichtlich-polizeilicher Rücksicht.” 2nd ed., 1821.

    SELMI, F.--“Studi di Tossicologia Chimica.” Bologna, 1871.

    SOBERNHEIM, JOS. FR. u. SIMON, J. F.--“Handbuch der praktischen
    Toxicologie,” &c. Berlin, 1838.

    SONNENSCHEIN, L.--“Handbuch der gerichtlichen Medicin.” Berlin,
    1860. A new edition by Dr. A. Classen. Berlin, 1881.

    TARDIEU, A.--“Étude Médico-Légale et Clinique sur l’Empoisonnement,
    avec la Collaboration de M. T. Roussin pour la partie de l’expertise
    relative à la Recherche Chimique des Poisons.” Paris, 1867.

    TAYLOR, ALFRED SWAINE.--“On Poisons in relation to Medical
    Jurisprudence and Medicine.” 3rd ed. 1875. Manual, 1879.

    ---- “Principles and Practice of Medical Jurisprudence.” 3 vols.
    London, 1873.

    WERBER, ANT.--“Lehrbuch der praktischen Toxicologie.” Erlangen,
    1869.

    WOOD, HORATIO C.--“Therapeutics, Materia Medica, and Toxicology.”
    Philadelphia, 1874.

    WOODMANN, W. BATHURST, and TIDY, CH.--“A Handy-Book of Forensic
    Medicine and Toxicology.” London, 1877.

    WORMLEY, THEODORE G.--“Micro-Chemistry of Poisons, including their
    Physiological, Pathological, and Legal Relations.” New York, 1857.

    WURTZ, A.--“Traité Elémentaire de Chimie Médicale, comprenant
    quelques notions de Toxicologie,” &c. 2nd ed. Paris, 1875.




PART II.


I.--Definition of Poison.

§ 14. The term “_Poison_” may be considered first in its legal, as
distinct from its scientific, aspect.

_The legal definition_ of “poison” is to be gathered from the various
statute-books of civilised nations.

The English law enacts that: “Whoever shall administer, or cause to be
administered to, or taken by any person, any poison or other destructive
thing, with intent to commit murder, shall be guilty of felony.”

Further, by the Criminal Consolidation Act, 1861: “Whosoever shall, by
any other means other than those specified in any of the preceding
sections of this Act, attempt to commit murder, shall be guilty of
felony.”

It is therefore evident that, by implication, the English law defines a
poison to be a destructive thing administered to, or taken by, a person,
and it must necessarily include, not only poisons which act on account
of their inherent chemical and other properties after absorption into
the blood, but mechanical irritants, and also specifically-tainted
fluids. Should, for example, a person give to another milk, or other
fluid, knowing, at the same time, that such fluid is contaminated by the
specific poison of scarlet fever, typhoid, or any serious malady capable
of being thus conveyed, I believe that such an offence could be brought
under the first of the sections quoted. In fine, the words “_destructive
thing_” are widely applicable, and may be extended to any substance,
gaseous, liquid, or solid, living or dead, which, if capable at all of
being taken within the body, may injure or destroy life. According to
this view, the legal idea of “poison” would include such matters as
boiling water, molten lead, specifically-infected fluids, the flesh of
animals dying of diseases which may be communicable to man, powdered
glass, diamond dust, &c. Evidence must, however, be given of guilty
intent.

The words, “administered to or taken by,” imply obviously that the
framers of the older statute considered the mouth as the only portal of
entrance for criminal poisoning, but the present law effectually guards
against any attempt to commit murder, no matter by what means. There is
thus ample provision for all the strange ways by which poison has been
introduced into the system, whether it be by the ear, nose, brain,
rectum, vagina, or any other conceivable way, so that, to borrow the
words of Mr. Greaves (_Notes on Criminal Law Consolidation_), “the
malicious may rest satisfied that every attempt to murder which their
perverted ingenuity may devise, or their fiendish malignity suggest,
will fall within some clause of this Act, and may be visited with penal
servitude for life.”

Since poison is often exhibited, not for the purpose of taking life, but
from various motives, and to accomplish various ends--as, for example,
to narcotise the robber’s victim (this especially in the East), to quiet
children, to create love in the opposite sex (love philters), to detect
the secret sipper by suitably preparing the wine, to expel the
inconvenient fruit of illicit affection, to cure inebriety by polluting
the drunkard’s drink with antimony, and, finally, to satisfy an aimless
spirit of mere wantonness and wickedness, the English law enacts “that
whosoever shall unlawfully or maliciously administer to, or cause to be
taken by, any other person, any poison or other destructive or noxious
thing, so as thereby to endanger the life of such person, or so as
thereby to inflict upon such person any grievous bodily harm, shall be
guilty of felony.”

There is also a special provision, framed, evidently, with reference to
volatile and stupefying poisons, such as chloroform, tetrachloride of
carbon, &c.:--

“Whoever shall unlawfully apply, or administer to, or cause to be taken
by any person, any chloroform, laudanum, or other stupefying or
overpowering drug, matter, or thing, with intent, in any such case,
thereby to enable himself or any other person to commit, or with intent,
&c., to assist any other person in committing, any indictable offence,
shall be guilty of felony.”

§ 15. The German statute, as with successive amendments it now stands,
enacts as follows:[27]--

[27] “Wer vorsätzlich einem Andern, um dessen Gesundheit zu beschädigen,
Gift oder andere Stoffe beibringt, welche die Gesundheit zu zerstören
geeignet sind, wird mit Zuchthaus von zwei bis zu zehn Jahren bestraft.

“Ist durch die Handlung eine schwere Körperverletzung verursacht worden,
so ist auf Zuchthaus nicht unter fünf Jahren, und wenn durch die
Handlung der Tod verursacht worden, auf Zuchthaus nicht unter zehn
Jahren oder auf lebenslängliches Zuchthaus zu erkennen.

“Ist die vorsätzliche rechtswidrige Handlung des Gift--&c.,--Beibringens
auf das ‘Tödten’ gerichtet, soll also durch dieselbe gewollter Weise der
Tod eines Anderen herbeigeführt werden, so kommt in betracht: Wer
vorsätzlich einen Menschen tödtet, wird, wenn er die Tödtung mit
Ueberlegung ausgeführt hat, wegen Mordes mit dem Tode bestraft.”

“Whoever wilfully administers (_beibringt_) to a person, for the purpose
of injuring health, poison, or any other substance having the property
of injuring health, will be punished by from two to ten years’
imprisonment.

“If by such act a serious bodily injury is caused, the imprisonment is
not to be less than five years; if death is the result, the imprisonment
is to be not under ten years or for life.

“If the death is wilfully caused by poison, it comes under the general
law: ‘Whoever wilfully kills a man, and if the killing is premeditated,
is on account of murder punishable with death.’”

The French law runs thus (Art. 301, _Penal Code_):--“Every attempt on
the life of a person, by the effect of substances which may cause death,
more or less suddenly, in whatever manner these substances may have been
employed or administered, and whatever may have been the results, is
called poisoning.”[28]

[28] “Est qualifié _empoisonnement_--tout attentat à la vie d’une
personne par l’effet de substances qui peuvent donner la mort plus ou
moins promptement, de quelque manière que ces substances aient été
employées ou administrées, et quelles qu’en aient été les suites.”--Art.
301, _Penal Code_.

There is also a penalty provided against any one who “shall have
occasioned the illness or incapacity for personal work of another, by
the voluntary administration, in any manner whatever, of substances
which, without being of a nature to cause death, are injurious to
health.”[29]

[29] “Celui qui aura occasionné à autrui une maladie ou incapacité de
travail personnel en lui administrant volontairement, de quelque manière
que ce soit, des substances qui, sans être de nature à donner la mort,
sont nuisibles à la santé.”--Art. 317, _Penal Code_.

§ 16. =Scientific Definition of a Poison.=--A true scientific definition
of a poison must exclude all those substances which act
mechanically,--the physical influences of heat, light, and electricity;
and parasitic diseases, whether caused by the growth of fungus, or the
invasion of an organism by animal parasites, as, for example,
“trichinosis,” which are not, so far as we know, associated with any
poisonous product excreted by the parasite;--on the other hand, it is
now recognised that pathogenic micro-organisms develop poisons, and the
symptoms of all true infections are but the effects of “toxines.” The
definition of poison, in a scientific sense, should be broad enough to
comprehend not only the human race, but the dual world of life, both
animal and vegetable.

Husemann and Kobert are almost the only writers on poisons who have
attempted, with more or less success, to define poison by a
generalisation, keeping in view the exclusion of the matters enumerated.
Husemann says--“We define poisons as such inorganic, or organic
substances as are in part capable of artificial preparation, in part
existing, ready-formed, in the animal or vegetable kingdom, which,
without being able to reproduce themselves, through the chemical nature
of their molecules under certain conditions, change in the healthy
organism the form and general relationship of the organic parts, and,
through annihilation of organs, or destruction of their functions,
injure health, or, under certain conditions, destroy life.” Kobert
says:--“Poisons are organic or inorganic unorganised substances
originating in the organism itself, or introduced into the organism,
either artificially prepared, or ready formed in nature, which through
their chemical properties, under certain conditions, so influence the
organs of living beings, that the health of these beings is seriously
influenced temporarily or permanently.”

In the first edition of this work I made an attempt to define a poison
thus:--_A substance of definite chemical composition, whether mineral or
organic, may be called a poison, if it is capable of being taken into
any living organism, and causes, by its own inherent chemical nature,
impairment or destruction of function_. I prefer this definition to
Kobert’s, and believe that it fairly agrees with what we know of
poisons.


II.--Classification of Poisons.

§ 17. At some future time, with a more intimate knowledge of the way in
which each poison acts upon the various forms of animal and vegetable
life, it may be possible to give a truly scientific and philosophical
classification of poisons--one based neither upon symptoms, upon local
effects, nor upon chemical structure, but upon a collation and
comparison of all the properties of a poison, whether chemical,
physical, or physiological. No perfect systematic arrangement is at
present attainable: we are either compelled to omit all classification,
or else to arrange poisons with a view to practical utility merely.

From the latter point of view, an arrangement simply according to the
most prominent symptoms is a good one, and, without doubt, an assistance
to the medical man summoned in haste to a case of real or suspected
poisoning. Indeed, under such circumstances, a scheme somewhat similar
to the following, probably occurs to every one versed in toxicology:--


A. POISONS CAUSING DEATH IMMEDIATELY, OR IN A FEW MINUTES.

There are but few poisons which destroy life in a few minutes. Omitting
the strong mineral acids, carbon monoxide, carbon dioxide, with the
irrespirable gases,--_Prussic acid_, _the cyanides_, _oxalic acid_, and
occasionally _strychnine_, are the chief poisons coming under this head.


B. IRRITANT POISONS (symptoms mainly pain, vomiting, and purging).

_Arsenic_, _antimony_, _phosphorus_, _cantharides_, _savin_, _ergot_,
_digitalis_, _colchicum_, _zinc_, _mercury_, _lead_, _copper_, _silver_,
_iron_, _baryta_, _chrome_, _yew_, _laburnum_, _and putrid animal
substances._


C. IRRITANT AND NARCOTIC POISONS (symptoms those of an irritant nature,
with the addition of more or less pronounced cerebral indications).

To this class more especially belong _oxalic acid_ and _the oxalates_,
with several poisons belonging to the purely narcotic class, but which
produce occasionally irritant effects.


D. POISONS MORE ESPECIALLY AFFECTING THE NERVOUS SYSTEM.

1. NARCOTICS (chief symptom insensibility, which may be preceded by more
or less cerebral excitement): _Opium_, _Chloral_, _Chloroform_.

2. DELIRIANTS (delirium for the most part a prominent symptom):
_Belladonna_, _hyoscyamus_, _stramonium_, _with others of the
Solanaceæ_, to which may be added--_poisonous fungi_, _Indian hemp_,
_lolium temulentum_, _œnanthe crocata_, and _camphor_.

3. CONVULSIVES.--Almost every poison has been known to produce
convulsive effects, but the only true convulsive poisons are the
_alkaloids of the strychnos class_.

4. COMPLEX NERVOUS PHENOMENA: _Aconite_, _digitalis_, _hemlock_,
_calabar bean_, _tobacco_, _lobelia inflata_, and _curara_.

       *       *       *       *       *

§ 18. KOBERT’S CLASSIFICATION.--The latest authority on
poisons--Kobert--has classified poisons according to the following
scheme:--


I. POISONS WHICH CAUSE COARSE ANATOMICAL CHANGES OF THE ORGANS.

    A. Those which specially irritate the part to which they are
    applied.

    1. _Acids._

    2. _Caustic alkalies._

    3. _Caustic salts_, especially those of the heavy metals.

    4. Locally irritating organic substances which neither can be
    classified as corrosive acids nor alkalies, nor as corrosive salts;
    such are:--_cantharidine_, _phrynine_, and others in the animal
    kingdom, _croton oil_ and _savin_ in the vegetable kingdom. Locally
    irritating colours, such as the _aniline dyes_.

    5. Gases and vapours which cause local irritation when breathed,
    such as _ammonia_, _chlorine_, _iodine_, _bromine_, and _sulphur
    dioxide_.

    B. Those which have but little effect locally, but change
    anatomically other parts of the body; such as _lead_, _phosphorus_,
    and others.


II. BLOOD POISONS.

    1. Blood poisons interfering with the circulation in a purely
    physical manner, such as _peroxide of hydrogen_, _ricine_, _abrine_.

    2. Poisons which have the property of dissolving the red blood
    corpuscle, such as the _saponins_.

    3. Poisons which, with or without primary solution of the red blood
    corpuscles, produce in the blood methæmoglobin; such as _potassic
    chlorate_, _hydrazine_, _nitrobenzene_, _aniline_, _picric acid_,
    _carbon disulphide_.

    4. Poisons having a peculiar action on the colouring matter of the
    blood, or on its decomposition products, such as _hydric sulphide_,
    _hydric cyanide_, and the _cyanides_ and _carbon monoxide_.


III. POISONS WHICH KILL WITHOUT THE PRODUCTION OF COARSE ANATOMICAL
CHANGE.

    1. Poisons affecting the cerebro-spinal system; such as
    _chloroform_, _ether_, _nitrous oxide_, _alcohol_, _chloral_,
    _cocaine_, _atropine_, _morphine_, _nicotine_, _coniine_,
    _aconitine_, _strychnine_, _curarine_, and others.

    2. Heart Poisons; such as, _digitalis_, _helleborin_, _muscarine_.


IV. POISONOUS PRODUCTS OF TISSUE CHANGE.

    1. Poisonous albumin.

    2. Poisons developed in food.

    3. Auto-poisoning, _e.g._ uræmia, glycosuria, oxaluria.

    4. The more important products of tissue change; such as, _fatty
    acids_, _oxyacids_, _amido-fatty acids_, _amines_, _diamines_, and
    _ptomaines_.

       *       *       *       *       *

§ 19. I have preferred an arrangement which, as far as possible, follows
the order in which a chemical expert would search for an unknown
poison--hence an arrangement partly chemical and partly symptomatic.
First the chief gases which figure in the mortality statistics are
treated, and then follow in order other poisons.

A chemist, given a liquid to examine, would naturally test first its
reaction, and, if strongly alkaline or strongly acid, would at once
direct his attention to the mineral acids or to the alkalies. In other
cases, he would proceed to separate volatile matters from those that
were fixed, lest substances such as prussic acid, chloroform, alcohol,
and phosphorus be dissipated or destroyed by his subsequent operations.

Distillation over, the alkaloids, glucosides, and their allies would
next be naturally sought, since they can be extracted by alcoholic and
ethereal solvents in such a manner as in no way to interfere with an
_after_-search for metals.

The metals are last in the list, because by suitable treatment, after
all organic substances are destroyed, either by actual fire or powerful
chemical agencies, even the volatile metals may be recovered. The metals
are arranged very nearly in the same order as that in which they would
be separated from a solution--viz., according to their behaviour to
hydric and ammoniac sulphides.

There are a few poisons, of course, such as the oxalates of the
alkalies, which might be overlooked, unless sought for specially; but it
is hoped that this is no valid objection to the arrangement suggested,
which, in greater detail, is as follows:--


A.--POISONOUS GASES.

  1. Carbon monoxide.
  2. Chlorine.
  3. Hydric sulphide.


B.--ACIDS AND ALKALIES.

  1. Sulphuric acid.
  2. Hydrochloric acid.
  3. Nitric acid.
  4. Potash.
  5. Soda.
  6. Ammonia.
  7. Neutral sodium, potassium, and ammonium salts.

In nearly all cases of death from any of the above, the analyst, from
the symptoms observed during life, from the surrounding circumstances,
and from the pathological appearances and evident chemical reactions of
the fluids submitted, is put at once on the right track, and has no
difficulty in obtaining decided results.


C.--POISONOUS SUBSTANCES CAPABLE OF BEING SEPARATED BY DISTILLATION FROM
EITHER NEUTRAL OR ACID LIQUIDS.

  1. Hydrocarbons.
  2. Camphor.
  3. Alcohols.
  4. Amyl-nitrite.
  5. Chloroform and other anæsthetics.
  6. Carbon disulphide.
  7. Carbolic acid.
  8. Nitro-benzene.
  9. Prussic acid.
  10. Phosphorus.

The volatile alkaloids, which may also be readily distilled by strongly
alkalising the fluid, because they admit of a rather different mode of
treatment, are not included in this class.


D.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE MOST
PART BY ALCOHOLIC SOLVENTS.


DIVISION I.--VEGETABLE ALKALOIDS.

   1. Liquid volatile alkaloids, alkaloids of hemlock, nicotine,
      piturie, sparteine, aniline.
   2. The opium group of alkaloids.
   3. The strychnine or tetanic group of alkaloids--strychnine, brucine,
      igasurine.
   4. The aconite group of alkaloids.
   5. The mydriatic group of alkaloids--atropine, hyoscyamine, solanin,
      cytisine.
   6. The alkaloids of the veratrines.
   7. Physostigmine.
   8. Pilocarpine.
   9. Taxine.
  10. Curarine.
  11. Colchicin.
  12. Muscarine and the active principles of certain fungi.

There would, perhaps, have been an advantage in arranging several of the
individual members somewhat differently--_e.g._, a group might be made
of poisons which, like pilocarpine and muscarine, are antagonistic to
atropine; and another group suggests itself, the physiological action of
which is the opposite of the strychnos class; solanin (although classed
as a mydriatic, and put near to atropine) has much of the nature of a
glucoside, and the same may be said of colchicin; so that, if the
classification were made solely on chemical grounds, solanin would have
followed colchicin, and thus have marked the transition from the
alkaloids to the glucosides.


DIVISION II.--GLUCOSIDES.

  1. The digitalis group.
  2. Other poisonous glucosides acting on the heart.
  3. Saponin.

The glucosides, when fairly pure, are easily recognised; they are
destitute of nitrogen, neutral in reaction, and split up into sugar and
other compounds when submitted to the action of saponifying agents, such
as boiling with dilute mineral acids.


DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF THE ORGANIC ACIDS.

  1. Santonin.
  2. Mezereon.

It is probable that this class will in a few years be extended, for
several other organic anitrogenous poisons exist, which, when better
known, will most likely prove to be anhydrides.


DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES NOT ADMITTING OF
CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS.

Ergot, picrotoxin, the poison of _Illicium religiosum_, cicutoxin,
_Æthusa cynapium_, _Œnanthe crocata_, croton oil, savin oil, the
toxalbumins of castor oil and _Abrus_.

The above division groups together various miscellaneous toxic
principles, none of which can at present be satisfactorily classified.


E.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL SUBSTANCES.


DIVISION I.--POISONS SECRETED BY THE LIVING.

  1. Poisonous amphibia.
  2. Poison of the scorpion.
  3. Poisonous fish.
  4. Poisonous insects--spiders, wasps, bees, beetles, &c.
  5. Snake poison.


DIVISION II.--POISONS FORMED IN DEAD ANIMAL MATTERS.

  1. Ptomaines.
  2. Poisoning by putrid or changed foods--sausage poisoning.


F.--THE OXALIC ACID GROUP.


G.--INORGANIC POISONS.


DIVISION I.--PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC
SULPHIDE--PRECIPITATE, YELLOW OR ORANGE.

    Arsenic, antimony, cadmium.


DIVISION II.--PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID
SOLUTION--BLACK.

    Lead, copper, bismuth, silver, mercury.


DIVISION III.--PRECIPITATED FROM A NEUTRAL SOLUTION BY HYDRIC SULPHIDE.

    Zinc, nickel, cobalt.


DIVISION IV.--PRECIPITATED BY AMMONIA SULPHIDE.

    Iron, chromium, thallium, aluminium.


DIVISION V.--ALKALINE EARTHS.

    Barium.


III.--Statistics.

§ 20. The number of deaths from poison (whether accidental, suicidal, or
homicidal), as compared with other forms of violent, as well as natural
deaths, possesses no small interest; and this is more especially true
when the statistics are studied in a comparative manner, and town be
compared with town, country with country.

The greater the development of commercial industries (especially those
necessitating the use or manufacture of powerful chemical agencies), the
more likely are accidents from poisons to occur. It may also be stated,
further, that the higher the mental development of a nation, the more
likely are its homicides to be caused by subtle poison--its suicides by
the euthanasia of chloral, morphine, or hemlock.

Other influences causing local diversity in the kind and frequency of
poisoning, are those of race, of religion, of age and sex, and the
mental stress concomitant with sudden political and social changes.

In the ten years from 1883-1892, there appear to have died from poison,
in England and Wales, 6616 persons, as shown in the following tables:--

DEATHS FROM POISON IN ENGLAND AND WALES DURING THE TEN YEARS 1883-92.

  +----------------------------+---------+---------+---------+---------+
  |                            |Accident |         |         |         |
  |                            |   or    |         |         |         |
  |                            | Negli-  |Suicide. | Murder. | Total.  |
  |                            | gence.  |    |    |    |    |    |    |
  +----------------------------+----+----+----+----+----+----+----+----+
  |                            | M. | F. | M. | F. | M. | F. | M. | F. |
  |                            |    |    |    |    |    |    |    |    |
  |           METALS.          |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Arsenic,                    |  37|  14|  37|  20|   1|   1|  75|  35|
  |Antimony,                   |   3| ...|   1|   2| ...| ...|   4|   2|
  |Copper,                     |   4|   1|   2|   1| ...| ...|   6|   2|
  |Lead,                       | 831| 209|   1|   2| ...| ...| 832| 211|
  |Silver Nitrate,             |   1| ...| ...| ...| ...| ...|   1| ...|
  |Zinc Chloride (or Sulphate),|   7| ...|   4| ...| ...| ...|  11| ...|
  |Mercury,                    |  22|  11|  16|   8|   2|   1|  40|  20|
  |Chromic Acid,               |   1| ...| ...| ...| ...| ...|   1| ...|
  |Iron Perchloride,           | ...| ...| ...|   1| ...| ...| ...|   1|
  |                            |    |    |    |    |    |    |    |    |
  |     ALKALINE EARTHS.       |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Lime,                       |   2| ...| ...|   1| ...| ...|   2|   1|
  |Barium Chloride,            |   1| ...| ...| ...| ...| ...|   1| ...|
  |                            |    |    |    |    |    |    |    |    |
  |  THE ALKALIES AND THEIR    |    |    |    |    |    |    |    |    |
  |          SALTS.            |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Ammonia,                    |  39|  25|  18|  16| ...| ...|  57|  41|
  |Caustic Soda,               |   3|   4| ...|   1| ...| ...|   3|   5|
  |   „    Potash,             |   8|  10|   1| ...| ...| ...|   9|  10|
  |Potassic Chlorate,          |   1| ...| ...| ...| ...| ...|   1| ...|
  |   „     Bichromate,        |   2|   2|   7|   3| ...| ...|   9|   5|
  |   „     Bromide,           |   1| ...| ...| ...| ...| ...|   1| ...|
  |   „     Binoxalate         |    |    |    |    |    |    |    |    |
  |         (Sorrel),          |   1|   3|   1|   4| ...| ...|   2|   7|
  |                            |    |    |    |    |    |    |    |    |
  |          ACIDS.            |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Sulphuric Acid,             |  30|   9|  29|  24|   1| ...|  60|  33|
  |Nitric     „                |  18|   7|  18|   9| ...| ...|  36|  16|
  |Hydrochloric Acid,          |  48|  18|  83|  55| ...| ...| 131|  73|
  |Oxalic         „            |  17|   6| 114|  86| ...| ...| 131|  92|
  |Tartaric       „            | ...|   1| ...| ...| ...| ...| ...|   1|
  |Acetic         „            |   4|   3| ...|   2| ...| ...|   4|   5|
  |Carbolic       „            | 169| 101| 219| 271| ...|   1| 388| 373|
  |Hydrofluoric   „            | ...| ...| ...|   1| ...| ...| ...|   1|
  |Phosphorus (including       |    |    |    |    |    |    |    |    |
  |Lucifer matches),           |  24|  47|  28|  56| ...| ...|  52| 103|
  |Iodine,                     |   6|   7|   1|   1| ...| ...|   7|   8|
  |                            |    |    |    |    |    |    |    |    |
  |      VOLATILE LIQUIDS.     |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Paraffin (Petroleum),       |   9|   2|   1| ...| ...| ...|  10|   2|
  |Benzoline,                  |   3|   2| ...|   1| ...| ...|   3|   3|
  |Naphtha,                    |   1| ...| ...| ...| ...| ...|   1| ...|
  |Carbon Bisulphide,          | ...| ...|   1| ...| ...| ...|   1| ...|
  |Turpentine,                 |   5|   1| ...|   3| ...| ...|   5|   4|
  |Methylated Spirit,          | ...|   2|   1|   2| ...| ...|   1|   4|
  |Alcohol,                    |  81|  24|   1|   2| ...| ...|  82|  26|
  |Chloroform,                 |  57|  41|   9|   5|   1| ...|  67|  46|
  |Ether,                      |   5|   2| ...| ...| ...| ...|   5|   2|
  |Spt. Etheris Nitrosi,       |   1| ...| ...| ...| ...| ...|   1| ...|
  |Anæsthetic (kind not        |    |    |    |    |    |    |    |    |
  |stated),                    |   4|   3| ...| ...| ...| ...|   4|   3|
  |Oil of Juniper,             |   1| ...| ...| ...| ...| ...|   1| ...|
  |                            |    |    |    |    |    |    |    |    |
  |   OPIATES AND NARCOTICS.   |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Opium, Laudanum--Morphia,   | 503| 373| 330| 167|  4 |  2 | 837| 542|
  |Soothing Syrup, Paregoric,  |    |    |    |    |    |    |    |    |
  |&c.                         |  18|  22|   2|   3| ...| ...|  20|  25|
  |Chlorodyne,                 |  56|  30|   8|   8| ...| ...|  64|  38|
  |Chloral,                    |  89|  22|  14|   1|  1 | ...| 104|  23|
  |                            |    |    |    |    |    |    |    |    |
  |         CYANIDES.          |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Prussic Acid, and Oil of    |    |    |    |    |    |    |    |    |
  |    Almonds,                |  17|  11| 203|  19|  2 |  8 | 222|  38|
  |Potassium Cyanide,          |  19|  21| 100|  22|  3 |  1 | 122|  44|
  |                            |    |    |    |    |    |    |    |    |
  |        ALKALOIDS.          |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Strychnine and Nux Vomica,  |  22|  21|  65|  85|  4 |  4 |  91| 110|
  |Vermin-Killer,              |   2|   6|  49|  69|  1 | ...|  52|  75|
  |Atropine,                   |   2| ...|   1| ...| ...| ...|   3| ...|
  |Belladonna,                 |  36|  20|  11|   9| ...| ...|  47|  29|
  |Aconite,                    |  19|  21|   9|  10| ...| ...|  28|  31|
  |Ipecacuanha,                |   1|   1| ...| ...| ...| ...|   1|   1|
  |Cocaine,                    |   3| ...| ...| ...| ...| ...|   3| ...|
  |                            |    |    |    |    |    |    |    |    |
  |       MISCELLANEOUS.       |    |    |    |    |    |    |    |    |
  |                            |    |    |    |    |    |    |    |    |
  |Antipyrine,                 |   1| ...| ...| ...| ...| ...|   1| ...|
  |Cantharides,                |   1| ...| ...|   1| ...| ...|   1|   1|
  |Camphorated Oil,            |   1| ...| ...| ...| ...| ...|   1| ...|
  |Croton Oil,                 |   1| ...| ...| ...| ...| ...|   1| ...|
  |Cayenne Pepper,             |   1| ...| ...| ...| ...| ...|   1| ...|
  |Syrup of Rhubarb,           |   1| ...| ...| ...| ...| ...|   1| ...|
  |Colchicum,                  |   2| ...| ...| ...| ...| ...|   2| ...|
  |Hemlock,                    |   3|   1| ...| ...| ...| ...|   3|   1|
  |Water Hemlock,              |   5|   6| ...| ...| ...| ...|   5|   6|
  |Colocynth,                  | ...|   2| ...| ...| ...| ...| ...|   2|
  |Castor Oil Seeds,           |   1|   1| ...| ...| ...| ...|   1|   1|
  |Laburnum Seeds,             |   2|   1| ...| ...| ...| ...|   2|   1|
  |Thorn Apple,                |   1| ...| ...| ...| ...| ...|   1| ...|
  |Yew Leaves or Berries,      |   3|   2| ...| ...| ...| ...|   3|   2|
  |Crow-foot,                  | ...|   1| ...| ...| ...| ...| ...|   1|
  |Whin-flower,                |   1| ...| ...| ...| ...| ...|   1| ...|
  |Pennyroyal,                 | ...|   1| ...| ...| ...| ...| ...|   1|
  |Meadow Crow-foot,           | ...|   1| ...| ...| ...| ...| ...|   1|
  |Arum Seeds,                 | ...|   1| ...| ...| ...| ...| ...|   1|
  |Bitter Aloes,               | ...|   1| ...|   1| ...| ...| ...|   2|
  |Cocculus Indicus,           | ...| ...|   1| ...| ...| ...|   1| ...|
  |Horse Chestnut,             | ...|   1| ...| ...| ...| ...| ...|   1|
  |Creosote,                   |   1| ...| ...| ...| ...| ...|   1| ...|
  |Spirits of Tar (Oil of Tar),|   2|   1| ...| ...| ...| ...|   2|   1|
  |Nitro-Glycerine,            |   1| ...| ...| ...| ...| ...|   1| ...|
  |Camphor,                    | ...|   1| ...| ...| ...| ...| ...|   1|
  |Tobacco,                    |   4| ...|   1| ...| ...| ...|   5| ...|
  |Lobelia,                    |   1| ...| ...| ...| ...| ...|   1| ...|
  |Fungi,                      |  13|  10| ...| ...| ...| ...|  13|  10|
  |Poisonous Weeds,            |   2| ...| ...| ...| ...| ...|   2| ...|
  |Hellebores,                 | ...| ...|   1|   1| ...| ...|   1|   1|
  |Kind not stated,            | 216| 158| 256| 167|  3 |  1 | 475| 326|
  |                            +----+----+----+----+----+----+----+----+
  |                            |2498|1292|1644|1140|  23|  19|4165|2551|
  |                            |  \    / |  \    / |  \    / |  \    / |
  |                            |   3790  |   2784  |    42   |   6616  |
  +----------------------------+---------+---------+---------+---------+

Although so large a number of substances destroy life by accident or
design, yet there are in the list only about 21 which kill about 2
persons or above each year: the 21 substances arranged in the order of
their fatality are as follows:--

                         Actual deaths in
                      ten years ending 1892.
  Caustic potash                19
  Poisonous fungi               23
  Aconite                       59
  Mercury                       60
  Belladonna                    76
  Sulphuric acid                93
  Ammonia                       98
  Chlorodyne                   102
  Alcohol                      108
  Arsenic                      110
  Chloroform                   113
  Vermin-killer                127
  Chloral                      127
  Phosphorus                   155
  Cyanide of potassium         166
  Strychnine                   201
  Nitric acid                  204
  Prussic acid                 260
  Carbolic acid                762
  Lead                        1043
  Opiates                     1324

In each decade there are changes in the position on the list. The most
significant difference between the statistics now given and the
statistics for the ten years ending 1880, published in the last edition
of this work, is that in the former decade carbolic acid occupied a
comparatively insignificant place; whereas in the ten years ending 1892,
deaths from carbolic acid poisoning are the most frequent form of fatal
poisoning save lead and opiates.

The following table gives some German statistics of poisoning:--

TABLE SHOWING THE ADMISSIONS INTO VARIOUS MEDICAL INSTITUTIONS[30] IN
BERLIN OF PERSONS SUFFERING FROM THE EFFECTS OF POISON DURING THE THREE
YEARS 1876, 1877, 1878.

[30] Viz., the Königl. Charité, Allg. Städtisches Krankenhaus,
Städtisches Baracken-Lazareth, Bethanien, St. Helwög’s-Lazarus,
Elisabethen-Krankenhaus, Augusta Hospital, and the Institut für
Staatsarzneikunde.

  +--------------------------------------+--------+--------+--------+
  |                                      | Males. |Females.| Total. |
  +--------------------------------------+--------+--------+--------+
  | Charcoal Vapour,                     |   77   |    78  |   155  |
  | Sulphuric Acid,                      |   24   |    54 }|        |
  | Hydrochloric Acid,                   |    4   |     4 }|    93  |
  | Nitric Acid, and Aqua Regia,         |    7   |   ... }|        |
  | Phosphorus,                          |   13   |    28  |    41  |
  | Cyanide of Potassium,                |   29   |     3 }|        |
  | Prussic Acid,                        |    5   |     1 }|    38  |
  | Oxalic Acid, and Oxalate of Potash,  |   11   |     8  |    19  |
  | Alcohol,                             |   12   |     2  |    14  |
  | Arsenic,                             |    7   |     5  |    12  |
  | Morphine,                            |    8   |     1 }|        |
  | Opium,                               |    2   |     1 }|    12  |
  | Potash or Soda Lye,                  |    2   |     6  |     8  |
  | Chloral,                             |    3   |     4  |     7  |
  | Chloroform,                          |    4   |     2  |     6  |
  | Sewer Gas,                           |    5   |   ...  |     5  |
  | Strychnine,                          |  ...   |     4  |     4  |
  | Atropine,                            |    1   |     2  |     3  |
  | Copper Sulphate,                     |    1   |     2  |     3  |
  | Nitrobenzol,                         |    2   |   ...  |     2  |
  | Carbolic Acid,                       |  ...   |     2  |     2  |
  | Chromic Acid,                        |    1   |     1  |     2  |
  | Burnt Alum,                          |  ...   |     1  |     1  |
  | Ammonium Sulphide,                   |    1   |   ...  |     1  |
  | Datura Stramonium,                   |  ...   |     1  |     1  |
  | Petroleum,                           |  ...   |     1  |     1  |
  | Benzine,                             |    1   |   ...  |     1  |
  | Ether,                               |    1   |   ...  |     1  |
  | Prussic Acid and Morphine,           |    1   |   ...  |     1  |
  | Prussic Acid and Chloral,            |    1   |   ...  |     1  |
  | Turpentine and Sal Ammoniac,         |  ...   |     1  |     1  |
  |                                      +--------+--------+--------+
  |                                      |  223   |   212  |   435  |
  +--------------------------------------+--------+--------+--------+

=Suicidal Poisoning.=--Poisons which kill more than one person
suicidally each year are only 19 in number, as follows:--

                            Deaths from suicide
                            during the ten years
                               ending 1892.

  Potassic bichromate              10
  Chloroform                       14
  Chloral                          15
  Chlorodyne                       16
  Aconite                          19
  Belladonna                       20
  Mercury                          24
  Nitric acid                      27
  Ammonia                          34
  Sulphuric acid                   53
  Arsenic                          77
  Phosphorus                       84
  Vermin-killer                   118
  Prussic acid                    122
  Hydrochloric acid               138
  Strychnine                      150
  Oxalic acid                     200
  Prussic acid                    222
  Opiates                         281
  Phenol                          290

In the ten years ending 1880, suicidal deaths from vermin-killers, from
prussic acid, from cyanide of potassium, and from opiates were all more
numerous than deaths from phenol, whereas at present phenol appears to
be the poison most likely to be chosen by a suicidal person.


Criminal Poisoning.

§ 22. Some useful statistics of criminal poisoning have been given by
Tardieu[31] for the 21 years 1851-1871, which may be summarised as
follows:--

[31] _Étude Médico-Légale sur l’Empoisonnement_, Paris, 1875.

  Total accusations of Poisoning in the 21 years,            793

  RESULTS OF THE POISONING:--
    Death,                                        280 }
    Illness,                                      346 }      872
    Negative,                                     246 }

  ACCUSED:--
    Men,                                          304 }      703
    Women,                                        399 }

  NATURE OF POISON EMPLOYED:--
    Arsenic,                                                 287
    Phosphorus,                                              267

         { Sulphate,                              120 }
  Copper { Acetate (Verdigris),                    39 }      159

        { Sulphuric Acid,                          36 }
  Acids { Hydrochloric Acid,                        8 }       47
        { Nitric Acid,                              3 }

  Cantharides,                                                30

  Nux Vomica,                                       5 }       12
  Strychnine,                                       7 }

          { Opium,                                  6 }
  Opiates { Laudanum,                               3 }       10
          { Sedative Water,                         1 }

  Salts of Mercury,                                            8

  Sulphate of Iron,                                            6

  Preparations of Antimony,                                    5

  Ammonia,                                                     4

  Cyanides     {Prussic Acid,                       2 }
               {Cyanide of Potassium,               2 }        4

  Hellebore,                                                   3

  Datura Stramonium,                                           3

  Powdered Glass,                                              3

  Digitalin,                                                   2

  Potash,                                                      2

  Sulphate of Zinc,                                            2

  Eau de Javelle (a solution of Hypochlorite of Potash),       1

  Tincture of Iodine,                                          1

  Croton Oil,                                                  1

  Nicotine,                                                    1

  Belladonna,                                                  1

  “Baume Fiovarenti,”                                          1

  Euphorbia,                                                   1

  Acetate of Lead,                                             1

  Carbonic Acid Gas,                                           1

  Laburnum Seeds,                                              1

  Colchicum,                                                   1

  Mushrooms,                                                   1

  Sulphuric Ether,                                             1
                                                             ---
  Total,                                                     867
                                                             ===

It hence may be concluded, according to these statistics of criminal
poisoning, that of 1000 attempts in France, either to injure or to
destroy human life by poison, the following is the most probable
selective order:--

  Arsenic,                                                      331
  Phosphorus,                                                   301
  Preparations of Copper,                                       183
  The Mineral Acids,                                             54
  Cantharides,                                                   35
  Strychnine,                                                    14
  Opiates,                                                       12
  Mercurial preparations,                                         9
  Antimonial preparations,                                        6
  Cyanides (that is, Prussic Acid and Potassic Cyanide),          5
  Preparations of Iron,                                           5

This list accounts for 955 poisonings, and the remaining 45 will be
distributed among the less used drugs and chemicals.


IV.--The Connection between Toxic Action and Chemical Composition.

§ 23. Considerable advance has been made of late years in the study of
the connection which exists between the chemical structure of the
molecule of organic substances and physiological effect. The results
obtained, though important, are as yet too fragmentary to justify any
great generalisation; the problem is a complicated one, and as Lauder
Brunton justly observes:--

“The physiological action of a drug does not depend entirely on its
chemical composition nor yet on its chemical structure, so far as that
can be indicated even by graphic formula, but upon conditions of
solubility, instability, and molecular relations, which we may hope to
discover in the future, but with which we are as yet imperfectly
acquainted.”[32]

[32] _Introduction to Modern Therapeutics_, Lond., 1892. 136.

The occurrence of hydroxyl, whether the substance belong to the simpler
chain carbon series or to the aromatic carbon compounds, appears to
usually endow the substance with more or less active and frequently
poisonous properties, as, for example, in the alcohols, and as in
hydroxylamine. It is also found that among the aromatic bodies the toxic
action is likely to increase with the number of hydroxyls: thus phenol
has one hydroxyl, resorcin two, and phloroglucin three; and the toxic
power is strictly in the same order, for, of the three, phenol is least
and phloroglucin most poisonous.

Replacing hydrogen by a halogen, especially by chlorine, in the fatty
acids mostly produces substances of narcotic properties, as, for
instance, monochloracetic acid. In the sulphur compounds, the entrance
of chlorine modifies the physiological action and intensifies toxicity:
thus ethyl sulphide (C₂H₅)₂S is a weak poison, monochlorethyl sulphide
C₂H₅C₂H₄ClS a strong poison, and dichlorethyl sulphide C₄H₈Cl₂S a very
strong poison: the vapour kills rabbits within a short time, and a trace
of the oil applied to the ear produces intense inflammation of both the
eyes and the ear.[33]

[33] V. Meyer, _Ber. d. Chem. Ges._, XX., 1725.

The weight of the molecule has an influence in the alcohols and acids of
the fatty series; for instance, ethyl, propyl, butyl, and amyl alcohols
show as they increase in carbon a regular increase in toxic power; the
narcotic actions of sodium propionate, butyrate, and valerianate also
increase with the rising carbon. Nitrogen in the triad condition in the
amines is far less poisonous than in the pentad condition.

Bamberger[34] distinguishes two classes of hydrogenised bases derived
from α and β naphthylamine, by the terms “acylic” and “aromatic.” The
acylic contains the four added hydrogens in the amidogen nucleus, the
aromatic in the other nucleus, thus

[34] _Ber._, xxii. 777-778.

      CH    CNH₂
      /\   /\
     /  \C/  \
  CH |   |   | CH
     |   |   |
  CH |   |   | CH
     \  /C\  /
      \/   \/
      CH    CH

  α Naphthylamine.

      CH    CH
      /\   /\
     /  \C/  \
  CH |   |   | CNH₂
     |   |   |
  CH |   |   | CH
     \  /C\  /
      \/   \/
      CH    CH

  β Naphthylamine.

      CH    CH₂
      /\   /\
     /  \C/  \
  CH |   |   | CNH₃
     |   |   |
  CH |   |   | CH₂
     \  /C\  /
      \/   \/
      CH    CH₂

  Acylic tetrahydro-α Naphthylamine.

       CH₂   CH
       /\   /\
      /  \C/  \
  CH₂ |   |   | CNH₂
      |   |   |
  CH₂ |   |   | CH
      \  /C\  /
       \/   \/
       CH₂   CH

  Aromatic tetrahydro-β Naphthylamine.

The acylic β tetrahydro-naphthylamine, the β
tetrahydroethylnaphthylamine, and the β tetrahydromethylnaphthylamine
all cause dilatation of the pupil and produce symptoms of excitation of
the cervical sympathetic nerve; the other members of the group are
inactive.

§ 24. The result of replacing hydrogen by alkyls in aromatic bodies has
been studied by Schmiedeberg and others; replacing the hydrogen of the
amidogen by ethyl or methyl, usually results in a body having a more or
less pronounced narcotic action. The rule is that methyl is stronger
than ethyl, but it does not always hold good; ortho-amido-phenol is not
in itself poisonous, but when two hydrogens of the amidogen group are
replaced by two methyls thus--

   HO
    /\
   /  \
  |    |NH₂
  |    |
  |    |
   \  /
    \/

   HO
    /\
   /  \
  |    |N(CH₃)₂
  |    |
  |    |
   \  /
    \/

the resulting body has a weak narcotic action.

It would naturally be inferred that the replacement of the H in the
hydroxyl by a third methyl would increase this narcotic action, but this
is not so: on the other hand, if there are three ethyl groups in the
same situation a decidedly narcotic body is produced.

The influence of position of an alkyl in the aromatic bodies is well
shown in ortho-, para- and meta-derivatives. Thus the author proved some
years ago that with regard to disinfecting properties, ortho-cresol was
more powerful than meta-; meta-cresol more powerful than para-; so again
ortho-aceto-toluid is poisonous, causing acute nephritis;
meta-aceto-toluid has but feeble toxic actions but is useful as an
antipyretic; and para-aceto-toluid is inactive.

In the trioxybenzenes, in which there are three hydroxyls, the toxic
action is greater when the hydroxyls are consecutive, as in pyrogallol,
than when they are symmetrical, as in phloroglucin.

    OH
    /\
   /  \
  |    |OH
  |    |
  |    |OH
   \  /
    \/

  Pyrogallol.

      OH
      /\
     /  \
    |    |
    |    |
  HO|    |OH
     \  /
      \/

  Phloroglucin.

The introduction of methyl into the complicated molecule of an alkaloid
often gives curious results: thus methyl strychnine and methyl brucine
instead of producing tetanus have an action on voluntary muscle like
curare.

Benzoyl-ecgonine has no local anæsthetic action, but the introduction of
methyl into the molecule endows it with a power of deadening the
sensation of the skin locally; on the other hand, cocethyl produces no
effect of this kind.

Drs. Crum Brown and Fraser[35] have suggested that there is some
relation between toxicity and the saturated or non-saturated condition
of the molecule.

[35] _Journ. Anat. and Phys._, vol. ii. 224.

Hinsberg and Treupel have studied the physiological effect of
substituting various alkyls for the hydrogen of the hydroxyl group in
para-acetamido-phenol.

Para-aceto-amido-phenol when given to dogs in doses of 0.5 grm. for
every kilogr. of body weight causes slight narcotic symptoms, with
slight paralysis; there is cyanosis and in the blood much methæmoglobin.

In men doses of half a gramme (7·7 grains) act as an antipyretic,
relieve neuralgia and have weak narcotic effects.

The following is the result of substituting certain alkyls for H in the
HO group.

(1) =Methyl.=--The narcotic action is strengthened and the antipyretic
action unaffected. The methæmoglobin in the blood is somewhat less.

(2) =Ethyl.=--Action very similar, but much less methæmoglobin is
produced.

(3) =Propyl.=--Antipyretic action a little weaker. Methæmoglobin in the
blood smaller than in para-acetamido-phenol, but more than when the
methyl or ethyl compound is administered.

(4) =Amyl.=--Antipyretic action decreased.

The smallest amount of toxicity is in the ethyl substitution; while the
maximum antipyretic and antineuralgic action belongs to the methyl
substitution.

Next substitution was tried in the Imid group. It was found that
substituting ethyl for H in the imid group annihilated the narcotic and
antipyretic properties. No methæmoglobin could be recognised in the
blood.

Lastly, simultaneous substitution of the H of the HO group by ethyl and
the substitution of an alkyl for the H in the NH group gave the
following results:--

=Methyl.=--In dogs the narcotic action was strengthened, the
methæmoglobin in the blood diminished. In men the narcotic action was
also more marked as well as the anti-neural action. The stomach and
kidneys were also stimulated.

=Ethyl.=--In dogs the narcotic action was much strengthened, while the
methæmoglobin was diminished. In men the antipyretic and anti-neural
actions were unaffected.

=Propyl.=--In dogs the narcotic action was feebler than with methyl or
ethyl, and in men there was diminished antipyretic action.

=Amyl.=--In dogs the narcotic action was much smaller.

From this latter series the conclusion is drawn that the maximum of
narcotic action is obtained by the introduction of methyl and the
maximum antipyretic action by the introduction of methyl or ethyl. The
ethyl substitution is, as before, the less toxic.[36]

[36] _Ueber die physiologische Wirkung des p-amido-phenol u. einiger
Derivate desselben._ O. Hinsberg u. G. Treupel, _Archiv f. Exp. Pathol.
u. Pharm._, B. 33, S. 216.

The effect of the entrance of an alkyl into the molecule of a substance
is not constant; sometimes the action of the poison is weakened,
sometimes strengthened. Thus, according to Stolnikow, dimethyl resorcin,
C₆H₄(OCH₃)₂, is more poisonous than resorcin C₆H₄(OH)₂. Anisol C₆H₅OCH₃,
according to Loew, is more poisonous to algæ, bacteria, and infusoria
than phenol C₆H₅OH. On the other hand, the replacement by methyl of an
atom of hydrogen in the aromatic oxyacids weakens their action; methyl
salicylic acid

       O.CH₃
      /
  C₆H₄
      \
       COOH

is weaker than salicylic acid

       OH
      /
  C₆H₄      .
      \
       COOH

Arsen-methyl chloride, As(CH₃)Cl₂, is strongly poisonous, but the
introduction of a second methyl As(CH₃)₂Cl makes a comparatively weak
poison.

§ 25. In some cases the increase of CO groups weakens the action of a
poison; thus, in allantoin there are three carbonyl (CO) groups; this
substance does not produce excitation of the spinal cord, but it
heightens muscular irritability and causes, like xanthin, muscular
rigidity; alloxantin, with a similar structure but containing six
carbonyl groups, does not possess this action.

  NH--CH--NH
   |  |   |
  CO  |   CO
   |  |   |
  NH--CO  NH₂

  Allantoin.

  NH--CO  CO--HN
   |  |   |   |
   |  | O |   |
   |  |/ \|   |
  CO--C---C   CO
   |  |   |   |
  NH--CO  CO--HN

  Alloxantin.

§ 26. A theory of general application has been put forward and supported
with great ability by Oscar Loew[37] which explains the action of
poisons by presuming that living has a different composition to dead
albumin; the albumin of the chemist is a dead body of a definite
composition and has a stable character; living albumin, such as
circulates in the blood or forms the protoplasm of the tissues, is not
“stable” but “labile”; Loew says:--“If the old idea is accepted that
living albumin is chemically the same substance as that which is dead,
numerous toxic phenomena are inexplicable. It is impossible, for
instance, to explain how it is that diamide N₂H₄ and hydroxylamine NH₂OH
are toxic, even with great dilution, on all living animals; whilst
neither of those substances have the smallest action on dead plasma or
the ordinary dissolved passive albumin, there must therefore be present
in the albumin of the living plasma a grouping of atoms in a “_labile_”
condition (_Atomgruppirungen labiler Art_) which are capable of entering
into reactions; such, according to our present knowledge, can only be
the aldehyde and the ketone groups. The first mentioned groups are more
labile and react in far greater dilution than the latter groups.”

[37] _Ein natürliches System der Gift-Wirkungen_, München, 1893.

Loew considers that all substances which enter into combination with
aldehyde or ketone groups must be poisonous to life generally. For
instance, hydroxylamine, diamide and its derivatives, phenylhydrazine,
free ammonia, phenol, prussic acid, hydric sulphide, sulphur dioxide and
the acid sulphites all enter into combination with aldehyde.

So again the formation of imide groups in the aromatic ring increases
any poisonous properties the original substance possesses, because the
imide group easily enters into combination with aldehyde; thus
piperidine (CH₂)₅NH is more poisonous than pyridine (CH)₅N; coniine
NH(CH₂)₄CH-CH₂-CH₂CH₃, is more poisonous than collidine
N(CH)₄C-CH-(CH₃)₂; pyrrol (CH)₄NH than pyridine (CH)₅N; and amarin,[38]

  C₆H₅-CH-NH
       |  \
       |   CH-C₆H₅,
       |  /
  C₆H₅-C=N

than hydrobenzamide

  C₆H₅-CH=N
          \
           CH-C₆H₅.
          /
  C₆H₅-CH=N

[38] Th. Weyl (_Lehrbuch der organischen Chemie_) states (p. 385) that
amarin is not poisonous, but Baccheti (_Jahr. d. Chemie_, 1855) has
shown that 250 mgrms. of the acetate will kill a dog, 80 mgrms. a
guinea-pig; and that it is poisonous to fishes, birds, and frogs:
hydrobenzamide in the same doses has no effect.

If the theory is true, then substances with “labile” amido groups, on
the one hand, must increase in toxic activity if a second amido group is
introduced; and, on the other, their toxic qualities must be diminished
if the amido group is changed into an imido group by the substitution of
an atom of hydrogen for an alkyl.

Observation has shown that both of these requirements are satisfied;
phenylenediamine is more poisonous than aniline; toluylenediamine more
poisonous than toluidine. Again, if an atom of hydrogen in the amido
(NH₂) group in aniline be replaced by an alkyl, _e.g._ methyl or ethyl,
the resulting substance does not produce muscular spasm; but if the same
alkyl is substituted for an atom of hydrogen in the benzene nucleus the
convulsive action remains unaffected.

If an acidyl, as for example the radical of acetic acid, enter into the
amido group, then the toxic action is notably weakened; thus,
acetanilide is weaker than aniline, and acetylphenylhydrazine is weaker
than phenylhydrazine. If the hydrogen of the imido group be replaced by
an alkyl or an acid radical, and therefore tertiary bound nitrogen
restored, the poisonous action is also weakened.

In xanthin there are three imido groups; the hydrogen of two of these
groups is replaced by methyl in theobromin; and in caffein the three
hydrogens of the three imido groups are replaced by three methyls,
thus:--

  NH--CH
  |   ║
  CO  C--NH
  |   |   \
  |   |    CO
  |   |   /
  NH--C==N

  Xanthin.

  N.CH₃--CH
  |      ║
  CO     C--N.CH₃
  |      |   \
  |      |    CO
  |      |   /
  NH-----C==N

  Theobromin.

  N.CH₃--CH
  |      ║
  CO     C--N.CH₃
  |      |   \
  |      |    CO
  |      |   /
  N.CH₃--C==N

  Caffein.

and experiment has shown that theobromin is weaker than xanthin, and
caffein still weaker than theobromin.

Loew[39] makes the following generalisations:--

[39] _Ein natürliches System der Gift-Wirkungen_, München, 1893.

1. Entrance of the carboxyl or sulpho groups weakens toxic action.

2. Entrance of a chlorine atom exalts the toxic character of the
catalytic poisons (Loew’s catalytic poisons are alcohols, ether,
chloroform, chloral, carbon tetrachloride, methylal, carbon disulphide
and volatile hydrocarbons).

3. Entrance of hydroxyl groups in the catalytic poisons of the fatty
series weakens toxic character; on the other hand, it exalts the
toxicity of the substituting poisons. (Examples of Loew’s class of
“substituting” poisons are hydroxylamine, phenylhydrazine, hydric
cyanide, hydric sulphide, aldehyde, and the phenols.)

4. A substance increases in poisonous character through every influence
which increases its power of reaction with aldehyde or amido groups. If,
for example, an amido or imido group in the poison molecule be made more
“labile,” or if thrice linked nitrogen is converted into nitrogen
connected by two bands, whether through addition of water or
transposition (_umlagerung_) or if a second amido group enters, the
poisonous quality is increased. Presence of a negative group may modify
the action.

5. Entrance of a nitro group strengthens the poisonous character. If a
carboxyl or a sulpho group is present in the molecule, or if, in passing
through the animal body, negative groups combine with the poison
molecule, or carboxyl groups are formed in the said molecule; in such
cases the poisonous character of the nitro group may not be apparent.

6. Substances with double carbon linkings are more poisonous than the
corresponding saturated substances. Thus neurine with the double linking
of the carbon of CH₂ is more poisonous than choline; vinylamine than
ethylamine.

          CH==CH₂
         /
  (CH₃)₃N
         \
          OH

  Neurine.

          CH₂--CH₂OH
         /
  (CH₃)₃N
         \
          OH

  Choline.

  CH₂
  ║
  CH.NH₂

  Vinylamine.

  CH₃
  |
  CH₂.NH₂

  Ethylamine.

§ 27. M. Ch. Michet[40] has investigated the comparative toxicity of the
metals by experiments on fish, using species of _Serranus_,
_Crenolabrus_, and _Julius_. The chloride of the metal was dissolved in
water and diluted until just that strength was attained in which the
fish would live 48 hours; this, when expressed in grammes per litre, he
called “_the limit of toxicity_.”

[40] “_De la Toxicité comparée des différents Métaux._” _Note de M. Ch.
Michet. Compt. Rend._, t. xciii., 1881, p. 649.

The following is the main result of the inquiry, by which it will be
seen that there was found no relation between “the limit of toxicity”
and the atomic weight.

TABLE SHOWING THE RESULTS OF EXPERIMENTS ON FISH.

    No. of                     Limit of
  Experiments.   Metal.        Toxicity.

      20.       Mercury,          ·00029
       7.       Copper,           ·0033
      20.       Zinc,             ·0084
      10.       Iron,             ·014
       7.       Cadmium,          ·017
       6.       Ammonium,         ·064
       7.       Potassium,        ·10
      10.       Nickel,           ·126
       9.       Cobalt,           ·126
      11.       Lithium,          ·3
      20.       Manganese         ·30
       6.       Barium,           ·78
       4.       Magnesium,       1·5
      20.       Strontium,       2·2
       5.       Calcium,         2·4
       6.       Sodium,         24·17


V.--Life-Tests; or the Identification of Poison by Experiments on
Animals.

§ 28. A philosophical investigation of poisons demands a complete
methodical examination into their action on every life form, from the
lowest to the highest. Our knowledge is more definite with regard to the
action of poisons on man, dogs, cats, rabbits, and frogs than on any
other species. It may be convenient here to make a few general remarks
as to the action of poisons on infusoria, the cephalopoda, and insects.

=Infusoria.=--The infusoria are extremely sensitive to the poisonous
alkaloids and other chemical agents. Strong doses of the alkaloids cause
a contraction of the cell contents, and somewhat rapid disintegration of
the whole body; moderate doses at first quicken the movements, then the
body gets perceptibly larger, and finally, as in the first case, there
is disintegration of the animal substance.

Rossbach[41] gives the following intimations of the proportion of the
toxic principle necessary to cause death:--Strychnine 1 part dissolved
in 1500 of water; veratrine 1 in 8000; quinine 1 in 5000; atropine 1 in
1000; the mineral acids 1 in 400-600; salts 1 in 200-300.

[41] N. J. Rossbach, _Pharm. Zeitschr. für Russland_, xix. 628.

The extraordinary sensitiveness of the infusoria, and the small amount
of material used in such experiments, would be practically useful if
there were any decided difference in the symptoms produced by different
poisons. But no one could be at all certain of even the class to which
the poison belongs were he to watch, without a previous knowledge of
what had been added to the water, the motions of poisoned infusoria.
Hence the fact is more curious than useful.

=Cephalopoda.=--The action of a few poisons on the cephalopoda has been
investigated by M. E. Yung.[42] Curara placed on the skin had no effect,
but on the branchiæ led to general paralysis. If given in even fifteen
times a greater dose than necessary to kill a rabbit, it was not always
fatal. Strychnine, dissolved in sea-water, in the proportion of 1 to
30,000, causes most marked symptoms. The first sign is relaxation of the
chromataphore muscle and the closing of the chromataphores; the animal
pales, the respiratory movements become more powerful, and at the end of
a notable augmentation in their number, they fall rapidly from the
normal number of 25 to 5 a minute. Then tetanus commences after a time,
varying with the dose of the poison; the arm stiffens and extends in
fan-like form, the entire body is convulsed, the respiration is in
jerks, the animal empties his pouch, and at the end of a few minutes is
dead, in a state of great muscular rigidity. If at this moment it is
opened, the venous heart is found still beating. Nicotine and other
poisons were experimented with, and the cephalopoda were found to be
generally sensitive to the active alkaloids, and to exhibit more or less
marked symptoms.

[42] _Compt. Rend._, t. xci. p. 306.

=Insects.=--The author devoted considerable time, in the autumn of 1882,
to observations on the effect of certain alkaloids on the common
blow-fly, thinking it possible that the insect would exhibit a
sufficient series of symptoms of physiological phenomena to enable it to
be used by the toxicologist as a living reagent. If so, the cheapness
and ubiquity of the tiny life during a considerable portion of the year
would recommend it for the purpose. Provided two blow-flies are caught
and placed beneath glass shades--the one poisoned, the other not--it is
surprising what a variety of symptoms can, with a little practice, be
distinguished. Nevertheless, the absence of pupils, and the want of
respiratory and cardiac movements, are, in an experimental point of
view, defects for which no amount or variety of merely muscular symptoms
can compensate.

From the nature of the case, we can only distinguish in the poisoned fly
dulness or vivacity of movement, loss of power in walking on smooth
surfaces, irritation of the integument, disorderly movements of the
limbs, protrusion of the fleshy proboscis, and paralysis, whether of
legs or wings. My experiments were chiefly made by smearing the extracts
or neutral solutions of poisons on the head of the fly. In this way some
of it is invariably taken into the system, partly by direct absorption,
and partly by the insect’s efforts to free itself from the foreign
substance, in which it uses its legs and proboscis. For the symptoms
witnessed after the application of saponin, digitalin, and aconitine,
the reader is referred to the articles on those substances.

In poisoning by sausages, bad meat, curarine, and in obscure cases
generally, in the present state of science, experiments on living
animals are absolutely necessary. In this, and in this way only, in very
many instances, can the expert prove the presence of zymotic, or show
the absence of chemical poison.

The Vivisection Act, however, effectually precludes the use of
life-tests in England save in licensed institutions. Hence the “methods”
of applying life-tests described in former editions will be omitted.

    § 29. =Effect of poisons on the heart of Cold-blooded Animals.=--The
    Vivisection Act does not, however, interfere with the use of certain
    living tests, such, for instance, as the testing of the action of
    poisons upon the recently extirpated hearts of cold-blooded animals.

[Illustration: Williams’ Apparatus.]

    The heart of the frog, of the turtle, of the tortoise, and of the
    shark will beat regularly for a long time after removal from the
    body, if supplied with a regular stream of nutrient fluid. The
    fluids used for this purpose are the blood of the herbivora diluted
    with common salt solution, or a serum albumin solution, or a 2 per
    cent. solution of gum arabic in which red blood corpuscles are
    suspended. The simplest apparatus to use is that known as
    “Williams’.” Williams’ apparatus consists of two glass bulbs (see
    diagram), the one, P, containing nutrient fluid to which a known
    quantity of the poison has been added; the other, N, containing the
    same fluid but to which no poison has been added; these bulbs are
    connected by caoutchouc tubing to a three-way tube, T, and each
    piece of caoutchouc tubing has a pressure screw clip, V¹ and V; the
    three-way tube is connected with a wider tube containing a valve
    float, F, which gives free passage of fluid in one direction only,
    that is, in the direction of the arrow; this last wide tube is
    connected with a Y piece of tubing, which again is connected with
    the aorta of the heart under examination, the other leg of the Y
    tube is connected with another wide tube, X, having a float valve,
    F²: the float containing a drop of mercury and permitting (like the
    float valve F) passage in one direction only of fluid, it is obvious
    that if the clip communicating with N is opened and the clip
    communicating with P is closed, the normal fluid will circulate
    alone through the heart; if, on the other hand, the P clip is open
    and the N clip closed, the poisoned blood will alone feed the heart.
    It is also clear that by raising or depressing the bulbs, the
    circulating fluid can be delivered at any pressure, high or low.
    Should a bubble of air get into the tubes, it can be got rid of by
    removing the cork at S and bringing the fluid up to the level of the
    top of the aperture. The observation is made by first ascertaining
    the number and character of the beats when the normal fluid is
    circulating, and then afterwards when the normal is replaced by the
    poisoned fluid. A simpler but less accurate process is to pith two
    frogs, excise their respective hearts, and place the hearts in
    watch-glasses containing either serum or a solution of common salt
    (strength 0·75 per cent.); to the one heart is now added a solution
    of the poison under examination, and the difference in the behaviour
    and character of the beats noted.

    The phenomena to be specially looked for are the following:--

  1. The heart at the height of the poisoning is arrested in diastole.
  2. The heart at the height of the poisoning is arrested in systole.

    =Arrest in diastole.=--The arrest may be preceded by the
    contractions becoming weaker and weaker, or after the so-called
    heart peristalsis; or it may be preceded by a condition in which the
    auricle shows a different frequency to the ventricle.

    The final diastole may be the diastole of paralysis or the diastole
    of irritation.

    The diastole of irritation is produced by a stimulus of the
    inhibitory ganglia, and only occurs after poisoning by the muscarine
    group of poisons. This condition may be recognised by the fact that
    contraction may be excited by mechanical and electrical stimuli or
    by the application of atropine solution; the latter paralyses the
    inhibitory nervous centres, and therefore sets the mechanism going
    again. The diastole of paralysis is the most frequent form of death.
    It may readily be distinguished from the muscarine diastole; for, in
    muscarine diastole, the heart is full of blood and larger than
    normal; but in the paralytic form the heart is not fully extended,
    besides which, although, if normal blood replace that which is
    poisoned, the beats may be restored for a short time, the response
    is incomplete, and the end is the same; besides which, atropine does
    not restore the beats. The diastole of paralysis may depend on
    paralysis of the so-called excito-motor ganglia (as with iodal), or
    from paralysis of the muscular structure (as with copper).

    § 30. =The effect of poisons on the iris.=--Several poisons affect
    the pupil, causing either contraction or dilatation. The most
    suitable animal is the cat; the pupil of the cat readily showing
    either state.

    =Toxic myosis, or toxic contraction of the pupil.=--There are two
    forms of toxic myosis, one of which is central in its origin. In
    this form, should the poison be applied to the eye itself, no marked
    contraction follows; the poison must be swallowed or injected
    subcutaneously to produce an effect. The contraction remains until
    death.

    The contraction in such a case is considered to be due to a
    paralysis of the dilatation centre; it is a “_myosis paralytica
    centralis_;” the best example of this is the contraction of the
    pupil caused by morphine.

    In the second case the poison, whether applied direct to the eye or
    entering the circulation by subcutaneous injection, contracts the
    pupil; the contraction persists if the eye is extirpated, but in all
    cases the contraction may be changed into dilatation by the use of
    atropine. An example of this kind of myosis is the action of
    muscarine. It is dependent on the stimulation of the ends of the
    nerves which contract the pupil, especially the ends of the _nervus
    oculomotorius_ supplying the sphincter iridis; this form of myosis
    is called _myosis spastica periphera_. A variety of this form is the
    _myosis spastica muscularis_, depending on stimulation of the musc.
    sphincter iridis, seen in poisoning by physostigmine. This causes
    strong contraction of the pupil when locally applied; the
    contraction is not influenced by small local applications of
    atropine, but it may be changed to dilatation by high doses.
    Subcutaneous injection of small doses of physostigmine does not
    alter the pupil, but large poisonous doses contracts the pupil in a
    marked manner.

    =Toxic mydriasis, or toxic dilatation of the pupil.=--The following
    varieties are to be noticed:--

    1. Toxic doses taken by the mouth or given by subcutaneous injection
    give rise to strong dilatation; this vanishes before death, giving
    place to moderate contraction. This form is due to stimulation of
    the dilatation centre, later passing into paralysis. An example is
    found in the action of aconite.

    2. After subcutaneous or local application, a dilatation neutralised
    by physostigmine in moderate doses. This is characteristic of
    β-tetrahydronaphthylamine.

    3. After subcutaneous injection, or if applied locally in very small
    doses, dilatation occurs persisting to death. Large doses of
    physostigmine neutralise the dilatation, but it is not influenced by
    muscarine or pilocarpine: this form is characteristic of atropine,
    and it has been called _mydriasis paralytica periphera_.

    The heart at the height of the poisoning stops in systole.

    =2. Arrest in systole.=--The systole preceding the arrest is far
    stronger than normal, the ventricle often contracting up into a
    little lump. Contraction of this kind is specially to be seen in
    poisoning by digitalis. In poisoning by digitalis the ventricle is
    arrested before the auricle; in muscarine poisoning the auricle
    stops before the ventricle. If the reservoir of Williams’ apparatus
    is raised so as to increase the pressure within the ventricle the
    beat may be restored for a time, to again cease.

    A frog’s heart under the influence of any poison may be finally
    divided into pieces so as to ascertain if any parts still contract;
    the significance of this is, that the particular ganglion supplying
    that portion of the heart has not been affected: the chief ganglia
    to be looked for are Remak’s, on the boundary of the sinus and
    auricle; Ludwig’s, on the auricle and the septum of the auricle;
    Bidder’s, on the atrioventricular border, especially in the valves;
    and Dogiel’s ganglion, between the muscular fibres. According to
    Dogiel, poisons acting like muscarine affect every portion of the
    heart, and atropine restores the contractile power of every portion.


VI.--General Method of Procedure in Searching for Poison.

§ 31. Mineral substances, or liquids containing only inorganic matters,
can cause no possible difficulty to any one who is practised in
analytical investigation; but the substances which exercise the skill of
the expert are organic fluids or solids.

The first thing to be done is to note accurately the manner in which the
samples have been packed, whether the seals have been tampered with,
whether the vessels or wrappers themselves are likely to have
contaminated the articles sent; and then to make a very careful
observation of the appearance, smell, colour, and reaction of the
matters, not forgetting to take the weight, if solid--the volume, if
liquid. All these are obvious precautions, requiring no particular
directions.

If the object of research is the stomach and its contents, the contents
should be carefully transferred to a tall conical glass; the organ cut
open, spread out on a sheet of glass, and examined minutely by a lens,
picking out any suspicious-looking substance for closer observation.
The mucous membrane should now be well cleansed by the aid of a
wash-bottle, and if there is any necessity for destroying the stomach,
it may be essential in important cases to have it photographed. The
washings having been added to the contents of the stomach, the sediment
is separated and submitted to inspection, for it must be remembered
that, irrespective of the discovery of poison, a knowledge of the nature
of the food last eaten by the deceased may be of extreme value.

If the death has really taken place from disease, and not from poison,
or if it has been caused by poison, and yet no definite hint of the
particular poison can be obtained either by the symptoms or by the
attendant circumstances, the analyst has the difficult task of
endeavouring to initiate a process of analysis which will be likely to
discover any poison in the animal, vegetable, or mineral kingdom. For
this purpose I have devised the following process, which differs from
those that have hitherto been published mainly in the prominence given
to operations in a high vacuum, and the utilisation of biological
experiment as a matter of routine. Taking one of the most difficult
cases that can occur--viz., one in which a small quantity only of an
organic solid or fluid is available--the best method of procedure is the
following:--

[Illustration]

A small portion is reserved and examined microscopically, and, if
thought desirable, submitted to various “cultivation” experiments. The
greater portion is at once examined for volatile matters, and having
been placed in a strong flask, and, if neutral or alkaline, feebly
acidulated with tartaric acid, connected with a second or receiving
flask by glass tubing and caoutchouc corks. The caoutchouc cork of the
receiving flask has a double perforation, so as to be able, by a second
bit of angle tubing, to be connected with the mercury-pump described in
the author’s work on “Foods,” the figure of which is here repeated (see
the accompanying figure). With a good water-pump having a sufficient
length of fall-tube, a vacuum may be also obtained that for practical
purposes is as efficient as one caused by mercury; if the fall-tube
delivers outside the laboratory over a drain, no offensive odour is
experienced when dealing with putrid, stinking liquids. A vacuum having
been obtained, and the receiving-flask surrounded with ice, a distillate
for preliminary testing may be generally got without the action of any
external heat; but if this is too slow, the flask containing the
substances or liquid under examination may be gently heated by a
water-bath--water, volatile oils, a variety of volatile substances, such
as prussic acid, hydrochloric acid, phosphorus, &c., if present, will
distil over. It will be well to free in this way the substance, as much
as possible, from volatile matters and water. When no more will come
over, the distillate may be carefully examined by redistillation and the
various appropriate tests.

[Illustration: This figure is from “Foods.” B is a bell-jar, which can
be adapted by a cork to a condenser; R is made of iron; the rim of the
bell-jar is immersed in mercury, which the deep groove receives.]

The next step is to dry the sample thoroughly. This is best effected
also in a vacuum by the use of the same apparatus, only this time the
receiving-flask is to be half filled with strong sulphuric acid. By now
applying very gentle heat to the first flask, and cooling the sulphuric
acid receiver, even such substances as the liver in twenty-four hours
may be obtained dry enough to powder.

Having by these means obtained a nearly dry friable mass, it is reduced
to a coarse powder, and extracted with petroleum ether; the extraction
may be effected either in a special apparatus (as, for example, in a
large “Soxhlet”), or in a beaker placed in the “Ether recovery
apparatus” (see fig.), which is adapted to an upright condenser. The
petroleum extract is evaporated and leaves the fatty matter, possibly
contaminated by traces of any alkaloid which the substance may have
contained; for, although most alkaloids are insoluble in petroleum
ether, yet they are taken up in small quantities by oils and fats, and
are extracted with the fat by petroleum ether. It is hence necessary
always to examine the petroleum extract by shaking it up with water,
slightly acidulated with sulphuric acid, which will extract from the fat
any trace of alkaloid, and will permit the discovery of such alkaloids
by the ordinary “group reagents.”

The substance now being freed for the most part from water and from fat,
is digested in the cold with absolute alcohol for some hours; the
alcohol is filtered off, and allowed to evaporate spontaneously, or, if
speed is an object, it may be distilled _in vacuo_. The treatment is
next with hot alcohol of 90 per cent., and, after filtering, the dry
residue is exhausted with ether. The ether and alcohol, having been
driven off, leave extracts which may be dissolved in water and tested,
both chemically and biologically, for alkaloids, glucosides, and organic
acids. It must also be remembered that there are a few metallic
compounds (as, for example, corrosive sublimate) which are soluble in
alcohol and ethereal solvents, and must not be overlooked.

The residue, after being thus acted upon successively by petroleum, by
alcohol, and by ether, is both water-free and fat-free, and also devoid
of all organic poisonous bases and principles, and it only remains to
treat it for metals. For this purpose, it is placed in a retort, and
distilled once or twice to dryness with a known quantity of strong, pure
hydrochloric acid.

If arsenic, in the form of arsenious acid, were present, it would distil
over as a trichloride, and be detected in the distillate; by raising the
heat, the organic matter is carbonised, and most of it destroyed. The
distillate is saturated with hydric sulphide, and any precipitate
separated and examined. The residue in the retort will contain the fixed
metals, such as zinc, copper, lead, &c. It is treated with dilute
hydrochloric acid, filtered, the filtrate saturated with SH₂ and any
precipitate collected. The filtrate is now treated with sufficient sodic
acetate to replace the hydric chloride, again saturated with SH₂ and any
precipitate collected and tested for _zinc_, _nickel_, and _cobalt_. By
this treatment, viz.:--

  1. Distillation in a vacuum at a low temperature,
  2. Collecting the volatile products,
  3. Dehydrating the organic substances,
  4. Dissolving out from the dry mass fatty matters and alkaloids,
     glucosides, &c., by ethereal and alcoholic solvents,
  5. Destroying organic matter and searching for metals,

--a very fair and complete analysis may be made from a small amount of
material. The process is, however, somewhat faulty in reference to
phosphorus, and also to oxalic acid and the oxalates; these poisons, if
suspected, should be specially searched for in the manner to be more
particularly described in the sections treating of them. In most cases,
there is sufficient material to allow of division into three parts--one
for organic poisons generally, one for inorganic, and a third for
reserve in case of accident. When such is the case, although, for
organic principles, the process of vacuum distillation just described
still holds good, it will be very much the most convenient way not to
use that portion for metals, but to operate on the portion reserved for
the inorganic poisons as follows by destruction of the organic matter.

The destruction of organic matter through simple distillation by means
of pure hydrochloric acid is at least equal to that by sulphuric acid,
chlorate of potash, and the carbonisation methods. The object of the
chemist not being to dissolve every fragment of cellular tissue, muscle,
and tendon, but simply all mineral ingredients, the less organic matter
which goes into solution the better. That hydrochloric acid would fail
to dissolve sulphate of baryta and sulphate of lead, and that sulphide
of arsenic is also almost insoluble in the acid, is no objection to the
process recommended, for it is always open to the analyst to treat the
residue specially for these substances. The sulphides precipitated by
hydric sulphide from an acid solution are--arsenic, antimony, tin,
cadmium, lead, bismuth, mercury, copper, and silver. Those not
precipitated are--iron, manganese, zinc, nickel, and cobalt.

As a rule, one poison alone is present; so that if there should be a
sulphide, it will belong only exceptionally to more than one metal.

The colour of the precipitate from hydric sulphide is either yellowish
or black. The yellow and orange precipitates are sulphur, sulphides of
arsenic, antimony, tin, and cadmium. In pure solutions they may be
almost distinguished by their different hues, but in solutions
contaminated by a little organic matter the colours may not be
distinctive. The sulphide of arsenic is of a pale yellow colour; and if
the very improbable circumstance should happen that arsenic, antimony,
and cadmium occur in the same solution, the sulphide of arsenic may be
first separated by ammonia, and the sulphide of antimony by sulphide of
sodium, leaving cadmic sulphide insoluble in both processes.

The black precipitates are--lead, bismuth, mercury, copper, and silver.
The black sulphide is freed from arsenic, if present, by ammonia, and
digested with dilute nitric acid, which will dissolve all the sulphides,
save those of mercury and tin, so that if a complete solution is
obtained (sulphur flocks excepted), it is evident that both these
substances are absent. The presence of copper is betrayed by the blue
colour of the nitric acid solution, and through its special reactions;
lead, by the deep yellow precipitate which falls by the addition of
chromate of potash and acetate of soda to the solution; bismuth, through
a white precipitate on dilution with water. If the nitric acid leaves a
black insoluble residue, this is probably sulphide of mercury, and
should be treated with concentrated hydrochloric acid to separate flocks
of sulphur, evaporated to dryness, again dissolved, and tested for
mercury by iodide of potassium, copper foil, &c., as described in the
article on _Mercury_. Zinc, nickel, and cobalt are likewise tested for
in the filtrate as described in the respective articles on these metals.


AUTENRIETH’S GENERAL PROCESS.

    § 32. A general method of procedure has been published by W.
    Autenrieth.[43]

[43] _Kurze Anleitung zur Auffindung der Gifte_, Freiburg, 1892.

    He divides poisonous substances, for the purposes of separation and
    detection, into three classes:--

    I. Poisons capable of distillation from an acid aqueous solution.
   II. Organic substances which are not capable of distillation from
       acid solutions.
  III. Metallic poisons.

    Where possible, the fluid or solids submitted to the research are
    divided into four equal parts, one of the parts to be kept in
    reserve in case of accident or as a control; one of the remaining
    three parts to be distilled; a second to be investigated for organic
    substances; and a third for metals. After the extraction of organic
    substances from part No. II. the residue may be added to No. III.
    for the purpose of search after metals; and, if the total quantity
    is small, the whole of the process may be conducted without
    division.


I. SUBSTANCES SEPARATED BY DISTILLATION.

    The substances are placed in a capacious flask, diluted if necessary
    with water to the consistence of a thin soup, and tartaric acid
    added to distinct acid reaction, and distilled.

    In this way phosphorus, prussic acid, carbolic acid, chloroform,
    chloral hydrate, nitrobenzol, aniline,[44] and alcohol may be
    separated and identified by the reactions given in the sections of
    this work describing those substances.

[44] Aniline is a weak base, so that, although a solution be acid, some
of the aniline distils over on heating.


II. ORGANIC POISONS NOT VOLATILE IN ACID SOLUTION.

    Part No. II. is mixed with double its volume of absolute alcohol,
    tartaric acid added to distinct acid reaction and placed in a flask
    connected with an inverted Liebig’s condenser; it is then warmed for
    15 to 20 minutes on the water-bath. After cooling, the mixture is
    filtered, the residue well washed with alcohol and evaporated to a
    thin syrup in a porcelain dish over the water-bath. The dish is then
    allowed to cool and digested with 100 c.c. of water; fat and
    resinous matters separate, the watery solution is filtered through
    Swedish paper previously moistened: if the fluid filtrate is clear
    it may be at once shaken up with ether, but if not clear, and
    especially if it is more or less slimy, it is evaporated again on
    the water-bath to the consistence of an extract: the extract treated
    with 60 to 80 c.c. of absolute alcohol (which precipitates mucus and
    dextrin-like substances), the alcohol evaporated off and the residue
    taken up with from 60 to 80 c.c. of distilled water; it is then
    shaken up with ether, as in Dragendorff’s process, and such
    substances as digitalin, picric acid, salicylic acid, antipyrin and
    others separated in this way and identified.

    After this treatment with ether, and the separation of the ether
    extract, the watery solution is strongly alkalised with caustic soda
    and shaken up again with ether, which dissolves almost every
    alkaloid save morphine and apomorphine; the ethereal extract is
    separated and any alkaloid left identified by suitable tests.

    The aqueous solution, now deprived of substances soluble in ether
    both from acid and from solutions made alkaline by soda, is now
    investigated for morphine and apomorphine; the apomorphine being
    separated by first acidifying a portion of the alkaline solution
    with hydrochloric acid, then alkalising with ammonia and shaking out
    with ether. The morphine is separated from the same solution by
    shaking out with warm chloroform.[45]

[45] Hot amyl alcohol would be better (see “Morphine”).


III. METALS.

    The substances are placed in a porcelain dish and diluted with a
    sufficient quantity of water to form a thin soup and 20 to 30 c.c.
    of pure hydrochloric acid added; the dish is placed on the
    water-bath and 2 grms. of potassic chlorate added. The contents are
    stirred from time to time, and successive quantities of potassic
    chlorate are again added, until the contents are coloured yellow.
    The heating is continued, with, if necessary, the addition of more
    acid, until all smell of chlorine has ceased. If there is
    considerable excess of acid, this is to be evaporated away by
    diluting with a little water and continuing to heat on the
    water-bath. The dish with its contents is cooled, a little water
    added, and the fluid is then filtered.

    The metals remaining on the filter are:--

  Silver chloride,
  Lead sulphate,
  Barium sulphate;

    in the filtrate will be all the other metals.

    The filtrate is put in a flask and heated to from 60 to 80 degrees
    and submitted to a slow stream of hydric sulphide gas; when the
    fluid is saturated with the gas, the flask is securely corked and
    allowed to rest for twelve hours; at the end of that time the fluid
    is filtered and the filter washed with water saturated with hydric
    sulphide.

    The still moist sulphides remaining on the filter are treated with
    yellow ammonium sulphide containing some free ammonia and washed
    with sulphide of ammonium water. Now remaining on the filter, if
    present at all, will be:--

  Mercury sulphide,
  Lead sulphide,
  Copper sulphide,
  Cadmium sulphide;

    in the filtrate may be:--

  Arsenic sulphide,
  Antimony sulphide,
  Tin sulphide,

    and there may also be a small portion of copper sulphide, because
    the latter is somewhat soluble in a considerable quantity of
    ammonium sulphide.

    The filtrate from the original hydric sulphide precipitate will
    contain, if present, the sulphides of zinc and chromium in solution.


INVESTIGATION OF THE SULPHIDES SOLUBLE IN AMMONIUM SULPHIDE, VIZ.,
ARSENIC, ANTIMONY, TIN.

    The ammonium sulphide solution is evaporated to dryness in a
    porcelain dish, strong nitric acid added and again dried. To this
    residue a little strong caustic soda solution is added, and then it
    is intimately mixed with three times its weight of a mixture
    composed of 2 of potassic nitrate to 1 of dry sodium hydrate. This
    is now cast, bit by bit, into a red-hot porcelain crucible. The
    whole is heated until it has melted into a colourless fluid.

    Presuming the original mass contained arsenic, antimony, and tin,
    the melt contains sodic arseniate, sodic pyro-antimonate, sodic
    stannate, and tin oxide; it may also contain a trace of copper
    oxide.

    The melt is cooled, dissolved in a little water, and sodium
    bicarbonate added so as to change any caustic soda remaining into
    carbonate, and to decompose the small amount of sodic stannate; the
    liquid is then filtered.

    The filtrate will contain the arsenic as sodic arseniate; while on
    the filter there will be pyro-antimonate of soda, tin oxide, and,
    possibly, a little copper oxide.

    The recognition of these substances now is not difficult (see the
    separate articles on _Antimony_, _Tin_, _Zinc_, _Arsenic_,
    _Copper_).


INVESTIGATION OF THE SULPHIDES INSOLUBLE IN SULPHIDE OF AMMONIUM, VIZ.,
MERCURY, LEAD, COPPER, CADMIUM.

    If the precipitate is contaminated with organic matter, it is
    treated with hydrochloric acid and potassic chlorate in the manner
    already described, p. 51.

    Afterwards it is once more saturated with hydric sulphide, the
    precipitate is collected on a filter, well washed, and the sulphides
    treated with moderately concentrated nitric acid (1 vol. nitric
    acid, 2 vols. water). The sulphides are best treated with this
    solvent on the filter; all the sulphides mentioned, save mercury
    sulphide, dissolve and pass into the filtrate. This mercury sulphide
    may be dissolved by nitro-muriatic acid, the solution evaporated to
    dryness, the residue dissolved in water acidified with hydrochloric
    acid and tested for mercury (see “Mercury”).

    The filtrate containing, it may be, nitrates of lead, copper and
    cadmium is evaporated nearly to dryness and taken up in a very
    little water. The lead is separated as sulphate by the addition of
    dilute sulphuric acid.

    The filtered solution, freed from lead, is treated with ammonia to
    alkaline reaction; if copper be present, a blue colour is produced,
    and this may be confirmed by other tests (see “Copper”). To detect
    cadmium in the presence of copper, potassic cyanide is added to the
    blue liquid until complete decolorisation, and the liquid treated
    with SH₂; if cadmium be present, it is thrown down as a yellow
    sulphide, while potassic cupro-cyanide remains in solution.


SEARCH FOR ZINC AND CHROMIUM.

    The filtrate from the hydric sulphide precipitate is divided into
    two parts; the one half is used in the search for zinc, the other
    half is used for chromium.

    =Search for Zinc.=--The liquid is alkalised with ammonia and then
    ammonium sulphide is added. There will always be a precipitate of a
    dark colour; the precipitate will contain earthy phosphates, iron
    and, in some cases, manganese. The liquid with the precipitate is
    treated with acetic acid to strong acid reaction and allowed to
    stand for several hours. The portion of the precipitate remaining
    undissolved is collected on a filter, washed, dried and heated to
    redness in a porcelain crucible. The residue thus heated is cooled
    and dissolved in a little dilute sulphuric acid. To the acid
    solution ammonia is added, and any precipitate formed is treated
    with acetic acid; should the precipitate not completely dissolve,
    phosphate of iron is present; this is filtered off, and if SH₂ be
    added to the filtrate, white zinc sulphide will come down (see
    “Zinc”).

    =Search for Chromium.=--The second part of the SH₂ filtrate is
    evaporated to a thin extract, mixed with double its weight of sodic
    nitrate, dried and cast, little by little, into a red-hot porcelain
    crucible. When the whole is fully melted, the crucible is removed
    from the flame, cooled, and the mass dissolved in water and
    filtered. Any chromium present will now be in solution in the easily
    recognised form of potassic chromate (see “Chromium”).


INVESTIGATION OF THE RESIDUE (p. 52) AFTER THE TREATMENT OF THE ORIGINAL
SUBSTANCE WITH HYDROCHLORIC ACID AND POTASSIC CHLORATE FOR PRESENCE OF
SILVER CHLORIDE, LEAD AND BARIUM SULPHATES.

    The residue is dried and intimately mixed with three times its
    weight of a mixture containing 2 parts of sodic nitrate and 1 part
    of sodium hydrate, This is added, little by little, into a red-hot
    porcelain crucible. The melted mass is cooled, dissolved in a little
    water, a current of CO₂ passed through the solution to convert any
    caustic soda into carbonate, and the solution boiled. The result
    will be an insoluble portion consisting of carbonates of lead and
    baryta, and of metallic silver. The mixture is filtered; the
    insoluble residue on the filter is warmed for some time with dilute
    nitric acid; the solution of nitrates of silver, lead and barium are
    concentrated on the water-bath nearly to dryness so as to get rid of
    any excess of acid, and the nitrates dissolved in water; then the
    silver is precipitated by hydrochloric acid, the lead by SH₂, and
    the barium by sulphuric acid.


VII.--The Spectroscope as an aid to the Identification of certain
Poisons.

§ 33. The spectra of many of the metals, of phosphine, of arsine and of
several other inorganic substances are characteristic and easily
obtained.

It is, however, from the employment of the _micro-spectroscope_ that the
toxicologist is likely to get most assistance.

[Illustration]

Oscar Brasch[46] has within the last few years studied spectroscopy in
relation to the alkaloids and organic poisons. Some of these, when mixed
with Froehde’s reagent, or with sulphuric acid, or with sulphuric acid
and potassic dichromate, or with nitric acid, give characteristic
colours, and the resulting solutions, when examined by a spectroscope,
for the most part show absorption bands; these bands may, occasionally,
assist materially in the identification of a poison. By far the best
apparatus is a micro-spectroscope of the Sorby and Browning type, to
which is added an apparatus for measuring the position on a scale of the
lines and bands. Seibert and Kraft of Wetzlar make an excellent
instrument, in which a small bright triangle is projected on the
spectrum; this can be moved by a screw, so that the apex may be brought
exactly in the centre of any line or band, and its position read on an
outside scale. The first thing to be done with such an instrument is to
determine the position on the scale of the chief Fraunhofer lines or of
the more characteristic lines of the alkalies and alkaline earths,[47]
the wave lengths of which are accurately known. If, now, the scale
divisions are set out as abscissæ, and the wave lengths in millionths of
a millimetre are made the ordinates of a diagram, and an equable curve
plotted out, as fully explained in the author’s work on “Foods,” it is
easy to convert the numbers on the scale into wave lengths, and so make
the readings applicable to any spectroscope. For the purpose of
graphical illustration the curve method is convenient, and is adopted in
the preceding diagrams, all taken from Oscar Brasch’s monograph. Where
the curve is highest there the absorption band is thickest; where the
curve is lowest there the band is weak. The fluid to be examined is
simply placed in a watch-glass, the watch-glass resting on the
microscope stand.

[46] _Ueber Verwendbarkeit der Spectroscopie zur Unterscheidung der
Farbenreactionen der Gifte im Interesse der forensischen Chemie_,
Dorpat, 1890.

[47] The alkalies and earths used for this purpose, with their wave
lengths, are as follows: KCl, a line in the red λ 770, in the violet λ
404. Lithium chloride, red line, 670·5; sodium chloride, yellow, 589;
strontium chloride, line in the blue, 461. It is also useful to measure
the green line of thallium chloride = 535.

[Illustration: CURVES INDICATING THE POSITION OF ABSORPTION BANDS ON
TREATING CERTAIN ALKALOIDS WITH REAGENTS.

NOTES TO CURVES INDICATING ABSORPTION BANDS.

   1. Strychnine, treated with sulphuric acid and potassic dichromate
      (violet).
   2. Brucine, treated with potassic nitrate and sulphuric acid (clear
      red).
   3. Quebrachine, treated with vanadium sulphate (dark blue).
   4. Quinine, Vogel’s reaction (red).
   5. Caffein, Murexid reaction (violet-red).
   6. Dephinoidin, Froehde’s reagent (cherry-red).
   7. Veratrine, treated with sulphuric acid (straw-yellow).
   8.     „        „             „           (cherry-red).
   9.     „        „             „           (carmine-red).
  10. Veratrine, Furfurol reaction (blue-violet).
  11. Sabadillin, treated with sulphuric acid (red).
  12. Veratroidine,     „          „          (brown-red).
  13. Jervine, Furfurol reaction (blue).
  14. Sabadine,   „        „     (blue).
  15. Sabadine, treated with sulphuric acid (cherry-red).
  16. Physostigmine,   „         „          (grass-green).
  17. Morphine, treated with Froehde’s reagent and sugar (dark-green).
  18. Narcotine, treated with a mixture of sulphuric acid and nitric
      acid (30 drops of sulphuric to 1 drop of nitric), (red).
  19. Codeine, treated with Froehde’s reagent and sugar (dark violet).
  20. Papaverine, treated with Froehde’s reagent (green-blue).
  21. Sanguinarin,      „         „              (violet-red).
  22. Chelidonin,       „      sulphate of vanadium (dark green).
  23. Solanin,          „      sulphuric acid and allowed to stand 4
                               hours (brown-red).
  24. Digitalin,        „      Erdmann’s reagent (red).
  25. Aniline,          „      sulphuric acid and potassic dichromate
      (blue).]

The wave lengths corresponding to the numbers on the scale in the
diagram are as follows:--

           W.L.
  0        732
  1        656
  2        589·2
  3        549·8
  4        510·2
  5        480·0
  6        458
  7        438


Examination of Blood, or of Blood-Stains.

§ 34. Spots, supposed to be blood--whether on linen, walls, or
weapons--should, in any important case, be photographed before any
chemical or microscopical examination is undertaken. Blood-spots,
according to the nature of the material to which they are adherent, have
certain naked eye peculiarities--_e.g._, blood on fabrics, if dry, has
at first a clear carmine-red colour, and part of it soaks into the
tissue. If, however, the tissue has been worn some time, or was
originally soiled, either from perspiration, grease, or filth, the
colour may not be obvious or very distinguishable from other stains;
nevertheless, the stains always impart a certain stiffness, as from
starch, to the tissue. If the blood has fallen on such substances as
wood or metal, the spot is black, has a bright glistening surface, and,
if observed by a lens, exhibits radiating fissures and a sort of
pattern, which, according to some, is peculiar to each species; so that
a skilled observer might identify occasionally, from the pattern alone,
the animal whence the blood was derived. The blood is dry and brittle,
and can often be detached, or a splinter of it, as it were, obtained.
The edges of the splinter, if submitted to transmitted light, are
observed to be red. Blood upon iron is frequently very intimately
adherent; this is specially the case if the stain is upon rusty iron,
for hæmatin forms a compound with iron oxide. Blood may also have to be
recovered from water in which soiled articles have been washed, or from
walls, or from the soil, &c. In such cases the spot is scraped off from
walls, plaster, or masonry, with as little of the foreign matters as may
be. It is also possible to obtain the colouring-matter of blood from its
solution in water, and present it for farther examination in a
concentrated form, by the use of certain precipitating agents (see p.
61).

In the following scheme for the examination of blood-stains, it is
presumed that only a few spots of blood, or, in any case, a small
quantity, is at the analyst’s disposal.

(1) The dried spot is submitted to the action of a cold saturated
solution of borax. This medium (recommended by Dragendorff)[48] does
certainly dissolve out of linen and cloth blood-colouring matter with
great facility. The best way to steep the spots in the solution is to
scrape the spot off the fabric, and to digest it in about a cubic
centimetre of the borax solution, which must not exceed 40°; the
coloured solution may be placed in a little glass cell, with parallel
walls, ·5 centimetre broad, and ·1 deep, and submitted to spectroscopic
examination, either by the ordinary spectroscope or by the
micro-spectroscope; if the latter is used, a very minute quantity can be
examined, even a single drop. In order to interpret the results of this
examination properly, it will be necessary to be intimately acquainted
with the spectroscopic appearances of both ancient and fresh blood.

[48] _Untersuchungen von Blutspuren_ in Maschka’s _Handbuch_, Bd. i.
Halfband 2.

§ 35. =Spectroscopic Appearances of Blood.=--If defibrinated blood[49]
be diluted with water until it contains about ·01 per cent. of
oxyhæmoglobin, and be examined by a spectroscope, the layer of liquid
being 1 centimetre thick, a single absorption band between the wave
lengths 583 and 575 is observed, and, under favourable circumstances,
there is also to be seen a very weak band from 550 to 532. With
solutions so dilute as this, there is no absorption at either the violet
or the red end of the spectrum. A solution containing ·09 per cent. of
oxyhæmoglobin shows very little absorption in the red end, but the
violet end is dark up to about the wave length 428. Two absorption bands
may now be distinctly seen. A solution containing ·37 per cent. of
oxyhæmoglobin shows absorption of the red end to about W.L. 720; the
violet is entirely, the blue partly, absorbed to about 453. The bands
are considerably broader, but the centre of the bands occupies the same
relative position. A solution containing as much as ·8 per cent. of
oxyhæmoglobin is very dark; the two bands have amalgamated, the red end
of the spectrum is absorbed nearly up to Fraunhofer’s line a; the green
is just visible between W.L. 498 and 518. Venous blood, or arterial
blood, which has been treated with reducing agents, such, for example,
as an alkaline sulphide, gives the spectrum of reduced hæmoglobin. If
the solution is equivalent to about ·2 per cent., a single broad band,
with the edges very little defined, is seen to occupy the space between
W.L. 595 and 538, the band being darkest about 550; both ends of the
spectrum are more absorbed than by a solution of oxyhæmoglobin of the
same strength. In the blood of persons or animals poisoned with hydric
sulphide--to the spectrum of reduced hæmoglobin, there is added a weak
absorption band in the red, with its centre nearly corresponding with
the Fraunhofer line C. Blood which has been exposed to carbon oxide has
a distinct spectrum, due, it would seem, to a special combination of
this gas with hæmoglobin; in other words, instead of oxygen, the oxygen
of oxyhæmoglobin has been displaced by carbon oxide, and crystals of
carbon oxide-hæmoglobin, isomorphous with those of oxyhæmoglobin, may be
obtained by suitable treatment. The spectrum of carbon oxide-hæmoglobin,
however, differs so little from that of normal blood, that it is only
comparison with the ordinary spectrum, or careful measurements, which
will enable any person, not very familiar with the different spectra of
blood, to detect it; with careful and painstaking observation the two
spectra are seen to be distinct. The difference between the carbon oxide
and the normal spectrum essentially consists in a slight moving of the
bands nearer to E. According to the measurements of Gamgee, the band α
of CO-hæmoglobin has its centre approximately at W.L. 572, and the band
β has for its centre W.L. from 534 to 538, according to concentration.
If a small quantity of an ammoniacal solution of ferrous tartrate or
citrate be added to blood containing carbon oxide, the bands do not
wholly fade, but persist more or less distinctly; whereas, if the same
solution is added to bright red normal blood, the two bands vanish
instantly and coalesce to form the spectrum of reduced hæmoglobin. When
either a solution of hæmoglobin or blood is exposed to the air for some
time, it loses its bright red colour, becomes brownish-red, and presents
an acid reaction. On examining the spectrum, the two bands have become
faint, or quite extinct; but there is a new band, the centre of which
(according to Gamgee) occupies W.L. 632, but (according to Preyer) 634.
In solutions of a certain strength, four bands may be seen, but in a
strong solution only one. This change in the spectrum is due to the
passing of the hæmoglobin into _methæmoglobin_, which may be considered
as an intermediate stage of decomposition, prior to the breaking up of
the hæmoglobin into hæmatin and proteids.

[49] In this brief notice of the spectroscopic appearances of the blood,
the measurements in wave lengths are, for the most part, after
Gamgee.--_Text-Book of Physiological Chemistry_, London, 1880.

A spectrum very similar to that of methæmoglobin is obtained by treating
ancient blood-stains with acetic acid--viz., the spectrum of _acid
hæmatin_, but the band is nearer to its centre, according to Gamgee,
corresponding to W.L. 640 (according to Preyer, 656·6). The portion of
the band is a little different in alkaline solution, the centre being
about 592. Hæmatin is one of the bodies into which hæmoglobin splits up
by the addition of such agents as strong acetic acid, or by the
decomposing influence of exposure; the view most generally accepted
being that the colouring-matter of the blood is hæmatin in combination
with one or more albuminoid bodies. The hæmatin obtained by treating
blood with acetic acid may be dissolved out by ether, and the ethereal
solution then exhibits a remarkable distinctive spectrum. Hence, in the
spectroscopic examination of blood, or solutions of blood, for
medico-legal purposes, if the blood is fresh, the spectrum likely to be
seen is either that of oxyhæmoglobin or hæmoglobin; but, if the
blood-stain is not recent, then the spectrum of either hæmatin or
methæmoglobin.

The colouring-matter of cochineal, to which alum, potassic carbonate,
and tartrate have been added, gives a spectrum very similar to that of
blood (see “Foods,” p. 82); but this is only the case when the solution
is fresh. The colour is at once discharged by chlorine, while the colour
of blood, although changed in hue, remains. The colouring-matter of
certain red feathers, purpurin-sulphuric acid, and a few other reds,
have some similarity to either the hæmatin or the hæmoglobin spectrum,
but the bands do not strictly coincide; besides, no one would trust to a
single test, and none of the colouring-matters other than blood yield
hæmatin.

The blood in CO poisoning has also other characteristics. It is of a
peculiar florid vermilion colour, a colour that is very persistent,
lasting for days and even weeks.

Normal blood mixed with 30 per cent. potash solution forms _greenish_
streaky clots, while blood charged with CO forms red streaky clots.

Normal blood diluted to 50 times its volume of water, and then treated
successively with yellow ammonium sulphide in the proportion of 2 to 25
c.c. of blood, followed by three drops of acetic acid, gives a grey
colour, while CO blood remains bright red. CO blood shaken with 4 times
its volume of lead acetate remains red, but normal blood becomes
brown.[50]

[50] M. Rubner, _Arch. Hyg._, x. 397.

Solutions of platinum chloride or zinc chloride give a bright red colour
with CO blood; normal blood is coloured brown or very dark brown.

Phospho-molybdic acid or 5 per cent. phenol gives a carmine-coloured
precipitate with CO blood, but a reddish-brown precipitate with normal
blood (sensitive to 16 per cent.).

A mixture of 2 c.c. of dilute acetic acid and 15 c.c. of 20 per cent.
potassic ferrocyanide solution added to 10 c.c. of CO blood produces an
intense bright red; normal blood becomes dark brown.

Four parts of CO blood, diluted with 4 parts of water and shaken with 3
vols. of 1 per cent. tannin solution, become at first bright red with a
bluish tinge, and remain so persistently. Normal blood, on the other
hand, also strikes bright red at first, but with a yellowish tinge; at
the end of 1 hour it becomes brownish, and finally in 24 hours grey.
This is stated to be delicate enough to detect 0·0023 per cent. in air.

If blood be diluted with 40 times its volume of water, and 5 drops of
phenylhydrazin solution be added, CO blood strikes rose-red; normal
blood grey-violet.[51]

[51] A. Welzel, _Centr. med. Wiss._, xxvii. 732-734.

Gustave Piotrowski[52] has experimented on the length of time blood
retains CO. The blood of dogs poisoned by this agent was kept in flasks,
and then the gas pumped out by means of a mercury pump on the following
dates:--

[52] _Compt. Rend. Soc. de Biol._, v. 433.

  Date.                Content of gas in CO.
  Jan.  12, 1892,          24·7 per cent.
    „   20,   „            23·5    „
    „   28,   „            22·2    „
  Feb.   8,   „            20·3    „
    „   16,   „            15·5    „
    „   26,   „            10·2    „
  March  3,   „             6·3    „
    „   14,   „             4·6    „
    „   22,   „             1·2    „

The same dog was buried on the 12th of January, and exhumed on March
28th, and the gas pumped out from some of the blood; this gas gave 11·7
per cent. of CO; hence it is clear that burial preserves CO blood from
change to a certain extent.

N. Gréhant[53] treated the poisoned blood of a dog with acetic acid, and
found it evolved 14·4 c.c. CO from 100 c.c. of blood.

[53] _Compt. Rend._, cvi. 289.

Stevenson, in one of the cases detailed at p. 67, found the blood in the
right auricle to contain 0·03 per cent. by weight of CO.

(2) =Preparation of Hæmatin Crystals=--(Teichmann’s crystals).--A
portion of the borax solution is diluted with 5 or 6 parts of water, and
one or more drops of a 5 or 6 per cent. solution of zinc acetate added,
so long as a brownish-coloured precipitate is thrown down. The
precipitate is filtered off by means of a miniature filter, and then
removed on to a watch-glass. The precipitate may now be dissolved in 1
or 2 c.c. of acetic acid, and examined by the spectroscope it will show
the spectrum of hæmatin. A minute crystal of sodic chloride being then
added to the acetic acid solution, it is allowed to evaporate to dryness
at the ordinary temperature, and crystals of hæmatin hydrochlorate
result. There are other methods of obtaining the crystals. When a drop
of fresh blood is simply boiled with glacial acetic acid, on
evaporation, prismatic crystals are obtained.

Hæmatin is insoluble in water, alcohol, chloroform, and in cold dilute
acetic and hydrochloric acids. It may, however, be dissolved in an
alcoholic solution of potassic carbonate, in solutions of the caustic
alkalies, and in boiling acetic and hydrochloric acids. Hoppe-Seyler
ascribes to the crystals the formula C₆₈H₇₀N₈Fe₂O₁₀2HCl. Thudichum
considers that the pure crystals contain no chlorine, and are therefore
those of hæmatin. It is the resistance of the hæmatin to decomposition
and to ordinary solvents that renders it possible to identify a certain
stain to be that of blood, after long periods of time. Dr. Tidy seems to
have been able to obtain blood reactions from a stain which was supposed
to be 100 years old. The crystals are of a dark-red colour, and present
themselves in three forms, of which that of the rhombic prism is the
most common (see fig.). But crystals like _b_, having six sides, also
occur, and also crystals similar to _c_.

[Illustration]

If the spot under examination has been scraped off an iron implement the
hæmatin is not so easily extracted, but Dragendorff states that borax
solution at 50° dissolves it, and separates it from the iron. Felletar
has also extracted blood in combination with iron rust, by means of warm
solution of caustic potash, and, after neutralisation with acetic acid,
has precipitated the hæmin by means of tannin, and obtained from the
tannin precipitate, by means of acetic acid, Teichmann’s crystals. A
little of the rust may also be placed in a test tube, powdered ammonium
chloride added, also a little strong ammonia, and after a time filtered;
a small quantity of the filtrate is placed on a slide with a crystal of
sodium chloride and evaporated at a gentle heat, then glacial acetic
acid added and allowed to cool; in this way hæmin crystals have been
obtained from a crowbar fifty days after having been blood-stained.[54]

[54] _Brit. Med. Journ._, Feb. 17, 1894.

(3) =Guaiacum Test.=--This test depends upon the fact that a solution of
hæmoglobin develops a beautiful blue colour, if brought into contact
with fresh tincture of guaiacum and peroxide of hydrogen. The simplest
way to obtain this reaction is to moisten the suspected stain with
distilled water; after allowing sufficient time for the water to
dissolve out some of the blood constituents, moisten a bit of
filter-paper with the weak solution thus obtained; drop on to the moist
space a single drop of tincture of guaiacum which has been prepared by
digesting the inner portions of guaiacum resin in alcohol, and which has
been already tested on known blood, so as to ascertain that it is really
good and efficient for the purpose; and, lastly, a few drops of peroxide
of hydrogen. Dragendorff uses his borax solution, and, after a little
dilution with water, adds the tincture and then Heunefeld’s turpentine
solution, which is composed of equal parts of absolute alcohol,
chloroform, and French turpentine, to which one part of acetic acid has
been added. The chloroform separates, and, if blood was present, is of a
blue colour.

§ 36. To prove by chemical and physical methods that a certain stain is
that of blood, is often only one step in the inquiry, the next question
being whether the blood is that of man or of animals. The
blood-corpuscles of man are larger than those of any domestic animal
inhabiting Europe. The diameter of the average red blood-corpuscle is
about the 1/126 of a millimetre, or 7·9 µ.[55] The corpuscles of man and
of mammals, generally speaking, are round, those of birds and reptiles
oval, so that there can be no confusion between man and birds, fishes or
reptiles; if the corpuscles are circular in shape the blood will be that
of a mammal. By careful measurements, Dr. Richardson, of Pennsylvania,
affirms that it is quite possible to distinguish human blood from that
of all common animals. He maintains, and it is true, that, by using very
high magnifying powers and taking much trouble, an expert can
satisfactorily identify human blood, if he has some half-dozen drops of
blood from different animals--such as the sheep, goat, horse, dog, cat,
&c., all fresh at hand for comparison, and _if the human blood is
normal_. However, when we come to the blood of persons suffering from
disease, there are changes in the diameter and even the form of the
corpuscles which much complicate the matter; while, in blood-stains of
any age, the blood-corpuscles, even with the most artfully-contrived
solvent, are so distorted in shape that he would be a bold man who
should venture on any definite conclusion as to whether the blood was
certainly human, more especially if he had to give evidence in a
criminal case.

[55] 1/3200 of an inch; the Greek letter µ is the micro-millimetre, or
1000th of a millimetre, ·00003937 inch.

Neumann affirms that the pattern which the fibrin or coagulum of the
blood forms is peculiar to each animal, and Dr. Day, of Geelong, has
independently confirmed his researches: this very interesting
observation perhaps has not received the attention it merits.

When there is sufficient of the blood present to obtain a few milligrms.
of ash, there is a means of distinguishing human blood from that of
other common mammals, which has been neglected by authorities on the
subject, and which may be found of real value. Its principle depends
upon the relative amounts of potassium and sodium in the blood of man as
compared with that in the blood of domestic animals. In the blood of the
cow, sheep, fowl, pig, and horse, the sodium very much exceeds the
potassium in the ash; thus the proportion of sodium oxide to that of
potassium oxide in the blood of the sheep is as K₂O ·1 : Na₂O ·6; in
that of the cow, as 1 : 8; in that of the domestic fowl, as 1 : 16;
while the same substances in human blood are sometimes equal, and vary
from 1 : 1 to 1 : 4 as extremes, the mean numbers being as 1 : 2·2. The
potassium is greater in quantity in the blood-corpuscles than in the
blood serum; but, even in blood serum, the same marked differences
between the blood of man and that of many animals is apparent. Thus, the
proportion of potash to soda being as 1 : 10 in human blood, the
proportion in sheep’s blood is 1 to 15·7; in horse’s serum as 1 to 16·4;
and in the ox as 1 to 17. Since blood, when burnt, leaves from 6 to 7
per thousand of ash, it follows that a quantitative analysis of the
relative amounts of potassium and sodium can only be satisfactorily
effected when sufficient of the blood is at the analyst’s disposal to
give a weighable quantity of mineral matter. On the other hand, much
work requires to be done before this method of determining that the
blood is either human, or, at all events, not that of an herbivorous
animal, can be relied on. We know but little as to the effect of the
ingestion of sodium or potassium salts on either man or animals, and it
is possible--nay, probable--that a more or less entire substitution of
the one for the other may, on certain diets, take place. Bunge seems in
some experiments to have found no sodium in the blood of either the cat
or the dog.

The source from which the blood has emanated may, in a few cases, be
conjectured from the discovery, by microscopical examination, of hair or
of buccal, nasal, or vaginal epithelium, &c., mixed with the
blood-stain.




PART III.--POISONOUS GASES: CARBON MONOXIDE--CHLORINE--HYDRIC SULPHIDE.


I.--Carbon Monoxide.

§ 37. Carbon monoxide, CO, is a colourless, odourless gas of 0·96709 sp.
gravity. A litre weighs 1·25133 grm. It is practically insoluble in
water. It unites with many metals, forming gaseous or volatile
compounds, _e.g._, nickel carbon oxide, Ni(CO)₄, is a fluid volatilising
at 40°. These compounds have, so far as is known, the same effects as
CO.

Whenever carbon is burned with an insufficient supply of air, CO in a
certain quantity is produced. It is always present in ordinary domestic
products of combustion, and must be exhaled from the various chimneys of
a large city in considerable volumes. A “smoky” chimney or a defective
flue will therefore introduce carbon monoxide into living-rooms. The
vapour from burning coke or burning charcoal is rich in carbon monoxide.
It is always a constituent of coal gas, in England the carbon monoxide
in coal gas amounting to about 8 per cent. Poisoning by coal gas is
practically poisoning by carbon monoxide. Carbon monoxide is also the
chief constituent in water gas.

Carbon monoxide poisoning occurs far more frequently in France and
Germany than in England; in those countries the vapour evolved from
burning charcoal is a favourite method of suicide, on account of the
supposed painlessness of the death. It has also occasionally been used
as an instrument of murder. In this country carbon monoxide poisoning
mainly takes place accidentally as the effect of breathing coal gas;
possibly it is the secret and undetected cause of ill health where
chimneys “smoke”; and it may have something to do with the sore throats
and debility so often noticed when persons breathe for long periods air
contaminated by small leakages of coal gas.

The large gas-burners (geysers) emit in burning under certain conditions
much carbon monoxide. It has been proved by Gréhant[56] that a bunsen
burner “lit below” also evolves large quantities of the same poisonous
gas.

[56] _Compt. Rend. Soc. de Biol._, ix. 779-780.

§ 38. =Symptoms.=--Nearly all the experience with regard to the symptoms
produced by carbon monoxide is derived from breathing not the pure gas,
but the gas diluted by air, by hydrogen or by carburetted hydrogen, as
in coal gas, or mixed with large quantities of carbon dioxide. Two
assistants of Christison breathed the pure gas: the one took from two to
three inhalations; he immediately became giddy, shivered, had headache
and then became unconscious. The second took a bigger dose, for, after
emptying his lungs as much as possible, he took from three to four
inhalations; he fell back paralysed, became unconscious and remained
half-an-hour insensible and had the appearance of death, the pulse being
almost extinguished. He was treated with inhalations of oxygen, but he
remained for the rest of the day extremely ill; he had convulsive
muscular movements, stupor, headache, and quick irregular pulse; on this
passing away he still suffered from nausea, giddiness, alternate feeling
of heat and chilliness, with some fever, and in the night had a restless
kind of sleep. The chemist Chenot was accidentally poisoned by the pure
gas, and is stated to have fell as if struck by lightning after a single
inspiration, and remained for a quarter of an hour unconscious. Other
recorded cases have shown very similar symptoms.

The pulse is at the onset large, full and frequent; it afterwards
becomes small, slow and irregular. The temperature sinks from 1° to 3°
C. The respiration at first slow, later becomes rattling. As vomiting
occurs often when the sufferer is insensible, the vomited matters have
been drawn by inspiration into the trachea and even into the bronchi, so
that death takes place by suffocation.

The fatal coma may last even when the person has been removed from the
gas from hours to days. Coma for three, four and five days from carbon
monoxide has been frequently observed. The longest case on record is
that of a person who was comatose for eight days, and died on the
twelfth day after the fatal inhalation. Consciousness in this case
returned, but the patient again fell into stupor and died.

The slighter kinds of poisoning by carbon monoxide, as in the
Staffordshire case recorded by Dr. Reid, in which for a long time a much
diluted gas has been breathed, produce pronounced headache and a general
feeling of ill health and _malaise_, deepening, it may be, into a fatal
slumber, unless the person is removed from the deadly atmosphere. To the
headache generally succeeds nausea, a feeling of oppression in the
temples, a noise in the ears, feebleness, anxiety and a dazed condition
deepening into coma. It is probably true that charcoal vapour is
comparatively painless, for when larger amounts of the gas are breathed
the insensibility comes on rapidly and the faces of those who have
succumbed as a rule are placid. Vomiting, without being constant, is a
frequent symptom, and in fatal cases the fæces and urine are passed
involuntarily. There are occasional deviations from this picture;
tetanic strychnine-like convulsions have been noticed and a condition of
excitement in the non-fatal cases as if from alcohol; in still rarer
cases temporary mania has been produced.

In non-fatal but moderately severe cases of poisoning sequelæ follow,
which in some respects imitate the sequelæ seen on recovery from the
infectious fevers. A weakness of the understanding, incapacity for
rational and connected thought, and even insanity have been noticed.
There is a special liability to local inflammations, which may pass into
gangrene. Various paralyses have been observed. Eruptions of the skin,
such as herpes, pemphigus and others. Sugar in the urine is an almost
constant concomitant of carbon monoxide poisoning.

§ 39. The poisonous action of carbon monoxide is, without doubt, due to
the fact that it is readily absorbed by the blood, entering into a
definite chemical compound with the hæmoglobin; this combination is more
stable than the similar compound with oxygen gas, and is therefore slow
in elimination.

Hence the blood of an animal remaining in an atmosphere containing
carbon monoxide is continually getting poorer in oxygen, richer in
carbon monoxide. Gréhant has shown that if an animal breathes for one
hour a mixture of 0·5 carbon monoxide to 1000 oxygen, the blood contains
at the end of that time one-third less oxygen than normal, and contains
152 times more carbon monoxide than in the mixture. An atmosphere of 10
per cent. carbon monoxide changes the blood so quickly, that after from
10 to 25 seconds the blood contains 4 per cent. of carbon monoxide, and
after from 75 to 90 seconds 18·4 per cent. Breathing even for half an
hour an atmosphere containing from 0·07 to 0·12 per cent. carbon
monoxide renders a fourth part of the red corpuscles of the blood
incapable of uniting with oxygen.

The blood is, however, never saturated with carbon monoxide, for the
animal dies long before this takes place.

The characteristics of the blood and its spectroscopic appearances are
described at p. 58.

Besides the action on the blood there is an action on the nervous
system. Kobert,[57] in relation to this subject, says:--“That CO has a
direct action on the nervous system is shown in a marked manner when an
atmosphere of oxygen, with at least 20 per cent. carbon oxide, is
breathed; for in the first minute there is acute cramp or total
paralysis of the limbs, when the blood in no way attains the saturation
sufficiently great to account for such symptoms. Geppert has, through a
special research, shown that an animal suffocated by withdrawal of
oxygen, increases the number and depth of the respirations; but when the
animal is submitted to CO, in which case there is quite as much a
withdrawal of oxygen as in the former case, yet the animal is not in a
condition to strengthen its respiratory movements; Geppert hence rightly
concludes that CO must have a primary specific injurious action on the
nerve centres. I (Kobert) am inclined to go a step further, and, on the
ground of unpublished researches, to maintain that CO not only affects
injuriously the ganglion cells of the brain, but also the peripheral
nerves (_e.g._, the phrenic), as well as divers other tissues, as
muscles and glands, and that it causes so rapidly such a high degree of
degeneration as not to be explained through simple slow suffocation;
even gangrene may be caused.”

[57] _Lehrbuch der Intoxicationen_, 526.

It is this rapid degeneration which is the cause of the enormous
increase of the products of the decomposition of albumin, found
experimentally in animals.

§ 40. =Post-mortem Appearances.=--The face, neck, chest, abdomen are
frequently covered with patches of irregular form and of clear rose-red
or bluish-red colour; these patches are not noticed on the back, and
thus do not depend upon the gravitation of the blood to the lower or
most dependent part of the body; similar red patches have been noticed
in poisoning by prussic acid; the cause of this phenomenon is ascribed
to the paralysis of the small arteries of the skin, which, therefore,
become injected with the changed blood. The blood throughout is
generally fluid, and of a fine peculiar red colour, with a bluish tinge.
The face is mostly calm, pale, and there is seldom any foam about the
lips. Putrefaction is mostly remarkably retarded. There is nearly always
a congestion of some of the internal organs; sometimes, and indeed
usually, the membranes of the brain are strongly injected; sometimes the
congestion is mainly in the lungs, which may be œdematous with effusion;
and in a third class of cases the congestion is most marked in the
abdominal cavity.

The right heart is commonly filled with blood, and the left side
contains only a little blood.

Poisoning by a small dose of carbon monoxide may produce but few
striking changes, and then it is only by a careful examination of the
blood that evidence of the real nature of the case will be obtained.

§ 41. =Mass poisonings by Carbon Monoxide.=--An interesting series of
cases of poisoning by water gas occurred at Leeds in 1889, and have been
recorded by Dr. Thos. Stevenson.[58]

[58] _Guy’s Hospital Reports_, 1889.

Water gas is made by placing coke in a vertical cylinder and heating the
coke to a red heat. Through the red-hot coke, air is forced up from
below for ten minutes; then the air is shut off and steam passes from
above downwards for four minutes; the gas passes through a scrubber, and
then through a ferric oxide purifier to remove SH₂. It contains about 50
per cent. of hydrogen and 40 per cent. of carbon monoxide, that is,
about five times more carbon monoxide than coal gas.

On November 20, 1889, two men, R. French and H. Fenwick, both
intemperate men, occupied a cabin at the Leeds Forge Works; the cabin
was 540 c. feet in capacity, and was lighted by two burners, each
burning 5·5 c. feet of water gas per hour; the cabin was warmed by a
cooking stove, also burning water gas, the products of combustion
escaping into the cabin. Both men went into the cabin after breakfast
(8.30 A.M.). French was seen often going to and fro, and Fenwick was
seen outside at 10.30 A.M. At 11.30 the foreman accompanied French to
the cabin, and found Fenwick asleep, as he thought. At 12.30 P.M.
French’s son took the men their dinner, which was afterwards found
uneaten. At that time French also appeared to be asleep; he was shaken
by his son, upon which he nodded to his son to leave. The door of the
cabin appears to have been shut, and all through the morning the lights
kept burning; no smell was experienced. At 2.30 P.M. both the men were
discovered dead. It was subsequently found that the stove was unlighted,
and the water gas supply turned on.

What attracted most attention to this case was the strange incident at
the _post-mortem_ examination. The autopsies were begun two days after
the death, November 22, in a room of 39,000 c. feet capacity. There were
present Mr. T. Scattergood (senior), Mr. Arthur Scattergood (junior),
Mr. Hargreaves, three local surgeons, Messrs. Brown, Loe and Jessop, and
two assistants, Pugh and Spray. Arthur Scattergood first fainted, Mr.
Scattergood, senior, also had some peculiar sensations, viz., tingling
in the head and slight giddiness; then Mr. Pugh became faint and
staggered; and Mr. Loe, Mr. Brown, and Mr. Spray all complained.

These symptoms were not produced, as was at first thought, by some
volatile gas or vapour emanating from the bodies of the poisoned men,
but, as subsequently discovered, admitted of a very simple explanation;
eight burners in the room were turned partly on and not lighted, and
each of the eight burners poured water gas into the room.

In 1891 occurred some cases of poisoning[59] by CO which are probably
unique. The cases in question happened in January in a family at
Darlaston. The first sign of anything unusual having happened to the
family most affected was the fact that up to 9 A.M., Sunday morning,
January 18, none of the family had been seen about. The house was broken
into by the neighbours; and the father, mother, and three children were
found in bed apparently asleep, and all efforts to rouse them utterly
failed. The medical men summoned arrived about 10 A.M. and found the
father and mother in a state of complete unconsciousness, and two of the
children, aged 11 and 14 years, suffering from pain and sickness and
diarrhœa; the third child had by this time been removed to a
neighbouring cottage.

[59] “Notes on cases of poisoning by the inhalation of carbon monoxide,”
by Dr. George Reid, Medical Officer of Health, County of Stafford.
_Public Health_, vol. iii. 364.

Dr. Partridge, who was in attendance, remained with the patients three
hours, when he also began to suffer from headache; while others, who
remained in the house longer, suffered more severely and complained of
an indefinite feeling of exhaustion. These symptoms pointed to some
exciting cause associated with the surroundings of the cottage;
consequently, in the afternoon the two children were removed to another
cottage, and later on the father and mother also. All the patients, with
the exception of the mother, who was still four days afterwards
suffering from the effects of an acute attack, had completely recovered.
The opinion that the illness was owing to some local cause was
subsequently strengthened by the fact that two canaries and a cat had
died in the night in the kitchen of the cottage; the former in a cage
and the latter in a cupboard, the door of which was open. Also in the
same house on the opposite side of the road, the occupants of which had
for some time suffered from headache and depression, two birds were
found dead in their cage in the kitchen. It is important to notice that
all these animals died in the respective kitchens of the cottages, and,
therefore, on the ground floor, while the families occupied the first
floor.

The father stated that for a fortnight or three weeks previous to the
serious illness, he and the whole family had complained of severe
frontal headache and a feeling of general depression. This feeling was
continuous day and night in the case of the rest of the family, but in
his case, during the day, after leaving the house for his work, it
gradually passed off, to return again during the night. The headaches
were so intense that the whole family regularly applied vinegar rags to
their heads, on going to bed each night during this period, for about
three weeks. About two o’clock on Sunday morning the headaches became so
severe that the mother got out of bed and renewed the application of
vinegar and water all round, after which they all fell asleep, and, so
far as the father and mother were concerned, remained completely
unconscious until Monday morning.

A man who occupied the house opposite the house tenanted by the
last-mentioned family informed the narrator (Dr. Reid) that on Sunday
morning the family, consisting of four, were taken seriously ill with a
feeling of sickness and depression accompanied by headache; and he also
stated that for some time they had smelt what he termed a “fire stink”
issuing from the cellar.

The cottage in which the family lived that had suffered so severely was
situated about 20 or 30 yards from the shaft of a disused coal mine, and
was the end house of a row of cottages. It had a cellar opening into the
outer air, but this opening was usually covered over by means of a piece
of wood. The adjoining house to this, the occupants of which had for
some time suffered from headache, although to a less extent, had a
cellar with a similar opening, but supplied with an ill-fitting cover.
The house on the opposite side of the road, in which the two birds were
found dead, had a cellar opening both at the front and the back; but
both these openings, until a little before the occurrence detailed, had
been kept closed. The cellars in all cases communicated with the houses
by means of doors opening into the kitchens. According to the general
account of the occupants, the cellars had smelled of “fire stink,”
which, in their opinion, proceeded from the adjoining mine.

The shaft of the disused mine communicated with a mine in working order,
and, to encourage the ventilation in this mine, a furnace had for some
weeks been lit and suspended in the shaft. This furnace had set fire to
the coal in the disused mine and smoke had been issuing from the shaft
for four weeks previously. Two days previous to the inquiry the opening
of the shaft had been closed over with a view to extinguish the fire.

Dr. Reid considered, from the symptoms and all the circumstances of the
case, that the illness was due to carbon monoxide gas penetrating into
the cellars from the mine, and from thence to the living- and
sleeping-rooms. A sample of the air yielded 0·015 per cent. of carbon
monoxide, although the sample had been taken after the cellar windows
had been open for twenty-four hours.

§ 42. =Detection of Carbon Monoxide.=--It may often be necessary to
detect carbon monoxide in air and to estimate its amount. The detection
in air, if the carbon monoxide is in any quantity, is easy enough; but
traces of carbon monoxide are difficult. Where amounts of carbon
monoxide in air from half a per cent. upwards are reasonably presumed to
exist, the air is measured in a gas measuring apparatus and passed into
an absorption pipette charged with alkaline pyrogallic acid, and when
all the oxygen has been abstracted, then the residual nitrogen and gases
are submitted to an ammoniacal solution of cuprous chloride.

The solution of cuprous chloride is prepared by dissolving 10·3 grms. of
copper oxide in 150 c.c. of strong hydrochloric acid and filling the
flask with copper turnings; the copper reduces the cupric chloride to
cuprous chloride; the end of the reduction is known by the solution
becoming colourless. The colourless acid solution is poured into some
1500 c.c. of water, and the cuprous chloride settles to the bottom as a
precipitate. The supernatant fluid is poured off as completely as
possible and the precipitate washed into a quarter litre flask, with 100
to 150 c.c. of distilled water and ammonia led into the solution until
it becomes of a pale blue colour. The solution is made up to 200 c.c. so
as to contain about 7·3 grms. per cent. of cuprous chloride.

Such a solution is an absorbent of carbon monoxide; it also absorbs
ethylene and acetylene.

A solution of cuprous chloride which has absorbed CO gives it up on
being treated with potassic bichromate and acid. It has been proposed by
Wanklyn to deprive large quantities of air of oxygen, then to absorb any
carbon monoxide present with cuprous chloride, and, lastly, to free the
cuprous chloride from the last gas by treatment with acid bichromate, so
as to be able to study the properties of a small quantity of pure gas.

By far the most reliable method to detect small quantities of carbon
monoxide is, however, as proposed by Hempel, to absorb it in the lungs
of a living animal.

A mouse is placed between two funnels joined together at their mouths by
a band of thin rubber; one of the ends of the double funnel is connected
with an aspirator, and the air thus sucked through, say for half an hour
or more; the mouse is then killed by drowning, and a control mouse,
which has not been exposed to a CO atmosphere, is also drowned; the
bodies of both mice are cut in two in the region of the heart, and the
blood collected. Each sample of blood is diluted in the same proportion
and spectroscopically examined in the manner detailed at p. 58.

Winkler found that, when large volumes of gas were used (at least 10
litres), 0·05 per cent. of carbon monoxide could be readily detected.


II.--Chlorine.

§ 43. Chlorine is a yellow-green gas, which may, by cold and pressure,
be condensed into a liquid. Its specific gravity is, as compared with
hydrogen, 35·37; as compared with air, 2·45; a litre under standard
conditions weighs 3·167 grms. It is soluble in water.

The usual method of preparation is the addition of hydrochloric acid to
bleaching powder, which latter substance is hypochlorite of lime mixed
with calcic chloride and, it may be, a little caustic lime. Another
method is to treat manganese dioxide with hydrochloric acid or to act on
manganese dioxide and common salt with sulphuric acid.

Accidents are liable to occur with chlorine gas from its extensive use
as a disinfectant and also in its manufacture. In the “Weldon” process
of manufacturing bleaching powder, a thick layer of lime is placed on
the floor of special chambers; chlorine gas is passed into these
chambers for about four days; then the gas is turned off; the unabsorbed
gas is drawn off by an exhaust or absorbed by a lime distributor and the
doors opened. Two hours afterwards the men go in to pack the powder. The
packers, in order to be able to work in the chambers, wear a respirator
consisting of about thirty folds of damp flannel; this is tightly bound
round the mouth with the nostrils free and resting upon it. The men are
obliged to inhale the breath through the flannel and exhale through the
nostril, otherwise they would, in technical jargon, be “gassed.” Some
also wear goggles to protect their eyes. Notwithstanding these
precautions they suffer generally from chest complaints.

§ 44. =Effects.=--Free chlorine, in the proportion of 0·04 to 0·06 per
thousand, taken into the lungs is dangerous to life, since directly
chlorine attacks a moist mucous membrane, hydrochloric acid is formed.
The effects of chlorine can hardly be differentiated from hydrochloric
acid gas, and Lehmann found that 1·5 per thousand of this latter gas
affected animals, causing at once uneasiness, evidence of pain with
great dyspnœa, and later coma. The eyes and the mucous membrane of the
nose were attacked. Anatomical changes took place in the cornea, as
evidenced by a white opacity.

In cases that recovered, a purulent discharge came from the nostrils
with occasional necrosis of the mucous membrane. The symptoms in man are
similar; there is great tightness of the breath, irritation of the nose
and eyes, cough and, with small repeated doses, bronchitis with all its
attendant evils. Bleaching powder taken by the mouth is not so deadly.
Hertwig has given 1000 grms. to horses, 30 grms. to sheep and goats, and
15 grms. to dogs without producing death. The symptoms in these cases
were quickening of the pulse and respiration, increased peristaltic
action of the bowels and a stimulation of the kidney secretion. The
urine smelt of chlorine.

§ 45. =Post-mortem Appearances.=--Hyperæmia of the lungs, with
ecchymoses and pneumonic patches with increased secretion of the
bronchial tubes. In the mucous membrane of the stomach, ecchymoses. The
alkalescence of the blood is diminished and there may be external signs
of bleaching. Only exceptionally has any chlorine smell been perceived
in the internal organs.

§ 46. =Detection of Free Chlorine.=--The usual method of detection is to
prepare a solution of iodide of potassium and starch and to soak strips
of filter-paper in this solution. Such a strip, when moistened and
submitted to a chlorine atmosphere, is at once turned blue, because
chlorine displaces iodine from its combination with potassium.
Litmus-paper, indigo blue or other vegetable colours are at once
bleached.

To estimate the amount of chlorine a known volume of the air is drawn
through a solution of potassium iodide, and the amount of iodine set
free, determined by titration with sodic hyposulphite, as detailed at p.
74.


III.--Hydric Sulphide (Sulphuretted Hydrogen).

§ 47. Hydric sulphide, SH₂, is a colourless transparent gas of sp.
gravity 1·178. It burns with a blue flame, forming water and sulphur
dioxide, and is soluble in water; water absorbing about three volumes
at ordinary temperatures. It is decomposed by either chlorine gas or
sulphur dioxide.

It is a common gas as a constituent of the air of sewers or cesspools,
and emanates from moist slag or moist earth containing pyrites or
metallic sulphides; it also occurs whenever albuminous matter putrefies;
hence it is a common constituent of the emanations from corpses of
either man or animals. It has a peculiar and intense odour, generally
compared to that of rotten eggs; this is really not a good comparison,
for it is comparing the gas with itself, rotten eggs always producing
SH₂; it is often associated with ammonium sulphide.

§ 48. =Effects.=--Pure hydric sulphide is never met with out of the
chemist’s laboratory, in which it is a common reagent either as a gas or
in solution; so that the few cases of poisoning by the pure gas, or
rather the pure gas mixed with ordinary air, have been confined to
laboratories.

The greater number of cases have occurred accidentally to men working in
sewers, or cleaning out cesspools and the like. In small quantities it
is always present in the air of towns, as shown by the blackening of any
silver ornament not kept bright by frequent use.

It is distinctly a blood poison, the gas uniting with the alkali of the
blood, and the sulphide thus produced partly decomposing again in the
lung and breathed out as SH₂. Lehmann[60] has studied the effects on
animals; an atmosphere containing from 1 to 3 per thousand of SH₂ kills
rabbits and cats within ten minutes; the symptoms are mainly convulsions
and great dyspnœa. An atmosphere containing from 0·4 to 0·8 per thousand
produces a local irritating action on the mucous membranes of the
respiratory tract, and death follows from an inflammatory œdema of the
lung preceded by convulsions; there is also a paralysis of the nervous
centres. Lehmann has recorded the case of three men who breathed 0·2 per
thousand of SH₂: within from five to eight minutes there was intense
irritation of the eyes, nose, and throat, and after thirty minutes they
were unable to bear the atmosphere any longer. Air containing 0·5 per
thousand of SH₂ is, according to Lehmann, the utmost amount that can be
breathed; this amount causes in half an hour smarting of the eyes, nasal
catarrh, dyspnœa, cough, palpitation, shivering, great muscular
weakness, headache and faintness with cold sweats. 0·7 to 0·8 per
thousand is dangerous to human life, and from 1 to 1·5 per thousand
destroys life rapidly. The symptoms may occur some little time after the
withdrawal of the person from the poisonous atmosphere; for example,
Cahn records the case of a student who prepared SH₂ in a laboratory and
was exposed to the gas for two hours; he then went home to dinner and
the symptoms first commenced in more than an hour after the first
breathing of pure air. Taylor[61] records an unusual case of poisoning
in 1857 at Cleator Moor. Some cottages had been built upon iron slag,
the slag contained sulphides of calcium and iron; a heavy storm of rain
washed through the slag and considerable volumes of SH₂ with, no doubt,
other gases diffused during the night through the cottages and killed
three adults and three children.

[60] K. B. Lehmann, _Arch. f. Hygiene_, Bd. xiv., 1892, 135.

[61] _Principles and Practice of Medl. Jurisp._, vol. ii. 122.

§ 49. =Post-mortem Appearances.=--The so-called apoplectic form of SH₂
poisoning, in which the sufferer dies within a minute or two, shows no
special change. The most frequent change in slower poisoning is,
according to Lehmann, œdema of the lungs. A green colour of the face and
of the whole body is sometimes present, but not constant. A
spectroscopic examination of the blood may also not lead to any
conclusion, the more especially as the spectrum of sulphur methæmoglobin
may occur in any putrid blood. The pupils in some cases have been found
dilated; in others not so.

=Chronic poisoning.=--Chronic poisoning by SH₂ is of considerable
interest in a public health point of view. The symptoms appear to be
conjunctivitis, headache, dyspepsia and anæmia. A predisposition to
boils has also been noted.

§ 50. =Detection.=--Both ammonium and hydric sulphides blacken silver
and filter-paper moistened with acetate of lead solution. To test for
hydric sulphide in air a known quantity may be aspirated through a
little solution of lead acetate. To estimate the quantity a decinormal
solution of iodine in potassium iodide[62] solution is used, and its
exact strength determined by d.n. sodic hyposulphite solution[63]; the
hyposulphite is run in from a burette into a known volume, _e.g._, 50
c.c., of the d.n. iodine solution, until the yellow colour is almost
gone; then a drop or two of fresh starch solution is added and the
hyposulphite run in carefully, drop by drop, until the blue colour of
the starch disappears. If now a known volume of air is drawn through 50
c.c. of the d.n. iodine solution, the reaction I₂ + SH₂ = 2HI + S will
take place, and for every 127 parts of iodine which have been converted
into hydriodic acid 17 parts by weight of SH₂ will be necessary; hence
on titrating the 50 c.c. of d.n. iodine solution, through which air
containing SH₂ has been passed, less hyposulphite will be used than on
the previous occasion, each c.c. of the hyposulphite solution being
equal to 1·11 c.c. or to 1·7 mgrm. of SH₂.

[62] 12·7 grms. of iodine, 16·6 grms. of potassium iodide, dissolved in
a litre of water.

[63] 24·8 grms. of sodic hyposulphite, dissolved in a litre of water.




PART IV.--ACIDS AND ALKALIES.

    SULPHURIC ACID--HYDROCHLORIC ACID--NITRIC ACID--ACETIC
    ACID--AMMONIA--POTASH--SODA--NEUTRAL SODIUM, POTASSIUM, AND AMMONIUM
    SALTS.


I.--Sulphuric Acid.

§ 51. Sulphuric acid (hydric sulphate, oil of vitriol, H₂SO₄) occurs in
commerce in varying degrees of strength or dilution; the strong
sulphuric acid of the manufacturer, containing 100 per cent. of real
acid (H₂SO₄), has a specific gravity of 1·850. The ordinary brown acid
of commerce, coloured by organic matter and holding in solution metallic
impurities, chiefly lead and arsenic, has a specific gravity of about
1·750; and contains 67·95 of anhydrous SO₃ = 85·42 of hydric sulphate.

There are also weaker acids used in commerce, particularly in
manufactories in which sulphuric acid is made, for special purposes
without rectification. The British Pharmacopœia sulphuric acid is
directed to be of 1·843 specific gravity, which corresponds to 78·6 per
cent. sulphuric anhydride, or 98·8 per cent. of hydric sulphate. The
dilute sulphuric acid of the pharmacopœia should have a specific gravity
of 1·094, and is usually said to correspond to 10·14 per cent. of
anhydrous sulphuric acid; but, if Ure’s Tables are correct, such equals
11·37 per cent.

The general characters of sulphuric acid are as follows:--When pure, it
is a colourless, or, when impure, a dark brown to black, oily liquid,
without odour at common temperatures, of an exceedingly acid taste,
charring most organic tissues rapidly, and, if mixed with water,
evolving much heat. If 4 parts of the strong acid are mixed with 1 part
of water at 0°, the mixture rises to a heat of 100°; a still greater
heat is evolved by mixing 75 parts of acid with 27 of water.

Sulphuric acid is powerfully hygroscopic--3 parts will, in an ordinary
atmosphere, increase to nearly 4 in twenty-four hours; in common with
all acids, it reddens litmus, yellows cochineal, and changes all
vegetable colours. There is another form of sulphuric acid, extensively
used in the arts, known under the name of “Nordhausen sulphuric acid,”
“fuming acid,” formula H₂S₂O₄. This acid is produced by the distillation
of dry ferrous sulphate, at a nearly white heat--either in earthenware
or in green glass retorts; the distillate is received in sulphuric acid.
As thus manufactured, it is a dark fuming liquid of 1·9 specific
gravity, and boiling at 53°. When artificially cooled down to 0°, the
acid gradually deposits crystals, which consist of a definite compound
of 2 atoms of anhydrous sulphuric acid and 1 atom of water. There is
some doubt as to the molecular composition of Nordhausen acid; it is
usually considered as hydric sulphate saturated with sulphur dioxide.
This acid is manufactured chiefly in Bohemia, and is used, on a large
scale, as a solvent for alizarine.

§ 52. =Sulphur Trioxide, or Sulphuric Anhydride= (SO₃), itself may be
met with in scientific laboratories, but is not in commerce. Sulphur
trioxide forms thin needle-shaped crystals, arranged in feathery groups.
Seen in mass, it is white, and has something the appearance of asbestos.
It fuses to a liquid at about 18°, boils at 35°, but, after this
operation has been performed, the substance assumes an allotropic
condition, and then remains solid up to 100°; above 100° it melts,
volatilises, and returns to its normal condition. Sulphuric anhydride
hisses when it is thrown into water, chemical combination taking place
and sulphuric acid being formed. Sulphur trioxide is excessively
corrosive and poisonous.

Besides the above forms of acid, there is an officinal preparation
called “Aromatic Sulphuric Acid,” made by digesting sulphuric acid,
rectified spirit, ginger, and cinnamon together. It contains 10·19 per
cent. of SO₃, alcohol, and principles extracted from cinnamon and
ginger.

§ 53. Sulphuric acid, in the free state, may not unfrequently be found
in nature. The author has had under examination an effluent water from a
Devonshire mine, which contained more than one grain of free sulphuric
acid per gallon, and was accused, with justice, of destroying the fish
in a river. It also exists in large quantities in volcanic springs. In a
torrent flowing from the volcano of Parcé, in the Andes, Boussingault
calculated that 15,000 tons of sulphuric acid and 11,000 tons of
hydrochloric acid were yearly carried down. In the animal and vegetable
kingdom, sulphuric acid exists, as a rule, in combination with bases,
but there is an exception in the saliva of the _Dolium galea_, a
Sicilian mollusc.

§ 54. =Statistics.=--When something like 900,000 tons of sulphuric acid
are produced annually in England alone, and when it is considered that
sulphuric acid is used in the manufacture of most other acids, in the
alkali trade, in the manufacture of indigo, in the soap trade, in the
manufacture of artificial manure, and in a number of technical
processes, there is no cause for surprise that it should be the annual
cause of many deaths.

The number of deaths from sulphuric acid will vary, other things being
equal, in each country, according to the manufactures in that country
employing sulphuric acid. The number of cases of poisoning in England
and Wales for ten years is given in the following table:--

DEATHS FROM SULPHURIC ACID IN ENGLAND AND WALES FOR THE TEN YEARS ENDING
1892.

                     ACCIDENT OR NEGLIGENCE.

  Ages,      1-5   5-15   15-25   25-65    65 &     Total
                                          upwards
  Males,      11     4       2      14       2        33
  Females,     4   ...       2       3     ...         9
            ---------------------------------------------
  Totals,     15     4       4      17       2        42
            ---------------------------------------------

                             SUICIDE.

  Ages,                   15-25   25-65             Total
  Males,                     4      25                29
  Females,                   5      19                24
                         ---------------------------------
  Totals                     9      44                53
                         ---------------------------------

During the ten years, no case of murder through sulphuric acid is on
record; hence the total deaths, as detailed in the tables, amount to 95,
or a little over 9 a year.

Falck,[64] in comparing different countries, considers the past
statistics to show that in France sulphuric acid has been the cause of
4·5 to 5·5 per cent. of the total deaths from poison, and in England 5·9
per cent. In England, France, and Denmark, taken together, 10·8, Prussia
10·6; while in certain cities, as Berlin and Vienna, the percentages are
much higher--Vienna showing 43·3 per cent., Berlin 90 per cent.

[64] _Lehrbuch der praktischen Toxicologie_, p. 54.

§ 55. =Accidental, Suicidal, and Criminal Poisoning.=--Deaths from
sulphuric acid are, for the most part, accidental, occasionally
suicidal, and, still more rarely, criminal. In 53 out of 113 cases
collected by Böhm, in which the cause of the poisoning could, with fair
accuracy, be ascertained, 45·3 per cent. were due to accident, 30·2 were
suicidal, and 24·5 per cent. were cases of criminal poisoning, the
victims being children.

The cause of the comparatively rare use of sulphuric acid by the
poisoner is obvious. First of all, the acid can never be mixed with food
without entirely changing its aspect; next, it is only in cases of
insensibility or paralysis that it could be administered to an adult,
unless given by force, or under very exceptional circumstances; and
lastly, the stains on the mouth and garments would at once betray, even
to uneducated persons, the presence of something wrong. As an agent of
murder, then, sulphuric acid is confined in its use to young children,
more especially to the newly born.

There is a remarkable case related by Haagan,[65] in which an adult man,
in full possession of his faculties, neither paralysed nor helpless, was
murdered by sulphuric acid. The wife of a day-labourer gave her husband
drops of sulphuric acid on sugar, instead of his medicine, and finally
finished the work by administering a spoonful of the acid. The spoon was
carried well to the back of the throat, so that the man took the acid at
a gulp. 11 grms. (171 grains) of sulphuric acid, partly in combination
with soda and potash, were separated from his stomach.

[65] Gross: _Die Strafrechtspflege in Deutschland_, 4, 1861, Heft I. S.
181.

Accidental poisoning is most common among children. The oily,
syrupy-looking sulphuric acid, when pure, may be mistaken for glycerin
or for syrup; and the dark commercial acid might, by a careless person,
be confounded with porter or any dark-looking medicine.

Serious and fatal mistakes have not unfrequently arisen from the use of
injections. Deutsch[66] relates how a midwife, in error, administered to
mother and child a sulphuric acid clyster; but little of the fluid could
in either case have actually reached the rectum, for the mother
recovered in eight days, and in a little time the infant was also
restored to health. Sulphuric acid has caused death by injections into
the vagina. H. C. Lombard[67] observed a case of this kind, in which a
woman, aged thirty, injected half a litre of sulphuric acid into the
vagina, for the purpose of procuring abortion. The result was not
immediately fatal, but the subsequent inflammation and its results so
occluded the natural passage that the birth became impossible, and a
Cæsarean section extracted a dead child, the mother also dying.

[66] _Preuss. Med. Vereins-Zeitung_, 1848, No. 13.

[67] _Journ. de Chim. Méd._, tom. vii., 1831.

An army physician prescribed for a patient an emollient clyster. Since
it was late at night, and the apothecary in bed, he prepared it himself;
but not finding linseed oil, woke the apothecary, who took a bottle out
of one of the recesses and placed it on the table. The bottle contained
sulphuric acid; a soldier noticed a peculiar odour and effervescence
when the syringe was charged, but this was unheeded by the doctor. The
patient immediately after the operation suffered the most acute agony,
and died the following day; before his death, the bedclothes were found
corroded by the acid, and a portion of the bowel itself came away.[68]

[68] Maschka’s _Handbuch_, p. 86; _Journal de Chimie Médicale_, t. i.
No. 8, 405, 1835.

§56. =Fatal Dose.=--The amount necessary to kill an adult man is not
strictly known; fatality so much depends on the concentration of the
acid and the condition of the person, more especially whether the
stomach is full or empty, that it will be impossible ever to arrive at
an accurate estimate. Christison’s case, in which 3·8 grms. (60 grains)
of concentrated acid killed an adult, is the smallest lethal dose on
record. Supposing that the man weighed 68½ kilo. (150 lbs.), this would
be in the proportion of ·05 grm. per kilo. There is also the case of a
child of one year, recorded by Taylor, in which 20 drops caused death.
If, however, it were asked in a court of law what dose of concentrated
sulphuric acid would be dangerous, the proper answer would be: so small
a quantity as from 2 to 3 drops of the strong undiluted acid might cause
death, more especially if conveyed to the back of the throat; for if it
is improbable that on such a supposition death would be sudden, yet
there is a possibility of permanent injury to the gullet, with the
result of subsequent contraction, and the usual long and painful
malnutrition thereby induced. It may be laid down, therefore, that all
quantities, even the smallest, of the _strong undiluted acid_ come under
the head of hurtful, noxious, and injurious.

§ 57. =Local Action of Sulphuric Acid.=--The action of the acid on
living animal tissues has been studied of late by C. Ph. Falck and L.
Vietor.[69] Concentrated acid precipitates albumen, and then redissolves
it; fibrin swells and becomes gelatinous; but if the acid is weak
(_e.g._, 4 to 6 per cent.) it is scarcely changed. Muscular fibre is at
first coloured amber-yellow, swells to a jelly, and then dissolves to a
red-brown turbid fluid. When applied to the mucous membrane of the
stomach, the mucous tissue and the muscular layer beneath are coloured
white, swell, and become an oily mass.

[69] _Deutsche Klinik_, 1864, Mo. 1-32, and Vietor’s
_Inaugur.-Dissert._, Marburg, 1803.

When applied to a rabbit’s ear,[70] the parenchyma becomes at first pale
grey and semi-transparent at the back of the ear; opposite the drop of
acid appear spots like grease or fat drops, which soon coalesce. The
epidermis with the hair remains adherent; the blood-vessels are narrowed
in calibre, and the blood, first in the veins, and then in the arteries,
is coloured green and then black, and fully coagulates. If the drop,
with horizontal holding of the ear, is dried in, an inflammatory zone
surrounds the burnt spot in which the blood circulates; but there is
complete stasis in the part to which the acid has been applied. If the
point of the ear is dipped in the acid, the cauterised part rolls
inwards; after the lapse of eighteen hours the part is brown and
parchment-like, with scattered points of coagulated blood; then there is
a slight swelling in the healthy tissues, and a small zone of redness;
within fourteen days a bladder-like greenish-yellow scab is formed, the
burnt part itself remaining dry. The vessels from the surrounding zone
of redness gradually penetrate towards the cauterised spot, the fluid
in the bleb becomes absorbed, and the destroyed tissues fall off in the
form of a crust.

[70] Samuel, _Entzündung u. Brand, in Virchow’s Archiv f. Path. Anat._,
Bd. 51, Hft. 1 u. 2, S. 41, 1870.

The changes that sulphuric acid cause in blood are as follows: the
fibrin is at first coagulated and then dissolved, and the colouring
matter becomes of a black colour. These changes do not require the
strongest acid, being seen with an acid of 60 per cent.

§ 58. The action of the acid on various non-living matters is as
follows: poured on all vegetable earth, there is an effervescence,
arising from decomposition of carbonates; any grass or vegetation
growing on the spot is blackened and dies; an analysis of the layer of
earth, on which the acid is poured, shows an excess of sulphates as
compared with a similar layer adjacent; the earth will only have an acid
reaction, if there has been more than sufficient acid to neutralise all
alkalies and alkaline earths.

Wood almost immediately blackens, and the spot remains moist.

Spots on paper become quickly dark, and sometimes exhibit a play of
colours, such as reddish-brown; ultimately the spot becomes very black,
and holes may be formed; even when the acid is dilute, the course is
very similar, for the acid dries in, until it reaches a sufficient
degree of concentration to attack the tissue. I found small drops of
sulphuric acid on a brussels carpet, which had a red pattern on a dark
green ground with light green flowers, act as follows: the spots on the
red at the end of a few hours were of a dark maroon colour, the green
was darkened, and the light green browned; at the end of twenty-four
hours but little change had taken place, nor could any one have guessed
the cause of the spots without a close examination. Spots of the strong
acid on thin cotton fabrics rapidly blackened, and actual holes were
formed in the course of an hour; the main difference to the naked eye,
between the stains of the acid and those produced by a red-hot body, lay
in the moistness of the spots. Indeed, the great distinction, without
considering chemical evidence, between recent burns of clothing by
sulphuric acid and by heat, is that in the one case--that of the
acid--the hole or spot is very moist; in the other very dry. It is easy
to imagine that this distinction may be of importance in a legal
investigation.

Spots of acid on clothing fall too often under the observation of all
those engaged in practical chemical work. However quickly a spot of acid
is wiped off, unless it is immediately neutralised by ammonia, it
ultimately makes a hole in the cloth; the spot, as a rule, whatever the
colour of the cloth, is of a blotting-paper red.

Sulphuric acid dropped on iron, attacks it, forming a sulphate, which
may be dissolved out by water. If the iron is exposed to the weather
the rain may wash away all traces of the acid, save the corrosion; but
it would be under those circumstances impossible to say whether the
corrosion was due to oxidation or a solvent.

To sum up briefly: the characters of sulphuric acid spots on organic
matters generally are black, brown, or red-coloured destructions of
tissue, moisture, acid-reaction (often after years), and lastly the
chemical evidence of sulphuric acid or sulphates in excess.

=Caution necessary in judging of Spots, &c.=--An important case, related
by Maschka, shows the necessity of great caution in interpreting
results, unless all the circumstances of a case be carefully collated. A
live coal fell on the bed of a weakly infant, five months old. The child
screamed, and woke the father, who was dozing by the fire; the man, in
terror, poured a large pot of water on the child and burning bed. The
child died the following day.

A _post-mortem_ examination showed a burn on the chest of the infant 2
inches in length. The tongue, pharynx, and gullet were all healthy; in
the stomach a patch of mucous membrane, about half an inch in extent,
was found to be brownish, friable, and very thin. A chemical examination
showed that the portion of the bed adjacent to the burnt place contained
free sulphuric acid. Here, then, was the following evidence: the sudden
death of a helpless infant, a carbonised bed-cover with free sulphuric
acid, and, lastly, an appearance in the stomach which, it might be said,
was not inconsistent with sulphuric acid poisoning. Yet a careful
sifting of the facts convinced the judges that no crime had been
committed, and that the child’s death was due to disease. Afterwards,
experiment showed that if a live coal fall on to any tissue, and be
drenched with water, free sulphuric acid is constantly found in the
neighbourhood of the burnt place.

§ 59. =Symptoms.=--The symptoms may be classed in two divisions,
viz.:--1. External effects of the acid. 2. Internal effects and symptoms
arising from its interior administration.

1. =External Effects.=--Of late years several instances have occurred in
which the acid has been used criminally to cause disfiguring burns of
the face. The offence has in all these cases been committed by women,
who, from motives of revengeful jealousy, have suddenly dashed a
quantity of the acid into the face of the object of their resentment. In
such cases, the phenomena observed are not widely different from those
attending scalds or burns from hot neutral fluids. There is destruction
of tissue, not necessarily deep, for the acid is almost immediately
wiped off; but if any should reach the eye, inflammation, so acute as to
lead to blindness, is the probable consequence. The skin is coloured at
first white, at a later period brown, and part of it may be, as it were,
dissolved. If the tract or skin touched by the acid is extensive, death
may result. The inflammatory processes in the skin are similar to those
noticed by Falck and Vietor in their experiments, already detailed (p.
79).

=Internal Effects of Acids generally.=--It may not be out of place,
before speaking of the internal effects of sulphuric acid, to make a few
remarks upon the action of acids generally. This action differs
according to the kind of animal; at all events, there is a great
difference between the action of acids on the herb-eating animals and
the carnivora; the latter bear large doses of acids well, the former
ill. For instance, the rabbit, if given a dose of any acid not
sufficient to produce local effects but sufficient to affect its
functions, will soon become paralysed and lie in a state of stupor, as
if dead; the same dose per kilo. will not affect the dog. The reason for
this is that the blood of the dog is able to neutralise the acid by
ammonia, and that the blood of the rabbit is destitute of this property.
Man is, in this respect, nearer to the dog than to the plant-eaters.
Stadelmann has shown that a man is able to ingest large relative doses
of oxybutyric acid, to neutralise the acid by ammonia, and to excrete it
by means of the kidneys as ammonium butyrate.

Acids, however, if given in doses too great to be neutralised, alike
affect plant- and flesh-eaters; death follows in all cases before the
blood becomes acid. Salkowsky[71] has, indeed, shown that the effect of
lessening the alkalinity of the blood by giving a rabbit food from which
it can extract no alkali produces a similar effect to the actual dosing
with an acid.

[71] Virchow’s _Archiv_, Bd. 58, 1.

2. =Internal Effects of Sulphuric Acid.=--When sulphuric acid is taken
internally, the acute and immediate symptom is pain. This, however, is
not constant, since, in a few recorded cases, no complaint of pain has
been made; but these cases are exceptional; as a rule, there will be
immediate and great suffering. The tongue swells, the throat is also
swollen and inflamed, swallowing of saliva even may be impossible. If
the acid has been in contact with the epiglottis and vocal apparatus,
there may be spasmodic croup and even fatal spasm of the glottis.

The acid, in its passage down the gullet, attacks energetically the
mucous membrane and also the lining of the stomach; but the action does
not stop there, for Lesser found in eighteen out of twenty-six cases (69
per cent.) that the corrosive action extended as far as the duodenum.
There is excessive vomiting and retching; the matters vomited are acid,
bloody, and slimy; great pieces of mucous membrane may be in this way
expelled, and the whole of the lining membrane of the gullet may be
thrown up entire. The bowels are, as a rule, constipated, but
exceptionally there has been diarrhœa; the urine is sometimes retained;
it invariably contains an excess of sulphates and often albumen, with
hyaline casts of the uriniferous tubes. The pulse is small and frequent,
the breathing slow, the skin very cold and covered with sweat; the
countenance expresses great anxiety, and the extremities may be affected
with cramps or convulsions. Death may take place within from twenty-four
to thirty-six hours, and be either preceded by dyspnœa or by
convulsions; consciousness is, as a rule, maintained to the end.

There are also more rapid cases than the above; a large dose of
sulphuric acid taken on an empty stomach may absolutely dissolve it, and
pass into the peritoneum; in such a case there is really no difference
in the symptoms between sudden perforation of the stomach from disease,
a penetrating wound of the abdomen, and any other sudden fatal lesion of
the organs in the abdominal cavity (for in all these instances the
symptoms are those of pure collapse); the patient is ashen pale, with
pulse quick and weak, and body bathed in cold sweat, and he rapidly
dies, it may be without much complaint of local pain.

If the patient live longer than twenty-four hours, the symptoms are
mainly those of inflammation of the whole mucous tract, from the mouth
to the stomach; and from this inflammation the patient may die in a
variable period, of from three to eleven days, after taking the poison.
In one case the death occurred suddenly, without any immediately
preceding symptoms rendering imminent death probable. If this second
stage is passed, then the loss of substance in the gullet and in the
stomach almost invariably causes impairment of function, leading to a
slow and painful death. The common sequence is stricture of the gullet,
combined with feeble digestion, and in a few instances stricture of the
pylorus. A curious sequel has been recorded by Mannkopf, viz., obstinate
intercostal neuralgia; it has been observed on the fourth, seventh, and
twenty-second day.

§ 60. =Treatment of Acute Poisoning by the Mineral Acids.=--The
immediate indication is the dilution and neutralisation of the acid. For
this purpose, finely-divided chalk, magnesia, or sodic carbonate may be
used, dissolved or suspended in much water. The use of the stomach-pump
is inadvisable, for the mucous membrane of the gullet may be so corroded
by the acid that the passage of the tube down will do injury; unless the
neutralisation is _immediate_, but little good is effected; hence it
will often occur that the bystanders, if at all conversant with the
matter, will have to use the first thing which comes to hand, such as
the plaster of a wall, &c.; and lastly, if even these rough antidotes
are not to be had, the best treatment is enormous doses of water, which
will dilute the acid and promote vomiting. The treatment of the
after-effects belongs to the province of ordinary medicine, and is based
upon general principles.

§ 61. =Post-mortem Appearances.=[72]--The general pathological
appearances to be found in the stomach and internal organs differ
according as the death is rapid or slow; if the death takes place within
twenty-four hours, the effects are fairly uniform, the differences being
only in degree; while, on the other hand, in those cases which terminate
fatally from the more remote effects of the acid, there is some variety.
It may be well to select two actual cases as types, the one patient
dying from acute poisoning, the other surviving for a time, and then
dying from ulceration and contraction of the digestive tract.

[72] It has been observed that putrefaction in cases of death from
sulphuric acid is slow. Casper suggests this may be due to the
neutralisation of ammonia; more probably it is owing to the antiseptic
properties all mineral acids possess.

A hatter, early in the morning, swallowed a large mouthful of strong
sulphuric acid, a preparation which he used in his work--(whether the
draught was taken accidentally or suicidally was never known). He died
within two hours. The whole tongue was sphacelated, parts of the mucous
membrane being dissolved; the inner surface of the gullet, as well as
the whole throat, was of a grey-black colour; the mucous membrane of the
stomach was coal-black, and so softened that it gave way like
blotting-paper under the forceps, the contents escaping into the cavity
of the abdomen. The peritoneum was also blackened as if burnt; probably
there had been perforation of the stomach during life; the mucous
membrane of the duodenum was swollen, hardened, and looked as if it had
been boiled; while the blood was of a cherry-red colour, and of the
consistence of a thin syrup. The rest of the organs were healthy; a
chemical research on the fluid which had been collected from the
stomach, gullet, and duodenum showed that it contained 87·25 grains of
free sulphuric acid.[73]

[73] Casper, vol. ii. case 194.

This is, perhaps, the most extreme case of destruction on record; the
cause of the unusually violent action is referable to the acid acting on
an empty stomach. It is important to note that even with this extensive
destruction of the stomach, life was prolonged for two hours.

The case I have selected to serve as a type of a chronic but fatal
illness produced from poisoning by sulphuric acid is one related by
Oscar Wyss. A cook, thirty-four years of age, who had suffered many
ailments, drank, on the 6th of November 1867, by mistake, at eight
o’clock in the morning, two mouthfuls of a mixture of 1 part of
sulphuric acid and 4 of water. Pain in the stomach and neck, and
vomiting of black masses, were the immediate symptoms, and two hours
later he was admitted into the hospital in a state of collapse, with
cold extremities, cyanosis of the face, &c. Copious draughts of milk
were given, and the patient vomited much, the vomit still consisting of
black pultaceous matters, in which, on a microscopical examination,
could be readily detected columnar epithelium of the stomach and mucous
tissue elements. The urine was of specific gravity 1·033,
non-albuminous; on analysis it contained 3·388 grms. of combined
sulphuric acid.

On the second day there was some improvement in the symptoms; the urine
contained 1·276 grm. of combined sulphuric acid; on the third day 2·665
grms. of combined sulphuric acid; and on the tenth day the patient
vomited up a complete cast of the mucous membrane of the gullet. The
patient remained in the hospital, and became gradually weaker from
stricture of the gullet and impairment of the digestive powers, and
died, two months after taking the poison, on the 5th of January 1868.

The stomach was found small, contracted, with many adhesions to the
pancreas and liver; it was about 12 centimetres long (4·7 inches), and
from 2 to 2·5 centimetres (·7 to ·9 inch) broad, contracted to somewhat
the form of a cat’s intestine; there were several transverse rugæ; the
walls were thickened at the small curvature, measurements giving 5 mm.
(·19 inch) in the middle, and beyond about 2·75 mm. (·11 inch); in the
upper two-thirds the lumen was so contracted as scarcely to admit the
point of the little finger. The inner surface was covered with a layer
of pus, with no trace of mucous tissue, and was everywhere pale red,
uneven, and crossed by cicatricial bands. In two parts, at the greater
curvature, the mucous surface was strongly injected in a ring-like form,
and in the middle of the ring was a deep funnel-shaped ulcer; a part of
the rest of the stomach was strongly injected and scattered over with
numerous punctiform, small, transparent bladders. The gullet was
contracted at the upper part (just below the epiglottis) from 20 to 22
mm. (·78 to ·86 inch) in diameter; it then gradually widened to measure
about 12 mm. (·47 inch) at the diaphragm; in the neighbourhood of the
last contraction the tissue was scarred, injected, and ulcerated; there
were also small abscesses opening into this portion of the gullet.

E. Fraenkel and F. Reiche[74] have studied the effects of sulphuric acid
on the kidney. In rapid cases they find a wide-spread coagulation of the
epithelium in the convoluted and straight urinary canaliculi, with
destruction of the kidney parenchyma, but no inflammation.

[74] Virchow’s _Archiv_, Bd. 131, f. 130.

§ 62. The museums of the different London hospitals afford excellent
material for the study of the effects of sulphuric acid on the pharynx,
gullet, and stomach; and it may be a matter of convenience to students
if the more typical examples at these different museums be noticed in
detail, so that the preparations themselves may be referred to.

    _In St. Bartholomew’s Museum_, No. 1942, is an example of excessive
    destruction of the stomach by sulphuric acid. The stomach is much
    contracted, and has a large aperture with ragged edges; the mucous
    membrane is thickened, charred, and blackened.

    No. 1941, in the same museum, is the stomach of a person who died
    from a large dose of sulphuric acid. When recent, it is described as
    of a deep red colour, mottled with black; appearances which, from
    long soaking in spirit, are not true at the present time; but the
    rough, shaggy state of the mucous tissue can be traced; the gullet
    and the pylorus appear the least affected.

    _St. George’s Hospital_, ser. ix., 146, 11 and 43, e.--The pharynx
    and œsophagus of a man who was brought into the hospital in a state
    of collapse, after a large but unknown dose of sulphuric acid. The
    lips were much eroded, the mucous membrane of the stomach, pharynx,
    and œsophagus show an extraordinary shreddy condition; the lining
    membrane of the stomach is much charred, and the action has extended
    to the duodenum; the muscular coat is not affected.

    _Guy’s Hospital_, No. 1799.--A preparation showing the mucous
    membrane of the stomach entirely denuded. The organ looks like a
    piece of thin paper.

    No. 1799²⁰. The stomach of a woman who poisoned herself by drinking
    a wine-glassful of acid before breakfast. She lived eleven days. The
    main symptoms were vomiting and purging, but there was no complaint
    of pain. There is extensive destruction of mucous membrane along the
    lesser curvature and towards the pyloric extremity; a portion of the
    mucous membrane is floating as a slough.

    No. 1799²⁵ is the gullet and stomach of a man who took about 3
    drachms of the strong acid. He lived three days without much
    apparent suffering, and died unexpectedly. The lining membrane of
    the œsophagus has the longitudinal wrinkles or furrows so often,
    nay, almost constantly, met with in poisoning by the acids. The
    mucous tissue of the stomach is raised in cloudy ridges, and
    blackened.

    No. 1799³⁵ is a wonderfully entire cast of the gullet from a woman
    who swallowed an ounce of sulphuric acid, and is said, according to
    the catalogue, to have recovered.

    _University College._--In this museum will be found an exquisite
    preparation of the effects of sulphuric acid. The mucous membrane of
    the œsophagus is divided into small quadrilateral areas by
    longitudinal and transverse furrows; the stomach is very brown, and
    covered with shreddy and filamentous tissue; the brown colour is
    without doubt the remains of extravasated and charred blood.

    No. 6201 is a wax cast representing the stomach of a woman who died
    after taking a large dose of sulphuric acid. A yellow mass was found
    in the stomach; there are two perforations, and the mucous membrane
    is entirely destroyed.

§ 63. =Chronic Poisoning by Sulphuric Acid.=--Weiske[75] has
experimentally proved that lambs, given for six months small doses of
sulphuric acid, grow thin, and their bones, with the exception of the
bones of the head and the long bones, are poor in lime salts, the
muscles also are poor in the same constituents. Kobert[76] thinks that
drunkards on the continent addicted to “Schnaps,” commonly a liquid
acidified with sulphuric acid to give it a sharp taste, often show
typical chronic sulphuric acid poisoning.

[75] H. Weiske, _Journ. f. Landwirthsch._, 1887, 417.

[76] _Lehrbuch der Intoxicationen_, S. 210.


Detection and Estimation of Free Sulphuric Acid.

§ 64. The general method of separating the mineral acids is as follows:
the tissues, or matters, are soaked in distilled water for some time. If
no free acid is present, the liquid will not redden litmus-paper, or
give an acid reaction with any of the numerous tinctorial agents in use
by the chemist for the purposes of titration. After sufficient digestion
in water, the liquid extract is made up to some definite bulk and
allowed to subside. Filtration is unnecessary. A small fractional part
(say, for example, should the whole be 250 c.c., 1/100th or 2·5 c.c.) is
taken, and using as an indicator cochineal or phenolphthalein, the total
acidity is estimated by a decinormal solution of soda. By this
preliminary operation, some guide for the conduct of the future more
exact operations is obtained. Should the liquid be very acid, a small
quantity of the whole is to be now taken, but if the acidity is feeble,
a larger quantity is necessary, and sufficient quinine then added to fix
the acid--100 parts of sulphuric acid are saturated by 342 parts of
quinine monohydrate. Therefore, on the supposition that all the free
acid is sulphuric, it will be found sufficient to add 3·5 parts of
quinine for every 1 part of acid, estimated as sulphuric, found by the
preliminary rough titration; and as it is inconvenient to deal with
large quantities of alkaloid, a fractional portion of the liquid extract
(representing not more than 50 mgrms. of acid) should be taken, which
will require 175 mgrms. of quinine.

On addition of the quinine, the neutralised liquid is evaporated to
dryness, or to approaching dryness, and then exhausted by strong
alcohol. The alcoholic extract is, after filtration, dried up, and the
quinine sulphate, nitrate, or hydrochlorate, as the case may be,
filtered off and extracted by boiling water, and precipitated by
ammonia, the end result being quinine hydrate (which may be filtered off
and used again for similar purposes) and a sulphate, nitrate or chloride
of ammonia in solution. It therefore remains to determine the nature and
quantity of the acids now combined with ammonia. The solution is made up
to a known bulk, and portions tested for chlorides by nitrate of silver,
and for nitrates by the copper or the ferrous sulphate test. If
sulphuric acid is present, there will be a precipitate of barium
sulphate, which, on account of its density and insolubility in nitric or
hydrochloric acids, is very characteristic. For estimating the sulphuric
acid thus found, it will only be necessary to take a known bulk of the
same liquid, heat it to boiling after acidifying by hydrochloric acid,
and then add a sufficient quantity of baric chloride solution. Unless
this exact process is followed, the analyst is likely to get a liquid
which refuses to filter clear, but if the sulphate be precipitated from
a hot liquid, it usually settles rapidly to the bottom of the vessel,
and the supernatant fluid can be decanted clear; the precipitate is
washed by decantation, and ultimately collected on a filter, dried, and
weighed.

The sulphate of baryta found, multiplied by ·3434, equals the sulphuric
anhydride.

The older process was to dissolve the free sulphuric acid out by
alcohol. As is well known, mineral sulphates are insoluble in, and are
precipitated by, alcohol, whereas sulphuric acid enters into solution.
The most valid objection, as a quantitative process, to the use of
alcohol, is the tendency which all mineral acids have to unite with
alcohol in organic combination, and thus, as it were, to disappear; and,
indeed, results are found, by experiment, to be below the truth when
alcohol is used. This objection does not hold good if either merely
qualitative evidence, or a fairly approximate quantation, is required.
In such a case, the vomited matters, the contents of the stomach, or a
watery extract of the tissues, are evaporated to a syrup, and then
extracted with strong alcohol and filtered; a little phenolphthalein
solution is added, and the acid alcohol exactly neutralised by an
alcoholic solution of clear decinormal or normal soda. According to the
acidity of the liquid, the amount used of the decinormal or normal soda
is noted, and then the whole evaporated to dryness, and finally heated
to gentle redness. The alkaline sulphate is next dissolved in very
dilute hydrochloric acid, and the solution precipitated by chloride of
barium in the usual way. The quantitative results, although low, would,
in the great majority of cases, answer the purpose sufficiently.

A test usually enumerated, Hilger’s test for mineral acid, may be
mentioned. A liquid, which contains a very minute quantity of mineral
acid, becomes of a blue colour (or, if 1 per cent. or above, of a green)
on the addition of a solution of methyl aniline violet; but this test,
although useful in examining vinegars (see “Foods,” p. 519), is not of
much value in toxicology, and the quinine method for this purpose meets
every conceivable case, both for qualitative and quantitative purposes.

§ 65. =The Urine.=--Although an excess of sulphates is found constantly
in the urine of persons who have taken large doses of sulphuric acid,
the latter has never been found in that liquid in a free state, so that
it will be useless to search for free acid. It is, therefore, only
necessary to add HCl to filter the fluid, and precipitate direct with an
excess of chloride of barium. It is better to operate in this manner
than to burn the urine to an ash, for in the latter case part of the
sulphates, in the presence of phosphates, are decomposed, and, on the
other hand, any organic sulphur combinations are liable to be estimated
as sulphates.

It may also be well to pass chlorine gas through the same urine which
has been treated with chloride of barium, and from which the sulphate
has been filtered off. The result of this treatment will be a second
precipitate of sulphate derived from sulphur, in a different form of
combination than that of sulphate.

The greatest amount of sulphuric acid as mineral and organic sulphate is
separated, according to Mannkopf[77] and Schultzen,[78] within five
hours after taking sulphuric acid; after three days the secretion, so
far as total sulphates is concerned, is normal.

[77] “Toxicologie der Schwefelsäure,” _Wiener med. Wochen._, 1862, 1863.

[78] _Archiv. f. Anatom. u. Physiol._, 1864.

The normal amount of sulphuric acid excreted daily, according to
Thudichum, is from 1·5 to 2·5 grms., and organic sulphur up to ·2 grm.
in the twenty-four hours, but very much more has been excreted by
healthy persons.

Lehmann made some observations on himself, and found that, on an animal
diet, he excreted no less than 10·399 grms. of sulphuric acid per day,
while on mixed food a little over 7 grms.; but, as Thudichum justly
observes, this great amount must be referred to individual peculiarity.
The amount of sulphates has a decided relation to diet. Animal food,
although not containing sulphates, yet, from the oxidation of the
sulphur-holding albumen, produces a urine rich in sulphate. Thus Vogel
found that a person, whose daily average was 2·02 grms., yielded 7·3 on
a meat diet. The internal use of sulphur, sulphides, and sulphates,
given in an ordinary medicinal way, is traceable in the urine,
increasing the sulphates. In chronic diseases the amount of sulphates is
decreased, in acute increased.

Finally, it would appear that the determination of sulphates in the
urine is not of much value, _save when the normal amount that the
individual secretes is primarily known_. On the other hand, a low amount
of sulphates in the urine of a person poisoned by sulphuric acid has not
been observed within three days of the taking of the poison, and one can
imagine cases in which such a low result might have forensic importance.

The presence of albumen in the urine has been considered by some a
constant result of sulphuric acid poisoning, but although when looked
for it is usually found, it cannot be considered constant. O.
Smoler,[79] in eighteen cases of various degrees of sulphuric acid
poisoning, found nothing abnormal in the urine. Wyss[80] found in the
later stages of a case indican and pus. E. Leyden and Ph. Munn[81]
always found blood in the urine, as well as albumen, with casts and
cellular elements. Mannkopf[82] found albuminuria in three cases out of
five; in two of the cases there were fibrinous casts; in two the albumen
disappeared at the end of the second or third day, but in one it
continued for more than twenty days. Bamberger[83] has observed an
increased albuminuria, with separation of the colouring matter of the
blood. In this case it was ascribed to the action of the acid on the
blood.

[79] _Archiv der Heilkunde red. v._ E. Wagner, 1869, Hft. 2, S. 181.

[80] _Wiener Medicinal-Halle_, 1861, Jahr. 6, No. 46.

[81] Virchow’s _Archiv f. path. Anat._, 1861. Bd. 22, Hft. 3 u. 4, S.
237.

[82] _Wien. med. Wochenschrift_, 1862, Nro. 35; 1863, Nro. 5.

[83] _Wien. Med.-Halle_, 1864, Nro. 29, 30.

§ 66. =The Blood.=--In Casper’s case, No. 193, the vena cava of a child,
who died within an hour after swallowing a large dose of sulphuric acid,
was filled with a cherry-red, strongly acid-reacting blood. Again,
Casper’s case, No. 200, is that of a young woman, aged 19, who died from
a poisonous dose of sulphuric acid. At the autopsy, four days after
death, the following peculiarities of the blood were thus noted:--“The
blood had an acid reaction, was dark, and had (as is usual in these
cases) a syrupy consistence, while the blood-corpuscles were quite
unchanged. The blood was treated with an excess of absolute alcohol,
filtered, the filtrate concentrated on a water-bath, the residue
exhausted with absolute alcohol, &c. It yielded a small quantity of
sulphuric acid.”

Other similar cases might be noted, but it must not for a moment be
supposed that the mass of the blood contains any free sulphuric acid
during life. The acidity of the blood in the vena cava may be ascribed
to _post-mortem_ endosmosis, the acid passing through the walls of the
stomach into the large vessel.

§ 67. =Sulphates.=--If the acid swallowed should have been entirely
neutralised by antidotes, such as chalk, &c., it becomes of the first
importance to ascertain, as far as possible, by means of a microscopical
examination, the nature of the food remaining in the stomach, and then
to calculate the probable contents in sulphates of the food thus known
to be eaten. It will be found that, with ordinary food, and under
ordinary circumstances, only small percentages of combined sulphuric
acid can be present.

As an example, take the ordinary rations of the soldier, viz.:--12 oz.
of meat, 24 oz. of bread, 16 oz. of potatoes, 8 oz. of other vegetables;
with sugar, salt, tea, coffee, and water. Now, if the whole quantity of
these substances were eaten at a meal, they would not contain more than
from 8 to 10 grains (·5 to ·6 grm.) of anhydrous sulphuric acid, in the
form of sulphates.

So far as the contents of the stomach are concerned, we have only to do
with sulphates introduced in the food, but when once the food passes
further along the intestinal canal, circumstances are altered, for we
have sulphur-holding secretions, which, with ordinary chemical methods,
yield sulphuric acid. Thus, even in the newly-born infant, according to
the analyses of Zweifler, the mineral constituents of meconium are
especially sulphate of lime, with a smaller quantity of sulphate of
potash. The amount of bile which flows into the whole tract of the
intestinal canal is estimated at about half a litre in the twenty-four
hours; the amount of sulphur found in bile varies from ·89 to 3 per
cent., so that in 500 c.c. we might, by oxidising the sulphur, obtain
from 2·2 to 7·5 grms. of sulphuric anhydride.

It is therefore certain that large quantities of organic
sulphur-compounds may be found in the human intestinal canal, for with
individuals who suffer from constipation, the residues of the biliary
secretion accumulate for many days. Hence, if the analyst searches for
sulphates in excretal matters, all methods involving destruction of
organic substances, whether by fire or by fluid-oxidising agents, are
wrong in principle, and there is nothing left save to separate soluble
sulphates by dialysis, or to precipitate direct out of an aqueous
extract.

Again, sulphate of magnesia is a common medicine, and so is sodic
sulphate; a possible medicinal dose of magnesia sulphate might amount to
56·7 grms. (2 oz.), the more usual dose being half that quantity.
Lastly, among the insane there are found patients who will eat
plaster-of-Paris, earth, and similar matters, so that, in special cases,
a very large amount of combined sulphuric acid may be found in the
intestinal tract, without any relation to poisoning by the free acid;
but in such instances it must be rare, indeed, that surrounding
circumstances or pathological evidence will not give a clue to the real
state of affairs.


II.--Hydrochloric Acid.

§ 68. _General Properties._--Hydrochloric acid, otherwise called
_muriatic acid_, _spirit of salt_, is, in a strictly chemical sense, a
pure gas, composed of 97·26 per cent. of chlorine, and 2·74 per cent. of
hydrogen; but, in an ordinary sense, it is a liquid, being a solution of
the gas itself.

Hydrochloric acid is made on an enormous scale in the United Kingdom,
the production being estimated at about a million tons annually.

The toxicology of hydrochloric acid is modern, for we have no evidence
that anything was known of it prior to the middle of the seventeenth
century, when Glauber prepared it in solution, and, in 1772, Priestley,
by treating common salt with sulphuric acid, isolated the pure gas.

The common liquid hydrochloric acid of commerce has a specific gravity
of from 1·15 to 1·20, and contains usually less than 40 parts of
hydrochloric acid in the 100 parts. The strength of pure samples of
hydrochloric acid can be told by the specific gravity, and a very close
approximation, in default of tables, may be obtained by simply
multiplying the decimal figures of the specific gravity by 200. For
example, an acid of 1·20 gravity would by this rule contain 40 per cent.
of real acid, for ·20 × 200 = 40.

The commercial acid is nearly always a little yellow, from the presence
of iron derived from metallic retorts, and usually contains small
quantities of chloride of arsenic,[84] derived from the sulphuric acid;
but the colourless hydrochloric acid specially made for laboratory and
medicinal use is nearly always pure.

[84] Some samples of hydrochloric acid have been found to contain as
much as 4 per cent. of chloride of arsenic, but this is very unusual.
Glenard found as a mean 2·5 grammes, As₂O₃ per kilogramme.

The uses of the liquid acid are mainly in the production of chlorine, as
a solvent for metals, and for medicinal and chemical purposes. Its
properties are briefly as follows:--

It is a colourless or faintly-yellow acid liquid, the depth of colour
depending on its purity, and especially its freedom from iron. The
liquid is volatile, and can be separated from fixed matters and the less
volatile acids by distillation; it has a strong attraction for water,
and fumes when exposed to the air, from becoming saturated with aqueous
vapour. If exposed to the vapour of ammonia, extremely dense clouds
arise, due to the formation of the solid ammonium chloride. The acid,
boiled with a small quantity of manganese binoxide, evolves chlorine.
Dioxide of lead has a similar action; the chlorine may be detected by
its bleaching action on a piece of paper dipped in indigo blue; a little
zinc foil immersed in the acid disengages hydrogen. These two
tests--viz., the production of chlorine by the one, and the production
of hydrogen by the other--separate and reveal the constituent parts of
the acid. Hydrochloric acid, in common with chlorides, gives a dense
precipitate with silver nitrate. The precipitate is insoluble in nitric
acid, but soluble in ammonia; it melts without decomposition. Exposed to
the light, it becomes of a purple or blackish colour. Every 100 parts of
silver chloride are equal to 25·43 of hydrochloric acid, HCl, and to
63·5 parts of the liquid acid of specific gravity 1·20.

The properties of pure hydrochloric acid gas are as follows:--Specific
gravity 1·262, consisting of equal volumes of hydrogen and chlorine,
united without condensation. 100 cubic inches must therefore have a
weight of 39·36 grains. The gas was liquefied by Faraday by means of a
pressure of 40 atmospheres at 10°; it was colourless, and had a less
refractive index than water.

Water absorbs the gas with avidity, 100 volumes of water absorbing
48,000 volumes of the gas, and becoming 142 volumes. The solution has
all the properties of strong hydrochloric acid, specific gravity 1·21.
The dilute hydrochloric acid of the Pharmacopœia should have a specific
gravity of 1·052, and be equivalent to 10·58 per cent. of HCl.

§69. =Statistics of Poisoning by Hydrochloric Acid.=--The following
tables give the deaths, with age and sex distribution, due to
hydrochloric acid for ten years (1883-92):--

DEATHS FROM HYDROCHLORIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS
ENDING 1892.

                        ACCIDENT OR NEGLIGENCE.

  Ages,     Under   1-5   5-15   15-25   25-65   65 and    Total
              1                                  above
  Males,       1    16      2      ...     26       3        48
  Females,   ...     8    ...      ...      9       1        18
            ----------------------------------------------------
  Totals,      1    24      2      ...     35       4        66
            ----------------------------------------------------

                               SUICIDE.

  Ages,                   5-15   15-25   25-65   65 and    Total
                                                 above
  Males,                  ...       2      73       8        83
  Females,                  1       8      42      65       116
                         ---------------------------------------
  Totals,                   1      10     115      73       199
                         ---------------------------------------

In 1889 a solitary case of the murder of a child is on record from
hydrochloric acid; hence, with that addition, the total deaths from
hydrochloric acid amount to 266 in the ten years, or about 26 a year.

§ 70. =Fatal Dose.=--The dose which destroys life is not known with any
accuracy. In two cases, adults have been killed by 14 grms. (half an
ounce) of the commercial acid; but, on the other hand, recovery is
recorded when more than double this quantity has been taken. A girl,
fifteen years of age, died from drinking a teaspoonful of the acid.[85]

[85] _Brit. Med. Journ._, March, 1871.

§ 71. =Amount of Free Acid in the Gastric Juice.=--Hydrochloric acid
exists in the gastric juice. This was first ascertained by Prout[86] in
1824; he separated it by distillation. The observation was afterwards
confirmed by Gmelin,[87] Children,[88] and Braconnot.[89] On the other
hand, Lehmann[90] pointed out that, as the stomach secretion contained,
without doubt, lactic acid, the act of distillation, in the presence of
this lactic acid, would set free hydrochloric acid from any alkaline
chlorides. Blondlot and Cl. Bernard also showed that the gastric juice
possessed no acid which would dissolve oxalate of lime, or develop
hydrogen when treated with iron filings; hence there could not be free
hydrochloric acid which, even in a diluted state, would respond to both
these tests. Then followed the researches of C. Schmidt,[91] who showed
that the gastric secretion of men, of sheep, and of dogs contained more
hydrochloric acid than would satisfy the bases present; and he
propounded the view that the gastric juice does not contain absolutely
free hydrochloric acid, but that it is in loose combination with the
pepsin.

[86] _Philosophical Transactions_, 1824, p. 45.

[87] P. Tiedmann and L. Gmelin, _Die Verdauung nach Versuchen_,
Heidelberg u. Leipsic, 1826, i.

[88] _Annals of Philosophy_, July, 1824.

[89] _Ann. de Chim._ t. lix. p. 348.

[90] _Journal f. prakt. Chemie_, Bd. xl. 47.

[91] Bidder u. Schmidt, _Verdauungs-Säfte_, &c.

The amount of acid in the stomach varies from moment to moment, and
therefore it is not possible to say what the average acidity of gastric
juice is. It has been shown that in the total absence of _free_
hydrochloric acid digestion may take place, because hydrochloric acid
forms a compound with pepsin which acts as a solvent on the food. The
amount of physiologically active acid varies with the food taken. It is
smallest when carbohydrates are consumed, greatest with meat. The
maximum amount that Jaksch found in his researches, when meat was
ingested, was ·09 per cent. of hydrochloric acid. It is probable that
anything above 0·2 per cent. of hydrochloric acid is either abnormal or
owing to the recent ingestion of hydrochloric acid.

§ 72. =Influence of Hydrochloric Acid on Vegetation.=--Hydrochloric acid
fumes, if emitted from works on a large scale, injure vegetation much.
In former years, before any legal obligations were placed upon
manufacturers for the condensing of the volatile products, the nuisance
from this cause was great. In 1823, the duty on salt being repealed by
the Government, an extraordinary impetus was given to the manufacture of
hydrochloric acid, and since all the volatile products at that time
escaped through short chimneys into the air, a considerable area of land
round the works was rendered quite unfit for growing plants. The present
law on the subject is, that the maximum quantity of acid escaping shall
not exceed 2 grains per cubic foot of the air, smoke, or chimney gases;
and, according to the reports of the alkali inspectors, the condensation
by the improved appliances is well within the Act, and about as perfect
as can be devised.

It appears from the reports of the Belgian Commission in 1855, when
virtually no precautions were taken, that the gases are liable to injure
vegetation to the extent of 2000 metres (2187 yards) around any active
works; the more watery vapour the air contains, the quicker is the gas
precipitated and carried to the earth. If the action of the vapour is
considerable, the leaves of plants dry and wither; the chlorophyll
becomes modified, and no longer gives the normal spectrum, while a
thickening of the rind of trees has also been noticed. The cereals
suffer much; they increase in stalk, but produce little grain. The
leguminosæ become spotted, and have an air of dryness and want of
vigour; while the potato, among plants utilised for food, appears to
have the strongest resistance. Vines are very sensitive to the gas.
Among trees, the alder seems most sensitive; then come fruit-trees, and
last, the hardy forest-trees--the poplar, the ash, the lime, the elm,
the maple, the birch, and the oak.[92]

[92] Those who desire to study more closely the effect of acids
generally on vegetation may consult the various papers of the alkali
inspectors contained in the Local Government Reports. See also
Schubarth, _Die saueren Gase, welche Schwefelsäure- und Soda-Fabriken
verbreiten_. _Verhandlungen des Vereins zur Beförderung des
Gewerbefleisses in Preussen_, 1857, S. 135. Dingler’s _Journal_, Bd.
145, S. 374-427.

Christel, _Ueber die Einwirkung von Säuren-Dämpfen auf die Vegetation_.

_Arch. f. Pharmacie_, 1871, p. 252.

_Vierteljahrsschrift für gerichtliche Medicin_, 17 Bd. S. 404, 1872.

§73. =Action upon Cloth and Manufactured Articles.=--On black cloth the
acid produces a green stain, which is not moist and shows no corrosion.
On most matters the stain is more or less reddish; after a little time
no free acid may be detected, by simply moistening the spot; but if the
stain is cut out and boiled with water, there may be some evidence of
free acid. The absence of moisture and corrosion distinguishes the stain
from that produced by sulphuric acid.

§74. =Poisonous Effects of Hydrochloric Acid Gas.=--Eulenberg[93] has
studied the effects of the vapour of this acid on rabbits and pigeons.
One of these experiments may be cited in detail. Hydrochloric acid gas,
prepared by heating together common salt and sulphuric acid, was passed
into a glass shade supported on a plate, and a rabbit was placed in the
transparent chamber thus formed. On the entrance of the vapour, there
was immediate blinking of the eyes, rubbing of the paws against the
nostrils, and emission of white fumes with the expired breath, while the
respiration was irregular (40 to the minute). After the lapse of ten
minutes, the gas was again introduced, until the atmosphere was quite
thick; the symptoms were similar to those detailed above, but more
violent; and in fourteen minutes from the commencement, the rabbit sank
down on its right side (respirations 32). When twenty-two minutes had
elapsed, the gas was again allowed to enter. The rabbit now lay quiet,
with closed eyes and laboured respiration, and, finally, after
half-an-hour of intermittent exposure to the gas, the animal was
removed.

[93] _Gewerbe Hygiene_, Berlin, 1876, S. 51.

The cornea were opalescent, and the eyes filled with water; there was
frequent shaking of the head and working of the forepaws. After three
minutes’ exposure to the air, the respirations were found to be 128 per
minute; this quickened respiration lasted for an hour, then gave place
to a shorter and more superficial breathing. On the second day after the
experiment, the rabbit suffered from laboured respiration (28 to the
minute) and pain, and there was a rattling in the bronchial tubes. The
animal died on the third day, death being preceded by slow respiration
(12 to the minute).

The appearances twenty-four hours after death were as follows:--The eyes
were coated with a thick slime, and both cornea were opalescent; there
was strong rigidity of the body. The pia mater covering the brain was
everywhere hyperæmic, and at the hinder border of both hemispheres
appeared a small clot, surrounded by a thin layer of bloody fluid. The
_plex. venos spin._ was filled with coagulated blood, and there was also
a thin extravasation of blood covering the medulla and pons. The lungs
were mottled bright brown-red; the middle lobe of the right lung was
dark brown, solid, and sank in water; the lower lobe of the same lung
and the upper lobe of the left lung were nearly in a similar condition,
but the edges were of a bright red. The parenchyma in the darker places
on section did not crepitate. On the cut surface was a little dark,
fluid, weakly-acid blood; the tracheal mucous membrane was injected. The
heart was filled with thick coagulated blood; the liver was congested,
of a reddish-brown colour, and rich in dark, fluid blood: in the vena
cava inferior was coagulated blood. The kidneys were not hyperæmic; the
intestines were superficially congested.

I think there can be little doubt that the symptoms during life, and the
appearances after death, in this case are perfectly consistent with the
following view:--The vapour acts first as a direct irritant, and is
capable of exciting inflammation in the lung and bronchial tissues; but
besides this, there is a secondary effect, only occurring when the gas
is in sufficient quantity, and the action sufficiently prolonged--viz.,
a direct coagulation of the blood in certain points of the living
vessels of the lungs. The consequence of this is a more or less general
backward engorgement, the right side of the heart becomes distended with
blood, and the ultimate cause of death is partly mechanical. The
hyperæmia of the brain membranes, and even the hæmorrhages, are quite
consistent with this view, and occur in cases where the obstruction to
the circulation is of a coarser and more obvious character, and can
therefore be better appreciated.

§ 75. =Effects of the Liquid Acid.=--There is one distinction between
poisoning by hydrochloric and the other mineral acids--namely, the
absence of corrosion of the skin. Ad. Lesser[94] has established, by
direct experiment, that it is not possible to make any permanent mark on
the skin by the application even of the strongest commercial acid (40
per cent.). Hence, in any case of suspected poisoning by acid, should
there be stains on the lips and face as from an acid, the presumption
will be rather against hydrochloric. The symptoms themselves differ very
little from those produced by sulphuric acid. The pathological
appearances also are not essentially different, but hydrochloric is a
weaker acid, and the extensive disorganisation, solution, and
perforation of the viscera, noticed occasionally with sulphuric acid,
have never been found in hydrochloric acid poisoning. We may quote here
the following case:--

[94] Virchow’s _Archiv f. path. Anat._, Bd. 83, Hft. 2, S. 215, 1881.

A woman, under the influence of great and sudden grief--not unmixed with
passion--drew a bottle from her pocket, and emptied it very quickly. She
immediately uttered a cry, writhed, and vomited a yellow-green fluid.
The abdomen also became enlarged. Milk was given her, but she could not
swallow it, and death took place, in convulsions, two hours after the
drinking of the poison.

The _post-mortem_ appearances were briefly as follows:--Mouth and tongue
free from textural change: much gas in the abdomen, more especially in
the stomach; the membranes of the brain congested; the lungs filled with
blood. The stomach was strongly pressed forward, of a dark brown-red,
and exhibited many irregular blackish spots, varying from two lines to
half an inch in diameter (the spots were drier and harder than the rest
of the stomach); the mucous membrane, internally, was generally
blackened, and changed to a carbonised, shaggy, slimy mass, while the
organ was filled with a blackish homogeneous pulp, which had no odour.
The gullet was also blackened. A considerable quantity of hydrochloric
acid was separated from the stomach.[95]

[95] _Preuss. Med. Vereinszeit. u. Friederichs Blätter f. gerichtl.
Anthropologie_, 1858, Hft. 6, S. 70.

The termination in this instance was unusually rapid. In a case detailed
by Casper,[96] in which a boy drank an unknown quantity of acid, death
took place in seven hours. In Guy’s Hospital museum, the duodenum and
stomach are preserved of a patient who is said to have died in nine and
a half hours from half an ounce of the acid. The same quantity, in a
case related by Taylor, caused death in eighteen hours. From these and
other instances, it may be presumed that death from acute poisoning by
hydrochloric acid will probably take place within twenty-four hours.
From the secondary effects, of course, death may take place at a remote
period, _e.g._, in a case recorded by Dr. Duncan (_Lancet_, April 12,
1890), a man drank about 1 oz. of HCl accidentally, was admitted to
Charing Cross Hospital the same day, and treated with small quantities
of sodium carbonate, and fed by the rectum. On the eighth day he brought
up 34 oz. of blood; in a month he left apparently perfectly well, but
was admitted again in about six weeks, and died of contraction of the
stomach and stricture of the pylorus on the ninety-fourth day.

[96] Case 230.--_Gerichtliche Medicin_, 6th Ed., Berlin, 1876.

§76. =Post-mortem Appearances.=--The pathological appearances are very
similar to those found in the case already detailed; though the skin of
the face may not be eroded in any way by the acid, yet the more delicate
mucous membrane of the mouth, gullet, &c., appears mostly to be changed,
and is usually white or whitish-brown. There is, however, in the museum
of the Royal College of Surgeons the stomach and gullet (No. 2386c.) of
an infant thirteen months old; the infant drank a tea-cupful of strong
hydrochloric acid, and died nine hours after the dose. The pharynx and
the upper end of the gullet is quite normal, the corrosive action
commencing at the lower end, so that, although the acid was
concentrated, not the slightest effect was produced on the delicate
mucous membrane of the throat and upper part of the gullet. The lower
end of the gullet and the whole of the stomach were intensely congested;
the rugæ of the latter were ecchymosed and blackened by the action of
the acid. There were also small hæmorrhages in the lungs, which were
ascribed to the action of the acid on the blood. Perforation of the
stomach has not been noticed in hydrochloric acid poisoning.

In Guy’s Hospital museum (prep. 1799¹⁰), the stomach and duodenum of the
case mentioned exhibit the mucous membrane considerably injected, with
extravasations of blood, which, at the time when the preparation was
first arranged, were of various hues, but are now somewhat altered,
through long keeping in spirit. In St. George’s Hospital museum (ser. x.
43, d. 200) are preserved the stomach and part of the duodenum of a
person who died from hydrochloric acid. The case is detailed in the
_Medical Times and Gazette_ for 1853, vol. ii. p. 513. The whole inner
surface appears to be in a sloughing state, and the larynx and lung were
also inflamed.

A preparation, presented by Mr. Bowman to King’s College Hospital
museum, exhibits the effects of a very large dose of hydrochloric acid.
The gullet has a shrivelled and worm-eaten appearance; the stomach is
injected with black blood, and was filled with an acid, grumous
matter.[97]

[97] A drawing of parts of the gullet and stomach is given in Guy and
Ferrier’s _Forensic Medicine_.

Looking at these and other museum preparations illustrating the effects
of sulphuric and hydrochloric acids, I was unable (in default of the
history of the cases) to distinguish between the two, by the naked eye
appearances, save in those cases in which the disorganisation was so
excessive as to render hydrochloric acid improbable. On the other hand,
the changes produced by nitric acid are so distinctive, that it is
impossible to mistake its action for that of any other acid. The nitric
acid pathological preparations may be picked out at a glance.


Detection and Estimation of Free Hydrochloric Acid.

§ 77. (1) =Detection.=--A large number of colouring reagents have been
proposed as tests for the presence of free mineral acid; among the best
is _methyl-aniline violet_ decolorised by a large amount of hydrochloric
acid; the violet turns to green with a moderate quantity, and to blue
with a small quantity.

=Tropæolin= (00), in the presence of free mineral acid, strikes a
ruby-red to a dark brown-red.

=Congo-red= is used in the form of paper dyed with the material; large
amounts of free hydrochloric acid strike blue-black, small quantities
blue.

=Günzburg’s test= is 2 parts phloroglucin and 1 part vanillin, dissolved
in 100 parts of alcohol. Fine red crystals are precipitated on the
addition of hydrochloric acid. To test the stomach contents for free
hydrochloric acid by means of this reagent, equal parts of the fluid and
the test are evaporated to dryness in the water-bath in a porcelain
dish. If free hydrochloric acid be present, the evaporated residue shows
a red colour; 1 mgrm. of acid can by this test be detected. The reaction
is not interfered with by organic acids, peptones, or albumin.

Jaksch speaks highly of _benzopurpurin_ as a test. Filter-paper is
soaked in a saturated aqueous solution of benzopurpurin 6 B (the variety
1 or 4 B is not so sensitive), and the filter-paper thus prepared
allowed to dry. On testing the contents of the stomach with the reagent,
if there is more than 4 parts per 1000 of hydrochloric acid the paper is
stained intensely blue-black; but if the colour is brown-black, this is
from butyric or lactic acids, or from a mixture of these acids with
hydrochloric acid. If the paper is washed with pure ether, and the
colour was due only to organic acids, the original hue of the paper is
restored; if the colour produced was due to a mixture of mineral and
organic acids, the brown-black colour is weakened; and, lastly, if due
to hydrochloric acid alone, the colour is not altered by washing with
ether. Acid salts have no action, nor is the test interfered with by
large amounts of albumins and peptones.

A. Villiers and M. Favolle[98] have published a sensitive test for
hydrochloric acid. The test consists of a saturated aqueous solution of
colourless aniline, 4 parts; glacial acetic acid, 1 part; 0·1 mgrm. of
hydrochloric acid strikes with this reagent a blue colour, 1 mgrm. a
black colour. The liquid under examination is brought by evaporation, or
by the addition of water, to 10 c.c. and placed in a flask; to this is
added 5 c.c. of a mixture of equal parts of sulphuric acid and water,
then 10 c.c. of a saturated solution of potassic permanganate, and
heated gently, conveying the gases into 3 to 5 c.c. of the reagent
contained in a test-tube immersed in water. If, however, bromine or
iodine (one or both) should be present, the process is modified as
follows:--The hydracids are precipitated by silver nitrate; the
precipitate is washed, transferred to a small flask, and treated with 10
c.c. of water and 1 c.c. of pure ammonia. With this strength of ammonia
the chloride of silver is dissolved easily, the iodide not at all, and
the bromide but slightly. The ammoniacal solution is filtered, boiled,
and treated with SH₂; the excess of SH₂ is expelled by boiling, the
liquid filtered, reduced to 10 c.c. by boiling or evaporation,
sulphuric acid and permanganate added as before, and the gases passed
into the aniline. The process is inapplicable to the detection of
chlorides or hydrochloric acid if cyanides are present, and it is more
adapted for traces of hydrochloric acid than for the quantities likely
to be met with in a toxicological inquiry.

[98] _Comptes Rend._, cxviii.

(2) =Quantitative estimation of Free Hydrochloric Acid.=--The contents
of the stomach are diluted to a known volume, say 250 or 500 c.c. A
fractional portion is taken, say 10 c.c., coloured with litmus or
phenol-phthalein, and a decinormal solution of soda added drop by drop
until the colour changes; this gives total acidity. Another 10 c.c. is
shaken with double its volume of ether three times, the fluid separated
from ether and titrated in the same way; this last titration will give
the acidity due to mineral acids and acid salts;[99] if the only mineral
acid present is hydrochloric acid the results will be near the truth if
reckoned as such, and this method, although not exact for physiological
research, is usually sufficient for the purpose of ascertaining the
amount of hydrochloric acid or other mineral acids in a case of
poisoning. It depends on the fact that ether extracts free organic
acids, such as butyric and lactic acids, but does not extract mineral
acids.

[99] To distinguish between acidity due to free acid and acid salts, or
to acidity due to the combined action of acid salts and free acids, the
method of Leo and Uffelmann is useful. A fractional portion of the
contents of the stomach is triturated with pure calcium carbonate; if
all the acidity is due to free acid, the fluid in a short time becomes
neutral to litmus; if, on the other hand, the acidity is due entirely to
acid salts, the fluid remains acid; or, if due to both acid and acid
salts, there is a proportionate diminution of acidity due to the
decomposition of the lime carbonate by the free acid. A quantitative
method has been devised upon these principles. See Leo, _Diagnostik der
Krankheiten der Verdauungsorgane_, Hirschwald, Berlin, 1890.

The free mineral acid, after extracting the organic acid by ether, can
also be saturated with cinchonine; this hydrochlorate of cinchonine is
extracted by chloroform, evaporated to dryness, and the residue
dissolved in water acidified by nitric acid and precipitated by silver
nitrate; the silver chloride produced is collected on a small filter,
washed, and the filter, with its contents, dried and ignited in a
porcelain crucible; the silver chloride, multiplied by 0·25426, equals
HCl.

The best method of estimating free hydrochloric acid in the stomach is
that of Sjokvist as modified by v. Jaksch;[100] it has the disadvantage
of its accuracy being interfered with by phosphates; it also does not
distinguish between actual free HCl and the loosely bound HCl with
albuminous matters,--this in a toxicological case is of small
importance, because the quantities of HCl found are likely to be large.

[100] _Klinische Diagnostik_, Dr. Rudolph v. Jaksch, Wien u. Leipzig,
1892. _Clinical Diagnosis_. English Translation, by Dr. Cagney. Second
Edition. London: Charles Griffin & Co., Limited.

The method is based upon the fact that if carbonate of baryta be added
to the contents of the stomach, the organic acids will decompose the
barium carbonate, forming butyrate, acetate, lactate, &c., of barium;
and the mineral acids, such as hydrochloric acid, will combine, forming
salts of barium.

On ignition, chloride of barium will be unaffected, while the organic
salts of barium will be converted into carbonate of barium, practically
insoluble in carbonic acid free water.

The contents of the stomach are coloured with litmus, and barium
carbonate added until the fluid is no longer acid (as shown by the
disappearance of the red colour); then the contents are evaporated to
dryness in a platinum dish, and ignited at a dull red heat; complete
burning to an ash is not necessary. After cooling, the burnt mass is
repeatedly exhausted with boiling water and filtered; the chloride of
barium is precipitated from the filtrate by means of dilute sulphuric
acid; the barium sulphate filtered off, washed, dried, and, after
ignition, weighed; 233 parts of barium sulphate equal 73 parts of HCl.

A method somewhat quicker, but depending on the same principles, has
been suggested by Braun.[101] A fractional part, say 10 c.c., of the
fluid contents is coloured by litmus and titrated with decinormal soda.
To the same quantity is added 2 or 3 more c.c. of decinormal soda than
the quantity used in the first titration; this alkaline liquid is
evaporated to dryness and ultimately ignited. To the ash is now added
exactly the quantity of decinormal sulphuric acid as the decinormal soda
last used to make it alkaline--that is to say, if the total acidity was
equal to 3·6 d.n. soda, and 5·0 d.n. soda was added to the 10 c.c.
evaporated to dryness and burned, then 5·6 c.c. of d.n. sulphuric acid
is added to the ash. The solution is now warmed to get rid of carbon
dioxide, and, after addition of a little phenolphthalein, titrated with
d.n. soda solution until the change of colour shows saturation, the
number of c.c. used, multiplied by 0·00365, equals the HCl.

[101] _Op. cit._, S. 157.

§78. In investigating the stains from hydrochloric acid on fabrics, or
the leaves of plants, any free hydrochloric acid may be separated by
boiling with water, and then investigating the aqueous extract. Should,
however, the stain be old, all free acid may have disappeared, and yet
some of the chlorine remain in organic combination with the tissue, or
in combination with bases. Dr. Angus Smith has found weighed portions of
leaves, &c., which had been exposed to the action of hydrochloric acid
fumes, richer in chlorides than similar parts of the plants not thus
exposed.

The most accurate method of investigation for the purpose of separating
chlorine from combination with organic matters is to cut out the
stained portions, weigh them, and burn them up in a combustion-tube,
the front portion of the tube being filled with caustic lime known to be
free from chlorides; a similar experiment must be made with the
unstained portions. In this way a considerable difference may often be
found; and it is not impossible, in some instances, to thus detect,
after the lapse of many years, that certain stains have been produced by
a chlorine-holding substance.


III.--Nitric Acid.

§ 79. =General Properties.=--Nitric acid--commonly known in England as
_aqua fortis_, chemically as _nitric acid_, _hydric nitrate_, or _nitric
monohydrate_--is a mono-hydrate of nitrogen pentoxide (N₂O₅), two
equivalents, or 126 parts, of nitric acid containing 108 of N₂O₅, and 18
of H₂O. Anhydrous nitric acid, or nitrogen pentoxide, can be obtained by
passing, with special precautions, dry chlorine over silver nitrate; the
products are free oxygen and nitrogen pentoxide, according to the
following equation:--

   Silver    Chlorine.    Silver      Nitrogen    Oxygen.
  Nitrate.               Chloride.   Pentoxide.
  Ag₂O,N₂O₅ +   2Cl     =   2AgCl   +   N₂O₅      +   O

By surrounding the receiver with a freezing mixture, the acid is
condensed in crystals, which dissolve in water, with emission of much
heat, forming nitric acid. Sometimes the crystals, though kept in sealed
tubes, decompose, and the tube, from the pressure of the liberated
gases, bursts with a dangerous explosion.

Pure nitric acid has a specific gravity of 1·52, and boils at 98°. Dr.
Ure examined the boiling point and other properties of nitric acid very
fully. An acid of 1·5 specific gravity boils at 98·8°; of specific
gravity 1·45, at 115·5°; specific gravity 1·40, at 118·8°; of specific
gravity 1·42, at 122·8°. The acid of specific gravity 1·42 is the
standard acid of the British Pharmacopœia. It can always be obtained by
distilling either strong or moderately weak nitric acid; for, on the one
hand, the acid on distillation gets weaker until the gravity of 1·42 is
reached, or, on the other, it becomes stronger.

There is little doubt that acid of 1·42 gravity is a definite hydrate,
consisting of 1 atom of dry acid and 4 atoms of water; it corresponds to
75 per cent.[102] of the liquid acid HNO₃. There are also at least two
other hydrates known--one an acid of 1·485 specific gravity,
corresponding to 1 atom of dry acid and 2 of water, and an acid of
specific gravity 1·334, corresponding to 1 atom of dry acid and 7 atoms
of water.

[102] The British Pharmacopœia states that the 1·42 acid equals 70 per
cent. of HNO₃; but this is not in accordance with Ure’s Tables, nor with
the facts.

In Germany the officinal acid is of 1·185 specific gravity,
corresponding to about 30 per cent. of HNO₃. The dilute nitric acid of
the Pharmacopœia is a colourless liquid, of specific gravity 1·101, and
should contain about 17·4 per cent. of acid. The acids used in various
industries are known respectively as _dyers’_ and _engravers’_ acid.
_Dyers’_ acid has a specific gravity of 1·33 to 1·34 (66° to 68° Twad.),
that is, strength from 56 to 58 per cent. of HNO₃. _Engravers’_ acid is
stronger; being of 1·40 specific gravity (80° Twad.); and contains 70
per cent. of HNO₃. Although the _pure_ acid of commerce is (and should
be) almost colourless, most commercial specimens are of hues from yellow
up to deep red. An acid saturated with red oxides of nitrogen is often
known as “fuming nitric acid.”

§ 80. =Use in the Arts.=--Nitric acid is employed very extensively in
the arts and manufactures. The dyer uses it as a solvent for tin in the
preparation of valuable mordants for calico and other fabrics; the
engraver uses it for etching copper. It is an indispensable agent in the
manufacture of gun-cotton, nitro-glycerin, picric acid, and sulphuric
acid; it is also used in the manufacture of tallow, in preparing the
felt for hats, and in the gilding trades. It is said to be utilised to
make yellowish or fawn-coloured spots on cigar leaves, so as to give
them the appearance of age and quality. It is also used as a medicine.

§ 81. =Statistics of Poisoning by Nitric Acid.=--In the ten years
1883-1892 no case of murder was ascribed to nitric acid, but it caused
accidentally 25 deaths, and was used in 27 cases of suicide.

The following tables give the age and sex distribution of these
deaths:--

DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS ENDING 1892 FROM NITRIC
ACID.

                ACCIDENT OR NEGLIGENCE.

  Ages,      1-5  5-15  15-25  25-65  65 and  Total
                                      above
  Males,      6     2      1      9    ...      18
  Females,    3   ...    ...      4    ...       7
             --------------------------------------
  Totals,     9     2      1     13    ...      25
             --------------------------------------

                       SUICIDE.

  Ages,                 15-25  25-65  65 and  Total
                                      above
  Males,                   3     14      1      18
  Females,                 1      8    ...       9
                       ----------------------------
  Totals,                  4     22      1      27
                       ----------------------------

§ 82. =Fatal Dose.=--The dose which causes death has not been
ascertained with any exactness. As in the case of sulphuric acid, we may
go so far as to say that it is possible for a few drops of the strong
acid to be fatal, for if brought into contact with the vocal apparatus,
fatal spasm of the glottis might be excited. The smallest dose on record
is 7·7 grms. (2 drachms), which killed a child aged 13.

§ 83. =Action of Nitric Acid on Vegetation.=--Nitric acid acts on plants
injuriously in a two-fold manner--viz., by direct corrosive action, and
also by decomposing the chlorides which all plants contain, thus setting
free chlorine, which decomposes and bleaches the chlorophyll. The action
is most intense on soft and delicate leaves, such as those of clover,
the cabbage, and all the cruciferæ. The tobacco plant is particularly
injured by nitric acid. Next to all herbaceous plants, trees, such as
the apple, pear, and fruit trees, generally suffer. The coniferæ,
whether from their impregnation with resin, or from some other cause,
possess a considerable resisting-power against nitric acid vapours, and
the same is true as regards the cereals; in the latter case, their
siliceous armour acts as a preserving agent.

§ 84. =Nitric Acid Vapour.=--The action of nitric acid in a state of
vapour, as evolved by warming potassic nitrate and sulphuric acid
together, has been studied by Eulenberg. A rabbit was placed under a
shade into which 63 grains of nitric acid in a state of vapour were
introduced. From the conditions of the experiment, some nitric peroxide
must also have been present. Irritation of the external mucous membranes
and embarrassment in breathing were observed. The animal in forty-five
minutes was removed, and suffered afterwards from a croupous bronchitis,
from which, however, it completely recovered in eleven days. A second
experiment with the same animal was followed by death. On inspection,
there was found strong injection of the cerebral membranes, with small
extravasations of blood; the lungs were excessively congested; the right
middle lobe especially was of a liver-brown colour, and empty of air: it
sank in water.

O. Lassar[103] has also made a series of researches on the influence of
nitric acid vapour, from which he concludes that the acid is not
absorbed by the blood, but acts only by its mechanical irritation, for
he could not trace, by means of an examination of the urine, any
evidence of such absorption.

[103] Hoppe-Seyler’s _Zeitschrift f. physiol. Chemie_, Bd. i. S.
165-173, 1877-78.

There are a few instances on record of the vapour having been fatal to
men; for example, the well-known case of Mr. Haywood, a chemist of
Sheffield, may be cited. In pouring a mixture of nitric and sulphuric
acids from a carboy of sixty pounds capacity, the vessel broke, and for
a few minutes he inhaled the mixed fumes. He died eleven hours after
the accident, although for the first three hours there were scarcely any
symptoms of an injurious effect having been produced. On inspection,
there was found intense congestion of the windpipe and bronchial tubes,
with effusion of blood in the latter. The lining membrane of the heart
and aorta was inflamed; unfortunately, the larynx was not examined.[104]

[104] _Lancet_, April 15, 1854, p. 430.

A very similar case happened in Edinburgh in 1863.[105] Two young men
were carrying a jar of nitric acid; the jar broke, and they attempted to
wipe up the acid from the floor. The one died ten hours after the
accident, the other in less than twenty-four hours. The symptoms were
mainly those of difficult breathing, and it is probable that death was
produced from suffocation. Dr. Taylor relates also, that having
accidentally inhaled the vapour in preparing gun-cotton, he suffered
from severe constriction of the throat, tightness in the chest, and
cough, for more than a week.[106]

[105] _Chemical News_, March 14, 1863, p. 132.

[106] _Principles and Practice of Medical Jurisprudence_, vol. i., 1873,
p. 218.

§ 85. =Effects of Liquid Nitric Acid.=--Poisoning by nitric acid, though
still rare, is naturally more frequent than formerly. At the beginning
of this century, Tartra[107] wrote a most excellent monograph on the
subject, and collated all the cases he could find, from the first
recorded instances related by Bembo[108] in Venetian history, down to
his own time. The number of deaths in those 400 years was but
fifty-five, while, in our century, at least fifty can be numbered. Most
of these (74 per cent.) are suicidal, a very few homicidal, the rest
accidental. In one of Tartra’s cases, some nitric acid was placed in the
wine of a drunken woman, with fatal effect. Osenbrüggen[109] relates the
case of a father murdering his six children by means of nitric acid; and
C. A. Büchner[110] that of a soldier who poured acid into the mouth of
his illegitimate infant. A curious case is one in which a man poisoned
his drunken wife by pouring the acid into her right ear; she died after
six weeks’ illness. All these instances prove again, if necessary, that
the acid is only likely to be used with murderous intent in the case of
young children, or of sleeping, drunken, or otherwise helpless people.

[107] Tartra, A. E., Dr., _Traité de l’Empoisonnement par l’Acide
Nitrique_, Paris, An. 10 (1802), pp. 300.

[108] _Bembo Cardinalis, Rerum Venetarium Historiæ_, lib. xii., lib. i.
p. 12, Paris Ed., 1551.

[109] _Allgem.-Deutsche Strafrechtszeitung, herausgeg. v. Frz. v.
Holtzendorff_, 5 Jahrg., 1865, Hft. 5, S. 273.

[110] Friederich’s _Blätter f. ger. Med._, 1866, Hft. 3, S. 187.

As an example of the way in which accidents are brought about by
heedlessness, may be cited the recent case of a woman who bought a small
quantity of aqua fortis for the purpose of allaying toothache by a
local application. She attempted to pour the acid direct from the bottle
into the cavity of the tooth; the acid went down her throat, and the
usual symptoms followed. She threw up a very perfect cast of the gullet
(preserved in University College museum), and rapidly died. Nitric acid
has been mistaken for various liquids, and has also been used by
injection as an abortive, in every respect having a toxicological
history similar to that of sulphuric acid.

§ 86. =Local Action.=--When strong nitric acid comes in contact with
organic matters, there is almost constantly a development of gas. The
tissue is first bleached, and then becomes of a more or less intense
yellow colour. Nitric acid spots on the skin are not removed by ammonia,
but become of an orange-red when moistened with potash and a solution of
cyanide of potassium. The yellow colour seems to show that picric acid
is one of the constant products of the reaction; sulphide of ammonium
forms a sort of soap with the epidermis thus attacked, and detaches it.

§ 87. =Symptoms.=--The symptoms and course of nitric acid poisoning
differ in a few details only from those of sulphuric acid. There is the
same instant pain and frequent vomiting, destruction of the mucous
membranes, and, in the less severe cases, after-contraction of the
gullet, &c.

One of the differences in the action of nitric and sulphuric acids is
the constant development of gas with the former. This, without doubt,
adds to the suffering. Tartra made several experiments on dead bodies,
and showed that very considerable distension of the intestinal canal, by
gaseous products, was the constant result; the tissues were corroded and
almost dissolved, being transformed, ultimately, into a sort of greasy
paste. The vomited matters are of a yellow colour, unless mixed with
blood, when they are of a dirty-brown hue, with shreds of yellow mucus,
and have the strong acid reaction and smell of nitric acid. The teeth
may be partially attacked from the solvent action of the acid on the
enamel. The fauces and tongue, at first blanched, soon acquire a
citron-yellow, or even a brown colour; the whole cavity may swell and
inflame, rendering the swallowing of liquids difficult, painful, and
sometimes impossible. The air passages may also become affected, and in
one case tracheotomy was performed for the relief of the breathing.[111]
The stomach rejects all remedies; there are symptoms of collapse; quick,
weak pulse, frequent shivering, obstinate constipation, and death (often
preceded by a kind of stupor) in from eighteen to twenty-four hours. The
intellectual faculties remain clear, save in a few rare instances.

[111] Arnott, _Med. Gaz._, vol. xii. p. 220.

C. A. Wunderlich has recorded an unusual case, in which the symptoms
were those of dysentery, and the large intestine was found acutely
inflamed, while the small one was little affected. The kidneys had the
same appearance as in Bright’s disease.[112] The smallest fatal dose
given by Taylor is from 2 drachms, which killed a child aged 13 years.
Should the dose of nitric acid be insufficient to kill at once, or, what
amounts to the same thing, should the acid be immediately diluted with
water, or in some way be neutralised, the patient, as in the case of
sulphuric acid, may yet die at a variable future time from stenosis of
the gullet, impaired digestion, &c. For example, in an interesting case
related by Tartra,[113] a woman, who had swallowed 42 grms. (1·5 oz.) of
nitric acid, feeling acute pain, took immediately a quantity of water,
and three hours afterwards was admitted into hospital, where she
received appropriate treatment. At the end of a month she left,
believing herself cured; but in a little while returned, and was
re-admitted, suffering from marasmus, extreme weakness, and constant
vomiting; ultimately she died. The _post-mortem_ examination revealed
extreme contraction of the intestinal canal throughout. The lumen would
hardly admit a penholder. The stomach was no larger than an ordinary
intestine, and adherent to adjacent organs; on its internal surface
there were spots, probably cicatrices; there were also changes in the
gullet, but not so marked. A somewhat similar case is related by the
same author in his thirteenth observation. In the Middlesex Hospital
there is preserved the stomach (No. 1363) of a man who died forty days
after swallowing 2 ozs. of nitric acid diluted in a tumbler of water.
The stomach is contracted, the mucous membrane of the lower part of the
gullet, the lesser curvature, and the pyloric end of the stomach is
extensively corroded, showing ulcerated patches commencing to cicatrize.

[112] _De Actionibus quibusdam Acidi Nitrici Caustico in Corpus Humanum
immissi. Programma Academ._, Lipsiæ, 1857, 4.

[113] _Op. cit._

§ 88. =Post-mortem Appearances.=--The pathological changes in the
tongue, gullet, and stomach can be readily studied from the preparations
in the different museums. The staining by the nitric acid appears
unchanged to the naked eye for many years; hence, most of the nitric
acid preparations are in an excellent state of preservation. A very good
example of the pathological changes is to be found in Nos. 1049 and
1050, University College museum.

    No. 1049 presents the tongue, pharynx, and larynx of a man who had
    swallowed a tea-cupful of nitric acid. The epithelium of the
    œsophagus is for the most part wanting, and hangs in shreds; the
    dorsum of the tongue, in front of the circumvallate papillæ, is
    excavated, and over its central part superficially ulcerated; in
    other places the tongue is encrusted with a thick, loose,
    fawn-coloured layer, formed probably of desquamated epithelium. The
    whole of the mucous surface is stained of a dirty yellow.

    No. 1050 is a preparation showing the tongue, gullet, and stomach of
    a person who died from the effects of nitric acid. The tongue in
    places is smooth and glazed; in others, slightly depressed and
    excavated. On the anterior wall and lower portion of the gullet two
    large sloughs exist.

    Although perforation of the stomach is not so common with nitric as
    with sulphuric acid, such an accident may occur, as shown in a
    preparation at Guy’s Hospital, in which there is a perforation at
    the cardiac end. All the mucous membrane has disappeared, and the
    inner surface is for the most part covered with flocculent shreds.
    Three ounces of nitric acid are said to have been swallowed, and the
    patient lived seventeen hours. There is the usual staining. There is
    also in the Middlesex Hospital (No. 1364) the œsophagus and stomach
    of a woman aged 30, who died six hours after swallowing 2 to 3 ozs.
    of strong nitric acid. The inner coats of the mucous membrane of the
    gullet and stomach are in part converted into opaque yellow and
    black eschars, and in part to a shreddy pulpy condition. At the most
    depending part of the stomach is a large ragged perforation, with
    pulpy margins, which allowed the contents of the stomach to escape
    into the peritoneal cavity.

    In St. Bartholomew’s museum, there is a very good specimen (No.
    1870) of the appearances in the gullet and stomach after poisoning
    by nitric acid. The case is detailed in _St. Bartholomew’s Hospital
    Reports_, vol. v. p. 247. A male died in fifteen hours after
    swallowing 1 oz. of nitric acid. The whole mucous membrane is
    wrinkled, or rather ploughed, into longitudinal furrows, the yellow
    discoloration stops abruptly, with an irregular border, at the
    commencement of the stomach, the epithelial and mucous coats of
    which are wanting--its surface being rough and of a brownish-red
    colour.

    The following preparations are to be found in the museum of the
    London Hospital:--A. b. 1. and A. b. 8.--A. b. 1. shows the pharynx,
    œsophagus, larynx, and stomach of a young woman, who, after taking
    half an ounce of nitric acid, died in eight hours. The staining is
    very intense; as an unusual feature, it may be noted that the larynx
    is almost as yellow as the œsophagus. The abrasion or solution of
    the epithelium on the dorsum of the tongue has dissected out the
    circumvallate and fungiform papillæ, so that they project with
    unusual distinctness. The lining membrane of the gullet throughout
    is divided into minute squares by longitudinal and transverse
    furrows. The mucous membrane of the stomach appears wholly
    destroyed, and presents a woolly appearance.

    A. b. 8. shows a very perfect cast of the œsophagus. The case was
    that of a woman, aged 35, who swallowed half an ounce of nitric
    acid. The symptoms for the first four days were the usual pain in
    the throat and stomach, which might be expected; the bowels were
    freely open, and the stools dark and offensive. On the sixth day,
    there was constant vomiting with offensive breath; on the ninth, the
    appearance of the patient was critical, and she threw up the cast
    preserved. She died on the tenth day after the taking of the acid.
    The gullet, stomach, trachea, and larynx were found after death much
    inflamed.

    The following preparations are in St. Thomas’ Hospital:--P. 5.--a
    stomach with gullet attached. The stomach is covered with
    yellowish-green patches of false membrane and deposit; the gullet
    has the usual longitudinal furrows so characteristic of corrosive
    fluids.

    P. 6. is also from a case of nitric acid poisoning. It shows the
    lining membrane of the stomach partly destroyed and shreddy, yet but
    little discoloured, the hue being a sort of delicate fawn.

    To these may be added a case described and figured by Lesser; to a
    baby, a few days old, an unknown quantity of fuming nitric acid was
    given; the child made a gurgling, choking sound, and died in a few
    minutes. The corpse, nine days after death, showed no signs of
    decomposition. The tongue and gums were yellow, the gullet less so,
    the stomach still less, and the small intestine had no yellow tint;
    the whole of the mouth, gullet, and stomach showed the corrosive
    action of the acid. The graduation of tint, Lesser remarks, is what
    is not seen when the yellow colour is due to poisoning by chromic
    acid or by strong solution of ferric perchloride; in such cases,
    wherever the liquid has gone, there is a yellowness.[114]

[114] A. Lesser, _Atlas der gerichtlichen Medicin_, Berlin, 1884, Tafel
i. fig. 2.

§ 89. =Detection and Estimation of Nitric Acid.=--The detection either
of free nitric acid or of its salts is not difficult. Free nitric acid,
after preliminary estimation of the total acidity by decinormal soda,
may be separated by the cinchonine process given at p. 100. On
precipitation by ammonia or soda solution, the nitrate of ammonia or
soda (and, it may be, other similarly combined acids) remain in
solution. If free nitric acid is present in small quantity only, it may
be necessary to evaporate the filtrate from the quinine nearly to
dryness, and to test the concentrated liquid for nitric acid. The
ordinary tests are as follows:--

(1.) Nitrates, treated with mercury or copper and strong sulphuric acid,
develop nitric oxide, recognised by red fumes, if mixed with air or
oxygen.

(2.) A nitrate dissolved in a small quantity of water, with the addition
of a crystal of ferrous sulphate (allowed to partially dissolve), and
then of strong sulphuric acid--poured through a funnel with a long tube
dipping to the bottom of the test-tube, so as to form a layer at the
bottom--strikes a brown colour at the junction of the liquid. When the
test is properly performed, there will be three layers--the uppermost
being the nitrate solution, the middle ferrous sulphate, and the lowest
sulphuric acid; the middle layer becomes of a smoky or black hue if a
nitrate is present. Organic matter interferes much with the reaction.

(3.) Nitrates in solution, treated in the cold with a zinc copper
couple, are decomposed first into nitrites, and then into ammonia. The
nitrites may be detected by a solution of metaphenyldiamine, which
strikes a red colour with an infinitesimal quantity. Hence, a solution
which gives no red colour with metaphenyldiamine, when submitted to the
action of a zinc copper couple, and tested from time to time, cannot
contain nitrites; therefore, no nitrates were originally present.

(4.) Nitrates, on being treated with strong sulphuric acid, and then a
solution of indigo carmine dropped in, decolorise the indigo; this is a
useful test--not conclusive in itself, but readily applied, and if the
cinchonine method of separation has been resorted to, with few sources
of error.

There is a process of separating nitric acid direct from any organic
tissue, which may sometimes be useful:--Place the substance in a strong,
wide-mouthed flask, closed by a caoutchouc cork, and in the flask put a
small, short test-tube, charged with a strong solution of ferrous
chloride in hydrochloric acid. The flask is connected to the mercury
pump (see fig. p. 47), and made perfectly vacuous by raising and
lowering the reservoir. When this is effected, the tube SS′P is adjusted
so as to deliver any gas evolved into a eudiometer, or other
gas-measuring apparatus. By a suitable movement of the flask, the acid
ferrous chloride is allowed to come in contact with the tissue, a gentle
heat applied to the flask, and gases are evolved. These may be carbon
dioxide, nitrogen, and nitric oxide. On the evolution of gas ceasing,
the carbon dioxide is absorbed by passing up under the mercury a little
caustic potash. When absorption is complete, the gas, consisting of
nitrogen and nitric oxide, may be measured. A bubble or two of oxygen is
now passed into the eudiometer; if nitric oxide is present, red fumes at
once develop. On absorbing the excess of oxygen and the nitric peroxide
by alkaline pyrogallate, and measuring the residual gas, it is easy to
calculate how much nitric oxide was originally present, according to the
principles laid down in “Foods,” p. 587.

It is also obvious that, by treating nitric oxide with oxygen, and
absorbing the nitric peroxide present by an alkaline liquid of known
strength and free from nitrates or ammonia, the resulting solution may
be dealt with by a zinc copper couple, and the ammonia developed by the
action of the couple directly estimated by titration by a decinormal
hydrochloric acid, if large in quantity, or by “_nesslerising_,” if
small in quantity. Crum’s method of estimating nitrates (“Foods,” p.
568) in the cases of minute stains on fabrics, &c., with a little
modification, may be occasionally applicable.


IV.--Acetic Acid.

    § 90. In the ten years ending 1893 nine deaths (four males and five
    females) occurred in England and Wales from drinking, by mistake or
    design, strong acetic acid.

    A few cases only have been recorded in medical literature although
    there have been many experiments on animals.

    The symptoms in the human subject consist of pain, vomiting, and
    convulsions.

    In animals it causes colic, paralysis of the extremities, bloody
    urine, and œdema of the lungs. The lethal dose for plant-eating
    animals is about 0·49 gramme per kilo.

    There should be no difficulty in recognising acetic acid; the odour
    alone is, in most cases, strong and unmistakable. Traces are
    detected by distilling, neutralising the distillate by soda,
    evaporating to dryness, and treating the residue as follows:--A
    portion warmed with alcohol and sulphuric acid gives a smell of
    acetic ether. Another portion is heated in a small tube of hard
    glass with arsenious acid; if acetic acid is present, or an acetate,
    a smell of kakodyl is produced.


V.--Ammonia.

§ 91. Ammonia, (NH₃), is met with either as a vapour or gas, or as a
solution of the pure gas in water.

=Properties.=--Pure ammonia gas is colourless, with a strong,
irritating, pungent odour, forming white fumes of ammonic chloride, if
exposed to hydric chloride vapour, and turning red moist litmus-paper
strongly blue. By intense cold, or by a pressure of 6½ atmospheres at
the ordinary temperature, the gas is readily liquefied; the liquid
ammonia boils at 38°; its observed specific gravity is ·731; it freezes
at -57·1°. Ammonia is readily absorbed by water; at 0° water will take
up 1000 times its own volume, and at ordinary temperatures about 600
times its volume. Alcohol also absorbs about 10 per cent. Ammonia is a
strong base, and forms a number of salts. Ammonia is one of the constant
products of the putrefaction of nitrogenous substances; it exists in the
atmosphere in small proportions, and in everything that contains water.
Indeed, water is the only compound equal to it in its universality of
diffusion. The minute quantities of ammonia thus diffused throughout
nature are probably never in the free state, but combinations of ammonia
with hydric nitrate, carbon dioxide, &c.

§ 92. =Uses.=[115]--A solution of ammonia in water has many applications
in the arts and industries; it is used in medicine, and is an
indispensable laboratory reagent.

[115] Sir B. W. Richardson has shown that ammonia possesses powerful
antiseptic properties.--_Brit. Med. Journal_, 1862.

The officinal caustic preparations of ammonia are--_ammoniæ liquor
fortior_ (_strong solution of ammonia_), which should contain 32·5 per
cent. of ammonia, and have a specific gravity of ·891.

_Liquor ammoniæ_ (_solution of ammonia_), specific gravity ·959, and
containing 10 per cent. of ammonia. There is also a _liniment of
ammonia_, composed of olive oil, 3 parts, and ammonia, 1 part.

_Spiritus Ammoniæ Fœtidus_ (_fœtid spirit of ammonia_).--A solution of
assafœtida in rectified spirit and ammonia solution, 100 parts by
measure, contains 10 of strong solution of ammonia.

Strong solution of ammonia is an important ingredient in the
“_linimentum camphoræ composita_” (_compound liniment of camphor_), the
composition of which is as follows:--camphor, 2·5 parts; oil of
lavender, ·125; strong solution of ammonia, 5·0; and rectified spirit,
15 parts. Its content of strong solution of ammonia is then about 22·6
per cent. (equivalent to 7·3 of NH₃).[116]

[116] There is a common liniment for horses used in stables, and
popularly known as “white oil.” It contains 1 part of ammonia, and 4
parts of olive or rape oil; not unfrequently turpentine is added.
Another veterinary liniment, called “egg oil,” contains ammonia, oil of
origanum, turpentine, and the yelks of eggs.

_The carbonate of ammonia_ is also caustic; it is considered to be a
compound of acid carbonate of ammonium, NH₄HCO₃, with carbamate of
ammonium, NH₄NH₂CO₂. It is in the form of colourless, crystalline
masses; the odour is powerfully ammoniacal; it is strongly alkaline, and
the taste is acrid. It completely volatilises with heat, is soluble in
water, and somewhat soluble in spirit.

The officinal preparation is the “_spiritus ammoniæ aromaticus_,” or
aromatic spirit of ammonia. It is made by distilling in a particular way
ammonic carbonate, 4 ozs.; strong solution of ammonia, 8 ozs.; rectified
spirit, 120 ozs.; water, 60 ozs.; volatile oil of nutmeg, 4½ drms.; and
oil of lemon, 6½ drms. Aromatic spirit of ammonia is a solution in a
weak spirit of neutral carbonate, flavoured with oil of lemon and
nutmeg; the specific gravity should be 0·896.

_Smelling salts_ (_sal volatile_) are composed of carbonate of ammonia.

§ 93. =Statistics.=--Falck has found throughout literature notices of
thirty cases of poisoning by ammonia, or some of its preparations. In
two of these it was used as a poison for the purpose of murder, and in
eight with suicidal intent; the remainder were all accidental. The two
criminal cases were those of children, who both died. Six out of eight
of the suicidal, and twelve of the twenty accidental cases also
terminated fatally.

Ammonia was the cause of 64 deaths (39 male, 25 female) by accident and
of 34 (18 male, 16 female) by suicide, making a total of 98 during the
ten years 1883-1892 in England and Wales. At present it occupies the
seventh place among poisons as a cause of accident, the ninth as a means
of suicide.

§ 94. =Poisoning by Ammonia Vapour.=--Strong ammoniacal vapour is fatal
to both animal and vegetable life. There are, however, but few instances
of poisoning by ammonia vapour; these few cases have been, without
exception, the result of accident. Two cases of death are recorded, due
to an attempt to rouse epileptics from stupor, by an injudicious use of
strong ammonia applied to the nostrils. In another case, when
hydrocyanic acid had been taken, there was the same result. An instance
is also on record of poisonous effects from the breaking of a bottle of
ammonia, and the sudden evolution in this way of an enormous volume of
the caustic gas. Lastly, a man employed in the manufacture of ice, by
means of the liquefaction of ammonia (Carré’s process), breathed the
vapour, and had a narrow escape for his life.

§ 95. =Symptoms.=--The symptoms observed in the last case may well serve
as a type of what may be expected to occur after breathing ammonia
vapour. The man remained from five to ten minutes in the stream of gas;
he then experienced a feeling of anxiety, and a sense of constriction in
the epigastrium, burning in the throat, and giddiness. He vomited. The
pulse was small and frequent, the face pale, the mouth and throat
strongly reddened, with increased secretion. Auscultation and percussion
of the chest elicited nothing abnormal, although during the course of
four days he had from time to time symptoms of suffocation, which were
relieved by emetics. He recovered by the eighth day.[117]

[117] Schmidt’s _Jahrbuch_, 1872, i. S. 30.

In experiments on animals, very similar symptoms are produced. There is
increased secretion of the eyes, nose, and mouth, with redness. The cry
of cats becomes remarkably hoarse, and they generally vomit. Great
difficulty in breathing and tetanic convulsions are present. When the
animal is confined in a small closed chamber, death takes place in about
a quarter of an hour.

_On section_, the bronchial tubes, to the finest ramifications, are
found to be filled with a tenacious mucus, and the air passages, from
the glottis throughout, reddened. The lungs are emphysematous, but have
not always any special colour; the heart contains but little coagulated
blood; the blood has a dark-red colour.

§ 96. The chronic effects of the gas, as shown in workmen engaged in
manufactures in which the fumes of ammonia are frequent, appear to be an
inflammation of the eyes and an affection of the skin. The latter is
thought to be due to the ammonia uniting to form a soap with the oil of
the lubricating skin glands. Some observers have also noticed deafness,
and a peculiar colour of the skin of the nose and forehead, among those
who work in guano manufactories. Its usual action on the body appears to
be a diminution of the healthy oxidation changes, and a general lowering
of bodily strength, with evident anæmia.

§ 97. =Ammonia in Solution.--Action on Plants.=--Solutions of strong
ammonia, or solutions of the carbonate, act injuriously on vegetable
life, while the neutral salts of ammonia are, on the contrary, excellent
manures. A 30 per cent. solution of ammonic carbonate kills most plants
within an hour, and it is indifferent whether the whole plant is watered
with this solution, or whether it is applied only to the leaves. If,
after this watering of the plant with ammonic carbonate water, the
injurious salt is washed out as far as possible by distilled water, or
by a weakly acidulated fluid, then the plant may recover, after having
shed more or less of its leaves. These facts sufficiently explain the
injurious effects noticed when urine is applied direct to plants, for
urine in a very short time becomes essentially a solution of ammonic
carbonate.

§ 98. =Action on Human Beings and Animal Life.=--The violence of the
action of caustic solutions of ammonia almost entirely depends on the
state of concentration.

The local action of the strong solution appears to be mainly the
extraction of water and the saponifying of fat, making a soluble soap.
On delicate tissues it has, therefore, a destructive action; but S.
Samuel[118] has shown that ammonia, when applied to the unbroken
epidermis, does not have the same intense action as potash or soda, nor
does it coagulate albumen. Blood, whether exposed to ammonia gas, or
mixed with solution of ammonia, becomes immediately dark-red; then,
later, through destruction of the blood corpuscles, very dark, even
black; lastly, a dirty brown-red. The oxygen is expelled, the hæmoglobin
destroyed, and the blood corpuscles dissolved.

[118] Virchow’s _Archiv f. path. Anat._, Bd. 51, Hft. 1 u. 2, S. 41,
&c., 1870.

The albumen of the blood is changed to alkali-albuminate, and the blood
itself will not coagulate. A more or less fluid condition of the blood
has always been noticed in the bodies of those poisoned by ammonia.

Blood exposed to ammonia, when viewed by the spectroscope, shows the
spectra of alkaline hæmatin, a weak absorption-band, in the
neighbourhood of D; but if the blood has been acted on for some time by
ammonia, then all absorption-bands vanish. These spectra, however, are
not peculiar to ammonia, the action of caustic potash or soda being
similar. The muscles are excited by ammonia, the functions of the nerves
are destroyed.

When a solution of strong ammonia is swallowed, there are two main
effects--(1) the action of the ammonia itself on the tissues it comes
into contact with, and (2) the effects of the vapour on the
air-passages. There are, therefore, immediate irritation, redness, and
swelling of the tongue and pharynx, a burning pain reaching from the
mouth to the stomach, with vomiting, and, it may be, nervous
symptoms. The saliva is notably increased. In a case reported by
Fonssagrives,[119] no less than 3 litres were expelled in the
twenty-four hours. Often the glands under the jaw and the lymphatics of
the neck are swollen.

[119] _L’Union Médicale_, 1857, No. 13, p. 49, No. 22, p. 90.

Doses of from 5 to 30 grammes of the strong solution of ammonia may kill
as quickly as prussic acid. In a case recorded by Christison,[120] death
occurred in four minutes from a large dose, doubtless partly by
suffocation. As sudden a result is also recorded by Plenk: a man, bitten
by a rabid dog, took a mouthful of spirits of ammonia, and died in four
minutes.

[120] Christison, 167.

If death does not occur rapidly, there may be other symptoms--dependent
not upon its merely local action, but upon its more remote effects.
These mainly consist in an excitation of the brain and spinal cord, and,
later, convulsive movements deepening into loss of consciousness. It has
been noticed that, with great relaxation of the muscular system, the
patients complain of every movement causing pain. With these general
symptoms added to the local injury, death may follow many days after the
swallowing of the fatal dose.

Death may also occur simply from the local injury done to the throat and
larynx, and the patient may linger some time. Thus, in a case quoted by
Taylor,[121] in which none of the poison appears actually to have been
swallowed, the man died nineteen days after taking the poison from
inflammation of the throat and larynx. As with the strong acids, so with
ammonia and the alkalies generally, death may also be caused many weeks
and even months afterwards from the effects of contraction of the
gullet, or from the impaired nutrition consequent upon the destruction,
more or less, of portions of the stomach or intestinal canal.

[121] _Principles of Jurisprudence_, i. p. 235.

§ 99. =Post-mortem Appearances.=--In recent cases there is an intense
redness of the intestinal canal, from the mouth to the stomach, and even
beyond, with here and there destruction of the mucous membrane, and even
perforation. A wax preparation in the museum of University College (No.
2378) shows the effects on the stomach produced by swallowing strong
ammonia; it is ashen-gray in colour, and most of the mucous membrane is,
as it were, dissolved away; the cardiac end is much congested.

The contents of the stomach are usually coloured with blood; the
bronchial tubes and glottis are almost constantly found inflamed--even a
croup-like (or diphtheritic) condition has been seen. Œdema of the
glottis should also be looked for: in one case this alone seems to have
accounted for death. The blood is of a clear-red colour, and fluid. A
smell of ammonia may be present.

If a sufficient time has elapsed for secondary effects to take place,
then there may be other appearances. Thus, in the case of a girl who,
falling into a fainting fit, was treated with a draught of undiluted
spirits of ammonia, and lived four weeks afterwards, the stomach
(preserved in St. George’s Hospital museum, 43 b, ser. ix.) is seen to
be much dilated and covered with cicatrices, and the pylorus is so
contracted as hardly to admit a small bougie. It has also been noticed
that there is generally a fatty degeneration of both the kidneys and
liver.

It need scarcely be observed that, in such cases, no free ammonia will
be found, and the question of the cause of death must necessarily be
wholly medical and pathological.

§ 100. =Separation of Ammonia.=--Ammonia is separated in all cases by
distillation, and if the organic or other liquid is already alkaline,
it is at once placed in a retort and distilled. If neutral or acid, a
little burnt magnesia may be added until the reaction is alkaline. It is
generally laid down that the contents of the stomach in a putrid
condition cannot be examined for ammonia, because ammonia is already
present as a product of decomposition; but even under these
circumstances it is possible to give an opinion whether ammonia _in
excess_ is present. For if, after carefully mixing the whole contents of
the stomach, and then drying a portion and reckoning from that weight
the total nitrogen (considering, for this purpose, the contents to
consist wholly of albumen, which yields about 16 per cent. of
nitrogen)--under these conditions, the contents of the stomach yield
more than 16 per cent. of nitrogen as ammonia reckoned on the dry
substance, it is tolerably certain that ammonia not derived from the
food or the tissues is present.

If, also, there is a sufficient evolution of ammonia to cause white
fumes, when a rod moistened with hydrochloric acid is brought near to
the liquid, this is an effect never noticed with a normal decomposition,
and renders the presence of extrinsic ammonia probable.

An alkaline-reacting distillate, which gives a brown colour with the
“nessler” reagent, and which, when carefully neutralised with sulphuric
acid, on evaporation to dryness by the careful heat of a water-bath,
leaves a crystalline mass that gives a copious precipitate with platinic
chloride, but is hardly at all soluble in absolute alcohol, can be no
other substance than ammonia.

§ 101. =Estimation.=--Ammonia is most quickly estimated by distilling,
receiving the distillate in decinormal acid, and then titrating back. It
may also be estimated as the double chloride of ammonium and platinum
(NH₄Cl)₂PtCl₄. The distillate is exactly neutralised by HCl, evaporated
to near dryness, and an alcoholic solution of platinic chloride added in
sufficient quantity to be always in slight excess, as shown by the
yellow colour of the supernatant fluid. The precipitate is collected,
washed with a little alcohol, dried, and weighed on a tared filter; 100
parts of the salt are equal to 7·6 of NH₃.


VI.--Caustic Potash and Soda.

§ 102. There is so little difference in the local effects produced by
potash and soda respectively, that it will be convenient to treat them
together.

=Potash= (=potassa caustica=).--Hydrate of potassium (KHO), atomic
weight 56, specific gravity 2·1.

=Properties.=--Pure hydrate of potassium is a compact, white solid,
usually met with in the form of sticks. When heated to a temperature a
little under redness, it melts to a nearly colourless liquid; in this
state it is intensely corrosive. It rapidly absorbs moisture from the
air, and moist potash also absorbs with great avidity carbon dioxide; it
is powerfully alkaline, changing red litmus to blue. It is soluble in
half its weight of cold water, great heat being evolved during solution;
it forms two definite hydrates--one, KHO + H₂O; the other, KHO + 2H₂O.
It is sparingly soluble in ether, but is dissolved by alcohol,
wood-spirit, fusel oil, and glycerin.

§ 103. =Pharmaceutical Preparations.=--Potassium hydrate, as well as the
solution of potash, is officinal in all pharmacopœias. The _liquor
potassæ_, or solution of potash, of the British Pharmacopœia, is a
strongly alkaline, caustic liquid, of 1·058 specific gravity, and
containing 5·84 per cent. by weight of KHO. It should, theoretically,
not effervesce, when treated with an acid, but its affinity for CO₂ is
so great that all solutions of potash, which have been in any way
exposed to air, contain a little carbonate. Caustic sticks of potash and
lime used to be officinal in the British Pharmacopœia. Filho’s caustic
is still in commerce, and is made by melting together two parts of
potassium hydrate and one part of lime in an iron ladle or vessel; the
melted mass is now moulded by pouring it into leaden moulds. Vienna
paste is composed of equal weights of potash and lime made into a paste
with rectified spirit or glycerin.

§ 104. =Carbonate of Potash= (K₂CO₃ + 1½H₂O), when pure, is in the form
of small white crystalline grains, alkaline in taste and reaction, and
rapidly deliquescing when exposed to moist air; it gives all the
chemical reactions of potassium oxide, and carbon dioxide. Carbonate of
potash, under the name of _salt of tartar_, or potashes, is sold by
oilmen for cleansing purposes. They supply it either in a fairly pure
state, or as a darkish moist mass containing many impurities.

§ 105. =Bicarbonate of Potash= (KHCO₃) is in the form of large
transparent rhombic prisms, and is not deliquescent. The effervescing
solution of potash (_liquor potassæ effervescens_) consists of 30 grains
of KHCO₃ in a pint of water (3·45 grms. per litre), and as much CO₂ as
the water will take up under a pressure of seven atmospheres.

§ 106. =Caustic Soda--Sodium Hydrate= (NaHO).--This substance is a white
solid, very similar in appearance to potassium hydrate; it absorbs
moisture from the air, and afterwards carbon dioxide, becoming solid
again, for the carbonate is not deliquescent. In this respect, then,
there is a great difference between potash and soda, for the former is
deliquescent both as hydrate and carbonate; a stick of potash in a
semi-liquid state, by exposure to the air, continues liquid, although
saturated with carbon dioxide. Pure sodium hydrate has a specific
gravity of 2·0; it dissolves in water with evolution of heat, and the
solution gives all the reactions of sodium hydrate, and absorbs carbon
dioxide as readily as the corresponding solution of potash. The _liquor
sodæ_ of the B.P. should contain 4·1 per cent. of NaHO.

§ 107. =Sodæ Carbonas--Carbonate of Soda=--(Na₂CO₃10H₂O).--The pure
carbonate of soda for medicinal use is in colourless and transparent
rhombic octahedrons; when exposed to air, the crystals effloresce and
crumble. The _sodæ carbonas exsiccata_, or dried carbonate of soda, is
simply the ordinary carbonate, deprived of its water of crystallisation,
which amounts to 62·93 per cent.

§ 108. =Bicarbonate of Soda= (NaHCO₃) occurs in the form of minute
crystals, or, more commonly, as a white powder. The _liquor sodæ
effervescens_ of the B.P. is a solution of the bicarbonate, 30 grains of
the salt in 20 ozs. of water (3·45 grms. per litre), the water being
charged with as much carbonic acid as it will hold under a pressure of
seven atmospheres. _The bicarbonate of soda lozenges_ (_trochisci sodæ
bicarbonatis_) contain in each lozenge 5 grains (327 mgrms.) of the
bicarbonate. The carbonate of soda sold for household purposes is of two
kinds--the one, “seconds,” of a dirty white colour and somewhat impure;
the other, “best,” is a white mass of much greater purity. _Javelle
water_ (_Eau de Javelle_) is a solution of hypochlorite of soda; its
action is poisonous, more from the caustic alkali than from the
chlorine, and may, therefore, be here included.

§ 109. =Statistics.=--Poisoning by the fixed alkalies is not so frequent
as poisoning by ammonia. Falck has collected, from medical literature,
27 cases, 2 of which were the criminal administering of _Eau de
Javelle_, and 5 were suicidal; 22, or 81·5 per cent., died--in 1 of the
cases after twenty-four hours; in the others, life was prolonged for
days, weeks, or months--in 1 case for twenty-seven months. In the ten
years 1883-1892, in England and Wales, there were 27 deaths from
poisoning by the fixed alkalies; 2 were suicidal (1 from potash, the
other from soda); the remaining 25 were due to accident; of these, 7 (3
males and 4 females) were from caustic soda, and 18 (8 males and 10
females) from caustic potash.

§ 110. =Effects on Animal and Vegetable Life.=--The fixed alkalies
destroy all vegetable life, if applied in strong solution or in
substance, by dehydrating and dissolving the tissues. The effects on
animal tissues are, in part, due also to the affinity of the alkalies
for water. They extract water from the tissues with which they come in
contact, and also attack the albuminous constituents, forming
alkali-albuminate, which swells on the addition of water, and, in a
large quantity, even dissolves. Cartilaginous and horny tissues are also
acted upon, and strong alkalies will dissolve hair, silk, &c. The action
of the alkali is by no means restricted to the part first touched, but
has a remarkable faculty of spreading in all directions.

§ 111. =Local Effects.=--The effects of strong alkali applied to the
epidermis are similar to, but not identical with, those produced by
strong acids. S. Samuel[122] has studied this experimentally on the ear
of the rabbit; a drop of a strong solution of caustic alkali, placed on
the ear of a white rabbit, caused stasis in the arteries and veins, with
first a greenish, then a black colour of the blood; the epidermis was
bleached, the hair loosened, and there quickly followed a greenish
coloration on the back of the ear, opposite to the place of application.
Around the burned spot appeared a circle of anastomising vessels, a
blister rose, and a slough separated in a few days. The whole thickness
of the ear was coloured yellowish-green, and, later, the spot became of
a rusty brown.

[122] Virchow’s _Archiv. f. path. Anat._, Bd. 51, Hft. 1 u. 2, 1870.

§ 112. =Symptoms.=--The symptoms observed when a person has swallowed a
dangerous dose of caustic (fixed) alkali are very similar to those
noticed with ammonia, with the important exception that there is no
respiratory trouble, unless the liquid has come into contact with the
glottis; nor has there been hitherto remarked the rapid death which has
taken place in a few ammonia poisonings, the shortest time hitherto
recorded being three hours, as related by Taylor, in a case in which a
boy had swallowed 3 ozs. of a strong solution of carbonate of potash.

There is instant pain, extending from the mouth to the stomach, and a
persistent and unpleasant taste; if the individual is not a determined
suicide, and the poison (as is mostly the case) has been taken
accidentally, the liquid is immediately ejected as much as possible, and
water, or other liquid at hand, drunk freely. Shock may at once occur,
and the patient die from collapse; but this, even with frightful
destruction of tissue, appears to be rare. Vomiting supervenes; what is
ejected is strongly alkaline, and streaked with blood, and has a soapy,
frothy appearance. There may be diarrhœa, great tenderness of the
abdomen, and quick pulse and fever. With caustic potash, there may be
also noticed its toxic effects (apart from local action) on the heart;
the pulse, in that case, is slow and weak, and loss of consciousness and
convulsions are not uncommon. If the collapse and after-inflammation are
recovered from, then, as in the case of the mineral acids, there is all
the horrid sequence of symptoms pointing to contractions and strictures
of the gullet or pylorus, and the subsequent dyspepsia, difficulty of
swallowing, and not unfrequently actual starvation.

§ 113. =Post-mortem Appearances.=--In cases of recent poisoning, spots
on the cheeks, lips, clothing, &c., giving evidence of the contact of
the alkali, should be looked for; but this evidence, in the case of
persons who have lived a few days, may be wanting. The mucous membrane
of the mouth, throat, gullet, and stomach is generally more or less
white--here and there denuded, and will be found in various stages of
inflammation and erosion, according to the amount taken, and the
concentration of the alkali. Where there is erosion, the base of the
eroded parts is not brown-yellow, but, as a rule, pale red. The gullet
is most affected at its lower part, and it is this part which is mostly
subject to stricture. Thus Böhm[123] found that in 18 cases of
contraction of the gullet, collected by him, 10 of the 18 showed the
contraction at the lower third.

[123] _Centralblatt für die Med. Wiss._, 1874.

The changes which the stomach may present if the patient has lived some
time, are well illustrated by a preparation in St. George’s museum (43
a. 264, ser. ix.). It is the stomach of a woman, aged 44, who had
swallowed a concentrated solution of carbonate of potash. She vomited
immediately after taking it, and lived about two months, during the
latter part of which she had to be nourished by injections. She died
mainly from starvation. The gullet in its lower part is seen to be much
contracted, its lining membrane destroyed, and the muscular coats
exposed. The coats of the stomach are thickened, but what chiefly
arrests the attention is a dense cicatrix at the pylorus, with an
aperture so small as only to admit a probe.

The colour of the stomach is generally bright red, but in that of a
child, preserved in Guy’s Hospital museum (No. 1798²⁴), the mucous
membrane is obliterated, the rugæ destroyed, and a dark-brown stain is a
noticeable feature. The stomach is not, however, necessarily affected.
In a preparation in the same museum (No. 1798²⁰) the mucous membrane of
the stomach of a child who swallowed soap-lees is seen to be almost
healthy, but the gullet is much discoloured. The action on the blood is
to change it into a gelatinous mass; the blood corpuscles are destroyed,
and the whole colour becomes of a dirty blackish-red; the spectroscopic
appearances are identical with those already described (see p. 114).

The question as to the effects of chronic poisoning by the alkalies or
their carbonates may arise. Little or nothing is, however, known of the
action of considerable quantities of alkalies taken daily. In a case
related by Dr. Tunstall,[124] a man for eighteen years had taken daily 2
ozs. of bicarbonate of soda for the purpose of relieving indigestion. He
died suddenly, and the stomach was found extensively diseased; but since
the man, before taking the alkali, had complained of pain, &c., it is
hardly well, from this one case, to draw any conclusion.

[124] _Med. Times_, Nov. 30, 1850, p. 564.

It is important to observe that the contents of the stomach may be acid,
although the death has been produced by caustic alkali. A child, aged 4,
drank from a cup some 14 per cent. soda lye. He vomited frequently, and
died in fifteen hours. The stomach contained 80 c.c. of sour-smelling
turbid fluid, the reaction of which was acid. There were hæmorrhagic
patches in the stomach, and signs of catarrhal inflammation; there was
also a similarly inflamed condition of the duodenum.[125]

[125] Lesser, _Atlas d. gericht. Med._, Tafel ii.

§ 114. =Chemical Analysis.=--The tests for potassium or sodium are too
well known to need more than enumeration. The intense yellow flame
produced when a sodium salt is submitted to a Bunsen flame, and the
bright sodium-line at D when viewed by the spectroscope, is a delicate
test; while potassium gives a dull red band in the red, and a faint but
very distinct line in the violet. Potassium salts are precipitated by
tartaric acid, while sodium salts do not yield this precipitate;
potassium salts also give a precipitate with platinic chloride insoluble
in strong alcohol, while the compound salt with sodium is rapidly
dissolved by alcohol or water. This fact is utilised in the separation
and estimation of the two alkalies.

§ 115. =Estimation of the Fixed Alkalies.=--To detect a fixed alkali in
the contents of the stomach, a convenient process is to proceed by
dialysis, and after twenty-four hours, to concentrate the outer liquid
by boiling, and then, if it is not too much coloured, to titrate
directly with a decinormal sulphuric acid. After exact neutralisation,
the liquid is evaporated to dryness, carbonised, the alkaline salts
lixiviated out with water, the sulphuric acid exactly precipitated by
baric chloride, and then, after separation of the sulphate, the liquid
treated with milk of lime. The filtrate is treated with a current of CO₂
gas, boiled, and any precipitate filtered off; the final filtrate will
contain only alkalies. The liquid may now be evaporated to dryness with
either hydrochloric or sulphuric acids, and the total alkalies weighed
as sulphates or chlorides. Should it be desirable to know exactly the
proportion of potassium to sodium, it is best to convert the alkalies
into chlorides--dry gently, ignite, and weigh; then dissolve in the
least possible quantity of water, and precipitate by platinic chloride,
which should be added so as to be a little in excess, but not much. The
liquid thus treated is evaporated nearly to dryness, and then extracted
with alcohol of 80 per cent., which dissolves out any of the double
chloride of platinum and sodium. Finally, the precipitate is collected
on a tared filter and weighed, after drying at 100°. In this way the
analyst both distinguishes between the salts of sodium and potassium,
and estimates the relative quantities of each. It is hardly necessary to
observe that, if the double chloride is wholly soluble in water or
alcohol, sodium alone is present. This, however, will never occur in
operating on organic tissues and fluids, for both alkalies are
invariably present. A correction must be made when complex organic
fluids are in this way treated for alkalies which may be naturally in
the fluid. Here the analyst will be guided by his preliminary
titration, which gives the total free alkalinity. In cases where the
alkali has been neutralised by acids, of course no free alkali will be
found, but the corresponding salt.


VII.--Neutral Sodium, Potassium, and Ammonium Salts.

    § 116. The neutral salts of the alkalies are poisonous, if
    administered in sufficient doses, and the poisonous effect of the
    sulphate, chloride, bromide, iodide, tartrate, and citrate appears
    to depend on the specific action of the alkali metal, rather than on
    the acid, or halogen in combination. According to the researches of
    Dr. Ringer and Dr. Harrington Sainsbury,[126] with regard to the
    relative toxicity of the three, as shown by their effect on the
    heart of a frog--first, the potassium salts were found to exert the
    most poisonous action, next come the ammonium, and, lastly, the
    sodium salts. The highest estimate would be that sodium salts are
    only one-tenth as poisonous as those of ammonium or potassium; the
    lowest, that the sodium salts are one-fifth: although the
    experiments mainly throw light upon the action of the alkalies on
    one organ only, yet the indications obtained probably hold good for
    the organism as a whole, and are pretty well borne out by clinical
    experience.

[126] _Lancet_, June 24, 1882.

    There appear to be four cases on record of poisoning by the above
    neutral salts; none of them belong to recent times, but lie between
    the years 1837-1856. Hence, the main knowledge which we possess of
    the poisonous action of the potassium salts is derived from
    experiments on animals.

    § 117. =Sodium Salts.=--Common salt in such enormous quantity as
    half a pound to a pound has destroyed human life, but these cases
    are so exceptional that the poisonous action of sodium salts is of
    scientific rather than practical interest.

    § 118. =Potassium Salts.=--Leaving for future consideration the
    nitrate and the chlorate of potassium, potassic sulphate and
    tartrate are substances which have destroyed human life.

    =Potassic Sulphate= (K₂SO₄) is in the form of colourless rhombic
    crystals, of bitter saline taste. It is soluble in 10 parts of
    water.

    =Hydropotassic Tartrate= (KHC₄H₄O₆), when pure, is in the form of
    rhombic crystals, tasting feebly acid. It is soluble in 210 parts of
    water at 17°.

    § 119. =Action on the Frog’s Heart.=--Both excitability and
    contractility are affected to a powerful degree. There is a
    remarkable slowing of the pulsations, irregularity, and, lastly,
    cessation of pulsation altogether.

    § 120. =Action on Warm-Blooded Animals.=--If a sufficient quantity
    of a solution of a potassic salt is injected into the blood-vessels
    of an animal, there is almost immediate death from arrest of the
    heart’s action. Smaller doses, subcutaneously applied, produce
    slowing of the pulse, dyspnœa, and convulsions, ending in death.
    Small doses produce a transitory diminution of the force of arterial
    pressure, which quickly passes, and the blood-pressure rises. There
    is at first, for a few seconds, increase in the number of
    pulsations, but later a remarkable slowing of the pulse. The rise in
    the blood-pressure occurs even after section of the spinal cord.
    Somewhat larger doses cause rapid lowering of the blood-pressure,
    and apparent cessation of the heart’s action; but if the thorax be
    then opened, the heart is seen to be contracting regularly, making
    some 120-160 rhythmic movements in the minute. If the respiration be
    now artificially maintained, and suitable pressure made on the walls
    of the chest, so as to empty the heart of blood, the blood-pressure
    quickly rises, and natural respiration may follow. An animal which
    lay thirty-six minutes apparently dead was in this way brought to
    life again (_Böhm_). The action of the salts of potassium on the
    blood is the same as that of sodium salts. The blood is coloured a
    brighter red, and the form of the corpuscles changed; they become
    shrivelled through loss of water. Voluntary muscle loses quickly its
    contractility when a solution of potash is injected into its
    vessels. Nerves also, when treated with a 1 per cent. solution of
    potassic chloride, become inexcitable.

    § 121. =Elimination.=--The potassium salts appear to leave the body
    through the kidneys, but are excreted much more slowly than the
    corresponding sodium salts. Thus, after injection of 4 grms. of
    potassic chloride--in the first sixteen hours ·748 grm. of KCl was
    excreted in the urine, and in the following twenty-four hours 2·677
    grms.

    § 122. =Nitrate of Potash= (KNO₃).--Pure potassic nitrate
    crystallises in large anhydrous hexagonal prisms with dihedral
    summits; it does not absorb water, and does not deliquesce. Its
    fusing point is about 340°; when melted it forms a transparent
    liquid, and loses a little of its oxygen, but this is for the most
    part retained by the liquid given off when the salt solidifies. At a
    red-heat it evolves oxygen, and is reduced first to nitrite; if the
    heat is continued, potassic oxide remains. The specific gravity of
    the fused salt is 2·06. It is not very soluble in cold water, 100
    parts dissolving only 26 at 15·6°; but boiling water dissolves it
    freely, 100 parts dissolving 240 of the salt.

    A solution of nitrate of potash, when treated with a zinc couple
    (see “Foods,” p. 566), is decomposed, the nitrate being first
    reduced to nitrite, as shown by its striking a red colour with
    metaphenylene-diamine, and then the nitrite farther decomposing, and
    ammonia appearing in the liquid. If the solution is alkalised, and
    treated with aluminium foil, hydrogen is evolved, and the same
    effect produced. As with all nitrates, potassic nitrate, on being
    heated in a test-tube with a little water, some copper filings, and
    sulphuric acid, evolves red fumes of nitric peroxide.

    § 123. =Statistics.=--Potassic nitrate, under the popular name of
    “_nitre_,” is a very common domestic remedy, and is also largely
    used as a medicine for cattle. There appear to be twenty cases of
    potassic nitrate poisoning on record--of these, eight were caused by
    the salts having been accidentally mistaken for magnesic sulphate,
    sodic sulphate, or other purgative salt; two cases were due to a
    similar mistake for common salt. In one instance, the nitrate was
    used in strong solution as an enema, but most of the cases were due
    to the taking of too large an internal dose.

    § 124. =Uses in the Arts=, &c.--Both sodic and potassic nitrates are
    called “nitre” by the public indiscriminately. Sodic nitrate is
    imported in large quantities from the rainless districts of Peru as
    a manure. Potassic nitrate is much used in the manufacture of
    gunpowder, in the preservation of animal substances, in the
    manufacture of gun cotton, of sulphuric and nitric acids, &c. The
    maximum medicinal dose of potassium nitrate is usually stated to be
    30 grains (1·9 grm.).

    § 125. =Action of Nitrates of Sodium and Potassium.=--Both of these
    salts are poisonous. Potassic nitrate has been taken with fatal
    result by man; the poisonous nature of sodic nitrate is established
    by experiments on animals. The action of the nitrates of the
    alkalies is separated from that of the other neutral salts of
    potassium, &c., because in this case the toxic action of the
    combined nitric acid plays no insignificant part. Large doses, 3-5
    grms. (46·3-77·2 grains), of potassic nitrate cause considerable
    uneasiness in the stomach and bowels; the digestion is disturbed;
    there may be vomiting and diarrhœa, and there is generally present a
    desire to urinate frequently. Still larger doses, 15-30 grms.
    (231·5-463 grains), rapidly produce all the symptoms of acute
    gastro-enteritis--great pain, frequent vomiting (the ejected matters
    being often bloody), with irregularity and slowing of the pulse;
    weakness, cold sweats, painful cramps in single muscles (especially
    in the calves of the legs); and, later, convulsions, aphonia, quick
    collapse, and death.

    In the case of a pregnant woman, a handful of “nitre” taken in
    mistake for Glauber’s salts produced abortion after half-an-hour.
    The woman recovered. Sodic nitrate subcutaneously applied to frogs
    kills them, in doses of ·026 grm. (·4 grain), in about two hours;
    there are fibrillar twitchings of single groups of muscles and
    narcosis. The heart dies last, but after ceasing to beat may, by a
    stimulus, be made again to contract. Rabbits, poisoned similarly by
    sodic nitrate, exhibit also narcotic symptoms; they lose
    consciousness, lie upon their side, and respond only to the sharpest
    stimuli. The breathing, as well as the heart, is “slowed,” and death
    follows after a few spasmodic inspirations.

    =Sodic nitrite= was found by Barth to be a more powerful poison,
    less than 6 mgrms. (·1 grain) being sufficient to kill a rabbit of
    455·5 grms. (7028 grains) weight, when subcutaneously injected. The
    symptoms were very similar to those produced by the nitrate.

    § 126. The _post-mortem_ appearances from potassic nitrate are as
    follows:--An inflamed condition of the stomach, with the mucous
    membrane dark in colour, and readily tearing; the contents of the
    stomach are often mixed with blood. In a case related by Orfila,
    there was even a small perforation by a large dose of potassic
    nitrate, and a remarkable preservation of the body was noted.

    It is believed that the action of the nitrates is to be partly
    explained by a reduction to nitrites, circulating in the blood as
    such. To detect nitrites in the blood, the best method is to place
    the blood in a dialyser, the outer liquid being alcohol. The
    alcoholic solution may be evaporated to dryness, extracted with
    water, and then tested by metaphenylene-diamine.

    § 127. =Potassic Chlorate= (KClO₃).--Potassic chlorate is in the
    form of colourless, tabular crystals with four or six sides. About 6
    parts of the salt are dissolved by 100 of water at 15°, the
    solubility increasing with the temperature, so that at 100° nearly
    60 parts dissolve; if strong sulphuric acid be dropped on the
    crystals, peroxide of chlorine is evolved; when rubbed with sulphur
    in a mortar, potassic chlorate detonates. When the salt is heated
    strongly, it first melts, and then decomposes, yielding oxygen gas,
    and is transformed into the perchlorate. If the heat is continued,
    this also is decomposed, and the final result is potassic chloride.

    § 128. =Uses.=--Potassic chlorate is largely used as an oxidiser in
    calico printing, and in dyeing, especially in the preparation of
    aniline black. A considerable quantity is consumed in the
    manufacture of lucifer matches and fireworks; it is also a
    convenient source of oxygen. Detonators for exploding dynamite are
    mixtures of fulminate of mercury and potassic chlorate. It is
    employed as a medicine both as an application to inflamed mucous
    membranes, and for internal administration; about 2000 tons of the
    salt for these various purposes are manufactured yearly in the
    United Kingdom.

    § 129. =Poisonous Properties.=--The facility with which potassic
    chlorate parts with its oxygen by the aid of heat, led to its very
    extensive employment in medicine. No drug, indeed, has been given
    more recklessly, or on a less scientific basis. Wherever there were
    sloughing wounds, low fevers, and malignant sore throats, especially
    those of a diphtheritic character, the practitioner administered
    potassic chlorate in colossal doses. If the patient died, it was
    ascribed to the malignity of the disease--if he recovered, to the
    oxygen of the salt; and it is possible, from the light which of
    recent years has been thrown on the action of potassic chlorate,
    that its too reckless use has led to many unrecorded accidents.

    § 130. =Experiments on Animals.=--F. Marchand[127] has studied the
    effects of potassic chlorate on animals, and on blood. If either
    potassic chlorate or sodic chlorate is mixed with fresh blood, it
    shows after a little while peculiar changes; the clear red colour at
    first produced passes, within a few hours, into a dark red-brown,
    which gradually becomes pure brown. This change is produced by a 1
    per cent. solution, in from fifteen to sixteen hours; and a 4 per
    cent. solution at 15° destroys every trace of oxyhæmoglobin within
    four hours. Soon the blood takes a syrupy consistence, and, with a
    2-4 per cent. solution of the salt, passes into a jelly-like mass.
    The jelly has much permanence, and resists putrefactive changes for
    a long time.

[127] _Virchow’s Archiv. f. path. Anat._, Bd. 77, Hft. 3, S. 455, 1879.

    Marchand fed a dog of 17 kilos. in weight with 5 grms. of potassic
    chlorate for a week. As there were no apparent symptoms, the dose
    was doubled for two days; and as there was still no visible effect,
    lastly, 50 grms. of sodic chlorate were given in 5 doses. In the
    following night the dog died. The blood was found after death to be
    of a sepia-brown colour, and remained unaltered when exposed to the
    air. The organs were generally of an unnatural brown colour; the
    spleen was enormously enlarged; the kidneys were swollen, and of a
    dark chocolate brown--on section, almost black-brown, the colour
    being nearly equal, both in the substance and in the capsule. A
    microscopical examination of the kidney showed the canaliculi to be
    filled with brownish cylinders consisting of altered blood. A
    spectroscopic examination of the blood showed weak hæmoglobin bands,
    and a narrow band in the red. With farther dilution, the hæmoglobin
    bands vanished, but the band in the red remained. The diluted blood,
    when exposed to the light, still remained of a coffee-brown colour;
    and on shaking, a white-brown froth was produced on the surface.

    A second experiment in which a hound of from 7-8 kilos. in weight
    was given 3-5 grm. doses of potassic chlorate in sixteen hours, and
    killed by bleeding seven to eight hours after the last dose, showed
    very similar appearances. The kidneys were intensely congested, and
    the peculiar brown colour was noticeable.

    § 131. =Effects on Man.=--I find in literature thirty-nine cases
    recorded, in which poisonous symptoms were directly ascribed to the
    action of chlorate of potassium; twenty-eight of these terminated
    fatally. A quadruple instance of poisoning, recorded by Brouardel
    and L’Hôte,[128] illustrates many of the points relative to the time
    at which the symptoms may be expected to commence, and the general
    aspect of potassic chlorate poisoning. The “_supérieure_” of a
    religious institution was in the habit of giving, for charitable
    purposes, a potion containing 15 grms. (3·8 drms.) of potassic
    chlorate, dissolved in 360 c.c. (about 12½ ozs.) of a vegetable
    infusion.

[128] _Annales d’Hygiène publique_, 1881, p. 232.

    This potion was administered to four children--viz., David, aged 2½;
    Cousin, aged 3½; Salmont, 2½; and Guérin, 2½. David took the whole
    in two and a half hours, the symptoms commenced after the potion was
    finished, and the child died five and a half hours after taking the
    first dose; there were vomiting and diarrhœa. Cousin took the
    medicine in seven hours; the symptoms also commenced after the last
    spoonful, and the death took place eight and a half hours from the
    first spoonful. The symptoms were mainly those of great depression;
    the lips were blue, the pulse feeble, there was no vomiting, no
    diarrhœa. Salmont took the medicine in nine hours, and died in
    twelve. There was some diarrhœa, the stools were of a green colour.
    Guérin took the whole in two hours, the symptoms commenced in four
    hours; the lips were very pale, the gums blue. Death took place in
    four days.

    There was an autopsy in the case of David only. The stomach showed a
    large ecchymosis on its mucous membrane, as if it had been burnt by
    an acid; the spleen was gorged with blood, and its tissue friable;
    the kidneys do not seem to have been thoroughly examined, but are
    said to have been tumefied. Potassic chlorate was discovered by
    dialysis. In the cases of the children just detailed, the symptoms
    appear to be a mixture of the depressing action of the potassium,
    and irritant action of the chlorate.

    § 132. In adults, the main symptoms are those of nephritis, and the
    fatal dose for an adult is somewhere about an ounce (28·3 grms.),
    but half this quantity would probably be dangerous, especially if
    given to a person who had congestion or disease of the kidneys.

    Dr. Jacobi[129] gives the following cases.

[129] _Amer. Med. Times_, 1860.

    Dr. Fountain in 1858, experimenting on himself, took 29·2 grms. (8·7
    drms.) of potassic chlorate; he died on the seventh day from
    nephritis. A young lady swallowed 30 grms. (8·5 drms.), when using
    it as a gargle; she died in a few days from nephritis. A man, thirty
    years of age, died in four days after having taken 48 grms. (12·3
    drms.) of sodic chlorate in six hours. The _shortest time_ in which
    I can find the salt to have been fatal, is a case related by Dr.
    Manouvriez, in which a woman took 45 grms., and died in five hours.
    The _smallest dose_ which has proved fatal is one in which an infant
    three years old was killed by 3 grms. (46·3 grains).

    Jacobi considers that the maximum dose to be given in divided doses
    during the twenty-four hours, to infants under three, should be from
    1-1·5 grm. (15·4-23·1 grains), to children from three years old, up
    to 2 grms. (30·8 grains); and adults from 6-8 grms. (92·6-123·4
    grains).

    § 133. =Elimination.=--Potassic chlorate is quickly absorbed by
    mucous membranes, and by the inflamed skin, and rapidly separated
    from the body by the action of the kidneys. Wöhler, as early as
    1824, recognised that it in great part passed out of the body
    unchanged, and, lately, Isambert, in conjunction with Hirne,[130]
    making quantitative estimations, recovered from the urine no less
    than 95 per cent. of the ingested salts. Otto Hehner has also made
    several auto-experiments, and taking 2½ drms., found that it could
    be detected in the urine an hour and a half afterwards. At that time
    17·23 per cent. of the salt had been excreted, and, by the end of
    eleven hours, 93·8 per cent. was recovered. It is then difficult to
    believe that the salt gives any oxygen to the tissues, for though it
    is true that in all the investigations a small percentage remains to
    be accounted for, and also that Binz,[131] making experiments by
    mixing solutions of potassic chlorate with moist organic substances,
    such as pus, yeast, fibrin, &c., has declared that, at a blood heat
    the chlorate is rapidly reduced, and is no longer recognisable as
    chlorate--yet it may be affirmed that potassic chlorate is recovered
    from the urine as completely as anything which is ever excreted by
    the body, and that deductions drawn from the changes undergone by
    the salt in solutions of fibrin, &c., have only an indirect bearing
    on the question.

[130] _Gaz. Méd. de Paris_, 1875, Nro. 17, 35, 41, 43.

[131] _Berlin klin. Wochenschr._, xi. 10, S. 119, 1874.

    § 134. The essential action of potassic chlorate seems to be that it
    causes a peculiar change in the blood, acting on the colouring
    matter and corpuscles; the latter lose their property as oxygen
    carriers; the hæmoglobin is in part destroyed; the corpuscles
    dissolved. The decomposed and altered blood-corpuscles are crowded
    into the kidneys, spleen, &c.; they block up the uriniferous
    canaliculi, and thus the organs present the curious colouring seen
    after death, and the kidneys become inflamed.


Detection and Estimation of Potassic Chlorate.

    § 135. Organic fluids are best submitted to dialysis; the dialysed
    fluid should then be concentrated and qualitative tests applied. One
    of the best tests for the presence of a chlorate is, without doubt,
    that recommended by Fresenius. The fluid to be tested is acidulated
    with a few drops of sulphuric acid; sulphate of indigo added
    sufficient to colour the solution blue, and finally a few drops of
    sulphurous acid. In presence of potassic or sodic chlorate, the blue
    colour immediately vanishes. This method is capable of detecting 1
    part in 128,000; provided the solution is not originally coloured,
    and but little organic matter is present.

    The urine can be examined direct, but if it contain albumen, the
    blue colour may disappear and yet chlorate be present; if too much
    sulphurous acid be also added, the test may give erroneous results.
    These are but trivial objections, however, for if the analyst
    obtains a response to the test, he will naturally confirm or
    disprove it by the following process:--

    The liquid under examination, organic or otherwise, is divided into
    two equal parts. In the one, all the chlorine present is
    precipitated as chloride by silver nitrate in the usual way, and the
    chloride of silver collected and weighed. In the other, the liquid
    is evaporated to dryness and well charred by a dull red heat, the
    ash dissolved in weak nitric acid, and the chlorides estimated as in
    the first case. If chlorates were present, there will be a
    difference between the two estimations, proportionate to the amount
    of chlorates which have been converted into chlorides by the
    carbonisation, and the first silver chloride subtracted from the
    second will give an argentic chloride which is to be referred to
    chlorate. In this way also the amount present may be quantitatively
    estimated, 100 parts of silver chloride equalling 85·4 of potassic
    chlorate.


Toxicological Detection of Alkali Salts.

(See also _ante_, p. 121.)

    § 136. Sodium, in combination, especially with chlorine, and also
    with sulphuric, carbonic, and phosphoric acids, is found in the
    plasma of the blood, in the urinary secretion, in the pancreatic
    juice, in human bile, and in serous transudations, &c. Potassium, in
    combination, is especially found in the red blood-corpuscles, in the
    muscles, in the nervous tissues, and in milk. Ammonia, in
    combination with acids, is naturally found in the stomach, in the
    contents of the intestine; it is also a natural constituent of the
    blood in small traces, and in a corpse is copiously evolved from
    putrefactive changes.

    It hence follows, that mere qualitative tests for these elements in
    the tissues or fluids of the body are of not the slightest use, for
    they are always present during the life of the healthiest
    individual, and can be found after death in persons dying from any
    malady whatever. To establish the fact of a person having taken an
    unusual dose of any of the alkali salts, by simply chemical
    evidence, it must be proved that the alkalies are present in unusual
    quantities or in an abnormal state of combination.

    In cases of rapid death, caused by sodic or potassic salts, they
    will be found in such quantity in the contents of the stomach, or in
    matters vomited, that there will probably be no difficulty in coming
    to a direct conclusion; but if some time has elapsed, the analyst
    may not find a sufficient ground for giving a decided judgment, the
    excretion of the alkali salts being very rapid.

    In most cases, it will be well to proceed as follows:--The contents
    of the stomach are, if necessary, diluted with distilled water, and
    divided into three parts, one of which is submitted to dialysis, and
    then the dialysed liquid evaporated to a small bulk and examined
    qualitatively, in order to ascertain whether a large amount of the
    alkaline salts is present, and in what form. In this way, the
    presence or absence of nitrate of potassium or sodium may be proved,
    or the iodide, bromide, sulphate, and chlorate detected.

    To find, in this way, nitrate of potassium, a coarse test is
    preferable to the finer tests dependent upon conversion of the
    nitrate into nitrites or into ammonia, for these tests are so
    delicate, that nitrates may be detected in traces; whereas, in this
    examination, to find traces is of no value. Hence, the old-fashioned
    test of treating the concentrated liquid in a test-tube with copper
    filings and then with sulphuric acid, and looking for the red fumes,
    is best, and will act very well, even should, as is commonly the
    case, some organic matters have passed through the dialyser.

    Chlorates are indicated if the liquid is divided into two parts and
    tested in the manner recommended at p. 127. If present in any
    quantity, chlorates or nitrates may be indicated by the brilliant
    combustion of the organic matter when heated to redness, as also by
    the action of strong sulphuric acid on the solid substances--in the
    one case, yellow vapours of peroxide of chlorine being evolved--in
    the other, the red fumes already mentioned of nitric peroxide.

    With regard to a substance such as the hydro-potassic tartrate, its
    insolubility in water renders it not easy of detection by dialysis;
    but its very insolubility will aid the analyst, for the contents of
    the stomach may be treated with water, and thus all soluble salts of
    the alkalies extracted. On now microscopically examining the
    insoluble residue, crystals of bitartrate, if present, will be
    readily seen. They may be picked up on a clean platinum wire and
    heated to redness in a Bunsen flame, and spectroscopically examined.
    After heating, the melted mass will have an alkaline reaction, and
    give a precipitate with platinic chloride. All other organic salts
    of potassium are soluble, and a white crystal giving such reaction
    must be hydro-potassic tartrate.

    =Ammonium Salts.=--If the body is fresh, and yet the salts of
    ammonium present in large amount, it is safe to conclude that they
    have an external origin; but there might be some considerable
    difficulty in criminal poisoning by a neutral salt of ammonium, and
    search for it in a highly putrid corpse. Probably, in such an
    exceptional case, there would be other evidence. With regard to the
    quantitative separation and estimation of the fixed alkalies in the
    ash of organic substances, the reader is referred to the processes
    given in “Foods,” p. 99, _et seq._, and in the present work, p. 121.




PART V.--MORE OR LESS VOLATILE POISONOUS SUBSTANCES CAPABLE OF BEING
SEPARATED BY DISTILLATION FROM NEUTRAL OR ACID LIQUIDS.

    HYDROCARBONS--CAMPHOR--ALCOHOL--AMYL NITRITE--ETHER--CHLOROFORM AND
    OTHER ANÆSTHETICS--CHLORAL--CARBON DISULPHIDE--CARBOLIC
    ACID--NITRO-BENZENE--PRUSSIC ACID--PHOSPHORUS.


I.--Hydrocarbons.


1. PETROLEUM.

    § 137. Petroleum is a general term for a mixture of hydrocarbons of
    the paraffin series, which are found naturally in certain parts of
    the world, and are in commerce under liquid and solid forms of
    various density. Crude petroleum is not imported into England, the
    original substance having previously undergone more or less
    rectification. The lighter and more volatile portions are known
    under the name of cymogene, rhigolene, gasolene, and naphtha.

    § 138. =Cymogene= has a specific gravity of ·590, and boils at 0°.
    It has been employed in refrigerating machines. It appears to
    consist chiefly of butane (C₄H₁₀).

    § 139. =Rhigolene= is now used in medicine in the form of spray to
    produce local anæsthesia. It boils at 18°, and has a density of
    ·650.

    § 140. =Gasolene= has a density of ·680-·688; it has received
    technical applications in the “naphthalising” of air and gas.

    § 141. =Benzoline= (=mineral naphtha=, =petroleum naphtha=,
    =petroleum spirit=, =petroleum ether=) is a mixture of the lighter
    series of hydro-carbons; the greater part consists of heptane, and
    there is also a considerable quantity of pentane (C₇H₁₆) present.
    The specific gravity varies from ·69 to ·74. It is very inflammable,
    and is used in sponge lamps, and also as a solvent for gutta-percha,
    naphthalene, paraffin, wax, and many other bodies. By the practical
    chemist it is much employed.

    The similarity of the terms _benzoline_ and _benzene_ has caused
    benzoline to be often confused with _benzol_ or _benzene_, the
    leading constituent of coal-tar naphtha (C₆H₆). Mr Allen[132] gives
    in the following table a summary of the chief points of distinction,
    both between petroleum naphtha, shale naphtha, and coal-tar naphtha.
    The table is founded upon the examination of particular samples, and
    commercial samples may present a few minor deviations.

[132] _Commercial Organic Analysis_, vol. ii. p. 31.

TABLE OF THE VARIETIES OF NAPHTHA.

  +---------------------+----------------------+----------------------+
  | Petroleum Naphtha.  |   Shale Naphtha.     |  Coal-tar Naphtha.   |
  +---------------------+----------------------+----------------------+
  |Contains at least 75 |Contains at least 60  |Consists almost wholly|
  |per cent. of heptane,|to 70 per cent. of    |of benzene, C₆H₆, and  |
  |C₇H₁₆, and other      |heptylene, C₇H₁₄, and  |other homologous     |
  |hydrocarbons of the  |other hydrocarbons of |hydrocarbons, with a  |
  |marsh gas or paraffin|the olefin series; the|small percentage of   |
  |series; the remainder|remainder paraffins.  |light hydrocarbons in |
  |apparently olefins,  |No trace of benzene or|some samples.         |
  |C_{n}H_{2n}, with    |its homologues.       |                      |
  |distinct traces of   |                      |                      |
  |benzene and its      |                      |                      |
  |homologues.          |                      |                      |
  |                     |                      |                      |
  |Specific gravity at  |Specific gravity at   |Specific gravity ·876.|
  |15°, ·600.           |15°, ·718.            |                      |
  |                     |                      |                      |
  |Distils between 65°  |Distils between 65°   |Distils between 80°   |
  |and 100°.            |and 100°.             |and 120°.             |
  |                     |                      |                      |
  |Dissolves coal-tar   |Behaves similarly to  |Readily dissolves     |
  |pitch, but slightly; |petroleum naphtha with|pitch, forming a deep |
  |liquid, but little   |regard to the solution|brown solution.       |
  |coloured even after  |of pitch.             |                      |
  |prolonged contact.   |                      |                      |
  |                     |                      |                      |
  |On shaking three     |When treated with     |The liquids form a    |
  |measures of the      |fused carbolic acid   |homogeneous mixture   |
  |sample with one      |crystals, the liquids |when treated with     |
  |measure of fused     |mix perfectly.        |fused carbolic acid   |
  |crystals of absolute |                      |crystals.             |
  |carbolic acid, no    |                      |                      |
  |solution. Liquids not|                      |                      |
  |miscible.            |                      |                      |
  |                     |                      |                      |
  |Combines with 10 per |Combines with upwards |Combines slowly with  |
  |cent. of its weight  |of 90 per cent. of its|30-40 per cent. of its|
  |of bromine in the    |weight of bromine.    |weight of bromine.    |
  |cold.                |                      |                      |
  +---------------------+----------------------+----------------------+

    § 142. =Paraffin Oil= (or =kerosine, mineral oil, photogen=, &c.) is
    the chief product resulting from the distillation of American
    petroleum--the usual specific gravity is about ·802--it is a mixture
    of hydrocarbons of the paraffin series. It should be free from the
    more volatile constituents, and hence should not take fire when a
    flame is applied near the surface of the cold liquid.

    § 143. =Effects of Petroleum.=--Since we have here to deal with a
    commercial substance of such different degrees of purity, and
    various samples of which are composed of such various proportions of
    different hydrocarbons, its action can only be stated in very
    general terms. Eulenberg[133] has experimented with the lighter
    products obtained from the distillation of Canadian petroleum. This
    contained sulphur products, and was extremely poisonous, the vapour
    killing a rabbit in a short time, with previous insensibility and
    convulsions. The autopsy showed a thin extravasation of blood on the
    surface of each of the bulbi, much coagulated blood in the heart,
    congested lungs, and a bloody mucus covering the tracheal mucous
    membrane. An experiment made on a cat with the lighter petroleum
    (which had no excess of sulphur) in the state of vapour, showed that
    it was an anæsthetic, the anæsthesia being accompanied by
    convulsions, which towards the end were tetanic and violent. The
    evaporation of 1·5 grm. in a close chamber killed the animal in
    three hours. The lungs were found congested, but little else was
    remarkable. Much petroleum vapour is breathed in certain factories,
    especially those in which petroleum is refined.[134] From this cause
    there have been rather frequent toxic symptoms among the workmen.
    Eulenberg[135] describes the symptoms as follows:--A person, after
    breathing an overdose of the vapour, becomes very pale, the lips are
    livid, the respiration slow, the heart’s action weak and scarcely to
    be felt. If he does not immediately go into the open air away from
    the poisonous vapour, these symptoms may pass on to insensibility,
    convulsions, and death. It often occasions a condition of the
    voluntary muscles similar to that induced by drunkenness, and on
    recovery the patient is troubled by singing in the ears and noises
    in the head. The smell and taste of the poison may remain for a long
    time.

[133] _Gewerbe-Hygiene._

[134] The vapour most likely to rise at the ordinary temperature, and
mix with the atmosphere, is that of the lighter series, from cymogene to
benzoline.

[135] _Op. cit._

    § 144. Poisoning by taking light petroleum into the stomach is not
    common. In a case recorded by Taylor,[136] a woman, for the purpose
    of suicide, swallowed a pint of petroleum, There followed a slight
    pain in the stomach, and a little febrile disturbance, and a
    powerful smell of petroleum remained about the body for six days;
    but she completely recovered. In August 1870 a sea-captain drank a
    quantity of paraffin, that is, lighting petroleum, and died in a few
    hours in an unconscious state. A child, 2 years old, was brought to
    King’s College Hospital within ten minutes after taking a
    teaspoonful of paraffin. It was semi-comatose and pale, with
    contracted pupils; there was no vomiting or purging. Emetics of
    sulphate of zinc were administered, and the child recovered in
    twenty-four hours. In another case treated at the same hospital, a
    child had swallowed an unknown quantity of paraffin. It fell into a
    comatose state, which simulated tubercular meningitis, and lasted
    for nearly three weeks.[137] In a case recorded by Mr Robert
    Smith,[138] a child, 4 years of age, had swallowed an unknown
    quantity of paraffin. A few minutes afterwards, the symptoms
    commenced; they were those of suffocation, with a constant cough;
    there was no expectoration; the tongue, gums, and cheeks were
    blanched and swollen where the fluid touched them; recovery
    followed. A woman, aged 32, who had taken a quarter of a pint of
    paraffin, was found unconscious and very cold; the stomach-pump was
    used, and she recovered.[139] Hence it is tolerably certain, from
    the above instances, that should a case of petroleum poisoning
    occur, the expert will not have to deal with infinitesimal
    quantities; but while the odour of the oil will probably be
    distinctly perceptible, there will be also a sufficient amount
    obtained either from matters vomited, or the contents of the
    stomach, &c., so that no difficulty will be experienced in
    identifying it.

[136] _Poisons_, p. 656

[137] _Brit. Med. Journ._, Sept. 16, 1876, p. 365.

[138] _Brit. Med. Journ._, Oct. 14, 1876.

[139] _Pharm. Journ._, Feb. 12, 1875; also for other cases see _Brit.
Med. Journ._, Nov. 4, 1876; and Köhler’s _Physiol. Therap._, p. 437.

    § 145. In order to separate petroleum from any liquid, the
    substances under examination must be carefully distilled in the
    manner recommended under “_Ether_.” The lighter petroleums will
    distil by the aid of a water-bath; but the heavier require a
    stronger heat; redistillation of the distillate may be necessary.
    The odour of the liquid, its inflammable character, and its other
    properties, will be sufficient for identification.


2. COAL-TAR-NAPHTHA--BENZENE.

    § 146. Coal-tar-naphtha in its crude state, is an extremely complex
    liquid, of a most disagreeable smell. Much benzene (C₆H₆) is present
    with higher homologues of the benzene series. Toluene (C₇H₈),
    naphthalene (C₁₀H₈), hydrocarbons of the paraffin series,
    especially hexane (C₆H₁₄), and hydrocarbons of the olefin series,
    especially pentylene, hexylene, and heptylene (C₅H₁₀, C₆H₁₂ and
    C₇H₁₄). Besides these, there are nitrogenised bases, such as
    aniline, picoline, and pyridine; phenols, especially carbolic acid;
    ammonia, ammonium sulphide, carbon disulphide, and probably other
    sulphur compounds; acetylene and aceto-nitrile. By distillation and
    fractional distillation are produced what are technically known
    ”_once run_” _naphtha_, _90 per cent. benzol_, _50 and 90 per cent.
    benzol_,[140] _30 per cent. benzol_, _solvent naphtha_, and residue
    known as “_last runnings_.”

[140] Or 50/90 benzol, this indicates that 50 per cent. distils over
below 100°; and 40, making in all 90, below 120°.

    § 147. Taylor[141] records a case in which a boy, aged 12, swallowed
    about 3 ozs. of naphtha, the kind usually sold for burning in lamps,
    and died with symptoms of narcotic poisoning. The child, after
    taking it, ran about in wild delirium, he then sank into a state of
    collapse, breathing stertorously, and the skin became cold and
    clammy. On vomiting being excited, he rejected about two
    tablespoonfuls of the naphtha, and recovered somewhat, but again
    fell into collapse with great muscular relaxation. The breathing was
    difficult; there were no convulsions; the eyes were fixed and
    glassy, the pupils contracted; there was frothing at the mouth. In
    spite of every effort to save him, he died in less than three hours
    after taking the poison. The body, examined three days after death,
    smelt strongly of naphtha, but the _post-mortem_ appearances were in
    no way peculiar, save that the stomach contained a pint of
    semi-fluid matter, from which a fluid, having the characteristics of
    impure benzene, was separated.

[141] _Op. cit._, p. 657.

    § 148. The effects of the vapour of benzene have been studied by
    Eulenberg in experiments on cats and rabbits, and there are also
    available observations on men[142] who have been accidentally
    exposed to its influence. From these sources of information, it is
    evident that the vapour of benzene has a distinctly narcotic effect,
    while influencing also in a marked degree the spinal cord. There
    are, as symptoms, noises in the head, convulsive trembling and
    twitchings of the muscles, with difficulty of breathing.

[142] Dr. Stone, _Med. Gaz._, 1848, vol. xii. p. 1077.


DETECTION AND SEPARATION OF BENZENE.

    § 149. Benzene is separated from liquids by distillation, and may be
    recognised by its odour, and by the properties described at p. 130.
    The best process of identification, perhaps, is to purify and
    convert it into nitro-benzene, and then into aniline, in the
    following manner:--

    1. =Purification.=--The liquid is agitated with a solution of
    caustic soda; this dissolves out of the benzene any bodies of an
    acid character, such as phenol, &c. The purified liquid should again
    be distilled, collecting that portion of the distillate which passes
    over between 65° and 100°; directly the thermometer attains nearly
    the 100°, the distillation should be stopped. The distillate, which
    contains all the benzene present, is next shaken with concentrated
    sulphuric acid in the cold; this will dissolve out all the
    hydrocarbons of the ethylene and acetylene series. On removing the
    layer of benzene from the acid, it must be again shaken up with
    dilute soda, so as to remove any trace of acid. The benzene is, by
    this rather complicated series of operations, obtained in a very
    fair state of purity, and may be converted into nitro-benzene, as
    follows:--

    2. =Conversion into Nitro-Benzene.=--The oily liquid is placed in a
    flask, and treated with four times its volume of fuming nitric acid.
    The flask must be furnished with an upright condenser; a vigorous
    action mostly takes place without the application of heat, but if
    this does not occur, the flask may be warmed for a few minutes.

    After the conversion is over, the liquid, while still warm, must be
    transferred into a burette furnished with a glass tap, or to a
    separating funnel, and all, except the top layer, run into cold
    water; if benzene was originally present, either oily drops of
    nitro-benzene will fall, or if the benzene was only in small
    quantity, a fine precipitate will gradually settle down to the
    bottom of the vessel, and a distinct bitter-almond smell be
    observed; but, if there be no benzene in the original liquid, and,
    consequently, no nitro-benzene formed, no such appearance will be
    observed.

    3. =Conversion into Aniline.=--The nitro-benzene may itself be
    identified by collecting it on a wet filter, dissolving it off the
    filter by alcohol, acidifying the alcoholic solution by hydrochloric
    acid, and then boiling it for some time with metallic zinc. In this
    way aniline is formed by reduction. On neutralising and diluting the
    liquid, and cautiously adding a little clear solution of
    bleaching-powder, a blue or purple colour passing to brown is in a
    little time produced.


3. TERPENES--ESSENTIAL OILS--OIL OF TURPENTINE.

    § 150. The terpenes are hydrocarbons of the general formula
    C_{n}H_{2n-4}. The natural terpenes are divided into three
    classes:--

    1. =The true terpenes=, _formula_ (C₁₀H₁₆)--a large number of
    essential oils, such as those of turpentine, orange peel, nutmeg,
    caraway, anise, thyme, &c., are mainly composed of terpenes.

    2. =The cedrenes=, _formula_ (C₁₅H₂₄)--the essential oil of cloves,
    rosewood, cubebs, calamus, cascarilla, and patchouli belong to this
    class.

    3. =The colophene hydrocarbons=, _formula_ (C₂₀H₃₂), represented by
    colophony.

    Of all these, oil of turpentine alone has any toxicological
    significance; it is, however, true that all the essential oils, if
    taken in considerable doses, are poisonous, and cause, for the most
    part, vascular excitement and complex nervous phenomena, but their
    action has not been very completely studied. They may all be
    separated by distillation, but a more convenient process for
    recovering an essential oil from a liquid is to shake it up with
    petroleum ether, separating the petroleum and evaporating
    spontaneously; by this means the oil is left in a fair state of
    purity.


4. OIL OF TURPENTINE--SPIRIT OF TURPENTINE--“TURPS.”

    § 151. Various species of pine yield a crude turpentine, holding in
    solution more or less resin. The turpentine may be obtained from
    this exudation by distillation, and when the first portion of the
    distillate is treated with alkali, and then redistilled, the final
    product is known under the name of “rectified oil of turpentine,”
    and is sometimes called “camphene.” It mainly consists of
    terebenthene. Terebenthene obtained from French turpentine differs
    in some respects from that obtained from English or American
    turpentine. They are both mobile, colourless liquids, having the
    well-known odour of turpentine and highly refractive; but the French
    terebenthene turns a ray of polarised light to the left -40·3° for
    the sodium ray, and the English to the right +21·5°; the latter
    terebenthene is known scientifically as austra-terebenthene. This
    action on polarised light is retained in the various compounds and
    polymers of the two turpentine oils.

    The specific gravity of turpentine oil is ·864; its boiling point,
    when consisting of pure terebenthene, 156°, but impurities may raise
    it up to 160°; it is combustible and burns with a smoky flame. Oil
    of turpentine is very soluble in ether, petroleum ether, carbon
    disulphide, chloroform, benzene, fixed and essential oils, and by
    the use of these solvents it is conveniently separated from the
    contents of the stomach. It is insoluble in water, glycerin, and
    dilute alkaline and acid solutions; and very soluble in absolute
    alcohol, from which it may be precipitated by the addition of water.

    It is polymerised by the action of strong sulphuric acid, the
    polymer, of course, boiling at a higher temperature than the
    original oil. With water it forms a crystalline hydrate
    (C₁₀H₂₀O₂,H₂O). On passing nitrosyl chloride gas into the oil,
    either pure or diluted with chloroform or alcohol, the mixture being
    cooled by ice, a white crystalline body is deposited, of the formula
    C₁₀H₁₆(NOCl). By treating this compound with alcoholic potash, the
    substitution product (C₁₀H₁₆NO) is obtained. By treating turpentine
    with an equal bulk of warm water, and shaking it in a large bottle
    with air, camphoric acid and peroxide of hydrogen are formed. When
    turpentine oil is left in contact with concentrated hydrochloric
    acid, there is formed terebenthene dihydrochloride (C₁₀H₁₆2HCl),
    which forms rhombic plates, insoluble in water, and decomposable by
    boiling alcoholic potash, with formation of terpinol, (C₁₀H₁₇)₂O.
    The dihydrochloride gives a colour-reaction with ferric chloride.
    This is an excellent test--not, it is true, confined to oil of
    turpentine--but common to the dihydrochlorides of all the terpenes.
    A few drops of the oil are stirred in a porcelain capsule with a
    drop of hydrochloric acid, and one of ferric chloride solution; on
    gently heating, there is produced first a rose colour, then a
    violet-red, and lastly a blue.

    § 152. =Effects of the Administration of Turpentine.=--L. W.
    Liersch[143] exposed animals to the vapour of turpentine, and found
    that a cat and a rabbit died within half an hour. There was observed
    uneasiness, reeling, want of power in the limbs (more especially in
    the hinder extremities), convulsions partial, or general, difficulty
    of respiration; and the heart’s action was quickened. Death took
    place, in part, from asphyxia, and in part was attributable to a
    direct action on the nervous centres. The autopsy showed congestion
    of the lungs, ecchymoses of the kidney, and much blood in the liver
    and spleen. Small doses of turpentine-vapour cause (according to Sir
    B. W. Richardson)[144] giddiness, deficient appetite, and anæmia.
    From half an ounce to an ounce is frequently prescribed in the
    country as a remedy for tape-worm; in smaller quantities it is found
    to be a useful medicine in a great variety of ailments. The larger
    doses produce a kind of intoxication with giddiness, followed often
    by purging and strangury, not unfrequently blood and albumen (or
    both) is found in the urine. When in medical practice I have given
    the oil, and seen it given by others, in large doses for tape-worm
    to adults, in perhaps 40 cases, but in no one instance were the
    symptoms severe; the slight intoxication subsided quickly, and in a
    few hours the patients recovered completely. Nevertheless it has
    been known to destroy the lives of children, and cause most serious
    symptoms in adults. Two fatal cases are mentioned by Taylor; one was
    that of a child who died fifteen hours after taking half an ounce of
    the oil; in another an infant, five months old, died rapidly from a
    teaspoonful. The symptoms in these fatal cases were profound coma
    and slight convulsions; the pupils were contracted, and there was
    slow and irregular breathing. Turpentine is eliminated in a changed
    form by the kidneys, and imparts an odour of violet to the urine;
    but the nature of the odoriferous principle has not yet been
    investigated.

[143] Clarus in Schmidt’s _Jahrbücher_, Bd. cxvii., i. 1863; and
_Vierteljahrsschr. für ger. Med._, xxii., Oct. 1862.

[144] _Brit. and For. Med.-Chir. Review_, April 1863.


II.--Camphor.

    § 153. A great many essential oils deposit, after exposure to air,
    camphors produced by oxidation of their terpenes. Ordinary camphor
    is imported in the rough state from China and Japan, and is prepared
    by distilling with water the wood of _Camphora officinarum_; it is
    resublimed in England. The formula of camphor is C₁₀H₁₆O; it has a
    density of ·986 to ·996; melts at 175°, and boils at 205°. It is
    readily sublimed, especially in a vacuum, and is indeed so volatile
    at all temperatures, that a lump of camphor exposed to the air
    wastes away. It is somewhat insoluble in water (about 1 part in
    1000), but this is enough to impart a distinct taste to the water;
    it is insoluble in chloroform, ether, acetone, acetic acid, carbon
    disulphide, and oils. It has a fragrant odour and a burning taste. A
    10 per cent. solution in alcohol turns a ray of polarised light to
    the right +42·8°. By distillation with zinc chloride, cymene and
    other products are produced. By prolonged treatment with nitric
    acid, camphor is oxidised to camphoric acid (C₁₀H₁₆O₄). Camphor
    unites with bromine to form a crystalline, unstable dibromide, which
    splits up on distillation into hydrobromic acid and monobrom-camphor
    (C₁₀H₁₅BrO). The latter is used in medicine; it crystallises in
    prisms fusible at 76°, and is readily soluble in alcohol.

    § 154. =Pharmaceutical Preparations.=--The preparations officinal in
    the British Pharmacopœia are _camphor water_--water saturated with
    camphor, containing about one part per thousand.

    =Camphor Liniment.=--A solution of camphor in olive oil, strength 25
    per cent.

    =Compound Camphor Liniment.=--Composed of camphor, oil of lavender,
    strong solution of ammonia and alcohol; strength in camphor about 11
    per cent.

    =Spirit of Camphor.=--A solution of camphor in spirit; strength, 10
    per cent.

    Camphor is also a constituent of the _compound tincture of camphor_;
    but in this case it may be considered only a flavouring agent. There
    is a homœopathic solution of camphor in spirit (Rubini’s Essence of
    Camphor). The solution is made by saturating alcohol with camphor;
    it is, therefore, very strong--about half the bulk consisting of
    camphor. Camphor is used in veterinary medicine, both externally and
    internally.

    § 155. =Symptoms.=--Camphor acts energetically on the brain and
    nervous system, especially if it is given in strong alcoholic
    solution, and thus placed under conditions favouring absorption.
    Some years ago, Dr. G. Johnson[145] published a series of cases
    arising from the injudicious use of “homœopathic solution of
    camphor,” from 7 to 40 drops of Rubini’s homœopathic camphor taken
    for colds, sore throat, &c., having produced coma, foaming at the
    mouth, convulsions, and partial paralysis. All the patients
    recovered, but their condition was for a little time alarming.

[145] _Brit. Med. Journ._, Feb. 27, 1878, p. 272; see also _ibid._, Feb.
1875.

    The cases of fatal poisoning by camphor are very rare. A woman, aged
    46, pregnant four months, took 12 grms. (about 184 grains) in a
    glass of brandy for the purpose of procuring abortion. In a very
    short time the symptoms commenced; she had intolerable headache, the
    face was flushed, and there was a sensation of burning in the
    stomach. In eight hours after taking the dose, she had strangury and
    vomiting, and the pain in the epigastrium was intense. These
    symptoms continued with more or less severity until the third day,
    when she became much worse. Her face was pale and livid, the eyes
    hollow, the skin cold and insensible, pulse weak and thready,
    breathing laboured. There were violent cramps in the stomach and
    retention of urine for twenty-four hours, and then coma. The patient
    lingered on yet another three days, aborted, and died.[146]

[146] _Journ. de Chim. Méd._, May 1860.

    Dr. Schaaf[147] has recorded three cases of poisoning--one of which
    was fatal. A woman gave about half a teaspoonful of a camphor
    solution to each of her three children, the ages being respectively
    five and three years and fifteen months. The symptoms noted were
    pallor of the face, a burning pain in the throat, thirst, vomiting,
    purging, convulsions, and afterwards coma. The youngest child died
    in seven hours; the others recovered. The smallest dose known to
    have produced violent symptoms in an adult is 1·3 grm. (20 grains);
    the largest dose known to have been recovered from is 10·4 grms.
    (160 grains).[148]

[147] _Journ. de Chim. Méd._, 1850, p. 507.

[148] Taylor on _Poisons_, 3rd ed., 661.

    § 156. =Post-mortem Appearances.=--The bodies of animals or persons
    dying from poisoning by camphor, smell strongly of the substance.
    The mucous membrane of the stomach has been found inflamed, but
    there seem to be no characteristic lesions.

    § 157. =Separation of Camphor from the Contents of the
    Stomach.=--The identification of camphor would probably in no case
    present any difficulty. It may be readily dissolved out from organic
    fluids by chloroform. If dissolved in fixed oils, enough for the
    purposes of identification may be obtained by simple distillation.
    It is precipitated from its alcoholic solution by the addition of
    water.


III.--Alcohols.


1. ETHYLIC ALCOHOL.

§ 158. The chemical properties of ordinary alcohol are fully described,
with the appropriate tests, in “Foods,” pp. 369-384, and the reader is
also referred to the same volume for the composition and strength of the
various alcoholic drinks.

=Statistics.=--If we were to include in one list the deaths indirectly
due to chronic, as well as acute poisoning by alcohol, it would stand
first of all poisons in order of frequency, but the taking of doses so
large as to cause death in a few hours is rare. The deaths from alcohol
are included by the English registrar-general under two heads, viz.,
those returned as dying from _delirium tremens_, and those certified as
due directly to intemperance.

During the twenty-five years, from 1868 to 1892, 30,219 deaths have been
registered as due to intemperance, which gives an average of 1209 per
year. The rate per million has varied during the period from 29 to 71;
and the figures taken as a whole show that deaths from intemperance
appear to be increasing; the increase may be only apparent, not real,
for it is a significant circumstance that deaths registered under liver
diseases show a corresponding decrease; it is, therefore, not unlikely
that deaths which formerly would be ascribed to liver disease, are more
often now stated to be the effects of intemperance.

Deaths directly due to large doses of alcohol are not uncommon; during
the ten years ending 1892, 105 deaths (81 males and 24 females) were
ascribed under the head of “accident or negligence” directly to alcohol.

[Illustration: CHART SHEWING DEATHS PER MILLION PERSONS LIVING, FROM
INTEMPERANCE & FROM LIVER DISEASES.

  THE MEDICAL “OFFICERS OF HEALTH” CHART.

  ENT. AT STA. HALL.

                        Notes.
                _Intemperance_  --------------
                _Liver disease_ ..............
  _The Scale for Intemperance is as printed._
  _That for Liver diseases is 10 times larger._]

§ 159. =Criminal or Accidental Alcoholic Poisoning.=--Suicide by
alcohol, in the common acceptation of the term, is rare, and murder
still rarer, though not unknown. In the ten years ending 1892, only
three deaths from alcohol (1 male and 2 females) are recorded as
suicidal. Perhaps the most common cause of fatal acute poisoning by
alcohol is either a foolish wager, by which a man bets that he can drink
so many glasses of spirits without bad effect; or else the drugging of a
person already drunk by his companions in a sportive spirit.

§ 160. =Fatal Dose.=--It is difficult to say what would be likely to
prove a lethal dose of alcohol, for a great deal depends, without doubt,
on the dilution of the spirit, since the mere local action of strong
alcohol on the mucous membranes of the stomach, &c., is severe (one may
almost say corrosive), and would aid the more remote effects. In
Maschka’s case,[149] a boy of nine years and a girl of five, died from
about two and a half ounces of spirit of 67 per cent. strength, or 48·2
c.c. (1·7 oz.) of absolute alcohol.

[149] Recorded by Maschka (_Gutachten der Prager Facultät_, iv. 239; see
also Maschka’s _Handbuch der gericht. Medicin_, Band. ii. p. 384). The
following is a brief summary:--Franz. Z., nine years old, and Caroline
Z., eight years old, were poisoned by their stepfather with spirit of 67
per cent. strength taken in small quantities by each--at first by
persuasion, and the remainder administered by force. About one-eighth of
a pint is said to have been given to each child. Both vomited somewhat,
then lying down, stertorous breathing at once came on, and they quickly
died. The autopsy, three days after death, showed dilatation of the
pupils; _rigor mortis_ present in the boy, not in the girl; and the
membranes of the brain filled with dark fluid blood. The smell of
alcohol was perceptible on opening the chest; the mucous membrane of the
bronchial tubes and gullet was normal, both lungs œdematous, the fine
tubes gorged with a bloody frothy fluid, and the mucous membrane of the
whole intestinal canal was reddened. The stomach was not, unfortunately,
examined, being reserved for chemical analysis. The heart was healthy;
the pericardium contained some straw-coloured fluid. Chemical analysis
gave an entirely negative result, which must have been from insufficient
material having been submitted to the analyst, for I cannot see how the
vapours of alcohol could have been detected by the smell, and yet have
evaded chemical processes.

In a case related by Taylor, a child, seven years old, died from some
quantity of brandy, probably about 113·4 c.c. (4 ozs.), which would be
equal to at least 56·7 c.c. (2 ozs.) of absolute alcohol. From other
cases in which the quantity of absolute alcohol can be, with some
approximation to the truth, valued, it is evident that, for any child
below ten or twelve, quantities of from 28·3 to 56·6 c.c. (1-2 ozs.) of
absolute alcohol contained in brandy, gin, &c., would be a highly
dangerous and probably fatal dose; while the toxic dose for adults is
somewhere between 71·8-141·7 c.c. (2·5-5 ozs.).

§ 161. =Symptoms.=--In the cases of rapid poisoning by a large dose of
alcohol, which alone concern us, the preliminary, and too familiar
excitement of the drunkard, may be hardly observable; but the second
stage, that of depression, rapidly sets in; the unhappy victim sinks
down to the ground helpless, the face pale, the eyes injected and
staring, the pupils dilated, acting sluggishly to light, and the skin
remarkably cold. Fräntzel[150] found, in a case in which the patient
survived, a temperature of only 24·6° in the rectum, and in that of
another person who died, a temperature of 23·8°. The mucous membranes
are of a peculiar dusky blue; the pulse, which at first is quick, soon
becomes slow and small; the respiration is also slowed, intermittent,
and stertorous; there is complete loss of consciousness and motion; the
breath smells strongly of the alcoholic drink, and if the coma continues
there may be vomiting and involuntary passing of excreta. Death
ultimately occurs through paralysis of the respiratory centres.
Convulsions in adults are rare, in children frequent. Death has more
than once been immediately caused, not by the poison, but by accidents
dependent upon loss of consciousness. Thus food has been sucked into the
air-tubes, or the person has fallen, so that the face was buried in
water, ordure, or mud; here suffocation has been induced by mechanical
causes.

[150] _Temperaturerniedrigung durch Alcoholintoxication, Charité
Annalen_, i. 371.

A remarkable course not known with any other narcotic is that in which
the symptoms remit, the person wakes up, as it were, moves about and
does one or more rational acts, and then suddenly dies. In this case
also, the death is not directly due to alcohol, but indirectly--the
alcohol having developed œdema, pneumonia, or other affection of the
lungs, which causes the sudden termination when the first effect of the
poison has gone off. The time that may elapse from the commencement of
coma till death varies from a few minutes to days; death has occurred
after a quarter of an hour, half an hour, and an hour. It has also been
prolonged to three, four, and six days, during the whole of which the
coma has continued. The average period may, however, be put at from six
to ten hours.

§ 162. =Post-mortem Appearances.=--Cadaveric rigidity lasts tolerably
long. Casper has seen it still existing nine days after death, and
Seidel[151] seven days (in February). Putrefaction is retarded in those
cases in which a very large dose has been taken, but this is not a very
noticeable or constant characteristic. The pupils are mostly dilated.
The smell of alcohol should be watched for; sometimes it is only present
in cases where but a short time has elapsed between the taking of the
poison and death; putrefaction may also conceal it, but under favourable
circumstances, especially if the weather is cold, the alcoholic smell
may remain a long time. Alcohol may cause the most intense redness and
congestion of the stomach. The most inflamed stomach I ever saw, short
of inflammation by the corrosive poisons, was that of a sailor, who died
suddenly after a twenty-four hours’ drinking bout: all the organs of the
body were fairly healthy, the man had suffered from no disease; analysis
could detect no poison but alcohol; and the history of the case,
moreover, proved clearly that it was a pure case of alcoholic poisoning.

[151] Seidel, Maschka’s _Handbuch_, Bd. ii. p. 380.

In a case related by Taylor, in which a child drank 4 ozs. of brandy and
died, the mucous membrane of the stomach presented patches of intense
redness, and in several places was thickened and softened, some portions
being actually detached and hanging loose, and there were evident signs
of extravasations of blood. The effect may not be confined to the
stomach, but extend to the duodenum and even to the whole intestinal
canal. The blood is generally dark and fluid, and usually the contents
of the skull are markedly hyperæmic, the pia very full of blood, the
sinuses and plexus gorged; occasionally, the brain-substance shows signs
of unusual congestion; serum is often found in the ventricles. The great
veins of the neck, the lungs, and the right side of the heart, are very
often found full of blood, and the left side empty. Œdema of the lungs
also occurs with tolerable frequency. The great veins of the abdomen are
also filled with blood, and if the coma has been prolonged, the bladder
will be distended with urine. A rare phenomenon has also been
noticed--namely, the occurrence of blebs on the extremities, &c., just
as if the part affected had been burnt or scalded. Lastly, with the
changes directly due to the fatal dose may be included all those
degenerations met with in the chronic drinker, provided the case had a
history of previous intemperance.

§ 163. =Excretion of Alcohol.=--Alcohol, in the diluted form, is quickly
absorbed by the blood-vessels of the stomach, &c., and circulates in the
blood; but what becomes of it afterwards is by no means settled. I think
there can be little doubt that the lungs are the main channels through
which it is eliminated; with persons given up to habits of intemperance,
the breath has constantly a very peculiar ethereal odour, probably
dependent upon some highly volatile oxidised product of alcohol.

Alcohol is eliminated in small proportion only by the kidneys.
Thudichum, in an experiment[152] by which 4000 grms. of absolute alcohol
were consumed by thirty-three men, could only find in the collected
urine 10 grms. of alcohol. The numerous experiments by Dupré also
establish the same truth, that but a fraction of the total alcohol
absorbed is excreted by the kidneys. According to Lallemand, Perrin, and
Duroy the content of the brain in alcohol is more than that of the
other organs. I have found also that the brain after death has a
wonderful attraction for alcohol, and yields it up at a water-heat very
slowly and with difficulty. In one experiment, in which a finely-divided
portion of brain, which had been soaking in alcohol for many weeks, was
submitted to a steam heat of 100°, twenty-four hours’ consecutive
heating failed to expel every trace of spirit.

[152] See Thudichum’s _Pathology of the Urine_, London, 1877, in which
both his own and Dr. Dupré’s experiments are summarised.

It is probable that true alcoholates of the chemical constituents of the
brain are formed. In the case of vegetable colloidal bodies, such, for
example, as the pulp of cherries, a similar attraction has been
observed, the fruit condensing, as it were, the alcohol in its own
tissues, and the outer liquid being of less alcoholic strength than that
which can be expressed from the steeped cherries. Alcohol is also
excreted by the sweat, and minute fractions have been found in the
fæces.

§ 164. =Toxicological Detection of Alcohol= (see “Foods,” pp.
406-419).--The living cells of the body produce minute quantities of
alcohol, as also some of the bacteria normally inhabiting the small
intestine produce small quantities of alcohol, and it is often found in
traces in putrefying fluids. Hence, mere qualitative proofs of the
presence of alcohol are insufficient on which to base an opinion as to
whether alcohol had been taken during life or not, and it will be
necessary to estimate the quantity accurately by some of the processes
detailed in “Foods,” p. 409, _et seq._ In those cases in which alcohol
is found in quantity in the stomach, there can, of course, be no
difficulty; in others, the whole of the alcohol may have been absorbed,
and chemical evidence, unless extremely definite, must be supplemented
by other facts.


2. AMYLIC ALCOHOL.

    § 165. =Amylic Alcohol=--_Formula_, C₅H₁₁HO.--There is more than one
    amylic alcohol according to theory; eight isomers are possible, and
    seven are known. The amylic alcohols are identical in their chemical
    composition, but differ in certain physical properties, primary
    amylic alcohol boiling at 137°, and iso-amyl alcohol at 131·6°. The
    latter has a specific gravity of ·8148, and is the variety produced
    by fermentation and present in fusel oil.

    § 166. The experiments of Eulenberg[153] on rabbits, Cross[154] on
    pigeons, Rabuteau[155] on frogs, and Furst on rabbits, with those of
    Sir B. W. Richardson[156] on various animals, have shown it to be a
    powerful poison, more especially if breathed in a state of vapour.

[153] _Gewerbe Hygiene_, 1876, p. 440.

[154] _De l’Alcohol Amylique et Méthyl sur l’Organisme (Thèse)_,
Strasburg, 1863.

[155] “Ueber die Wirkung des Aethyl, Butyl u. Amyl Alcohols,” _L’Union_,
Nos. 90, 91, 1870. Schmidt’s _Jahrb._, Bd. 149, p. 263.

[156] _Trans. Brit. Association_, 1864, 1865, and 1866. Also, _Brit. and
Foreign Med. Chir. Rev._, Jan. 7, 1867, p. 247.

    Richardson, as the result of his investigations, considers that amyl
    alcohol when breathed sets up quite a peculiar class of symptoms
    which last for many hours, and are of such a character, that it
    might be thought impossible for the animal to recover, although they
    have not been known to prove fatal. There is muscular paralysis with
    paroxysms of tremulous convulsions; the spasms are excited by
    touching the animal, breathing upon it, or otherwise subjecting it
    to trifling excitation.

    § 167. Hitherto, neither the impure fusel oil, nor the purer
    chemical preparation, has had any toxicological importance. Should
    it be necessary at any time to recover small quantities from organic
    liquids, the easiest way is to shake the liquid up with chloroform,
    which readily dissolves amylic alcohol, and on evaporation leaves it
    in a state pure enough to be identified. Amyl alcohol is identified
    by the following tests:--(1) Its physical properties; (2) if warmed
    with twice its volume of strong sulphuric acid, a rose or red colour
    is produced; (3) heated with an acetate and strong sulphuric acid,
    _amyl acetate_, which has the odour of the jargonelle pear, is
    formed; (4) heated with sulphuric acid and potassic dichromate,
    valeric aldehyde is first produced, and then valeric acid is formed;
    the latter has a most peculiar and strong odour.

    § 168. =Amyl Nitrite, Iso-amyl Ester Nitrite= (C₅H₁₁NO₂).--Boiling
    point 97° to 99°, specific gravity ·877. Amyl nitrite is a limpid,
    and, generally, slightly yellow liquid; it has a peculiar and
    characteristic odour. On heating with alcoholic potash, the products
    are nitrite of potash and amylic alcohol; the amylic alcohol may be
    distilled off and identified. The presence of a nitrite in the
    alkaline solution is readily shown by the colour produced, by adding
    a few drops of a solution of meta-phenylenediamine.

    Sir B. W. Richardson and others have investigated the action of amyl
    nitrite, as well as that of the acetate and iodide; they all act in
    a similar manner, the nitrite being most potent. After absorption,
    the effects of amyl nitrite are especially seen on the heart and
    circulation: the heart acts violently, there is first dilatation of
    the capillaries, then this is followed by diminished action of the
    heart and contraction of the capillaries.

    According to Richardson, it suspends the animation of frogs. No
    other substance known will thus suspend a frog’s animation for so
    long a time without killing it. Under favourable circumstances, the
    animal will remain apparently dead for many days, and yet recover.
    Warm-blooded animals may be thrown by amyl nitrite into a cataleptic
    condition. It is not an anæsthetic, and by its use consciousness is
    not destroyed, unless a condition approaching death be first
    produced. When this occurs there is rarely recovery, the animal
    passes into actual death.

    =Post-Mortem Appearances.=--If administered quickly, the lungs and
    all the other organs are found blanched and free from blood, the
    right side of the heart gorged with blood, the left empty, the brain
    being free from congestion. If administered slowly, the brain is
    found congested, and there is blood both on the left and right sides
    of the heart.


IV.--Ether.

§ 169. =Ether, Ethylic Ether, Ethyl Oxide,= (C₂H₅)₂O.--Ethylic ether is
a highly mobile liquid of peculiar penetrating odour and sweetish
pungent taste. It is perfectly colourless, and evaporates so rapidly,
that when applied in the form of spray to the skin, the latter becomes
frozen, and is thus deprived of sensibility.

Pure ether has a density of ·713, its boiling-point is 35°, but
commercial samples, which often contain water (1 part of water is
soluble in 35 of ether), may have a higher gravity, and also a higher
boiling-point. The readiest way to know whether an ether is anhydrous or
not, is to shake it up with a little carbon disulphide. If it is
hydrous, the mixture is milky. Methylated ether is largely used in
commerce; its disagreeable odour is due to contamination by methylated
compounds; otherwise the ether made from methylated spirit is ethylic
ether, for methylic ether is a gas which escapes during the process.
Hence the term “methylated” ether is misleading, for it contains no
methylic ether, but is essentially a somewhat impure ethylic ether.

§ 170. =Ether as a Poison.=--Ether has but little toxicological
importance. There are a few cases of death from its use as an
anæsthetic, and a few cases of suicide. Ether is used by some people as
a stimulant, but ether drinkers are uncommon. It causes an intoxication
very similar to that of alcohol, but of brief duration. In a case of
chronic ether-taking recorded by Martin,[157] in which a woman took
daily doses of ether for the purpose of allaying a gastric trouble, the
patient suffered from shivering or trembling of the hands and feet,
muscular weakness, cramp in the calves of the legs, pain in the breast
and back, intermittent headaches, palpitation, singing in the ears,
vomitings, and wakefulness; the ether being discontinued, the patient
recovered. In one of Orfila’s experiments, half an ounce of ether was
administered to a dog. The animal died insensible in three hours. The
mucous membrane of the stomach was found highly inflamed, the
inflammation extending somewhat into the duodenum; the rest of the canal
was healthy. The lungs were gorged with fluid blood.

[157] Virchow’s _Jahresber._, 1870.

§ 171. =Fatal Dose.=--The fatal dose of ether, when taken as a liquid,
is not known. 4 grms. (1·28 drms.) cause toxic symptoms, but the effect
soon passes. Buchanan has seen a brandy-drinker consume 25 grms. (7
drms.) and yet survive. It is probable that most adults would be killed
by a fluid ounce (28·4 c.c.).

§ 172. =Ether as an Anæsthetic.=--Ether is now much used as an
anæsthetic, and generally in conjunction with chloroform. Anæsthesia by
ether is said to compare favourably with that produced by chloroform. In
92,000 cases of operations performed under ether, the proportion dying
from the effects of the anæsthetic was only ·3 per 10,000 (Morgan),
while chloroform gives a higher number (see p. 149). The mortality in
America, again, from a mixture of chloroform and ether in 11,000 cases
is reckoned at 1·7 per 10,000; but this proportion is rather above some
of the calculations relative to the mortality from pure chloroform, so
that the question can hardly be considered settled. The symptoms of
ether narcosis are very similar to those produced by chloroform. The
chief point of difference appears to be its action on the heart. Ether,
when first breathed, stimulates the heart’s action, and the
after-depression that follows never reaches so high a grade as with
chloroform. Ether is said to kill by paralysing the respiration, and in
cases which end fatally the breathing is seen to stop suddenly:
convulsions have not been noticed. The _post-mortem_ appearances, as in
the case of chloroform, are not characteristic.

§ 173. =Separation of Ether from Organic Fluids, &c.=--Despite the low
boiling-point of ether, it is by no means easy to separate it from
organic substances _so as to recover the whole of the ether present_.
The best way is to place the matters in a flask connected with an
ordinary Liebig’s condenser, the tube of the latter at its farther end
fitting closely into the doubly perforated cork of a flask. Into the
second perforation is adapted an upright tube about 2 feet long, which
may be of small diameter, and must be surrounded by a freezing mixture
of ice and salt. The upper end of this tube is closed by a thistle-head
funnel with syphon, and in the bend of the syphon a little mercury
serves as a valve. Heat is now applied to the flask by means of a
water-bath, and continued for several hours; the liquid which has
distilled over is then treated with dry calcic chloride and redistilled
exactly in the same way. To this distillate again a similar process may
be used, substituting dry potassic carbonate for the calcic chloride. It
is only by operating on these principles that the expert can recover in
an approximate state of anhydrous purity such a volatile liquid. Having
thus obtained it pure, it may be identified (1) by its smell, (2) by its
boiling-point, (3) by its inflammability, and (4) by its reducing
chromic acid. The latter test may be applied to the vapour. An asbestos
fibre is soaked in a mixture of strong sulphuric acid and potassic
dichromate, and then placed in the tube connected with the flask--the
ethereal (or alcoholic) vapour passing over the fibre, immediately
reduces the chromic acid to chromic oxide, with the production of a
green colour.


V.--Chloroform.

CHLOROFORM, TRICHLOROMETHANE OR METHENYL CHLORIDE (CHCl₃).

§ 174. Chloroform appears to have been discovered independently by
Soubeiran and Liebig, about 1830. It was first employed in medicine by
Simpson, of Edinburgh, as an anæsthetic. Pure chloroform has a density
of 1·491 at 17°, and boils at 60·8°; but commercial samples have
gravities of from 1·47 to 1·491. It is a colourless liquid, strongly
refracting light; it cannot be ignited by itself, but, when mixed with
alcohol, burns with a smoky flame edged with green. Its odour is heavy,
but rather pleasant; the taste is sweet and burning.

Chloroform sinks in water, and is only slightly soluble in that fluid
(·44 in 100 c.c.), it is perfectly neutral in reaction, and very
volatile. When rubbed on the skin, it should completely evaporate,
leaving no odour. Pure absolute chloroform gives an opaline mixture if
mixed with from 1 to 5 volumes of alcohol, but with any quantity above 5
volumes the mixture is clear; it mixes in all proportions with ether.
Chloroform coagulates albumen, and is an excellent solvent for most
organic bases--camphor, caoutchouc, amber, opal, and all common resins.
It dissolves phosphorus and sulphur slightly--more freely iodine and
bromine. It floats on hydric sulphate, which only attacks it at a
boiling heat.

Chloroform is frequently impure from faulty manufacture or
decomposition. The impurities to be sought are alcohol, methylated
chloroform,[158] dichloride of ethylene (C₂H₄Cl₂), chloride of ethyl
(C₂H₅Cl), aldehyde, chlorine, hydrochloric, hypochlorous, and traces of
sulphuric acid: there have also been found chlorinated oils. One of the
best tests for contamination by alcohol, wood spirit, or ether, is that
known as Roussin’s; dinitrosulphide of iron[159] is added to chloroform.
If it contain any of these impurities, it acquires a dark colour, but if
pure, remains bright and colourless.

[158] Methylated chloroform is that which is prepared from methylated
spirit. It is liable to more impurities than that made from pure
alcohol, but, of course, its composition is the same, and it has
recently been manufactured from this source almost chemically pure.

[159] Made by slowly adding ferric sulphate to a boiling solution of
ammonic sulphide and potassic nitrite, as long as the precipitate
continues to redissolve, and then filtering the solution.

The presence of alcohol or ether, or both, may also be discovered by the
bichromate test, which is best applied as follows:--A few milligrammes
of potassic bichromate are placed at the bottom of a test-tube with four
or five drops of sulphuric acid, which liberates the chromic acid; next,
a very little water is added to dissolve the chromic acid; and lastly,
the chloroform. The whole is now shaken, and allowed to separate. If the
chloroform is pure, the mass is hardly tinged a greenish-yellow, and no
layer separates. If, however, there is anything like 5 per cent. of
alcohol or ether present, the deep green of chromium chloride appears,
and there is a distinct layer at the bottom of the tube.

Another way to detect alcohol in chloroform, and also to make an
approximate estimation of its quantity, is to place 20 c.c. of
chloroform in a burette, and then add 80 c.c. of water. On shaking
violently, pure chloroform will sink to the bottom in clear globules,
and the measurement will be as nearly as possible the original quantity;
but if anything like a percentage of alcohol be present, the chloroform
is seen to be diminished in quantity, and its surface is opalescent, the
diminution being caused by the water dissolving out the alcohol. The
addition of a few drops of potash solution destroys the meniscus, and
allows of a close reading of the volume. The supernatant water may be
utilised for the detection of other impurities, and tested for sulphuric
acid by baric chloride, for free chlorine and hypochlorous acid by
starch and potassic iodide, and for hydrochloric acid by silver
nitrate.[160] Fuchsine, proposed by Stœdeler, is also a delicate reagent
for the presence of alcohol in chloroform, the sample becoming red in
the presence of alcohol, and the tint being proportionate to the
quantity present. The most delicate test for alcohol is, however, the
iodoform test fully described in “Foods,” p. 375.[161] Dichloride of
ethylene is detected by shaking up the chloroform with dry potassic
carbonate, and then adding metallic potassium. This does not act on pure
chloroform, but only in presence of ethylene dichloride, when the
gaseous chlor-ethylene (C₂H₃Cl) is evolved. Ethyl-chloride is detected
by distilling the chloroform and collecting the first portions of the
distillate; it will have a distinct odour of ethyl-chloride should it be
present. Methyl compounds and empyreumatic oils are roughly detected by
allowing the chloroform to evaporate on a cloth. If present, the cloth,
when the chloroform has evaporated, will have a peculiar disagreeable
odour. Aldehyde is recognised by its reducing action on argentic
nitrate; the mineral acids by the reddening of litmus paper, and the
appropriate tests. Hypochlorous acid first reddens, and then bleaches,
litmus-paper.

[160] Neither an alcoholic nor an aqueous solution of silver nitrate
causes the slightest change in pure chloroform.

[161] An attempt has been made by Besnou to estimate the amount of
alcohol by the specific gravity. He found that a chloroform of 1·4945
gravity, mixed with 5 per cent. of alcohol, gave a specific gravity of
1·4772; 10 per cent., 1·4602; 20 per cent., 1·4262; and 25 per cent.,
1·4090. It would, therefore, seem that every percentage of alcohol
lowers the gravity by ·0034.

Dr. Dott, _Pharm. Journ._, 1894, p. 629, gives the following
tests:--Specific gravity, 1·490 to 1·495. On allowing ½ fluid drm. to
evaporate from a clean surface, no foreign odour is perceptible at any
stage of the evaporation. When 1 fluid drm. is agitated with an equal
volume of solution of silver nitrate, no precipitate or turbidity is
produced after standing for five minutes. On shaking up the chloroform
with half its volume of distilled water, the water should not redden
litmus-paper. When shaken with an equal volume of sulphuric acid, little
or no colour should be imparted to the acid.

§ 175. The ordinary method of manufacturing chloroform is by distilling
alcohol with chlorinated lime; but another mode is now much in
use--viz., the decomposition of chloral hydrate. By distilling it with a
weak alkali, this process yields such a pure chloroform, that, for
medicinal purposes, it should supersede every other.


Poisonous Effects of Chloroform.


1. AS A LIQUID.

§ 176. =Statistics.=--Falck finds recorded in medical literature 27
cases of poisoning by chloroform having been swallowed--of these 15 were
men, 9 were women, and 3 children. Eighteen of the cases were suicidal,
and 10 of the 18 died; the remainder took the liquid by mistake.

§ 177. =Local Action of Chloroform.=--When applied to the skin or mucous
membranes in such a way that the fluid cannot evaporate--as, for
example, by means of a cloth steeped in chloroform laid on the bare
skin, and covered over with some impervious material--there is a burning
sensation, which soon ceases, and leaves the part anæsthetised, while
the skin, at the same time, is reddened and sometimes even blistered.

§ 178. Chloroform added to blood, or passed through it in the state of
vapour, causes it to assume a peculiar brownish colour owing to
destruction of the red corpuscles and solution of the hæmoglobin in the
plasma. The change does not require the presence of atmospheric air, but
takes place equally in an atmosphere of hydrogen. It has been shown by
Schmiedeberg that the chloroform enters in some way into a state of
combination with the blood-corpuscles, for the entire quantity cannot be
recovered by distillation; whereas the plasma, similarly treated, yields
the entire quantity which has in the first place been added.
Schmiedeberg also asserts that the oxygen is in firmer combination with
the chloroformised blood than usual, as shown by its slow extraction by
stannous oxide. Muscle, exposed to chloroform liquid by arterial
injection, quickly loses excitability and becomes rigid. Nerves are
first stimulated, and then their function for the time is annihilated;
but on evaporation of the chloroform, the function is restored.

§ 179. =General Effects of the Liquid.=--However poisonous in a state of
vapour, chloroform cannot be considered an extremely active poison when
taken into the stomach as a liquid, for enormous quantities, relatively,
have been drunk without fatal effect. Thus, there is the case recorded
by Taylor, in which a man, who had swallowed 113·4 grms. (4 ozs.),
walked a considerable distance after taking the dose. He subsequently
fell into a state of coma, with dilated pupils, stertorous breathing,
and imperceptible pulse. These symptoms were followed by convulsions,
but the patient recovered in five days.

In a case related by Burkart,[162] a woman desired to kill herself with
chloroform, and procured for that purpose 50 grms. (a little less than
one ounce and a half); she drank some of it, but the burning taste and
the sense of heat in the mouth, throat, and stomach, prevented her from
taking the whole at once. After a few moments, the pain passing off, she
essayed to drink the remainder, and did swallow the greater portion of
it, but was again prevented by the suffering it caused. Finally, she
poured what remained on a cloth, and placing it over her face, soon sank
into a deep narcosis. She was found lying on the bed very pale, with
blue lips, and foaming a little at the mouth; the head was rigidly bent
backwards, the extremities were lax, the eyes were turned upwards and
inwards, the pupils dilated and inactive, the face and extremities were
cold, the body somewhat warmer, there was no pulse at the wrist, the
carotids beat feebly, the breathing was deep and rattling, and after
five or six inspirations ceased. By the aid of artificial respiration,
&c., she recovered in an hour.

[162] _Vierteljahrsschr. für ger. Med._, 1876.

A still larger dose has been recovered from in the case of a young man,
aged 23,[163] who had swallowed no less than 75 grms. (2·6 ozs.) of
chloroform, but yet, in a few hours, awoke from the stupor. He
complained of a burning pain in the stomach; on the following day he
suffered from vomiting, and on the third day symptoms of jaundice
appeared,--a feature which has been several times noticed as an effect
of chloroform.

[163] _Brit. Med. Journ._, 1879.

On the other hand, even small doses have been known to destroy life. In
a case related by Taylor, a boy, aged 4, swallowed 3·8 grms. (1 drm.) of
chloroform and died in three hours, notwithstanding that every effort
was used for his recovery.

§ 180. The smallest dose that has proved fatal _to an adult_ is 15 grms.
(a little over 4 drms.).

From twenty-two cases in which the quantity taken had been ascertained
with some degree of accuracy, Falck draws the following conclusions:--In
eight of the cases the dose was between 4 and 30 grms., and one death
resulted from 15 grms. As for the other fourteen persons, the doses
varied from 35 to 380 grms., and eight of these patients died--two after
40, two after 45, one after 60, 90, 120, and 180 grms. respectively.
Hence, under conditions favouring the action of the poison, 15 grms.
(4·3 drms.) may be fatal to an adult, while doses of 40 grms. (11·3
drms.) and upwards will almost certainly kill.

§ 181. =Symptoms.=--The symptoms can be well gathered from the cases
quoted. They commence shortly after the taking of the poison; and,
indeed, the local action of the liquid immediately causes first a
burning sensation, followed by numbness.

Often after a few minutes, precisely as when the vapour is administered,
a peculiar, excited condition supervenes, accompanied, it may be, by
delirium. The next stage is narcosis, and the patient lies with pale
face and livid lips, &c., as described at p. 147; the end of the scene
is often preceded by convulsions. Sometimes, however, consciousness
returns, and the irritation of the mucous membranes of the
gastro-intestinal canal is shown by bloody vomiting and bloody stools,
with considerable pain and general suffering. In this way, a person may
linger several days after the ingestion of the poison. In a case
observed by Pomeroy, the fatal malady was prolonged for eight days.
Among those who recover, a common _sequela_, as before mentioned, is
jaundice.

A third form of symptoms has been occasionally observed, viz.:--The
person awakes from the coma, the breathing and pulse become again
natural, and all danger seems to have passed, when suddenly, after a
longer or shorter time, without warning, a state of general depression
and collapse supervenes, and death occurs.

§ 182. =Post-mortem Appearances.=--The _post-mortem_ appearances from a
fatal dose of liquid chloroform mainly resolve themselves into redness
of the mucous membrane of the stomach, though occasionally, as in
Pomeroy’s case, there may be an ulceration. In a case recorded by
Hoffman,[164] a woman, aged 30, drank 35 to 40 grms. of chloroform and
died within the hour. Almost the whole of the chloroform taken was found
in the stomach, as a heavy fluid, coloured green, through the bile. The
epithelium of the pharynx, epiglottis, and gullet was of a dirty colour,
partly detached, whitened, softened, and easily stripped off. The mucous
membrane of the stomach was much altered in colour and consistence, and,
with the duodenum, was covered with a tenacious grey slime. There was no
ecchymosis.

[164] _Lehrbuch der ger. Medicin_, 2te Aufl.


2. THE VAPOUR OF CHLOROFORM.

§ 183. =Statistics.=--Accidents occur far more frequently in the use of
chloroform vapour for anæsthetic purposes than in the use of the liquid.

Most of the cases of death through chloroform vapour, are those caused
accidentally in surgical and medical practice. A smaller number are
suicidal, while for criminal purposes, its use is extremely infrequent.

The percentage of deaths caused by chloroform administered during
operations is unaccountably different in different years, times, and
places. The diversity of opinion on the subject is partly (though not
entirely) explicable, by the degrees of purity in the anæsthetic
administered, the different modes of administration, the varying lengths
of time of the anæsthesia, and the varying severity of the operations.

During the Crimean War, according to Baudens and Quesnoy, 30,000
operations were done under chloroform, but only one death occurred
attributable to the anæsthetic. Sansom[165] puts the average mortality
at ·75 per 10,000, Nussbaum at 1·3, Richardson at 2·8,[166] Morgan[167]
at 3·4. In the American war of secession, in 11,000 operations, there
were seven deaths--that is, 6·3 per 10,000, the highest number on a
large scale which appears to be on record. In the ten years 1883-1892,
103 deaths are attributed to chloroform in England and Wales, viz., 88
deaths (57 males, 31 females) from accidents (no doubt in its use as a
general anæsthetic), 14 (9 males, 5 females) from suicide, and a
solitary case of murder.

[165] _Chloroform: its Action, &c._, London, 1865.

[166] _Med. Times and Gazette_, 1870.

[167] _Med. Soc. of Virginia_, 1872.

§ 184. =Suicidal and Criminal Poisoning by Chloroform.=--Suicidal
poisoning by chloroform will generally be indicated by the surrounding
circumstances; and in no case hitherto reported has there been any
difficulty or obscurity as to whether the narcosis was self-induced or
not. An interesting case is related by Schauenstein,[168] in which a
physician resolved to commit suicide by chloroform, a commencing
amaurosis having preyed upon his mind, and his choice having been
determined by witnessing an accidental death by this agent. He
accordingly plugged his nostrils, fitted on to the face an appropriate
mask, and fastened it by strips of adhesive plaster. In such an
instance, there could be no doubt of the suicidal intent, and the
question of accident would be entirely out of the question.

[168] Maschka: _Handbuch der gerichtlich. Medicin_, p. 787, Tübingen,
1882.

A dentist in Potsdam,[169] in a state of great mental depression from
embarrassed circumstances, killed his wife, himself, and two children by
chloroform. Such crimes are fortunately very rare.

[169] Casper: _Handbuch der ger. Med._

There is a vulgar idea that it is possible, by holding a cloth saturated
with chloroform to the mouth of a sleeping person (or one, indeed,
perfectly awake), to produce _sudden_ insensibility; but such an
occurrence is against all experimental and clinical evidence. It is true
that a nervous person might, under such circumstances, faint and become
insensible by mere nervous shock; but a true sudden narcosis is
impossible.

Dolbeau has made some interesting experiments in order to ascertain
whether, under any circumstances, a sleeping person might be
anæsthetised. The main result appears to answer the question in the
affirmative, at least with certain persons; but even with these, it can
only be done by using the greatest skill and care, first allowing the
sleeper to breathe very dilute chloroform vapour, and then gradually
exhibiting stronger doses, and taking the cloth or inhaler away on the
slightest symptom of approaching wakefulness. In 75 per cent. of the
cases, however, the individuals awoke almost immediately on being
exposed to the vapour. This cautious and scientific narcosis, then, is
not likely to be used by the criminal class, or, if used, to be
successful.

§ 185. =Physiological Effects.=--Chloroform is a protoplasmic poison.
According to Jumelle, plants can even be narcotised, ceasing to
assimilate and no longer being sensitive to the stimulus of light.
Isolated animal cells, like leucocytes, lose through chloroform vapour
their power of spontaneous movement, and many bacteria cease to multiply
if in contact with chloroform water. According to Binx, chloroform
narcosis in man is to be explained through its producing a weak
coagulation of the cerebral ganglion cells. As already mentioned,
chloroform has an affinity for the red blood-corpuscles. Chloroform
stimulates the peripheral ends of the nerves of sensation, so that it
causes irritation of the skin or mucous membranes when locally applied.
Flourens considers that chloroform first affects the cerebrum, then the
cerebellum, and finally the spinal cord; the action is at first
stimulating, afterwards paralysing. Most anæsthetics diminish equally
the excitability of the grey and the white nervous substance of the
brain, and this is the case with chloroform, ether, and morphine; but
apparently this is not the case with chloral hydrate, which only
diminishes the conductivity of the cortical substance of the brain, and
leaves the grey substance intact. Corresponding to the cerebral
paralysis, the blood pressure sinks, and the heart beats slower and
weaker.[170] The Hyderabad Commission made 735 researches on dogs and
monkeys, and found that in fatal narcosis, so far as these animals are
concerned, the respiration ceased before the heart, and this may be
considered the normal mode of death; but it is probably going too far to
say that it is the exclusive form of death in man, for there have been
published cases in which the heart failed first.

[170] Kobert’s _Lehrbuch der Intoxicationen_.

§ 186. =Symptoms.=--There is but little outward difference between man
and animals, in regard to the symptoms caused by breathing chloroform;
in the former we have the advantage that the sensations preceding
narcosis can be described by the individual.

The action of chloroform is usually divided into three more or less
distinct stages. In the _first_ there is a “drunken” condition, changes
in the sense of smell and taste, and it may be hallucinations of vision
and hearing; there are also often curious creeping sensations about the
skin, and sometimes excessive muscular action, causing violent
struggles. I have also seen epileptiform convulsions, and delirium is
almost always present. The face during this stage is generally flushed,
covered with perspiration, and the pupils contracted. The first stage
may last from one minute to several, and passes into the _second stage_,
or that of depression. Spontaneous movements cease, sensibility to all
external stimuli vanishes, the patient falls into a deep sleep, the
consciousness is entirely lost, and reflex movements are more and more
annihilated. The temperature is less than normal, the respirations are
slow, and the pulse is full and slow. The pupils in this stage are
usually dilated, all the muscles are relaxed, and the limbs can be bent
about in any direction. If now the inhalation of chloroform is
intermitted, the patient wakes within a period which is usually from
twenty to forty minutes, but may be several hours, after the last
inhalation.

The _third stage_ is that of paralysis; the pulse becomes irregular, the
respirations superficial, there is a cyanotic colouring of the lips and
skin, while the pupils become widely dilated. Death follows quickly
through paralysis of the respiratory centre, the respirations first
ceasing, then the pulse; in a few cases, the heart ceases first to beat.

According to Sansom’s facts,[171] in 100 cases of death by chloroform,
44·6 per cent. occurred before the full narcosis had been attained, that
is in the first stage, 34·7 during the second stage, and 20·6 shortly
after. So, also, Kappeler has recorded that in 101 cases of death from
chloroform, 47·7 per cent. occurred before the full effect, and 52·2
during the full effect. This confirms the dictum of Billroth, that in
all stages of anæsthesia by chloroform, death may occur. The _quantity_
of chloroform, which, when inhaled in a given time, will produce death,
is unknown; for all depends upon the greater or less admixture of air,
and probably on other conditions. It has been laid down, that the
inhalation of chloroform should be so managed as to insure that the air
breathed shall never contain more than 3·9 per cent. of chloroform.
Fifteen drops have caused death, but Taylor, on the other hand, records
a case of tetanus, treated at Guy’s Hospital, in which no less a
quantity than 700 grms. (22·5 ozs.) was inhaled in twenty-four hours.
Frequent breathing of chloroform in no way renders the individual safe
from fatal accident. A lady[172] having repeatedly taken chloroform, was
anæsthetised by the same agent merely for the purpose of having a tooth
extracted. About 6 grms. (1·5 drm.) were poured on a cloth, and after
nine to ten inspirations, dangerous symptoms began--rattling breathing
and convulsive movements--and, despite all remedies, she died.

[171] _Op. cit._

[172] _Edin. Med. Journ._, 1855.

§ 187. Chronic chloroform poisoning is not unknown. It leads to various
ailments, and seems to have been in one or two instances the cause of
insanity.

Buchner records the case of an opium-eater, who afterwards took to
chloroform; he suffered from periodic mania. In a remarkable case
related by Meric, the patient, who had also first been a morphine-eater,
took 350 grms. of chloroform in five days by inhalation; as often as he
woke he would chloroform himself again to sleep. In this case, there was
also mental disturbance, and instances in which chloroform produced
marked mental aberration are recorded by Böhm[173] and by Vigla.[174]

[173] Ziemssen’s _Handbuch_, Bd. 15.

[174] _Med. Times_, 1855.

§ 188. =Post-mortem Appearances.=--The lesions found on section are
neither peculiar to, nor characteristic of, chloroform poisoning. It has
been noted that bubbles of gas are, from time to time, to be observed
after death in the blood of those poisoned by chloroform, but it is
doubtful whether the bubbles are not merely those to be found in any
other corpse--in 189 cases, only eighteen times were these gas-bubbles
observed,[175] so that, even if they are characteristic, the chances in
a given case that they will _not_ be seen are greater than the reverse.
The smell of chloroform may be present, but has been noticed very
seldom.

[175] Schauenstein (_Op. cit._).

§ 189. =The detection and estimation of chloroform= from organic
substances is not difficult, its low boiling-point causing it to distil
readily. Accordingly (whatever may be the ultimate modifications, as
suggested by different experimenters), the first step is to bring the
substances, unless fluid, into a pulp with water, and submit this pulp
to distillation by the heat of a water-bath. If the liquid operated upon
possesses no particular odour, the chloroform may in this way be
recognised in the distillate, which, if necessary, may be redistilled in
the same manner, so as to concentrate the volatile matters in a small
compass.

There are four chief tests for the identification of chloroform:--

(1.) The final distillate is tested with a little aniline, and an
alcoholic solution of soda or potash lye; either immediately, or upon
gently warming the liquid, there is a peculiar and penetrating odour of
phenylcarbylamine, C₆H₅NC; it is produced by the following reaction:--

  CHCl₃ + 3KOH + C₆H₅NH₂ = C₆H₅NC + 3KCl + 3H₂O.

Chloral, trichloracetic acid, bromoform and iodoform also give the same
reaction; on the other hand, ethylidene chloride does not yield under
these circumstances any carbylamine (isonitrile).

(2.) Chloroform reduces Fehling’s alkaline copper solution, _when
applied to a distillate_, thus excluding a host of more fixed bodies
which have the same reaction; it is a very excellent test, and may be
made quantitative. The reaction is as follows:--

  CHCl₃ + 5KHO + 2CuO = Cu₂O + K₂CO₃ + 3KCl + 3H₂O;

thus, every 100 parts of cuprous oxide equals 83·75 of chloroform.

(3.) The fluid to be tested (which, if acid, should be neutralised), is
distilled in a slow current of hydrogen, and the vapour conducted
through a short bit of red-hot combustion-tube containing platinum
gauze. Under these circumstances, the chloroform is decomposed and
hydrochloric acid formed; hence, the issuing vapour has an acid reaction
to test-paper, and if led into a solution of silver nitrate, gives the
usual precipitate of argentic chloride. Every 100 parts of silver
chloride equal 27·758 of chloroform.

(4.) The fluid is mixed with a little thymol and potash; if chloroform
be present, a reddish-violet colour is developed, becoming more distinct
on the application of heat.[176]

[176] S. Vidali in _Deutsch-Amerikan. Apoth.-Zeitung_, vol. iij., Aug.
15, 1882.

§ 190. For the quantitative estimation of chloroform the method
recommended by Schmiedeberg[177] is, however, the best. A
combustion-tube of 24 to 26 cm. long, and 10 to 12 mm. in diameter, open
at both ends, is furnished at the one end with a plug of asbestos, while
the middle part, to within 5-6 cm. of the other end, is filled with
pieces of caustic lime, from the size of a lentil to that of half a pea.
The lime must be pure, and is made by heating a carbonate which has been
precipitated from calcic nitrate. The other end of the tube is closed by
a cork, carrying a silver tube, 16-18 cm. long, and 4 mm. thick. The end
containing the asbestos plug is fitted by a cork to a glass tube. The
combustion-tube thus prepared is placed in the ordinary
combustion-furnace; the flask containing the chloroform is adapted, and
the distillation slowly proceeded with. It is best to add a tube, bent
at right angles and going to the bottom of the flask, to draw air
continuously through the apparatus. During the whole process, the tube
containing the lime is kept at a red heat. The chloroform is decomposed,
and the chlorine combines with the lime. The resulting calcic chloride,
mixed with much unchanged lime, is, at the end of the operation, cooled,
dissolved in dilute nitric acid, and precipitated with silver nitrate.
Any silver chloride is collected and weighed and calculated into
chloroform.[178]

[177] _Ueber die quantitative Bestimmung des Chloroforms im Blute._
Inaug. Dissert., Dorpat, 1866.

[178] S. Vidali has made the ingenious suggestion of developing hydrogen
in the usual way, by means of zinc and sulphuric acid, in the liquid
supposed to contain chloroform, to ignite the hydrogen, as in Marsh’s
test, when it issues from the tube, and then to hold in the flame a
clean copper wire. Since any chloroform is burnt up in the hydrogen
flame to hydrochloric acid, the chloride of copper immediately
volatilises and colours the flame green.


VI.--Other Anæsthetics.

    § 191. When chlorine acts upon marsh-gas, the hydrogen can be
    displaced atom by atom; and from the original methane (CH₄) can be
    successively obtained chloromethane or methyl chloride (CH₃Cl),
    dichloromethane, or methene dichloride, methylene dichloride
    (CH₂Cl₂), trichloromethane, or chloroform (CHCl₃), already
    described, and carbon tetrachloride (CCl₄). All these are, more or
    less, capable of producing anæsthesia; but none of them, save
    chloroform, are of any toxicological importance.

    Methene dichloride, recommended by Sir B. W. Richardson as an
    anæsthetic, has come somewhat into use. It is a colourless, very
    volatile liquid, of specific gravity 1·360, and boiling at 41°. It
    burns with a smoky flame, and dissolves iodine with a brown colour.

    § 192. =Pentane= (C₅H₁₂).--There are three isomers of pentane; that
    which is used as an anæsthetic is normal pentane,
    CH₃-CH₂-CH₂-CH₂-CH₃; its boiling-point is 37-38°. It is one of the
    constituents of petroleum ether.

    Under the name of “Pental” it is used in certain hospitals
    extensively, for instance, at the Kaiser Friederich’s Children’s
    Hospital, Berlin.[179] It is stated to have no action on the heart.

[179] _Zeit. f. Kinderheilk._, Bd. iii.-iv., 1893.

    One death[180] has been recorded from its use:--A lad, aged 14, was
    put under pental for the purpose of having two molars painlessly
    extracted. He was only a minute or two insensible, and 4-5 grms. of
    pental was the quantity stated to have been inhaled. The boy spat
    out after the operation, then suddenly fainted and died. The
    _post-mortem_ showed œdema of the lungs; the right side of the heart
    was empty. The organs of the body smelled strongly of pental.

[180] Dr. Bremme, _Vierteljahrsschr. f. gerichtliche Medicin_, Bd. v.,
1893.

    § 193. =Aldehyde= (Acetaldehyde), C₂H₄O =

        O
       //
  CH₃-C   ,
       \
        H

    a fluid obtained by the careful oxidation of alcohol (boiling-point,
    20·8°), is in large doses toxic; in smaller, it acts as a narcotic.

    =Metaldehyde= (C₂H₄O₂)₂, obtained by treating acetaldehyde at a low
    temperature with hydrochloric acid. It occurs in the form of prisms,
    which sublime at about 112°; it is also poisonous.

    § 194. =Paraldehyde= (C₆H₁₂O₃) is a colourless fluid, boiling at
    124°; specific gravity ·998 at 15°. By the action of cold it may be
    obtained in crystals, the melting point of which is 10·5°. It is
    soluble in eight parts of water at 13°; in warm water it is less
    soluble; hence, on warming a solution, it becomes turbid.
    Paraldehyde acts very similarly to chloral; it causes a deep sleep,
    and (judging by experiments on animals) produces no convulsive
    movements.


VII.--Chloral.

§ 195. =Chloral Hydrate= (C₂H₃Cl₃O₂) is made by mixing equivalent
quantities of anhydrous chloral[181] and water. The purest chloral is in
the form of small, granular, sugar-like crystals. When less pure, the
crystals are larger. These melt into a clear fluid at from 48° to 49°,
and the melted mass solidifies again at 48·9°. Chloral boils at 97·5°;
it is not very soluble in cold chloroform, requiring four times its
weight. The only substance with which chloral hydrate may well be
confused is chloral alcoholate (C₄H₇Cl₃O₂), but chloral alcoholate melts
at a lower temperature (45°), and boils at a higher (113·5°); it is
easily soluble in cold chloroform, and inflames readily, whereas chloral
scarcely burns.

[181] Anhydrous chloral (C₂HCl₃O) is an oily liquid, of specific gravity
1·502 at 18°; it boils at 97·7°. It is obtained by the prolonged action
of chlorine on absolute alcohol.

Chloral hydrate completely volatilises, and can be distilled in a vacuum
without change. If, however, boiled in air, it undergoes slow
decomposition, the first portions of the distillate being overhydrated,
the last underhydrated; the boiling-point, therefore, undergoes a
continuous rise. The amount of hydration of a commercial sample is of
practical importance; if too much water is present, the chloral
deliquesces, especially in warm weather; if too little, it may become
acid, and in part insoluble from the formation of meta-chloral
(C₆H₃Cl₉O₃). Chloral hydrate, by the action of the volatile or fixed
alkalies, is decomposed, an alkaline formiate and chloroform resulting
thus--

  C₂HCl₃O,H₂O + NaHO = NaCHO₂ + H₂O + CHCl₃.

Trichlor-acetic acid is decomposed in a similar manner.

=Statistics.=--Chloral caused, during the ten years 1883-1892 in England
and Wales, 127 deaths--viz., 111 (89 males, 22 females) accidentally, 15
(14 males, 1 female) from suicide, and a case in which chloral was the
agent of murder.

§ 196. =Detection.=--It is, of course, obvious that after splitting up
chloral into chloroform, the latter can be detected by distillation and
applying the tests given at p. 152 and _seq._ Chloral hydrate is soluble
in one and a half times its weight of water; the solution should be
perfectly neutral to litmus. It is also soluble in ether, in alcohol,
and in carbon disulphide. It may be extracted from its solution by
shaking out with ether. There should be no cloudiness when a solution is
tested with silver nitrate in the cold; if, however, to a boiling
solution nitrate of silver and a little ammonia are added, there is a
mirror of reduced silver.

§ 197. The assay of chloral hydrate in solutions is best effected by
distilling the solution with slaked lime; the distillate is received in
water contained in a graduated tube kept at a low temperature. The
chloroform sinks to the bottom, and is directly read off; the number of
c.c. multiplied by 2·064 equals the weight of the chloral hydrate
present.

Another method, accurate but only applicable to the fairly pure
substance, is to dissolve 1 to 2 grms. in water, remove any free acid by
baric carbonate, and then treat the liquid thus purified by a known
volume of standard soda. The soda is now titrated back, using litmus as
an indicator, each c.c. of normal alkali neutralised by the sample
corresponds to 0·1655 grm. of chloral hydrate. Small quantities of
chloral hydrate may be conveniently recovered from complex liquids by
shaking them up with ether, and removing the ethereal layer, in the tube
represented in the figure.[182] The ether must be allowed to evaporate
spontaneously; but there is in this way much loss of chloral. The best
method of estimating minute quantities is to alkalise the liquid, and
slowly distil the vapour through a red-hot combustion-tube charged with
pure lime, as in the process described at p. 153. A dilute solution of
chloral may also be treated with a zinc-copper couple, the nascent
hydrogen breaks the molecule up, and the resulting chloride may be
titrated, as in water analyses, by silver nitrate and potassic chromate.

[Illustration]

[182] The figure is from “Foods”; the description may be here
repeated:--A is a tube of any dimensions most convenient to the analyst.
Ordinary burette size will perhaps be the most suitable for routine
work; the tube is furnished with a stopcock and is bent at B, the tube
at K having a very small but not quite capillary bore. The lower end is
attached to a length of pressure-tubing, and is connected with a small
reservoir of mercury, moving up and down by means of a pulley. To use
the apparatus: Fill the tube with mercury by opening the clamp at H, and
the stopcock at B, and raising the reservoir until the mercury, if
allowed, would flow out of the beak. Now, the beak is dipped into the
liquid to be extracted with the solvent, and by lowering the reservoir,
a strong vacuum is created, which draws the liquid into the tube; in the
same way the ether is made to follow. Should the liquid be so thick that
it is not possible to get it in by means of suction, the lower end of
the tube is disconnected, and the syrupy mass worked in through the wide
end. When the ether has been sucked into the apparatus, it is emptied of
mercury by lowering the reservoir, and then firmly clamped at H, and the
stopcock also closed. The tube may now be shaken, and then allowed to
stand for the liquids to separate. When there is a good line of
demarcation, by raising the reservoir after opening the clamp and
stopcock, the whole of the light solvent can be run out of the tube into
a flask or beaker, and recovered by distillation. For heavy solvents
(such as chloroform), which sink to the bottom, a simple burette, with a
fine exit tube is preferable; but for petroleum ether, ordinary ether,
&c., the apparatus figured is extremely useful.

§ 198. =Effects of Chloral Hydrate on Animals.=--Experiments on animals
have taught us all that is known of the physiological action of
chloral. It has been shown that the drug influences very considerably
the circulation, at first exciting the heart’s action, and then
paralysing the automatic centre. The heart, as in animals poisoned by
atropine, stops in diastole, and the blood-pressure sinks in proportion
to the progressive paralysis of the cardiac centre. At the same time,
the respiration is slowed and finally ceases, while the heart continues
to beat. The body temperature of the warm-blooded animals is very
remarkably depressed, according to Falck, even to 7·6°. Vomiting has
been rather frequently observed with dogs and cats, even when the drug
has been taken into the system by subcutaneous injection.

The secretion of milk, according to Röhrig, is also diminished. Reflex
actions through small doses are intensified; through large, much
diminished. ·025-·05 grm. (·4-·7 grain), injected subcutaneously into
frogs, causes a slowing of the respiration, a diminution of reflex
excitability, and lastly, its complete cessation; this condition lasts
several hours; at length the animal returns to its normal state. If the
dose is raised to ·1 grm. (1·5 grain) after the cessation of reflex
movements, the heart is paralysed--and a paralysis not due to any
central action of the vagus, but to a direct action on the cardiac
ganglia. Rabbits of the ordinary weight of 2 kilos. are fully narcotised
by the subcutaneous injection of 1 grm.; the sleep is very profound, and
lasts several hours; the animal wakes up spontaneously, and is
apparently none the worse. If 2 grms. are administered, the narcotic
effects, rapidly developed, are much prolonged. There is a remarkable
diminution of temperature, and the animal dies, the respiration ceasing
without convulsion or other sign. Moderate-sized dogs require 6 grms.
for a full narcosis, and the symptoms are similar; they also wake after
many hours, in apparent good health.[183]

[183] C. Ph. Falck has divided the symptoms into (1) Preliminary
hypnotic; (2) an adynamic state; and (3) a comatose condition.

§ 199. Liebreich considered that the action of chloral was due to its
being broken up by the alkali of the blood, and the system being thus
brought into a state precisely similar to its condition when
anæsthetised by chloroform vapour. This view has, however, been proved
to be erroneous. Chloral hydrate can, it is true, be decomposed in some
degree by the blood at 40°; but the action must be prolonged for several
hours. A 1 per cent. solution of alkali does not decompose chloral at a
blood-heat in the time within which chloral acts in the body; and since
narcotic effects are commonly observed when, in the fatty group,
hydrogen has been displaced by chlorine, it is more probable that
chloral hydrate is absorbed and circulates in the blood as such, and is
not broken up into chloroform and an alkaline formiate.

§ 200. =Effects of Chloral Hydrate on Man.=--Since the year 1869, in
which chloral was first introduced to medicine, it has been the cause
of a number of accidental and other cases of poisoning. I find, up to
the year 1884, recorded in medical literature, thirty-one cases of
poisoning by chloral hydrate. This number is a small proportion only of
the actual number dying from this cause. In nearly all the cases the
poison was taken by the mouth, but in one instance the patient died in
three hours, after having injected into the rectum 5·86 grms. of chloral
hydrate. There is also on record a case in which, for the purpose of
producing surgical anæsthesia, 6 grms. of chloral were injected into the
veins; the man died in as many minutes.[184]

[184] This dangerous practice was introduced by M. Ore. In a case of
traumatic tetanus, in which M. Ore injected into the veins 9 grms. of
chloral in 10 grms. of water, there was profound insensibility, lasting
eleven hours, during which time a painful operation on the thumb was
performed. The next day 10 grms. were injected, when the insensibility
lasted eight hours; and 9 grms. were injected on each of the two
following days. The man recovered. In another case, Ore anæsthetised
immediately a patient by plunging the subcutaneous needle of his syringe
into the radial vein, and injected 10 grms. of chloral hydrate with 30
of water. The patient became insensible before the whole quantity was
injected with “_une immobilité rappellant celle du cadavre_.” On
finishing the operation, the patient was roused immediately by the
application of an electric current, one pole on the left side of the
neck, the other on the epigastrium. _Journ. de Pharm. et de Chimie._, t.
19, p. 314.

§ 201. =Fatal Dose.=--It is impossible to state with any exactness the
precise quantity of chloral which may cause death. Children bear it
better, in proportion, than adults, while old persons (especially those
with weak hearts, and those inclined to apoplexy) are likely to be
strongly affected by very small doses. A dose of ·19 grm. (3 grains) has
been fatal to a child a year old in ten hours. On the other hand,
according to Bouchut’s observations on 10,000 children, he considers
that the full therapeutic effect of chloral can be obtained safely with
them in the following ratio:--

  Children of 1 to 3 years, dose  1 to 1·5 grm. (15·4 to 23·1 grains)
      „       3  „ 5   „     „    2  „ 3    „   (30·8  „ 46·3   „   )
      „       5  „ 7   „     „    3  „ 4    „   (46·3  „ 61·7   „   )

  These quantities being dissolved in 100 c.c. of water.

These doses are certainly too high, and it would be dangerous to take
them as a guide, since death has occurred in a child, aged 5, from a
dose of 3 grms. (46·3 grains). Medical men in England consider 20 grains
a very full dose for a child of four years old, and 50 for an adult,
while a case is recorded in which a dose of 1·9 grm. (30 grains) proved
fatal in thirty-five hours to a young lady aged 20. On the other hand,
we find a case[185] in which, to a patient suffering from epileptic
mania, a dose of 31·1 grms. (1·1 oz.) of chloral hydrate was
administered; she sank into a deep sleep in five minutes. Subcutaneous
injections of strychnine were applied, and after sleeping for
forty-eight hours, there was recovery. On the third day a vivid
scarlatinal rash appeared, followed by desquamation. The examples
quoted--the fatal dose of 1·9 grm., and recovery from 31 grms.--are the
two extremes for adults. From other cases, it appears tolerably plain
that most people would recover, especially with appropriate treatment,
from a single dose under 8 grms., but anything above that quantity taken
at one time would be very dangerous, and doses of 10 grms. and above,
almost always fatal. If, however, 8 grms. were taken in divided doses
during the twenty-four hours, it could (according to Sir B. W.
Richardson) be done with safety. The time from the taking of the poison
till death varies considerably, and is in part dependent on the dose.

[185] _Chicago Medical Review_, 1882.

In seven cases of lethal poisoning, three persons who took the small
doses of 1·25, 2·5, and 1·95 grms. respectively, lived from eight to ten
hours; two, taking 4 and 5 grms. respectively, died very shortly after
the administration of the chloral. In a sixth case, related by Brown, in
which 3·12 grms. had been taken, the patient lived an hour; and in
another, after a dose of 5 grms., recorded by Jolly, death took place
within a quarter of an hour.

§ 202. =Symptoms.=--With moderate doses there are practically no
symptoms, save a drowsiness coming on imperceptibly, and followed by
heavy sleep. With doses up to 2 grms. (30·8 grains), the hypnotic state
is perfectly under the command of the will, and if the person chooses to
walk about or engage in any occupation, he can ward off sleep; but with
those doses which lead to danger, the narcosis is completely
uncontrollable, the appearance of the sleeper is often strikingly like
that of a drunken person. There is great diminution of temperature
commencing in from five to twenty minutes after taking the
dose--occasionally sleep is preceded by a delirious state. During the
deep slumber the face is much flushed, and in a few cases the sleep
passes directly into death without any marked change. In others,
symptoms of collapse appear, and the patient sinks through exhaustion.

§ 203. With some persons doses, which, in themselves, are insufficient
to cause death, yet have a peculiar effect on the mental faculties. A
case of great medico-legal interest is described by the patient himself,
Dr. Manjot.[186] He took in three doses, hourly, 12 grms. of chloral
hydrate. After the first dose the pain, for which he had recourse to
chloral, vanished; but Manjot, although he had all the appearance of
being perfectly conscious, yet had not the slightest knowledge of what
he was doing or speaking. He took the other two doses, and sank into a
deep sleep which lasted twelve hours. He then awoke and answered
questions with difficulty, but could not move; he lay for the next
twelve hours in a half slumber, and the following night slept
soundly--to wake up recovered.

[186] _Gaz. des Hôp._, 1875.

§ 204. The treatment of acute chloral poisoning which has been most
successful is that by strychnine injections, and the application of
warmth to counteract the loss of temperature which is so constant a
phenomenon. As an illustration of the treatment by strychnine, an
interesting case recorded by Levinstein[187] may be quoted.

[187] _Vierteljahrsschr. f. ger. Med._, Bd. xx., 1874.

A man, thirty-five years old, took at one dose, for the purpose of
suicide, 24 grms. of chloral hydrate. In half an hour afterwards he was
found in a deep sleep, with flushed face, swollen veins, and a pulse 160
in the minute. After a further half hour, the congestion of the head was
still more striking; the temperature was 39·5°; the pulse hard and
bounding 92; the breathing laboured, at times intermittent.

Artificial respiration was at once commenced, but in spite of this, in
about another half hour, the face became deadly pale, the temperature
sank to 32·9°. The pupils contracted, and the pulse was scarcely to be
felt; 3 mgrms. (·04 grain) of strychnine were now injected
subcutaneously; this caused tetanic convulsions in the upper part of the
body and trismus. The heart’s action again became somewhat stronger, the
temperature rose to 33·3°, and the pupils dilated; but soon followed,
again, depression of the heart’s action, and the respiration could only
be kept going by faradisation. Two mgrms. (·03 grain) of strychnine were
once more injected, and the heart’s action improved. During the
succeeding six hours the respiration had to be assisted by faradisation.
The temperature gradually rose to 36·5°; ten hours after taking the dose
the patient lay in a deep sleep, breathing spontaneously and reacting to
external stimuli with a temperature of 38·5°. Eighteen hours from the
commencement, the respiration again became irregular, and the galvanic
current was anew applied. The last application aroused the sleeper, he
took some milk and again slept; after twenty-seven hours he could be
awakened by calling, &c., but had not full consciousness; he again took
some milk and sank to sleep. It was not until thirty-two hours had
elapsed from the ingestion of the poison that he awoke spontaneously;
there were no after effects.

§ 205. =Chronic Poisoning by Chloral Hydrate.=--An enormous number of
people habitually take chloral hydrate. The history of the habit is
usually that some physician has given them a chloral prescription for
neuralgia, for loss of sleep, or other cause, and finding that they can
conjure sleep, oblivion, and loss (it may be) of suffering whenever they
choose, they go on repeating it from day to day until it becomes a
necessity of their existence. A dangerous facility to chloral-drinking
is the existence of patent medicines, advertised as sleep-producers, and
containing chloral as the active ingredient. A lady, aged 35, died in
1876, at Exeter, from an overdose of “Hunter’s solution of chloral, or
sedative draught and sleep producer.” Its strength was stated at the
inquest to be 25 grains to the drachm (41·6 per cent.).[188]

[188] _Exeter and Plymouth Gazette_, Jan. 12, 1876.

The evil results of this chloral-drinking are especially to be looked
for in the mental faculties, and the alienists have had since 1869 a new
insanity-producing factor. In the asylums may usually be found several
cases of melancholia and mania referred rightly (or wrongly) to
chloral-drinking. Symptoms other than cerebral are chilliness of the
body, inclination to fainting, clonic convulsions, and a want of
co-ordination of the muscles of the lower extremities. In a case
recorded by Husband,[189] a lady, after twelve days’ treatment by
chloral hydrate, in doses of from 1 to 2 grms. (15·4 to 30·8 grains),
suffered from a scarlatina-like rash, which was followed by
desquamation. Among the insane, it has also been noticed that its use
has been followed by nettle-rash and petechiæ (Reimer and others).

[189] _Lancet_, 1871.

§ 206. =Excretion of Chloral.=--Chloral hydrate is separated in the
urine partly as urochloral acid (C₈H₁₁Cl₃O₇). Butylchloral is separated
as butyl urochloral acid (C₁₀H₁₅Cl₂O₇). Urochloral acid is crystalline,
soluble in water, in alcohol, and in ether, reduces copper from
Fehling’s solution, and rotates a ray of polarised light to the left.
Urochloral acid, on boiling with either dilute sulphuric or hydrochloric
acid, splits up into trichlorethyl alcohol and glycuronic acid--

  C₈H₁₁Cl₃O₇ + H₂O = C₂H₃Cl₃O + C₆H₁₀O₇.

Trichloralcohol is an oily fluid (boiling-point 150°-152°); it yields by
oxidation trichloracetic acid.

Urobutyl chloral acid gives on treatment with mineral acids
trichlorbutyl alcohol and glycuronic acid.

To separate urochloral acid from the urine the following process has
been found successful:--

The urine is evaporated to a syrup at the heat of the water-bath, and
then strongly acidulated with sulphuric acid and repeatedly shaken out
in a separating tube with a mixture of 3 vols. of ether and 1 vol. of
alcohol. The ether-alcohol is separated and distilled off, the acid
residue is neutralised with KHO, or potassic carbonate, and evaporated;
the dry mass is then taken up with 90 per cent. alcohol, the filtrate
precipitated with ether, and the precipitate washed with ether and
absolute alcohol.

Next the precipitate is boiled with absolute alcohol and filtered hot.
On cooling, the potassium salt of urochloral acid separates out in tufts
of silky needles. The crystals are dried over sulphuric acid and again
washed several times with absolute alcohol and ether to remove
impurities.

To obtain the free acid, the potassium salt is dissolved in a little
water and acidulated with hydrochloric acid; the liquid is then shaken
out in a separating tube, with a mixture of 8 vols. of ether and 1 of
alcohol. The ether-alcohol is distilled off, the residue treated with
moist silver oxide until no farther separation of silver chloride
occurs, the silver chloride is separated by filtration, the soluble
silver salt decomposed by SH₂, and the filtrate carefully evaporated to
a syrup; after a few hours, the acid crystallises in stars of needles.

Urobutylchloral acid can be obtained in quite a similar way.[190]

[190] V. Mering u. Musculus, _Ber._, viii. 662; v. Mering, _ibid._, xv.
1019; E. Kulz, _Ber._, xv., 1538.

§ 207. =Separation of Chloral from Organic Matters.=--It will be most
convenient to place the organic fluid or pulped-up solid, mixed with
water, in a retort, to acidify with tartaric acid, and to distil.

Chloral hydrate distils over from a liquid acidified with tartaric acid;
to obtain the whole of the chloral requires distillation in a vacuum
almost to dryness.

The distillation will, unless there is also some partly decomposed
chloral, not smell of chloroform, and yet give chloroform reactions.

To identify it, to the distillate should be added a little burnt
magnesia, and the distillate thus treated boiled for half an hour in a
flask connected with an inverted condenser; in this way the chloral
hydrate is changed into chloroform and magnesium formate--

  2CCl₃CH(OH)₂ + MgO = 2CHCl₃ + (HCOO)₂Mg + H₂O.

The fluid may now be tested for formic acid: it will give a black
precipitate with solution of silver nitrate--

  (HCOO)₂Mg + 4AgNO₃ = 4Ag + Mg(NO₃)₂ + 2CO₂ + 2HNO₃.

It will give a white precipitate of calomel when treated with mercuric
chloride solution--

  (HCOO)₂Mg + 4HgCl₂ = 2Hg₂Cl₂ + MgCl₂ + 2HCl + 2CO₂.

Chloral (or chloroform), when boiled with resorcinol and the liquid made
strongly alkaline with NaHO, gives a red colour, which disappears on
acidifying and is restored by alkalies. If, on the other hand, there is
an excess of resorcinol and only a very small quantity of NaHO used, the
product shows a yellowish-green fluorescence; 1/10 of a milligramme of
chloral hydrate gives this reaction distinctly when boiled with 50
mgrms. of resorcinol and 5 drops of a normal solution of sodium
hydrate.[191]

[191] C. Schwarz, _Pharm. Zeit._, xxxiii. 419.

Dr. Frank Ogston[192] has recommended sulphide of ammonium to be added
to any liquid as a test for chloral. The contents of the stomach are
filtered or submitted to dialysis, and the test applied direct. If
chloral is present, there is first an orange-yellow colour; on standing,
the fluid becomes more and more brown, then troubled, an amorphous
precipitate falls to the bottom, and a peculiar odour is developed. With
10 mgrms. of chloral in 1 c.c. of water, there is an evident
precipitate, and the odour can readily be perceived; with 1 mgrm.
dissolved in 1 c.c. of water, there is an orange-yellow colour, and also
the odour, but no precipitate; with ·1 mgrm. in 1 c.c. of water, there
is a weak, pale, straw-yellow colour, which can scarcely be called
characteristic. The only substance giving in neutral solutions the same
reactions is antimony; but, on the addition of a few drops of acid, the
antimony falls as an orange-yellow precipitate, while, if chloral alone
is present, there is a light white precipitate of sulphur.

[192] _Vierteljahrsschrift f. gerichtl. Medicin_, 1879, Bd. xxx. Hft. 1,
S. 268.


VIII.--Bisulphide of Carbon.

§ 208. Bisulphide of carbon--_carbon disulphide_, _carbon sulphide_
(CS₂)--is a colourless, volatile fluid, strongly refracting light.
Commercial samples have a most repulsive and penetrating odour, but
chemically pure carbon sulphide has a smell which is not disagreeable.
The boiling-point is 47°; the specific gravity at 0° is 1·293. It is
very inflammable, burning with a blue flame, and evolving sulphur
dioxide; is little soluble in water, but mixes easily with alcohol or
ether. Bisulphide of carbon, on account of its solvent powers for
sulphur, phosphorus, oils, resins, caoutchouc, gutta-percha, &c., is in
great request in certain industries. It is also utilised for
disinfecting purposes, the liquid being burnt in a lamp.

§ 209. =Poisoning by Carbon Bisulphide.=--In spite of the cheapness and
numerous applications of this liquid, poisoning is very rare. There
appears to be a case on record of attempted self-destruction by this
agent, in which a man took 2 ozs. (56·7 c.c.) of the liquid, but without
a fatal result. The symptoms in this case were pallor of the face, wide
pupils, frequent and weak pulse, lessened bodily temperature, and
spasmodic convulsions. Carbon disulphide was detected in the breath by
leading the expired air through an alcoholic solution of
triethyl-phosphin, with which it struck a red colour. It could also be
found in the urine in the same way. An intense burning in the throat,
giddiness, and headache lasted for several days.

§ 210. Experiments on animals have been frequent, and it is found to be
fatal to all forms of animal life. There is, indeed, no more convenient
agent for the destruction of various noxious insects, such as moths, the
weevils in biscuits, the common bug, &c., than bisulphide of carbon. It
has also been recommended for use in exterminating mice and rats.[193]
Different animals show various degrees of sensitiveness to the vapour;
frogs and cats being less affected by it than birds, rabbits, and
guinea-pigs. It is a blood poison; methæmoglobin is formed, and there is
disintegration of the red blood corpuscles. There is complete anæsthesia
of the whole body, and death occurs through paralysis of the respiratory
centre, but artificial respiration fails to restore life.

[193] Cloëz, _Compt. Rend._, t. 63, 85.

§ 211. =Chronic Poisoning.=--Of some importance is the chronic poisoning
by carbon disulphide, occasionally met with in manufactures
necessitating the daily use of large quantities for dissolving
caoutchouc, &c. When taken thus in the form of vapour daily for some
time, it gives rise to a complex series of symptoms which may be divided
into two principal stages--viz., a stage of excitement and one of
depression. In the first phase, there is more or less permanent
headache, with considerable indigestion, and its attendant loss of
appetite, nausea, &c. The sensitiveness of the skin is also heightened,
and there are curious sensations of creeping, &c. The mind at the same
time in some degree suffers, the temper becomes irritable, and singing
in the ears and noises in the head have been noticed. In one factory a
workman suffered from an acute mania, which subsided in two days upon
removing him from the noxious vapour (_Eulenberg_). The sleep is
disturbed by dreams, and, according to Delpech,[194] there is
considerable sexual excitement, but this statement has in no way been
confirmed. Pains in the limbs are a constant phenomenon, and the French
observers have noticed spasmodic contractions of certain groups of
muscles.

[194] _Mémoire sur les Accidents que développe chez les ouvrières en
caoutchouc du sulfure de carb. en vapeur_, Paris, 1856.

The stage of depression begins with a more or less pronounced anæsthesia
of the skin. This is not confined to the outer skin, but also affects
the mucous membranes; patients complain that they feel as if the tongue
were covered with a cloth. The anæsthesia is very general. In a case
recorded by Bernhardt,[195] a girl, twenty-two years old, who had worked
six weeks in a caoutchouc factory, suffered from mental weakness and
digestive troubles; there was anæsthesia and algesis of the whole skin.
In these advanced cases the mental debility is very pronounced, and
there is also weakness of the muscular system. Paralysis of the lower
limbs has been noted, and in one instance a man had his right hand
paralysed for two months. It seems uncertain how long a person is likely
to suffer from the effects of the vapour after he is removed from its
influence. If the first stage of poisoning only is experienced, then
recovery is generally rapid; but if mental and muscular weakness and
anæsthesia of the skin have been developed, a year has been known to
elapse without any considerable improvement, and permanent injury to the
health may be feared.

[195] _Ber. klin. Wochenschrift_, No. 32, 1866.

§ 212. =Post-mortem Appearances.=--The pathological appearances found
after sudden death from disulphide of carbon are but little different to
those found after fatal chloroform breathing.

§ 213. =Detection and Separation of Carbon Disulphide.=--The extreme
volatility of the liquid renders it easy to separate it from organic
liquids by distillation with reduced pressure in a stream of CO₂. Carbon
disulphide is best identified by (1) Hofman’s test, viz., passing the
vapour into an ethereal solution of triethyl-phosphin, (C₂H₅)₃P. Carbon
disulphide forms with triethyl-phosphin a compound which crystallises in
red scales. The crystals melt at 95° C., and have the following
formula--P(C₂H₅)₃CS₂. This will detect 0·54 mgrm. Should the quantity of
bisulphide be small, no crystals may be obtained, but the liquid will
become of a red colour. (2) CS₂ gives, with an alcoholic solution of
potash, a precipitate of potassic xanthate, CS₂C₂H₅OK.

    § 214. =Xanthogenic acid or ethyloxide-sulphocarbonate= (CS₂C₂H₅OH)
    is prepared by decomposing potassic xanthogenate by diluted
    hydrochloric or sulphuric acid. It is a colourless fluid, having an
    unpleasant odour, and a weakly acid and rather bitter taste. It
    burns with a blue colour, and is easily decomposed at 24°, splitting
    up into ethylic alcohol and hydric sulphide. It is very poisonous,
    and has an anæsthetic action similar to bisulphide of carbon. Its
    properties are probably due to CS₂ being liberated within the body.

    § 215. =Potassic xanthogenate= (CS₂C₂H₅OK) and =potassic
    xanthamylate= (CS₂C₅H₁₁OK) (the latter being prepared by the
    substitution of amyl alcohol for ethyl alcohol), both on the
    application of a heat below that of the body, develop CS₂, and are
    poisonous, inducing symptoms very similar to those already detailed.


IX.--The Tar Acids--Phenol--Cresol.

§ 216. =Carbolic Acid. Syn. Phenol, Phenyl Alcohol, Phenylic Hydrate;
Phenic Acid; Coal-Tar Creasote.=--The formula for carbolic acid is
C₆H₅HO. The pure substance appears at the ordinary temperature as a
colourless solid, crystallising in long prisms; the fusibility of the
crystals is given variously by different authors: from my own
observation, the pure crystals melt at 40°-41°, any lower melting-point
being due to the presence of cresylic acid or other impurity; the
crystals again become solid about 15°. Melted carbolic acid forms a
colourless limpid fluid, sinking in water. It boils under the ordinary
pressure at 182°, and distils without decomposition; it is very readily
and completely distilled in a vacuum at about the temperature of 100°.
After the crystals have been exposed to the air, they absorb water, and
a hydrate is formed containing 16·07 per cent. of water. The hydrate
melts at 17°, any greater hydration prevents the crystallisation of the
acid; a carbolic acid, containing about 27 per cent. of water, and
probably corresponding to the formula C₆H₆O,2H₂O, is obtained by
gradually adding water to carbolic acid so long as it continues to be
dissolved. Such a hydrate dissolves in 11·1 times its measure of water,
and contains 8·56 per cent. of real carbolic acid. Carbolic acid does
not redden litmus, but produces a greasy stain on paper, disappearing on
exposure to the air; it has a peculiar smell, a burning numbing taste,
and in the fluid state it strongly refracts light. Heated to a high
temperature it takes fire, and burns with a sooty flame.

When an aqueous solution of carbolic acid is shaken up with ether,
benzene, carbon disulphide, or chloroform, it is fully dissolved by the
solvent, and is thus easily separated from most solutions in which it
exists in the free state. Petroleum ether, on the other hand, only
slightly dissolves it in the cold, more on warming. Carbolic acid mixes
in all proportions with glycerin, glacial or acetic acid, and alcohol.
It coagulates albumen, the precipitate being soluble in an excess of
albumen; it also dissolves iodine, without changing its properties. It
dissolves many resins, and also sulphur, but, on boiling, sulphuretted
hydrogen is disengaged. Indigo blue is soluble in hot carbolic acid, and
may be obtained in crystals on cooling. Carbolic acid is contained in
castoreum, a secretion derived from the beaver, but it has not yet been
detected in the vegetable kingdom. The source of carbolic acid is at
present coal-tar, from which it is obtained by a process of
distillation. There are, however, a variety of chemical actions in the
course of which carbolic acid is formed.

§ 217. The common disinfecting carbolic acid is a dark reddish liquid,
with a very strong odour; at present there is very little phenol in it;
it is mainly composed of meta- and para-cresol. It is officinal in
Germany, and there must contain at least 50 per cent. of the pure
carbolic acid. The pure crystallised carbolic acid is officinal in our
own and all the continental pharmacopœias. In the British Pharmacopœia,
a solution of carbolic acid in glycerin is officinal; the proportions
are 1 part of carbolic acid and 4 parts of glycerin, that is, strength
by measure = 20 per cent. The Pharmacopœia Germanica has a _liquor natri
carbolici_, made with 5 parts carbolic acid, 1 caustic soda, and 4 of
water; strength in carbolic acid = 50 per cent. There is also a strongly
alkaline crude sodic carbolate in use as a preservative of wood.

There are various disinfecting fluids containing amounts of carbolic
acid, from 10 per cent. upwards. Many of these are somewhat complex
mixtures, but, as a rule, any poisonous properties they possess are
mainly due to their content of phenol or cresol. A great variety of
disinfecting powders, under various names, are also in commerce,
deriving their activity from carbolic acid. Macdougall’s disinfecting
powder is made by adding a certain proportion of impure carbolic acid to
a calcic sulphite, which is prepared by passing sulphur dioxide over
ignited limestone.

=Calvert’s carbolic acid powder= is made by adding carbolic acid to the
siliceous residue obtained from the manufacture of aluminic sulphate
from shale. There are also various carbolates which, by heating or
decomposing with sulphuric acid, give off carbolic acid.

=Carbolic acid soaps= are also made on a large scale--the acid is free,
and some of the soaps contain as much as 10 per cent. In the inferior
carbolic acid soaps there is little or no carbolic acid, but cresylic
takes its place. Neither the soaps nor the powders have hitherto
attained any toxicological importance, but the alkaline carbolates are
very poisonous.

§ 218. =The chief uses= of carbolic acid are indicated by the foregoing
enumeration of the principal preparations used in medicine and commerce.
The bulk of the carbolic acid manufactured is for the purposes of
disinfection. It is also utilised in the preparation of certain
colouring matters or dyes, and during the last few years has had another
application in the manufacture of salicylic acid. In medicine it is
administered occasionally internally, while the antiseptic movement in
surgery, initiated by Lister, has given it great prominence in surgical
operations.

§ 219. =Statistics.=--The tar acids, _i.e._, pure carbolic acid and the
impure acids sold under the name of carbolic acid, but consisting (as
stated before) mainly of cresol, are, of all powerful poisons, the most
accessible, and the most recklessly distributed. We find them at the
bedside of the sick, in back-kitchens, in stables, in public and private
closets and urinals, and, indeed, in almost all places where there are
likely to be foul odours or decomposing matters. It is, therefore, no
wonder that poisoning by carbolic acid has, of late years, assumed large
proportions. The acid has become vulgarised, and quite as popularly
known, as the most common household drugs or chemicals.[196] This
familiarity is the growth of a very few years, since it was not
discovered until 1834, and does not seem to have been used by Lister
until about 1863. It was not known to the people generally until much
later. At present it occupies the third place in fatality of all
poisons in England. The following table shows that, in the past ten
years, carbolic acid has killed 741 people, either accidentally or
suicidally; there is also one case of murder by carbolic acid within the
same period, bringing the total up to 742:--

[196] Although this is so, yet much ignorance still prevails as to its
real nature. In a case reported in the _Pharm. Journ._, 1881, p. 334, a
woman, thirty years of age, drank two-thirds of an ounce of liquid
labelled “_Pure Carbolic Acid_” by mistake, and died in two hours. She
read the label, and a lodger also read it, but did not know what it
meant.

DEATHS FROM CARBOLIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS
ENDING 1892.

                       ACCIDENT OR NEGLIGENCE.

  Ages,       0-1  1-5  5-15  15-25  25-65  65 and  Total
                                            above
  Males,       2   39    13      5     83      8     150
  Females,     2   21     7     13     51      7     101
              -------------------------------------------
  Totals,      4   60    20     18    134     15     251
              -------------------------------------------

                               SUICIDE.

  Ages,                       15-25  25-65  65 and  Total
                                            above
  Males,                        26    186      7     219
  Females,                      72    194      5     271
                             ----------------------------
  Totals,                       98    380     12     490
                             ----------------------------

Falck has collected, since the year 1868, no less than 87 cases of
poisoning from carbolic acid recorded in medical literature. In one of
the cases the individual died in nine hours from a large dose of
carbolate of soda; in a second, violent symptoms were induced by
breathing for three hours carbolic acid vapour; in the remaining 85, the
poisoning was caused by the liquid acid. Of these 85 persons, 7 had
taken the poison with suicidal intent, and of the 7, 5 died; 39 were
poisoned through the medicinal use of carbolic acid, 27 of the 39 by the
antiseptic treatment of wounds by carbolic acid dressings, and of these
8 terminated fatally; in 8 cases, symptoms of poisoning followed the
rubbing or painting of the acid on the skin for the cure of scabies,
favus, or psoriasis, and 6 of these patients died. In 4 cases, carbolic
acid enemata, administered for the purpose of dislodging ascarides, gave
rise to symptoms of poisoning, and in one instance death followed.

The substitution of carbolic acid for medicine happened as follows:--

                                                 Cases.
  Taken instead of Tincture of Opium,              1
    „      „       Infusion of Senna,              3
    „      „       Mineral Water,                  2
    „      „       other Mixtures,                 3
    „   inwardly instead of applied outwardly,     3
                                                  --
                                                  12

Of these 12, 8 died.

Again, 10 persons took carbolic acid in mistake for various alcoholic
drinks, such as schnapps, brandy, rum, or beer, and 9 of the 10
succumbed; 17 persons drank carbolic acid simply “by mistake,” and of
these 13 died. Thus, of the whole 85 cases, no less than 51 ended
fatally--nearly 60 per cent.

It must be always borne in mind that, with regard to statistics
generally, the term “carbolic acid” is not used by coroners, juries, or
medical men, in a strictly chemical sense, the term being made to
include disinfecting fluids which are almost wholly composed of the
cresols, and contain scarcely any phenol. In this article, with regard
to symptoms and pathological appearances, it is only occasionally
possible to state whether the pure medicinal crystalline phenol or a
mixture of tar-acids was the cause of poisoning.

§ 220. =Fatal Dose.=--The minimum fatal dose for cats, dogs, and
rabbits, appears to be from ·4 to ·5 grm. per kilogram. Falck has put
the minimum lethal dose for man at 15 grms. (231·5 grains), which would
be about ·2 per kilo., basing his estimate on the following reasoning.
In 33 cases he had a fairly exact record of the amount of acid taken,
and out of the 33, he selects only those cases which are of use for the
decision of the question. Among adults, in 5 cases the dose was 30
grms., and all the 5 cases terminated by death, in times varying from
five minutes to an hour and a half. By other 5 adults a dose of 15 grms.
was taken; of the 5, 3 men and a woman died, in times varying from
forty-five minutes to thirty hours, while 1 woman recovered. Doses of
11·5, 10·8, and 9 grms. were taken by different men, and recovered from;
on the other hand, a suicide who took one and a half teaspoonful (about
6 grms.) of the concentrated acid, died in fifty minutes. Doses of ·3 to
3 grms. have caused symptoms of poisoning, but the patients recovered,
while higher doses than 15 grms. in 12 cases, with only one exception,
caused death. Hence, it may be considered tolerably well established,
that 15 grms. (231·5 grains) may be taken as representing the minimum
lethal dose.

The largest dose from which a person appears to have recovered is, I
believe, that given in a case recorded by Davidson, in which 150 grms.
of crude carbolic acid had been taken. It must, however, be remembered
that, as this was the impure acid, probably only half of it was really
carbolic acid. The German Pharmacopœia prescribes as a maximum dose ·05
grm (·7 grain) of the crystallised acid, and a daily maximum quantity
given in divided doses of ·15 grm. (2·3 grains).

§ 221. =Effects on Animals.=--Carbolic acid is poisonous to both animal
and vegetable life.

=Infusoria.=--One part of the acid in 10,000 parts of water rapidly
kills ciliated animalcules,--the movements become sluggish, the sarcode
substance darker, and the cilia in a little time cease moving.

=Fish.=--One part of the acid in 7000 of water kills dace, minnows,
roach, and gold fish. In this amount of dilution the effect is not
apparent immediately; but, at the end of a few hours, the movements of
the fish become sluggish, they frequently rise to the surface to
breathe, and at the end of twenty-four hours are found dead. Quantities
of carbolic acid, such as 1 part in 100,000 of water, appear to affect
the health of fish, and render them more liable to be attacked by the
fungus growth which is so destructive to fish-life in certain years.

=Frogs.=--If ·01 to ·02 grm. of carbolic acid be dissolved in a litre of
water in which a frog is placed, there is almost immediately signs of
uneasiness in the animal, showing that pain from local contact is
experienced; a sleepy condition follows, with exaltation of reflex
sensibility; convulsions succeed, generally, though not always; then
reflex sensibility is diminished, ultimately vanishes, and death occurs;
the muscles and nerves still respond to the electric current, and the
heart beats, but slowly and weakly, for a little after the respiration
has ceased.

§ 222. =Warm-blooded Animals.=--For a rabbit of the average weight of 2
kilos., ·15 grm. is an active dose, and ·3 a lethal dose (that is ·15
per kilo.). The sleepy condition of the frog is not noticed, and the
chief symptoms are clonic convulsions with dilatation of the pupils, the
convulsions passing into death, without a noticeable paralytic stage.
The symptoms observed in poisoned dogs are almost precisely similar, the
dose, according to body-weight, being the same. It has, however, been
noticed that with doses large enough to produce convulsions, a weak
condition has supervened, causing death in several days. There appears
to be no cumulative action, since equal toxic doses can be given to
animals for some time, and the last dose has no greater effect than the
first or intermediate ones. The pathological appearances met with in
animals poisoned by the minimum lethal doses referred to are not
characteristic; but there is a remarkable retardation of putrefaction.

§ 223. =Symptoms in Man, external application.=--A 5 per cent. solution
of carbolic acid, applied to the skin, causes a peculiar numbness,
followed, it may be, by irritation. Young subjects, and those with
sensitive skins, sometimes exhibit a pustular eruption, and concentrated
solutions cause more or less destruction of the skin. Lemaire[197]
describes the action of carbolic acid on the skin as causing a slight
inflammation, with desquamation of the epithelium, followed by a very
permanent brown stain, but this he alone has observed. Applied to the
mucous membrane, carbolic acid turns the epithelial covering white; the
epithelium, however, is soon thrown off, and the place rapidly heals;
there is the same numbing, aconite-like feeling before noticed. The
vapour of carbolic acid causes redness of the conjunctivæ, and
irritation of the air-passages. If the application is continued, the
mucous membrane swells, whitens, and pours out an abundant secretion.

[197] Lemaire, Jul., “_De l’Acide phénique_,” Paris, 1864.

Dr. Whitelock, of Greenock, has related two instances in which children
were treated with carbolic acid lotion (strength 2½ per cent.) as an
application to the scalp for ringworm; in both, symptoms of poisoning
occurred--in the one, the symptoms at once appeared; in the other they
were delayed some days. In order to satisfy his mind, the experiment was
repeated twice, and each time gastric and urinary troubles followed.

Nussbaum, of Munich, records a case[198] in which symptoms were induced
by the forcible injection of a solution of carbolic acid into the cavity
of an abscess.

[198] _Leitfaden zur antiseptischer Wundbehandlung_, 141.

Macphail[199] gives two cases of poisoning by carbolic acid from
external use. In the one, a large tumour had been removed from a woman
aged 30, and the wound covered with gauze steeped in a solution of
carbolic acid, in glycerin, strength 10 per cent.; subsequently, there
was high fever, with diminished sulphates in the urine, which smelt
strongly of carbolic acid, and was very dark. On substituting boracic
acid, none of these troubles were observed. The second case was that of
a servant suffering from axillary abscess; the wound was syringed out
with carbolic acid solution, of strength 2½ per cent., when effects were
produced similar to those in the first case. It was noted that in both
these cases the pulse was slowed. Scattered throughout surgical and
medical literature, there are many other cases recorded, though not all
so clear as those cited. Several cases are also on record in which
poisonous symptoms (and even death) have resulted from the application
of carbolic acid lotion as a remedy for scabies or itch.

[199] “Carbolic Acid Poisoning (Surgical),” by S. Rutherford Macphail,
M.B., _Ed. Med. Journal_, cccxiv., Aug. 1881, p. 134.

A surgeon prescribed for two joiners who suffered from scabies a lotion,
which was intended to contain 30 grms. of carbolic acid in 240 c.c. of
water; but the actual contents of the flasks were afterwards from
analysis estimated by Hoppe-Seyler to be 33·26 grms., and the quantity
used by each to be equal to 13·37 grms. (206 grains) of carbolic acid.
One of the men died; the survivor described his own symptoms as
follows:--He and his companion stood in front of the fire, and rubbed
the lotion in; he rubbed it into his legs, breast, and the front part of
his body; the other parts were mutually rubbed. Whilst rubbing his right
arm, and drying it before the fire, he felt a burning sensation, a
tightness and giddiness, and mentioned his sensations to his companion,
who laughed. This condition lasted from five to seven minutes, but he
did not remember whether his companion complained of anything, nor did
he know what became of him, nor how he himself came to be in bed. He was
found holding on to the joiner’s bench, looking with wide staring eyes,
like a drunken man, and was delirious for half an hour. The following
night he slept uneasily and complained of headache and burning of the
skin. The pulse was 68, the appearance of the urine, appetite, and sense
of taste were normal; the bowels confined. He soon recovered.

The other joiner seems to have died as suddenly as if he had taken
prussic acid. He called to his mother, “_Ich habe einen Rausch_,” and
died with pale livid face, after taking two deep, short inspirations.

The _post-mortem_ examination showed the sinuses filled with much fluid
blood, and the vessels of the pia mater congested. Frothy, dark, fluid
blood was found in the lungs, which were hyperæmic; the mucous tissues
of the epiglottis and air-tubes were reddened, and covered with a frothy
slime. Both ventricles--the venæ cavæ and the vessels of the spleen and
kidneys--were filled with dark fluid blood. The muscles were very red;
there was no special odour. Hoppe-Seyler recognised carbolic acid in the
blood and different organs of the body.[200]

[200] R. Köhler, _Würtem. Med. Corr. Bl._, xlii., No. 6, April 1872; H.
Abelin, _Schmidt’s Jahrbücher_, 1877, Bd. 173, S. 163.

In another case, a child died from the outward use of a 2 per cent.
solution of carbolic acid. It is described as follows:--An infant of
seven weeks old suffered from varicella, and one of the pustules became
the centre of an erysipelatous inflammation. To this place a 2 per cent.
solution of carbolic acid was applied by means of a compress steeped in
the acid; the following morning the temperature rose from 36·5° (97·7°
F.) to 37° (98·6° F.), and poisonous symptoms appeared. The urine was
coloured dark. There were sweats, vomitings, and contracted pupils,
spasmodic twitchings of the eyelids and eyes, with strabismus, slow
respiration, and, lastly, inability to swallow. Under the influence of
stimulating remedies the condition temporarily improved, but the child
died twenty-three and a half hours after the first application. An
examination showed that the vessels of the brain and the tissue of the
lungs were abnormally full of blood. The liver was softer than natural,
and exhibited a notable yellowishness in the centre of the acini.
Somewhat similar appearances were noticed in the kidneys, the
microscopic examination of which showed the _tubuli contorti_ enlarged
and filled with fatty globules. In several places the epithelium was
denuded, in other places swollen, and with the nuclei very visible.

In an American case,[201] death followed the application of carbolic
acid to a wound. A boy had been bitten by a dog, and to the wound, at
one o’clock in the afternoon, a lotion, consisting of nine parts of
carbolic acid and one of glycerin, was applied. At seven o’clock in the
evening the child was unconscious, and died at one o’clock the following
day.

[201] _American Journal of Pharmacy_, vol. li., 4th Ser.; vol. ix.,
1879, p. 57.

§ 224. =Internal Administration.=--Carbolic acid may be taken into the
system, not alone by the mouth, but by the lungs, as in breathing
carbolic acid spray or carbolic acid vapour. It is also absorbed by the
skin when outwardly applied, or in the dressing or the spraying of
wounds with carbolic acid. Lastly, the ordinary poisonous effects have
been produced by absorption from the bowel, when administered as an
enema. When swallowed undiluted, and in a concentrated form, the
symptoms may be those of early collapse, and speedy death. Hence, the
course is very similar to that witnessed in poisoning by the mineral
acids.

If lethal, but not excessive doses of the diluted acid are taken, the
symptoms are--a burning in the mouth and throat, a peculiarly unpleasant
persistent taste, and vomiting. There is faintness with pallor of the
face, which is covered by a clammy sweat, and the patient soon becomes
unconscious, the pulse small and thready, and the pupils sluggish to
light. The respiration is profoundly affected; there is dyspnœa, and the
breathing becomes shallow. Death occurs from paralysis of the
respiratory apparatus, and the heart is observed to beat for a little
after the respiration has ceased. All these symptoms may occur from the
application of the acid to the skin or to mucous membranes, and have
been noticed when solutions of but moderate strength have been
used--e.g., there are cases in gynæcological practice in which the
mucous membrane (perhaps eroded) of the uterus has been irrigated with
carbolic acid injections. Thus, Küster[202] relates a case in which,
four days after confinement, the uterus was washed out with a 2 per
cent. solution of carbolic acid without evil result. Afterwards a 5 per
cent. solution was used, but it at once caused violent symptoms of
poisoning, the face became livid, clonic convulsions came on, and at
first loss of consciousness, which after an hour returned. The patient
died on the ninth day. There was intense diphtheria of the uterus and
vagina. Several other similar cases (although not attended with such
marked or fatal effects) are on record.[203]

[202] _Centralblatt. f. Gynäkologie_, ii. 14, 1878.

[203] A practitioner in Calcutta injected into the bowel of a boy, aged
5, an enema of diluted carbolic acid, which, according to his own
statement, was 1 part in 60, and the whole quantity represented 144
grains of the acid. The child became insensible a few minutes after the
operation, and died within four hours. There was no _post-mortem_
examination; the body smelt strongly of carbolic acid.--_Lancet_, May
19, 1883.

§ 225. The symptoms of carbolic acid poisoning admit of considerable
variation from those already described. The condition is occasionally
that of deep coma. The convulsions may be general, or may affect only
certain groups of muscles. Convulsive twitchings of the face alone, and
also muscular twitchings only of the legs, have been noticed. In all
cases, however, a marked change occurs in the urine. Subissi[204] has
noted the occurrence of abortion, both in the pig and the mare, as a
result of carbolic acid, but this effect has not hitherto been recorded
in the human subject.

[204] _L’Archivio della Veterinaria Ital._, xi., 1874.

It has been experimentally shown by Küster, that previous loss of blood,
or the presence of septic fever, renders animals more sensitive to
carbolic acid. It is also said that children are more sensitive than
adults.

The course of carbolic acid poisoning is very rapid. In 35 cases
collected by Falck, in which the period from the taking of the poison to
the moment of death was accurately noted, the course was as follows:--12
patients died within the first hour, and in the second hour 3; so that
within two hours 15 died. Between the third and the twelfth hour, 10
died; between the thirteenth and the twenty-fourth hour, 7 died; and
between the twenty-fifth and the sixtieth hour, only 3 died. Therefore,
slightly over 71 per cent. died within twelve hours, and 91·4 per cent.
within the twenty-four hours.

§ 226. =Changes in the Urine.=--The urine of patients who have absorbed
in any way carbolic acid is dark in colour, and may smell strongly of
the acid. It is now established--chiefly by the experiments and
observations of Baumann[205]--that carbolic acid, when introduced into
the body, is mainly eliminated in the form of phenyl-sulphuric acid,
C₆H₅HSO₄, or more strictly speaking as potassic phenyl-sulphate,
C₆H₅KSO₄, a substance which is not precipitated by chloride of barium
until it has been decomposed by boiling with a mineral acid. Cresol is
similarly excreted as cresol-sulphuric acid, C₆H₄CH₃HSO₄, ortho-, meta-,
or para-, according to the kind of cresol injected; a portion may also
appear as hydro-tolu-chinone-sulphuric acid. Hence it is that, with
doses of phenol or cresol continually increasing, the amount of
sulphates naturally in the urine (as estimated by simply acidifying with
hydrochloric acid, and precipitating in the cold with chloride of
barium) continually decreases, and may at last vanish, for all the
sulphuric acid present is united with the phenol. On the other hand, the
precipitate obtained by prolonged boiling of the strongly acidified
urine, after filtering off any BaSO₄ thrown down in the cold, is ever
increasing.

[205] _Pflüger’s Archiv_, 13, 1876, 289.

Thus, a dog voided urine which contained in 100 c.c., ·262 grm. of
precipitable sulphuric acid, and ·006 of organically-combined sulphuric
acid; his back was now painted with carbolic acid, and the normal
proportions were reversed, the precipitable sulphuric acid became ·004
grm., while the organically-combined was ·190 in 100 c.c. In addition to
phenyl-sulphuric acid, it is now sufficiently established[206] that
hydroquinone

  (    OH)
  (C₆H₄  )
  (    OH)

(paradihydroxyl phenol) and pyrocatechin

  (    OH)
  (C₆H₄  )
  (    OH)

(orthodihydroxyl phenol) are constant products of a portion of the
phenol. The hydroquinone appears in the urine, in the first place, as
the corresponding ether-sulphuric acid, which is colourless; but a
portion of it is set free, and this free hydroquinone (especially in
alkaline urine) is quickly oxidised to a brownish product, and hence the
peculiar colour of urine. Out of dark coloured carbolic acid urine the
hydroquinone and its products of decomposition can be obtained by
shaking with ether; on separation of the ether, an extract is obtained,
reducing alkaline silver solution, and developing quinone on warming
with ferric chloride.

[206] E. Baumann and C. Preuss, _Zeitschrift f. phys. Chemie_, iii. 156;
_Anleitung zur Harn-Analyse_, W. F. Löbisch, Leipzig, 1881, pp. 142,
160; Schmiedeberg, _Chem. Centrbl._ (3), 13, 598.

To separate pyro-catechin, 200 c.c. of urine may be evaporated to an
extract, the extract treated with strong alcohol, the alcoholic liquid
evaporated, and the extract then treated with ether. On separation and
evaporation of the ether, a yellowish mass is left, from which the
pyro-catechin may be extracted by washing with a small quantity of
water. This solution will reduce silver solution in the cold, or, if
treated with a few drops of ferric chloride solution, show a marked
green colour, changing on being alkalised by a solution of sodic
hydro-carbonate to violet, and then on being acidified by acetic acid,
changing back again to green. According to Thudichum,[207] the urine of
men and dogs, after the ingestion of carbolic acid, contains a blue
pigment.

[207] _On the Pathology of the Urine_, Lond., 1877, p. 198.

§ 227. =The Action of Carbolic Acid considered
physiologically.=--Researches on animals have elucidated, in a great
measure, the mode in which carbolic acid acts, and the general sequence
of effects, but there is still much to be learnt.

E. Küster[208] has shown that the temperature of dogs, when doses of
carbolic acid in solution are injected subcutaneously, or into the
veins, is immediately, or very soon after the operation, raised. With
small and moderate doses, this effect is but slight--from half to a
whole degree--on the day after the injection the temperature sinks below
the normal point, and only slowly becomes again natural. With doses that
are just lethal, first a rise and then a rapid sinking of temperature
are observed; but with those excessive doses which speedily kill, the
temperature at once sinks without a preliminary rise. The action on the
heart is not very marked, but there is always a slowing of the cardiac
pulsations; according to Hoppe-Seyler the arteries are relaxed. The
respiration is much quickened; this acceleration is due to an
excitement of the vagus centre, since Salkowsky has shown that section
of the vagus produces a retardation of the respiratory wave. Direct
application of the acid to muscles or nerves quickly destroys their
excitability without a previous stage of excitement. The main cause of
the lethal action of carbolic acid--putting on one side those cases in
which it may kill by its local corrosive action--appears to be paralysis
of the respiratory nervous centres. The convulsions arise from the
spinal cord. On the cessation of the convulsions, the superficial nature
of the breathing assists other changes by preventing the due oxidation
of the blood.

[208] _Archiv f. klin. Chirurgie_, Bd. 23, S. 133, 1879.

§ 228. Carbolic acid is separated from the body in the forms already
mentioned, a small portion is also excreted by the skin. Salkowsky
considers that, with rabbits, he has also found oxalic acid in the urine
as an oxidation product. According to the researches of Binnendijk,[209]
the separation of carbolic acid by the urine commences very quickly
after its ingestion; and, under favourable circumstances, it may be
completely excreted within from twelve to sixteen hours. It must be
remembered that normally a small amount of phenol may be present in the
animal body, as the result of the digestion of albuminous substances or
of their putrefaction. The amount excreted by healthy men when feeding
on mixed diet, Engel,[210] by experiment, estimates to be in the
twenty-four hours 15 mgrms.

[209] _Journal de Pharmacie et de Chimie._

[210] _Annal. de Chimie et de Physique_, 5 Sér. T. 20, p. 230, 1880.

§ 229. =Post-mortem Appearances.=--No fact is better ascertained from
experiments on animals than the following:--That with lethal doses of
carbolic acid, administered by subcutaneous injection, or introduced by
the veins, no appearances may be found after death which can be called
at all characteristic. Further, in the cases in which death has occurred
from the outward application of the acid for the cure of scabies, &c.,
no lesion was ascertained after death which could--apart from the
history of the case and chemical evidence--with any confidence be
ascribed to a poison.

On the other hand, when somewhat large doses of the acid are taken by
the mouth, very coarse and appreciable changes are produced in the upper
portion of the alimentary tract. There may be brownish, wrinkled spots
on the cheek or lips; the mucous membrane of the mouth, throat, and
gullet is often white, and if the acid was concentrated, eroded. The
stomach is sometimes thickened, contracted, and blanched, a condition
well shown in a pathological preparation (ix. 206, 43 _f_) in St.
George’s Hospital. The mucous membrane, indeed, may be quite as much
destroyed as if a mineral acid had been taken. Thus, in Guy’s Hospital
museum (1799⁴⁰), there is preserved the stomach of a child who died
from taking accidentally carbolic acid. It looks like a piece of paper,
and is very white, with fawn-coloured spots; the rugæ are absent, and
the mucous membrane seems to have entirely vanished. Not unfrequently
the stomach exhibits white spots with roundish edges. The duodenum is
often affected, and the action is not always limited to the first part
of the intestine.

The respiratory passages are often inflamed, and the lungs infiltrated
and congested. As death takes place from an asphyxiated condition, the
veins of the head and brain, and the blood-vessels of the liver, kidney
and spleen, are gorged with blood, and the right side of the heart
distended, while the left is empty. On the other hand, a person may die
of sudden nervous shock from the ingestion of a large quantity of the
acid, and in such a case the _post-mortem_ appearances will not then
exhibit precisely the characters just detailed. Putrefaction is retarded
according to the dose, and there is often a smell of carbolic acid.[211]
If any urine is contained in the bladder, it will probably be dark, and
present the characters of carbolic urine, detailed at p. 174.

[211] In order to detect this odour, it is well to open the head first,
lest the putrefaction of the internal viscera be so great as to mask the
odour.


Tests for Carbolic Acid.

§ 230. 1. =The Pinewood Test.=--Certain pinewood gives a beautiful blue
colour when moistened first with carbolic acid, and afterwards with
hydrochloric acid, and exposed to the light. Some species of pine give a
blue colour with hydrochloric acid alone, and such must not be used;
others do not respond to the test for carbolic acid. Hence it is
necessary to try the chips of wood first, to see how they act, and with
this precaution the test is very serviceable, and, in cautious hands, no
error will be made.

2. =Ammonia and Hypochlorite Test.=--If to a solution containing even so
small a quantity as 1 part of carbolic acid in 5000 parts of water,
first, about a quarter of its volume of ammonia hydrate be added, and
then a small quantity of sodic hypochlorite solution, avoiding excess, a
blue colour appears, warming quickens the reaction: the blue is
permanent, but turns to red with acids. If there is a smaller quantity
than the above proportion of acid, the reaction may be still produced
feebly after standing for some time.

3. =Ferric Chloride.=--One part of phenol in 3000 parts of water can be
detected by adding a solution of ferric chloride; a fine violet colour
is produced. This is also a very good test, when applied to a
distillate; but if applied to a complex liquid, the disturbing action of
neutral salts and other substances may be too great to make the
reaction under those circumstances of service.

4. =Bromine.=--The most satisfactory test of all is treatment of the
liquid by bromine-water. A precipitate of tri-bromo-phenol (C₆H₃Br₃O) is
rapidly or slowly formed, according to the strength of the solution; in
detecting very minute quantities the precipitate must be given time to
form. According to Allen,[212] a solution containing but 1/60000 of
carbolic acid gave the reaction after standing twenty-four hours.

[212] _Commercial Organic Analysis_, vol. i. p. 306.

The properties of the precipitate are as follows:--It is crystalline,
and under the microscope is seen to consist of fine stars of needles;
its smell is peculiar; it is insoluble in water and acid liquids, but
soluble in alkalies, ether, and absolute alcohol; a very minute quantity
of water suffices to precipitate it from an alcoholic solution; it is
therefore essential to the success of the test that the watery liquid to
be examined is either neutral or acid in reaction.

§ 231. Tri-bromo-phenol may be used for the quantitative estimation of
carbolic acid, 100 parts of tri-bromo-phenol are equal to 29·8 of
carbolic acid; by the action of sodium amalgam, tri-bromo-phenol is
changed back into carbolic acid.

That bromine-water precipitates several volatile and fixed alkaloids
from their solutions is no objection to the bromine test, for it may be
applied to a distillation product, the bases having been previously
fixed by sulphuric acid. Besides, the properties of tri-bromo-phenol are
distinct enough, and therefore there is no valid objection to the test.
It is the best hitherto discovered. There are also other reactions, such
as that Millon’s reagent strikes a red--molybdic acid, in concentrated
sulphuric acid, a blue--and potassic dichromate, with sulphuric acid, a
brown colour--but to these there are objections. Again, we have the
_Euchlorine_ test, in which the procedure is as follows:--A test-tube is
taken, and concentrated hydrochloric acid is allowed to act therein upon
potassic chlorate. After the gas has been evolved for from 30 to 40
seconds, the liquid is diluted with 1½ volume of water, the gas removed
by blowing through a tube, and solution of strong ammonia poured in so
as to form a layer on the top; after blowing out the white fumes of
ammonium chloride, a few drops of the sample to be tested are added. In
the presence of carbolic acid, a rose-red, blood-red, or red-brown tint
is produced, according to the quantity present. Carbolic acid may be
confounded with _cresol_ or with _creasote_, but the distinction between
pure carbolic acid, pure cresol, and creasote is plain.

§ 232. =Cresol (Cresylic Acid, Methyl-phenol)=,

       OH
      /
  C₆H₄     .
      \
       CH₃

--There are three cresols--ortho-, meta-, and para-. Ordinary
commercial cresol is a mixture of the three, but contains but little
ortho-cresol; the more important properties of the pure cresols are set
out in the following table:--

  +--------+-----------------+----------------+---------------------+
  |        | Melting-point.  | Boiling-point. | Converted by fusion |
  |        |                 |                | with Potash into--  |
  +--------+-----------------+----------------+---------------------+
  |Ortho-, |   31-31·5° C.   |    188·0°      |   Salicylic Acid    |
  |        |                 |                | (Ortho-oxybenzoic   |
  |        |                 |                |      acid).         |
  |        |                 |                |                     |
  |Meta-,  |Fluid at ordinary|    201·0°      |  Meta-oxybenzoic    |
  |        |   temperature.  |                |      acid.          |
  |        |                 |                |                     |
  |Para-,  |     36°         |    198°        |Para-oxybenzoic acid.|
  +--------+-----------------+----------------+---------------------+

Pure ortho-, meta-, or para-cresol have been obtained by synthetical
methods; they cannot be said to be in ordinary commerce.

=Commercial cresol= is at ordinary temperatures a liquid, and cannot be
obtained in a crystalline state by freezing. Its boiling-point is from
198° to 203°; it is almost insoluble in strong ammonia, and, when 16
volumes are added, it then forms crystalline scales. On the other hand,
carbolic acid is soluble in an equal volume of ammonia, and is then
precipitated by the addition of 1½ volume of water. Cresol is insoluble
in small quantities of pure 6 per cent. soda solution; with a large
excess, it forms crystalline scales; while carbolic acid is freely
soluble in small or large quantities of alkaline solutions.

Cold petroleum spirit dissolves cresol, but no crystalline scales can be
separated out by a freezing mixture. Carbolic acid, on the contrary, is
but sparingly soluble in cold petroleum, and a solution of carbolic acid
in hot petroleum, when exposed to sudden cold produced by a freezing
mixture, separates out crystals from the upper layer of liquid. Cresol
is miscible with glycerin of specific gravity 1·258 in all proportions;
1 measure of glycerin mixed with 1 measure of cresol is completely
precipitated by 1 measure of water. Carbolic acid, under the same
circumstances, is not precipitated. The density of cresol is about
1·044. It forms with bromine a tri-bromo-cresol, but this is liquid at
ordinary temperatures, while tri-bromo-phenol is solid. On the other
hand, it resembles carbolic acid in its reactions with ferric chloride
and with nitric and sulphuric acid.

    § 233. =Creasote= or =Kreozote= is a term applied to the mixture of
    crude phenols obtained from the distillation of wood-tar. It
    consists of a mixture of substances of which the chief are guaiacol
    or oxycresol (C₇H₈O₂), boiling at 200°, and creasol (C₈H₁₀O₂),
    boiling at 217°; also in small quantities phlorol (C₈H₁₀O), methyl
    creasol (C₉H₁₂O₂), and other bodies. Morson’s English creasote is
    prepared from Stockholm tar, and boils at about 217°, consisting
    chiefly of creasol; it is not easy, by mere chemical tests, to
    distinguish creasote from cresylic acid. Creasote, in its reactions
    with sulphuric and nitric acid, bromine and gelatin, is similar to
    carbolic and cresylic acids, and its solubility in most solvents is
    also similar. It is, however, distinguished from the tar acids by
    its insolubility in Price’s glycerin, specific gravity 1·258,
    whether 1, 2, or 3 volumes of glycerin be employed. But the best
    test is its action on an ethereal solution of nitro-cellulose.
    Creasote mixes freely with the B.P. collodium, while cresylic acid
    or carbolic acid at once coagulates the latter. With complicated
    mixtures containing carbolic acid, cresol, and creasote, the only
    method of applying these tests with advantage is to submit the
    mixture to fractional distillation.

    Flückiger[213] tests for small quantities of carbolic acid in
    creasote, by mixing a watery solution of the sample with one-fourth
    of its volume of ammonia hydrate, wetting the inside of a porcelain
    dish with this solution, and then carefully blowing bromine fumes on
    to the surface. A fine blue colour appears if carbolic acid is
    present, but if the sample consists of creasote only, then it is
    dirty green or brown. Excess of bromine spoils the reaction.[214]

[213] _Arch. der Pharmacie_, cxiii. p. 30.

[214] Creasote is, without doubt, poisonous, though but little is known
of its action, and very few experiments are on record in which pure
creasote has been employed. Eulenberg has studied the symptoms in
rabbits, by submitting them to vaporised creasote--_i.e._, the vapour
from 20 drops of creasote diffused through a glass shade under which a
rabbit was confined. There was at once great uneasiness, with a watery
discharge from the eyes, and after seven minutes the rabbit fell on its
side, and was slightly convulsed. The cornea was troubled, and the eyes
prominent; a white slime flowed from the mouth and eyes. After fifteen
minutes there was narcosis, with lessened reflex action; the temperature
was almost normal. There was rattling breathing, and in half an hour the
animal died, the respiration ceasing, and fluid blood escaping from the
nose. Section after death showed the brain to be hyperæmic, the mucous
membranes of the air-passages to be covered with a thin layer of fluid
blood, and the lungs to be congested; the right side of the heart was
gorged with fluid blood.

The _post-mortem_ appearances and the symptoms generally are, therefore,
closely allied to those produced by carbolic acid. A dark colour of the
urine has also been noticed.

§ 234. =Carbolic Acid in Organic Fluids or in the Tissues of the
Body.=--If the routine process given at page 51, where the organic fluid
is distilled in a vacuum after acidifying with tartaric acid, is
employed, phenol or cresol, if present, will certainly be found in the
distillate. If, however, a special search be made for the acids, then
the fluid must be well acidified with sulphuric acid, and distilled in
the usual way. The distillation should be continued as long as possible,
and the distillate shaken up with ether in the apparatus figured at page
156. On separation and evaporation of the ether, the tar acids, if
present, will be left in a pure enough form to show its reactions. The
same process applies to the tissues, which, in a finely-divided state,
are boiled and distilled with dilute sulphuric acid, and the distillate
treated as just detailed.

Like most poisons, carbolic acid has a selective attraction for certain
organs, so that, unless all the organs are examined, it is by no means
indifferent which particular portion is selected for the inquiry.
Hoppe-Seyler applied carbolic acid to the abdomen and thighs of dogs,
and when the symptoms were at their height bled them to death, and
separately examined the parts. In one case, the blood yielded ·00369 per
cent.; the brain, ·0034 per cent.; the liver, ·00125; and the kidneys,
·00423 per cent. of their weight of carbolic acid. The liver then
contains only one-third of the quantity found in an equal weight of
blood, and, therefore, the acid has no selective affinity for that
organ. On the other hand, the nervous tissue, and especially the
kidneys, appear to concentrate it.

§ 235. =Examination of the Urine for Phenol or Cresol.=--It has been
previously stated (see p. 174) that the urine will not contain these as
such, but as compounds--viz., phenyl or cresyl sulphate of potassium. By
boiling with a mineral acid, these compounds may be broken up, and the
acids obtained, either by distillation or by extraction with ether. To
detect very minute quantities, a large quantity of the urine should be
evaporated down to a syrup, and treated with hydrochloric acid and
ether. On evaporating off the ether, the residue should be distilled
with dilute sulphuric acid, and this distillate then tested with
bromine-water, and the tri-bromo-phenol or cresol collected, identified,
and weighed.

Thudichum[215] has separated crystals of potassic phenyl-sulphate itself
from the urine of patients treated endermically by carbolic acid, as
follows:--

[215] _Pathology of the Urine_, p. 193.

The urine was evaporated to a syrup, extracted with alcohol of 90 per
cent., treated with an alcoholic solution of oxalic acid as long as this
produced a precipitate, and then shaken with an equal volume of ether.
The mixture was next filtered, neutralised with potassic carbonate,
evaporated to a small bulk, and again taken up with alcohol. Some
oxalate and carbonate of potassium were separated, and, on evaporation
to a syrup, crystals of potassic phenyl-sulphate were obtained. They
gave to analysis 46·25 per cent. H₂SO₄, and 18·1 K--theory requiring
46·2 of H₂SO₄ and 18·4 of K. Alkaline phenyl-sulphates strike a deep
purple colour with ferric chloride. To estimate the amount of
phenyl-sulphate or cresol-sulphate in the urine, the normal sulphates
may be separated by the addition of chloride of barium in the cold,
first acidifying with hydrochloric acid. On boiling the liquid a second
crop of sulphate is obtained, due to the breaking up of the compound
sulphate, and from this second weight the amount of acid can be
obtained, _e.g._, in the case of phenol--C₆H₅HSO₄ : BaSO₄ :: 174 : 233.

    § 236. =Assay of Disinfectants, Carbolic Acid Powders, &c.=--For the
    assay of crude carbolic acid, Mr. Charles Lowe[216] uses the
    following process:--A thousand parts of the sample are distilled
    without any special condensing arrangement; water first comes over,
    and is then followed by an oily fluid. When a hundred parts of the
    latter, as measured in a graduated tube, have been collected, the
    receiver is changed. The volume of water is read off. If the oily
    liquid floats on the water, it contains light oil of tar; if it is
    heavier than the water, it is regarded as hydrated acid, containing
    50 per cent. of real carbolic acid. The next portion consists of
    anhydrous cresylic and carbolic acids, and 625 volumes are distilled
    over; the remainder in the retort consists wholly of cresylic acid
    and the higher homologues. The relative proportions of carbolic and
    cresylic acids are approximately determined by taking the
    solidifying point, which should be between 15·5° and 24°, and having
    ascertained this temperature, imitating it by making mixtures of
    known proportions of carbolic and cresylic acids.

[216] _Allen’s Commercial Organic Analysis_, vol. i. p. 311.

    E. Waller[217] has recommended the following process for the
    estimation of carbolic acid. It is based on the precipitation of the
    tar acids by bromine, and, of course, all phenols precipitated in
    this way will be returned as carbolic acid. The solutions necessary
    are--

[217] _Chem. News_, April 1, 1881, p. 152.

    1. A solution containing 10 grms. of pure carbolic acid to the
    litre; this serves as a standard solution.

    2. A solution of bromine in water.

    3. Solution of alum in dilute sulphuric acid. A litre of 10 per
    cent. sulphuric acid is shaken with alum crystals until saturated.

    The actual process is as follows:--10 grms. of the sample are
    weighed out and run into a litre flask, water added, and the mixture
    shaken. The flask being finally filled up to the neck, some of the
    solution is now filtered through a dry filter, and 10 c.c. of this
    filtrate is placed in a 6 or 8-ounce stoppered bottle, and 30 c.c.
    of the alum solution added. In a similar bottle 10 c.c. of the
    standard solution of carbolic acid are placed, and a similar
    quantity of alum solution is added, as in the first bottle. The
    bromine-water is now run into the bottle containing the standard
    solution of carbolic acid from a burette until there is no further
    precipitate; the bottle is stoppered and shaken after every
    addition. Towards the end of the reaction the precipitate forms but
    slowly, and when the carbolic acid is saturated, the slight excess
    of bromine-water gives the solution a pale yellow tint. The solution
    from the sample is treated in the same way, and from the amount of
    bromine-water used, the percentage of the sample is obtained by
    making the usual calculations. Thus, supposing that 5 c.c. of the
    standard required 15 c.c. of the bromine-water for precipitation,
    and 10 c.c. of the solution of the sample required 17 c.c., the
    calculation would be 15 × 2 : 17 = 100 : _x_ per cent. With most
    samples of crude carbolic acid, the precipitate does not readily
    separate. It is then best to add a little of the precipitate already
    obtained by testing the standard solution, which rapidly clears the
    liquid.

    =Koppeschaar’s volumetric method= is more exact, but also more
    elaborate, than the one just described. Caustic normal soda is
    treated with bromine until permanently yellow, and the excess of
    bromine is then driven off by boiling. The liquid now contains 5NaBr
    + NaBrO₃, and on adding this to a solution containing carbolic acid,
    and a sufficient quantity of hydrochloric acid to combine with the
    sodium, the following reactions occur:--

  (1.) 5NaBr + NaBrO₃ + 6HCl = 6NaCl + 6Br + 3H₂O;

    and

  (2.) C₆H₆O + 6Br = C₆H₃Br₃O + 3HBr.

    Any excess of bromine liberated in the first reaction above that
    necessary for the second, will exist in the free state, and from the
    amount of bromine which remains free the quantity of carbolic acid
    can be calculated, always provided the strength of the bromine
    solution is first known. The volumetric part of the analysis,
    therefore, merely amounts to the determination of free bromine,
    which is best found by causing it to react on potassium iodide, and
    ascertaining the amount of free iodine by titration with a standard
    solution of sodium thiosulphate. In other words, titrate in this way
    the standard alkaline bromine solution, using as an indicator starch
    paste until the blue colour disappears. Another method of indicating
    the end of the reaction is by the use of strips of paper first
    soaked in starch solution, and dried, and then the same papers
    moistened with zinc iodide, and again dried; the least excess of
    bromine sets free iodine, and strikes a blue colour.

    =Colorimetric Method of Estimation.=--A very simple and ever-ready
    way of approximately estimating minute quantities of the phenols
    consists in shaking up 10 grms. of the sample with water, allowing
    any tar or insoluble impurities to subside. Ten c.c. of the clear
    fluid are then taken, and half a c.c. of a 5 per cent. solution of
    ferric chloride added. The colour produced is imitated by a standard
    solution of carbolic acid, and a similar amount of the reagent, on
    the usual principles of colorimetric analysis.

    § 237. =Carbolic Acid Powders.=--Siliceous carbolic acid powders are
    placed in a retort and distilled. Towards the end the heat may be
    raised to approaching redness. The distillate separates into two
    portions--the one aqueous, the other consisting of the acids--and
    the volume may be read off, if the distillate be received in a
    graduated receiver. Carbolic acid powders, having lime as a basis,
    may be distilled in the same way, after first decomposing with
    sulphuric acid. The estimation of the neutral tar oils in the
    distillate is easily performed by shaking the distillate with
    caustic soda solution, which dissolves completely the tar acids. The
    volume of the oils may be directly read off if the receiver is a
    graduated tube. Allen[218] has suggested the addition of a known
    volume of petroleum to the distillate, which dissolves the tar oils,
    and easily separates, and thus the volume may be more accurately
    determined, a correction being of course made by subtracting the
    volume of petroleum first added.

[218] _Op. cit._, i. p. 310.

    § 238. =Carbolic Acid Soap.=--A convenient quantity of soap is
    carefully weighed, and dissolved in a solution of caustic soda by
    means of heat. A saturated solution of salt is next added,
    sufficient to precipitate entirely the soap, which is filtered off;
    the filtrate is acidified with hydrochloric acid, and bromine water
    added. The precipitated tribromo-phenol is first melted by heat,
    then allowed to cool, and the mass removed from the liquid, dried,
    and weighed.


X.--Nitro-Benzene.

§ 239.--Nitro-benzene is the product resulting from the action of strong
nitric acid on benzene. Its chemical formula is C₆H₅NO₂. When pure, it
is of a pale yellow colour, of a density of 1·186, and boils at from
205° to 210°. It may be obtained in prismatic crystals by exposure to a
temperature of 3°. Its smell is exactly the same as that from the oil or
essence of bitter almonds; and it is from this circumstance, under the
name of “essence of mirbane,” much used in the preparation of perfumes
and flavouring agents.

In commerce there are three kinds of nitro-benzene--the purest, with the
characters given above; a heavier nitro-benzene, boiling at 210° to
220°; and a very heavy variety, boiling at 222° to 235° The last is
specially used for the preparation of aniline, or aniline blue.
Nitro-benzene has been used as an adulterant of bitter almond oil, but
the detection is easy (see “Foods,” p. 551). Nitro-benzene was first
discovered by Mitscherlich in 1834, and its poisonous properties were
first pointed out by Casper[219] in 1859. Its technical use in perfumes,
&c., dates from about 1848, and in the twenty-eight years intervening
between that date and 1876, Jübell[220] has collected 42 cases of
poisoning by this agent, 13 of which were fatal. One of these cases was
suicidal, the rest accidental.

[219] _Vierteljahrsschrift für ger. Med._, 1859, Bd. xvi. p. 1.

[220] _Die Vergiftungen mit Blausäure u. Nitro-benzol in forensischer
Beziehung_, Erlangen, 1876.

§ 240. =Effects of Poisoning by Nitro-benzene.=--Nitro-benzene is a very
powerful poison, whether taken in the form of vapour or as a liquid. The
action of the vapour on animals has been studied by Eulenberg[221] and
others. One experiment will serve as an illustration. Fifteen grms. of
nitro-benzene were evaporated on warm sand under a glass shade, into
which a cat was introduced. There was immediately observed in the animal
much salivation, and quickened and laboured breathing. After thirty
minutes’ exposure, on removing the shade to repeat the dose of 15 grms.,
the cat for the moment escaped. On being put back there was again
noticed the salivation and running at the eyes, with giddiness, and
repeated rising and falling. The animal at last, about one hour and
forty minutes after the first dose, succumbed with dyspnœa, and died
with progressive paralysis of the respiration. The membranes of the
brain were found gorged with blood, the lungs liver-coloured, the mucous
membrane of the trachea--to the finest sub-divisions of the
bronchia--reddened, inflamed, and clothed with a fine frothy mucus. The
left side of the heart was filled with thick black blood. The bladder
contained 8 grms. of clear urine, in which aniline was discovered. There
was a notable smell of bitter almonds.

[221] _Gewerbe Hygiene_, S. 607, Berlin, 1876.

§ 241. The effects of the vapour on man are somewhat different in their
details to those just described. In a remarkable case related by Dr.
Letheby, a man, aged 42, had spilt some nitro-benzene over his clothes.
He went about several hours breathing an atmosphere of nitro-benzene, he
then became drowsy, his expression was stupid, and his gait unsteady,
presenting all the appearances of intoxication. The stupor suddenly
deepened into coma, and the man died; the fatal course being altogether
about nine hours--viz., four hours before coma, and five hours of total
insensibility.

An interesting case of poisoning by the vapour is recorded by
Taylor.[222] A woman, aged 30, tasted a liquid used for flavouring
pastry, which was afterwards chemically identified as pure
nitro-benzene. She immediately spat it out, finding that it had an acrid
taste, and probably did not swallow more than a drop. In replacing the
bottle, however, she spilt about a tablespoonful, and allowed it to
remain for some minutes; it was a small room, and the vapour rapidly
pervaded it, and caused illness in herself as well as in a
fellow-servant. She had a strange feeling of numbness in the tongue, and
in three hours and a quarter after the accident was seen by a medical
man; she then presented all the appearances of prussic acid poisoning.
The eyes were bright and glassy, the features pale and ghastly, the lips
and nails purple, as if stained with blackberries, the skin clammy, and
the pulse feeble, but the mind was then clear. An emetic was
administered, but she suddenly became unconscious; the emetic acted, and
brought up a fluid with an odour of nitro-benzene. The stomach-pump was
also used, but the liquid obtained had scarcely any odour of
nitro-benzene. In about eleven hours consciousness returned, and in
about seventeen hours she partially recovered, but complained of flashes
of light and strange colours before her eyes. Recovery was not complete
for weeks. In this case the small quantity swallowed would probably of
itself have produced no symptoms, and the effects are to be mainly
ascribed to the breathing of the vapour.

[222] _Poisons_, Third Edition, p. 665.

§ 242. The liquid, when swallowed, acts almost precisely in the same way
as the vapour, and the symptoms resemble very much those produced by
prussic acid. The great distinction between prussic acid and
nitro-benzene poisoning is that, in the latter, there is an interval
between the taking of the poison and its effects. This is, indeed, one
of the strangest phenomena of nitro-benzene poisoning, for the person,
after taking it, may appear perfectly well for periods varying from a
quarter of an hour to two or three hours, or even longer, and then there
may be most alarming symptoms, followed by rapid death. Poisoning by
nitro-benzene satisfies the ideal of the dramatist, who requires, for
the purposes of his plot, poisons not acting at once, but with an
interval sufficiently prolonged to admit of lengthy rhapsodies and a
complicated _dénouement_. On drinking the poison there is a burning
taste in the mouth, shortly followed by a very striking blueness or
purple appearance of the lips, tongue, skin, nails, and even the
conjunctivæ. This curious colour of the skin has, in one or two
instances, been witnessed an hour before any feeling of illness
manifested itself; vomiting then comes on, the vomited matter smelling
of nitro-benzene. The skin is cold, there is great depression, and the
pulse is small and weak. The respiration is affected, the breathing
being slow and irregular, the breath smelling strongly of the liquid,
and the odour often persisting for days. A further stage is that of loss
of consciousness, and this comes on with all the suddenness of a fit of
apoplexy. The coma is also similar in appearance to apoplectic coma,
but there have frequently been seen trismus and convulsions of the
extremities. The pupils are dilated and do not react to light, and
reflex sensibility is sometimes completely extinguished. Cases vary a
little in their main features; in a few the blue skin and the deep sleep
are the only symptoms noted. Death, for the most part, occurs after a
period of from eight to twenty-four hours (occasionally as soon as four
or five hours) after taking the poison.

From the following remarkable train of symptoms in a dog, it is
probable, indeed, that nitro-benzene, taken by a human being, might
produce death, after a rather prolonged period of time, by its secondary
effects:--To a half-bred greyhound[223] were administered 15 grms. of
nitro-benzene, when shortly after there were noticed much salivation,
shivering, and muscular twitchings. The same dose was repeated at the
end of five, of seven, and of eight hours respectively, so that the dog
altogether took 60 grms., but with no other apparent symptom than the
profuse salivation. On the following day, the dog voided a tapeworm;
vomiting supervened; the heart’s action was quickened, and the breathing
difficult; convulsions followed, and the pupils were seen to be dilated.
For eight days the dog suffered from dyspnœa, quickened pulse, shivering
of the legs or of the whole body, tetanic spasms, bloody motions, great
thirst and debility. The temperature gradually sank under 25°, and the
animal finally died. The autopsy showed, as the most striking change,
the whole mucous membrane of the intestinal tract covered with a yellow
layer, which chemical analysis proved to be caused by picric acid, and
in the urine, liver, and lungs, aniline was discovered.

[223] Eulenberg, _Gewerbe Hygiene_, S. 607.

§ 243. =Fatal Dose.=--It is probable, from recorded cases, that 1 grm.
(15·4 grains) would be quite sufficient to kill an adult, and, under
favourable circumstances, less than that quantity. It would seem that
spirituous liquids especially hasten and intensify the action of
nitro-benzene, so that a drunken person, _cæteris paribus_, taking the
poison with spirits, would be more affected than taking it under other
conditions.

In a case related by Stevenson,[224] in which so small a quantity as
1·74 grm. was taken in seven doses, spread over more than forty-eight
hours; there were yet extremely alarming symptoms, and the patient seems
to have had a narrow escape. On the other hand, a woman admitted into
the General Hospital, Vienna, took 100 grms. (about 3½ ozs.) and
recovered; on admission she was in a highly cyanotic condition, with
small pulse, superficial respiration, and dribbling of urine, which
contained nitro-benzol. Artificial respiration was practised, and
camphor injections were administered. Under this treatment consciousness
was restored, and the patient recovered. On the fourth day the urine
resembled that of a case of cystitis (_Lancet_, Jan. 16, 1894). The
quantity of nitro-benzene which would be fatal, if breathed, is not
known with any accuracy.

[224] This case is not uninteresting. Through a mistake in reading an
extremely illegible prescription, M. S. S., æt. 21, was supplied by a
druggist with the following mixture;--

  ℞. Benzole-Nit., ʒiij.
     Ol. Menth, pep., ʒss.
     Ol. Olivæ, ʒx.
     gutt. xxx., t. ds.

He took on sugar seven doses, each of 20 minims, equalling in all 23
min. (or by weight 27·1 grains, 1·74 grm.) of nitro-benzene--viz., three
doses on the first day, three on the second, and one on the morning of
the third day. The first two days he was observed to be looking pale and
ill, but went on with his work until the seventh dose, which he took on
the third day at 9 A.M. About 2 P.M. (or six hours after taking the
seventh dose), he fell down insensible, the body pale blue, and with all
the symptoms already described in the text, and usually seen in
nitro-benzene poisoning. With suitable treatment he recovered. The next
morning, from 8 ounces of urine some nitro-benzene was extracted by
shaking with chloroform.--Thos. Stevenson, M.D., in _Guy’s Hospital
Reports_, MS., vol. xxi., 1876.

§ 244. =Pathological Appearances.=--The more characteristic appearances
seem to be, a dark brown or even black colour of the blood, which
coagulates with difficulty (an appearance of the blood that has even
been noticed during life), venous hyperæmia of the brain and its
membranes, and general venous engorgement. In the stomach, when the
fluid has been swallowed, the mucous membrane is sometimes reddened
diffusely, and occasionally shows ecchymoses of a punctiform character.

§ 245. =The essential action of nitro-benzene= is of considerable
physiological interest. The blood is certainly in some way changed, and
gives the spectrum of acid hæmatin.[225] Filehne has found that the
blood loses, in a great degree, the power of carrying and imparting
oxygen to the tissues, and its content of carbon dioxide is also
increased. Thus, the normal amount of oxygen gas which the arterial
blood of a hound will give up is 17 per cent.; but in the case of a dog
which had been poisoned with nitro-benzene, it sank to 1 per cent.
During the dyspnœa from which the dog suffered, the carbon dioxide
exhaled was greater than the normal amount, and the arterial blood (the
natural content of which should have been 30 per cent. of this gas),
only gave up 9 per cent. Filehne seeks to explain the peculiar colour of
the skin by the condition of the blood, but the explanation is not
altogether satisfactory. Some part of the nitro-benzene, without doubt,
is reduced to aniline in the body--an assertion often made, and as often
contradicted--but it has been found in too many cases to admit of
question. It would also seem from the experiment on the dog (p. 186),
that a conversion into picric acid is not impossible. A yellow colour
of the skin and conjunctivæ, as if picric-acid-stained, has been noticed
in men suffering under slow poisoning by nitro-benzene.

[225] Filehne, W., “_Ueber die Gift-Wirkungen des Nitrobenzols_,” _Arch.
für exper. Pathol. u. Pharm._, ix. 329.

§ 246. =Detection and Separation of Nitro-Benzene from the Animal
Tissues.=--It is evident from the changes which nitro-benzene may
undergo that the expert, in any case of suspected nitro-benzene
poisoning, must specially look (1) for nitro-benzene, (2) for aniline,
and (3) for picric acid. The best general method for the separation of
nitro-benzene is to shake up the liquid (or finely-divided solid) with
light benzoline (petroleum ether), which readily dissolves
nitro-benzene. On evaporation of the petroleum ether, the nitro-benzene
is left, perhaps mixed with fatty matters. On treating with cold water,
the fats rise to the surface, and the nitro-benzene sinks to the bottom;
so that, by means of a separating funnel, the nitro-benzene may be
easily removed from animal fats. The oily drops, or fine precipitate
believed to be nitro-benzene, may be dissolved in spirit and reduced to
aniline by the use of nascent hydrogen, developed from iron filings by
hydrochloric acid, and the fluid tested with bleaching powder, or, the
aniline itself may be recovered by alkalising the fluid, and shaking up
with ether in the separation-tube (p. 156), the ether dissolves the
aniline, and leaves it, on spontaneous evaporation, as an oily yellowish
mass, which, on the addition of a few drops of sodic hypochlorite,
strikes a blue or violet-blue--with acids, a rose-red--and with bromine,
a flesh-red. It gives alkaloidal reactions with such general reagents as
platinum chloride, picric acid, &c. Aniline itself may be extracted from
the tissues and fluids of the body by petroleum ether, but in any
special search it will be better to treat the organs as in Stas’
process--that is, with strong alcohol, acidified with sulphuric acid.
After a suitable digestion in this menstruum, filter, and then, after
evaporating the alcohol, dissolve the alcoholic extract in water;
alkalise the aqueous solution, and extract the aniline by shaking it up
with light benzoline. On separating the benzoline, the aniline will be
left, and may be dissolved in feebly-acid water, and the tests before
enumerated tried.

Malpurgo[226] recommends the following test for nitro-benzene:--2 drops
of melted phenol, 3 drops of water, and a fragment of caustic potash are
boiled in a small porcelain dish, and to the boiling liquid the aqueous
solution to be tested is added. On prolonged boiling, if nitro-benzene
is present, a crimson ring is produced at the edges of the liquid; this
crimson colour, on the addition of a little bleaching powder, turns
emerald-green.

[226] _Zeit. anal. Chem._, xxxii. 235.

Oil of bitter almonds may be distinguished from nitro-benzene by the
action of manganese dioxide and sulphuric acid; bitter almond oil
treated in this way loses its odour, nitro-benzene is unaltered. To
apply the test, the liquid must be heated on the water-bath for a little
time.


XI.--Dinitro-benzol.

§ 247. =Dinitro-benzol=, C₆H₄(NO₂)₂ (ortho-, meta-, para-).--The
ortho-compound is produced by the action of nitric acid on benzol, aided
by heat in the absence of strong sulphuric acid to fix water. Some of
the para-dinitro-benzol is at the same time produced. The meta-compound
is obtained by the action of fuming nitric acid on nitro-benzol at a
boiling temperature.

The physical properties of the three dinitro-benzols are briefly as
follows:--

Ortho-d. is in the form of needles; m.p. 118°.

Meta-d. crystallises in plates; m.p. 90°.

Para-d. crystallises, like the ortho-compound, in needles, but the
melting-point is much higher, 171° to 172°.

Just as nitro-benzol by reduction yields aniline, so do the
nitro-benzols on reduction yield ortho-, meta-, or para-phenylene
diamines.

Meta-phenylene diamine is an excellent test for nitrites; and, since the
commercial varieties of dinitro-benzol either consist mainly or in part
of meta-dinitro-benzol, the toxicological detection is fairly simple,
and is based upon the conversion of the dinitro-benzol into
meta-phenylene-diamine.

Dinitro-benzol is at present largely employed in the manufacture of
explosives, such as roburite, sicherheit, and others. It has produced
much illness among the workpeople in the manufactures, and amongst
miners whose duty it has been to handle such explosives.

§ 248. =Effects of Dinitro-benzol.=--Huber[227] finds that if
dinitro-benzol is given to frogs by the mouth in doses of from 100 to
200 mgrms., death takes place in a few hours. Doses of from 2·5 to 5
mgrms. cause general dulness and ultimately complete paralysis, and
death in from one to six days.

[227] “_Beiträge zur Giftwirkung des Dinitrobenzols_,” A. Huber,
Virchow’s _Archiv_, 1891, Bd. 126, S. 240.

Rabbits are killed by doses of 400 mgrms., in time varying from
twenty-two hours to four days.

In a single experiment on a small dog, the weight of which was 5525
grms., the dog died in six hours after a dose of 600 mgrms.

It is therefore probable that a dose of 100 mgrms. per kilo would kill
most warm-blooded animals.

A transient exposure to dinitro-benzol vapours in man causes serious
symptoms; for instance, in one of Huber’s cases, a student of chemistry
had been engaged for one hour and a half only in preparing
dinitro-benzol, and soon afterwards his comrades remarked that his face
was of a deep blue colour. On admission to hospital, on the evening of
the same day, he complained of slight headache and sleeplessness; both
cheeks, the lips, the muscles of the ear, the mucous membrane of the
lips and cheeks, and even the tongue, were all of a more or less intense
blue-grey colour. The pulse was dicrotic, 124; T. 37·2°. The next
morning the pulse was slower, and by the third day the patient had
recovered.

Excellent accounts of the effects of dinitro-benzol in roburite
factories have been published by Dr. Ross[228] and Professor White,[229]
of Wigan. Mr. Simeon Snell[230] has also published some most interesting
cases of illness, cases which have been as completely investigated as
possible. As an example of the symptoms produced, one of Mr. Snell’s
cases may be here quoted.

[228] _Medical Chronicle_, 1889, 89.

[229] _Practitioner_, 1889, ii. 15.

[230] _Brit. Med. Journ._, March 3, 1894.

[Illustration: Diagram of Visual Field.]

C. F. W., aged 38, consulted Mr. Snell for his defective sight on April
9, 1892. He had been a mixer at a factory for the manufacture of
explosives. He was jaundiced, the conjunctiva yellow, and the lips blue.
He was short of breath, and after the day’s work experienced aching of
the forearms and legs and tingling of the fingers. The urine was black
in colour, of sp. gr. 1024; it was examined spectroscopically by Mr.
MacMunn, who reported the black colour as due neither to indican, nor to
blood, nor bile, but to be caused by some pigment belonging to the
aromatic series. The patient’s sight had been failing since the previous
Christmas. Vision in the right eye was 6/24, left 6/36, both optic
papillæ were somewhat pale. In each eye there was a central scotoma for
red, and contraction of the field (see diagram). The man gradually gave
up the work, and ultimately seems to have recovered. It is, however,
interesting to note that, after having left the work for some weeks, he
went back for a single day to the “mixing,” and was taken very ill,
being insensible and delirious for five hours.

§ 249. =The Blood in Nitro-benzol Poisoning.=--The effect on the blood
has been specially studied by Huber.[231] The blood of rabbits poisoned
by dinitro-benzol is of a dark chocolate colour, and the microscope
shows destruction of the red corpuscles; the amount of destruction may
be gathered from the following:--the blood corpuscles of a rabbit before
the experiment numbered 5,588,000 per cubic centimetre; a day after the
experiment 4,856,000; a day later 1,004,000; on the third day the rabbit
died.

[231] _Op. cit._

In one rabbit, although the corpuscles sank to 1,416,000, yet recovery
took place.

Dr. MacMunn[232] has examined specimens of blood from two of Mr. Snell’s
patients; he found a distinct departure from the normal; the red
corpuscles were smaller than usual, about 5 or 6 µ in diameter, and the
appearances were like those seen in pernicious anæmia. Huber, in some of
his experiments on animals, found a spectroscopic change in the blood,
viz., certain absorption bands, one in the red between C and D, and two
in the green between D and E; the action of reducing agents on this
dinitro-benzol blood, as viewed in a spectroscope provided with a scale
in which C = 48, D = 62, and E = 80·5, was as follows:--

[232] _Op. cit._

                                       Dinitro-Bands.
                                 In Red.        In Green.
                                               -----/\-----
                                  50-52        62-66  70-77
  After NH₄SO₄,                   53-55        62-66  70-77
    „   NH₃,                      54-58        60-65  70-77
    „   NH₄SO₄ + NH₃,             52-55        60-65  70-77

Taking the symptoms as a whole, there has been noted:--a blue colour of
the lips, not unfrequently extending over the whole face, and even the
conjunctivæ have been of a marked blue colour, giving the sufferer a
strange livid appearance. In other cases there have been jaundice, the
conjunctivæ and the skin generally being yellow, the lips blue.
Occasionally gastric symptoms are present. Sleeplessness is common, and
not unfrequently there is some want of muscular co-ordination, and the
man staggers as if drunk. In more than one case there has been noticed
sudden delirium. There is in chronic cases always more or less anæmia,
and the urine is remarkable in its colour, which ranges from a slightly
dark hue up to positive blackness. In a large proportion of cases there
is ophthalmic trouble, the characteristics of which (according to Mr.
Snell) are “failure of sight, often to a considerable degree, in a more
or less equal extent on the two sides; concentric attraction of visual
field with, in many cases, a central colour scotoma; enlargement of
retinal vessels, especially the veins; some blurring, never extensive,
of edges of disc, and a varying degree of pallor of its surface--the
condition of retinal vessels spoken of being observed in workers with
the dinitro-benzol, independently of complaints of defective sight.
Cessation of work leads to recovery.”

§ 250. =Detection of Dinitro-benzol.=--Dinitro-benzol may be detected in
urine, in blood, and in fluids generally, by the following
process:--Place tinfoil in the fluid, and add hydrochloric acid to
strong acidity, after allowing the hydrogen to be developed for at least
an hour, make the fluid alkaline by caustic soda, and extract with ether
in a separating tube; any metaphenylene-diamine will be contained in the
ether; remove the ether into a flask, and distil it off; dissolve the
residue in a little water.

Acidify a solution of sodium nitrite with dilute sulphuric acid; on
adding the solution, if it contains metaphenylene-diamine, a yellow to
red colour will be produced, from the formation of Bismarck brown
(triamido-phenol).


XII.--Hydrocyanic Acid.

§ 251. =Hydrocyanic Acid= (=hydric cyanide=)--specific gravity of liquid
0·7058 at 18° C., boiling-point 26·5° (80° F.), HCy = 27.--The anhydrous
acid is not an article of commerce, and is only met with in the
laboratory. It is a colourless, transparent liquid, and so extremely
volatile that, if a drop fall on a glass plate, a portion of it freezes.
It has a very peculiar peach-blossom odour, and is intensely poisonous.
It reddens litmus freely and transiently, dissolves red oxide of mercury
freely, forms a white precipitate of argentic cyanide when treated with
silver nitrate, and responds to the other tests described hereafter.

§ 252. =Medicinal Preparations of Prussic Acid.=--The B.P. acid is a
watery solution of prussic acid; its specific gravity should be 0·997,
and it should contain 2 per cent. of the anhydrous acid, 2 per cent. is
also the amount specified in the pharmacopœias of Switzerland and
Norway, and in that of Borussica (VI. ed.); the latter ordains, however,
a spirituous solution, and the Norwegian an addition of 1 per cent. of
concentrated sulphuric acid. The French prussic acid is ordered to be
prepared of a strength equalling 10 per cent.

The adulterations or impurities of prussic acid are hydrochloric,
sulphuric,[233] and formic acids. Traces of silver may be found in the
French acid, which is prepared from cyanide of silver. Tartaric acid is
also occasionally present. Hydrochloric acid is most readily detected by
neutralising with ammonia, and evaporating to dryness in a water-bath;
the ammonium cyanide decomposes and volatilises, leaving as a saline
residue chloride of ammonium. This may easily be identified by the
precipitate of chloride of silver, which its solution gives on testing
with silver nitrate, and the deep brown precipitate with Nessler
solution. Sulphuric acid is, of course, detected by chloride of barium;
formic acid by boiling a small quantity with a little mercuric oxide; if
present, the oxide will be reduced, and metallic mercury fall as a grey
precipitate. Silver, tartaric acid, and any other fixed impurities are
detected by evaporating the acid to dryness, and examining any residue
which may be left. It may be well to give the various strengths of the
acids of commerce in a tabular form:--

[233] A trace of sulphuric or hydrochloric acid should not be called an
_adulteration_, for it greatly assists the preservation, and therefore
makes the acid of greater therapeutic efficiency.

                                                            Per cent.

  British Pharmacopœia, Switzerland, and Bor. (vj),            2
  France,                                                     10
  Vauquelin’s Acid,                                            3·3
  Scheele’s    „                                          4 to 5[234]
  Riner’s      „                                              10
  Robiquet’s   „                                              50
  Schraeder’s  „                                               1·5
  Duflos’      „                                               9
  Pfaff’s      „                                              10
  Koller’s     „                                              25

[234] Strength very uncertain.

In English commerce, the analyst will scarcely meet with any acid
stronger than Scheele’s 5 per cent.

Impure oil of bitter almonds contains hydric cyanide in variable
quantity, from 5 per cent. up to 14 per cent. There is an officinal
preparation obtained by digesting cherry-laurel leaves in water, and
then distilling a certain portion over. This _Aqua Lauro-cerasi_ belongs
to the old school of pharmacy, and is of uncertain strength, but varies
from ·7 to 1 per cent. of HCN.

§ 253. =Poisoning by Prussic Acid.=--Irrespective of suicidal or
criminal poisoning, accidents from prussic acid may occur--

1. From the use of the cyanides in the arts.

2. From the somewhat extensive distribution of the acid, or rather of
prussic-acid producing substances in the vegetable kingdom.

1. =In the Arts.=--The galvanic silvering[235] and gilding of metals,
photography, the colouring of black silks, the manufacture of Berlin
blue, the dyeing of woollen cloth, and in a few other manufacturing
processes, the alkaline cyanides are used, and not unfrequently fumes of
prussic acid developed.

[235] The preparation used for the silvering of copper vessels is a
solution of cyanide of silver in potassic cyanide, to which is added
finely powdered chalk. Manipulations with this fluid easily develop
hydrocyanic acid fumes, which, in one case related by Martin (_Aerztl.
Intelligenzbl._, p. 135, 1872), were powerful enough to produce symptoms
of poisoning.

2. =In the Animal Kingdom.=--One of the myriapods (_Chilognathen_)
contains glands at the roots of the hairs, which secrete prussic acid;
when the insect is seized, the poisonous secretion is poured out from
the so-called _foramina repugnatoria_.

3. =In the Vegetable Kingdom.=--A few plants contain cyanides, and many
contain amygdalin, or bodies formed on the type of amygdalin. In the
presence of emulsin (or similar principles) and water, this breaks up
into prussic acid and other compounds--an interesting reaction usually
represented thus--

  C₂₀H₂₇NO₁₁ + 2H₂O = CNH + C₇H₆O + 2C₆H₁₂O₆.

1 equivalent of amygdalin--_i.e._, 457 parts--yielding 1 equivalent of
CNH or 27 parts; in other words, 100 parts of amygdalin yield
theoretically 5·909 parts of prussic acid,[236] so that, the amount of
either being known, the other can be calculated from it.

[236] According to Liebig and Wöhler, 17 grms. of amygdalin yield 1 of
prussic acid (_i.e._, 5·7 per cent.) and 8 of oil of bitter almonds.
Thirty-four parts of amygdalin, mixed with 66 of emulsin of almonds,
give a fluid equalling the strength of acid of most pharmacopœias, viz.,
2 per cent.

Greshoff[237] has discovered an amygdalin-like glucoside in the two
tropical trees _Pygeum parriflorum_ and _P. latifolium_. The same author
states that the leaves of _Gymnema latifolium_, one of the Asclepiads,
yields to distillation benzaldehyde hydrocyanide. Both _Lasia_ and
_Cyrtosperma_, plants belonging to the natural family of the Orontads,
contain in their flowers potassic cyanide. _Pangium edule_, according to
Greshoff, contains so much potassic cyanide that he was able to prepare
a considerable quantity of that salt from one sample of the plant. An
Indian plant (_Hydnocarpus inebrians_) also contains a cyanide, and has
been used for the purpose of destroying fish. Among the Tiliads,
Greshoff found that _Echinocarpus Sigun_ yielded hydrocyanic acid on
distillation. Even the common linseed contains a glucoside which breaks
up into sugar, prussic acid, and a ketone.

[237] M. Greshoff--_Erster Bericht über die Untersuchung von
Pflanzenstoffen Niederländisch-Indiens. Mittheilungen aus dem
chemisch-pharmakologischen Laboratorium des botan. Gartens des Staates_,
vii., Batavia, 1890, Niederländisch. Dr. Greshoff’s research indicates
that there are several other cyanide-yielding plants than those
mentioned in the text.

The following plants, with many others, all yield, by appropriate
treatment, more or less prussic acid:--Bitter almonds (_Amygdalus
communis_); the _Amygdalus persica_; the cherry laurel (_Prunus
laurocerasus_); the kernels of the plum (_Prunus domestica_); the bark,
leaves, flowers, and fruit of the wild service-tree (_Prunus padus_);
the kernels of the common cherry and the apple; the leaves of the
_Prunus capricida_; the bark of the _Pr. virginiana_; the flowers and
kernels of the _Pr. spinosa_; the leaves of the _Cerasus acida_; the
bark and almost all parts of the _Sorbus aucuparia_, _S. hybrida_, and
_S. torminalis_; the young twigs of the _Cratægus oxyacantha_; the
leaves and partly also the flowers of the shrubby _Spiræaceæ_, such as
_Spiræa aruncus_, _S. sorbifolia_, and _S. japonica_;[238] together with
the roots of the bitter and sweet _Cassava_.

[238] The bark and green parts of the _Prunus avium_, L., _Prunus
mahaleb_, L., and herbaceous _Spirææ_ yield no prussic acid.

In only a few of these, however, has the exact amount of either prussic
acid or amygdalin been determined; 1 grm. of bitter almond pulp is about
equal to 2½ mgrms. of anhydrous prussic acid. The kernels from the
stones of the cherry, according to Geiseler, yield 3 per cent. of
amygdalin; therefore, 1 grm. equals 1·7 mgrm. of HCN.

§ 254. The wild service-tree (_Prunus padus_) and the cherry-laurel
(_Prunus Laurocerasus_) contain, not amygdalin but a compound of
amygdalin with amygdalic acid; to this has been given the name of
laurocerasin. It was formerly known as amorphous amygdalin; its formula
is C₄₀H₅₅NO₂₄; 933 parts are equivalent to 27 of hydric cyanide--that
is, 100 parts equal to 2·89.

In the bark of the service-tree, Lehmann found ·7 per cent. of
laurocerasin (= ·02 HCN), and in the leaves of the cherry-laurel 1·38
per cent. (= 0·39 HCN).

Francis,[239] in a research on the prussic acid in cassava root, gives
as the mean in the sweet cassava ·0168 per cent., in the bitter ·0275
per cent., the maximum in each being respectively ·0238 per cent., and
·0442 per cent. The bitter-fresh cassava root has long been known as a
very dangerous poison; but the sweet has hitherto been considered
harmless, although it is evident that it also contains a considerable
quantity of prussic acid.

[239] “On Prussic Acid from Cassava,” _Analyst_, April 1877, p. 5.

The kernels of the peach contain about 2·85 per cent. amygdalin (= ·17
HCN); those of the plum ·96 per cent. (= ·056 HCN); and apple pips ·6
per cent. (= ·035 per cent. HCN).

It is of great practical value to know, even approximately, the quantity
of prussic acid contained in various fruits, since it has been adopted
as a defence in criminal cases that the deceased was poisoned by prussic
acid developed in substances eaten.

§ 255. =Statistics.=--Poisoning by the cyanides (prussic acid or
cyanide of potassium) occupies the third place among poisons in order
of frequency in this country, and accounts for about 40 deaths annually.

In the ten years ending 1892 there were recorded no less than 395 cases
of accidental, suicidal, or homicidal poisoning by prussic acid and
potassic cyanide. The further statistical details may be gathered from
the following tables:--

DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS 1883-1892 FROM PRUSSIC
ACID AND POTASSIC CYANIDE.

           PRUSSIC ACID (ACCIDENT OR NEGLIGENCE).

  Ages,       0-1  1-5  5-15  15-25  25-65  65 and  Total
                                            above
  Males,      ...    1    1      1     12      1      16
  Females,      1    1  ...      2      7    ...      11
             --------------------------------------------
  Totals,       1    2    1      3     19      1      27
             --------------------------------------------

       CYANIDE OF POTASSIUM (ACCIDENT OR NEGLIGENCE).

  Ages,            1-5  5-15  15-25  25-65  65 and  Total
                                            above
  Males,             1    1      4      1    ...       7
  Females,           1  ...    ...      3    ...       4
                  ---------------------------------------
  Totals,            2    1      4      4    ...      11
                  ---------------------------------------

                   PRUSSIC ACID (SUICIDE).

  Ages,                       15-25  25-65  65 and  Total
                                            above
  Males,                        23    156     23     202
  Females,                       5     13      1      19
                             ----------------------------
  Totals,                       28    169     24     221
                             ----------------------------

                  POTASSIUM CYANIDE (SUICIDE).

  Ages,                 5-15  15-25  25-65  65 and  Total
                                            above
  Males,                  1      6     88      5     100
  Females,              ...      6     15      1      22
                       ----------------------------------
  Totals,                 1     12    103      6     122
                       ----------------------------------

To these figures must be added 10 cases of murder (2 males and 8
females) by prussic acid, and 4 cases of murder (3 males and 1 female)
by potassic cyanide.

In order to ascertain the proportion in which the various forms of
commercial cyanides cause death, and also the proportion of accidental,
suicidal, and criminal deaths from the same cause, Falck collated twelve
years of statistics from medical literature with the following result:--

In 51 cases of cyanide poisoning, 29 were caused by potassic cyanide, 9
by hydric cyanide, 5 by oil of bitter almonds, 3 by peach stones (these
3 were children, and are classed as “domestic,” that is, taking the
kernels as a food), 3 by bitter almonds (1 of the 3 suicidal and
followed by death, the other 2 “domestic”), 1 by tartaric acid and
potassic cyanide (a suicidal case, an apothecary), and 1 by
ferro-cyanide of potassium and tartaric acid. Of the 43 cases first
mentioned, 21 were suicidal, 7 criminal, 8 domestic, and 7 medicinal;
the 43 patients were 24 men, 14 children, and 5 women.

The cyanides are very rarely used for the purpose of murder: a poison
which has a strong smell and a perceptible taste, and which also kills
with a rapidity only equalled by deadly bullet or knife-wounds, betrays
its presence with too many circumstances of a tragic character to find
favour in the dark and secret schemes of those who desire to take life
by poison. In 793 poisoning cases of a criminal character in France, 4
only were by the cyanides.

Hydric and potassic cyanides were once the favourite means of
self-destruction employed by suicidal photographers, chemists,
scientific medical men, and others in positions where such means are
always at hand; but, of late years, the popular knowledge of poisons has
increased, and self-poisoning by the cyanides scarcely belongs to a
particular class. A fair proportion of the deaths are also due to
accident or unfortunate mistakes, and a still smaller number to the
immoderate or improper use of cyanide-containing vegetable products.

§ 256. =Accidental and Criminal Poisoning by Prussic Acid.=--The poison
is almost always taken by the mouth into the stomach, but occasionally
in other ways--such, for example, as in the case of the illustrious
chemist, Scheele, who died from inhalation of the vapour of the acid
which he himself discovered, owing to the breaking of a flask. There is
also the case related by Tardieu, in which cyanide of potassium was
introduced under the nails; and that mentioned by Carrière,[240] in
which a woman gave herself, with suicidal intent, an enema containing
cyanide of potassium. It has been shown by experiments, in which every
care was taken to render it impossible for the fumes to be inhaled, that
hydrocyanic acid applied to the eye of warm-blooded animals may destroy
life in a few minutes.[241]

[240] “_Empoisonnement par le cyanure de potassium,--guérison_,”
_Bullet. général de Thérap._, 1869, No. 30.

[241] N. Gréhant, _Compt. rend. Soc. Biol._ [9], xi. 64, 65.

With regard to errors in dispensing, the most tragic case on record is
that related by Arnold:[242]--A pharmaceutist had put in a mixture for a
child potassic cyanide instead of potassic chlorate, and the child died
after the first dose: the chemist, however, convinced that he had made
no mistake, to show the harmlessness of the preparation, drank some of
it, and there and then died; while Dr. Arnold himself, incautiously
tasting the draught, fell insensible, and was unconscious for six hours.

[242] Arnold, A. B., “Case of Poisoning by the Cyanide of Potassium,”
_Amer. Journ. of Med. Scien._, 1869.

§ 257. =Fatal Dose.=--Notwithstanding the great number of persons who in
every civilised country fall victims to the cyanides, it is yet somewhat
doubtful what is the minimum dose likely to kill an adult healthy man.
The explanation of this uncertainty is to be sought mainly in the
varying strength of commercial prussic acid, which varies from 1·5
(Schraeder’s) to 50 per cent. (Robiquet’s), and also in the varying
condition of the person taking the poison, more especially whether the
stomach be full or empty. In by far the greater number, the dose taken
has been much beyond that necessary to produce death, but this
observation is true of most poisonings.

The dictum of Taylor, that a quantity of commercial prussic acid,
equivalent to 1 English grain (65 mgrm.) of the anhydrous acid, would,
under ordinary circumstances, be sufficient to destroy adult life, has
been generally accepted by all toxicologists. The minimum lethal dose of
potassic cyanide is similarly put at 2·41 grains (·157 grm.). As to
bitter almonds, if it be considered that as a mean they contain 2·5 per
cent. of amygdalin, then it would take 45 grms., or about 80 almonds, to
produce a lethal dose for an adult; with children less--in fact, 4 to 6
bitter almonds are said to have produced poisoning in a child.

§ 258. =Action of Hydric and Potassic Cyanides on Living
Organisms.=--Both hydric cyanide and potassic cyanide are poisonous to
all living forms, vegetable or animal, with the exception of certain
fungi. The cold-blooded animals take a larger relative dose than the
warm-blooded, and the mammalia are somewhat more sensitive to the
poisonous action of the cyanides than birds; but all are destroyed in a
very similar manner, and without any essential difference of action. The
symptoms produced by hydric and potassic cyanide are identical, and, as
regards general symptoms, what is true as to the one is also true as to
the other. There is, however, one important difference in the action of
these two substances, if the mere local action is considered, for
potassic cyanide is very alkaline, possessing even caustic properties. I
have seen, _e.g._, the gastric mucous membrane of a woman, who had taken
an excessive dose of potassic cyanide on an empty stomach, so inflamed
and swollen, that its state was similar to that induced by a moderate
quantity of solution of potash. On the other hand, the acid properties
of hydric cyanide are very feeble, and its effect on mucous membranes or
the skin in no way resembles that of the mineral acids.

It attacks the animal system in two ways: the one, a profound
interference with the ordinary metabolic changes; the other, a paralysis
of the nervous centres. Schönbein discovered that it affected the blood
corpuscles in a peculiar way; normal blood decomposes with great ease
hydrogen peroxide into oxygen and water. If to normal venous blood a
little peroxide of hydrogen be added, the blood at once becomes bright
red; but if a trace of prussic acid be present, it is of a dark brown
colour. The blood corpuscles, therefore, lose their power of conveying
oxygen to all parts of the system, and the phenomena of asphyxia are
produced. Geppert[243] has proved that this is really the case by
showing, in a series of researches, that, under the action of hydric
cyanide, less oxygen is taken up, and less carbon dioxide formed than
normal, even if the percentage of oxygen in the atmosphere breathed is
artificially increased. The deficiency of oxygen is in part due to the
fact that substances like lactic acid, the products of incomplete
combustion, are formed instead of CO₂.

[243] Geppert, _Ueber das Wesen der CNH-Vergift; mit einer Tafel_,
Berlin, 1889; _Sep.-Abdr. aus Ztschr. f. klin. Med._, Bd. xv.

At the same time the protoplasm of the tissues is paralysed, and unable
to take up the loosely bound oxygen presented. This explains a striking
symptom which has been noticed by many observers, that is, if
hydrocyanic acid be injected into an animal, the venous blood becomes of
a bright red colour; in warm-blooded animals this bright colour is
transitory, but in cold-blooded animals, in which the oxidation process
is slower, the blood remains bright red.

§ 259. =Symptoms observed in Animals.=--The main differences between the
symptoms induced in cold-blooded and warm-blooded animals, by a fatal
dose of hydric cyanide, are as follows:--

The respiration in frogs is at first somewhat dyspnœic, then much
slowed, and at length it ceases. The heart, at first slowed, later
contracts irregularly, and at length gradually stops; but it may
continue to beat for several minutes after the respiration has ceased.
But all these progressive symptoms are without convulsion. Among
warm-blooded animals, on the contrary, convulsions are constant, and the
sequence of the symptoms appears to be--dyspnœa, slowing of the pulse,
giddiness, falling down, then convulsions with expulsion of the urine
and fæces; dilatation of the pupils, exophthalmus, and finally cessation
of the pulse and breathing. The convulsions also frequently pass into
general paralysis, with loss of reflex movements, weak, infrequent
breathing, irregular, quick, and very frequent pulse, and considerable
diminution of temperature.

The commencement of the symptoms in animals is extremely rapid, the
rapidity varying according to the dose and the concentration of the
acid. It was formerly thought that the death from a large dose of the
concentrated acid followed far more quickly than could be accounted for
by the blood carrying the poison to the nervous centres; but Blake was
among the first to point out that this doubt was not supported by facts
carefully observed, since there is always a sufficient interval between
the entry of the poison into the body and the first symptoms, to support
the theory that the poison is absorbed in the usual manner. Even when
Preyer injected a cubic centimetre of 60 per cent. acid into the jugular
vein of a rabbit, twenty-nine seconds elapsed before the symptoms
commenced. Besides, we have direct experiments showing that the
acid--when applied to wounds in limbs, the vessels of which are tied,
while the free nervous communication is left open--only acts when the
ligature is removed. Magendie describes, in his usual graphic manner,
how he killed a dog by injecting into the jugular vein prussic acid, and
“_the dog died instantly, as if struck by a cannon ball_,” but it is
probable that the interval of time was not accurately noted. A few
seconds pass very rapidly, and might be occupied even by slowly pressing
the piston of the syringe down, and in the absence of accurate
measurements, it is surprising how comparatively long intervals of time
are unconsciously shortened by the mind. In any case, this observation
by Magendie has not been confirmed by the accurate tests of the more
recent experimenters; and it is universally acknowledged that, although
with strong doses of hydric cyanide injected into the circulation--or,
in other words, introduced into the system--in the most favourable
conditions for its speediest action, death occurs with appalling
suddenness, yet that it takes a time sufficiently long to admit of
explanation in the manner suggested. This has forensic importance, which
will be again alluded to. Experiments on animals show that a large dose
of a dilute acid kills quite as quickly as an equivalent dose of a
stronger acid, and in some cases it even seems to act more rapidly. If
the death does not take place within a few minutes, life may be
prolonged for hours, and even, in rare cases, days, and yet the result
be death. Coullon poisoned a dog with prussic acid; it lived for
nineteen days, and then died; but this is quite an exceptional case, and
when the fatal issue is prolonged beyond an hour, the chance of recovery
is considerable.

§ 260. The length of time dogs poisoned by fatal doses survive,
generally varies from two to fifteen minutes. The symptoms are
convulsions, insensibility of the cornea, cessation of respiration, and,
finally, the heart stops--the heart continuing to beat several minutes
after the cessation of the respirations.[244] When the dose is short of
a fatal one, the symptoms are as follows:--Evident giddiness and
distress; the tongue is protruded, the breath is taken in short, hurried
gasps, there is salivation, and convulsions rapidly set in, preceded, it
may be, by a cry. The convulsions pass into paralysis and insensibility.
After remaining in this state some time, the animal again wakes up, as
it were, very often howls, and is again convulsed; finally, it sinks
into a deep sleep, and wakes up well.

[244] N. Gréhant, _Compt. rend._, t. 109, pp. 502, 503.

Preyer noticed a striking difference in the symptoms after section of
the vagus in animals, which varied according to whether the poison was
administered by the lungs, or subcutaneously. In the first case, if the
dose is small, the respirations are diminished in frequency; then this
is followed by normal breathing; if the dose is larger, there is an
increase in the frequency of the respirations. Lastly, if a very large
quantity is introduced into the lungs, death quickly follows, with
respirations diminished in frequency. On the other hand, when the poison
is injected subcutaneously, small doses have no influence on the
breathing; but with large doses, there is an increase in the frequency
of the respirations, which sink again below the normal standard.

§ 261. =Symptoms in Man.=--When a fatal but not excessive dose of either
potassic or hydric cyanide is taken, the sequence of symptoms is as
follows:--Salivation, with a feeling of constriction in the throat,
nausea, and occasionally vomiting. After a few minutes a peculiar
constricting pain in the chest is felt, and the breathing is distinctly
affected. Giddiness and confusion of sight rapidly set in, and the
person falls to the ground in convulsions similar to those of epilepsy.
The convulsions are either general, or attacking only certain groups of
muscles; there is often true trismus, and the jaws are so firmly closed
that nothing will part them. The respiration is peculiar, the
inspiration is short, the expiration prolonged,[245] and between the two
there is a long interval ever becoming more protracted as death is
imminent. The skin is pale, or blue, or greyish-blue; the eyes are
glassy and staring, with dilated pupils; the mouth is covered with foam,
and the breath smells of the poison; the pulse, at first quick and
small, sinks in a little while in frequency, and at length cannot be
felt. Involuntary evacuation of fæces, urine, and semen is often
observed, and occasionally there has been vomiting, and a portion of the
vomit has been aspirated into the air-passages. Finally, the convulsions
pass into paralysis, abolition of reflex sensibility, and gradual
ceasing of the respiration. With large doses these different stages may
occur, but the course is so rapid that they are merged the one into the
other, and are undistinguishable. The shortest time between the taking
of the acid and the commencement of the symptoms may be put at about ten
seconds. If, however, a large amount of the vapour is inhaled at once,
this period may be rather lessened. The interval of time is so short
that any witnesses generally unintentionally exaggerate, and aver that
the effects were witnessed _before_ the swallowing of the liquid--“As
the cup was at his lips”--“He had hardly drunk it,” &c. There is
probably a short interval of consciousness, then come giddiness, and, it
may be, a cry for assistance; and lastly, there is a falling down in
convulsions, and a speedy death. Convulsions are not always present, the
victim occasionally appears to sink lifeless at once. Thus, in a case
related by Hufeland, a man was seen to swallow a quantity of acid,
equivalent to 40 grains of the pure acid--that is, about forty times
more than sufficient to kill him. He staggered a few paces, and then
fell dead, without sound or convulsion.

[245] In a case quoted by Seidel (Maschka’s _Handbuch_, p. 321), a man,
36 years of age, four or five minutes after swallowing 150 mgrms.
anhydrous HCN in spirits, lay apparently lifeless, without pulse or
breathing. After a few minutes was noticed an extraordinary deep
expiration, by which the ribs were drawn in almost to the spine, and the
chest made quite hollow.

§ 262. The very short interval that may thus intervene between the
taking of a dose of prussic acid and loss of consciousness, may be
utilised by the sufferer in doing various acts, and thus this interval
becomes of immense medico-legal importance. The question is simply
this:--What can be done by a person in full possession of his faculties
in ten seconds? I have found from experiment that, after drinking a
liquid from a bottle, the bottle may be corked, the individual can get
into bed, and arrange the bedclothes in a suitable manner; he may also
throw the bottle away, or out of the window; and, indeed, with practice,
in that short time a number of rapid and complicated acts may be
performed. This is borne out both by experiments on animals and by
recorded cases.

In Mr. Nunneley’s numerous experiments on dogs, one of the animals,
after taking poison, “went down three or four steps of the stairs, saw
that the door at the bottom was closed, and came back again.” A second
went down, came up, and went again down the steps of a long winding
staircase, and a third retained sufficient vigour to jump over another
dog, and then leap across the top of a staircase.

In a remarkable case related by Dr. Guy,[246] in which a young man,
after drinking more wine than usual, was seized by a sudden impulse to
take prussic acid, and drank about 2 drachms, producing symptoms which,
had it not been for prompt treatment, would, in all probability, have
ended fatally--the interval is again noteworthy. After taking the poison
in bed, he rose, walked round the foot of a chest of drawers, standing
within a few yards of the bedside, placed the stopper firmly in the
bottle, and then walked back to bed with the intention of getting into
it; but here a giddiness seized him, and he sat down on the edge, and
became insensible.

[246] _Forensic Medicine_, 4th ed., p. 615.

A case related by Taylor is still stronger. A woman, after swallowing a
fatal dose of essence of almonds, went to a well in the yard, drew
water, and drank a considerable quantity. She then ascended two flights
of stairs and called her child, again descended a flight of stairs, fell
on her bed, and died within half an hour from the taking of the poison.

Nevertheless, these cases and similar ones are exceptional, and only
show what is possible, not what is usual, the rule being that after
fatal doses no voluntary act of significance--save, it may be, a cry
for assistance--is performed.[247]

[247] Dr. J. Autal, a Hungarian chemist, states that cobalt nitrate is
an efficacious antidote to poisoning by either HCN or KCN. The brief
interval between the taking of a fatal dose and death can, however, be
rarely utilised.--_Lancet_, Jan. 16, 1894.

§ 263. =Chronic poisoning by hydric cyanide= is said to occur among
photographers, gilders, and those who are engaged daily in the
preparation or handling of either hydric or potassic cyanides. The
symptoms are those of feeble poisoning, headache, giddiness, noises in
the ears, difficult respiration, pain over the heart, a feeling of
constriction in the throat, loss of appetite, nausea, obstinate
constipation, full pulse, with pallor and offensive breath.
Koritschoner[248] has made some observations on patients who were made
to breathe at intervals, during many weeks, prussic acid vapour, with
the idea that such a treatment would destroy the tubercle bacilli.
Twenty-five per cent. of those treated in this way suffered from redness
of the pharynx, salivation, headache, nausea, vomiting, slow pulse, and
even albuminuria.

[248] _Wiener klin. Woch._, 1891.

§ 264. =Post-mortem Appearances.=[249]--If we for the moment leave out
of consideration any changes which may be seen in the stomach after
doses of potassic cyanide, then it may be affirmed that the pathological
changes produced by hydric and potassic cyanides mainly coincide with
those produced by suffocation. The most striking appearance is the
presence of bright red spots; these bright red spots or patches are
confined to the surface of the body, the blood in the deeper parts being
of the ordinary venous hue, unless, indeed, an enormous dose has been
taken; in that case the whole mass of blood may be bright red; this
bright colour is due, according to Kobert, to the formation of
cyanmethæmoglobin. The lungs and right heart are full of blood, and
there is a backward engorgement produced by the pulmonic block. The
veins of the neck and the vessels of the head generally are full of
blood, and, in like manner, the liver and kidneys are congested. In the
mucous membrane of the bronchial tubes there is a bloody foam, the lungs
are gorged, and often œdematous in portions; ecchymoses are seen in the
pleura and other serous membranes; and everywhere, unless concealed by
putrefaction, or some strong-smelling ethereal oil, there is an odour of
hydric cyanide.

[249] Hydric cyanide has, according to C. Brame, a remarkable antiseptic
action, and if administered in sufficient quantity to animals, preserves
them after death for a month. He considers that there is some more or
less definite combination with the tissues.

Casper has rightly recommended the head to be opened and examined first,
so as to detect the odour, if present, in the brain. The abdominal and
chest cavities usually possess a putrefactive smell, but the brain is
longer conserved, so that, if this course be adopted, there is a greater
probability of detecting the odour.

The stomach in poisoning by hydric cyanide is not inflamed, but if
alcohol has been taken at the same time, or previously, there may be
more or less redness.

In poisoning by potassic cyanide, the appearances are mainly the same as
those just detailed, with, it may be, the addition of caustic local
action. I have, however, seen, in the case of a gentleman who drank
accidentally a considerable dose of potassic cyanide just after a full
meal, not the slightest trace of any redness, still less of corrosion.
Here the contents of the stomach protected the mucous membrane, or
possibly the larger amount of acid poured out during digestion
sufficiently neutralised the alkali. Potassic cyanide, in very strong
solution, may cause erosions of the lips, and the caustic effect may be
traced in the mouth, throat, gullet, to the stomach and duodenum; but
this is unusual, and the local effects are, as a rule, confined to the
stomach and duodenum. The mucous membrane is coloured blood-red, reacts
strongly alkaline,[250] is swollen, and it may be even ulcerated. The
upper layers of the epithelium are also often dyed with the
colouring-matter of the blood, which has been dissolved out by the
cyanide. This last change is a _post-mortem_ effect, and can be imitated
by digesting the mucous membrane of a healthy stomach in a solution of
cyanide. The intensity of these changes are, of course, entirely
dependent on the dose and emptiness of the stomach. If the dose is so
small as just to destroy life, there may be but little redness or
swelling of the stomach, although empty at the time of taking the
poison. In those cases in which there has been vomiting, and a part of
the vomit has been drawn into the air-passages, there may be also
inflammatory changes in the larynx. If essence of almonds has been
swallowed, the same slight inflammation may be seen which has been
observed with other essential oils, but no erosion, no strong alkaline
reaction, nor anything approaching the effects of the caustic cyanide.

[250] The following case came under my own observation:--A stout woman,
35 years of age, the wife of a French polisher, drank, in a fit of rage,
a solution of cyanide of potassium. It was estimated that about 15
grains of the solid substance were swallowed. She died within an hour.
The face was flushed, the body not decomposed; the mouth smelt strongly
of cyanide; the stomach had about an ounce of bloody fluid in it, and
was in a most intense state of congestion. There was commencing fatty
degeneration of the liver, the kidneys were flabby, and the capsule
adherent. The contents of the stomach showed cyanide of potassium, and
the blood was very fluid. The woman was known to be of intemperate
habits.

In poisoning by bitter almonds no inflammatory change in the mucous
membrane of the coats of the stomach would be anticipated, yet in one
recorded case there seems to have been an eroded and inflamed patch.

§ 265. =Tests for Hydrocyanic Acid and Cyanide of Potassium.=--(1.) The
addition of silver nitrate to a solution containing prussic acid, or a
soluble cyanide,[251] produces a precipitate of argentic cyanide. 100
parts of argentic cyanide are composed of 80·60 Ag and 19·4 CN,
equivalent to 20·1 HCN. It is a white anhydrous precipitate, soluble
either in ammonia or in a solution of cyanide of potassium. It is
soluble in hot dilute nitric acid, but separates on cooling. A particle
of silver cyanide, moistened with strong ammonia, develops needles;
silver chloride treated similarly, octahedral crystals. It is insoluble
in water. Upon ignition it is decomposed into CN and metallic silver,
mixed with a little paracyanide of silver.

[251] In the case of testing in this way for the alkaline cyanides, the
solution must contain a little free nitric acid.

A very neat process for the identification of cyanide of silver is the
following:--Place the perfectly dry cyanide in a closed or sealed tube,
containing a few crystals of iodine. On heating slightly, iodide of
cyanogen is sublimed in beautiful needles. These crystals again may be
dissolved in a dilute solution of potash, a little ferrous sulphate
added, and hydrochloric acid, and in this way Prussian blue produced. If
the quantity to be tested is small, the vapour of the acid may be
evolved in a very short test-tube, the mouth of which is closed by the
ordinary thin discs of microscopic glass, the under surface of which is
moistened with a solution of nitrate of silver; the resulting crystals
of silver cyanide are very characteristic, and readily identified by the
microscope.

(2.) If, instead of silver nitrate, the disc be moistened with a
solution of sulphate of iron (to which has been added a little potash),
and exposed to the vapour a short time, and then some dilute
hydrochloric acid added, the moistened surface first becomes yellow,
then green, lastly, and permanently, blue. No other blue compound of
iron (with the exception of Prussian blue) is insoluble in dilute
hydrochloric acid.

(3.) A third, and perhaps the most delicate of all, is the so-called
sulphur test. A yellow sulphide of ammonium, containing free sulphur, is
prepared by saturating ammonia by SH₂, first suspending in the fluid a
little finely-precipitated sulphur (or an old, ill-preserved solution of
sulphide of ammonium may be used). Two watch-glasses are now taken; in
the one the fluid containing prussic acid is put, and the second
(previously moistened with the sulphide of ammonium described) is
inverted over it. The glasses are conveniently placed for a few minutes
in the water-oven; the upper one is then removed, the moist surface
evaporated to dryness in the water-bath, a little water added, and then
a small drop of solution of chloride of iron. If hydrocyanic acid is
present, the sulphocyanide of iron will be formed of a striking
blood-red colour.

(4.) The reaction usually called Schönbein’s, or Pagenstecher and
Schönbein’s[252] (but long known,[253] and used before the publication
of their paper), consists of guaiacum paper, moistened with a very
dilute solution of sulphate of copper (1 : 2000). This becomes blue if
exposed to the vapour of hydrocyanic acid. Unfortunately, the same
reaction is produced by ammonia, ozone, nitric acid, hypochlorous acid,
iodine, bromine, chromate of potash, and other oxidising agents, so that
its usefulness is greatly restricted.

[252] _Neues Repert. de Pharm._, 18, 356.

[253] This reaction (with tincture of guaiacum and copper) has been long
known. “I remember a pharmaceutist, who attended my father’s laboratory,
showing me this test in 1828 or 1829.”--Mohr’s _Toxicologie_, p. 92.

(5.) A very delicate test for prussic acid is as follows:--About
one-half centigrm. of ammonia, ferrous sulphate (or other pure ferrous
salt), and the same quantity of uranic nitrate, are dissolved in 50 c.c.
of water, and 1 c.c. of this test-liquid is placed in a porcelain dish.
On now adding a drop of a liquid containing the smallest quantity of
prussic acid, a grey-purple colour, or a distinct purple precipitate is
produced.[254]

[254] M. Carey Lea, _Amer. Journ. of Science_ [3], ix. pp. 121-123; _J.
C. Society_, 1876, vol. i. p. 112.

(6.) A hot solution of potassic cyanide, mixed with picric acid, assumes
a blood-red colour, due to the formation of picro-cyanic acid. Free HCN
does not give this reaction, and therefore must first be neutralised by
an alkali.

(7.) =Schönbein’s Test.=--To a few drops of defibrinated ox-blood are
added a few drops of the carefully-neutralised distillate supposed to
contain prussic acid, and then a little neutral peroxide of hydrogen is
added. If the distillate contains no prussic acid, then the mixture
becomes of a bright pure red and froths strongly; if, on the other hand,
a trace of prussic acid be present, the liquid becomes brown and does
not froth, or only slightly does so.

(8.) =Kobert’s Test.=--A 1-4 per cent. solution of blood, to which a
trace of ferridcyanide of potassium is added, is prepared, and the
neutralised distillate added to this solution. If hydric cyanide be
present, then the liquid becomes of a bright red colour, and, examined
spectroscopically, instead of the spectrum of methæmoglobin, will be
seen the spectrum of cyanmethæmoglobin. Kobert proposes to examine the
blood of the poisoned, for the purpose of diagnosis, during life. A drop
of blood from a healthy person, and a drop of blood from the patient,
are examined side by side, according to the process just given.

§ 266. =Separation of Hydric Cyanide or Potassic Cyanide from Organic
Matters, such as the Contents of the Stomach, &c.=--It is very
necessary, before specially searching for hydric cyanide in the contents
of the stomach, to be able to say, by careful and methodical
examination, whether there are or are not any fragments of bitter
almonds, of apples, peaches, or other substance likely to produce hydric
cyanide. If potassic cyanide has been taken, simple distillation will
always reveal its presence, because it is found partly decomposed into
hydric cyanide by the action of the gastric acids. Nevertheless, an acid
should always be added, and if, as in the routine process given at p.
48, there is reasonable doubt for suspecting that there will be no
cyanide present, it will be best to add tartaric acid (for this organic
acid will in no way interfere with subsequent operations), and distil,
as recommended, in a vacuum. If, however, from the odour and from the
history of the case, it is pretty sure to be a case of poisoning by
hydric or potassic cyanide, then the substances, if fluid, are at once
placed in a retort or flask, and acidified with a suitable quantity of
sulphuric acid, or if the tissues or other solid matters are under
examination, they are finely divided, or pulped, and distilled, after
acidifying with sulphuric acid as before. It may be well here, as a
caution, to remark that the analyst must not commit the unpardonable
error of first producing a cyanide by reagents acting on animal matters,
and then detecting as a poison the cyanide thus manufactured. If, for
example, a healthy liver is carbonised by nitric acid, saturated with
potash, and then burnt up, cyanide of potassium is always one of the
products; and, indeed, the ashes of a great variety of nitrogenous
organic substances may contain cyanides--cyanides not pre-existing, but
manufactured by combination. By the action of nitric acid even on
sugar,[255] hydric cyanide is produced.

[255] _Chemical News_, 68, p. 75.

The old method of distillation was to distil by the gentle heat of a
water-bath, receiving the distillate in a little weak potash water, and
not prolonging the process beyond a few hours. The experiments of
Sokoloff, however, throw a grave doubt on the suitability of this simple
method for quantitative results.

N. Sokoloff[256] recommends the animal substances to be treated by water
strongly acidified with hydric sulphate, and then to be distilled in the
water-bath for from two to three days; or to be distilled for
twenty-four hours, by the aid of an oil-bath, at a high temperature. He
gives the following example of quantitative analysis by the old process
of merely distilling for a few hours, and by the new:--

[256] _Ber. d. deutsch. chem. Gesellsch._, Berlin, ix. p. 1023.

=Old Process.=--(1.) Body of a hound--age, 2 years; weight, 5180 grms.;
dose administered, 57 mgrms. HCN; death in fifteen minutes. After five
days there was found in the saliva 0·6 mgrm., stomach 3·2 mgrms., in the
rest of the intestines 2·6 mgrms., in the muscles 4·1--total, 10·5.

(2.) Weight of body, 4000 grms.; dose given, 38 mgrms.; death in eleven
minutes. After fifteen days, in the saliva 0·8, in the stomach 7·2, in
the rest of the intestines 2·2, in the muscles 3·2--total, 13·4.

=New Process.=--Weight of body, 5700 grams; dose, 57 mgrms.; death in
twenty-four minutes. After fifteen days, in the saliva 1·1 mgrm., in the
stomach 2·6, in the rest of the intestines 9·6, in the muscles 31·9, and
in the whole, 45·2 mgrms. Duration of process, thirteen hours.

From a second hound, weighing 6800 grms.; dose, 67 mgrms.; 25·1 mgrms.
were separated three days after death.

From a third hound, weighing 5920 grms.; dose, 98 mgrms.; after forty
days, by distillation on a sand-bath, there were separated 2·8 mgrms.
from the saliva, 4·8 from the stomach, 16·8 from the intestines, 23·6
from the muscles--total, 48 mgrms.

It would also appear that he has separated 51·2 mgrms. of anhydrous acid
from the corpse of a dog which had been poisoned by 57 mgrms. of acid,
and buried sixty days.[257]

[257] Without wishing to discredit the statements of M. Sokoloff, we may
point out that a loss of half-a-dozen mgrms. only appears rather
extraordinary.

From another canine corpse, three days laid in an oven, and left for
twenty-seven days at the ordinary temperature, 5·1 mgrms. were recovered
out of a fatal dose of 38 mgrms.

The estimation was in each case performed by titrating the distillate
with argentic nitrate, the sulphur compounds having been previously got
rid of by saturating the distillate with KHO, and precipitating by lead
acetate.

Venturoli[258] has, on the contrary, got good quantitative results
without distillation at all. A current of pure hydrogen gas is passed
through the liquid to be tested and the gas finally made to bubble
through silver nitrate. He states that the whole of the hydric cyanide
present is carried over in an hour. Metallic cyanides must be decomposed
by sulphuric acid or tartaric acid. Mercury cyanide must be decomposed
with SH₂, the solution acidified with tartaric acid, neutralised with
freshly precipitated calcic carbonate to fix any ferro- or
ferri-cyanides present, and hydrogen passed in and the issuing gases led
first through a solution of bismuth nitrate to remove SH₂ and then into
the silver solution.

[258] L’Orosi. xv. 85-88.

§ 267. =How long after Death can Hydric or Potassic Cyanides be
Detected?=--Sokoloff appears to have separated prussic acid from the
body of hounds at very long periods after death--in one case sixty days.
Dragendorff recognised potassic cyanide in the stomach of a hound after
it had been four weeks in his laboratory,[259] and in man eight days
after burial. Casper also, in his 211th case, states that more than 18
mgrms. of anhydrous prussic acid were obtained from a corpse eight days
after death.[260] Dr. E. Tillner[261] has recognised potassic cyanide in
a corpse four months after death. Lastly, Struve[262] put 300 grms. of
flesh, 400 of common water, and 2·378 of KCy in a flask, and then opened
the flask after 547 days. The detection was easy, and the estimation
agreed with the amount placed there at first. So that, even in very
advanced stages of putrefaction, and at periods after death extending
beyond many months, the detection of prussic acid cannot be pronounced
impossible.

[259] Dragendorff, G., _Beitr. zur gericht. Chem._, p. 59.

[260] Casper’s _Pract. Handbuch der gerichtlichen Medicin_, p. 561.

[261] _Vierteljahr. f. gerichtl. Med._, Berlin, 1881, p. 193.

[262] _Zeitschrift f. anal. Chemie_, von Fresenius, 1873, xii. p. 4.

§ 268. =Estimation of Hydrocyanic Acid or Potassic Cyanide.=--In all
cases, the readiest method of estimating prussic acid (whether it be in
the distillate from organic substances or in aqueous solution) is to
saturate it with soda or potash, and titrate the alkaline cyanide thus
formed with nitrate of silver. The process is based on the fact that
there is first formed a soluble compound (KCy, AgCy), which the
slightest excess of silver breaks up, and the insoluble cyanide is at
once precipitated. If grains are used, 17 grains of nitrate of silver
are dissolved in water, the solution made up to exactly 1000 grain
measures, each grain measure equalling ·0054 grain of anhydrous
hydrocyanic acid. If grammes are employed, the strength of the nitrate
of silver solution should be 1·7 grm. to the litre, each c.c. then =
·0054 hydrocyanic acid, or ·01302 grm. of potassic cyanide.

Essential oil of bitter almonds may also be titrated in this way,
provided it is diluted with sufficient spirit to prevent turbidity from
separation of the essential oil. If hydrocyanic acid is determined
gravimetrically (which is sometimes convenient, when only a single
estimation is to be made), it is precipitated as cyanide of silver, the
characters of which have been already described.

    § 269. =Case of Poisoning by Bitter Almonds.=--Instances of
    poisoning by bitter almonds are very rare. The following interesting
    case is recorded by Maschka:--

    A maid-servant, 31 years of age, after a quarrel with her lover, ate
    a quantity of bitter almonds. In a few minutes she sighed,
    complained of being unwell and faint; she vomited twice, and, after
    about ten minutes more had elapsed, fell senseless and was
    convulsed. An hour afterwards, a physician found her insensible, the
    eyes rolled upwards, the thumb clenched within the shut fists, and
    the breathing rattling, the pulse very slow. She died within an
    hour-and-a-half from the first symptoms.

    The autopsy showed the organs generally healthy, but all, save the
    liver, exhaling a faint smell of bitter almonds. The right side of
    the heart was full of fluid dark blood, the left was empty. Both
    lungs were rich in blood, which smelt of prussic acid. The stomach
    was not inflamed--it held 250 grms. of a yellow fluid, containing
    white flocks smelling of bitter almond oil. In the most dependent
    portion of the stomach there was a swollen patch of mucous membrane,
    partially denuded of epithelium. The mucous membrane of the duodenum
    was also swollen and slightly red. The contents of the stomach were
    acid, and yielded, on distillation, hydride of benzole and hydric
    cyanide. Residues of the almonds themselves were also found, and
    the whole quantity taken by the woman from various data was
    calculated to be 1200 grains of bitter almonds, equal to 43 grains
    of amygdalin, or 2·5 grains of pure hydric cyanide.


Poisonous Cyanides other than Hydric and Potassic Cyanides.

    § 270. The action of both _sodic and ammonic cyanides_ is precisely
    similar to that of potassic cyanide. With regard to ammonic cyanide,
    there are several experiments by Eulenberg,[263] showing that its
    vapour is intensely poisonous.

[263] _Gewerbe Hygiene_, p. 385.

    A weak stream of ammonic cyanide vapour was passed into glass
    shades, under which pigeons were confined. After a minute, symptoms
    of distress commenced, then followed convulsions and speedy death.
    The _post-mortem_ signs were similar to those produced by prussic
    acid, and this substance was separated from the liver and lungs.

    § 271. With regard to the _double cyanides_, all those are poisonous
    from which hydric cyanide can be separated through dilute acids,
    while those which, like potassic ferro-cyanide, do not admit of this
    decomposition, may be often taken with impunity, and are only
    poisonous under certain conditions.

    Sonnenschein records the death of a colourist, after he had taken a
    dose of potassic ferro-cyanide and then one of tartaric acid; and
    Volz describes the death of a man, who took potassic ferro-cyanide
    and afterwards equal parts of nitric and hydrochloric acids. In this
    latter case, death took place within the hour, with all the symptoms
    of poisoning by hydric cyanide; so that it is not entirely true, as
    most text-books declare, that ferro-cyanide is in no degree
    poisonous. Carbon dioxide will decompose potassic ferro-cyanide at
    72°-74°, potass ferrous cyanide being precipitated--K₂Fe₂(CN)₆. A
    similar action takes place if ferro-cyanide is mixed with a solution
    of peptone and casein, and digested at blood heat[264] (from 37° to
    40° C.), so that it is believed that when ferro-cyanide is swallowed
    HCN is liberated, but the quantity is usually so small at any given
    moment that no injury is caused: but there are conditions in which
    it may kill speedily.[265]

[264] Autenrieth, _Arch. Pharm._, 231, 99-109.

[265] The presence of ferro-cyanide is easily detected. The liquid is,
if necessary, filtered and then acidified with hydrochloric acid and a
few drops of ferric chloride added; if the liquid contains
ferro-cyanide, there is immediate production of Prussian blue. It may
happen that potassic or sodic cyanide has been taken as well as
ferro-cyanide, and it will be necessary then to devise a process by
which only the prussic acid from the simple cyanide is distilled over.
According to Autenrieth, if sodium hydrocarbonate is added to the liquid
in sufficient quantity and the liquid distilled, the hydric cyanide that
comes over is derived wholly from the sodium or potassium cyanide.
Should mercury cyanide and ferro-cyanide be taken together, then this
process requires modification; bicarbonate of soda is added as before,
and then a few c.c. of water saturated with hydric sulphide; under these
circumstances, only the hydric cyanide derived from the mercury cyanide
distils over. If the bicarbonate of soda is omitted, the distillate
contains hydric cyanide derived from the ferro-cyanide.

    =Mercuric cyanide=, it has been often said, acts precisely like
    mercuric chloride (corrosive sublimate), and a poisonous action is
    attributed to it not traceable to cyanogen; but this is erroneous
    teaching. Bernard[266] declares that it is decomposed by the gastric
    juice, and hydric cyanide set free; while Pelikan puts it in the
    same series as ammonic and potassic cyanides. Lastly,
    Tolmatscheff,[267] by direct experiment, has found its action to
    resemble closely that of hydric cyanide.[268]

[266] _Substances Toxiques_, pp. 66-103.

[267] “_Einige Bemerkungen über die Wirkung von Cyanquecksilber_,” in
Hoppe-Seyler’s _Med. Chem. Untersuchungen_, 2 Heft, p. 279.

[268] Mercury cyanide may be detected in a liquid after acidifying with
tartaric acid, and adding a few c.c. of SH₂ water and then distilling.
S. Lopes suggests another process: the liquid is acidified with tartaric
acid, ammonium chloride added in excess, and the liquid is distilled. A
double chloride of ammonium and mercury is formed, and HCN distils over
with the steam.--_J. Pharm._, xxvii. 550-553.

    =Silver cyanide= acts, according to the experiments of Nunneley,
    also like hydric cyanide, but very much weaker.

    =Hydric sulphocyanide= in very large doses is poisonous.

    =Potassic sulphocyanide=, according to Dubreuil and Legros,[269] if
    subcutaneously injected, causes first local paralysis of the
    muscles, and later, convulsions.

[269] _Compt. rend._, t. 64, 1867, p. 561.

    =Cyanogen chloride= (CNCl) and also the compound (C₃N₃Cl₃)--the one
    a liquid, boiling at 15°, the other a solid, which may be obtained
    in crystals--are both poisonous, acting like hydric cyanide.

    =Methyl cyanide= is a liquid obtained by distillation of a mixture
    of calcic methyl sulphate and potassic cyanide. It boils at 77°, and
    is intensely poisonous. Eulenberg[270] has made with this substance
    several experiments on pigeons. An example of one will suffice:--A
    young pigeon was placed under a glass shade, into which methyl
    cyanide vapour, developed from calcic methyl sulphate and potassic
    cyanide, was admitted. The pigeon immediately became restless, and
    the fæces were expelled. In forty seconds it was slightly convulsed,
    and was removed after a few minutes’ exposure. The pupils were then
    observed not to be dilated, but the respiration had ceased; the legs
    were feebly twitching; the heart still beat, but irregularly; a
    turbid white fluid dropped out of the beak, and after six minutes
    life was extinct.

[270] _Gewerbe Hygiene_, p. 392.

    The pathological appearances were as follows:--In the beak much
    watery fluid; the membranes covering the brain weakly injected; the
    _plexus venosus spinalis_ strongly injected; in the region of the
    cervical vertebra a small extravasation between the dura mater and
    the bone; the right lung of a clear cherry-red colour, and the left
    lung partly of the same colour, the parenchyma presented the same
    hue as the surface; on section of the lungs a whitish froth exuded
    from the cut surface. In the cellular tissue of the trachea, there
    were extravasations 5 mm. in diameter; the mucous membrane of the
    air-passages was pale; the right ventricle and the left auricle of
    the heart were filled with coagulated and fluid dark red blood;
    liver and kidneys normal; the blood dark red and very fluid,
    becoming bright cherry-red on exposure to the air; blood corpuscles
    unchanged. Cyanogen was separated, and identified from the lungs and
    the liver.

    =Cyanuric acid= (C₃O₃N₃H₃), one of the decomposition products
    obtained from urea, is poisonous, the symptoms and pathological
    effects closely resembling those due to hydric cyanide. In
    experiments on animals, there has been no difficulty in detecting
    prussic acid in the lungs and liver after poisoning by cyanuric
    acid.


XIII.--Phosphorus.

§ 272. =Phosphorus.=--Atomic weight 31, specific gravity 1·77 to 1·840.
Phosphorus melts at from 44·4° to 44·5° to a pale yellow oily fluid. The
boiling-point is about 290°.

The phosphorus of commerce is usually preserved under water in the form
of waxy, semi-transparent sticks; if exposed to the air white fumes are
given off, luminous in the dark, with a peculiar onion-like odour. On
heating phosphorus it readily inflames, burning with a very white flame.

At 0° phosphorus is brittle; the same quality may be imparted to it by a
mere trace of sulphur. Phosphorus may be obtained in dodecahedral
crystals by slowly cooling large melted masses. It may also be obtained
crystalline by evaporating a solution in bisulphide of carbon or hot
naphtha in a current of carbon dioxide. It is usually stated to be
absolutely insoluble in water, but Julius Hartmann[271] contests this,
having found in some experiments that 100 grms. of water digested with
phosphorus for sixty-four hours at 38·5° dissolved ·000127 grm. He also
investigated the solvent action of bile, and found that 100 grms. of
bile under the same conditions, dissolved ·02424 grm., and that the
solubility of phosphorus rose both in water and bile when the
temperature was increased. Phosphorus is somewhat soluble in alcohol and
ether, and also, to some extent, in fatty and ethereal oils; but the
best solvent is carbon disulphide.

[271] _Zur acuten Phosphor-Vergiftung_, Dorpat, 1866.

The following is the order of solubility in certain menstrua, the
figures representing the number of parts by weight of the solvent
required to dissolve 1 part of phosphorus:--

  Carbon Disulphide,                      4
  Almond Oil,                           100
  Concentrated Acetic Acid,[272]        100
  Ether,                                250
  Alcohol, specific gravity ·822,       400
  Glycerin,                             588

[272] Phosphorus is very little soluble in cold acetic acid, and the
solubility given is only correct when the boiling acid acts for some
time on the phosphorus.

Phosphorus exists in, or can be converted into, several allotropic
modifications, of which the red or amorphous phosphorus is the most
important. This is effected by heating it for some time, in the absence
of air, from 230° to 235°. It is not poisonous.[273] Commercial red
phosphorus does, however, contain very small quantities of unchanged or
ordinary phosphorus--according to Fresenius, from ·6 per cent.
downwards; it also contains phosphorous acid, and about 4·6 per cent. of
other impurities, among which is graphite.[274]

[273] A hound took 200 grms. of red phosphorus in twelve days, and
remained healthy.--Sonnenschein.

[274] Schrotter, _Chem. News_, vol. xxxvi. p. 198.

§ 273. =Phosphuretted Hydrogen.=--=Phosphine= (PH₃), mol. weight 34,
specific gravity 1·178, percentage composition, phosphorus 91·43,
hydrogen 8·57 by weight. The absolutely pure gas is not spontaneously
inflammable, but that made by the ordinary process is so. It is a
colourless, highly poisonous gas, which does not support combustion, but
is itself combustible, burning to phosphoric acid (PH₃ + 2O₂ = PO₄H₃).
Extremely dangerous explosive mixtures may be made by combining
phosphine and air or oxygen. Phosphine, when quite dry, burns with a
white flame, but if mixed with aqueous vapour, it is green; hence a
hydrogen flame containing a mixture of PH₃ possesses a green colour.

If sulphur is heated in a stream of phosphine, hydric sulphide and
sulphur phosphide are the products. Oxides of the metals, heated with
phosphine, yield phosphides with formation of water. Iodine, warmed in
phosphine, gives white crystals of iodine phosphonium, and biniodide of
phosphorus, 5I + 4PH₃ = 3PIH₄ + PI₂. Chlorine inflames the gas, the
final result being hydric chloride and chloride of phosphorus, PH₃ + 8Cl
= 3ClH + PCl₅. One of the most important decompositions for our purpose
is the action of phosphine on a solution of nitrate of silver; there is
a separation of metallic silver, and nitric and phosphoric acids are
found in solution, thus--8AgNO₃ + PH₃ + 4OH₂ = 8Ag + 8HNO₃ + PO₄H₃. This
is, however, rather the end reaction; for, at first, there is a
separation of a black precipitate composed of phosphor-silver. The
excess of silver can be separated by hydric chloride, and the phosphoric
acid made evident by the addition of molybdic acid in excess.

§ 274. =The medicinal preparations of phosphorus= are not numerous; it
is usually prescribed in the form of pills, made by manufacturers of
coated pills on a large scale. The pills are composed of phosphorus,
balsam of Tolu, yellow wax, and curd soap, and 3 grains equal 1/30 grain
of phosphorus. There is also a _phosphorated oil_, containing about 1
part of phosphorus in 100; that of the French Pharmacopœia is made with
1 part of dried phosphorus dissolved in 50 parts of warm almond oil;
that of the German has 1 part in 80; the strength of the former is
therefore 2 per cent., of the latter 1·25 per cent. The medicinal dose
of phosphorus is from 1/100 to 1/30 grain.

§ 275. =Matches and Vermin Pastes.=--An acquaintance with the percentage
of phosphorus in the different pastes and matches of commerce will be
found useful. Most of the vermin-destroying pastes contain from 1 to 2
per cent. of phosphorus.

A phosphorus paste that was fatal to a child,[275] and gave rise to
serious symptoms in others, was composed as follows:--

[275] Casper’s 204th case.

                                Per cent.
  Phosphorus,                      1·4
  Flowers of sulphur,             42·2
  Flour,                          42·2
  Sugar,                          14·2
                                 ------
                                 100·00

Three common receipts give the following proportions:--

                                Per cent.
  Phosphorus,                      1·5
  Lard,                           18·4
  Sugar,                          18·4
  Flour,                          61·7
                                 ------
                                 100·00

                               Per cent.
  Phosphorus,                      1·2
  Warm water,                     26·7
  Rye flour,                      26·7
  Melted butter,                  26·7
  Sugar,                          18·7
                                 ------
                                 100·00

                                Per cent.
  Phosphorus,                      1·6
  Nut oil,                        15·7
  Warm water,                     31·5
  Flour,                          31·5
  Sugar,                          19·7
                                 ------
                                 100·00

A very common phosphorus paste, to be bought everywhere in England, is
sold in little pots; the whole amount of phosphorus contained in these
varies from ·324 to ·388 grm. (5 to 6 grains), the active constituent
being a little over 4 per cent. Matches differ much in composition. Six
matchheads, which had been placed in an apple for criminal purposes, and
were submitted to Tardieu, were found to contain 20 mgrms. of
phosphorus--_i.e._, ·33 grm. in 100. Mayet found in 100 matches 55
mgrms. of phosphorus. Gonning[276] analysed ten different kinds of
phosphorus matches with the following result:--Three English samples
contained in 100 matches 34, 33, and 32 mgrms. of phosphorus: a Belgian
sample, 38 mgrms.; and 5 others of unknown origin, 12, 17, 28, 32, and
41 mgrms. respectively. Some of the published formularies are as
follows:--

[276] _Nederlandsch Tijdschr. voor Geneesk._, Afl. i., 1866.

  (1.) Glue,                 6 parts.
       Phosphorus,           4   „    or 14·4 per cent.
       Nitre,               10   „
       Red ochre,            5   „
       Blue smalts,          2   „

  (2.) Phosphorus,           9 parts, or 16·3 per cent.
       Gum,                 16   „
       Nitre,               14   „
       Smalts,              16   „

  (3.) Phosphorus,           4 parts, or 14·4 per cent.
       Glue,                 6   „
       Nitre,               10   „
       Red lead,             5   „
       Smalts,               2   „

  (4.) Phosphorus,          17 parts, or 17 per cent.
       Glue,                21   „
       Nitre,               38   „
       Red lead,            24   „

Phosphorus poisoning by matches will, however, shortly become very rare,
for those containing the ordinary variety of phosphorus are gradually
being superseded by matches of excellent quality, which contain no
phosphorus whatever.

§ 276. =Statistics.=--The following table gives the deaths for ten years
from phosphorus poisoning in England and Wales:--

DEATHS FROM PHOSPHORUS IN ENGLAND AND WALES DURING THE TEN YEARS ENDING
1892.

                   ACCIDENT OR NEGLIGENCE.

  Ages,       1-5   5-15   15-25   25-65   65 and  Total
                                           above
  Males,       11     1       2       8     ...      22
  Females,     15     2      11       5     ...      33
             -------------------------------------------
    Totals,    26     3      13      13     ...      55
             -------------------------------------------

                           SUICIDE.

  Ages,             5-15   15-25   25-65   65 and  Total
                                           above
  Males,              1       6      20       1      28
  Females,            6      33      24       1      64
                   -------------------------------------
      Totals,         7      39      44       2      92
                   -------------------------------------

Phosphorus as a cause of death through accident or negligence occupies
the eighth place among poisons, and as a cause of suicide the ninth.

A far greater number of cases of poisoning by phosphorus occur yearly in
France and Germany than in England. Phosphorus may be considered as the
favourite poison which the common people on the Continent employ for the
purpose of self-destruction. It is an agent within the reach of anyone
who has 2 sous in his pocket, wherewith to buy a box of matches, but to
the educated and those who know the horrible and prolonged torture
ensuing from a toxic dose of phosphorus, such a means of exit from life
will never be favoured.

Otto Schraube[277] has collected 92 cases from Meischner’s work,[278]
and added 16 which had come under his own observation, giving in all 108
cases. Seventy-one (or 65 per cent.) of these were suicidal--of the
suicides 24 were males, 47 females (12 of the latter being prostitutes);
21 of the cases were those of murder, 11 were accidental, and in 3 the
cause was not ascertained. The number of cases in successive years, and
the kind of poison used, is given as follows:--

[277] Schmidt’s _Jahrbuch der ger. Med._, 1867, Bd. 186, S. 209-248.

[278] _Die acute Phosphorose und einige Reflexionen über die acute gelbe
Leberatrophie, &c., Inaug. Diss._, Leipzig, 1864.

                                      Phosphorus in    Phosphorus
  Number of Cases.    In the Years      Substance,      Matches.
                                       or as Paste.

         15            1798-1850           13               2
         36            1850-1860           15              21
         41            1860-1864            6              35
         16            1864-1867            5              11

Of the 108 cases, 18 persons recovered and 90 (or 83·3 per cent.) died.

Falck also has collected 76 cases of poisoning from various sources
during eleven years; 55 were suicidal, 5 homicidal[279] (murders), and
the rest accidental. Of the latter, 2 were caused by the use of
phosphorus as a medicine, 13 by accidents due to phosphorus being in the
house; in 1 case phosphorus was taken intentionally to try the effects
of an antidote.[280] With regard to the form in which the poison was
taken, 2 of the 76, as already mentioned, took it as prescribed by
physicians, the remaining 74 were divided between poisonings by
phosphorus paste (22) and matches (52) = 70 per cent. Of the 76 cases, 6
were children, 43 adult males, 13 adult females, and 14 adults, sex not
given. Of the 76 cases, 42, or 55·3 per cent., died--a much smaller rate
of mortality than that shown by Schraube’s collection.

[279] Dr. Dannenberg has shown by direct experiment that a poisonous
dose of phosphorus may be introduced into spirits or coffee, and the
mixture have but little odour or taste of phosphorus.--Schuchardt in
Maschka’s _Handbuch_.

[280] Géry, “_Ueber Terpentinessenz als Gegenmittel gegen Phosphor_,” in
_Gaz. Hebd. de Méd._, 2 sér., x. 2, 1873.

§ 277. =Fatal Dose.=--The smallest dose on record is that mentioned by
Lobenstein Lobel, of Jena, where a lunatic died from taking 7·5 mgrms.
(·116 grain). There are other cases clearly indicating that this small
quantity may produce dangerous symptoms in a healthy adult.

§ 278. =Effects of Phosphorus.=--Phosphorus is excessively poisonous,
and will destroy life, provided only that it enters the body in a fine
state of division, but if taken in coarse pieces no symptoms may follow,
for it has been proved that single lumps of phosphorus will go the whole
length of a dog’s intestinal canal without causing appreciable loss of
weight, and without destroying life.[281] Magendie injected _oleum
phosphoratum_ into the veins, and although the animals experimented on
exhaled white fumes, and not a few died asphyxiated, yet no symptoms of
phosphorus poisoning resulted--an observation confirmed by others--the
reason being that the phosphorus particles in a comparatively coarse
state of division were arrested in the capillaries of the lung, and may
be said to have been, as it were, outside the body. On the other hand,
A. Brunner,[282] working in L. Hermann’s laboratory, having injected
into the veins phosphorus in such a fine emulsion that the phosphorus
could pass the lung capillaries, found that there were no exhalations of
white fumes, but that the ordinary symptoms of phosphorus poisoning soon
manifested themselves. Phosphorus paste, by the method of manufacture,
is in a state of extreme sub-division, and hence all the phosphorus
pastes are extremely poisonous.

[281] Reveil, _Ann. d’Hygiène Publ._ (3), xii. p. 370.

[282] _Arch. f. d. Ges. Physiologie_, iii. p. 1.

§ 279. In a few poisons there is a difference, more or less marked,
between the general symptoms produced on man, and those noticeable in
the different classes of animals; but with phosphorus, the effects on
animals appear to agree fairly with those witnessed most frequently in
man. Tardieu (who has written perhaps the best and most complete
clinical record of phosphorus poisoning extant) divides the cases under
three classes, and to use his own words:--“I think it useful to
establish that poisoning by phosphorus in its course, sometimes rapid,
sometimes slow, exhibits in its symptoms three distinct forms--a common
form, a nervous form, and a hæmorrhagic form. I recognise that, in
certain cases, these three forms may succeed each other, and may only
constitute periods of poisoning; but it is incontestable that each of
them may show itself alone, and occupy the whole course of the illness
produced by the poison.”[283] Premising that the common form is a
blending of irritant, nervous, and hæmorrhagic symptoms, I adopt here in
part Tardieu’s division. The name of “hæmorrhagic form” may be given to
that in which hæmorrhage is the predominant feature, and the “nervous”
to that in which the brain and spinal cord are from the first affected.
There yet remain, however, a few cases which have an entirely anomalous
course, and do not fall under any of the three classes.

[283] _Étude Médico-Légale et Clinique sur l’Empoisonnement_, Paris,
1875, p. 483.

From a study of 121 recorded cases of phosphorus poisoning, I believe
the relative frequency of the different forms to be as follows:--The
common form 83 per cent., hæmorrhagic 10 per cent., nervous 6 per cent.,
anomalous 1 per cent. The “anomalous” are probably over-estimated, for
the reason that cases presenting ordinary features are not necessarily
published, but others are nearly always chronicled in detail.

§ 280. =Common Form.=--At the moment of swallowing, a disagreeable taste
and smell are generally experienced, and there may be immediate and
intense pain in the throat, gullet, and stomach, and almost immediate
retching and vomiting. The throat and tongue also may become swollen and
painful; but in a considerable number of cases the symptoms are not at
once apparent, but are delayed from one to six hours--rarely longer. The
person’s breath may be phosphorescent before he feels in any way
affected, and he may go about his business and perform a number of acts
requiring both time and mental integrity. Pain in the stomach (which, in
some of the cases, takes the form of violent cramp and vomiting)
succeeds; the matters vomited may shine in the dark, and are often
tinged with blood. Diarrhœa is sometimes present, sometimes absent;
sleeplessness for the first night or two is very common. The pulse is
variable, sometimes frequent, sometimes slow; the temperature in the
morning is usually from 36·0° to 36·5°, in the evening 37° to 38°.

The next symptom is jaundice. I have notes of the exact occurrence of
jaundice in 23 cases, as follows:--In 1 within twenty-four hours, in 3
within thirty-six hours, in 3 within two days, in 11 within three days,
in 1 within four days, in 1 within five days, in 1 within nine days, in
1 within eighteen days, and in 1 within twenty-seven days; so that in
about 78 per cent. jaundice occurred before the end of the third day.
Out of 26 cases, in which the patients lived long enough for the
occurrence of jaundice, in 3 (or 11 per cent.) it was entirely absent.
In 132 cases recorded by Lewin, Meischner, and Heisler, jaundice
occurred in 65, or about 49 per cent., but it must be remembered, that
in many of these cases the individual died before it had time to
develop. The jaundice having thoroughly pronounced itself, the system
may be considered as not only under the influence of the toxic action of
phosphorus, but as suffering in addition from all the accidents
incidental to the retention of the biliary secretion in the blood; nor
is there from this point any special difference between phosphorus
poisoning and certain affections of the liver--such, for example, as
acute yellow atrophy. There is retention of urine, sleeplessness,
headache, frequent vomiting, painful and often involuntary evacuations
from the bowels, and occasionally skin affections, such as urticaria or
erythema. The case terminates either by acute delirium with fever,
followed by fatal coma, or, in a few instances, coma comes on, and the
patient passes to death in sleep without delirium. In this common form
there is in a few cases, at the end of from twenty-four to thirty hours,
a remission of the symptoms, and a non-medical observer might imagine
that the patient was about to recover without further discomfort; but
then jaundice supervenes, and the course is as described. Infants often
do not live long enough for the jaundiced stage to develop, but die
within twenty-four hours, the chief symptoms being vomiting and
convulsions.

§ 281. =Hæmorrhagic Form.=--The symptoms set in as just detailed, and
jaundice appears, but accompanied by a new and terrible train of
events--viz., great effusion of blood. In some cases the blood has been
poured out simultaneously from the nose, mouth, bladder, kidneys, and
bowels. Among women there is excessive hæmorrhagia. The liver is found
to be swollen and painful; the bodily weakness is great. Such cases are
usually of long duration, and a person may die months after taking the
poison from weakness, anæmia, and general cachexia. In many of its
phases the hæmorrhagic form resembles scurvy, and, as in scurvy, there
are spots of purpura all over the body.

§ 282. =The nervous form= is less common than the two forms just
described. From the beginning, there are strange creeping sensations
about the limbs, followed by painful cramps, repeated faintings, and
great somnolence. Jaundice, as usual, sets in, erythematous spots appear
on the skin, and, about the fifth day, delirium of an acute character
breaks out, and lock-jaw and convulsions close the scene.

The following are one or two brief abstracts of anomalous cases in which
symptoms are either wanting, or run a course entirely different from any
of the three forms described:--

A woman, aged 20, took about 3 grains of phosphorus in the form of
rat-paste. She took the poison at six in the evening, behaved according
to her wont, and sat down and wrote a letter to the king. During the
night she vomited once, and died the next morning at six o’clock,
exactly twelve hours after taking the poison. There appear to have been
no symptoms whatever, save the single vomiting, to which may be added
that in the course of the evening her breath had a phosphorus odour and
was luminous.[284]

[284] Casper’s 205th case.

A girl swallowed a quantity of phosphorus paste, but there were no
marked symptoms until the fifth day, on which there was sickness and
purging. She died on the seventh day. A remarkable blueness of the
finger nails was observed a little before death, and was noticeable
afterwards.[285]

[285] Taylor on _Poisons_, p. 277.

§ 283. =Sequelæ.=--In several cases in which the patients have recovered
from phosphorus poisoning, there have been observed paralytic
affections.[286] O. Bollinger has recorded a case in which paralysis of
the foot followed;[287] in another, published by Bettelheim,[288] there
were peculiar cerebral and spinal symptoms. Most of these cases are to
be explained as disturbance or loss of function from small hæmorrhages
in the nervous substance.

[286] See Gallavardin, _Les Paralyses Phosphoriques_, Paris, 1865.

[287] _Deutsches Archiv f. klin. Med._, Bd. 6, Hft. 1, S. 94, 1869.

[288] _Wiener Med. Presse_, 1868, No. 41.

§ 284. =Period at which the first Symptoms commence.=--The time when the
symptoms commence is occasionally of importance from a forensic point of
view. I find that out of 28 cases in which the commencement of evident
symptoms--_i.e._, pain, or vomiting, or illness--is precisely recorded,
in 8 the symptoms were described as either immediate or within a few
minutes after swallowing the poison; in 6 the symptoms commenced within
the hour; in 3 within two hours; in other 3 within four hours; and in 1
within six hours. One was delayed until the lapse of twelve hours, 1
from sixteen to eighteen hours, 1 two, and another five days. We may,
therefore, expect that in half the cases which may occur, the symptoms
will commence within the hour, and more than 80 per cent. within six
hours.

§ 285. =Period of Death.=--In 129 cases death took place as follows:--In
17 within twenty-four hours, in 30 within two days, in 103 within seven
days. Three patients lived eight days, 6 nine days, 13 ten days, 1
eleven days, 1 sixteen days, 1 seventeen days, and 1 survived eight
months. It hence follows that 79·8 per cent. of the fatal cases die
within the week.

§ 286. =Phosphorus Vapour.=--There are one or two cases on record of
acute poisoning by phosphorus in the form of vapour. The symptoms are
somewhat different from the effects produced by the finely-divided
solid, and in general terms it may be said that phosphorus vapour is
more apt to produce the rarer “nervous” form of poisoning than the solid
phosphorus.

Bouchardat[289] mentions the case of a druggist who, while preparing a
large quantity of rat-poison in a close room, inhaled phosphorus vapour.
He fainted repeatedly, fell into a complete state of prostration, and
died within a week.

[289] _Annuaire de Thérap._, 1874, p. 109; Schuchardt in Maschka’s
_Handbuch_; also Schmidt’s _Jahrbuch_, 1846, Bd. 51, S. 101.

The following interesting case came under the observation of Professor
Magnus Huss:--A man, thirty-nine years old, married, was admitted into
the Seraphin-Lazareth, Stockholm, on the 2nd of February 1842. He had
been occupied three years in the manufacture of phosphorus matches, and
inhabited the room in which the materials were preserved. He had always
been well-conducted in every way, and in good health, until a year
previously, when a large quantity of the material for the manufacture of
the matches accidentally caught fire and exploded. In his endeavours to
extinguish the flames, he breathed a large quantity of the vapour, and
he fell for a time unconscious. The spine afterwards became so weak that
he could not hold himself up, and he lost, in a great measure, power
over his legs and arms. On admission, his condition was as follows:--He
could make a few uncertain and staggering steps, his knees trembled, his
arms shook, and if he attempted to grasp anything when he lay in bed,
there were involuntary twitchings of groups of muscles. There was no
pain; the sensibility of the skin was unchanged; he had formication in
the left arm; the spine was neither sensitive to pressure, nor unusually
sensitive to heat (as, _e.g._, to the application of a hot sponge); the
organs of special sense were not affected, but his speech was somewhat
thick. He lived to 1845 in the same condition, but the paralysis became
worse. There does not seem to have been any autopsy.

The effects of phosphorus vapour may be still further elucidated by one
of Eulenberg’s[290] experiments on a rabbit. The vapour of burning
phosphorus, mixed with much air, was admitted into a wooden hutch in
which a strong rabbit sat. After 5 mgrms. of phosphorus had been in this
manner consumed, the only symptoms in half an hour were salivation, and
quickened and somewhat laboured respiration. After twenty-four hours had
elapsed there was sudden indisposition, the animal fell as if lifeless,
with the hind extremities stretched out, and intestinal movements were
visible; there was also expulsion of the urine. These epileptiform
seizures seem to have continued more or less for twelve days, and then
ceased. After fourteen days the experiment was repeated on the same
rabbit. The animal remained exposed to the vapour for three-quarters of
an hour, when the epilepsy showed itself as before, and, indeed, almost
regularly after feeding. Between the attacks the respiration was slowed.
Eight weeks afterwards there was an intense icterus, which disappeared
at the end of ten weeks.

[290] _Gewerbe Hygiene_, p. 255.

§ 287. =Chronic phosphorus poisoning= has frequently been noticed in
persons engaged either in the manufacture of phosphorus or in its
technical application. Some have held that the symptoms are due to an
oxidation product of phosphorus rather than to phosphorus itself; but in
one of Eulenberg’s experiments, in which a dove was killed by breathing
phosphorus fumes evolved by phosphorus oil, phosphorus was chemically
recognised in the free state in the lungs. The most constant and
peculiar effect of breathing small quantities of phosphorus vapour is a
necrosis of the lower jaw. There is first inflammation of the periosteum
of the jaw, which proceeds to suppuration and necrosis of a greater or
smaller portion. The effects may develop with great suddenness, and end
fatally. Thus Fournier and Olliver[291] relate the case of a girl,
fourteen years old, who, after working four years in a phosphorus
manufactory, was suddenly affected with periostitis of the upper jaw,
and with intense anæmia. An eruption of purpuric spots ensued, and she
died comatose. There is now little doubt, that minute doses of
phosphorus have a specific action on the bones generally, and more
especially on the bones of the jaw. Wegner[292] administered small daily
doses to young animals, both in the state of vapour, and as a
finely-divided solid. The condition of the bones was found to be more
compact than normal, the medullary canals being smaller than in healthy
bone, the ossification was quickened. The formation of callus in
fractured limbs was also increased.

[291] _Gaz. hebd. de Méd._, 29, p. 461, 1868.

[292] Virchow’s _Arch. f. path. Anat._, lv. 11.

§ 288. =Changes in the Urinary Secretion.=--It has been before stated
that, at a certain period of the illness, the renal secretion is
scantier than in health, the urine diminishing, according to Lebert and
Wyss’s[293] researches, to one-half on the third, fourth, or fifth day.
It frequently contains albumen, blood, and casts. When jaundice is
present, the urine has then all the characters noticed in icterus;
leucin and tyrosin, always present in acute yellow atrophy of the liver,
have been found in small quantity in jaundice through phosphorus; lactic
acid is also present. The urea is much diminished, and, according to
Schultzen and Riess,[294] may be towards death entirely absent. Lastly,
it is said that there is an exhalation of either phosphorus vapour or
phosphine from such urine. In some cases the urine is normal, _e.g._, in
a case recorded by E. H. Starling, M.D., and F. G. Hopkins, B.Sc.
(_Guy’s Hospital Report_, 1890), in which a girl, aged 18, died on the
fifth day after taking phosphorus paste, the liver was fatty, and there
was jaundice; but the urine contained neither leucin nor tyrosin, and
was stated to be generally normal.

[293] _Archiv Générale de Méd._, 6 Sér., Tom. 12, 1868, p. 709.

[294] _Annalen der Charité_, Berlin.

§ 289. =Changes in the blood= during life have been several times
observed. In a case attended by M. Romellære of Brussels,[295] in which
a man took the paste from 300 matches, and under treatment by turpentine
recovered, the blood was frequently examined, and the leucocytes found
much increased in number. There is a curious conflict of evidence as to
whether phosphorus prevents coagulation of the blood or not. Nasse
asserted that phosphorated oil given to a dog fully prevented
coagulation; P. I. Liebreck[296] also, in a series of researches, found
the blood dark, fluid, and in perfect solution. These observations were
also supported by V. Bibra and Schuchardt.[297] Nevertheless, Lebert and
Wyss found the blood, whether in the veins or in extravasations, in a
normal condition. Phosphorus increases the fatty contents of the blood.
Ritter found that phosphorus mixed with starch, and given to a dog,
raised the fatty content from the normal 2 per 1000 up to 3·41 and 3·47
per 1000. Eug. Menard[298] saw in the blood from the jugular and portal
veins, as well as in extravasations, microscopic fat globules and fine
needle-shaped crystals soluble in ether.

[295] Tardieu, _op. cit._, Case 31.

[296] _Diss. de Venefico Phosphoreo Acuto_, Upsal, 1845.

[297] V. Bibra u. Geist, _Die Krankheiten der Arbeiter in den
Phosphorzundholz Fabriken_, 1847, S. 59, &c.; Henle u. v. Pfeuffer’s
_Zeitschr. f. ration. Med._, N. F., Bd. 7, Hft. 3, 1857.

[298] _Étude Expérimentale sur quelques lésions de l’Empoisonnement aigu
par le Phosphore (Thèse)_, Strasbourg, 1869.

§ 290. =Antidote--Treatment.=--After emptying the stomach by means of
emetics or by the stomach-pump, oil of turpentine in full medicinal
doses, say 2·5 c.c. (about 40 min.), frequently administered, seems to
act as a true antidote, and a large percentage of cases treated early in
this way recover.

§ 291. =Poisonous Effects of Phosphine (phosphuretted
hydrogen).=--Experiments on pigeons, on rats, and other animals, and a
few very rare cases among men, have shown that phosphine has an exciting
action on the respiratory mucous membranes, and a secondary action on
the nervous system. Eulenberg[299] exposed a pigeon to an atmosphere
containing 1·68 per cent. of phosphine. There was immediate unrest; at
the end of three minutes, quickened and laboured breathing (100 a
minute); after seven minutes, the bird lay prostrate, with shivering of
the body and wide open beak; after eight minutes, there was vomiting;
after nine minutes, slow breathing (34 per minute); after twelve
minutes, convulsive movements of the wings; and after thirteen minutes,
general convulsions and death.

[299] _Gewerbe Hygiene_, p. 273.

The membranes of the brain were found strongly injected, and there were
extravasations. In the mucous membrane of the crop there was also an
extravasation. The lungs externally and throughout were of a dirty
brown-red colour; the entire heart was filled with coagulated blood,
which was weakly acid in reaction.

In a second experiment with another pigeon, there was no striking
symptom save that of increased frequency of respiration and loss of
appetite; at the end of four days it was found dead. There was much
congestion of the cerebral veins and vessels, the mucous membrane of the
trachea and bronchi were weakly injected, and the first showed a thin,
plastic, diphtheritic-like exudation.

Dr. Henderson’s[300] researches on rats may also be noticed here. He
found that an atmosphere consisting entirely of phosphine killed rats
within ten minutes, an atmosphere with 1 per cent. in half an hour. The
symptoms observed were almost exactly similar to those noticed in the
first experiment on the pigeon quoted above, and the _post-mortem_
appearances were not dissimilar. With smaller quantities of the gas, the
first symptom was increased frequency of the respiration; then the
animals showed signs of suffering intense irritation of the skin,
scratching and biting at it incessantly; afterwards they became drowsy,
and assumed a very peculiar attitude, sitting down on all-fours, with
the back bent forward, and the nose pushed backwards between the
forepaws, so as to bring the forehead against the floor of the cage.
When in this position, the rat presented the appearance of a curled-up
hedgehog. Phosphine, when injected into the rectum, is also fatal; the
animals exhale some of the gas from the lungs, and the breath,
therefore, reduces solutions of silver nitrate.[301]

[300] _Journ. Anat. and Physiol._, vol. xiii. p. 19.

[301] Dybskowsky, _Med. Chem. Untersuchungen aus Hoppe-Seyler’s Labor.
in Tübingen_, p. 57.

Brenner[302] has recorded the case of a man twenty-eight years old, a
pharmaceutist, who is supposed to have suffered from illness caused by
repeated inhalations of minute quantities of phosphine. He was engaged
for two and a half years in the preparation of hypophosphites; his
illness commenced with spots before the eyes, and inability to fix the
attention. His teeth became very brittle, and healthy as well as carious
broke off from very slight causes. Finally, a weakness of the arms and
limbs developed in the course of nine months into complete locomotor
ataxy.

[302] _St. Petersburg Med. Zeitschr._, 4 Hft., 1865.

§ 292. Blood takes up far more phosphine than water. Dybskowsky found
that putting the coefficient of solubility of phosphine in pure water at
·1122 at 15°, the coefficient for venous blood was ·13, and for arterial
26·73; hence the richer the blood is in oxygen the more phosphine is
absorbed. It seems probable that the poisonous gas reacts on the
oxyhæmoglobin of the blood, and phosphorous acid is formed. This is
supported by the fact that a watery extract of such blood reduces silver
nitrate, and has been also found feebly acid. The dark blood obtained
from animals poisoned by phosphine, when examined spectroscopically, has
been found to exhibit a band in the violet.

§ 293. =Post-mortem Appearances.=--There are a few perfectly well
authenticated cases showing that phosphorus may cause death, and yet no
lesion be discovered afterwards. Thus, Tardieu[303] cites a case in
which a woman, aged 45, poisoned herself with phosphorus, and died
suddenly the seventh day afterwards. Dr. Mascarel examined the viscera
with the greatest care, but could discover absolutely no abnormal
conditions; the only symptoms during life were vomiting, and afterwards
a little indigestion. It may, however, be remarked that the microscope
does not seem to have been employed, and that probably a close
examination of the heart would have revealed some alteration of its
ultimate structure. The case quoted, by Taylor[304] may also be
mentioned, in which a child was caught in the act of sucking phosphorus
matches, and died ten days afterwards in convulsions. None of the
ordinary _post-mortem_ signs of poisoning by phosphorus were met with,
but the intestines were reddened throughout, and there were no less than
ten invaginations; but the case is altogether a doubtful one, and no
phosphorus may actually have been taken. It is very difficult to give in
a limited space anything like a full picture of the different lesions
found after death from phosphorus, for they vary according as to whether
the death is speedy or prolonged, whether the phosphorus has been taken
as a finely-divided solid, or in the form of vapour, &c. It may,
however, be shortly said, that the most common changes are fatty
infiltration of the liver and kidneys, fatty degeneration of the heart,
enlargement of the liver, ecchymoses in the serous membranes, in the
muscular, in the fatty, and in the mucous tissues. When death occurs
before jaundice supervenes, there may be little in the aspect of the
corpse to raise a suspicion of poison; but if intense jaundice has
existed during life, the yellow staining of the skin, and it may be,
spots of purpura, will suggest to the experienced pathologist the
possibility of phosphorus poisoning. In the mouth and throat there will
seldom be anything abnormal. In one or two cases of rapid death among
infants, some traces of the matches which had been sucked were found
clinging to the gums. The stomach may be healthy, but the most common
appearance is a swelling of the mucous membrane and superficial
erosions. Virchow,[305] who was the first to call attention to this
peculiar grey swelling of the intestinal mucous membrane under the name
of _gastritis glandularis_ or _gastradenitis_, shows that it is due to a
fatty degeneration of the epithelial cells, and that it is by no means
peculiar to phosphorus poisoning. The swelling may be seen in
properly-prepared sections to have its essential seat in the glands of
the mucous membrane; the glands are enlarged, their openings filled with
large cells, and each single cell is finely granular. Little centres of
hæmorrhage, often microscopically small, are seen, and may be the
centres of small inflammations; their usual situation is on the summit
of the rugæ. Very similar changes are witnessed after death from
septicæmia, pyæmia, diphtheria, and other diseases. The softening of the
stomach, gangrene, and deep erosions, recorded by the earlier authors,
have not been observed of late years, and probably were due to
_post-mortem_ changes, and not to processes during life. The same
changes are to be seen in the intestines, and there are numerous
extravasations in the peritoneum.

[303] _L’Empoisonnement_, p. 520.

[304] _Poisons_, 3rd ed., p. 276.

[305] Virchow’s _Archiv. f. path. Anat._, Bd. 31, Hft. 3, 399.

The liver shows of all the organs the most characteristic signs; a more
or less advanced fatty infiltration of its structure takes place, which
was first described as caused by phosphorus by Hauff in 1860.[306] It
is the most constant pathological evidence both in man and animal, and
seems to occur at a very early period, Munk and Leyden having found a
fatty degeneration in the liver far advanced in twenty-four hours[307]
after poisoning. In rats and mice poisoned with paste, I have found this
evident to the naked eye twelve hours after the fatal dose. The liver is
mostly large, but in a case[308] recorded in the _Lancet_, July 14,
1888, the liver was shrunken; it has a pale yellow (or sometimes an
intense yellow) colour; on section the cut surface presents a mottled
appearance; the serous envelopes, especially along the course of the
vessels, exhibit extravasations of blood. The liver itself is more
deficient in blood than in the normal condition, and the more bloodless
it is, the greater the fatty infiltration.

[306] Hauff collected 12 cases, and found a fatty liver in
11.--_Würtemb. Med. Corresp. Bl._, 1860, No. 34.

[307] _Die acute Phosphor-Vergiftung_, Berlin, 1865.

[308] This case, from the similarity of the pathological appearances to
those produced by yellow atrophy, deserves fuller notice:--“Frances A.
Cowley, aged 20, on her own admission, took some rat paste on Tuesday,
June 19th. Death ensued eleven days later. The initial symptoms were not
very marked. Nausea and vomiting continued with moderate severity for a
few days and then ceased. There ensued a feeling of depression. Towards
the end insensibility, icterus, and somewhat profuse metrorrhagia
supervened. At the necropsy the skin and conjunctivæ were observed of a
bright yellow colour. There was no organic disease save of a recent
nature, and entirely attributable to the action of the poison ingested.
The stomach contained about three-quarters of a pint of dark
claret-coloured fluid, consisting largely of blood derived from
capillary hæmorrhage from the mucous membrane. There was no solution of
continuity of the mucous membrane, which showed traces of recent
irritation. The whole surface presented a yellow icteric tint, except
the summits of some of the rugæ, which were of a bright pink colour.
There was also faint wrinkling of the mucous membrane. The upper part of
the small intestine was affected in much the same manner as the stomach.
The large intestine contained a quantity of almost colourless fæces. The
liver was shrunken, weighing only 26 ozs., and both on its outer and
sectional surface exactly resembled the appearances produced by acute
yellow atrophy, except that there were greater congestion and
interstitial hæmorrhage in patches. The lobules of the liver were in
many places unrecognisable; in others they stood in bold relief as
brilliant canary-yellow patches, standing in strong contrast to the deep
dark-red areas of congestion and extravasation. The gall-bladder
contained about 2 drachms of thin greyish fluid, apparently all but
devoid of bile. The urinary bladder was empty; the kidneys were
enlarged; the cortex was very pale and bile-stained, of greater depth
than natural, and of softer consistence. The spleen was not enlarged,
nor was it in the least degree softened. In addition to the bleeding
from the uterus noticed during life, there was capillary hæmorrhage into
the right lung and pleura, into the pericardium, and, as already
mentioned, into the stomach. The brain was healthy.”

In the Museum of the Royal College of Surgeons there is a preparation
(No. 2737) of the section of a liver derived from a case of phosphorus
poisoning.

A girl, aged 18, after two days’ illness, was admitted into Guy’s
Hospital. She confessed to having eaten a piece of bread coated with
phosphorus paste. She had great abdominal pain, and died on the seventh
day after taking the phosphorus. A few hours before her death she was
profoundly and suddenly collapsed. The liver weighed 66 ozs. The
outlines of the hepatic lobules were very distinct, each central vein
being surrounded by an opaque yellowish zone; when fresh the hue was
more uniform, and the section was yellowish-white in colour. A
microscopical examination of the hepatic cells showed them laden with
fat globules, especially in the central parts of the liver.

The microscopic appearances are also characteristic. In a case of
suicidal poisoning by phosphorus, in which death took place on the
seventh day, the liver was very carefully examined by Dr. G. F. Goodart,
who reported as follows:--

    “Under a low power the structure of the liver is still readily
    recognisable, and in this the specimen differs from slides of three
    cases of acute yellow atrophy that I have in my possession. The
    hepatic cells are present in large numbers, and have their natural
    trabecular arrangement. The columns are abnormally separated by
    dilated blood or lymph-spaces, and the individual cells are cloudy
    and ill-defined. The portal channels are everywhere characterised by
    a crowd of small nuclei which stain with logwood deeply. The
    epithelium of the smaller ducts is cloudy, and blocks the tubes in
    many cases. Under a high power (one-fifth) it is seen that the
    hepatic cells are exceedingly ill-defined in outline, and full of
    granules and even drops of oil. But in many parts, even where the
    cells themselves are hazy, the nucleus is still fairly visible. It
    appears to me that, in opposition to what others have described, the
    nuclei of the cells have in great measure resisted the degenerative
    process. The change in the cells is uniform throughout each lobule,
    but some lobules are rather more affected than others. The
    blood-spaces between the cells are empty, and the liver appears to
    be very bloodless. The portal canals are uniformly studded with
    small round nuclei or cells, which are in part, and might be said in
    great part, due to increase of the connective tissue or to a
    cirrhotic process. But I am more disposed to favour the view that
    they are due to migration from the blood-vessels, because they are
    so uniform in size, and the hepatic cells and connective tissue in
    their neighbourhood are undergoing no changes in the way of growth
    whatever. I cannot detect any fatty changes in the vessels, but some
    of the smaller biliary ducts contain some cloudy albuminous
    material, and their nucleation is not distinct. No retained biliary
    pigment is visible.”[309]

[309] “A Recent Case of Suicide,” by Herbert J. Capon, M.D.--_Lancet_,
March 18, 1882.

Oscar Wyss,[310] in the case of a woman twenty-three years old, who died
on the fifth day after taking phosphorus, describes, in addition to the
fatty appearance of the cells, a new formation of cells lying between
the lobules and in part surrounding the gall-ducts and the branches of
the portal vein and hepatic artery.

[310] Virchow’s _Archiv. f. path. Anat._, Bd. 33, Hft. 3, S. 432, 1865.

Salkowsky[311] found in animals, which he killed a few hours after
administering to them toxic doses of phosphorus, notable hyperæmia of
the throat, intestine, liver, and kidneys--both the latter organs being
larger than usual. The liver cells were swollen, and the nuclei very
evident, but they contained no fat, fatty drops being formed afterwards.

[311] _Ibid._, Bd. 34, Hft. 1 u. 2, S. 73, 1865.

§ 294. =The kidneys= exhibit alterations very similar and analogous to
those of the liver. They are mostly enlarged, congested, and flabby,
with extravasations under the capsule, and show microscopic changes
essentially consisting in a fatty degeneration of the epithelium. In
cases attended with hæmorrhage, the tubuli may be here and there filled
with blood. The fatty epithelium is especially seen in the contorted
tubes, and the walls of the vessels, both of the capsule and of the
malpighian bodies, also undergo the same fatty change. In cases in which
death has occurred rapidly, the kidneys have been found almost healthy,
or a little congested only. The pancreas has also been found with its
structure in part replaced by fatty elements.

Of great significance are also the fatty changes in the general muscular
system, and more especially in the heart. The muscular fibres of the
heart quickly lose their transverse striæ, which are replaced by drops
of fat. Probably this change is the cause of the sudden death not
unfrequently met with in phosphorus poisoning.

=In the lungs=, when the phosphorus is taken in substance, there is
little “naked-eye” change, but Perls,[312] by manometric researches, has
shown that the elasticity is always decreased. According to experiments
on animals, when the vapour is breathed, the mucous membrane is red,
congested, swollen, and has an acid reaction.

[312] Deutsch. _Archiv f. klin. Med._, vi. Hft. 1, S. 1, 1869.

=In the nervous system= no change has been remarked, save occasionally
hæmorrhagic points and extravasations.

§ 295. =Diagnostic Differences between Acute Yellow Atrophy of the Liver
and Fatty Liver produced by Phosphorus.=--O. Schultzen and O. L. Riess
have collected and compared ten cases of fatty liver from phosphorus
poisoning, and four cases of acute yellow atrophy of the liver, and,
according to them, the chief points of distinction are as follows:--In
phosphorus poisoning the liver is large, doughy, equally yellow, and
with the acini well marked; while in acute yellow atrophy the liver is
diminished in size, tough, leathery, and of a dirty yellow hue, the
acini not being well mapped out. The “phosphorus” liver, again, presents
the cells filled with large fat drops, or entirely replaced by them; but
in the “atrophy” liver, the cells are replaced by a finely-nucleated
detritus and through newly-formed cellular tissue. Yellow atrophy seems
to be essentially an inflammation of the intralobular connective tissue,
while in phosphorus poisoning the cells become gorged by an infiltration
of fat, which presses upon the vessels and lessens the blood supply,
and the liver, in consequence, may, after a time, waste.

There is also a clinical distinction during life, not only in the
lessening bulk of the liver in yellow atrophy, in opposition to the
increase of size in the large phosphorus liver, but also in the
composition of the renal secretion. In yellow atrophy the urine contains
so much leucine and tyrosin, that the simple addition of acetic acid
causes at once a precipitate. Schultzen and Riess also found in the
urine, in cases of yellow atrophy, _oxymandelic acid_ (C₈H₈O₄), but in
cases of phosphorus poisoning a nitrogenised acid, fusing at 184° to
185°.

According to Maschka, grey-white, knotty, fæcal masses are found in the
intestines in yellow atrophy, but never in cases of phosphorus
poisoning. In the latter, it is more common to find a slight intestinal
catarrh and fluid excreta.

§ 296. =The Detection of Phosphorus=.--The following are the chief
methods in use for the separation and detection of phosphorus:[313]--

[313] It has been recommended to dissolve the phosphorus out from
organic matters by carbon disulphide. On evaporation of the latter the
phosphorus is recognised by its physical properties. Such a method is of
but limited application, although it may sometimes be found useful. I
have successfully employed it in the extraction of phosphorus from the
crop of a fowl; but on this occasion it happened to be present in large
quantity.

1. =Mitscherlich’s Process=.--The essential feature of this process is
simply distillation of free phosphorus, and observation of its luminous
properties as the vapour condenses in the condensing tube. The
conditions necessary for success are--(1) that the apparatus should be
in total darkness;[314] and (2) that there should be no substance
present, such as alcohol or ammonia,[315] which, distilling over with
the phosphorus-vapour, could destroy its luminosity. A convenient
apparatus, and one certain to be in all laboratories, is an ordinary
Florence flask, containing the liquid to be tested, fitted to a glass
Liebig’s condenser, supported on an iron sand-bath (which may, or may
not, have a thin layer of sand), and heated by a Fletcher’s low
temperature burner. The distillate is received into a flask. This
apparatus, if in darkness, works well; but should the observer wish to
work in daylight, the condenser must be enclosed in a box perfectly
impervious to light, and having a hole through which the luminosity of
the tube may be seen, the head of the operator and the box being covered
with a cloth. If there be a stream of water passing continuously
through the condenser, a beautiful luminous ring of light appears in the
upper part of the tube, where it remains fixed for some time. Should,
however, the refrigeration be imperfect, the luminosity travels slowly
down the tube into the receiver. In any case, the delicacy of the test
is extraordinary.[316] If the organic liquid is alkaline, or even
neutral, there will certainly be some evolution of ammonia, which will
distil over before the phosphorus, and retard (or, if in sufficient
quantity, destroy) the luminosity. In such a case it is well, as a
precaution, to add enough sulphuric acid to fix the ammonia, omitting
such addition if the liquid to be operated upon is acid.

[314] Any considerable amount of phosphorescence can, however, be
observed in twilight.

[315] Many volatile substances destroy the luminous appearance of
phosphorus vapour, _e.g._, chlorine, hydric sulphide, sulphur dioxide,
carbon disulphide, ether, alcohol, petroleum, turpentine, creasote, and
most essential oils. On the other hand, bromine, hydrochloric acid,
camphor, and carbonate of ammonia do not seem to interfere much with the
phosphorescence.

[316] Fresenius states that he and Neubauer, with 1 mgrm. of phosphorus
in 200,000, recognised the light, which lasted for half an
hour.--_Zeitschr. f. anal. Chem._, i. p. 336.

2. =The Production of Phosphine= (PH₃).--Any method which produces
phosphine (phosphuretted hydrogen), enabling that gas to be passed
through nitrate of silver solution, may be used for the detection of
phosphorus. Thus, Sonnenschein states that he has found phosphorus in
extraordinary small amount, mixed with various substances, by heating
with potash in a flask, and passing the phosphine into silver nitrate,
separating the excess of silver, and recognising the phosphoric acid by
the addition of molybdate of ammonia.[317]

[317] Sonnenschein, _Handbuch der gerichtlichen Chemie_, Berlin, 1869.

The usual way is, however, to produce phosphine by means of the action
on free phosphorus of nascent hydrogen evolved on dissolving metallic
zinc in dilute sulphuric acid. Phosphine is formed by the action of
nascent hydrogen on solid phosphorus, phosphorous acid, and
hypophosphorous acid; but no phosphine can be formed in this way by the
action of hydrogen on phosphoric acid.

Since it may happen that no free phosphorus is present, but yet the
first product (phosphorous acid) of its oxidation, the production of
phosphine becomes a necessary test to make on failure of Mitscherlich’s
test; if no result follows the proper application of the two processes,
the probability is that phosphorus has not been taken.

Blondlot and Dusart evolve hydrogen from zinc and dilute sulphuric acid,
and pass the gas into silver nitrate; if the gas is pure, there is of
course no reduction; the liquid to be tested is then added to the
hydrogen-generating liquid, and if phosphorous or hypophosphorous acids
be present, a black precipitate of phosphor-silver will be produced. To
prove that this black precipitate is neither that produced by SH₂, nor
by antimony nor arsenic, the precipitate is collected and placed in the
apparatus to be presently described, and the spectroscopic appearances
of the phosphine flame observed.

3. =Tests Dependent on the Combustion of Phosphine= (PH₃).--A hydrogen
flame, containing only a minute trace of phosphorus, or of the lower
products of its oxidation, acquires a beautiful green tint, and
possesses a characteristic _spectrum_. In order to obtain the latter in
its best form, the amount of phosphine must not be too large, or the
flame will become whitish and livid, and the bands lose their defined
character, rendering the spectrum continuous. Again, the orifice of the
tube whence the gas escapes must not be too small; and the best result
is obtained when the flame is cooled.

M. Salet has proposed two excellent methods for the observation of
phosphine by the spectroscope:--

(1) He projects the phosphorus-flame on a plane vertical surface,
maintained constantly cold by means of a thin layer of running water;
the green colour is especially produced in the neighbourhood of the cool
surface.

(2) At the level of the base of the flame, there is an annular space,
through which a stream of cold air is continually blown upwards. Thus
cooled, the light is very pronounced, and the band δ, which is almost
invisible in the ordinary method of examination, is plainly seen.[318]

[318] Consult _Spectres Lumineux_, par M. Lecoq de Boisbaudran, Paris,
1874. See also Christofle and Beilstrom’s “Abhandlung,” in _Fresenius’
Zeitschr. f. anal. Chem._, B. 2, p. 465, and B. 3, p. 147.

An apparatus (devised by Blondlot, and improved by Fresenius) for the
production of the phosphine flame in medico-legal research, is
represented in the following diagram:--

[Illustration]

Several of the details of this apparatus may be modified at the
convenience of the operator. A is a vessel containing sulphuric acid; B
is partly filled with granulated zinc, and hydrogen may be developed at
pleasure; _c_ contains a solution of nitrate of silver; _d_ is a tube at
which the gas can be lit; _e_, a flask containing the fluid to be
tested, and provided with a tube _f_, at which also the gas issuing can
be ignited. The orifice should be provided with a platinum nozzle. When
the hydrogen has displaced the air, both tubes are lit, and the two
flames, being side by side, can be compared. Should any phosphorus come
over from the zinc (a possibility which the interposed silver nitrate
ought to guard against), it is detected; the last flask is now gently
warmed, and if the flame is green, or, indeed, in any case, it should be
examined by the spectroscope.[319]

[319] F. Selmi has proposed the simple dipping of a platinum loop into a
liquid containing phosphoric acid, and then inserting it into the tip of
a hydrogen flame.

§ 297. The spectrum, when fully developed, shows one band in the orange
and yellow between C and D, but very close to D, and several bands in
the green. But the bands δ, γ, α, and β are the most characteristic. The
band δ has its centre about the wave-length 599·4; it is easily
distinguished when the slit of the spectroscope is a little wide, but
may be invisible if the slit is too narrow. It is best seen by M.
Salet’s second process, and, when cooled by a brisk current of air, it
broadens, and may extend closer to D. The band γ has a somewhat decided
border towards E, while it is nebulous towards D, and it is, therefore,
very difficult to say where it begins or where it ends; its centre may,
however, be put at very near 109 of Boisbaudran’s scale, corresponding
to W. L. 560·5, if the flame is free. This band is more distinct than β,
but with a strong current of air the reverse is the case. The middle of
the important band α is nearly marked by Fraunhofer’s line E.
Boisbaudran gives it as coinciding with 122 of his scale W. L. 526·3. In
ordinary conditions (that is, with a free uncooled flame) this is the
brightest and most marked of all the bands. The approximate middle of
the band β is W. L. 510·6 (Boisbaudran’s scale 129·00).

=Lipowitz’s Sulphur Test.=--Sulphur has the peculiar property of
condensing phosphorus on its surface, and of this Lipowitz proposed to
take advantage. Pieces of sulphur are digested some time with the liquid
under research, subsequently removed, and slightly dried. When examined
in the dark, should phosphorus be present, they gleam strongly if rubbed
with the finger, and develop a phosphorus odour. The test is wanting in
delicacy, nor can it well be made quantitative; it has, however, an
advantage in certain cases, _e.g._, the detection of phosphorus in an
alcoholic liquid.

Scherer’s test, as modified by Hager,[320] is a very delicate and
almost decisive test. The substances to be examined are placed in a
flask with a little lead acetate (to prevent the possibility of any
hydric sulphide being evolved), some ether added, and a strip of
filter-paper soaked in a solution of silver nitrate is then suspended in
the flask; this is conveniently done by making a slit in the bottom of
the cork, and in the slit securing the paper. The closed flask is placed
in the dark, and if phosphorus is present, in a few minutes there is a
black stain. It may be objected that arsine will cause a similar
staining, but then arsine could hardly be developed under the
circumstances given. It is scarcely necessary to observe that the paper
must be wet.

[320] _Pharm. Central-halle_, 20, 353.

§ 298. =Chemical Examination of the Urine.=--It may be desirable, in any
case of suspected phosphorus poisoning, to examine the renal secretion
for leucin and tyrosin, &c. Leucin may be found as a deposit in the
urine. Its general appearance is that of little oval or round discs,
looking like drops of fat. It can be recognised by taking up one or more
of these little bodies and placing them in the author’s subliming cell
(see § 314). By careful heating it will sublime wholly on to the upper
cover. On now adding a little nitric acid to the sublimed leucin, and
drying, and then to the dried residue adding a droplet of a solution of
sodium hydrate, leucin forms an oily drop. Tyrosin also may occur as a
sediment of little heaps of fine needles. The best test for tyrosin is
to dissolve in hot water, and then add a drop of a solution of mercuric
nitrate and mercurous nitrate, when a rose colour is at once developed,
if the tyrosin is in very minute quantity; but if in more than traces,
there is a distinct crimson precipitate. To separate leucin and tyrosin
from the urine, the best process is as follows:--The urine is filtered
from any deposit, evaporated to a thin syrup, and decanted from the
second deposit that forms. The two deposits are mixed together and
treated with dilute ammonia, which will dissolve out any tyrosin and
leave it in needles, if the ammonia is spontaneously evaporated on a
watch-glass. The urine is then diluted and treated with neutral and
basic acetates of lead, filtered, and the lead thrown out of the
filtrate by hydric sulphide. The filtrate is evaporated to a syrup, and
it then deposits leucin mixed with some tyrosin. If, however, the syrup
refuses to crystallise, it is treated with cold absolute alcohol, and
filtered, the residue is then boiled up with spirit of wine, which
extracts leucin, and deposits it on cooling in a crystalline form. To
obtain oxymandelic acid, the mother liquor, from which leucin and
tyrosin have been extracted, is precipitated with absolute alcohol,
filtered, and then the alcoholic solution evaporated to a syrup. This
syrup is acidified by sulphuric acid, and extracted with ether; the
ether is filtered off and evaporated to dryness; the dry residue will be
in the form of oily drops and crystals. The crystals are collected,
dissolved in water, and the solution precipitated by lead acetate to
remove colouring-matters; after filtration it is finally precipitated
by basic acetate. On decomposition of the basic acetate, by suspending
in water and saturating with hydric sulphide, the ultimate filtrate on
evaporation deposits colourless, flexible needles of oxymandelic acid.
The nitrogenised acid which Schultzen and Riess obtained from urine in a
case of phosphorus poisoning, was found in an alcohol and ether
extract--warts of rhombic scales separating out of the syrupy residue.
These scales gave no precipitate with basic acetate, but formed a
compound with silver nitrate. The silver compound was in the form of
shining white needles, and contained 33·9 per cent. of silver; the acid
was decomposed by heat, and with lime yielded aniline. Its melting-point
is given at from 184° to 185°. The occurrence of some volatile substance
in phosphorus urine, which blackens nitrate of silver, and which is
probably phosphine, was first noticed by Selmi.[321] Pesci and Stroppa
have confirmed Selmi’s researches. It is even given off in the cold.

[321] _Giornale Internaz. della Scienza Med._, 1879, Nro. 5, p. 645.

§ 299. =The quantitative estimation of phosphorus= is best carried out
by oxidising it into phosphoric acid, and estimating as ammon. magnesian
phosphate. To effect this, the substances are distilled in an atmosphere
of CO₂ into a flask with water, to which a tube containing silver
nitrate is attached; the latter retains all phosphine, the former solid
phosphorus. If necessary, the distillate may be again distilled into
AgNO₃; and in any case the contents of the [U]-tube and flask are mixed,
oxidised with nitromuriatic acid, filtered from silver chloride, and the
phosphoric acid determined in the usual way.

In the case of a child poisoned by lucifer matches, Sonnenschein
estimated the free phosphorus in the following way:--The contents of the
stomach were diluted with water, a measured part filtered, and the
phosphoric acid estimated. The other portion was then oxidised by HCl
and potassic chlorate, and the phosphoric acid estimated--the difference
being calculated as free phosphorus.

§ 300. =How long can Phosphorus be recognised after Death?=--One of the
most important matters for consideration is the time after death in
which free phosphorus, or free phosphoric acids, can be detected. Any
phosphorus changed into ammon. mag. phosphate, or into any other salt,
is for medico-legal purposes entirely lost, since the expert can only
take cognisance of the substance either in a free state, as phosphine,
or as a free acid.

The question, again, may be asked in court--Does the decomposition of
animal substances rich in phosphorus develop phosphine? The answer to
this is, that no such reaction has been observed.

A case is related[322] in which phosphorus was recognised, although the
body had been buried for several weeks and then exhumed.

[322] _Pharm. Zeitsch. f. Russl._, Jahrg. 2, p. 87.

The expert of pharmacy of the Provincial Government Board of Breslau has
also made some experiments in this direction, which are worthy of
note:--Four guinea-pigs were poisoned, each by 0·023 grm. of phosphorus;
they died in a few hours, and were buried in sandy-loam soil, 0·5 metre
deep. Exhumation of the first took place four weeks after. The
putrefying organs--heart, liver, spleen, stomach, and all the
intestines--tested by Mitscherlich’s method of distillation, showed
characteristic phosphorescence for nearly one hour.

The second animal was exhumed after eight weeks in a highly putrescent
state. Its entrails, on distillation, showed the phosphorescent
appearance for thirty-five minutes.

The third animal was taken from the earth after twelve weeks, but no
free phosphorus could be detected, although there was evidence of the
lower form of oxidation (PO₃) by Blondlot’s method.

The fourth animal was exhumed after fifteen weeks, but neither free
phosphorus nor PO₃ could be detected.[323]

[323] _Vierteljahrsschrift für gerichtliche Medicin_, Jan. 7, 1876; see
also _Zeitschr. f. anal. Chemie_, 1872.

A man, as well as a cat, was poisoned by phosphorus. On analysis,
twenty-nine days after death, negative results were alone
obtained.--_Sonnenschein._

It will thus be evident that there is no constant rule, and that, even
when decomposition is much advanced, an examination _may_ be
successful.




PART VI.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE
MOST PART BY ALCOHOLIC SOLVENTS.


DIVISION I.--VEGETABLE ALKALOIDS.


I.--General Methods of Testing and Extracting Alkaloids.

§ 301. =General Tests for Alkaloids.=--In order to ascertain whether an
alkaloid is present or not, a method of extraction must be pursued
which, while disposing of fatty matters, salts, &c., shall dissolve as
little as possible of foreign substances--such a method, _e.g._, as the
original process of Stas, or one of its modern modifications.

If to the acid aqueous solution finally obtained by this method a dilute
solution of soda be added, drop by drop, until it is rendered feebly
alkaline, _and no precipitate appear_, whatever other poisonous
plant-constituents may be present, all ordinary alkaloids[324] are
absent.

[324] In the case of morphine tartrate, this test will not answer. See
the article on Morphine.

In addition to this negative test, there are also a number of substances
which give well-marked crystalline or amorphous precipitates with
alkaloids.

§ 302. These may be called “group reagents.” The chief members of the
group-reagents are--Iodine dissolved in hydriodic acid, iodine dissolved
in potassic iodide solution, bromine dissolved in potassic bromide
solution, hydrargo-potassic iodide, bismuth-potassic iodide, cadmic
potassic iodide; the chlorides of gold, of platinum, and mercury; picric
acid, gallic acid, tannin, chromate of potash, bichromate of potash,
phospho-molybdic acid, phospho-tungstic acid, silico-tungstic acid, and
Fröhde’s reagent. It will be useful to make a few general remarks on
some of these reagents.

=Iodine in hydriodic acid= gives either crystalline or amorphous
precipitates with nearly all alkaloids; the compound with morphine, for
example, is in very definite needles; with dilute solutions of
atropine, the precipitate is in the form of minute dots, but the
majority of the precipitates are amorphous, and all are more or less
coloured.

=Iodine dissolved in a solution of potassic iodide= gives with alkaloids
a reddish or red-brown precipitate, and this in perhaps a greater
dilution than almost any reagent. When added to an aqueous solution, the
precipitates are amorphous, but if added to an alcoholic solution,
certain alkaloids then form crystalline precipitates; this, for example,
is the case with berberine and narceine. By treating the precipitate
with aqueous sulphurous acid, a sulphate of the alkaloid is formed and
hydriodic acid, so that by suitable operations the alkaloid may readily
be recovered from this compound. A solution of bromine in potassic
bromide solution also gives similar precipitates to the above, but it
forms insoluble compounds with phenol, orcin, and other substances.

=Mercuric potassic iodide= is prepared by decomposing mercuric chloride
with potassic iodide in excess. The proportions are 13·546 grms. of
mercuric chloride and 49·8 of potassic iodide, and water sufficient to
measure, when dissolved, 1 litre. The precipitates from this reagent are
white and flocculent; many of them become, on standing, crystalline.

=Bismuthic potassic iodide= in solution precipitates alkaloids, and the
compounds formed are of great insolubility, but it also forms compounds
with the various albuminoid bodies.

=Chloride of gold= forms with the alkaloids compounds, many of which are
crystalline, and most admit of utilisation for quantitative
determinations. Chloride of gold does not precipitate amides or ammonium
compounds, and on this account its value is great. The precipitates are
yellow, and after a while are partly decomposed, when the colour is of a
reddish-brown.

=Platinic chloride= also forms precipitates with most of the alkaloids,
but since it also precipitates ammonia and potassic salts, it is
inferior to gold chloride in utility.

§ 303. (1.) =Phosphomolybdic Acid as a Reagent for
Alkaloids.=--_Preparation_; Molybdate of ammonia is precipitated by
phosphate of soda; and the well-washed yellow precipitate is suspended
in water and warmed with carbonate of soda, until it is entirely
dissolved. This solution is evaporated to dryness, and the ammonia fully
expelled by heating. If the molybdic acid is fairly reduced by this
means, it is to be moistened by nitric acid, and the heating repeated.
The now dry residue is warmed with water, nitric acid added to strong
acid reaction, and the mixture diluted with water, so that 10 parts of
the solution contain 1 of the dry salt. The precipitates of the
alkaloids are as follows:--

  Aniline,                 Bright-yellow, flocculent.
  Morphine,                      „             „
  Narcotine,               Brownish-yellow,    „
  Quinine,                 Whitish-yellow,     „
  Cinchonine,                    „             „
  Codeine,                 Brownish-yellow, voluminous.
  Strychnine,              White-yellow,        „
  Brucine,                 Yelk-yellow, flocculent.
  Veratrine,               Bright-yellow,    „
  Jervine,                       „           „
  Aconitine,                     „           „
  Emetine,                       „           „
  Theine,                  Bright-yellow, voluminous.
  Theobromine,                   „             „
  Solanine,                Citron-yellow, pulverulent.
  Atropine,                Bright-yellow, flocculent.
  Hyoscyamine,                   „             „
  Colchicine,              Orange-yellow,      „
  Delphinine,              Grey-yellow, voluminous.
  Berberine,               Dirty-yellow, flocculent.
  Coniine,                 Bright-yellow, voluminous.
  Nicotine,                      „            „
  Piperine,                Brownish-yellow, flocculent.

(2.) =Silico-Tungstic Acid as a Reagent for Alkaloids.=--Sodium
tungstate is boiled with freshly precipitated gelatinous silica. To the
solution is added mercurous nitrate, which precipitates the yellow
mercurous silico-tungstate. This is filtered, well-washed, and
decomposed by an equivalent quantity of hydrochloric acid;
silico-tungstic acid then goes into solution, and mercurous chloride
(calomel) remains behind. The clear filtrate is evaporated to drive off
the excess of hydrochloric acid, and furnishes, on spontaneous
evaporation, large, shining, colourless octahedra of silico-tungstic
acid, which effloresce in the air, melt at 36°, and are easily soluble
in water or alcohol.

This agent produces no insoluble precipitate with any metallic salt.
Cæsium and rubidium salts, even in dilute solutions, are precipitated by
it; neutral solutions of ammonium chloride give with it a white
precipitate, soluble with difficulty in large quantities of water. It
precipitates solutions of the salts of quinine, cinchonine, morphine,
atropine, &c.; if in extremely dilute solution, an opalescence only is
produced: for instance, it has been observed that cinchonine
hydrochlorate in 1/200000, quinia hydrochlorate in 1/20000,
morphia hydrochlorate in 1/15285 dilution, all gave a distinct
opalescence.--_Archiv der Pharm._, Nov., Dr. Richard Godeffroy.

(3.) =Scheibler’s Method for Alkaloids: Phospho-Tungstic
Acid.=--Ordinary commercial sodium tungstate is digested with half its
weight of phosphoric acid, specific gravity 1·13, and the whole allowed
to stand for some days, when the acid separates in crystals. A solution
of these crystals will give a distinct precipitate with the most minute
quantities of alkaloids, 1/200000 of strychnine, and 1/100000 of
quinine. The alkaloid is liberated by digestion with barium hydrate (or
calcium hydrate); and if volatile, may be distilled off, if fixed,
dissolved out by chloroform. In complex mixtures, colouring-matter may
be removed by plumbic acetate, the lead thrown out by SH₂, and
concentrated, so as to remove the excess of SH₂.

§ 304. =Schulze’s reagent= is phospho-antimonic acid. It is prepared by
dropping a strong solution of antimony trichloride into a saturated
solution of sodic phosphate. The precipitation of the alkaloids is
effected by this reagent in a sulphuric acid solution.

§ 305. =Dragendorff’s reagent= is a solution of potass-bismuth iodide;
it is prepared by dissolving bismuth iodide in a hot solution of
potassium iodide, and then diluting with an equal volume of iodide of
potassium solution. On the addition of an acid solution of an alkaloid,
a kermes-red precipitate falls down, which is in many cases crystalline.

=Marm’s reagent= is a solution of potass-cadmium iodide. It is made on
similar principles.

=Potass-zinc iodide= in solution is also made similarly. The
precipitates produced in solutions of narceine and codeine are
crystalline and very characteristic.

§ 306. =Colour Tests.=--=Fröhde’s reagent= is made by dissolving 1 part
of sodic molybdate in 10 parts of strong sulphuric acid; it strikes
distinctive colours with many alkaloids.

=Mandelin’s reagent= is a solution of meta-vanadate of ammonia in mono-
or dihydrated sulphuric acid. The strength should be 1 part of the salt
to 200 of the acid. This reagent strikes a colour with many alkaloids,
and aids to their identification. It is specially useful to supplement
and correct other tests. The following table gives the chief colour
reactions, with the alkaloids. (See also p. 55 for the spectroscopic
appearances of certain of the colour tests.)


METHODS OF SEPARATION.

§ 307. =Stas’s Process.=--The original method of Stas[325] (afterwards
modified by Otto)[326] consisted in extraction of the organic matters by
strong alcohol, with the addition of tartaric acid; the filtered
solution was then carefully neutralised with soda, and shaken up with
ether, the ethereal solution being separated by a pipette. Subsequent
chemists proposed chloroform instead of ether,[327] the additional use
of amyl-alcohol,[328] and the substitution of acetic, hydrochloric, and
sulphuric for tartaric acid.

[325] _Annal d. Chem. u. Pharm._, 84, 379.

[326] _Ib._, 100, 44. _Anleitung zur Ausmittel. d. Gifte._

[327] Rodgers and Girwood, _Pharm. Journ. and Trans._, xvi. 497;
Prollin’s _Chem. Centralb._, 1857, 231; Thomas, _Zeitschr. für analyt.
Chem._, i. 517, &c.

[328] Erdmann and v. Ushlar, _Ann. Chem. Pharm._, cxx. pp. 121-360.


COLOUR REACTIONS[329] OF CERTAIN ALKALOIDS.

[329] Caustic potash also gives characteristic colours with certain
alkaloids. Out of seventy-two alkaloids (using 0·5 mgrm.), the following
alone gave characteristic colours when fused with KHO:--Quinine,
grass-green, and peculiar odour; quinidine, becoming yellower and
finally brown; cinchonine, at first brownish-red to violet, with green
edges, later, bluish-green; cinchonidine, blue passing into grey;
cocaine, greenish-yellow, turning to blue, and then dirty red on strong
heating.--W. Lenz, _Zeit. f. anal. Chem._, 25, 29-32.

  +-----------+-----------------+------------------+-------------------+
  |  Name of  |Strong Sulphuric | Fröhde’s Reagent.|Mandelin’s Reagent.|
  |Substance. |     Acid.       |                  |                   |
  +-----------+-----------------+------------------+-------------------+
  |           |                 |                  |                   |
  |Strychnine.|       ...       |        ...       |Violet-blue, then  |
  |           |                 |                  |lastly cinnabar-   |
  |           |                 |                  |red.               |
  |           |                 |                  |                   |
  |Brucine.   |Pale red.        |Red, then yellow. |Yellow-red to      |
  |           |                 |                  |orange, afterwards |
  |           |                 |                  |blood-red.         |
  |           |                 |                  |                   |
  |Curarine.  |Fine red.        |        ...       |        ...        |
  |           |                 |                  |                   |
  |Quinine.   |       ...       |Greenish.         |Weak orange, then  |
  |           |                 |                  |blue-green, lastly |
  |           |                 |                  |green-brown.       |
  |           |                 |                  |                   |
  |Atropine.  |       ...       |        ...       |Red, then yellow-  |
  |           |                 |                  |red, and lastly    |
  |           |                 |                  |yellow.            |
  |           |                 |                  |                   |
  |Aconitine. |       ...       |        ...       |         ...       |
  |           |                 |                  |                   |
  |Veratrine. |Yellow, then     |Gamboge-yellow,   |Yellow, orange,    |
  |           |orange, blood-   |then cherry-red.  |blood-red, lastly  |
  |           |red, lastly      |                  |carmine-red.       |
  |           |carmine-red.     |                  |                   |
  |           |                 |                  |                   |
  |Morphine.  |       ...       |Violet, green,    |Reddish, then      |
  |           |                 |blue-green, and   |blue-violet.       |
  |           |                 |yellow.           |                   |
  |           |                 |                  |                   |
  |Narcotine. |Yellow, then     |Green, then brown-|Cinnabar-red, then |
  |           |raspberry colour.|green, yellow,    |carmine-red.       |
  |           |                 |lastly red.       |                   |
  |           |                 |                  |                   |
  |Codeine.   |        ...      |Dirty green, then |Green-blue to blue.|
  |           |                 |blue, lastly      |                   |
  |           |                 |yellow.           |                   |
  |           |                 |                  |                   |
  |Papaverine.|        ...      |Green, then blue- |Blue-green to blue.|
  |           |                 |violet, lastly    |                   |
  |           |                 |cherry-red.       |                   |
  |           |                 |                  |                   |
  |Thebaine.  |Blood-red, then  |Orange, then      |Red to orange.     |
  |           |yellow-red.      |colourless.       |                   |
  |           |                 |                  |                   |
  |Narceine.  |Grey-brown, then |Brown, green, red,|Violet, then       |
  |           |blood-red.       |lastly blue.      |orange.            |
  |           |                 |                  |                   |
  |Nicotine.  |        ...      |Yellowish, then   |Transitory dark    |
  |           |                 |red.              |colour.            |
  |           |                 |                  |                   |
  |Coniine.   |        ...      |Yellow.           |        ...        |
  |           |                 |                  |                   |
  |Colchicine.|Intense yellow.  |Yellow to         |Blue-green, then   |
  |           |                 |green-yellow.     |brown.             |
  |           |                 |                  |                   |
  |Delphini-  |Red.             |Red-brown.        |Red-brown to brown.|
  |dine.      |                 |                  |                   |
  |           |                 |                  |                   |
  |Solanine.  |Red-yellow, then |Cherry-red,       |Yellow-orange,     |
  |           |brown.           |red-brown, yellow,|cherry-red, and    |
  |           |                 |yellow-green.     |lastly violet.     |
  +-----------+-----------------+------------------+-------------------+

§ 308. =Selmi’s Process for Separating Alkaloids.=--A method of
separating alkaloids from an ethereal solution has been proposed by
Selmi.[330] The alcoholic extract of the viscera, acidified and
filtered, is evaporated at 65°; the residue taken up with water,
filtered, and decolorised by basic acetate of lead. The lead is thrown
out by sulphuretted hydrogen; the solution, after concentration,
repeatedly extracted with ether; and the ethereal solution saturated
with dry CO₂, which generally precipitates some of the alkaloids. The
ethereal solution is then poured into clean vessels, and mixed with
about half its volume of water, through which a current of CO₂ is passed
for twenty minutes; this may cause the precipitation of other alkaloids
not thrown down by dry CO₂. If the whole of the alkaloids are not
obtained by these means, the solution is dehydrated by agitation with
barium oxide, and a solution of tartaric acid in ether is added (care
being taken to avoid excess); this throws down any alkaloid still
present. The detection of any yet remaining in the viscera is effected
by mixing with barium hydrate and a little water, and agitating with
_purified_ amylic alcohol; from the alcohol the alkaloids may be
subsequently extracted by agitation with very dilute sulphuric acid.

[330] F. Selmi, _Gazett. Chim. Ital._, vj. 153-166, and _Journ. Chem.
Soc._, i., 1877, 93.

Another ingenious method (also the suggestion of Selmi) is to treat the
organic substance with alcohol, to which a little sulphuric acid has
been added, to filter, digest with alcohol, and refilter. The filtrates
are united, evaporated down to a smaller bulk, filtered, concentrated to
a syrup, alkalised by barium hydrate, and, after the addition of freshly
ignited barium oxide and some powdered glass, exhausted with dry ether;
the ether filtered, the filtrate digested with lead hydrate; the
ethereal solution filtered, evaporated to dryness, and finally again
taken up with ether, which, this time, should leave on evaporation the
alkaloid almost pure.

§ 309. =Dragendorff’s Process.=--To Dragendorff we owe an elaborate
general method of separation, since it is applicable not only to
alkaloids, but to glucosides, and other active principles derived from
plants. His process is essentially a combination of those already known,
and its distinctive features are the shaking up--(1) of the acid fluid
with the solvent, thus removing colouring matters and certain
non-alkaloidal principles; and (2) of the same fluid made alkaline. The
following is his method in full. It may be advantageously used when the
analyst has to search generally for vegetable poison, although it is, of
course, far too elaborate for every case; and where, from any
circumstance, there is good ground for suspecting the presence of one or
two particular alkaloids or poisons, the process may be much shortened
and modified.[331]

[331] Dragendorff’s _Gerichtlich-chemische Ermittelung von Giften_, St.
Petersburg, 1876, p. 141.

I. The substance, in as finely-divided form as possible, is digested for
a few hours in water acidified with sulphuric acid, at a temperature of
40° to 50°, and this operation is repeated two or three times, with
filtering and pressing of the substances; later, the extracts are
united. This treatment (if the temperature mentioned is not exceeded)
does not decompose the majority of alkaloids or other active substances;
but there are a few (_e.g._, solanine and colchicine) which would be
altered by it; and, if such are suspected, maceration at the common
temperature is necessary, with substitution of acetic for sulphuric
acid.[332]

[332] When blood is to be examined, it is better to dry it, and then
powder and extract with water acidified with dilute sulphuric acid.
However, if the so-called volatile alkaloids are suspected, this
modification is to be omitted.

II. The extract is next evaporated until it begins to be of a syrupy
consistence; the residue mixed with three to four times its volume of
alcohol, macerated for twenty-four hours at about 34°, allowed to become
quite cool, and filtered from the foreign matters which have separated.
The residue is washed with alcohol of 70 per cent.

III. The filtrate is freed from alcohol by distillation, the watery
residue poured into a capacious flask, diluted (if necessary) with
water, and filtered. Acid as it is, it is extracted at the common
temperature, with frequent shaking, by freshly-rectified petroleum
ether; and, after the fluids have again separated, the petroleum ether
is removed, carrying with it certain impurities (colouring matter, &c.),
which are in this way advantageously displaced. By this operation
ethereal oils, carbolic acid, picric acid, &c., which have not been
distilled, besides piperin, may also be separated. The shaking up with
petroleum ether is repeated several times (as long as anything remains
to be dissolved), and the products are evaporated on several
watch-glasses.

RESIDUE OF PETROLEUM ETHER FROM THE ACID SOLUTION.

  1. IT IS CRYSTALLINE.   2. IT IS AMORPHOUS.     3. IT IS VOLATILE,
                                                  with a powerful
                                                  odour;
                                                         _ethereal oil,
                                                    carbolic acid, &c._

  A. _It is yellowish_,   A. It is fixed.
  and with difficulty
  volatilised.

  α. The crystals are     α. Concentrated sul-
  dissolved by concen-    phuric acid dissolves
  trated sulphuric        it immediately--
  acid, with the pro-     violet, and later
  duction of a clear      greenish-blue.
  yellow colour, pass-      _Constituents of the
  ing into brown and           black hellebore._
  greenish-brown.
             _Piperin._

  β. The solution in sulphuric acid   β. It dissolves with a yellow
  remains yellow; potassic cyanide    colour, changing into fallow-
  and caustic potash colour it, on    brown.
  warming, blood-red.                    _Constituents of aconite plant
                      _Picric acid._  and products of the decomposition
                                                         of Aconitine._

  B. IT IS COLOURLESS, LIQUEFIES      B. IT IS WHITE, SHARP-TASTING,
  EASILY, AND SMELLS STRONGLY.        AND REDDENS THE SKIN.
      _Camphor and similar matters._                        _Capsicin._

It may be expected that the substances mentioned under the heads 1, 2,
and 3 will be, in general, fully obtained by degrees. This is not the
case, however, as regards piperin and picric acid.

IV. The watery fluid is now similarly shaken up with benzene, and the
benzene removed and evaporated. Should the evaporated residue show signs
of an alkaloid (and especially of theine), the watery fluid is treated
several times with a fresh mixture of benzene, till a little of the
last-obtained benzene extraction leaves on evaporation no residue. The
benzene extracts are now united, and washed by shaking with distilled
water; again separated and filtered, the greater part of the benzene
distilled from the filtrate, and the remainder of the fluid divided and
evaporated on several watch-glasses.

The evaporated residue may contain theine, colchicine, cubebin,
digitalin, cantharidin, colocynthin, elaterin, caryophylline, absinthin,
cascarillin, populin, santonin, &c., and traces of veratrine,
delphinine, physostigmine, and berberine.

A remnant of piperin and picric acid may remain from the previous
treatment with petroleum ether.

THE BENZENE RESIDUE FROM THE ACID SOLUTION.

  1. IT IS CRYSTALLINE.               2. IT IS AMORPHOUS.

  A. WELL-FORMED, COLOURLESS          A. COLOURLESS OR PALE YELLOW
  CRYSTALS.                           RESIDUE.

  α. Sulphuric acid dissolves the     α. Sulphuric acid dissolves it at
  hair-like crystals without change   first yellow; the solution be-
  of colour; evaporation with chlo-   coming later red. Fröhde’s re-
  rine water, and subsequent treat-   agent does not colour it violet.
  ment with ammonia, gives a                                _Elaterin._
  murexide reaction.       _Theine._

  β. Sulphuric acid leaves the        β. Sulphuric acid dissolves red;
  rhombic crystals uncoloured. The    Fröhde’s reagent violet-red;[333]
  substance, taken up by oil, and     tannic acid does not precipitate.
  applied to the skin, produces a                            _Populin._
  blister.            _Cantharidin._

  γ. Sulphuric acid leaves the        γ. Sulphuric acid dissolves it
  scaly crystals at first un-         with a red colour; Fröhde’s
  coloured, then slowly develops a    reagent[334] a beautiful cherry-
  reddening. It does not blister.     red; tannic acid precipitates a
  Warm alcoholic potash-lye colours   yellowish-white.   _Colocynthin._
  it a transitory red.   _Santonin._

  δ. Sulphuric acid colours the       δ. Sulphuric acid colours it
  crystals almost black, whilst it    gradually a beautiful red, whilst
  takes itself a beautiful red        tannin does not precipitate.
  colour.                 _Cubebin._     _Constituents of the Pimento._

  B. CRYSTALS PALE TO CLEAR YELLOW.   B. PURE YELLOW RESIDUE.

  α. _Piperin._                       α. Sulphuric acid dissolves it
                                      yellow; on the addition of nitric
                                      acid, this solution is green,
                                      quickly changing to blue and
                                      violet.             _Colchicine._

  β. _Picric Acid._                   β. Sulphuric acid dissolves with
                                      separation of a violet powder;
                                      caustic potash colours it red;
                                      sulphide of ammonia violet, and,
                                      by heating, indigo-blue.
                                                     _Chrysammic acid._

  γ. Caustic potash dissolves it
  purple.                 _Aloetin._

  C. MOSTLY UNDEFINED COLOURLESS      C. A GREENISH BITTER RESIDUE,
  CRYSTALS.                           which dissolves brown in concen-
                                      trated sulphuric acid; in
                                      Fröhde’s reagent, likewise, at
                                      first brown, then at the edge
                                      green, changing into blue-violet,
                                      and lastly violet.  _Constituents
                                           of wormwood, with absynthin,
                                          besides quassiin, menyanthin,
                                         ericolin, daphnin, cnicin, and
                                                               others._

  α. Sulphuric acid dissolves it
  green-brown; bromine colours this
  solution red; dilution with water
  again green. The substance
  renders the heart-action of a
  frog slower.          _Digitalin._

  β. Sulphuric acid dissolves it
  orange, then brown, lastly red-
  violet. Nitric acid dissolves it
  yellow, and water separates as a
  jelly out of the latter solution.
  Sulphuric acid and bromine do not
  colour it red.        _Gratiolin._

  γ. Sulphuric acid dissolves it
  red-brown. Bromine produces in
  this solution red-violet
  stripes. It does not act on
  frogs.              _Cascarillin._

  D. GENERALLY UNDEFINED YELLOW CRYSTALLISATION.--Sulphuric acid dis-
  solves it olive-green. The alcoholic solution gives with potassic
  iodide a colourless and green crystalline precipitate.    _Berberin._

[333] Fröhde’s reagent is described at page 239.

[334] Fröhde’s reagent is described at page 239.

V. As a complete exhaustion of the watery solution is not yet attained
by the benzene agency, another solvent is tried.

THE WATERY SOLUTION IS NOW EXTRACTED IN THE SAME WAY BY CHLOROFORM.

In chloroform the following substances are especially taken
up:--Theobromine, narceine, papaverine, cinchonine, jervine, besides
picrotoxin, syringin, digitalin, helleborin, convallamarin, saponin,
senegin, smilacin. Lastly, portions of the bodies named in Process IV.,
which benzene failed to extract entirely, enter into solution, as well
as traces of brucine, narcotine, physostigmine, veratrine, delphinine.
The evaporation of the chloroform is conducted at the ordinary
temperature in four or five watch-glasses.

THE CHLOROFORM RESIDUE FROM THE ACID SOLUTION.[335]

[335] Chloroform removes small portions of acetate of aconitine from
acid solution, Dunstan and Umney, _J. C. S._, 1892, p. 338.

  1. THE RESIDUE IS MORE OR LESS      2. THE RESIDUE IS AMORPHOUS.
  MARKEDLY CRYSTALLINE.

  A. _It gives in the sulphuric       A. _In acetic acid solution it
  acid solution evidence of an        renders the action of the frog’s
  alkaloid by its action towards      heart slower, or produces local
  iodine and iodide of potassium._    anæsthesia._

                                      _aa_. It does not produce local
                                      anæsthesia.

  α. Sulphuric acid dissolves it      α. Sulphuric acid dissolves it
  without the production of colour,   red-brown, bromine produces a
  and chlorine and ammonia give no    beautiful purple colour, water
  murexide reaction.   _Cinchonine._  changes it into green, hydro-
                                      chloric acid dissolves it
                                      greenish-brown.      _Digitalin._

  β. Sulphuric acid dissolves it      β. Sulphuric acid dissolves it
  without colour, chlorine and        yellow, then brown-red; on ad-
  ammonia give, as with theine, a     dition of water this solution be-
  murexide reaction.  _Theobromine._  comes violet. Hydrochloric acid,
                                      on warming, dissolves it red.
                                                       _Convallamarin._

                                      _bb_. It produces local anæsthe-
                                      sia.

                                      α. Sulphuric acid dissolves it
                                      brown. The solution becomes, by
                                      extracting with water, violet,
                                      and can even be diluted with two
                                      volumes of water without losing
                                      its colour.            _Saponin._

                                      β. Sulphuric acid dissolves it
                                      yellow. On diluting with water
                                      the same reaction occurs as in
                                      the previous case, but more
                                      feebly.                _Senegin._

  γ. Sulphuric acid does not colour   γ. Sulphuric acid dissolves
  in the cold; on warming, the        brown, and the solution becomes
  solution becomes a blue violet.     red by the addition of a little
                       _Papaverine._  water. The action is very weak.
                                                            _Smilacin._

                                      _cc_. Sulphuric acid dissolves it
                                      with the production of a dirty
                                      red, hydrochloric acid, in the
                                      cold, with that of a reddish-
                                      brown colour, and the last solu-
                                      tion becomes brown on boiling.
                                        _Constituents of the hellebore,
                                                 particularly Jervine._

  δ. Sulphuric acid dissolves it in
  the cold with the production of a
  blue colour.  _Unknown impurities,
          many commercial samples of
                        Papaverine._

  ε. Sulphuric acid dissolves it at
  first grey-brown; the solution
  becomes in about twenty-four
  hours blood-red. Iodine water
  colours it blue.       _Narceine._

  B. IT GIVES NO ALKALOID REACTION.   B. Is inactive, and becomes blue
                                      by sulphuric acid; by Fröhde’s
                                      reagent[336] dark cherry-red.
                                      Hydrochloric acid dissolves it
                                      red. The solution becomes, by
                                      boiling, colourless.  _Syringin._

  α. Sulphuric acid dissolves it
  with a beautiful yellow colour;
  mixed with nitre, then moistened
  with sulphuric acid, and lastly
  treated with concentrated soda-
  lye, it is coloured a brick-red.
                       _Picrotoxin._

  β. Sulphuric acid dissolves it
  with the production of a splendid
  red colour. The substance renders
  the heart-action of a frog slower.
                       _Helleborin._

[336] Described at p. 239.

VI. THE WATERY FLUID IS NOW AGAIN SHAKEN UP WITH PETROLEUM ETHER,

in order to take up the rest of the chloroform, and the watery fluid is
saturated with ammonia. The watery solution of _aconitine_ and _emetine_
is liable to undergo, through free ammonia, a partial decomposition;
but, on the other hand, it is quite possible to obtain, with very small
mixtures of the substances, satisfactory reactions, even out of
ammoniacal solutions.

VII. THE AMMONIACAL WATERY FLUID WITH PETROLEUM ETHER.

In the earlier stages Dragendorff advises the shaking up with petroleum
ether at about 40°, and the removal of the ether as quickly as possible
whilst warm. This is with the intention of separating by this fluid
strychnine, brucine, emetine, quinine, veratrine, &c. Finding, however,
that a full extraction by petroleum ether is either difficult or not
practicable, he prefers, as we have seen, to conclude the operation by
other agents, coming back again upon the ether for certain special
cases. Such are the volatile alkaloids; and here he recommends
treatment of the fluid by _cold_ petroleum ether, taking care _not_ to
hasten the removal of the latter. Strychnine and other fixed alkaloids
are then only taken up in small quantities, and the greater portion
remains for the later treatment of the watery fluid by benzene.

A portion of the petroleum ether, supposed to contain in solution
volatile alkaloids, is evaporated in two watch-glasses; to the one,
strong hydrochloric acid is added, the other being evaporated without
this agent. On the evaporation of the petroleum ether, it is seen
whether the first portion is crystalline or amorphous, or whether the
second leaves behind a strongly-smelling fluid mass, which denotes a
volatile alkaloid. If the residue in both glasses is without odour and
fixed, the absence of volatile acids and the presence of fixed
alkaloids, strychnine, emetine, veratrine, &c., are indicated.

THE PETROLEUM ETHER RESIDUE FROM AMMONIACAL SOLUTION.

  1. IT IS FIXED AND     2. IT IS FIXED AND       3. IT IS FIXED AND
  CRYSTALLINE.           AMORPHOUS.               ODOROUS.

  A. _The crystals are                            A. _On adding to the
  volatilised with                                watch-glass a little
  difficulty._                                    hydrochloric acid,
                                                  crystals are left
                                                  behind._

  _aa._ Sulphuric acid                            _aa._ Its solution is
  dissolves it without                            not precipitated by
  colour.                                         platin chloride.

  α. Potassic chromate   α. The purest sulphuric  α. The crystals of the
  colours this solution  acid dissolves it        hydrochloric compound
  a transitory blue,     almost without colour;   act on polarised
  then red.              sulphuric acid con-      light; and are mostly
          _Strychnine._  taining nitric acid,     needle-shaped and
                         red quickly becoming     columnar.    _Coniine
                         orange.                   and Methyl-Coniine._
                                      _Brucine._

  β. Potassic chromate   β. Sulphuric acid dis-   β. The crystals are
  does not colour it     solves it yellow,        cubical or tetra-
  blue; with chlorine    becoming deep red.       hedral.      _Alkaloid
  water and ammonia it              _Veratrine._         from Capsicum._
  gives a green colour.
             _Quinine._

                         γ. Sulphuric acid dis-
                         solves it brown-green;
                         Fröhde’s reagent red,
                         changing into green.
                                      _Emetine._

                                                  _bb_. The solution of
                                                  the hydrochlorate of
                                                  the alkaloid is pre-
                                                  cipitated by platin
                                                  chloride.
                                                          _Sarracinin._

  γ. Sulphuric acid                               B. The residue of the
  dissolves it yellow,                            hydrochlorate of the
  and the solution be-                            alkaloid is amor-
  comes gradually a                               phous, or, by further
  beautiful deep red.                             additions of HCl,
         _Sabadilline._                           becomes crystalline.

  δ. The crystals are
  easily volatilised.
             _Coniine._

                                                  _aa._ Its diluted
                                                  aqueous solution is
                                                  precipitated by
                                                  platin chloride.

                                                  α. The hydrochlorate
                                                  salt, being quickly
                                                  treated with Fröhde’s
                                                  reagent, gives after
                                                  about two minutes a
                                                  violet solution which
                                                  gradually fades.
                                                            _Lobeliin._

                                                  β. The hydrochlorate
                                                  smells like nicotine,
                                                  and becomes by
                                                  Fröhde’s reagent
                                                  yellow, and after
                                                  twenty-four hours
                                                  pale red. _Nicotine._

                                                  γ. The hydrochlorate
                                                  is without odour, the
                                                  free base smells
                                                  faintly like aniline.
                                                           _Sparteine._

                                                  _bb._ The substance
                                                  is not precipitated
                                                  from a diluted solu-
                                                  tion by platin
                                                  chloride.

                                                  α. Its petroleum
                                                  ether solution pro-
                                                  duces no turbidity
                                                  with a solution of
                                                  picric acid in petro-
                                                  leum ether; but it
                                                  leaves behind, when
                                                  mixed with the above,
                                                  crystals mostly of
                                                  three-sided plates.
                                                      _Trimethylamine._

                                                  β. The petroleum
                                                  ether solution gives,
                                                  on evaporation, when
                                                  treated similarly,
                                                  moss-like crystals.
                                                  The substance is made
                                                  blue by chloride of
                                                  lime, as well as by
                                                  diluted sulphuric
                                                  acid and bichromate
                                                  of potash. _Aniline._

                                                  γ. The alkaloid does
                                                  not smell like
                                                  methylamine, and is
                                                  not coloured by chlo-
                                                  ride of lime, sul-
                                                  phuric acid, or chro-
                                                  mate of potash.
                                                  _Volatile alkaloid of
                                                          the Pimento._

VIII. THE AMMONIACAL SOLUTION IS SHAKEN UP WITH BENZENE.

In most cases petroleum ether, benzene, and chloroform are more easily
separated from acid watery fluids than from ammoniacal, benzene and
chloroform causing here a difficulty which has perhaps deterred many
from using this method. Dragendorff, however, maintains that he has
never examined a fluid in which he could not obtain a complete
separation of the benzene and water. If the upper benzene layer is fully
gelatinous and emulsive, the under layer of water is to be removed with
a pipette as far as possible, and the benzene with a few drops of
absolute alcohol and filtration. As a rule, the water goes through first
alone, and by the time the greater part has run through, the jelly in
the filter, by dint of stirring, has become separated from the benzene,
and, finally, the jelly shrinks up to a minimum, and the clear benzene
filters off. Dragendorff filters mostly into a burette, from which
ultimately the benzene and the water are separated.

The principal alkaloids which are dissolved in benzene are--strychnine,
methyl and ethyl strychnine, brucine, emetine, quinine, cinchonine,
atropine, hyoscyamine, physostigmine, aconitine, nepalin, the alkaloid
of the _Aconitum lycoctonum_, aconellin, napellin, delphinine,
veratrine, sabatrin, sabadilline, codeine, thebaine, and narcotine.

THE BENZENE RESIDUE DERIVED FROM THE AMMONIACAL SOLUTION.

  1. IT IS FOR THE MOST PART CRYS-    2. IT IS FOR THE MOST PART AMOR-
  TALLINE.                            PHOUS.

  _a._ Sulphuric acid dissolves it    _a._ Pure sulphuric acid dis-
  without colour, the solution        solves it either whitish-red or
  being coloured neither on stand-    yellowish.
  ing nor on the addition of nitric
  acid.

  _aa._ It dilates the pupil of a
  cat.

  α. Platin chloride does not pre-    α. The solution becomes by nitric
  cipitate the aqueous solution.      acid immediately red, then quickly
  The sulphuric acid solution gives,  orange.                _Brucine._
  on warming, a peculiar smell.
                         _Atropine._

  β. Platin chloride applied to the   β. The solution becomes by little
  solution precipitates.              and little brownish-red. The sub-
                     _Hyoscyamine._   stance is coloured red by chlo-
                                      ride of lime solution, and it
                                      contracts the pupil.
                                                       _Physostigmine._

  _bb._ It does not dilate the
  pupil.

  α. The sulphuric acid solution
  becomes blue by chromate of
  potash.

  αα. The substance applied to a
  frog produces tetanus.
                       _Strychnine._

  ββ. It lowers the number of res-
  pirations in a frog.    _Ethyl and
                 Methyl Strychnine._

  β. Sulphuric acid and bichromate
  of potash do not colour it blue.

  αα. The sulphuric acid watery so-
  lution is fluorescent, and be-
  comes green on the addition of
  chlorine water and ammonia.
           _Quinine and Cinchonine._

  (The last is more difficult to
  dissolve in petroleum ether than
  quinine.)

  ββ. The solution is not fluores-
  cent.                _Cinchonine._

  _b._ Sulphuric acid dissolves it    _b._ Pure sulphuric acid dis-
  at first colourless; the solution   solves it yellow, and the solu-
  takes on standing a rose or         tion becomes later beautiful red
  violet-blue; on addition of         (with delphinine, more quickly a
  nitric acid, a blood-red or brown   darker cherry-red.)
  coloration.

  α. A solution in diluted sulphuric  α. The hydrochloric acid solution
  acid becomes, on heating, deep      gradually becomes red on heating.
  blood-red, and, when cooled,
  violet, with nitric acid. The
  aqueous solution is precipitated
  by ammonia.           _Narcotine._

                                      αα. The substance acts on a
                                      frog, causing, in large doses,
                                      tetanus.             _Veratrine._

                                      ββ. It is almost without action
                                      on frogs.             _Sabatrin._

  β. The solution in diluted sul-     β. The hydrochloric acid solution
  phuric acid becomes, on heating,    does not, on heating, become red.
  a beautiful blue. Excess of ammo-                       _Delphinine._
  nia does not precipitate in a
  diluted watery solution.
                          _Codeine._

  _c._ Sulphuric acid dissolves it    _c._ Pure sulphuric acid dis-
  with the production of a yellow     solves it yellow, and the solu-
  colour.                             tion becomes later red-brown, and
                                      gradually violet-red.

  α. The solution remains yellow      α. The substance even in small
  on standing.          _Acolyctin._  doses paralyses frogs, and
                                      dilates the pupil of a cat’s eye.
                                      Ether dissolves it with diffi-
                                      culty.                 _Nepalin._

  β. It becomes beautifully red.      β. It is easily soluble in ether,
                      _Sabadilline._  its effects are not so marked,
                                      and it does not dilate the pupil.
                                                           _Aconitine._

                                      γ. Its effects are still feeble;
                                      it does not dilate the pupil, and
                                      is with difficulty dissolved by
                                      ether.                _Napellin._

  _d._ Sulphuric acid dissolves it    _d._ Sulphuric acid dissolves it
  with an immediate deep red-brown    with a dark green colour, and the
  colour.                _Thebaine._  solution becomes, even after a
                                      few seconds, a beautiful blood-
                                      red.   _Alkaloidal substances out
                                          of the  Aconitum lycoctonum._

  _e._ Sulphuric acid dissolves it    _e._  Sulphuric acid dissolves it
  immediately blue.      _Substances  brown-green, and Fröhde’s reagent
       accompanying the Papaverins._  red, becoming beautifully green.
                                                             _Emetine._

IX. SHAKING OF THE AMMONIACAL WATERY SOLUTION WITH CHLOROFORM.

This extracts the remainder of the cinchonine and papaverine, narceine,
and a small portion of morphine, as well as an alkaloid from the
celandine.

THE RESIDUE FROM THE CHLOROFORM.

  _aa._ The solution, on warming, is only slightly coloured.

  α. But, after it is again cooled, it strikes with nitric acid a
  violet-blue; chloride of iron mixed with the substance gives a blue
  colour; Fröhde’s reagent also dissolves it violet.        _Morphine._

  β. It is not coloured by nitric acid; it is also indifferent to
  chloride of iron.                                       _Cinchonine._

  _bb._ The solution becomes by warming violet-blue.      _Papaverine._

  γ. Sulphuric acid dissolves it greenish-brown, and the solution
  becomes, on standing, blood-red.                          _Narceine._

  δ. Sulphuric acid dissolves it a violet-blue. _Alkaloidal constituent
                                                     of the Celandine._

X. SHAKING UP OF THE WATERY FLUID WITH AMYL ALCOHOL.

From this process, besides morphine and solanine, as well as salicin,
the remnants of the convallamarin, saponin, senegin, and narceine are
also to be expected.

THE AMYL ALCOHOL RESIDUE.

  _a._ Sulphuric acid dissolves it without colour in the cold.
                                                _Morphine_ (see above).

  _b._ Sulphuric acid dissolves it with the production of a clear
  yellow-red and the solution becomes brownish. Iodine water colours it
  a deep brown. The alcoholic solution gelatinises.         _Solanine._

  _c._ Sulphuric acid dissolves it green-brown, becoming red.
                                                _Narceine_ (see above).

  _d._ Sulphuric acid dissolves it yellow, then brown-red, becoming
  violet on dilution with water. Hydrochloric acid dissolves it, and it
  becomes red on warming. It stops the heart-action in the systole.
                                                       _Convallamarin._

  _e._ Hydrochloric acid dissolves it for the most part without colour.
                                                             _Saponin._

  _f._ As the foregoing, but acting more feebly.             _Senegin._

  _g._ Sulphuric acid dissolves it immediately a pure red. On warming
  with sulphuric acid and bichromate of potash, a smell of salicylic
  acid is developed.                                         _Salicin._

XI. DRYING THE WATERY FLUID WITH THE ADDITION OF POWDERED GLASS, AND
EXTRACTION OF THE FINELY-DIVIDED RESIDUE BY CHLOROFORM.

The residue of the first chloroform extract lessens the number of
respirations of a frog; the residue of the second and third chloroform
extract becomes, by sulphuric acid and bichromate of potash, blue,
passing into a permanent red.

  Another portion of this residue becomes red on warming with diluted
  sulphuric acid.                                           _Curarine._


SHORTER PROCESS FOR SEPARATING SOME OF THE ALKALOIDS.

§ 310. A shorter process, recommended conditionally by Dragendorff, for
brucine, strychnine, quinine, cinchonine, and emetine, is as follows:--

The substance, if necessary, is finely divided, and treated with
sulphuric acid (dilute) until it has a marked acid reaction. To every
100 c.c. of the pulp (which has been diluted with distilled water to
admit of its being filtered later), at least 5 to 10 c.c. of diluted
sulphuric acid (1 : 5) are added. It is digested at 50° for a few hours,
filtered, and the residue treated again with 100 c.c. of water at 50°.
This extract is, after a few hours, again filtered; both the filtrates
are mixed and evaporated in the water-bath to almost the consistency of
a thin syrup. The fluid, however, must not be concentrated too much, or
fully evaporated to dryness. The residue is now placed in a flask, and
treated with three to four times its volume of alcohol of 90 to 95 per
cent.; the mixture is macerated for twenty-four hours, and then
filtered. The filtrate is distilled alcohol-free, or nearly so, but a
small amount of alcohol remaining is not objectionable. The watery fluid
is diluted to about 50 c.c., and treated with pure benzene; the mixture
is shaken, and after a little time the benzene removed--an operation
which is repeated. After the removal the second time of the benzene, the
watery fluid is made alkaline with ammonia, warmed to 40° or 50°, and
the free alkaloid extracted by twice shaking it up with two different
applications of benzene. On evaporation of the latter, if the alkaloid
is not left pure, it can be dissolved in acid, precipitated by ammonia,
and again extracted by benzene.

    § 311. =Scheibler’s Process=.--A method very different from those
    just described is one practised by Scheibler. This is to precipitate
    the phosphotungstate of the alkaloid, and then to liberate the
    latter by digesting the precipitate with either hydrate of barium or
    hydrate of calcium, dissolving it out by chloroform, or, if
    volatile, by simple distillation. The convenience of Scheibler’s
    process is great, and it admits of very general application. In
    complex mixtures, it will usually be found best to precede the
    addition of phosphotungstic acid[337] by that of acetate of lead, in
    order to remove colouring matter, &c.; the excess of lead must in
    its turn be thrown out by SH₂, and the excess of SH₂ be got rid of
    by evaporation. Phosphotungstic acid is a very delicate test for the
    alkaloids, giving a distinct precipitate with the most minute
    quantities (1/200000 of strychnine and 1/100000 of quinine). A very
    similar method is practised by Sonnenschein and others with the aid
    of phospho-molybdic acid. The details of Scheibler’s process are as
    follows:--

[337] The method of preparing this reagent is as follows:--Ordinary
commercial sodium tungstate is treated with half its weight of
phosphoric acid, specific gravity, 1·13, and then allowed to stand for
some days. Phosphotungstic acid separates in crystals.

    The organic mixture is repeatedly extracted by water strongly
    acidified with sulphuric acid; the extract is evaporated at 30° to
    the consistence of a thin syrup; then diluted with water, and, after
    several hours’ standing, filtered in a cool place. To the filtered
    fluid phosphotungstic acid is added in excess, the precipitate
    filtered, washed with water to which some phosphotungstic acid
    solution has been added, and, whilst still moist, rinsed into a
    flask. Caustic baryta or carbonate of potash is added to alkaline
    reaction, and after the flask has been connected with bulbs
    containing HCl, it is heated at first slowly, then more strongly.
    Ammonia and any volatile alkaloids are driven over into the acid,
    and are there fixed, and can be examined later by suitable methods.
    The residue in the flask is carefully evaporated to dryness (the
    excess of baryta having been precipitated by CO₂), and then
    extracted by strong alcohol. On evaporation of the alcohol, the
    alkaloid is generally sufficiently pure to be examined, or, if not
    so, it may be obtained pure by re-solution, &c.

The author has had considerable experience of Scheibler’s process, and
has used it in precipitating various animal fluids, but has generally
found the precipitate bulky and difficult to manage.

    § 312. =Grandval and Lajoux’s Method=.[338]--The alkaloids are
    precipitated from a solution slightly acidified by hydrochloric or
    sulphuric acid by a solution of hydrarg-potassium iodide. The
    precipitate is collected on a filter, washed and then transferred to
    a flask; drop by drop, a solution of sodium sulphide is added; after
    each addition the suspended precipitate is shaken and allowed to
    stand for a few minutes, and a drop of the liquid taken out and
    tested with lead acetate; directly a slight brown colour appears,
    sufficient sodic sulphide has been added. The liquid is now left for
    half-an-hour, with occasional shaking. Then sulphuric acid is added
    until it is just acid, and the liquid is filtered and the mercury
    sulphide well washed. In the filtrate will be the sulphate of any
    alkaloid in solution; this liquid is now made alkaline with soda
    carbonate and shaken up, as in Dragendorff’s process, with
    appropriate solvents; such, for example, as ether, or chloroform, or
    acetone, or amylic alcohol, according to the particular alkaloid the
    analyst is searching for, and the solvent finally separated and
    allowed to evaporate, when the alkaloid is found in the residue.

[338] “Dosage des alcaloides à l’aide de l’iodure double de mercure et
de potassium,” par MM. A. Grandval et Henri Lajoux, _Journ. de
Pharmacie_, 5 sér. t. xxviii. 152-156.

    § 313. =Identification of the Alkaloids=.--Having obtained, in one
    way or other, a crystalline or amorphous substance, supposed to be
    an alkaloid, or, at all events, an active vegetable principle, the
    next step is to identify it. If the tests given in Dragendorff’s
    process have been applied, the observer will have already gone a
    good way towards the identification of the substance; but it is, of
    course, dangerous to trust to one reaction.

    In medico-legal researches there is seldom any considerable quantity
    of the material to work upon. Hence the greatest care must be taken
    from the commencement not to waste the substance in useless tests,
    but to study well at the outset what--by the method of extraction
    used, the microscopic appearance, the reaction to litmus paper, and
    the solubility in different menstrua--it is likely to be. However
    minute the quantity may be, it is essential to divide it into
    different parts, in order to apply a variety of tests; but as any
    attempt to do this on the solid substance will probably entail loss,
    the best way is to dissolve it in a watch-glass in half a c.c. of
    alcohol, ether, or other suitable solvent. Droplets of this solution
    are then placed on watch-glasses or slips of microscopic glass, and
    to these drops, by the aid of a glass rod, different reagents can be
    applied, and the changes watched under the microscope as the drops
    slowly evaporate.

§ 314. =Sublimation of the Alkaloids.=--A very beautiful and elegant aid
to the identification of alkaloids, and vegetable principles generally,
is their behaviour towards heat.

Alkaloids, glucosides, the organic acids, &c., when carefully heated,
either--(1) sublime wholly without decomposition (like theine, cytisin,
and others); or (2) partially sublime with decomposition; or (3) are
changed into new bodies (as, for example, gallic acid); or (4) melt and
then char; or (5) simply char and burn away.

Many of these phenomena are striking and characteristic, taking place at
different temperatures, subliming in characteristic forms, or leaving
characteristic residues.

One of the first to employ sublimation systematically, as a means of
recognition of the alkaloids, &c., was Helwig.[339] His method was to
place a small quantity (from ½ to 1/4000 of a mgrm.) in a depression on
platinum foil, cover it with a slip of glass, and then carefully heat by
a small flame. After Helwig, Dr. Guy[340] greatly improved the process
by using porcelain discs, and more especially by the adoption of a
convenient apparatus, which may be termed “the subliming cell.” It is
essentially composed of a ring of glass from ⅛ to ⅔ of an inch in
thickness, such as may be obtained by sections of tubing, the cut
surfaces being ground perfectly smooth. This circle is converted into a
closed cell by resting it on one of the ordinary thin discs of glass
used as a covering for microscopic purposes, and supporting a similar
disc. The cell was placed on a brass plate, provided with a nipple,
which carried a thermometer, and was heated by a small flame applied
midway between the thermometer and the cell; the heat was raised very
gradually, and the temperature at which any change took place was noted.
In this way Dr. Guy made determinations of the subliming points of a
large number of substances, and the microscopic appearances of the
sublimates were described with the greatest fidelity and accuracy. On
repeating with care Dr. Guy’s determinations, however, I could in no
single instance agree with his subliming points, nor with the apparatus
he figures and describes could two consecutive observations exactly
coincide. Further, on examining the various subliming temperatures of
substances, as stated by different authors, the widest discrepancies
were found--differences of 2 or even 3 degrees might be referred to
errors of observation, a want of exact coincidence in the thermometers
employed, and the like; but to what, for example, can we ascribe the
irreconcilable statements which have been made with regard to theine?
According to Strauch, this substance sublimes at 177°; according to
Mulder, at 184·7°. But that both of these observations deviate more than
70° from the truth may be proved by any one who cares to place a few
mgrms. of theine, enclosed between two watch-glasses, over the
water-bath; in a few minutes a distinct sublimate will condense on the
upper glass, and, in point of fact, theine will be found to sublime
several degrees below 100°.

[339] _Das Mikroskop in der Toxicologie_.

[340] _Pharm. Journ. Trans_. (2), viij. 719; ix. 10, 58. _Forensic
Medicine_, London, 1875.

Since this great divergency of opinion is not found either in the
specific gravity, or the boiling-points, or any of the like
determinations of the physical properties of a substance, it is
self-evident that the processes hitherto used for the determination of
subliming points are faulty. The sources of error are chiefly--

(1.) Defects in the apparatus employed--the temperature read being
rather that of the metallic surface in the immediate vicinity of the
thermometer than of the substance itself.

(2.) The want of agreement among observers as to what should be called a
sublimate--one considering a sublimate only that which is evident to the
naked eye, another taking cognisance of the earliest microscopic film.

(3.) No two persons employing the same process.

With regard to the apparatus employed, I adopt Dr. Guy’s subliming cell;
but the cell, instead of resting on a metallic solid, floats on a
metallic fluid. For any temperature a little above 100° this fluid is
mercury, but for higher temperatures fusible metal is preferable.

[Illustration: SUBLIMING CELL.]

The exact procedure is as follows:--A porcelain crucible (_a_ in fig.),
about 3 inches in diameter, is nearly filled with mercury or fusible
metal, as the case may be; a minute speck (or two or three crystals of
the substance to be examined) is placed on a thin disc of microscopic
covering glass, floated on the liquid, and the cell is completed by the
glass ring and upper disc. The porcelain crucible is supported on a
brass plate (_b_), fixed to a retort-stand in the usual way, and
protected from the unequal cooling effects of currents of air by being
covered by a flask (_c_), from which the bottom has been removed. The
neck of the flask conveniently supports a thermometer, which passes
through a cork, and the bulb of the thermometer is immersed in the bath
of liquid metal. In the first examination of a substance the temperature
is raised somewhat rapidly, taking off the upper disc with a forceps at
every 10° and exchanging it for a fresh disc, until the substance is
destroyed. The second examination is conducted much more slowly, and the
discs exchanged at every 4° or 5°, whilst the final determination is
effected by raising the temperature with great caution, and exchanging
the discs at about the points of change (already partially determined)
at every half degree. All the discs are examined microscopically. The
most convenient definition of a sublimate is this--the most minute
films, dots, or crystals, which can be observed by ¼-inch power, and
which are obtained by keeping the subliming cell at a definite
temperature for 60 seconds. The commencement of many sublimates assumes
the shape of dots of extraordinary minuteness, quite invisible to the
unaided eye; and, on the other hand, since the practical value of
sublimation is mainly as an aid to other methods for the recognition of
substances, if we go beyond _short_ intervals of time, the operation,
otherwise simple and speedy, becomes cumbersome, and loses its general
applicability.

There is also considerable discrepancy of statement with regard to the
melting-point of alkaloidal bodies; in many instances a viscous state
intervenes before the final complete resolution into fluid, and one
observer will consider the viscous state, the other complete fluidity,
as the melting-point.

In the melting-points given below, the same apparatus was used, but the
substance was simply placed on a thin disc of glass floating on the
metallic bath before described (the cell not being completed), and
examined from time to time microscopically, for by this means alone can
the first drops formed by the most minute and closely-adherent crystals
to the glass be discovered.

=Cocaine= melts at 93°, and gives a faint sublimate at 98°; if put
between two watch-glasses on the water-bath, in fifteen minutes there is
a good cloud on the upper glass.

=Aconitine= turns brown, and melts at 179° C.; it gives no
characteristic sublimate up to 190°.

=Morphine=, at 150°, clouds the upper disc with nebulæ; the nebulæ are
resolved by high magnifying powers into minute dots; these dots
gradually become coarser, and are generally converted into crystals at
188°; the alkaloid browns at or about 200°.

=Thebaine= sublimes in theine-like crystals at 135°; at higher
temperatures (160° to 200°), needles, cubes, and prisms are observed.
The residue on the lower disc, if examined before carbonisation, is
fawn-coloured with non-characteristic spots.

=Narcotine= gives no sublimate; it melts at 155° into a yellow liquid,
which, on raising the temperature, ever becomes browner to final
blackness. On examining the residue before carbonisation, it is a rich
brown amorphous substance; but if narcotine be heated two or three
degrees above its melting-point, and then cooled slowly, the residue is
crystalline--long, fine needles radiating from centres being common.

=Narceine= gives no sublimate; it melts at 134° into a colourless
liquid, which undergoes at higher temperatures the usual transition of
brown colours. The substance, heated a few degrees above its
melting-point, and then allowed to cool slowly, shows a straw-coloured
residue, divided into lobes or drops containing feathery crystals.

=Papaverine= gives no sublimate; it melts at 130°. The residue, heated a
little above its melting-point, and then slowly cooled, is amorphous, of
a light-brown colour, and in no way characteristic.

=Hyoscyamine= gives no crystalline sublimate; it melts at 89°, and
appears to volatilise in great part without decomposition. It melts into
an almost colourless fluid, which, when solid, may exhibit a network not
unlike vegetable parenchyma; on moistening the network with water,
interlacing crystals immediately appear. If, however, hyoscyamine be
kept at 94° to 95° for a few minutes, and then slowly cooled, the edges
of the spots are arborescent, and the spots themselves crystalline.

=Atropine= (daturine) melts at 97°; at 123° a faint mist appears on the
upper disc. Crystals cannot be obtained; the residue is not
characteristic.

=Solanine.=--The upper disc is dimmed with nebulæ at 190°, which are
coarser and more distinct at higher temperatures; at 200° it begins to
brown, and then melts; the residue consists of amber-brown,
non-characteristic drops.

=Strychnine= gives a minute sublimate of fine needles, often disposed in
lines, at 169°; about 221° it melts, the residue (at that temperature)
is resinous.

=Brucine= melts at 151° into a pale yellow liquid, at higher
temperatures becoming deep-brown. If the lower disc, after melting, be
examined, no crystals are observed, the residue being quite transparent,
with branching lines like the twigs of a leafless tree; light mists,
produced rather by decomposition than by true sublimation, condense on
the upper disc at 185°, and above.

=Saponin= neither melts nor sublimes; it begins to brown about 145°, is
almost black at 185°, and quite so at 190°.

=Delphinine= begins to brown about 102°; it becomes amber at 119°, and
melts, and bubbles appear. There is no crystalline sublimate; residue
not characteristic.

=Pilocarpine= gives a distinct crystalline sublimate at 153°; but thin
mists, consisting of fine dots, may be observed as low as 140°.
Pilocarpine melts at 159°; the sublimates at 160° to 170° are in light
yellow drops. If these drops are treated with water, and the water
evaporated, feathery crystals are obtained; the residue is resinous.

=Theine= wholly sublimes; the first sublimate is minute dots, at 79°; at
half a degree above that very small crystals may be obtained; and at
such a temperature as 120°, the crystals are often long and silky.

=Theobromine= likewise wholly sublimes; nebulæ at 134°, crystals at
170°, and above.

=Salicin= melts at 170°; it gives no crystalline sublimate. The melted
mass remains up to 180° almost perfectly colourless; above that
temperature browning is evident. The residue is not characteristic.

=Picrotoxin= gives no crystalline sublimate. The lowest temperature at
which it sublimes is 128°; the usual nebulæ then make their appearance;
between 165° and 170° there is slight browning; at 170° it melts. The
residue, slowly cooled, is not characteristic.

=Cantharidin= sublimes very scantily between 82° and 83°; at 85° the
sublimate is copious.

The active principles of plants may, in regard to their behaviour to
heat, be classed for practical purposes into--

  1. Those which give a decided crystalline sublimate:
     (_a._) Below 100°, _e.g._, cocaine, theine, thebaine, cantharidin.
     (_b._) Between 100° and 150°, _e.g._, quinetum.
     (_c._) Between 150° and 200°, _e.g._, strychnine, morphine,
            pilocarpine.
  2. Those which melt, but give no crystalline sublimate:
     (_a._) Below 100°, _e.g._, hyoscyamine, atropine.
     (_b._) Between 100° and 150°, _e.g._, papaverine.
     (_c._) Between 150° and 200°, _e.g._, salicin.
     (_d._) Above 200°, _e.g._, solanine.
  3. Those which neither melt nor give a crystalline sublimate, _e.g._,
     saponin.

§ 315. =Melting-point.=--The method of sublimation just given also
determines the melting-point; such a determination will, however, seldom
compare with the melting-points of the various alkaloids as given in
text-books, because the latter melting-points are not determined in the
same way. The usual method of determining melting-points is to place a
very small quantity in a glass tube closed at one end; the tube should
be almost capillary. The tube is fastened to a thermometer by means of
platinum wire, and then the bulb of the thermometer, with its attached
tube, is immersed in strong sulphuric acid or paraffin, contained in a
flask. The thermometer should be suspended midway in the liquid and heat
carefully applied, so as to raise the temperature gradually and equably.
It will be found that rapidly raising the heat gives a different
melting-point to that which is obtained by slowly raising the heat.
During the process careful watching is necessary: most substances change
in hue before they actually melt. A constant melting-point, however
often a substance is purified by recrystallisation, is a sign of purity.

§ 316. =Identification by Organic Analysis.=--In a few cases (and in a
few only) the analyst may have sufficient material at hand to make an
organic analysis, either as a means of identification or to confirm
other tests. By the vacuum process described in “Foods,” in which carbon
and nitrogen are determined by measuring the gases evolved by burning
the organic substance in as complete a vacuum as can be obtained, very
minute quantities of a substance can be dealt with, and the carbon and
nitrogen determined with fair accuracy. It is found in practice that the
carbon determinations appear more reliable than those of the nitrogen,
and there are obvious reasons why this should be so.

Theoretically, with the improved gas-measuring appliances, it is
possible to measure a c.c. of gas; but few chemists would care to create
a formula on less than 10 c.c. of CO₂. Now, since 10 c.c. of CO₂ is
equal to 6·33 mgrms. of carbon, and alkaloids average at least half
their weight of carbon, it follows that 12 mgrms. of alkaloid represent
about the smallest quantity with which a reliable single combustion can
be made.

The following table gives a considerable number of the alkaloids and
alkaloidal bodies, arranged according to their content in carbon:--

TABLE SHOWING THE CONTENT OF CARBON AND NITROGEN IN VARIOUS ALKALOIDAL
BODIES.

                              Carbon.    Nitrogen.

  Asparagin,                   36·36       21·21
  Methylamine,                 38·71       45·17
  Betaine,                     44·44       10·37
  Theobromine,                 46·67       31·11
  Theine,                      49·48       28·86
  Indican,                     49·60        2·22
  Muscarine,                   50·42       11·77
  Lauro-cerasin,               52·47        1·53
  Amanitine,                   57·69       13·46
  Narceine,                    59·63        3·02
  Colchicine,                  60·53        4·15
  Oxyacanthine,                60·57        4·42
  Solanine,                    60·66        1·68
  Trimethylamine,              61·02       23·73
  Jervine,                     61·03        5·14
  Sabadilline,                 61·29        3·46
  Aconitine,                   61·21        2·16
  Nepaline,                    63·09        2·12
  Colchicein,                  63·44        4·38
  Veratroidine,                63·8         3·1
  Narcotine,                   63·92        3·39
  Veratrine,                   64·42        2·91
  Delphinine,                  64·55        3·42
  Physostigmine,               65·49       15·27
  Rhœadine,                    65·79        3·65
  Cocaine,                     66·44        4·84
  Gelsemine,                   67·00        7·10
  Conhydrine,                  67·12        9·79
  Staphisagrine,               67·5         3·6
  Chelidonine,                 68·06       12·34
  Atropine, Hyoscyamine,       70·58        4·84
  Sanguinarine,                70·59        4·33
  Papaverine,                  70·79        4·13
  Delphinoidine,               70·9         3·9
  Morphine and Piperine,       71·58        4·91
  Berberine,                   71·64        4·18
  Codeine,                     72·24        4·68
  Thebaine,                    73·31        4·50
  Cytisine,                    73·85       12·92
  Nicotine,                    74·08       17·28
  Quinine,                     75·02        8·64
  Coniine,                     76·81       11·20
  Strychnine,                  77·24        8·92
  Curarine,                    81·51        5·28

§ 317. =Quantitative Estimation of the Alkaloids.=--For medico-legal
purposes the alkaloid obtained is usually weighed directly, but for
technical purposes other processes are used. One of the most convenient
of these is titration with normal or decinormal sulphuric acid, a method
applicable to a few alkaloids of marked basic powers--_e.g._, quinine is
readily and with accuracy estimated in this way, the alkaloid being
dissolved in a known volume of the acid, and then titrated back with
soda. If a large number of observations are to be made, an acid may be
prepared so that each c.c. equals 1 mgrm. of quinine. A reagent of
general application is found in the so-called _Mayer’s reagent_, which
consists of 13·546 grms. of mercuric chloride, and 49·8 grms. of iodide
of potassium in a litre of water. Each c.c. of such solution
precipitates--

  Of Strychnine,   ·0167  grm.
   „ Brucine,      ·0233   „
   „ Quinine,      ·0108   „
   „ Cinchonine,   ·0102   „
   „ Quinidine,    ·0120   „
   „ Atropine,     ·0145   „
   „ Aconitine,    ·0268   „
   „ Veratrine,    ·0269   „
   „ Morphine,     ·0200   „
   „ Narcotine,    ·0213   „
   „ Nicotine,     ·00405  „
   „ Coniine,      ·00416  „

The final reaction is found by filtering, from time to time, a drop on
to a glass plate, resting on a blackened surface, and adding the test
until no precipitate appears. The results are only accurate when the
strength of the solution of the alkaloid is about 1 : 200; so that it is
absolutely necessary first to ascertain approximatively the amount
present, and then to dilute or concentrate, as the case may be, until
the proportion mentioned is obtained.

A convenient method of obtaining the sulphate of an alkaloid for
quantitative purposes, and especially from organic fluids, is that
recommended by Wagner. The fluid is acidulated with sulphuric acid, and
the alkaloid precipitated by a solution of iodine in iodide of
potassium. The precipitate is collected and dissolved in an aqueous
solution of hyposulphite of soda. The filtered solution is again
precipitated with the iodine reagent, and the precipitate dissolved in
sulphurous acid, which, on evaporation, leaves behind the pure sulphate
of the base.

It is also very useful for quantitative purposes to combine an alkaloid
with gold or platinum, by treating the solution with the chlorides of
either of those metals--the rule as to selection being to give that
metal the preference which yields the most insoluble and the most
crystallisable compound.

The following table gives the percentage of gold or platinum left on
ignition of the double salt:--

                          Gold.   Platinum.

  Atropine,               31·57      ...
  Aconitine               20·0       ...
  Amanitine,              44·23      ...
  Berberine,              29·16     18·11
  Brucine,                 ...      16·52
  Cinchonine,              ...      27·36
  Cinchonidine,            ...      27·87
  Codeine,                 ...      19·11
  Coniine,                 ...      29·38
  Curarine,                ...      32·65
  Delphinine,             26·7       ...
  Delphinoidine,          29·0      15·8
  Emetine,                 ...      29·7
  Hyoscyamine,            34·6       ...
  Morphine,                ...      19·52
  Muscarine,              43·01      ...
  Narcotine,              15·7      15·9
  Narceine,                ...      14·52
  Nicotine,                ...      34·25
  Papaverine,              ...      17·82
  Pilocarpine,            35·5      23·6 to 25·2.
  Piperine,                ...      12·7
  Quinine,                40·0      26·26
  Strychnine,             29·15     18·16
  Thebaine,                ...      18·71
  Theine,                 37·02     24·58
  Theobromine,             ...      25·55
  Veratrine,              21·01      ...


II.--Liquid Volatile Alkaloids.

THE ALKALOIDS OF HEMLOCK--NICOTINE--PITURIE--SPARTEINE.


1. THE ALKALOIDS OF HEMLOCK (CONIUM).

§ 318. The _Conium maculatum_, or spotted hemlock, is a rather common
umbelliferous plant, growing in waste places, and flowering from about
the beginning of June to August. The stem is from three to five feet
high, smooth, branched, and spotted with purple; the leaflets of the
partial involucres are unilateral, ovate, lanceolate, with an attenuate
point shorter than the umbels; the seeds are destitute of vittæ, and
have five prominent crenate wavy ridges. The whole plant is fœtid and
poisonous. Conium owes its active properties to a volatile liquid
alkaloid, _Coniine_, united with a crystalline alkaloid, _Conhydrine_.

§ 319. =Coniine= (=conia=, =conicine=), (C₈H₁₇N)--specific gravity 0·862
at 0°; melting-point, -2·5°; boiling-point, 166·6°. Pure coniine has
been prepared synthetically by Ladenburg, and found to be
propyl-piperidine C₅H₁₀NC₃H₇, but the synthetically-prepared piperidine
has no action on polarised light. By uniting it with dextro-tartaric
acid, and evaporating, it is possible to separate the substance into
dextro-propyl-piperidine and lævo-propyl-piperidine. The former is in
every respect identical with coniine from hemlock; it is a clear, oily
fluid, possessing a peculiarly unpleasant, mousey odour. One part is
soluble in 150 parts of water,[341] in 6 parts of ether, and in almost
all proportions of amyl alcohol, chloroform, and benzene. It readily
volatilises, and, provided air is excluded, may be distilled unchanged.
It ignites easily, and burns with a smoky flame. It acts as a strong
base, precipitating the oxides of metals and alkaline earths from their
solutions, and it coagulates albumen. Coniine forms salts with
hydrochloric acid (C₈H₁₅N.HCl), phosphoric acid, iodic acid, and oxalic
acid, which are in well-marked crystals. The sulphate, nitrate, acetate,
and tartrate are, on the other hand, non-crystalline.

[341] The saturated watery solution of coniine at 15°, becomes cloudy if
gently warmed, and clears again on cooling.

If coniine is oxidised with nitric acid, or bichromate of potash, and
diluted sulphuric acid, butyric acid is formed; and since the latter has
an unmistakable odour, and other characteristic properties, it has been
proposed as a test for coniine. This may be conveniently performed
thus:--A crystal of potassic bichromate is put at the bottom of a
test-tube, and some diluted sulphuric acid with a drop of the supposed
coniine added. On heating, the butyric acid reveals itself by its odour,
and can be distilled into baryta water, the butyrate of baryta being
subsequently separated in the usual way, and decomposed by sulphuric
acid, &c.

Another test for coniine is the following:--If dropped into a solution
of alloxan, the latter is coloured after a few minutes an intense
purple-red, and white needle-shaped crystals are separated, which
dissolve in cold potash-lye into a beautiful purple-blue, and emit an
odour of the base.[342] Dry hydrochloric acid gives a purple-red, then
an indigo-blue colour, with coniine; but if the acid is not dry, there
is formed a bluish-green crystalline mass. This test, however, is of
little value to the toxicologist, the pure substance alone responding
with any definite result.

[342] Schwarzenbach, _Vierteljahrsschr. f. prakt. Pharm._, viij. 170.

The ordinary precipitating agents, according to Dragendorff, act as
follows:--

  Potass bismuth iodide.
    1 : 2000, a strong orange precipitate.
    1 : 3000. The drop of the reagent is surrounded with a muddy border.
    1 : 4000. The drop of the reagent is surrounded with a muddy border.
    1 : 5000, still perceptible.
    1 : 6000. The last limit of the reaction.

Phosphomolybdic acid gives a strong yellow precipitate; limit, 1 : 5000.

Potass. mercuric iodide gives a cheesy precipitate; limit, 1 : 1000 in
neutral, 1 : 800 in acid, solutions.

Potass. cadmic iodide gives an amorphous precipitate, 1 : 300. The
precipitate is soluble in excess of the precipitant. (Nicotine, under
similar circumstances, gives a crystalline precipitate.)

Flückiger recommends the following reaction:[343]--“Add to 10 drops of
ether in a shallow glass crystallising dish 2 drops of coniine, and
cover with filter paper. Set upon the paper a common-sized watch-glass
containing bromine water, and invert a beaker over the whole
arrangement. Needle-shaped crystals of coniine hydro-bromine soon form
in the dish as well as in the watch-glass.” Hydrochloric acid, used in
the same way, instead of bromine water, forms with coniine microscopic
needles of coniine hydrochlorate; both the hydro-bromide and the
hydrochlorate doubly refract light. Nicotine does not respond to this
reaction.

[343] _Reactions_, by F. A. Flückiger, Detroit, 1893.

Coniine forms with carbon disulphide a thiosulphate and a sulphite. If
carbon disulphide, therefore, be shaken with an aqueous solution of
coniine, the watery solution gives a brown precipitate with copper
sulphate, colours ferric chloride solution dark brown red, and gives a
milky opalescence with dilute acids. If coniine itself is added to
carbon disulphide, there is evolution of heat, separation of sulphur,
and formation of thiosulphate. Nicotine does not respond to this
reaction.

§ 320. =Other Coniine Bases.=--Methyl- and ethyl-coniine have been
prepared synthetically, and are both similar in action to coniine, but
somewhat more like curarine. By the reduction of coniine with zinc dust
conyrine (C₈H₁₁N) is formed; between coniine and conyrine stands
coniceine (C₈H₁₅NO). De Coninck has made synthetically by the addition
of 6 atoms of hydrogen to β collidine, a new fluid alkaloid (C₈H₁₁N + 6H
= C₈H₁₇N), which he has called _isocicutine_: it has the same formula as
coniine. Paraconiine Schiff prepared synthetically from ammonia and
normal butyl aldehyde; it has the formula C₈H₁₅N, and therefore differs
from coniine in containing two atoms less of hydrogen. All the above
have a similar physiological action to coniine. α-stillbazoline
(C₁₁H₁₉N), prepared by Baurath from benzaldehyde and picoline, is
analogous to coniine, and according to Falck has similar action, but is
more powerful.

§ 321. =Pharmaceutical Preparations.=--The percentage of coniine in the
plant itself, and in pharmaceutical preparations, can be approximately
determined by distilling the coniine over, in a partial vacuum,[344]
and titrating the distillate with Mayer’s reagent, each c.c. = about
·00416 grm. of coniine. It appears to be necessary to add powdered
potassic chloride and a small quantity of diluted sulphuric acid before
titrating, or the precipitate does not separate. In any case, the end of
the reaction is difficult to observe.[345]

[344] This is easily effected by uniting a flask containing the
alkaloidal fluid, air-tight, with a Liebig’s condenser and a receiver,
the latter being connected with Bunsen’s water-pump, or one of the
numerous exhausting apparatuses now in use in every laboratory.

[345] Dragendorff, _Die Chemische Werthbestimmung einiger starkwirkender
Droguen_, St. Petersb., 1874.

The fresh plant is said to contain from about ·04 to ·09 per cent., and
the fruit about 0·7 per cent. of coniine.

The officinal preparations are--the leaves, the fruit, a tincture of the
fruit, an extract of the leaves, the juice of the leaves (_Succus
conii_), a compound hemlock pill (composed of extract of hemlock,
ipecacuanha, and treacle), an inhalation of coniine (_Vapor conii_), and
a poultice (_Cataplasma conii_) made with the leaves.

§ 322. =Statistics of Coniine Poisoning.=--F. A. Falck[346] has been
able to collect 17 cases of death recorded in medical literature, up to
the year 1880, from either coniine or hemlock. Two of these cases were
criminal (murders), 1 suicidal, 2 cases in which coniine had been used
medicinally (in one instance the extract had been applied to a cancerous
breast; in the other, death was produced from the injection of an
infusion of hemlock leaves). The remaining 12 were cases in which the
root, leaves, or other portions of the plant had been ignorantly or
accidentally eaten.

[346] _Prakt. Toxicologie_, p. 273.

§ 323. =Effects on Animals.=--It destroys all forms of animal life. The
author made some years ago an investigation as to its action on the
common blow-fly. Droplets of coniine were applied to various parts of
blow-flies, which were then placed under glass shades. The symptoms
began within a minute by signs of external irritation, there were rapid
motions of the wings, and quick and aimless movements of the legs.
Torpor set in speedily, the buzz soon ceased, and the insects lay on
their sides, motionless, but for occasional twitching of the legs. The
wings, as a rule, became completely paralysed before the legs, and death
occurred at a rather variable time, from ten minutes to two hours. If
placed in a current of air in the sun, a fly completely under the
influence of coniine may recover. Coniine causes in frogs, similar to
curarine, peripheral paralysis of the motor nerves, combined with a
transitory stimulation, and afterwards a paralysis of the motor centres;
in frogs the paralysis is not preceded by convulsions. Dragendorff
experimented on the action of coniine when given to five cats, the
quantities used being ·05 to ·5 grm. The symptoms came on almost
immediately, but with the smaller dose given to a large cat, no effect
was witnessed until twenty-five minutes afterwards; this was the longest
interval. One of the earliest phenomena was dilatation of the pupil,
followed by weakness of the limbs passing into paralysis, the hinder
legs being affected prior to the fore. The respiration became troubled,
and the frequency of the breathing diminished; the heart in each case
acted irregularly, and the sensation generally was blunted; death was
preceded by convulsions. In the cases in which the larger dose of ·4 to
·5 grm. was administered, death took place within the hour, one animal
dying in eight minutes, a second in eighteen minutes, a third in twenty
minutes, and a fourth in fifty-eight minutes. With the smaller dose of
·051 grm. given to a large cat, death did not take place until eight
hours and forty-seven minutes after administration.

§ 324. =Effects on Man.=--In a case recorded by Bennet,[347] and quoted
in most works on forensic medicine, the symptoms were those of general
muscular weakness deepening into paralysis. The patient had eaten
hemlock in mistake for parsley; in about twenty minutes he experienced
weakness in the lower extremities, and staggered in walking like a
drunken man; within two hours there was perfect paralysis of both upper
and lower extremities, and he died in three and a quarter hours. In
another case, related by Taylor, the symptoms were also mainly those of
paralysis, and in other instances stupor, coma, and slight convulsions
have been noted.

[347] _Edin. Med. and Surg. Journ._, July 1845, p. 169.

§ 325. =Physiological Action.=--It is generally agreed that coniine
paralyses, first the ends of the motor nerves, afterwards their trunks,
and lastly, the motor centre itself. At a later period the sensory
nerves participate. In the earlier stage the respiration is quickened,
the pupils contracted, and the blood-pressure increased; but on the
development of paralysis the breathing becomes slowed, the capillaries
relaxed, and the blood-pressure sinks. Death takes place from cessation
of the respiration, and not primarily from the heart, the heart beating
after the breathing has stopped. Coniine is eliminated by the urine, and
is also in part separated by the lungs, while a portion is, perhaps,
decomposed in the body.

§ 326. =Post-mortem Appearances.=--There is nothing characteristic in
the appearances after death.

=Fatal Dose.=--The fatal dose of coniine is not accurately known; it is
about 150 mgrms. (2·3 grains). In the case of Louise Berger, 10 to 15
drops appear to have caused death in a few minutes. The auto-experiments
of Dworzak, Heinrich, and Dillaberger would indicate that one drop may
cause unpleasant symptoms. Albers, in the treatment of a woman suffering
from cancer of the breast, witnessed convulsions and loss of
consciousness from a third dose of 4 mgrms. (·06 grain); and Eulenberg,
its full narcotic effects on a child after subcutaneous injection of 1
mgrm. (·015 grain).

§ 327. =Separation of Coniine from Organic Matters or Tissues.=--The
substances are digested with water, acidulated with H₂SO₄, at a
temperature not exceeding 40°, and then filtered. If the filtrate should
be excessive, it must be concentrated; alcohol is then added, the liquid
refiltered, and from the filtrate the alcohol separated by distillation.

On cooling, the acid fluid is agitated with benzene, and the latter
separated in the usual way. The fluid is now alkalised with ammonia, and
shaken up once or twice with its own volume of petroleum ether; the
latter is separated and washed with distilled water, and the alkaloid is
obtained almost pure. If the petroleum ether leaves no residue, it is
certain that the alkaloid was not present in the contents of the stomach
or intestine.

The affinity of coniine with ether or chloroform is such, that its
solution in either of these fluids, passed through a _dry_ filter,
scarcely retains a drop of water. In this way it may be conveniently
purified, the impurities dissolved by water remaining behind.

In searching for coniine, the stomach, intestines, blood, urine, liver,
and lungs are the parts which should be examined. According to
Dragendorff, it has been discovered in the body of a cat six weeks after
death.

Great care must be exercised in identifying any volatile alkaloid as
coniine, for the sources of error seem to be numerous. In one case[348]
a volatile coniine-like ptomaine, was separated from a corpse, and
thought to be coniine; but Otto found that in its behaviour to platinic
chloride, it differed from coniine; it was very poisonous--·07 was fatal
to a frog, ·44 to a pigeon, in a few minutes. In the seeds of _Lupinus
luteus_ there is a series of coniine-like substances,[349] but they do
not give the characteristic crystals with hydrochloric acid.

[348] Otto, _Anleitung z. Ausmittlung d. Gifte_, 1875.

[349] Sievert, _Zeitschrift für Naturwissenschaften_.


2. TOBACCO--NICOTINE.

§ 328. The different forms of tobacco are furnished by three species of
the tobacco plant, viz., _Nicotianum tabacum_, _N. rustica_, and _N.
persica_.

Havanna, French, Dutch, and the American tobaccos are in the main
derived from _N. tabacum_; Turkish, Syrian, and the Latakia tobaccos are
the produce of _N. rustica_. There seems at present to be little of _N.
persica_ in commerce.

All the species of tobacco contain a liquid, volatile, poisonous
alkaloid (_Nicotine_), probably united in the plant with citric and
malic acids. There is also present in tobacco an unimportant camphor
(_nicotianin_). The general composition of the plant may be gathered
from the following table:--

TABLE SHOWING THE COMPOSITION OF FRESH LEAVES OF TOBACCO (POSSELT AND
RIENMANN).

  Nicotine,                                          0·060
  Concrete volatile oil,                             0·010
  Bitter extractive,                                 2·870
  Gum with malate of lime,                           1·740
  Chlorophyl,                                        0·267
  Albumen and gluten,                                1·308
  Malic acid,                                        0·510
  Lignine and a trace of starch,                     4·969
  Salts (sulphate, nitrate, and malate of potash, }
  chloride of potassium, phosphate and malate     }  0·734
  of lime, and malate of ammonia,)                }
  Silica,                                            0·088
  Water,                                            88·280
                                                   -------
                                                   100·836

§ 329. =Quantitative Estimation of Nicotine in Tobacco.=--The best
process (although not a perfectly accurate one) is the following:--25
grms. of the tobacco are mixed with milk of lime, and allowed to stand
until there is no odour of ammonia; the mixture is then exhausted by
petroleum ether, the ether shaken up with a slight excess of normal
sulphuric acid, and titrated back by baryta water; the sulphate of
baryta may be collected and weighed, so as to control the results. With
regard to the percentage of nicotine in commercial tobacco, Kosutany
found from 1·686 to 3·738 per cent. in dry tobacco; Letheby, in six
samples, from 1·5 to 3·2 per cent.; whilst Schlössing gives for Havanna
2 per cent., Maryland 2·29 per cent., Kentucky 6·09 per cent., Virginian
6·87 per cent., and for French tobacco, quantities varying from 3·22 to
7·96 per cent. Again, Lenoble found in Paraguay tobacco from 1·8 to 6
per cent.; and Wittstein, in six sorts of tobacco in Germany, 1·54 to
2·72 per cent.

Mr. Cox[350] has recently determined the amount of nicotine in a number
of tobaccos. The results are tabulated in the following table as
follows:--

[350] _Pharm. Journ._, Jan. 20, 1894.

TABLE OF RESULTS, ARRANGED ACCORDING TO PER CENT. OF NICOTINE.

  Variety examined.                      Nicotine
                                         per cent.

   1. Syrian leaves (_a_),                  ·612
   2. American chewing,                     ·935
   3. Syrian leaves (_b_),                 1·093
   4. Chinese leaves,                      1·902
   5. Turkish (coarse cut),                2·500
   6. Golden Virginia (whole strips),      2·501
   7. Gold Flake (Virginia),               2·501
   8. “Navy-cut” (light coloured),         2·530
   9. Light returns (Kentucky),            2·733
  10. “Navy-cut” (dark “all tobacco”),     3·640
  11. Best “Birds-eye,”                    3·931
  12. Cut Cavendish (_a_),                 4·212
  13. “Best Shag” (_a_),                   4·907
  14. “Cut Cavendish” (_b_),               4·970
  15. “Best Shag” (_b_),                   5·000
  16. French tobacco,                      8·711
  17. Algerian tobacco (_a_),              8·813
  18. Algerian tobacco (_b_),              8·900

It is therefore obvious that the strength of tobacco in nicotine varies
between wide limits.

Twenty-five grammes (or more or less, according to the amount of the
sample at disposal) of the dried and powdered tobacco were intimately
mixed with slaked lime, and distilled in a current of steam until the
condensed steam was no longer alkaline; the distillate was slightly
acidulated with dilute H₂SO₄, and evaporated to a conveniently small
bulk. This was made alkaline with soda, and agitated repeatedly with
successive portions of ether. The separated batches of ethereal solution
of nicotine were then mixed and exposed to the air in a cool place. This
exposure to the air carries away ammonia, if any be present, as well as
ether.

Water was added to the ethereal residue, and the amount of nicotine
present determined by decinormal H₂SO₄, using methyl-orange as an
indicator. One c.c. of decinormal H₂SO₄ represents 0·0162 gramme of
nicotine (C₁₀H₁₄N₂).

§ 330. =Nicotine= (C₁₀H₁₄N₂).--Hexahydro dipyridyl (C₅H₄N)₂H₆, when
pure, is an oily, colourless fluid, of 1·0111, specific gravity at
15°.[351] It evaporates under 100° in white clouds, and boils at about
240°, at which temperature it partly distils over unchanged, and is
partly decomposed--a brown resinous product remaining. It volatilises
with aqueous and amyl alcohol vapour notably, and is not even fixed at
-10°. It has a strong alkaline reaction, and rotates a ray of polarised
light to the right. Its odour, especially on warming, is strong and
unpleasantly like tobacco, and it has a sharp caustic taste. It absorbs
water exposed to the air, and dissolves in water in all proportions,
partly separating from such solution on the addition of a caustic
alkali. The aqueous solution acts in many respects like ammonia,
saturating acids fully, and may therefore be in certain cases estimated
with accuracy by titration, 49 parts of H₂SO₄ corresponding to 162 of
nicotine. It gives on oxidation nicotinic acid = m(β) pyridincarbo acid
C₅H₄N(COOH), and by oxidation with elimination of water dipyridyl
(C₅H₄N)₂, and through reduction dipiperydil (C₅H₁₀N)₂.

[351] J. Skalweit, _Ber. der. deutsch. Chem. Gesell._, 14, 1809.

Alcohol and ether dissolve nicotine in every proportion; if such
solutions are distilled, nicotine goes over first. The salts which it
forms with hydrochloric, nitric, and phosphoric acids crystallise with
difficulty; tartaric and oxalic acid form white crystalline salts, and
the latter, oxalate of nicotine, is soluble in alcohol, a property which
distinguishes it from the oxalate of ammonia. The best salts are the
oxalate and the acid tartrate of nicotine, from which to regenerate
nicotine in a pure state.

Hydrochloride of nicotine is more easily volatilised than the pure base.
Nicotine is precipitated by alkalies, &c., also by many oxyhydrates,
lead, copper, &c. By the action of light, it is soon coloured yellow and
brown, and becomes thick, in which state it leaves, on evaporation, a
brown resinous substance, only partly soluble in petroleum ether.

A very excellent test for nicotine, as confirmatory of others, is the
beautiful, long, needle-like crystals obtained by adding to an ethereal
solution of nicotine a solution of iodine in ether. The crystals require
a few hours to form.

Chlorine gas colours nicotine blood-red or brown; the product is soluble
in alcohol, and separates on evaporation in crystals.

Cyanogen also colours nicotine brown; the product out of alcohol is not
crystalline. Platin chloride throws down a reddish crystalline
precipitate, soluble on warming; and gallic acid gives a flocculent
precipitate. A drop of nicotine poured on dry chromic acid blazes up,
and gives out an odour of tobacco camphor; if the ignition does not
occur in the cold, it is produced by a gentle heat. It is scarcely
possible to confound nicotine with ammonia, by reason of its odour; and,
moreover, ammonia may always be excluded by converting the base into the
oxalate, and dissolving in absolute alcohol.

On the other hand, a confusion between coniine and nicotine is apt to
occur when small quantities only are dealt with. It may, however, be
guarded against by the following tests:--

(1.) If coniine be converted into oxalate, the oxalate dissolved in
alcohol, and coniine regenerated by distillation (best in _vacuo_) with
caustic lye, and then hydrochloric acid added, a crystalline
hydrochlorate of coniine is formed, which doubly refracts light, and is
in needle-shaped or columnar crystals, or dendritic, moss-like forms.
The columns afterwards become torn, and little rows of cubical,
octahedral, and tetrahedral crystals (often cross or dagger-shaped) grow
out of yellow amorphous masses. Crystalline forms of this kind are rare,
save in the case of dilute solutions of chloride of ammonium (the
presence of the latter is, of course, rendered by the treatment
impossible); and nicotine does not give anything similar to this
reaction.

(2.) Coniine coagulates albumen; nicotine does not.

(3.) Nicotine yields a characteristic crystalline precipitate with an
aqueous solution of mercuric chloride; the similar precipitate of
coniine is amorphous.

(4.) Nicotine does not react with CS₂ to form thiosulphate (see p. 266).

§ 331. =Effects on Animals.=--Nicotine is rapidly fatal to all animal
life--from the lowest to the highest forms. That tobacco-smoke is
inimical to insect-life is known to everybody; very minute quantities in
water kill infusoria. Fish of 30 grms. weight die in a few minutes from
a milligram of nicotine; the symptoms observed are rapid movements, then
shivering and speedy paralysis, with decreased motion of the gills, and
death. With frogs, if doses not too large are employed, there is first
great restlessness, then strong tetanic convulsions, and a very peculiar
position of the limbs; the respiration after fatal doses soon ceases,
but the heart beats even after death. Birds also show tetanic
convulsions followed by paralysis and speedy death. The symptoms
witnessed in mammals poisoned by nicotine are not essentially
dissimilar. With large doses the effect is similar to that of prussic
acid--viz., a cry, one or two shuddering convulsions, and death. If the
dose is not too large, there is trembling of the limbs, excretion of
fæces and urine, a peculiar condition of stupor, a staggering gait, and
then the animal falls on its side. The respiration, at first quickened,
is afterwards slowed, and becomes deeper than natural; the pulse, also,
with moderate doses, is first slowed, then rises in frequency, and
finally, again falls. Tetanic convulsions soon develop, during the
tetanus the pupils have been noticed to be contracted, but afterwards
dilated, the tongue and mouth are livid, and the vessels of the ear
dilated. Very characteristic of nicotine poisoning as witnessed in the
cat, the rabbit, and the dog, is its peculiarly violent action, for
after the administration of from one to two drops, the whole course from
the commencement of symptoms to the death may take place in five
minutes. F. Vas has drawn the smoke of tobacco from an immense pipe, and
condensed the products; he finds the well-washed tarry products without
physiological action, but the soluble liquid affected the health of
rabbits,--they lost weight, the number of the blood corpuscles was
decreased, and the hæmoglobin of the blood diminished.[352]

[352] _Archiv. f. Exper. Pathol. u. Pharm._, Bd. 33.

The larger animals, such as the horse, are affected similarly to the
smaller domestic animals. A veterinary surgeon, Mr. John Howard, of
Woolwich,[353] has recorded a case in which a horse suffered from the
most violent symptoms of nicotine-poisoning, after an application to his
skin of a strong decoction of tobacco. The symptoms were trembling,
particularly at the posterior part of the shoulders, as well as at the
flanks, and both fore and hind extremities; the superficial muscles were
generally relaxed and felt flabby; and the pupils were widely dilated.
There was also violent dyspnœa, the respirations being quick and short,
pulse 32 per minute, and extremely feeble, fluttering, and indistinct.
When made to walk, the animal appeared to have partly lost the use of
his hind limbs, the posterior quarter rolling from side to side in an
unsteady manner, the legs crossing each other, knuckling over, and
appearing to be seriously threatened with paralysis. The anus was very
prominent, the bowels extremely irritable, and tenesmus was present. He
passed much flatus, and at intervals of three or four minutes, small
quantities of fæces in balls, partly in the liquid state, and coated
with slimy mucus. There was a staring, giddy, intoxicated appearance
about the head and eyes, the visible mucous membrane being of a dark-red
colour. A great tendency to collapse was evident, but by treatment with
cold douches and exposure to the open air, the horse recovered.

[353] _Veter. Journal_, vol. iii.

In a case occurring in 1863, in which six horses ate oats which had been
kept in a granary with tobacco, the symptoms were mainly those of
narcosis, and the animals died.[354]

[354] _Annales Vétérinaires_, Bruxelles, 1868.

§ 332. =Effects on Man.=--Poisoning by the pure alkaloid nicotine is so
rare that, up to the present, only three cases are on record. The first
of these is ever memorable in the history of toxicology, being the first
instance in which a pure alkaloid had been criminally used. The
detection of the poison exercised the attention of the celebrated
chemist Stas. I allude, of course, to the poisoning of M. Fougnies by
Count Bocarmé and his wife. For the unabridged narrative of this
interesting case the reader may consult Tardieu’s _Étude Médico-Légale
sur L’Empoisonnement_.

Bocarmé actually studied chemistry in order to prepare the alkaloid
himself, and, after having succeeded in enticing his victim to the
chateau of Bitremont, administered the poison forcibly. It acted
immediately, and death took place in five minutes. Bocarmé now attempted
to hide all traces of the nicotine by pouring strong acetic acid into
the mouth and over the body of the deceased. The wickedness and cruelty
of the crime were only equalled by the clumsy and unskilful manner of
its perpetration. The quantity of nicotine actually used in this case
must have been enormous, for Stas separated no less than ·4 grm. from
the stomach of the victim.

The second known case of nicotine-poisoning was that of a man who took
it for the purpose of suicide. The case is related by Taylor. It
occurred in June 1863. The gentleman drank an unknown quantity from a
bottle; he stared wildly, fell to the floor, heaving a deep sigh, and
died quietly without convulsion. The third case happened at
Cherbourg,[355] where an officer committed suicide by taking nicotine,
but how much had been swallowed, and what were the symptoms, are equally
unknown, for no one saw him during life.

[355] _Ann. d’Hygiène_, 1861, x. p. 404.

Poisoning by nicotine, pure and simple, then is rare. Tobacco-poisoning
is very common, and has probably been experienced in a mild degree by
every smoker in first acquiring the habit. Nearly all the fatal cases
are to be ascribed to accident; but criminal cases are not unknown.
Christison relates an instance in which tobacco in the form of snuff was
put into whisky for the purpose of robbery. In 1854, a man was accused
of attempting to poison his wife by putting snuff into her ale, but
acquitted. In another case, the father of a child, ten weeks old, killed
the infant by putting tobacco into its mouth. He defended himself by
saying that it was applied to make the child sleep.

In October 1855,[356] a drunken sailor swallowed (perhaps for the
purpose of suicide) his quid of tobacco, containing from about half an
ounce to an ounce. He had it some time in his mouth, and in half an hour
suffered from frightful tetanic convulsions. There was also diarrhœa;
the pupils were dilated widely; the heart’s action became irregular; and
towards the end the pupils again contracted. He died in a sort of
syncope, seven hours after swallowing the tobacco.

[356] _Edin. Med. Journ._, 1855.

§ 333. In 1829 a curious instance of poisoning occurred in the case of
two girls, eighteen years of age, who suffered from severe symptoms of
tobacco-poisoning after drinking some coffee. They recovered; and it was
found that tobacco had been mixed with the coffee-berries, and both
ground up together.[357]

[357] Barkhausen, _Pr. Ver. Ztg._, v. 17, p. 83, 1838.

Accidents have occurred from children playing with old pipes. In
1877[358] a child, aged three, used for an hour an old tobacco-pipe, and
blew soap bubbles with it. Symptoms of poisoning soon showed themselves,
and the child died in three days.

[358] _Pharm. Journ._ [3], 377, 1877.

Tobacco-juice, as expressed or distilled by the heat developed in the
usual method of smoking, is very poisonous. Sonnenschein relates the
case of a drunken student, who was given a dram to drink, into which his
fellows had poured the juice from their pipes. The result was fatal.
Death from smoking is not unknown.[359] Helwig saw death follow in the
case of two brothers, who smoked seventeen and eighteen German pipefuls
of tobacco. Marshall Hall[360] records the case of a young man, nineteen
years of age, who, after learning to smoke for two days, attempted two
consecutive pipes. He suffered from very serious symptoms, and did not
completely recover for several days. Gordon has also recorded severe
poisoning from the consecutive smoking of nine cigars. The external
application of the leaf may, as already shown in the case of the horse,
produce all the effects of the internal administration of nicotine. The
old instance, related by Hildebrand, of the illness of a whole squadron
of hussars who attempted to smuggle tobacco by concealing the leaf next
to their skin, is well known, and is supported by several recent and
similar cases. The common practice of the peasantry, in many parts of
England, of applying tobacco to stop the bleeding of wounds, and also as
a sort of poultice to local swellings, has certainly its dangers. The
symptoms--whether nicotine has been taken by absorption through the
broken or unbroken skin, by the bowel, by absorption through smoking, or
by the expressed juice, or the consumption of the leaf itself--show no
very great difference, save in the question of time. Pure nicotine acts
with as great a rapidity as prussic acid; while if, so to speak, it is
entangled in tobacco, it takes more time to be separated and absorbed;
besides which, nicotine, taken in the concentrated condition, is a
strong enough base to have slight caustic effects, and thus leaves some
local evidences of its presence. In order to investigate the effects of
pure nicotine, Dworzak and Heinrich made auto-experiments, beginning
with 1 mgrm. This small dose produced unpleasant sensations in the mouth
and throat, salivation, and a peculiar feeling spreading from the region
of the stomach to the fingers and toes. With 2 mgrms. there was
headache, giddiness, numbness, disturbances of vision, torpor, dulness
of hearing, and quickened respirations. With 3 to 4 mgrms., in about
forty minutes there was a great feeling of faintness, intense
depression, weakness, with pallid face and cold extremities, sickness,
and purging. One experimenter had shivering of the extremities and
cramps of the muscles of the back, with difficult breathing. The second
suffered from muscular weakness, fainting, fits of shivering, and
creeping sensations about the arms. In two or three hours the severer
effects passed away, but recovery was not complete for two or three
days. It is therefore evident, from these experiments and from other
cases, that excessive muscular prostration, difficult breathing, tetanic
cramps, diarrhœa, and vomiting, with irregular pulse, represent both
tobacco and nicotine poisoning. The rapidly-fatal result of pure
nicotine has been already mentioned; but with tobacco-poisoning the case
may terminate lethally in eighteen minutes. This rapid termination is
unusual, with children it is commonly about an hour and a half, although
in the case previously mentioned, death did not take place for two days.

[359] The question as to whether there is much nicotine in tobacco-smoke
cannot be considered settled; but it is probable that most of the
poisonous symptoms produced are referable to the pyridene bases of the
general formula (C_{n}H_{2n-5}N). Vohl and Eulenberg (_Arch. Pharmac._,
2, cxlvi. p. 130) made some very careful experiments on the smoke of
strong tobacco, burnt both in pipes and also in cigars. The method
adopted was to draw the smoke first through potash, and then through
dilute sulphuric acid. The potash absorbed prussic acid, hydric
sulphide, formic, acetic, propionic, butyric, valeric, and carbolic
acids; while in the acid the bases were fixed, and these were found to
consist of the whole series of pyridene bases, from pyridene (C₅H₅N),
boil. point 117°, picoline (C₆H₇N), boil. point 133°, lutidine (C₇H₉N),
boil. point 154°, upwards. When smoked in pipes, the chief yield was
pyridene; when in cigars, collidine (C₈H₁₁N); and in general,
pipe-smoking was found to produce a greater number of volatile bases.
The action of these bases has been investigated by several observers.
They all have a special action on the organism, and all show an increase
in physiological activity as the series is ascended. The lowest produce
merely excitement from irritation of the encephalic nervous centres, and
the highest, paralysis of those centres. Death proceeds from gradual
failure of the respiratory movements, leading to asphyxia--(Kendrick and
Dewar, _Proc. Roy. Soc._, xxii. 442; xxiii. 290). The most recent
experimental work is that of A. Gautier; he found that tobacco smoked in
a pipe produced basic compounds, a large quantity of nicotine, and a
higher homologue of nicotine, C₁₁H₁₆N₂, which pre-exists in tobacco
leaves, and a base C₆H₉NO, which seems to be a hydrate of
picoline--(_Compt. Rend._, t. cxv. p. 992, 993). The derivatives of the
pyridene series are also active. The methiodides strongly excite the
brain and paralyse the extremities. A similar but more energetic action
is exerted by the ethyl and allyl derivatives; the iodyallyl derivatives
are strong poisons. Methylic pyridene carboxylate is almost inactive,
but the corresponding ammonium salt gives rise to symptoms resembling
epilepsy--(Ramsay, _Phil. Mag._, v. 4, 241). One member of the pyridene
series β-lutidine has been elaborately investigated by C. Greville
Williams and W. H. Waters--(_Proc. Roy. Soc._, vol. xxxii. p. 162,
1881). They conclude that it affects the heart profoundly, causing an
increase in its tonicity, but the action is almost confined to the
ventricles. The auricles are but little affected, and continue to beat
after the ventricles have stopped. The rate of the heart’s beat is
slowed, and the inhibitory power of the vagus arrested. By its action on
the nervous cells of the spinal cord, it in the first place lengthens
the time of reflex action, and then arrests that function. Finally, they
point out that it is antagonistic to strychnine, and may be successfully
employed to arrest the action of strychnine on the spinal cord.

[360] _Edin. Med. and Surg. Jour._, xii., 1816.

§ 334. =Physiological Action.=--Nicotine is absorbed into the blood and
excreted unchanged, in part by the kidneys and in part by the saliva
(_Dragendorff_). According to the researches of Rosenthal and
Krocker,[361] nicotine acts energetically on the brain, at first
exciting it, and then lessening its activity; the spinal marrow is
similarly affected. The convulsions appear to have a cerebral origin;
paralysis of the peripheral nerves follows later than that of the nerve
centres, whilst muscular irritability is unaffected. The convulsions are
not influenced by artificial respiration, and are therefore to be
considered as due to the direct influence of the alkaloid on the nervous
system. Nicotine has a striking influence on the respiration, first
quickening, then slowing, and lastly arresting the respiratory
movements: section of the vagus is without influence on this action.
The cause of death is evidently due to the rapid benumbing and paralysis
of the respiratory centre. Death never follows from heart-paralysis,
although nicotine powerfully influences the heart’s action, small doses
exciting the terminations of the vagus in the heart, and causing a
slowing of the beats. Large doses paralyse both the controlling and
exciting nerve-centres of the heart; the heart then beats fast,
irregularly, and weakly. The blood-vessels are first narrowed, then
dilated, and, as a consequence, the blood-pressure first rises, then
falls. Nicotine has a special action on the intestines. As O. Nasse[362]
has shown, there is a strong contraction of the whole tract, especially
of the small intestine, the lumen of which may be, through a continuous
tetanus, rendered very small. This is ascribed to the peripheral
excitation of the intestinal nerves and the ganglia. The uterus is also
excited to strong contraction by nicotine; the secretions of the bile
and saliva are increased.

[361] _Ueber die Wirkung des Nicotines auf den thierischen Organismus_,
Berlin, 1868.

[362] _Beiträge zur Physiologie der Darmbewegung, Leipsic_, 1866.

§ 335. =Fatal Dose.=--The fatal dose for dogs is from ½ to 2 drops; for
rabbits, a quarter of a drop; for an adult not accustomed to tobacco the
lethal dose is probably 6 mgrms.

§ 336. =Post-mortem Appearances.=--There seem to be no appearances so
distinctive as to be justly ascribed to nicotine or tobacco-poisoning
and no other.

A more or less fluid condition of the blood, and, generally, the signs
of death by the lungs, are those most frequently found. In
tobacco-poisoning, when the leaves themselves have been swallowed, there
may be some inflammatory redness of the stomach and intestine.

§ 337. =Separation of Nicotine from Organic Matters, &c.=--The process
for the isolation of nicotine is precisely that used for coniine (see p.
269). It appears that it is unaltered by putrefaction, and may be
separated and recognised by appropriate means a long time after death.
Orfila detected it in an animal two or three months after death; Melsens
discovered the alkaloid unmistakably in the tongues of two dogs, which
had been buried in a vessel filled with earth for seven years; and it
has been found, by several experiments, in animals buried for shorter
periods. Nicotine should always be looked for in the tongue and mucous
membrane of the mouth, as well as in the usual viscera. The case may be
much complicated if the person supposed to be poisoned should have been
a smoker; for the defence would naturally be that there had been either
excessive smoking or chewing, or even swallowing accidentally a quid of
tobacco.[363] A ptomaine has been discovered similar to nicotine.
Wolckenhaar separated also an alkaloid not unlike nicotine from the
corpse of a woman addicted to intemperate habits; but this base was not
poisonous, nor did it give any crystals when an ethereal solution was
added to an ether solution of iodine. It will be well always to support
the chemical evidence by tests on animal life, since the intensely
poisonous action of nicotine seems not to be shared by the nicotine-like
ptomaines.

[363] In an experiment of Dragendorff’s, nicotine is said to have been
detected in 35 grms. of the saliva of a person who had half an hour
previously smoked a cigar.


3. PITURIE.[364]

[364] See “The Alkaloid from Piturie,” by Prof. Leversidge, _Chem.
News_, March 18 and 25, 1881.

    § 338. Piturie (C₆H₈N) is a liquid, nicotine-like alkaloid, obtained
    from the _Duboisia hopwoodii_, a small shrub or tree belonging to
    the natural order _Solanaceæ_, indigenous in Australia. The natives
    mix piturie leaves with ashes from some other plant, and chew them.
    Piturie is obtained by extracting the plant with boiling water
    acidified with sulphuric acid, concentrating the liquid by
    evaporation, and then alkalising and distilling with caustic soda,
    and receiving the distillate in hydrochloric acid. The solution of
    the hydrochlorate is afterwards alkalised and shaken up with ether,
    which readily dissolves out the piturie. The ether solution of
    piturie is evaporated to dryness in a current of hydrogen, and the
    crude piturie purified by distillation in hydrogen, or by changing
    it into its salts, and again recovering, &c. It is clear and
    colourless when pure and fresh, but becomes yellow or brown when
    exposed to air and light. It boils and distils at 243° to 244°. It
    is soluble in all proportions in alcohol, water, and ether; its
    taste is acrid and pungent; it is volatile at ordinary temperatures,
    causing white fumes with hydrochloric acid; it is very irritating to
    the mucous membranes, having a smell like nicotine at first, and
    then, when it becomes browner, like pyridine. It forms salts with
    acids, but the acetate, sulphate, and hydrochlorate are varnish-like
    films having no trace of crystallisation; the oxalate is a
    crystalline salt. Piturie gives precipitates with mercuric chloride,
    cupric sulphate, gold chloride, mercur-potassic iodide, tannin, and
    an alcoholic solution of iodine. If an ethereal solution of iodine
    is added to an ethereal solution of piturie, a precipitate of
    yellowish-red needles, readily soluble in alcohol, is deposited. The
    iodine compound melts at 110°, while the iodine compound of nicotine
    melts at 100°. Piturie is distinguished from coniine by its aqueous
    solution not becoming turbid either on heating or on the addition of
    chlorine water; it differs from picoline in specific gravity,
    picoline being ·9613 specific gravity at 0°, and piturie sinking in
    water; it differs from aniline by not being coloured by chlorinated
    lime. From nicotine it has several distinguishing marks, one of the
    best being that it does not change colour on warming with
    hydrochloric acid and the addition to the mixture afterwards of a
    little nitric acid. The physiological action seems to be but little
    different from that of nicotine. It is, of course, poisonous, but as
    yet has no forensic importance.


4. SPARTEINE.

    § 339. In 1851 Stenhouse[365] separated a poisonous volatile
    alkaloid from _Spartium scoparium_, the common broom, to which he
    gave the name of sparteine. At the same time a crystalline
    non-poisonous substance, _scoparin_, was discovered.

[365] _Phil. Trans._, 1851.

    Sparteine is separated from the plant by extraction with sulphuric
    acid holding water, and then alkalising the acid solution and
    distilling: it has the formula (C₁₅H₂₆N₂), and belongs to the class
    of tertiary diamines. It is a clear, thick, oily substance, scarcely
    soluble in water, to which it imparts a strong, alkaline reaction;
    it is soluble in alcohol, in ether, and chloroform; insoluble in
    benzene and in petroleum; it boils at 288°. Sparteine neutralises
    acids fully, but the oxalate is the only one which can be readily
    obtained in crystals. It forms crystalline salts with platinic
    chloride, with gold chloride, with mercuric chloride, and with zinc
    chloride. The picrate is an especially beautiful salt, crystallising
    in long needles, which, when dried and heated, explode. On sealing
    sparteine up in a tube with ethyl iodide and alcohol, and heating to
    100° for an hour, ethyl sparteine iodide separates in long,
    needle-like crystals, which are somewhat insoluble in cold alcohol.

    =Effect on Animals.=--A single drop kills a rabbit; the symptoms are
    similar to those produced by nicotine, but the pupils are
    dilated.[366]

[366] To the nicotine group, gelsemine (C₂₄H₂₈N₂O₄) and oxalathylin
(C₆H₁₀N₂) also belong, in a physiological sense, but gelsemine, like
sparteine, dilates the pupil.


5. ANILINE.

    § 340. =Properties.=--Aniline or amido-benzol (C₆H₅NH₂) is made by
    the reduction of nitro-benzol. It is an oily fluid, colourless when
    quite pure, but gradually assuming a yellow tinge on exposure to the
    air. It has a peculiar and distinctive smell. It boils at 182·5°,
    and can be congealed by a cold of 8°. It is slightly soluble in
    water, 100 parts of water at 16° retaining about 3 of aniline, and
    easily soluble in alcohol, ether, and chloroform. It does not blue
    red-litmus paper, but nevertheless acts as a weak alkali, for it
    precipitates iron from its salts. It forms a large number of
    crystalline salts. The hydrochloride crystallises in white plates,
    and has a melting-point of 192°. The platinum compound has the
    formula of (C₆H₅NH₂HCl)₂PtCl₄, and crystallises in yellow needles.

    § 341. =Symptoms and Effects.=--Aniline, like picric acid,
    coagulates albumin. Aniline is a blood poison; it produces, even
    during life, in some obscure way, methæmoglobin, and it
    disintegrates the red blood corpuscles; both these effects lessen
    the power of the blood corpuscles to convey oxygen to the tissues,
    hence the cyanosis observed so frequently in aniline poisoning is
    explained. Engelhardt[367] has found that aniline black is produced;
    in every drop of blood there are fine black granules, the total
    effect of which produce a pale blue or grey-blue colour of the skin.
    Aniline has also an action on the central nervous system, at first
    stimulating, and then paralysing. Schmiedeberg finds that
    para-amido-phenol-ether-sulphuric acid is produced, and appears in
    the urine as an alkali salt; a small quantity of fuchsine is also
    produced, and has been found in the urine. Some aniline may be
    excreted unchanged.

[367] _Beiträge zur Tox. des Anilins. Inaug.-Diss._, Dorpat, 1888.

    The symptoms are giddiness, weakness, cyanosis, blueness of the
    skin, sinking of the temperature, and dilatation of the pupil. The
    pulse is small and frequent, the skin moist and cold. The patient
    smells of aniline. Towards the end coma and convulsions set in. The
    urine may be brown to brown-black, and may contain hyaline
    cylinders. The blood shows the spectrum of methæmoglobin, and has
    the peculiarities already mentioned. Should the patient recover,
    jaundice often follows. The outward application of aniline produces
    eczema.

    Chronic poisoning by aniline is occasionally seen among workers in
    the manufacture of aniline. Headache, loss of muscular power,
    diminished sensibility of the skin, vomiting, loss of appetite,
    pallor, eruptions on the skin, and general malaise are the chief
    symptoms. The perspiration has been noticed to have a reddish
    colour.

    Cases of aniline poisoning are not common; Dr. Fred. J. Smith has
    recorded one in the _Lancet_ of January 13, 1894.[368] The patient,
    a woman, 42 years of age, of alcoholic tendencies, swallowed, 13th
    December 1893, at 1.40 P.M., about 3 ounces of marking ink, the
    greatest part of which consisted of aniline; in a very little while
    she became unconscious, and remained so until death. At 3 P.M. her
    lips were of a dark purple, the general surface of the skin was
    deadly white, with a slight bluish tinge; the pupils were small and
    sluggish, the breathing stertorous, and the pulse full and slow--60
    per minute. The stomach was washed out, ether injected, and oxygen
    administered, but the patient died comatose almost exactly twelve
    hours after the poison had been taken.

[368] See also a case reported by K. Dehio, in which a person drank 10
grms. and recovered, _Ber. klinis. Wochen._, 1888, Nr. 1.

    The _post-mortem_ examination showed slight congestion of the lungs;
    the heart was relaxed in all its chambers, and empty of blood; it
    had a peculiar green-blue appearance. All the organs were healthy.
    The blood was not spectroscopically examined.

    § 342. =Fatal Dose.=--This is not known, but an adult would probably
    be killed by a single dose of anything over 6 grms. Recovery under
    treatment has been known after 10 grms.; the fatal dose for rabbits
    is 1-1·5 grms., for dogs 3-5 grms.

    § 343. =Detection of Aniline.=--Aniline is easily separated and
    detected. Organic fluids are alkalised by a solution of potash, and
    distilled. The organs, finely divided, are extracted with water
    acidulated with sulphuric acid, the fluid filtered, and then
    alkalised and distilled. The distillate is shaken up with ether, the
    ether separated and allowed to evaporate spontaneously. Any aniline
    will be in the residue left after evaporation of the ether, and may
    be identified by the following tests:--An aqueous solution of
    aniline or its salts is coloured blue by a little chloride of lime
    or hypochlorite of soda; later on the mixture becomes red. The blue
    colour has an absorption band, when examined spectroscopically,
    extending from W.L. 656 to 560, and therefore in the red and yellow
    from Fraunhofer’s line C, and overlapping D. Another test for
    aniline is the addition of kairine, hydrochloric acid, and sodium
    nitrite, which strikes a blue colour.


III.--The Opium Group of Alkaloids.

§ 344. =General Composition.=--Opium contains a larger number of basic
substances than any plant known. The list reaches at present to 18 or 19
nitrogenised bases, and almost each year there have been additions. Some
of these alkaloids exist in very small proportion, and have been little
studied. Morphine and narcotine are those which, alone, are
toxicologically important. Opium is a gummy mass, consisting of the
juice of the incised unripe fruit of the _Papaver somniferum_ hardened
in the air. The following is a nearly complete list of the constituents
which have been found in opium:--

  Morphine, C₁₇H₁₉NO₃.
  Narcotine, C₂₂H₂₃NO₇.
  Narceine, C₂₃H₂₉NO₉.
  Apomorphine, C₁₇H₁₇NO₂ } By dehydration of morphine and codeine
  Apocodeine, C₁₈H₁₉NO₂  } respectively.
  Pseudomorphine, C₁₇H₁₉NO₄.
  Codamine, C₂₀H₂₅NO₄.
  Ladanine, C₂₀H₂₅NO₄.
  Ladanosine, C₂₁H₂₇NO₄.
  Protapine, C₂₀H₁₉NO₅.
  Cryptopine, C₂₁H₂₃NO₅.
  Lanthopine, C₂₃H₂₅NO₄.
  Hydrocotarnine, C₁₂H₁₅NO₃.
  Opianine, C₂₁H₂₁NO₇.
  Cnoscopine, C₃₄H₃₆N₂O₁₁.
  Rhœadine, C₂₀H₂₁NO₇.
  Codeine, C₁₈H₂₁NO₃.
  Thebaine, C₁₉H₂₁NO₃.
  Papaverine, C₂₀H₂₁NO₄.
  Meconidine, C₂₁H₂₃NO₄.
  Meconin, C₁₀H₁₀O₄.
  Meconic acid, C₇H₄O₇.
  Thebolactic acid.
  Fat.
  Resin.
  Caoutchouc.
  Gummy matters--Vegetable mucus.
  Ash, containing the usual constituents.

The various opiums differ, the one from the other, in the percentages of
alkaloids, so that only a very general statement of the mean composition
of opium can be made. The following statement may, however, be accepted
as fairly representative of these differences:--

                                            Per cent.
  Morphine,                                  6 to 15
  Narcotine,                                 4 to  8
  Other alkaloids,                           5 to  2
  Meconin,                                   Under 1
  Meconic acid,                              3 to  8
  Peculiar resin and caoutchouc,             5 to 10
  Fat,                                       1 to  4
  Gum and soluble humoid acid matters,      40 to 50
  Insoluble matters and mucus,              18 to 20
  Ash,                                       4 to  8
  Water,                                     8 to 30

The general results of the analysis of 12 samples of Turkey opium,
purchased by Mr. Bott,[369] from leading druggists in London, Dublin,
and Edinburgh, are as follows:--

[369] _Year Book of Pharmacy_, 1876.

=Water.=--Highest, 31·2; lowest, 18·4; mean, 22·4 per cent.

=Insoluble Residue.=--Highest, 47·9; lowest, 25·45; mean, 32·48 per
cent.

=Aqueous Extract.=--Highest, 56·15; lowest, 20·90; mean, 45·90 per cent.

=Crude Morphine= (containing about 7/10 of pure morphine).--Highest,
12·30; lowest, 6·76; mean, 9·92 per cent., which equals 12·3 per cent.
of the dried drug.

=Persian Opium=, examined in the same way, varied in crude morphine from
2·1 to 8·5 per cent.; Malwa, from 5·88 to 7·30. In 18 samples of
different kinds of opium, the mean percentage of crude morphine was 8·88
per cent. (11 per cent. of the dried opium). According to Guibourt,
Smyrna opium, dried at 100°, yields 11·7 to 21·46 per cent., the mean
being 12 to 14 per cent.; Egyptian, from 5·8 to 12 per cent.; Persian,
11·37 per cent. In East Indian Patna opium, for medical use, he found
7·72; in a sample used for smoking, 5·27 per cent.; in Algerian opium,
12·1 per cent.; in French opium, 14·8 to 22·9 per cent.

§ 345. =Action of Solvents on Opium.=--The action of various solvents on
opium has been more especially studied by several scientists who are
engaged in the extraction of the alkaloids.

=Water= dissolves nearly everything except resin, caoutchouc, and woody
fibre. Free morphine would be left insoluble; but it seems always to be
combined with meconic and acetic acids. The solubility of free narcotine
in water is extremely small.

=Alcohol= dissolves resin and caoutchouc, and all the alkaloids and
their combinations, with meconic acid, &c.

=Amylic Alcohol= dissolves all the alkaloids, if they are in a free
state, and it also takes up a little of the resin.

=Ether, Benzene, and Carbon Sulphide= do not dissolve the resin, and
only slightly morphine, if free; but they dissolve the other free
alkaloids as well as caoutchouc.

=Acids= dissolve all the alkaloids and the resin.

=Fixed Alkalies=, in excess, dissolve in part resin; they also dissolve
morphine freely; narcotine remains insoluble.

=Lime Water= dissolves morphine, but is a solvent for narcotine only in
presence of morphine.

=Ammonia= dissolves only traces of morphine; but narceine and codeine
readily. It does not dissolve the other alkaloids, nor does it dissolve
the resin.

§ 346. =Assay of Opium.=--The following processes may be described:--

=Process of Teschemacher and Smith.=--This process, with a few
modifications, is as follows:--10 grms. of opium are as completely
exhausted with proof spirit at a boiling temperature as possible. The
resulting alcoholic extract is treated with a few drops of ammonium
oxalate solution, and the solution is almost neutralised with ammonia.
The solution is concentrated to one-third, cooled, and filtered. The
filtrate is farther concentrated to 5 c.c., and transferred to a small
flask, it is washed into this flask by 4 c.c. of water, and 3 c.c. of 90
per cent. alcohol; next 2 c.c. solution of ammonia (sp. gr. 0·960) and
25 c.c. of dry ether are added. The flask is corked, shaken, and then
allowed to rest over-night.

The ether is decanted as completely as possible. Two filter papers are
taken and counterpoised--that is to say, they are made precisely the
same weight. The filters are placed one inside the other, and the
precipitate collected on the inner one; the precipitate is washed with
morphinated water--that is to say, water in which morphine has been
digested for some days. The filter papers with their contents are washed
with benzene and dried, the outer paper put on the pan of the balance
carrying the weights, and the inner filter with the precipitate weighed.
The precipitate is now digested with a known volume of decinormal acid,
and then the excess of acid ascertained by titration with decinormal
alkali, using either litmus or methyl orange; each c.c. of decinormal
acid is equal to 30·3 mgrms. of morphine.[370]

[370] _Pharm. Journal_, xix. 45, 82; xxii. 746. Wright and Farr,
_Chemist and Druggist_, 1893, i. 78.

=Dott’s Process.=--Dott has recently proposed a new process, which he
states has given good results. The process is as follows:--10 grammes
of powdered opium are digested with 25 c.c. water; 1·8 gramme barium
chloride dissolved in about 12 c.c. water is then added, the solution
made up to 50 c.c., well mixed, and after a short time filtered. 22 c.c.
(representing 5 grammes opium) are mixed with dilute sulphuric acid in
quantity just sufficient to precipitate the barium. About 1 c.c. is
required, and the solution should be warmed to cause the precipitate to
subside, and the solution to filter clear. To this filtered solution a
little dilute ammonia, about 0·5 c.c. is added to neutralise the free
acid, and the solution concentrated to 6 or 7 c.c., and allowed to cool.
1 c.c. spirit and 1 c.c. ether are then added, and next ammonia in
slight excess. The ammonia should be added gradually until there is no
further precipitation, and a perceptible odour of ammonia remains after
well stirring and breaking down any lumps with the stirring rod. After
three hours the precipitate is collected on counterpoised filters and
washed. Before filtering, it should be noted that the solution has a
faint odour of ammonia: if not, one or two drops of ammonia solution
should be added. The dried precipitate is washed with benzene or
chloroform, dried, and weighed. It is then titrated with _n_/10 acid,
until the morphine is neutralised, as indicated by the solution
reddening litmus paper.[371]

[371] Other methods of opium assay have been published: see Mr. A. B.
Prescott’s method (_Proceedings of Amer. Pharm. Assoc._, 1878); Allen
(_Commercial Org. Analysis_, vol. ii. p. 473); E. R. Squibb’s
modification of Flückiger’s method (_Pharm. Journ._ (3), xii. p. 724); a
rapid mode of opium assay, MM. Portes and Lanjlois (_Journ. de Pharm. et
de Chim._, Nov. 1881); _Year Book of Pharmacy_, 1882.

To the above may be added--(1.) _Schacht’s Method._--5 to 10 grms. of
dry, finely-powdered opium are digested with sufficient distilled water
to make a thin pulp. After twenty-four hours the whole is thrown on a
weighed filter, and washed until the washings are almost colourless and
tasteless. The portion insoluble in water is dried at 100° and weighed;
in good opium this should not exceed 40 per cent. The filtrate is
evaporated until it is about one-fifth of the weight of the opium taken
originally; cooled, filtered, and treated with pure animal charcoal,
until the dark brown colour is changed into a brownish-yellow. The
liquid is then refiltered, precipitated with a slight excess of ammonia,
allowed to stand in an open vessel until all odour of ammonia
disappears, and at the same time frequently stirred, in order that the
precipitate may not become crystalline--a form which is always more
difficult to purify. The precipitate is now collected on a tared filter,
washed, dried, and weighed. With an opium containing 10 per cent. of
morphine, its weight is usually 14 per cent. A portion of the
precipitate is then detached from the filter, weighed, and exhausted,
first with ether, and afterwards with boiling alcohol (0·81 specific
gravity). Being thus purified from narcotine, and containing a little
colouring-matter only, it may now be dried and weighed, and the amount
of morphine calculated, on the whole, from the data obtained.

(2.) _Fleury_ has proposed a titration by oxalic acid as follows:--2
grms. of the powdered opium are macerated a few hours with 8 c.c. of
aqueous oxalate of ammonia, brought on a filter, and washed with 5 c.c.
of water. To the filtrate an equal volume of 80 per cent. alcohol and
ammonia to alkaline reaction is added; and, after standing twenty-four
hours in a closed flask, it is filtered, and the flask rinsed out with
some c.c. of 40 per cent. alcohol. The filter, with its contents, after
drying, is placed in the same flask (which should not be cleansed), a
few drops of alcoholic logwood solution are added, with an excess of
oxalic acid solution of known strength, the whole being made up to 100
c.c. This is divided into two parts, and the excess of acid titrated
back with diluted soda-lye. If the oxalic acid solution is of the
strength of 4·42 grms. to the litre, every c.c. of the oxalic acid
solution which has become bound up with morphine, corresponds to 0·02
grm. of morphine.

§ 347. =Medicinal and other Preparations of Opium.=--The chief mixtures,
pills, and other forms, officinal and non-officinal, in which opium may
be met with, are as follows:--


(1.) OFFICINAL.

=Compound Tincture of Camphor=, P. B. (Paregoric).--Opium, camphor,
benzoic acid, oil of anise, and proof spirit: the opium is in the
proportion of about 0·4 per cent., or 1 grain of opium in 240 minims.

=Ammoniated Tincture of Opium= (Scotch paregoric).--Strong solution of
ammonia, rectified spirit, opium, oil of anise, saffron, and benzoic
acid. Nearly 1 per cent. or 1 grain of opium in every 96 minims.

  =The Compound Powder of Kino=, P. B.
    Opium,                     5 per cent.
    Cinnamon,                 20     „
    Kino,                     75     „

  =The Compound Powder of Opium=, P. B.
    Opium,                    10·00 per cent.
    Black Pepper,             13·33     „
    Ginger,                   33·33     „
    Caraway Fruit,            40·00     „
    Tragacanth,                3·33     „

  =Pill of Lead and Opium=, P. B.
    Acetate of Lead,          75·0 per cent.
    Opium,                    12·5     „
    Confection of Roses,      12·5     „

=Tincture of Opium= (=Laudanum=).--Opium and proof spirit. One grain of
opium in 14·8 min.--that is, about 6·7 parts by weight in 100 by
measure.

The amount of opium actually contained in laudanum has been investigated
by Mr. Woodland,[372] from fourteen samples purchased from London and
provincial chemists. The highest percentage of extract was 5·01, the
lowest 3·21, the mean being 4·24; the highest percentage of morphine was
·70 per cent., the lowest ·32, the mean being ·51 per cent. It is,
therefore, clear that laudanum is a liquid of very uncertain strength.

[372] _Year Book of Pharmacy_, 1882.

=Aromatic Powder of Chalk and Opium.=--Opium 2·5 per cent., the rest of
the constituents being cinnamon, nutmeg, saffron, cloves, cardamoms, and
sugar.

=Compound Powder of Ipecacuanha= (Dover’s Powder).

  Opium,                   10 per cent.
  Ipecacuanha,             10     „
  Sulphate of Potash,      80     „

=Confection of Opium= (=Confectio opii=) is composed of syrup and
compound powder of opium; according to its formula, it contains 2·4 per
cent. of opium by weight.

=Extract of Opium= contains the solid constituents capable of extraction
by water; it should contain 20 per cent. of morphine, and is therefore
about double the strength of dry powdered opium.

=Liquid Extract of Opium= has been also examined by Mr. Woodland:[373]
ten samples yielded as a mean 3·95 per cent. of dry extract, the highest
number being 4·92 per cent., the lowest 3·02. The mean percentage of
morphine was ·28 per cent., the highest amount being ·37, and the lowest
·19 per cent.

[373] _Op. cit._

=Liniment of Opium= is composed of equal parts of laudanum and soap
liniment; it should contain about 0·0375 per cent. morphine.

=The Compound Soap-pill= is made of soap and opium, one part of opium in
every 5·5 of the mass--_i.e._, about 18 per cent.

=Ipecacuanha and Morphine Lozenges=, as the last, with the addition of
ipecacuanha; each lozenge contains 1/36 grain (1·8 mgrms.) morphine
hydrochlorate, 1/12 grain (5·4 mgrms.) ipecacuanha.

=Morphia Suppositories= are made with hydrochlorate of morphine,
benzoated lard, white wax, and oil of theobroma; each suppository
contains ½ grain (32·4 mgrms.) of morphine salt.

=Opium Lozenges= are composed of opium extract, tincture of tolu, sugar,
gum, extract of liquorice, and water. Each lozenge contains 1/10 grain
(6·4 mgrms.) of extract of opium, or about 1/50 grain (1·3 mgrm.)
morphine.

=The Ointment of Galls and Opium= contains one part of opium in 14·75
parts of the ointment--_i.e._, opium 6·7 per cent.

=Opium Wine=, P. B.--Sherry, opium extract, cinnamon, and cloves. About
5 of opium extract by weight in 100 parts by measure (22 grains to the
ounce).

=Solutions of Morphine=, both of the acetate and hydrochlorate, P. B.,
are made with a little free acid, and with rectified spirit. The
strength of each is half a grain in each fluid drachm (·0324 grm. in
3·549), or ·91 part by weight in 100 by measure.

=Solution of Bimeconate of Morphine.=--One fluid oz. contains 5½ grains
of bimeconate of morphine.

=Morphia Lozenges= are made with the same accessories as opium lozenges,
substituting morphine for opium; each lozenge contains 1/36 grain of
hydrochlorate of morphia (1·8 mgrm.).

=Syrup of Poppies.=--The ordinary syrup of poppies is sweetened
laudanum. It should, however, be what it is described--viz., a syrup of
poppy-heads. As such, it is said to contain one grain of extract of
opium to the ounce.


(2.) PATENT AND OTHER NON-OFFICINAL PREPARATIONS OF OPIUM.

    =Godfrey’s Cordial= is made on rather a large scale, and is variable
    in strength and composition. It usually contains about 1½ grains of
    opium in each fluid ounce,[374] and, as other constituents:
    sassafras, molasses or treacle, rectified spirit, and various
    flavouring ingredients, especially ginger, cloves, and coriander;
    aniseed and caraways may also be detected.

[374] If made according to Dr. Paris’ formula, 1⅙ grains in an ounce.

    =Grinrod’s Remedy for Spasms= consists of hydrochlorate of morphine,
    spirit of sal-volatile, ether, and camphor julep; strength, 1 grain
    of the hydrochlorate in every 6 ounces.

    =Lemaurier’s Odontalgic Essence= is acetate of morphine dissolved in
    cherry-laurel water; strength, 1 grain to the ounce.

    =Nepenthe= is a preparation very similar to _Liq. Opii sedativ._,
    and is of about the same strength as laudanum.[375]

[375] It may be regarded as a purified alcoholic solution of meconate of
morphia, with a little excess of acid, and of about the same strength as
laudanum.--_Taylor._

    =Black Drop= (known also by various names, such as Armstrong’s Black
    Drop) is essentially an acetic acid solution of the constituents of
    opium. It is usually considered to be of four times the strength of
    laudanum. The wholesale receipt for it is: Laudanum, 1 oz., and
    distilled vinegar 1 quart, digested for a fortnight. The original
    formula proposed by the Quaker doctor of Durham, Edward Tunstall,
    is--Opium, sliced, ½ lb.; good verjuice,[376] 3 pints; and nutmeg,
    1½ oz.; boiled down to a syrup thickness; ¼ lb. of sugar and 2
    teaspoonfuls of yeast are then added. The whole is set in a warm
    place for six or eight weeks, after which it is evaporated in the
    open air until it becomes of the consistence of a syrup. It is
    lastly decanted and filtered, a little sugar is added, and the
    liquid made up to 2 pints.

[376] Verjuice is the juice of the wild crab.

    =“Nurse’s Drops”= seem to be composed of oil of caraway and
    laudanum.

    =Powell’s Balsam of Aniseed=, according to evidence in the case of
    _Pharmaceutical Society v. Armson_ (_Pharm. Journ._, 1894), contains
    in every oz. 1/10 grain of morphine.

    =Dalby’s Carminative=--

  Carbonate of magnesia,                                40  grains.
  Tincture of castor, and compound tincture  of cardamoms,
  of each                                               15  drops.
  Laudanum,                                              5    „
  Oil of aniseed,                                        3    „
  Oil of nutmeg,                                         2    „
  Oil of peppermint,                                     1    „
  Peppermint water,                                      2  fl. ounces

    Dose, from a half to one teaspoonful. Another recipe has no
    laudanum, but instead syrup of poppies.

    =Chlorodyne=--Brown’s Chlorodyne is composed of--

  Chloroform,                                            6  drachms.
  Chloric ether,                                         1     „
  Tincture of capsicum,                                   ½    „
  Hydrochlorate of morphine,                             8  grains.
  Scheele’s prussic acid,                               12  drops
  Tincture of Indian hemp,                               1  drachm.
  Treacle,                                               1     „

    =Atkinson’s Infant Preserver=--

  Carbonate of magnesia,                                 6  drachms.
  White sugar,                                           2  ounces
  Oil of aniseed,                                       20  drops.
  Spirit of sal-volatile,                                2½ drachms.
  Laudanum,                                              1     „
  Syrup of saffron,                                      1  ounce.
  Caraway water, to make up,                             1  pint.

    =Boerhave’s Odontalgic Essence=--

  Opium,                                                  ½ drachm.
  Oil of cloves,                                         2    „
  Powdered camphor,                                      5    „
  Rectified spirit,                                      1½ fl. ounce.

§ 348. =Statistics.=--During the ten years 1883-1892 no less than 1424
deaths in England and Wales were attributed to some form or other of
opium or its active constituents; 45 of these deaths were ascribed to
various forms of soothing syrup or to patent medicines containing opium
or morphine; 876 were due to accident or negligence; 497 were suicidal
and 6 were homicidal deaths. The age and sex distribution of the deaths
ascribed to accident and those ascribed to suicide are detailed in the
following tabular statement:--

DEATHS IN ENGLAND AND WALES DURING THE TEN YEARS 1883-1892 FROM OPIUM,
LAUDANUM, MORPHINE, &c.

                          ACCIDENT.

  Ages,        0-1  1-5  5-15  15-25  25-65  65 and  Total
                                             above
  Males,        72   27    1     16    302     85     503
  Females,      50   23    4     21    189     86     373
              --------------------------------------------
    Total,     122   50    5     37    491    171     876
              --------------------------------------------

                          SUICIDE.

  Ages,                  5-15  15-25  25-65  65 and  Total
                                             above
  Males,                   1     26    269     34     330
  Females,               ...     24    126     17     167
                        ----------------------------------
  Total,                   1     50    395     51     497
                        ----------------------------------

Of European countries, England has the greatest proportional number of
opium poisonings. In France, opium or morphine poisoning accounts for
about 1 per cent. of the whole; and Denmark, Sweden, Switzerland,
Germany, all give very small proportional numbers; arsenic, phosphorus,
and the acids taking the place of opiates. The more considerable
mortality arises, in great measure, from the pernicious practice--both
of the hard-working English mother and of the baby-farmer--of giving
infants various forms of opium sold under the name of “_soothing
syrups_,” “_infants’ friends_,” “_infants’ preservatives_,” “_nurses’
drops_” and the like, to allay restlessness, and to keep them during the
greater part of their existence asleep. Another fertile cause of
accidental poisoning is mistakes in dispensing; but these mistakes seem
to happen more frequently on the Continent than in England. This is in
some degree due to the decimal system, which has its dangers as well as
its advantages, _e.g._:--A physician ordered ·5 decigrm. of morphine
acetate in a mixture for a child, but omitted the decimal point, and the
apothecary, therefore, gave ten times the dose desired, with fatal
effect. Again, morphine hydrochlorate, acetate, and similar soluble
salts are liable to be mistaken for other white powders, and in this way
unfortunate accidents have occurred--accidents that, with proper
dispensing arrangements, should be impossible.

§ 349. =Poisoning of Children by Opium.=--The drugging of children by
opium--sometimes with a view to destroy life, sometimes merely for the
sake of the continual narcotism of the infant--is especially rife in
India.[377] A little solid opium is applied to the roof of the mouth, or
smeared on the tongue, and some Indian mothers have been known to
plaster the nipples with opium, so that the child imbibes it with the
milk. Europeans, again and again, have discovered the native nurses
administering opiates to the infants under their care, and it is feared
that in many cases detection is avoided.

[377] See Dr. Chevers’s _Jurisprudence_, 3rd ed., 232 _et seq._

The ignorant use of poppy-tea has frequently caused the death of young
children; thus in 1875 an inquest was held at Chelsea on the body of a
little boy two years and a half old. He had been suffering from
whooping-cough and enlargement of the bowels, and poppy-tea was by the
advice of a neighbour given to him. Two poppy-heads were used in making
a quart of tea, and the boy, after drinking a great portion of it, fell
into a deep sleep, and died with all the symptoms of narcotic poisoning.

§ 350. =Doses of Opium and Morphia.=--Opium in the solid state is
prescribed for adults in quantities not exceeding 3 grains, the usual
dose being from 16·2 mgrms. to 64·8 mgrms. (¼ to 1 grain). The extract
of opium is given in exactly the same proportions (special
circumstances, such as the habitual use of opium, excepted); the dose of
all the compounds of opium is mainly regulated by the proportion of
opium contained in them.

The dose for children (who bear opium ill) is usually very small; single
drops of laudanum are given to infants at the breast, and the dose
cautiously increased according to age. Most practitioners would consider
half a grain a very full dose, and, in cases requiring it, would seldom
prescribe at first more than 1/16 to ¼ grain.

The dose of solid opium for a horse is from 1·77 grm. to 7·08 grms. (½
drachm to 2 drachms); in extreme cases, however, 4 drachms (14·16 grms.)
have been given.

The dose for large cattle is from ·648 grm. to 3·88 grms. (10 to 60
grains); for calves, ·648 grm. (10 grains); for dogs it is greatly
regulated by the size of the animal, 16·2 to 129·6 mgrms. (¼ grain to 2
grains).

=Fatal Dose.=--Cases are recorded of infants dying from extremely small
doses of opium, _e.g._, ·7, 4·3, and 8·1 mgrms. (1/90, 1/15, and ⅛ of a
grain); but in such instances one cannot help suspecting some mistake.
It may, however, be freely conceded that a very small quantity might be
fatal to infants, and that 3 mgrms. given to a child under one year
would probably develop serious symptoms.

The smallest dose of solid opium known to have proved fatal to adults
was equal to 259 mgrms. (4 grains) of crude opium (_Taylor_), and the
smallest dose of the tincture (laudanum), 7·0 c.c. (2 drachms),
(_Taylor_); the latter is, however, as already shown, uncertain in its
composition.

A dangerous dose (save under special circumstances) is:--For a horse,
14·17 grms. (4 drachms); for cattle, 7·04 grms. (2 drachms); for a dog
of the size and strength of a foxhound, 204 mgrms. (3 grains).

Enormous and otherwise fatal doses may be taken under certain conditions
by persons who are not opium-eaters. I have seen 13 cgrms. (2 grains) of
morphine acetate injected hypodermically in a strong man suffering from
rabies with but little effect. Tetanus, strychnine, convulsions, and
excessive pain all decrease the sensibility of the nervous system to
opium.

§ 351. =General Method for the Detection of Opium.=--It is usually laid
down in forensic works that, where poisoning by opium is suspected, it
is sufficient to detect the presence of meconic acid in order to
establish that of opium. In a case of adult poisoning there is generally
substance enough available to obtain one or more alkaloids, and the
presence of opium may, without a reasonable doubt, be proved, if meconic
acid (as well as either morphine, narcotine, thebaine, or other opium
alkaloid) has been detected. Pills containing either solid opium or the
tincture usually betray the presence of the drug by the odour, and in
such a case there can be no possible difficulty in isolating morphine
and meconic acid, with probably one or two other alkaloids. The method
of extraction from organic fluids is the same as before described, but
it may, of course, be modified for any special purpose. If opium, or a
preparation of opium, be submitted to Dragendorff’s process (see p.
242), the following is a sketch of the chief points to be noticed.

If the solution is _acid_--

(1.) =Benzene= mainly extracts _meconin_, which dissolves in sulphuric
acid very gradually (in twenty-four to forty-eight hours), with a green
colour passing into red. Meconin has no alkaloidal reaction.

(2.) =Amyl alcohol= dissolves small quantities of _meconic acid_,
identified by striking a blood-red colour with ferric chloride.

If now the amyl alcohol is removed with the aid of petroleum ether, and
the fluid made alkaline by ammonia--

(1.) =Benzene= extracts _narcotine_, _codeine_, and _thebaine_. On
evaporation of the benzene the alkaloidal residue may be dissolved in
water, acidified with sulphuric acid, and after filtration, on adding
ammonia _in excess_, _thebaine and narcotine_ are precipitated,
_codeine_ remaining in solution. The dried precipitate, if it contain
thebaine, becomes blood-red when treated with cold concentrated
sulphuric acid, while narcotine is shown by a violet colour developing
gradually when the substance is dissolved in dilute sulphuric acid 1 :
5, and gently warmed. The codeine in the ammoniacal solution can be
recovered by shaking up with benzene, and recognised by the red colour
which the solid substance gives when treated with a little sugar and
sulphuric acid.

(2.) =Chloroform= especially dissolves the _narceine_, which, on
evaporation of the chloroform, may be identified by its general
characters, and by its solution in Fröhde’s reagent becoming a beautiful
blue colour. Small quantities of morphine may be extracted with codeine.

(3.) =Amyl alcohol= extracts from the alkaline solution morphine,
identified by its physical characters, by its forming a crystalline
precipitate with iodine and hydriodic acid, and the reaction with iodic
acid to be described.

§ 352. =Morphine= (C₁₇H₁₇NO(OH)₂ + H₂O).--Morphine occurs in commerce as
a white powder, sp. gr. 1·205, usually in the form of more or less
perfect six-sided prisms, but sometimes in that of white silky needles.
When heated in the subliming cell (described at pp. 257-8), faint
nebulæ, resolved by high microscopic powers into minute dots, appear on
the upper disc at 150°. As the temperature is raised the spots become
coarser, and at 188° distinct crystals may be obtained, the best being
formed at nearly 200°, at which temperature morphine begins distinctly
to brown, melt, and carbonise. At temperatures below 188°, instead of
minute dots, the sublimate may consist of white circular spots or
foliated patterns. One part of morphine, according to P. Chastaing, is
soluble at a temperature of 3° in 33,333 parts of water; at 22°, in 4545
parts; at 42°, 4280; and at 100°, 4562. It is scarcely soluble in ether
or benzene. Absolute alcohol, according to Pettenkofer, dissolves in the
cold one-fortieth of its weight; boiling, one-thirtieth. Amyl alcohol,
in the cold, dissolves one-fourth per cent., and still more if the
alkaloid be thrown out of an aqueous acid solution by ammonia in the
presence of amyl alcohol; for under such circumstances the morphine has
no time to become crystalline. According to Schlimpert, 1 part of
morphine requires 60 of chloroform for solution; according to
Pettenkofer, 175.

Morphine is easily soluble in dilute acids, as well as in solutions of
the caustic alkalies and alkaline earths; carbonated alkalies and
chloride of ammonium also dissolve small quantities. The acid watery,
and the alcoholic solutions, turn the plane of polarisation to the left;
for sulphuric, nitric, and hydrochloric acids [α]_r_ = 89·8°; in
alkaline solution the polarisation is less, [α]_r_ = 45·22°. It is
alkaline in reaction, neutralising acids fully; and, in fact, a
convenient method of titrating morphine is by the use of a centinormal
sulphuric acid--each c.c. equals 2·85 mgrms. of anhydrous morphine.

§ 353. The salts of morphine are for the most part crystalline, and are
all bitter, neutral, and poisonous. They are insoluble in amylic
alcohol, ether, chloroform, benzene, or petroleum ether.

=Morphine meconate= is one of the most soluble of the morphine salts; it
is freely soluble in water. Of all salts this is most suitable for
subcutaneous injection; it is the form in which the alkaloid exists in
opium.

=Morphine hydrochlorate= (C₁₇H₁₉NO₃HCl) crystallises in silky fibres; it
is readily soluble in alcohol, and is soluble in cold, more freely in
boiling water. The purest morphine hydrochlorate is colourless, but that
which is most frequently met with in commerce is fawn or buff-coloured.

=Morphine acetate= is a crystallisable salt, soluble in water or
alcohol; it is in part decomposed by boiling the aqueous solution, some
of the acetic acid escaping.

=Morphine Tartrates.=--These are readily soluble salts, and it is
important to note that the morphine might escape detection, if the
expert trusted alone to the usual test of an alkaloidal salt giving a
precipitate when the solution is alkalised by the fixed or volatile
alkalies; for the tartrates of morphine do not give this reaction, nor
do they give any precipitate with calcic chloride. By adding a solution
of potassium acetate in spirit, and also alcohol and a little acetic
acid to the concentrated solution, the tartrate is decomposed, and acid
tartrate of potassium is precipitated in the insoluble form; the
morphine in the form of acetate remains in solution, and then gives the
usual reactions.

The solubility of morphine salts in water and alcohol has been
investigated by Mr. J. U. Lloyd. His results are as follows:--

  =Morphine Acetate.=

   11·70 parts of water by weight at 15·0° dissolve 1 part of morphine
         acetate.
   61·5  parts of water by weight at 100° dissolve 1 part of morphine
         acetate.
   68·30 parts of alcohol by weight (·820 specific gravity) at 15·0°
         dissolve 1 part of morphine acetate.
   13·30 parts of alcohol by weight (·820 specific gravity) at 100°
         dissolve 1 part of morphine acetate.

  =Morphine Hydrochlorate.=

   23·40 parts of water dissolve at 15° 1 morphine hydrochlorate.
     ·51 part of water dissolves at 100° 1 morphine hydrochlorate.
   62·70 parts of alcohol (·820 specific gravity) dissolve at 15° 1
         morphine hydrochlorate.
   30·80 parts of alcohol (·820 specific gravity) dissolve at 100° 1
         morphine hydrochlorate.

  =Morphine Sulphate.=

   21·60 parts of water at 15° dissolve 1 morphine sulphate.
     ·75 part of water at 100° dissolves 1 morphine sulphate.
  701·5  parts of alcohol (·820) at 15° dissolve 1 morphine sulphate.
  144·00 parts of alcohol (·820) at 100° dissolve 1 morphine sulphate.

§ 354. =Constitution of Morphine.=--The chief facts bearing on the
constitution of morphine are as follows:--

It certainly contains two hydroxyl groups, because by the action of
acetic anhydride, acetyl morphine and diacetyl morphine,
C₁₇H₁₈(CH₃CO)NO₃ and C₁₇H₁₇(CH₃CO)₂NO₃ are produced. The formation of
the monomethyl ether of morphine (codeine), C₁₇H₁₇(OH)(OCH₃)NO, is also
a testimony to the existence of hydroxyl groups. One of the hydroxyl
groups has phenolic functions, the other alcoholic functions. By
suitable oxidation morphine yields trinitrophenol (picric acid), and by
fusion with an alkali, protocatechuic acid; both of these reactions
suggest a benzene ring. On distilling with zinc dust phenanthrene,
pyridine, pyrrol, trimethylamine, and ammonia are formed; evidence of a
pyridine nucleus. If morphine is mixed with 10 to 15 times its weight of
a 20 per cent. solution of potash, and heated at 180° for from four to
six hours, air being excluded, a phenol-like compound is formed, and a
volatile amine, ethylmethylamine (the amine boils at 34° to 35°, and its
hydrochloride melts at 133°). This reaction is interpreted by Z. H.
Skrauk[378] and L. Wiegmann to indicate that the nitrogen is directly
connected with two alkyl groups--that is, ethyl and methyl.

[378] _Monatsb._, x. 110-114.

G. N. Vis,[379] after a careful review of the whole of the reactions of
morphine, has proposed the following constitutional formula as the one
that agrees best with the facts:--

  CH--CH--CH--CH--CH----------------C--CH--CH
  |       |   |   |                 |  |
  CH--CH--CH--O   NMe--CH₂--CH(OH)--C--CH--CH

[379] _J. pr. Chemie_ (2), xlvii. 584. Knorr’s formula is--

          CHOH--CHO--CH₂
         /      |       \
  OH.C₁₀H₅       |        >
         \      |       /
          CH₂---CH.NMeCH₂

_Ber._, xxii. 1113-1119.

§ 355. =Tests for Morphine.=--(1.) One hundredth of a milligrm. of pure
morphine gives a blue colour to a paste of ammonium molybdate in
sulphuric acid; 20 mgrms. of ammonium molybdate are rubbed with a glass
rod in a porcelain dish, and well mixed with 5 drops of pure strong
sulphuric acid and the morphine in a solid form applied; titanic acid
and tungstates give similar reactions.

(2.) Morphine possesses strong reducing properties; a little solid
morphine dissolved in a solution of ferric chloride gives a Prussian
blue precipitate when ferridcyanide solution is added. A number of
ptomaines and other substances also respond to this test, so that in
itself it is not conclusive.

(3.) =Iodic Acid Test.=--The substance supposed to be morphine is
converted into a soluble salt by adding to acid reaction a few drops of
hydrochloric acid, and then evaporating to dryness. The salt thus
obtained is dissolved in as little water as possible--this, as in
toxicological researches only small quantities are recovered, will
probably be but a few drops. A little of the solution is now mixed with
a very small quantity of starch paste, and evaporated to dryness at a
gentle heat in a porcelain dish. After cooling, a drop of a solution of
1 part of iodic acid in 15 of water is added to the dry residue; and if
even the 1/20000 of a grain of morphine be present, a blue colour will
be developed.

Another way of working the iodic acid test is to add the iodic acid
solution to the liquid in which morphine is supposed to be dissolved,
and then shake the liquid up with a few drops of carbon disulphide. If
morphine be present, the carbon disulphide floats to the top distinctly
coloured pink. Other substances, however, also set free iodine from
iodic acid, and it has, therefore, been proposed to distinguish morphine
from these by the after addition of ammonia. If ammonia is added to the
solution, which has been shaken up with carbon disulphide, the pink or
red colour of the carbon disulphide is deepened, if morphine was
present; on the contrary, if morphine was _not_ present, it is either
discharged or much weakened.

=Other Reactions.=--There are some very interesting reactions besides
the two characteristic tests just mentioned. If a saturated solution of
chloride of zinc be added to a little solid morphine, and heated over
the water-bath for from fifteen minutes to half-an-hour, the liquid
develops a beautiful and persistent green colour. This would be an
excellent test for morphine were it not for the fact that the colour is
produced with only pure morphine. For example, I was unable to get the
reaction from morphine in very well-formed crystals precipitated from
ordinary laudanum by ammonia, the least trace of resinous or
colouring-matter seriously interfering. By the action of nitric acid on
morphine, the liquid becomes orange-red, and an acid product of the
formula C₁₀H₉NO₉ is produced, which, when heated in a closed tube with
water at 100°, yields trinitrophenol or picric acid. This interesting
reaction points very decidedly to the phenolic character of morphine. On
adding a drop of sulphuric acid to solid morphine in the cold, the
morphine solution becomes of a faint pink; on gently warming and
continuing the heat until the acid begins to volatilise, the colour
changes through a series of brownish and indefinite hues up to black. On
cooling and treating the black spot with water, a green solution is
obtained, agreeing in hue with the same green produced by chloride of
zinc. Vidali[380] has proposed the following test:--Morphine is
dissolved in strong sulphuric acid, and a little arsenate of sodium is
added; on gently warming, a passing blue colour develops; on raising the
temperature higher, the liquid changes into green, then into blue, and
finally again into green. Codeine acts very similarly. The following
test originated with Siebold (_American Journal of Pharmacy_, 1873, p.
544):--The supposed morphine is heated gently with a few drops of
concentrated sulphuric acid and a little pure potassic perchlorate. If
morphine be present the liquid immediately takes a pronounced brown
colour--a reaction said to be peculiar to morphine, and to succeed with
1/10 of a mgrm. In order to obtain absolutely pure perchlorate, potassic
perchlorate is heated with hydrochloric acid so long as it disengages
chlorine; it is then washed with distilled water, dried, and preserved
for use. There is also a test known as “Pellagri’s”; it depends on the
production of apomorphine. The suspected alkaloid is dissolved in a
little strong hydrochloric acid, and then a drop of concentrated
sulphuric acid is added, and the mixture heated for a little time from
100° to 120°, until it assumes a purple-black colour. It is now cooled,
some hydrochloric acid again added, and the mixture neutralised with
sodic carbonate. If morphine be present, on the addition of iodine in
hydriodic acid, a cherry-red colour is produced, passing into green.
Morphine and codeine are believed alone to give this reaction.

[380] D. Vidali, _Bull. Farmaceut._, Milano, 1881, p. 197; D. E. Dott,
_Year Book of Pharmacy_, 1882.

The acetate of morphine, and morphine itself, when added to ferric
chloride solution, develop a blue colour. When 1 molecule of morphine is
dissolved in alcohol, containing 1 molecule of sodium hydroxide, and 2
vols. of methyl iodide are added, and the mixture gently heated, a
violent reaction sets in and the main product is codeine methiodide
(C₁₇H₁₈NO₂OCH,MeI). If only half the quantity of methyl iodide is added,
then free codeine is in small quantity produced; if ethyl iodide be
substituted for methyl, a new base is formed homologous with
codeine--codeine is therefore the methyl ether of morphine. If morphine
is heated with iodide of methyl and absolute alcohol in a closed tube
for half an hour at 100°, methyl iodide of morphine is obtained in
colourless, glittering, quadratic crystals, easily soluble in water
(C₁₇H₁₉NO₃MeI + H₂O); similarly the ethyl iodide compound can be
produced.

If morphine is heated for from two to three hours in a closed tube with
dilute hydrochloric acid, water is eliminated--

  (C₁₇H₁₉NO₃ = C₁₇H₁₇NO₂ + H₂O),

and the hydrochlorate of apomorphine is produced. This succeeds when
even ½ mgrm. is heated with 1/10 c.c. of strong HCl, and the tests for
apomorphine applied.

If concentrated sulphuric acid be digested on morphine for twelve to
fifteen hours (or heated for half an hour at 100°), on adding to the
cooled violet-coloured solution either a crystal of nitrate of potash or
of chlorate of potash, or a drop of dilute nitric acid, a beautiful
violet-blue colour is produced, which passes gradually into a dark
blood-red. 1/100 of a mgrm. will respond distinctly to this test.
Fröhde’s reagent strikes with morphine a beautiful violet colour,
passing from blue into dirty green, and finally almost vanishing. 1/200
of a mgrm. will respond to the test, but it is not itself conclusive,
since papaverine and certain glucosides give an identical reaction.

§ 356. =Symptoms of Opium and Morphine Poisoning.=--The symptoms of
opium and morphine poisoning are so much alike, that clinically it is
impossible to distinguish them; therefore they may be considered
together.

=Action on Animals--Frogs.=--The action of morphine or opium on frogs is
peculiar: the animal at first springs restlessly about, and then falls
into a condition extremely analogous to that seen in strychnine
poisoning, every motion or external irritation producing a tetanic
convulsion. This condition is, however, sometimes not observed. The
tetanic stage is followed by paralysis of reflex movements and cessation
of breathing, the heart continuing to beat.

=Dogs.=--0·2 to 0·5 grm. of morphine meconate, or acetate, injected
directly into the circulation of a dog, shows its effects almost
immediately. The dog becomes uneasy, and moves its jaws and tongue as if
some peculiar taste were experienced; it may bark or utter a whine, and
then in a minute or two falls into a profound sleep, which is often so
deep that while it lasts--usually several hours--an operation may be
performed. In whatever attitude the limbs are placed, they remain. The
respiration is rapid and stertorous, and most reflex actions are
extinguished. Towards the end of the sleep, any sudden noise may startle
the animal, and when he wakes his faculties are evidently confused. A
partial paralysis of the hind legs has often been noticed, and then the
dog, with his tail and pelvis low, has something the attitude of the
hyena. Hence this condition (first, I believe, noticed by Bernard) has
been called the “hyenoid” state. If the dose is larger than 2 to 3 grms.
(31 to 46 grains), the symptoms are not dissimilar, save that they
terminate in death, which is generally preceded by convulsions.[381]

[381] MM. Grasset and Amblard have studied the action of morphine in
causing convulsions in the mammalia. They found that if small doses of
hydrochlorate of morphine (from 1 to 15 centigrammes) are administered
to dogs, the brief sleep which is produced may be accompanied by partial
muscular contractions (in one paw, for instance), which are renewed at
variable intervals. Then occur true convulsive shocks in the whole body
or in the hind limbs. After an interval, the phenomena recur in more
intense degree, and are followed by true convulsions. Regularly, ten or
sixteen times a minute, at each inspiration, the hind limbs present a
series of convulsive movements, which may become general. Sometimes they
are excited by external stimulation, but they are usually spontaneous.
The sleep may continue profound during this convulsive period, or it may
become distinctly lighter. These convulsive phenomena may continue, with
intervals, for an hour. Differences are observed with different animals;
but the chief characters of the phenomena are as described. In certain
animals, and with small doses, there may be a brief convulsive phase at
the commencement of the sleep, but it is much less constant than the
later period of spasm. These convulsions, the authors believe, have not
previously been described, except as a consequence of very large doses,
amounting to grammes. The period of cerebral excitement, described by
Claude Bernard as occurring at the commencement of the sleep from
morphine, is a phenomenon of a different order. The conclusions drawn
from the experiments are--(1) That morphia is not diametrically opposed
to thebaine, as is often stated, since it has, to a certain degree, the
convulsive properties of the latter alkaloid. (2) That the excitomotor
action of opium cannot be exclusively attributed to the convulsive
alkaloids, but is, in fact, due to those which are soporific. According
to the ordinary composition of opium, 5 centigrammes of morphine
represent about a milligramme of thebaine. But these experiments show
that the quantity of morphine has a much more powerful convulsive action
than a milligramme of thebaine. (3) There is not the supposed antagonism
between the action of morphine on the frog and on the mammalia. (4) The
researches hitherto undertaken on the antagonism between morphine and
other agents need to be repeated, and a separate study made of the
substances which antagonise the convulsive and soporific action.

=Goats.=--According to Guinard, goats are proof against the narcotic
influence of morphine. Large doses kill goats, but death is caused by
interference with the respiratory function. A young goat weighing 30
kilos, showed little effect beyond a slightly increased cerebral
excitability after two doses of 8 and 8·5 grms. respectively of morphine
hydrochlorate had been administered by intravenous injection, the second
being given an hour and a half after the first. To the same animal two
days afterwards 195 grms. were administered in the same way, yet the
goat recovered. The lethal dose for a goat seems to be no less than 1000
times that which will produce narcotism in man, and lies somewhere
between 0·25 to 0·30 per kilo. of the body weight.[382]

[382] _Compt. Rend._, t. cxvi. pp. 520-522.

=Cats and the Felidæ.=--According to Guinard,[383] morphine injected
subcutaneously or intravenously into cats, in doses varying from 0·4
mgrm. to 90 mgrms. per kilo., never produces sleep or narcotic
prostration. On the contrary, it causes a remarkable degree of
excitement, increasing in intensity with the dose given. This excitement
is evidently accompanied by disorder in the functions of the brain, and
if the dose is large convulsions set in, ending in death. According to
Milne-Edwards, the same symptoms are produced in lions and tigers.

[383] _Compt. Rend._, t. cxi. pp. 981-983. The _bovine_ animals also get
excited, and no narcotic effect is produced by dosing them with
morphine.--_Compt. Rend. Soc. de Biologie_, t. iv., v.

=Birds=, especially pigeons, are able to eat almost incredible
quantities of opium. A pigeon is said[384] to have consumed 801 grains
of opium, mixed with its food, in fourteen days. The explanation of this
is that the poison is not absorbed; for subcutaneous injections of salts
of morphine act rapidly on all birds hitherto experimented upon.

[384] Hermann’s _Lehrbuch der exper. Toxicologie_, p. 374.

§ 357. =Physiological Action.=--From experiments on animals, the
essential action of morphine on the nervous and arterial systems has in
some measure been examined. There is no very considerable action on the
heart. The beats are first accelerated, then diminished in frequency;
but very large doses introduced directly into the circulation at once
diminish the pulsations, and no acceleration is noticed. The slowing may
go on to heart-paralysis. The slowing is central in its origin, for on
the vagi being cut, morphine always quickens. With regard to the
peripheric ends of the vagi, small doses excite, large paralyse. If all
the nerves going to the heart are divided, there is first a considerable
acceleration, and then a slowing and weakening of the pulsations. The
arterial blood-pressure, at first increased, is afterwards diminished.
This increase of blood-pressure is noticed during the acceleration of
the pulse, and also during some portion of the time during which the
pulse is slowed. Stockman and D. B. Dott,[385] experimenting on rabbits
and frogs, consider that a medium dose of morphine first of all
depresses the spinal cord and then excites it, for tetanus follows. If
morphine is in sufficient quantity thrown into the circulation then
tetanus at once occurs. It would thus appear that depression and
stimulation is entirely a matter of dosage. Gescheidlen, in his
researches on the frog, found the motor nerves at first excited, and
then depressed. When the doses were large, there was scarcely any
excitement, but the reverse effect, in the neighbourhood of the place of
application. According to other observers, the function of the motor
nerves may be annihilated.[386] According to Meihuizen, reflex action,
at first much diminished, is later, after several hours, normal, and
later still again increased. The intestinal movements are transitorily
increased. In the dog there has been noticed a greater flow of saliva
than usual, and the flow of bile from the gall-bladder is diminished.
The pupils in animals are mostly contracted, but, if convulsions occur
towards death, they are dilated.

[385] _Brit. Med. Journ._ (2), 1890, 189-192.

[386] _Arch. f. d. Ges. Physiol._, vii. p. 201.

§ 358. =Physiological Effect of Morphine Derivatives.=--By introducing
methyl, or amyl, or ethyl, into the morphine molecule, the narcotic
action is diminished, while the tetanic effects are increased. Acetyl,
diacetyl, benzoyl, and dibenzoyl morphine, morphine sulphuric ether, and
nitrosomorphine are all weaker narcotics than morphine, but, on the
other hand, they depress the functions of the spinal cord and bring on,
in large doses, tetanus.

The introduction of two methyl groups into morphine, as in
metho-codeine, C₁₇H₁₇MeNO(OH)-Me, entirely alters the physiological
effect. This compound has an action on voluntary muscle causing gradual
paralysis.

The chlorine derivatives, trichlormorphine and chlorcodeine, have the
characteristic action of the morphine group on the central nervous
system and, in addition, act energetically as muscle poisons, soon
destroying the contractile power of the voluntary muscles with which
they first come into contact at the place of injection, and more
gradually affecting the other muscles of the body.[387]

[387] R. Stockman and Dott, _Brit. Med. Journ._ (2), 1890, 189-192.

§ 359. =Action on Man.=--There are at least three forms of opium
poisoning:--(1) _The common form_, as seen in about 99 per cent. of
cases; (2) A very _sudden form_, in which death takes place with fearful
rapidity (the _foudroyante_ variety of the French);[388] and (3) a very
rare entirely _abnormal form_, in which there is no coma, but
convulsions.

[388] Tardieu, _Étude Méd. Légale sur l’Empoisonnement._

In the _common form_ there are three stages, viz.:--(1) Excitement; (2)
Narcosis; (3) Coma. In from half an hour to an hour[389] the first
symptoms commence, the pulse is quickened, the pupils are contracted,
the face flushes, and the hands and feet reddened,--in other words, the
capillary circulation is active. This stage has some analogy to the
action of alcohol; the ideas mostly flow with great rapidity, and
instead of a feeling of sleepiness, the reverse is the case. It,
however, insensibly, and more or less rapidly, passes into the next
stage of heaviness and stupor. There is an irresistible tendency to
sleep; the pulse and the respiration become slower; the conjunctivæ are
reddened; the face and head often flushed. In some cases there is great
irritability of the skin, and an eruption of nettle-rash. If the poison
has been taken by the mouth, vomiting may be present. The bowels are
usually--in fact almost invariably--constipated. There is also some loss
of power over the bladder.

[389] In a remarkable case related by Taylor, a lady took a large dose
(supposed to be 1½ oz.) of laudanum, and there were no symptoms for four
and a half hours. She died in twenty-two hours.

In the next stage, the narcosis deepens into dangerous coma; the patient
can no longer be roused by noises, shaking, or external stimuli; the
breathing is loud and stertorous; the face often pale; the body covered
with a clammy sweat. The pupils are still contracted, but they may in
the last hours of life dilate: and it is generally agreed that, if a
corpse is found with the pupils dilated, this circumstance, taken in
itself, does not contra-indicate opium or morphine poisoning. Death
occasionally terminates by convulsion.

The _sudden form_ is that in which the individual sinks into a deep
sleep almost immediately--that is, within five or ten minutes--and dies
in a few hours. In these rapid cases the pupils are said to be
constantly dilated.

Examples of the _convulsive form_ are to be sought among opium-eaters,
or persons under otherwise abnormal conditions.

A man, forty years old, who had taken opiates daily since his
twenty-second year--his dose being 6 grms. (92·4 grains) of solid
opium--when out hunting, of which sport he was passionately fond, took
cold, and, as a remedy, administered to himself three times his
accustomed dose. Very shortly there was contraction of the left arm,
disturbance of vision, pain in the stomach, faintness, inability to
speak, and unconsciousness which lasted half an hour. Intermittent
convulsions now set in, and pains in the limbs. There was neither
somnolence nor delirium, but great agitation; repeated vomiting and
diarrhœa followed. After five hours these symptoms ceased; but he was
excessively prostrate.[390] There was complete recovery.

[390] Demontporcellet, _De l’Usage Quotidien de l’Opium_, Paris, 1874.

One may hazard a surmise that, in such a case, tolerance has been
established for morphine, but not for other morphine alkaloids in the
same degree, and that the marked nervous symptoms were in no small
degree the effect of some of the homologous alkaloids, which, in such an
enormous dose, would be taken in sufficient quantity to have a
physiological action.

There are several instances of a relapsing or remittent form of
poisoning--a form in which the patient more or less completely recovers
consciousness, and then sinks back into a fatal slumber. One of the best
known is the case of the Hon. Mrs Anson (January 1859), who swallowed an
ounce and a half of laudanum by mistake. After remaining in a comatose
condition for more than nine hours, she revived. The face became
natural, the pulse steady. She was able to recognise her daughter, and
in a thick voice to give an account of the mistake. But this lasted only
ten minutes, when she again became comatose, and died in fourteen
hours.[391]

[391] Taylor, _op. cit._

In a Swedish case quoted by Maschka,[392] a girl, nine years old, in
weak health and suffering from slight bronchitis, had been given a
non-officinal acetate of morphia lozenge, which was supposed to contain
5 mgrms. (·075 grain) of morphine acetate. She took the lozenge at eight
in the evening; soon slept, woke at ten, got out of bed, laughed,
talked, and joked with the nurse, again got into bed, and very quickly
fell asleep. At four A.M. the nurse came and found her breathing with a
rattling sound, and the physician, who arrived an hour later, found the
girl in a state of coma, with contracted pupils, breathing stertorously,
and the pulse scarcely to be felt. Despite all attempts to rouse the
patient, she died at eight in the morning, twelve hours after taking the
lozenge.

[392] Maschka’s _Handbuch_, Band ii. p. 438; also Svenska, _Läk-Sällsk.
Förhandl._, Apr. 1, p. 90; Apr. 8, p. 160, 1873. For other cases see
Nasmyth, _Edin. Med. Journ._, Dec. 1878; Kirby, _Dub. Med. Press_, Dec.
24, 1845; W. Boyd Muschet, _Med. Times and Gaz._, March 20, 1858.

The _post-mortem_ examination showed some hyperæmia of the brain and
serous effusion in the ventricles, and there was also tubercle in the
pleura. Three lozenges similar to the one taken by the patient were
chemically investigated by Hamberg, who found that the amount of acetate
was very small, and that the lozenges, instead of morphine acetate,
might be considered as prepared with almost pure morphine; the content
in the three of morphine being respectively 35, 37, and 42 mgrms. (that
is, from half a grain to three-fifths of a grain). There was a
difference of opinion among the experts as to whether in this case the
child died from morphine poisoning or not--a difference solely to be
attributed to the waking up of the child two hours after taking the
poison. Now, considering the great probability that a large dose for a
weakly child of that age had been taken, and that this is not the only
case in which a relapse has occurred, it seems just to infer that it was
really a case of poisoning.

As unusual symptoms (or rather sequelæ) may be noted in a few cases,
hemiplegia, which soon passes off; a weakness of the lower extremities
may also be left, and inability to empty the bladder thoroughly; but
usually on recovery from a large dose of opium, there is simply
heaviness of the head, a dry tongue, constipation, and loss of appetite.
All these symptoms in healthy people vanish in a day or two. There have
also been noticed slight albuminuria, eruptions on the skin, loss of
taste, and numbness of parts of the body.

Opium, whether taken in substance, or still more by subcutaneous
injection, in some individuals constantly causes faintness. In my own
case, I have several times taken a single grain of opium to relieve
either pain or a catarrh; almost invariably within an hour afterwards
there has been great coldness of the hands and feet, lividity of the
face, a feeling of deadly faintness followed by vomiting; this stage
(which has seldom lasted more than half an hour) passed, the usual
narcotic effects have been produced.

Some years ago I injected one-sixth of a grain of morphine hydrochlorate
subcutaneously into an old gentleman, who was suffering from acute
lumbago, but was otherwise healthy, and had no heart disease which could
be detected; the malady was instantly relieved, and he called out, “I am
well; it is most extraordinary.” He went out of the front door, and
walked some fifty yards, and then was observed to reel about like a
drunken man. He was supported back and laid in the horizontal posture;
the face was livid, the pulse could scarcely be felt, and there was
complete loss of consciousness. This state lasted about an hour, and
without a doubt the man nearly died. Medical men in practice, who have
been in the habit of using hypodermic injections of morphine, have had
experiences very similar to this and other cases, and although I know of
no actual death, yet it is evident that morphine, when injected
hypodermically even in a moderate dose, may kill by syncope, and within
a few minutes.[393] Absorption by hypodermic administration is so rapid
that by the time, or even before the needle of the syringe is withdrawn,
a contraction of the pupil may be observed.

[393] See a case of morphia poisoning by hypodermic injection, and
recovery, by Philip E. Hill, M.R.C.S., _Lancet_, Sept. 30, 1882. In this
instance a third of a grain introduced subcutaneously caused most
dangerous symptoms in a gardener, aged 48.

Opium or morphine is poisonous by whatever channel it gains access to
the system, the intestinal mucous membrane absorbs it readily, and
narcotic effects may be produced by external applications, whether a
wound is present or not. A case of absorption of opium by a wound is
related in Chevers’s _Jurisprudence_.[394] A Burman boy, about nine or
ten years of age, was struck on the forehead by a brick-bat, causing a
gaping wound about an inch long; his parents stuffed the wound with
opium. On the third day after the accident, and the opium still
remaining in the wound, he became semi-comatose, and, in short, had all
the symptoms of opium narcosis; with treatment he recovered. The
unbroken skin also readily absorbs the drug. Tardieu states that he had
seen 30 grms. of laudanum, applied on a poultice to the abdomen, produce
death. Christison has also cited a case in which a soldier suffered from
erysipelas, and died in a narcotic state, apparently produced from the
too free application of laudanum to the inflamed part.

[394] Third ed., p. 228.

To these cases may be added the one cited by Taylor, in which a druggist
applied 30 grains of morphine to the surface of an ulcerated breast, and
the woman died with all the symptoms of narcotic poisoning ten hours
after the application--an event scarcely surprising. It is a curious
question whether sufficient of the poison enters into the
secretions--_e.g._, the milk--to render it poisonous. An inquest was
held in Manchester, Nov. 1875, on the body of a male child two days old,
in which it seemed probable that death had occurred through the mother’s
milk. She was a confirmed opium-eater, taking a solid ounce per week.

§ 360. =Diagnosis of Opium Poisoning.=--The diagnosis is at times
between poisoning by opium or other narcotic substances, at others,
between opium and disease. Insensibility from chloral, from alcohol,
from belladonna or atropine, and from carbon oxide gas, are all more or
less like opium poisoning. With regard to chloral, it may be that only
chemical analysis and surrounding circumstances can clear up the matter.
In alcohol poisoning, the breath commonly smells very strongly of
alcohol, and there is no difficulty in separating it from the contents
of the stomach, &c., besides which the stomach is usually red and
inflamed. Atropine and belladonna invariably dilate the pupil, and
although just before death opium has the same effect, yet we must hold
that mostly opium contracts, and that a widely-dilated pupil during life
would, _per se_, lead us to suspect that opium had not been used,
although, as before mentioned, too much stress must not be laid upon the
state of the pupils. In carbon oxide, the peculiar rose-red condition of
the body affords a striking contrast to the pallor which, for the most
part, accompanies opium poisoning. In the rare cases in which
convulsions are a prominent symptom, it may be doubtful whether opium or
strychnine has been taken, but the convulsions hitherto noticed in opium
poisoning seem to me to have been rather of an epileptiform character,
and very different from the effects of strychnine. No rules can be laid
down for cases which do not run a normal course; in medicine such are
being constantly met with, and require all the care and acumen of the
trained observer. Cases of disease render a diagnosis often extremely
difficult, and the more so in those instances in which a dose of
laudanum or other opiate has been administered. In a case under my own
observation, a woman, suffering from emphysema and bronchitis, sent to a
chemist for a sleeping draught, which she took directly it arrived. A
short time afterwards she fell into a profound slumber, and died within
six hours. The draught had been contained in an ounce-and-a-half bottle;
the bottle was empty, and the druggist stated in evidence that it only
contained 20 minims of laudanum, 10 grains of potassic bromide, and
water. On, however, diluting the single drop remaining in the bottle,
and imitating its colour with several samples of laudanum diluted in the
same way, I came to the conclusion that the quantity of laudanum which
the bottle originally contained was far in excess of that which had been
stated, and that it was over 1 drachm and under 2 drachms. The body was
pallid, the pupils strongly contracted, the vessels of the brain
membranes were filled with fluid blood, and there was about an ounce of
serous fluid in each ventricle. The lungs were excessively
emphysematous, and there was much secretion in the bronchi; the liver
was slightly cirrhotic. The blood, the liver, and the contents of the
stomach were exhaustively analysed with the greatest care, but no trace
of morphine, narcotine, or meconic acid could be separated, although the
woman did not live more than six hours after taking the draught. I gave
the opinion that it was, in the woman’s state, improper to prescribe a
sedative of that kind, and that probably death had been accelerated, if
not directly caused, by opium.

Deaths by apoplexy will only simulate opium-poisoning during life; a
_post-mortem_ examination will at once reveal the true nature of the
malady. In epilepsy, however, it is different, and more than once an
epileptic fit has occurred and been followed by coma--a coma which
certainly cannot be distinguished from that produced by a narcotic
poison. Death in this stage may follow, and on examining the body no
lesion may be found.

§ 361. =Opium-eating.=--The consumption of opium is a very ancient
practice among Eastern nations, and the picture, drawn by novelist and
traveller, of poor, dried-up, yellow mortals addicted to this vice, with
their faculties torpid, their skin hanging in wrinkles on their wasted
bodies, the conjunctivæ tinged with bile, the bowels so inactive that
there is scarcely an excretion in the course of a week, the mental
faculties verging on idiocy and imbecility, is only true of a percentage
of those who are addicted to the habit. In the _British Medical Journal_
for 1894, Jan. 13 and 20, will be found a careful digest of the
evidence collated from 100 Indian medical officers, from which it
appears that opium is taken habitually by a very large number of the
population throughout India, those who are accustomed to the drug taking
it in quantities of from 10 to 20 grains in the twenty-four hours; so
long as this amount is not exceeded they do not appear to suffer
ill-health or any injurious effect. The native wrestlers even use it
whilst training. The habitual consumption of opium by individuals has a
direct medico-legal bearing. Thus in India, among the Rajpoots, from
time immemorial, infused opium has been the drink both of reconciliation
and of ordinary greeting, and it is no evidence of death by poison if
even a considerable quantity of opium be found in the stomach after
death, for this circumstance taken alone would, unless the history of
the case was further known, be considered insufficient proof. So, again,
in all climates, and among all races, it is entirely unknown what
quantity of an opiate should be considered a poisonous dose for an
opium-eater. Almost incredible quantities have, indeed, been consumed by
such persons, and the commonly-received explanation, that the drug, in
these cases, passes out unabsorbed, can scarcely be correct, for Hermann
mentions the case of a lady of Zurich who daily injected subcutaneously
1 to 2 grms. (15-31 grains) of a morphine salt. In a case of uterine
cancer, recorded by Dr. W. C. Cass,[395] 20 grains of morphine in the
twelve hours were frequently used subcutaneously; during thirteen months
the hypodermic syringe was used 1350 times, the dose each time being 5
grains. It is not credible that an alkaloid introduced into the body
hypodermically should not be absorbed.

[395] _Lancet_, March 25, 1882. See also Dr. Boulton’s case, _Lancet_,
March 18, 1882.

Opium-smoking is another form in which the drug is used, but it is an
open question as to what poisonous alkaloids are in opium smoke. It is
scarcely probable that morphine should be a constituent, for its
subliming point is high, and it will rather be deposited in the cooler
portion of the pipe. Opium, specially prepared for smoking, is called
“Chandoo”; it is dried at a temperature not exceeding 240°. H.
Moissan[396] has investigated the products of smoking chandoo, but only
found a small quantity of morphine. N. Gréhant and E. Martin[397] have
also experimented with opium smoke; they found it to have no appreciable
effect on a dog; one of the writers smoked twenty pipes in succession,
containing altogether 4 grms. of chandoo. After the fourth pipe there
was some headache, at the tenth pipe and onwards giddiness. Half an hour
after the last pipe the giddiness and headache rapidly went off. In any
case, opium-smoking seems to injure the health of Asiatics but little.
Mr. Vice-Consul King, of Kew-Kiang, in a tour through Upper Yangtse and
Stechnan, was thrown much into the company of junk sailors and others,
“almost every adult of whom smoked more or less.” He says:--“Their work
was of the hardest and rudest, rising at four and working with hardly
any intermission till dark, having constantly to strip and plunge into
the stream in all seasons, and this often in the most dangerous parts.
The quantity of food they eat was simply prodigious, and from this and
their work it seems fairly to be inferred that their constitution was
robust. The two most addicted to the habit were the pilot and the ship’s
cook. On the incessant watchfulness and steady nerve of the former the
safety of the junk and all on board depended, while the second worked so
hard from 3 A.M. to 10 P.M., and often longer, and seemed so independent
of sleep or rest, that to catch him seated or idle was sufficient cause
for good-humoured banter. This latter had a conserve of opium and sugar
which he chewed during the day, as he was only able to smoke at night.”

[396] _Compt. Rend._, cxv. 988-992.

[397] _Compt. Rend._, 1012-1014.

§ 362. =Treatment of Opium or Morphine Poisoning.=--The first thing to
be done is doubtless to empty the stomach by means of the flexible
stomach tube; the end of a sufficiently long piece of indiarubber tubing
is passed down into the pharynx and allowed to be carried into the
stomach by means of the natural involuntary movements of the muscles of
the pharynx and gullet; suction is then applied to the free end and the
contents syphoned out; the stomach is, by means of a funnel attached to
the tube, washed out with warm water, and then some coffee administered
in the same way.

Should morphine have been taken, and permanganate of potash be at hand,
it has been shown that under such circumstances potassic permanganate is
a perfect antidote, decomposing at once any morphine remaining in the
stomach, but it, of course, will have no effect upon any morphine which
has already been absorbed. In a case of opium poisoning, reported in the
_Lancet_ of June 2, 1894, by W. J. C. Merry, M.B., inhalations of
oxygen, preceded by emptying the stomach and other means, appeared to
save a man, who, three hours before the treatment, had drank 2 ozs. of
chlorodyne. It is also the received treatment to ward off the fatal
sleep by stimulation; the patient is walked about, flicked with a towel,
made to smell strong ammonia, and so forth. This stimulation must,
however, be an addition, but must never replace the measures first
detailed.

§ 363. =Post-mortem Appearances.=--There are no characteristic
appearances after death save hyperæmia of the brain and blood-vessels of
the membranes, with generally serous effusion into the ventricles. The
pupils are sometimes contracted, sometimes dilated, the dilatation
occurring, as before mentioned, in the act of dying. The external
surface of the body is either livid or pale. The lungs are commonly
hyperæmic, the bladder full of urine; still, in not a few cases, there
is nothing abnormal, and in no single case could a pathologist, from the
appearance of the organs only, declare the cause of death with
confidence.

§ 364. =Separation of Morphine from Animal Tissues and
Fluids.=--Formerly a large proportion of the opium and morphine cases
submitted to chemical experts led to no results; but owing to the
improved processes now adopted, failure, though still common, is less
frequent. The constituents of opium taken into the blood undergo partial
destruction in the animal body, but a portion may be found in the
secretions, more especially in the urine and fæces. First
Bouchardat[398] and then Lefort[399] ascertained the excretion of
morphine by the urine after medicinal doses; Dragendorff and Kauzmann
showed that the appearance of morphine in the urine was constant, and
that it could be easily ascertained and separated from the urine of men
and animals; and Levinstein[400] has also shown that the elimination
from a single dose may extend over five or six days. The method used by
Dragendorff to extract morphine from either urine or blood is to shake
the liquid (acidified with a mineral acid) several times with amyl
alcohol, which, on removal, separates urea and any bile acids. The
liquid thus purified is then alkalised, and shaken up with amyl alcohol,
and this amyl alcohol should contain any morphine that was present. On
evaporation it may be pure enough to admit of identification, but if
not, it may be redissolved and purified on the usual principles.
Considerable variety of results seems to be obtained by different
experimenters. Landsberg[401] injected hypodermically doses of ·2 to ·4
grm. of morphine hydrochlorate into dogs, making four experiments in
all, but failed to detect morphine in the urine. A large dose with 2·4
mgrms. of the salt gave the same result. On the other hand, ·8 grm. of
morphine hydrochlorate injected direct into the jugular vein, was partly
excreted by the kidneys, for 90 c.c. of the urine yielded a small
quantity of morphine. Voit, again, examined the urine and fæces of a man
who had taken morphine for years; he could detect none in the urine, but
separated morphine from the fæces.[402] Morphine may occasionally be
recognised in the blood. Dragendorff[403] found it in the blood of a cat
twenty-five minutes after a subcutaneous dose, and he also separated it
from the blood of a man who died of morphine poisoning in six hours.
Haidlen[404] recognised morphine in the blood of a suicide who had taken
opium extract.

[398] _Bull. Gén. de Thérap._, Dec. 1861.

[399] _Journ. de Chim._, xi. 93, 1861.

[400] _Berl. klin. Wochenschr._, 1876, 27.

[401] _Pflüger’s Archiv._, 23, 433, 413-433. _Chem. Soc. Journ._, May
1882, 543.

[402] _Arch. Pharm._, pp. [3], vii. pp. 23-26.

[403] Kauzmann, _Beiträge für den gerichtlich-chemischen Nachweis des
Morphia u. Narcotins_, Dissert., Dorpat, 1868. Dragendorff, _Pharm.
Zeitschr. f. Russland_, 1868, Hft. 4.

[404] _Würtbg. Correspondenzbl._, xxxiv. 16, 1863.

On the other hand, in a case recorded at p. 304, where a woman died in
six hours from a moderate dose, probably of laudanum, although the
quantity of blood operated upon was over a pound in weight, and every
care was taken, the results were entirely negative. In poisoning by
laudanum there may be some remaining in the stomach, and also if large
doses of morphine have been taken by the mouth; but when morphine has
been administered hypodermically, and in all cases in which several
hours have elapsed, one may almost say that the organ in which there is
the least probability of finding the poison is the stomach. It may, in
some cases, be necessary to operate on a very large scale;--to examine
the fæces, mince up the whole liver, the kidney, spleen, and lungs, and
treat them with acid alcohol. The urine will also have to be examined,
and as much blood as can be obtained. In cases where all the evidence
points to a minute quantity (under a grain) of morphine, it is decidedly
best to add these various extracts together, to distil off the alcohol
at a very gentle heat, to dry the residue in a vacuum, to dissolve again
in absolute alcohol, filter, evaporate again to dryness, dissolve in
water, and then use the following process:--

§ 365. =Extraction of Morphine.=--To specially search for morphine in
such a fluid as the urine, it is, according to the author’s experience,
best to proceed strictly as follows:--The urine is precipitated with
acetate of lead, the powdered lead salt being added to the warm urine
contained in a beaker on the water-bath, until a further addition no
longer produces a precipitate; the urine is then filtered, the lead
precipitate washed, and the excess of lead thrown down by SH₂; the lead
having been filtered off, and the precipitate washed, the urine is
concentrated down to a syrup in a vacuum. The syrup is now placed in a
separating tube (if not acid, it is acidified with hydrochloric acid),
and shaken up successively with petroleum ether, chloroform, ether, and,
lastly, with amylic alcohol (the latter should be warm); finally, the
small amount of amylic alcohol left dissolved in the liquid is got rid
of by shaking it up with petroleum ether. To get rid of the last traces
of petroleum ether, it may be necessary to turn the liquid into an
evaporating dish, and gently heat for a little time over the water-bath.
The acid liquid is now again transferred to the separating tube, and
shaken up with ether, after being made alkaline with ammonia; this will
remove nearly all alkaloids save morphine,--under the circumstances, a
very small quantity of morphine may indeed be taken up by the ether, but
not the main bulk. After separating the ether, the liquid is again made
slightly acid, so as to be able to precipitate morphine in the presence
of the solvent; the tube is warmed on the water-bath, at least its own
bulk of hot amylic alcohol added and the liquid made alkaline, and the
whole well shaken. The amylic alcohol is removed in the usual way, and
shaken with a small quantity of decinormal sulphuric acid; this washes
out the alkaloid from the amyl alcohol, and the same amyl alcohol can be
used again and again. It is best to extract the liquid for morphine at
least thrice, and to operate with both the solution and the amyl hot.
The decinormal acid liquid is made slightly alkaline with ammonia, and
allowed to stand for at least twelve hours; any precipitate is collected
and washed with ether, and then with water; the alkaline liquid from
which the morphine has been separated is concentrated to the bulk of 5
c.c. on the water bath, and again allowed to stand for twelve hours; a
little more morphine may often in this way be obtained.

The author in some test experiments, in which weighed small quantities
of morphine (60-80 mgrms.) were dissolved in a little decinormal
sulphuric acid, and added to large quantities of urine, found the
process given to yield from 80 to 85 per cent. of the alkaloid added,
and it was always recovered in fine crystals of a slight brown tint,
which responded well to tests.

Various other methods were tried, but the best was the one given; the
method not only separates the alkaloid with but little loss, but also in
a sufficiently pure state to admit of identification.

From the tissues the alkaloid may be dissolved out by the general method
given at p. 239, and the ultimate aqueous solution, reduced to a bulk of
not more than 25 c.c., treated by the ethereal solvents in the way just
described.

§ 366. =Narcotine= (C₂₂H₂₃NO₇) crystallises out of alcohol or ether in
colourless, transparent, glittering needles, or groups of needles,
belonging to the orthorhombic system.

It is only slightly soluble in boiling, and almost insoluble in cold
water. One part requires 100 parts of cold, and 20 of boiling 84 per
cent. alcohol; 126 parts of cold, 48 of boiling ether (specific gravity
0·735); 2·69 parts of chloroform; 400 of olive oil; 60 of acetic ether;
300 of amyl alcohol; and 22 parts of benzene, for solution. The neutral
solution of narcotine turns the plane of polarisation to the left [α]_r_
= 130·6; the acid solution to the right. Narcotine has no effect on red
litmus paper.

Narcotine gives no crystalline sublimate; its behaviour in the subliming
cell is described at p. 259. Its melting-point, taken in a tube, is
about 176°.

=Behaviour of Narcotine with Reagents.=--Narcotine, dissolved in dilute
hydrochloric acid, and then treated with a little bromine, gives a
yellow precipitate, which on boiling is dissolved; by gradually adding
solution of bromine and boiling, a fine rose colour is produced,
readily destroyed by excess of bromine. This is perhaps the best test
for the presence of narcotine. Concentrated sulphuric acid dissolves
narcotine; the solution in the cold is at first colourless, after a few
minutes yellow, and in the course of a day or longer the tints gradually
deepen. If the solution is warmed, it first becomes orange-red, then at
the margin violet-blue; and if heated until hydric sulphate begins to
volatilise, the colour is an intense red-violet. If the heating is not
carried so far, but the solution allowed to cool, a delicate cherry-red
hue slowly develops. If the sulphuric acid solution contains 1 : 2000 of
the alkaloid, this test is very evident; with 1 : 40,000, the colour is
only a faint carmine.--_A. Husemann._

A solution of narcotine in pure sulphuric acid, to which a drop of
nitric acid has been added, becomes of a red colour; if the solution is
warmed to 150°, hypochlorite of soda develops a carmine-red; and
chloride of iron, first a violet, then a cherry-red. The precipitants of
narcotine are--phosphomolybdic acid, picric acid, sulphocyanide of
potash, potassio cadmic iodide, mercuric chloride, platinic chloride,
auric chloride, and several other reagents.

From the brown mass left after heating narcotine above 200°,
hydrochloric acid extracts a small portion of a base but little studied.
The residue consists of humopic acid (C₄₀H₁₉O₁₄), which can be obtained
by dissolving in caustic potash, precipitating with HCl, dissolving the
precipitate in boiling alcohol, and finally throwing it down by water.

§ 367. =Effects.=--Narcotine in itself has toxic action only in rather
large doses; from 1 to 2 grms. have been given to man, and slight
hypnotic effects have followed. It is poisonous in very large doses; an
ordinary-sized cat is killed by 3 grms. The symptoms are mainly
convulsions.

§ 368. =Codeine= (=Codomethylene=), C₁₇H₁₇OCH₃(OH)NO + H₂O, is the
methyl of morphine; it is an alkaloid contained in opium in small
quantity only. Mulder, indeed, quotes ·66 to ·77 per cent. as present in
Smyrna opium, but Merck and Schindler give ·25 per cent. Schindler found
in Constantinople, ·5 per cent.; and Merck, in Bengal, ·5 per cent.
also.

Codeine crystallises out of dry ether in small, colourless, anhydrous,
crystals; but crystallised slowly from an aqueous solution, the crystals
are either in well-defined octahedra, or in prisms, containing one atom
of water, and melting in boiling-water to an oily fluid. The anhydrous
crystals have a melting-point of 150°, and solidify again on cooling.
Its watery solution is alkaline to litmus paper.

It requires 80 parts of cold, 17 of boiling water, 10 parts of benzole,
and 7 parts of amyl alcohol respectively, for solution. Alcohol,
benzene, ether, carbon disulphide, and chloroform freely dissolve it,
but in petroleum ether it is almost insoluble. Further, it is also
soluble in aqueous ammonia, and in dilute acids, but insoluble in
excess of caustic potash or soda, and may thus be thrown out of an
aqueous solution. A solution of codeine turns the plane of polarisation
to the left, [α]_r_ = 118·2°.

Concentrated sulphuric acid dissolves codeine without colour, but after
eight days the solution becomes blue; this reaction is quicker if the
acid contains a trace of nitric acid. If the sulphuric acid solution be
warmed to 150°, and a drop of nitric acid be added after cooling, a
blood-red colour is produced. Fröhde’s reagent produces a dirty green
colour, soon becoming Prussian blue, and terminating after twenty-four
hours in a pale yellow.

Cyanogen gas, led into an alcoholic solution of codeine, gives first a
yellow and then a brown colour; lastly, a crystalline precipitate falls.
On warming with a little sulphuric acid and ferric chloride, a blue
colour is produced. This blue colour is apparently common to all ethers
of the codeine class.

Of the group reagents, the following precipitate solutions of
codeine:--Mercuric potassium iodide, mercuric chloride, mercuric
bromide, picric acid, and tannin solutions. The following do not
precipitate:--Mercuric cyanide and potassium ferrocyanide solutions.
Potassium dichromate gives no immediate precipitate, but crystals form
on long standing. It does not give the reaction with iodic acid like
morphine; it is distinguished from narceine by dropping a small particle
of iodine into the aqueous solution, the iodine particle does not become
surrounded with fine crystals.

§ 369. =Effects.=--The physiological action of codeine on animals has
been investigated by Claude Bernard, Magendie, Crum Brown and Fraser,
Falck, and a large number of others.[405] It has also been administered
to man, and has taken in some degree the place of morphine. Claude
Bernard showed that, when given to dogs in sufficient quantity to
produce sleep, the sleep was different in some respects to that of
morphine sleep, especially in its after-effects. Thus, in his usual
graphic way, he describes the following experiment:--“Two young dogs,
accustomed to play together, and both a little beyond the average size,
received in the cellular tissue of the axillæ, by the aid of a
subcutaneous syringe, the one 5 centigrammes of morphine hydrochloride,
the other 5 centigrammes of codeine hydrochloride. At the end of a
quarter of an hour both dogs showed signs of narcosis. They were placed
on their backs in the experimental trough, and slept tranquilly for
three or four hours. When the animals woke, they presented the most
striking contrast. The morphine dog ran with a hyena-like gait
(_démarche hyénoid_), the eye wild, recognising no one, not even his
codeine comrade, who vainly bit him playfully, and jumped sportively on
his back. It was not until the next day that the morphine dog regained
his spirits and usual humour. A couple of days after, the two dogs being
in good health, I repeated the same experiment, but in an inverse
order--that is to say, I gave the codeine to that which previously had
the morphine, and _vice versâ_. Both dogs slept about as long as the
first time; but on waking the attitudes were completely reversed, just
as the administration of the two substances had been. The dog which, two
days before, after having been codeinised, woke lively and gay, was now
bewildered and half paralysed at the end of his morphine sleep; whilst
the other was wide awake and in the best spirits.”

[405] _Ann. Chem. Phys._ [5], 27, pp. 273-288; also, _Journ. Chem.
Soc._, No. ccxliv., 1883, p. 358.

Subsequent experimenters found what Bernard does not mention--viz., that
codeine produced epileptiform convulsions. Falck made some very careful
experiments on pigeons, frogs, and rabbits. To all these in high enough
doses it was fatal. Falk puts the minimum lethal dose for a rabbit at
51·2 mgrms. per kilo. Given to man, it produces a sleep very similar to
that described by Claude Bernard--that is, a sleep which is very
natural, and does not leave any after-effect. Therefore it is declared
to be the best alkaloid of a narcotic nature to give when lengthened
slumber is desired, more especially since it does not confine the
bowels, nor has it been found to produce any eruption on the skin.
Before it has a full narcotic effect, vomiting has often been excited,
and in a few cases purging. The maximum dose for an adult is about ·1
grm. (1·5 grain); three times this quantity, ·3 grms. (4-5 grains),
would probably produce unpleasant, if not dangerous, symptoms.[406]

[406] For further details as to the action of codeine, the reader is
referred to L. O. Wach’s monograph, _Das Codein_ (1868), which contains
reference to the earlier literature. See also Harley, _The Old Vegetable
Neurotics_, London.

    § 370. =Narceine=, C₂₃H₂₇NO₈ + 3H₂O.--Two of the three molecules of
    water are expelled at 100°, the other molecule requires a higher
    temperature; anhydrous narceine is hygroscopic, and melts in a tube
    at about 140°; when exposed to air it unites with one molecule of
    water, and then melts at about 160°.

    The constitution of narceine is probably that of a substituted
    phenylbenzylketone, and the following structural formula has been
    attributed to it:[407]--

[407] M. Freund and G. B. Frankforter, _Annalen_, 277, pp. 20-58.

      3       I:2   4  1’         2’
    COOH,C₆H₂-(OMe)₂CO-CH₂-C₆H(CH₂-CH₂NMe₂)
         O
  3 or 6/ \
     OMe   CH₂
        \ /
         O

    It therefore contains three methoxyl groups.

    Narceine forms good crystals, the form being that of long,
    four-sided rhombic prisms or fine bushy united needles.

    Narceine hydrochloride crystallises with 5½H₂O and with 3H₂O; the
    anhydrous salt melts at 190°-192°. The platinochloride is a definite
    salt, m.p. 190°-191°; it decomposes at 195°-196°. The nitrate forms
    good crystals, which decompose at 97°. Narceine also forms
    crystalline salts with potassium and sodium; these may be obtained
    by heating the base at 60°-70° with a 33 per cent. of NaHO or KHO.

    The potassium compound melts at 90°, the sodium at 159°-160°. The
    alkaloid is regenerated when the alkali salts are treated with acids
    or with CO₂. Crude narceine may be purified by means of the sodium
    salt; the latter is dissolved in alcohol and precipitated with
    ether.

    It is soluble in alcohol, but almost insoluble in alcohol and ether,
    or benzene and ether; it is slightly soluble in ether, carbon
    disulphide, and chloroform. It has no reaction on moist litmus
    paper.

    Benzole and petroleum ether extract narceine neither from acid nor
    alkaline solutions; chloroform extracts narceine both from acid and
    from alkaline solutions, the latter in small proportion only.
    Narceine turns the plane of polarisation to the left, [α]_r_ =
    66·7°. Narceine may be separated from narcotine by the addition of
    ammonia to the acid aqueous solution; narcotine is fully
    precipitated by ammonia, but narceine is left in solution.

    In the subliming cell it melts at 134°, but gives no crystalline
    sublimate. The tube melting-point of the trihydrate is 170°. The
    melted substance is at first colourless; but on raising the
    temperature, the usual transitions of colour through different
    shades of brown to black are observed. If melted, and kept a few
    degrees above its melting-point, and then cooled slowly, the residue
    is straw-coloured, divided into lobes, most of which contain
    feathery crystals.

    At high temperatures narceine develops a herring-like odour; the
    residue becomes darkish blue with iron chloride. Concentrated nitric
    acid dissolves it with a yellow colour; on heating, red vapours are
    produced; the fluid contains crystals of oxalic acid, and develops
    with potash a volatile base. Concentrated sulphuric acid colours
    pure narceine brown; but if impure, a blood-red or blue colour may
    be produced. It does not reduce iron salts.

    Fröhde’s reagent colours it first brown-green, then red, passing
    into blue. Narceine forms precipitates with bichromate of potash,
    chloride of gold, bichloride of platinum, and several other
    reagents. The one formed by the addition of potassio zinc iodide is
    in hair-like crystals, which after twenty-four hours become blue.

    Weak iodine solution colours narceine crystals a black-blue; they
    dissolve in water at 100° without colour, but on cooling again
    separate with a violet or blue colour. If on a saturated solution of
    narceine a particle of iodine is strewn, fine needle-like grey
    crystals form around the iodine. A drop of “Nessler” solution, added
    to solid narceine, at once strikes a brown colour; on diluting the
    drop with a little water, beautiful little bundles of crystals
    appear.--_Flückiger._

    The following group reagents precipitate narceine:--picric acid,
    tannin solution, and potassium dichromate on long standing. The
    following give no precipitate:--mercuric cyanide, mercuric potas.
    iodide, mercuric chloride, mercuric bromide, and potas. ferrocyanide
    solutions.

    § 371. =Effects.=--The physiological action of narceine has been
    variously interpreted by different observers. Claude Bernard[408]
    thought it the most somniferous of the opium alkaloids. He said that
    “the narceinic sleep was characterised by a profound calm and
    absence of the excitability of morphine, the animals narcotised by
    narceine on awaking returning to their natural state without
    enfeeblement of the hind limbs or other sequelæ.” It has been amply
    confirmed that narceine possesses somniferous properties, but
    certainly not to the extent that Bernard’s observations led
    physiologists to expect. In large doses there is some irritation of
    the stomach and intestines, and vomiting occurs, and even diarrhœa;
    moderate doses induce constipation. The maximum medicinal dose may
    be put at ·14 grm. (or 2·26 grains), and a probably dangerous dose
    would be three times that quantity.[409]

[408] _Compt. Rend._, lix. p. 406, 1864.

[409] See J. Bouchardat, _La Narcéine_, Thèse, Paris, 1865; Harley, _The
Old Vegetable Neurotics_, Lond.; Ch. Liné, _Études sur la Narcéine et
son Emploi Thérapeutique_, Thèse, Paris, 1865; also, Husemann’s
_Planzenstoffe_, in which these and other researches are summarised.

    § 372. =Papaverine= (C₂₁H₂₁NO₄) crystallises from alcohol in white
    needles or scales. It possesses scarcely any alkaline reaction, but
    its salts have an acid reaction; it has but little effect on a ray
    of polarised light. It is almost insoluble in water; it is easily
    soluble in acetone, amyl alcohol, alcohol, and chloroform. One part
    of the alkaloid is dissolved in 36·6 of benzene, and in 76 parts of
    amyl alcohol. Petroleum ether dissolves it by the aid of heat, but
    the alkaloid separates in crystals on cooling. Chloroform extracts
    it from either acid or alkaline solutions. Papaverine gives no
    crystalline sublimate. The melting-point of pure samples in a tube
    is 147°, with scarcely any colour; it solidifies again to crystals
    on cooling; in the subliming cell it melts at 130°, and decomposes
    about 149°; the vapours are alkaline; the residue is amorphous,
    light brown, and is not characteristic. Concentrated sulphuric acid
    colours it a deep violet-blue, and dissolves it to a violet, slowly
    fading. This solution, by permanganate of potash, is first green and
    then grey. Fröhde’s reagent gives a beautiful violet colour, which
    becomes blue, and vanishes after twenty-four hours. Diluted
    solutions of salts of papaverine are not precipitated by
    phosphomolybdic acid. It is precipitated by ammonia, by the caustic
    and carbonated alkalies, by potassic-cadmic iodide, iodine in
    hydriodic acid, and by alkaloidal reagents generally--save by the
    important exception mentioned above. A solution in amyl alcohol is
    also precipitated by bromine; the precipitate is crystalline. An
    alcoholic solution of platinic chloride also separates papaverine
    platin chloride in crystals. An alcoholic solution of iodine, added
    to an alcoholic solution of papaverine, separates in a little time
    crystals of the composition C₂₁H₂₁NO₄I₃. From the mother-liquor, by
    concentration, can be obtained needles of another iodine
    combination, C₂₁H₂₁NO₄I₅; the latter heated above 100° parts with
    free iodine. These compounds with iodine are decomposed by ammonia
    and potash, papaverine separating. The decomposition may be watched
    under the microscope. Nitric acid precipitates from a solution of
    the sulphate a white nitrate soluble in excess; the precipitate does
    not appear at once, but forms in the course of an hour; it is at
    first amorphous, but subsequently crystalline; this, with its
    physical properties, is a great assistance to identification.

    § 373. =Effects.=--Claude Bernard ranked papaverine with the
    convulsants; probably the papaverine he had was impure. In any case,
    subsequent observations have shown that it is to be classed rather
    with the hypnotic principles of opium. Leidesdorf[410] administered
    it to the insane, and noted slowness of the pulse, muscular
    weakness, and drowsiness to follow. The doses were given
    subcutaneously (·42 grm. of the hydrochloride). Baxt,[411]
    experimenting with the frog, found that a milligramme caused deep
    sleep and slowing of the heart’s action. This action on the heart is
    witnessed also on the recently-removed frog’s heart. Guinea-pigs,
    and other small animals poisoned by strychnine or thebaine, and then
    given papaverine, did not seem to be so soon affected with tetanus
    as when no such remedy was administered. The fatal dose of
    papaverine for a man is unknown. I should conjecture that the least
    quantity that would cause dangerous symptoms would be 1 grm. (15·4
    grains).

[410] _Ztschr. d. Wien. Aerzte_, pp. 13, 115, 1868.

[411] _Arch. Anat. Phys._, p. 70, 1869.

    § 374. =Thebaine=, C₁₇H₁₅NO(OCH₃)₂.--Opium seldom contains much more
    than 1 per cent. of this alkaloid. It usually forms needles or short
    crystals. It is alkaline, and by rubbing becomes negatively
    electric. It is almost insoluble in water, aqueous ammonia, and
    solutions of the alkalies. It requires 10 parts of cold alcohol for
    solution, and dissolves readily in hot. Ether, hot or cold, is also
    a good solvent. 100 parts of benzene are required for 5·27 parts of
    thebaine, and 100 of amyl alcohol for 1·67 parts. Chloroform
    dissolves thebaine with difficulty out of both acid and alkaline
    solutions; petroleum ether extracts it from neither. Thebaine melts
    in a tube at 193°, sublimes at 135°. The sublimate is in minute
    crystals, similar to theine; at higher temperatures (160° to 200°)
    needles, cubes, and prisms are obtained. The residue is fawn
    coloured. Fröhde’s reagent (as well as concentrated sulphuric acid)
    dissolves it, with the production of a blood-red colour, passing
    gradually into yellow. The precipitate with picric acid is yellow
    and amorphous; with tannic acid yellow; with gold chloride,
    red-yellow; and with platinic chloride, citron-yellow, gradually
    becoming crystalline. A concentrated alcoholic solution of thebaine,
    just neutralised with HCl, deposits well-formed rhombic crystals of
    the composition C₁₉H₂₁NO₃HCl + H₂O.

    If 200 mgrms. of thebaine are heated to boiling with 1·4 c.c. of HCl
    and 2·8 c.c. of water, and the solution diluted, after boiling, with
    4 c.c. of water, crystals of thebaine hydrochloride form in the
    yellow fluid in the course of a few hours.--_Flückiger._

    § 375. =Effects.=--There is no disagreement of opinion as to the
    action of thebaine. By the united testimony of all who have
    experimented with it, the alkaloid belongs to those poisons which
    produce tetanus, and the symptoms can scarcely be differentiated
    from strychnia. In Baxt’s experiments on frogs he showed that there
    was some considerable difference in details in the general course of
    the symptoms, according to the dose of the poison. A small dose
    (such, for example, as ·75 mgrm.) injected into a frog
    subcutaneously produces immediate excitement, the animal jumping
    about, and this stage lasting for about a minute; it then becomes
    quieter, and has from three to six minutes’ sleep; in a little time
    this comatose state is followed by reflex tetanic spasms and then
    spontaneous tetanic spasms. With three times the dose, the tetanic
    convulsions commence early, and death takes place in from two to six
    hours. Baxt[412] found 6 to 7 mgrms. kill rabbits with tetanic
    convulsions in from fifteen to twenty-five minutes. Crum Brown and
    Fraser also found that 12 mgrms. injected into rabbits were fatal;
    it may then be presumed that the lethal dose for a rabbit is about 5
    mgrms. per kilo. A frog’s heart under the action of thebaine, and
    removed from the body, beats quicker and ceases earlier than one in
    distilled water. Thebaine has been administered to the insane
    subcutaneously in doses of from 12 to 40 mgrms., when a rise of
    temperature and an increase in the respiratory movements and in the
    circulation were noticed.[413]

[412] _Sitzungsber. d. Wien. Akadem._, lvi. pp. 2, 89, 1867; _Arch. f.
Anat. u. Physiol._, Hft. 1, p. 112, 1869.

[413] F. W. Müller, _Das Thebaine, eine Monographie_, Diss., Marburg
1868.

    The fatal dose for a man is not known; ·5 grm., or about 8 grains,
    would probably be a poisonous quantity.

    § 376. =Cryptopine= (C₂₁H₂₃NO₅) was discovered by T. & H. Smith in
    1867.[414] It is only contained in very minute traces in
    opium--something like ·003 per cent. It is a crystalline substance,
    the crystals being colourless, six-sided prisms, without odour, but
    with a bitter taste, causing an after-sensation like peppermint. The
    crystals melt at 217°, and congeal in a crystalline form again at
    171°; at high temperatures they are decomposed with evolution of
    ammoniacal vapour. Cryptopine is insoluble, or almost so, in ether,
    water, and oil of turpentine; it is soluble in acetone, benzene, and
    chloroform; the latter is the best solvent, or hot alcohol; it is
    insoluble in aqueous ammonia and in solutions of the caustic
    alkaloids. Cryptopine is strongly basic, neutralising fully mineral
    acids. Concentrated sulphuric acid colours cryptopine pure blue, the
    tint gradually fading from absorption of water from the atmosphere.
    On a crystal of potassic nitrate being added, the colour changes
    into a permanent green. With ferric chloride cryptopine gives no
    colour--thus distinguishing it from morphine. The physiological
    properties of cryptopine have been investigated by Dr. Harley;[415]
    it has a narcotic action, about double as strong as narceine, and
    four times weaker than morphine. Munk and Sippell[416] found that it
    gave rise in animals to paralysis of the limbs, and occasionally
    asphyxic convulsions before death.

[414] _Pharm. Journ. Trans._ [2], viii. pp. 495 and 716.

[415] _The Old Vegetable Neurotics._

[416] Munk, _Versuche über die Wirkung des Cryptopins_, Berlin, 1873.
Sippell, _Beiträge zur Kentniss des Cryptopins_, Marburg, 1874.

    § 377. =Rhœadine= (C₂₁H₂₁NO₆).--Rhœadine was separated from _Papaver
    rhœas_ by Hesse, and has also been found in _Papaver somniferum_ and
    in opium. Rhœadine is in the form of small anhydrous tasteless
    prisms, melting at 230° and partly subliming. In a vacuum
    sublimation is almost complete, and at a much lower temperature. It
    is a very insoluble substance, and is scarcely dissolved, when
    crystalline, by water, alcohol, ether, chloroform, benzene, and
    solutions of the fixed or volatile alkalies. When in an amorphous
    state it is rather soluble in ether, and may be dissolved out of any
    substance by treating with dilute acetic acid, and neutralising by
    ammonia, and shaking up with ether before the precipitate becomes
    crystalline. Rhœadine is easily recognised by its striking a red
    colour with hydrochloric acid. Either spontaneously or on gentle
    warming, the colour is produced--one part of rhœadine will colour in
    this way 10,000 parts of acid water blue or purple-red, 200,000
    rose-red, and 800,000 pale red. The reaction depends on a splitting
    up of the rhœadine into a colourless substance, _rhœadin_, and a red
    colouring-matter. Rhœadine is not poisonous.

    § 378. =Pseudomorphine= (C₁₇H₁₉NO₄).--Pseudomorphine was discovered
    by Pelletier and Thiboumery in 1835. As precipitated by ammonia out
    of the hot solution, pseudomorphine falls as a white crystalline
    precipitate; but if the solution is cold, the precipitate is
    gelatinous. It possesses no taste, and has no action on vegetable
    colours. On heating, it decomposes and then melts. It dissolves
    easily in caustic alkalies and in milk of lime, but is insoluble in
    all the ordinary alcoholic and ethereal solvents, as well as in
    diluted sulphuric acid. The most soluble salt is the hydrochlorate
    (C₁₇H₁₉NO₄HCl + H₂O), and that requires 70 parts of water at 20° for
    solution. Various salts, such as the sulphate, oxalate, &c., may be
    prepared from the hydrochlorate by double decomposition.
    Concentrated sulphuric acid dissolves pseudomorphine gradually, with
    the production of an olive-green colour.

    § 379. =Opianine= (C₆₆H₇₂N₄O₂₁).--Opianine crystallises in
    colourless, glittering ortho-rhombic needles. Ammonia precipitates
    it from its solution in hydrochloric acid as a fine white powder. It
    is without odour, and has a bitter taste. It is a strong base, and
    is soluble in cold, but slightly soluble in boiling water. It is
    also but little soluble in boiling alcohol.

    An alcoholic solution of the alkaloid gives a voluminous precipitate
    with mercuric chloride; after standing a little time, the
    precipitate becomes crystalline, the crystals being in the shape of
    fine needles. They have the following composition--C₆₆H₇₂N₄O₂₁,
    2HCl, 2HgCl--and are with difficulty soluble in water or alcohol.

    Opianine, administered to cats in doses of ·145 grm., produces
    complex symptoms--_e.g._, dilated pupils, foaming at the mouth,
    uncertain gait, paralysis of the hinder extremities, and stupor--but
    the alkaloid is rare, and few experiments have been made with it.

    § 380. =Apomorphine= (C₁₇H₁₉NO₃).--Apomorphine is a derivative of
    morphine, and is readily prepared by saponifying morphine by heating
    it with dilute hydrochloric acid in sealed tubes. The result is
    apomorphine hydrochloride, the morphine losing one molecule of
    water, according to the equation C₁₇H₁₉NO₃ = C₁₇H₁₇NO₂ + H₂O.

    To extract apomorphine, the bases are precipitated by sodic
    bicarbonate, and the precipitate extracted by ether or chloroform,
    either of which solvents leaves morphine undissolved. The
    apomorphine is again converted into hydrochloride, and once more
    precipitated by sodic bicarbonate, and is lastly obtained as a
    snow-white substance, rapidly becoming green on exposure to the air.
    The mass dissolves with a beautiful green colour in water, and also
    in alcohol, whilst it colours ether purple-red, and chloroform
    violet.

    A test for apomorphine is the following:--The chloride is dissolved
    in a little acetic acid and shaken with a crystal of potassic iodate
    (KIO₃); this immediately turns red from liberated iodine on shaking
    it up with a little chloroform; on standing, the chloroform sinks to
    the bottom, and is coloured by the alkaloid a beautiful blue colour;
    on now carefully pouring a little CS₂ on the surface of the liquid
    at the point of junction it is coloured amethyst owing to dissolved
    iodine, and apocodeine gives a similar reaction.

    Apomorphine is the purest and most active emetic known: whether
    injected beneath the skin or taken by the mouth, the effect is the
    same--there is considerable depression, faintness, and then
    vomiting. The dose for an adult is about 6 mgrms. (·092 grain)
    subcutaneously administered.

    § 381. The reactions of some of the rarer alkaloids of opium with
    sulphuric acid and ferric chloride are as follows: none of them have
    at present any toxicological importance:--

TABLE SHOWING SOME OF THE REACTIONS OF THE RARER ALKALOIDS OF OPIUM.

  +---------------+---------+----------------------+----------------+
  |   Alkaloid.   |Formula. |  Reaction with Warm  | Reaction with  |
  |               |         |   Sulphuric Acid.    |Ferric Chloride.|
  +---------------+---------+----------------------+----------------+
  |Codamine,      |C₂₀H₂₅NO₄ {|Dirty red-violet      |}               |
  |               |        {|colour, turning dark  |} Dark green.   |
  |Landamine,     |C₂₀H₂₅NO₄ {|violet on the         |}               |
  |               |        {|addition of HNO₃.     |}               |
  |               |         |                      |                |
  |Landanosine,   |C₂₀H₂₇NO₄ }|Dirty green to        |}               |
  |               |        }|brownish-green.       |} No colour.    |
  |Protapine,     |C₂₀H₁₉NO₅ }|                      |}               |
  |               |         |                      |                |
  |Lanthopine,    |C₂₃H₂₅NO₄  |Dark brown or black.  |  No colour.    |
  |               |         |                      |                |
  |Hydrocotarnine,|C₁₂H₁₅NO₃ {|Dirty red-violet;     |}               |
  |               |        {|not changed by        |} No colour.    |
  |               |        {|trace of HNO₃.        |}               |
  +---------------+---------+----------------------+----------------+

    § 382. =Tritopine= (C₄₂H₅₄N₂O₇).--This is a rare alkaloid that has
    been found in small quantities in opium. It is crystalline,
    separating in transparent prisms. Melting-point 182°. It is soluble
    in alcohol and chloroform, and slightly soluble in ether.[417]

[417] E. Kander, _Arch. Pharm._, 228, pp. 419-431.

    § 383. =Meconin (Opianyl)= (C₁₀H₁₀O₄) is in the form of white
    glittering needles, which melt under water at 77° and in air at 90°,
    again coagulating at 75°. It may be sublimed in beautiful crystals.
    It is soluble in 22 parts of boiling, and 700 of cold water;
    dissolves easily in alcohol, ether, acetic acid, and ethereal oil,
    and is not precipitated by acetate of lead. Its solution in
    concentrated sulphuric acid becomes, on warming, purple, and gives,
    on the addition of water, a brown precipitate. Meconin may be
    prepared by treating narcotine with nitric acid. Meconin, in large
    doses, is a feeble narcotic; 1·25 grm. (20 grains) has been given to
    man without result.

    § 384. =Meconic Acid= (C₇H₄O₇) crystallises in white shining scales
    or small rhombic prisms, with three atoms of water (C₇H₄O₇ + 3H₂O),
    but at 100° this is lost, and it becomes an opaque white mass. It
    reddens litmus, and has a sourish taste. It is soluble in 115 parts
    of cold, but dissolves in 4 parts of boiling water; it dissolves
    easily in alcohol, less so in ether. It forms well-marked salts; the
    barium and calcium salt crystallise with one atom of water, the
    former having the composition BaH₄(C₇HO₇)₂; the latter, if ammonium
    meconate is precipitated by calcium chloride, CaH₄(C₇HO₇)₂; but if
    calcium chloride is added to the acid itself, the salt has the
    composition C₇H₂CaO₇ + H₂O. If meconic acid is gently heated, it
    decomposes into carbon dioxide and comenic acid (C₆H₄O₅). If the
    heat is stronger, pyromeconic acid (C₅H₄O₃)--carbon dioxide, water,
    acetic acid, and benzole are formed. Pyromeconic acid is readily
    sublimed in large transparent tables. Chloride of iron, and soluble
    iron salts generally, give with meconic acid (even in great
    dilution) a lively red colour, which is not altered by heat, nor by
    the addition of HCl nor by that of gold chloride. Sugar of lead and
    nitrate of silver each give a white precipitate; and mercurous and
    mercuric nitrates white and yellow precipitates. In any case where
    the analyst has found only meconic acid, the question may be raised
    in court as to whether it is a poison or not. The early experiments
    of Sertürner,[418] Langer, Vogel, Sömmering, and Grape[419] showed
    that, in comparatively speaking large doses, it had but little, if
    any, action on dogs or men. Albers[420] has, however, experimented
    on frogs, and found that in doses of ·1 to ·2 grm. there is, first,
    a narcotic action, and later, convulsions and death. According to
    Schroff,[421] there is a slight narcotic action on man.

[418] _Ann. Phys._, xxv. 56; xxvii. 183.

[419] _De opio et de illis quibus constat partibus_, Berol., 1822.

[420] _Arch. Path. Anat._, xxvi. 248.

[421] _Med. Jahresb._, 1869.

The most generally accepted view at the present time is that the
physiological action of meconic acid is similar to that of lactic
acid--viz., large doses cause some depression and feeble narcosis.

In a special research amongst organic fluids for meconic acid, the
substances are extracted by alcohol _feebly_ acidulated with nitric
acid; on filtration the alcohol, after the addition of a little water,
is distilled off, and to the remaining fluid a solution of acetate of
lead is added, and the whole filtered. The filtrate will contain any
alkaloids, whilst meconic acid, if present, is bound up with the lead on
the filter. The meconate of lead may be either washed or digested in
strong acetic acid to purify it, suspended in water, and freed from lead
by SH₂; the filtrate from the lead sulphide may be tested by ferric
chloride, or preferably, at once evaporated to dryness, and weighed.
After this operation it is identified. If the quantity is so small that
it cannot be conveniently weighed, it may be estimated colorimetrically,
by having a standard solution of meconic acid, containing 1 mgrm. in
every c.c. A few drops of neutral ferric chloride are added in a Nessler
cylinder to the liquid under examination; and the tint thus obtained is
imitated in the usual way, in another cylinder, by means of ferric
chloride, the standard solution, and water. It is also obvious that the
weight of the meconic acid may be increased by converting it into the
barium salt--100 parts of anhydrous baric meconate, (Ba₂C₇H₂O₇), being
equivalent to 42·3 of meconic acid (C₇H₄O₇).


IV.--The Strychnine or Tetanus-Producing[422] Group of Alkaloids.

[422] To this group also belong some of the opium alkaloids. See
“Thebaine,” “Landamine,” “Codeine,” “Hydrocotarnine.”


1. NUX VOMICA GROUP--STRYCHNINE--BRUCINE--IGASURINE.

§ 385. Nux vomica is found in commerce both in the entire state and as a
powder. It is the seed of the _Strychnos nux vomica_, or Koochla tree.
The seed is about the size of a shilling, round, flattened,
concavo-convex, of a yellowish-grey or light-brown colour, covered with
a velvety down of fine, radiating, silky hairs, which are coloured by a
solution of iodine beautiful gold-yellow; the texture is tough,
leathery, and not easily pulverised; the taste is intensely bitter. The
powder is not unlike that of liquorice, and, if met with in the pure
state, gives a dark orange-red colour with nitric acid, which is
destroyed by chloride of tin; the aqueous infusion gives a precipitate
with tincture of galls, is reddened by nitric acid, and gives an
olive-green tint with persulphate of iron. The best method, however, of
recognising quickly and with certainty that the substance under
examination is nux vomica powder, is to extract strychnine from it by
the following simple process:--The powder is completely exhausted by
boiling alcohol (90 per cent.), the alcoholic extract evaporated to
dryness, and then treated with water; the aqueous solution is passed
through a wet filter, and concentrated by evaporation to a small bulk.
To this liquid a drop or so of a concentrated solution of picric acid is
added, and the yellow precipitate of picrates thus obtained is
separated, treated with nitric acid, the picric acid removed by ether,
and the pure alkaloid precipitated by soda, and shaken out by
chloroform.

§ 386. =Chemical Composition.=--Nux vomica contains at least four
distinct principles:--

  (1.) Strychnine.
  (2.) Brucine.
  (3.) Igasurine.
  (4.) Strychnic or igasuric acid.

§ 387. =Strychnine= (C₂₁H₂₂N₂O₂) is contained in the bean of S.
_ignatius_, in the bark (_false angustura bark_) and seeds of the
_Strychnos nux vomica_, in the _Strychnos colubrina_, L., in the
_Strychnos tieuté_, Lesch, and probably in various other plants of the
same genus.

Commercial strychnine is met with either in colourless crystals or as a
white powder, the most usual form being that of the alkaloid itself; but
the nitrate, sulphate, and acetate are also sold to a small extent.

The _microscopical appearance_ of strychnine, as thrown down by the
solution of vapour of ammonia, may be referred to three leading
forms--the long rectangular prism, the short hexagonal prism, or the
regular octahedron. If obtained from the slow evaporation of an
alcoholic solution, it is usually in the form of four-sided pyramids or
long prisms; but if obtained by speedy evaporation or rapid cooling, it
appears as a white granular powder. If obtained from a benzene solution,
the deposit is usually crystalline, but without a constant form, though
at times the crystals are extremely distinct, the short six-sided prism
prevailing; but triangular plates, dodecahedral, rhomboidal, and
pentagonal, may also be met with. An ethereal solution on evaporation
assumes dendritic forms, but may contain octahedra and four-sided
prisms. A chloroform solution deposits rosettes, veined leaves, stellate
dotted needles, circles with broken radii, and branched and reticulated
forms of great delicacy and beauty.--_Guy._

Strychnine is very insoluble in water, although readily dissolved by
acidulated water. According to Wormley’s repeated experiments, one part
of strychnine dissolves in 8333 parts of cold water; and, according to
Pelletier and Cahours, it dissolves in 6667 parts of cold, and 2500
parts of boiling water. It may be convenient, then, to remember that a
gallon of cold water would hardly dissolve more than 10 grains (·142
grm. per litre); the same amount, if boiling, about 30 grains (·426 grm.
per litre) of strychnine. The solubility of one part of strychnine in
other menstrua is as follows:--Cold alcohol, 0·833 specific gravity,
120, boiling, 10 parts (_Wittstein_); cold alcohol, 0·936 specific
gravity, 240 parts (_Merck_); cold alcohol, 0·815 specific gravity, 107
parts (_Dragendorff_); amyl alcohol, 181 parts; benzene, 164;
chloroform, 6·9 (_Schlimpert_), 5 (_Pettenkofer_); ether, 1250 parts;
carbon disulphide, 485 parts; glycerin, 300 parts. Creosote and
essential and fixed oils also dissolve strychnine.

Of all the above solvents, it is evident that chloroform is the best for
purposes of separation, and next to chloroform, benzene.

If a speck of strychnine be placed in the subliming cell, it will be
found to sublime usually in a crystalline form at 169°. A common form at
this temperature, according to the writer’s own observations, is minute
needles, disposed in lines; but, as Dr. Guy has remarked, the sublimate
may consist of drops, of waving patterns, and various other forms; and,
further, while the sublimates of morphia are made up of curved lines,
those of strychnine consist of lines either straight or slightly
curved, with parallel feathery lines at right angles. On continuing the
heat, strychnine melts at about 221°, and the lower disc, if removed and
examined, is found to have a resinous residue; but it still continues to
yield sublimates until reduced to a spot of carbon. The melting-point
taken in a tube is 268°.

Strychnine is so powerfully bitter, that one part dissolved in 70,000 of
water is distinctly perceptible; it is a strong base, with a marked
alkaline reaction, neutralising the strongest acids fully, and
precipitating many metallic oxides from their combinations, often with
the formation of double salts. Most of the salts of strychnine are
crystalline, and all extremely bitter. Strychnine, in the presence of
oxygen, combines with SH₂ to form a beautiful crystalline compound:--

  2C₂₁H₂₂N₂O₂ + 6H₂S + O₃ = 2C₂₁H₂₂N₂O₂3H₂S₂ + 3H₂O.

On treatment with an acid this compound yields H₂S₂.--Schmidt, _Ber.
Deutsch. Chem. Ges._, 8, 1267.

An alcoholic solution of strychnine turns the plane of polarisation to
the left, [α]_r_ = -132·08° to 136·78° (_Bouchardat_); but acid
solutions show a much smaller rotatory power.

The salts used in medicine are--the _sulphate_, officinal only in the
French pharmacopœia; the _nitrate_, officinal in the German, Austrian,
Swiss, Norse, and Dutch pharmacopœias; and the _acetate_, well known in
commerce, but not officinal.

The commercial =Sulphate= (C₂₁H₂₂N₂O₂H₂SO₄ + 2H₂O) is an acid salt
crystallising in needles which lose water at 150°, the neutral sulphate
(2C₂₁H₂₂N₂O₂,H₂SO₄ + 7H₂O) crystallises in four-sided, orthorhombic
prisms, and is soluble in about 50 parts of cold water.

The =Nitrate= (C₂₁H₂₂N₂O₂,HNO₃) crystallises on evaporation from a warm
solution of the alkaloid in dilute nitric acid, in silky needles, mostly
collected in groups. The solubility of this salt is considerable, one
part dissolving in 50 of cold, in 2 of boiling water; its solubility in
boiling and cold alcohol is almost the same, taking 60 of the former and
2 of the latter.

The =Acetate= crystallises in tufts of needles; as stated, it is not
officinal in any of the European pharmacopœias.

The chief precipitates or sparingly soluble crystalline compounds of
strychnine are--

(1.) =The Chromate of Strychnine= (C₂₁H₂₂N₂O₂CrHO₂), formed by adding a
neutral solution of chromate of potash to a solution of a strychnine
salt, crystallises out of hot water in beautiful, very insoluble,
orange-yellow needles, mixed with plates of various size and thickness.
The salt is of great practical use to the analyst; for by its aid
strychnine may be separated from a variety of substances, and in part
from brucine--the colour tests being either applied direct to the
strychnine chromate, or the chromate decomposed by ammonia, and the
strychnine recovered from the alkaline liquid by chloroform.

(2.) =Sulphocyanide of Strychnine= (C₂₁H₂₂N₂O₂CNHS) is a thick, white
precipitate, produced by the addition of a solution of potassic
sulphocyanide to that of a strychnine salt; on warming it dissolves, but
on cooling reappears in the form of long silky needles.

(3.) =Double Salts.=--The platinum compound obtained by adding a
solution of platinic chloride to one of strychnine chloride has the
composition C₂₁H₂₂N₂O₂HClPtCl₂, and crystallises out of weak boiling
alcohol (in which it is somewhat soluble) in gold-like scales. The
similar palladium compound (C₂₁H₂₂N₂O₂HCl,PdCl) is in dark brown
needles, and the gold compound (C₂₁H₂₂N₂O₂HClAuCl₃) in orange-coloured
needles.

(4.) =Strychnine Trichloride.=--The action of chlorine on strychnine--by
which chlorine is substituted for a portion of the hydrogen--has been
proposed as a test. The alkaloid is dissolved in very dilute HCl, so as
to be only just acid; on now passing through chlorine gas, a white
insoluble precipitate is formed, which may be recrystallised from ether;
it has probably the composition C₂₁H₁₉Cl₃N₂O₂, and is extremely
insoluble in water.

(5.) =The Iodide of Strychnine= (C₂₁H₂₂N₂O₂HI₃) is obtained by the
action of iodine solution on strychnine sulphate; on solution of the
precipitate in alcohol, and evaporation, it forms violet-coloured
crystals, very similar to those of potassic permanganate.

§ 388. =Pharmaceutical and other Preparations of Nux Vomica and
Strychnine, with Suggestions for their Valuation.=

=An aqueous extract of nux vomica=, officinal in the German
pharmacopœia, appears to contain principally brucine, with a small
percentage of strychnine; the proportion of brucine to strychnine being
about four-fifths to one-fifth. Blossfield found in a sample 4·3 per
cent. of total alkaloid, and two samples examined by Grundmann consisted
(No. 1) of strychnine, 0·6 per cent.; brucine, 2·58 per cent.--total,
3·18 per cent.; (No. 2) strychnine, 0·68 per cent.; brucine, 2·62 per
cent.--total, 3·3 per cent. A sample examined by Dragendorff
yielded--strychnine, 0·8 per cent.; brucine, 3·2 per cent.--total, 4 per
cent. The maximum medicinal dose is put at ·6 grm. (9⁹⁄₁₄ grains).

=The spirituous extract of nux vomica=, officinal in the British and all
the Continental pharmacopœias, differs from the aqueous in containing a
much larger proportion of alkaloids, viz., about 15 per cent., and about
half the total quantity being strychnine. The medicinal dose is
21·6-64·8 mgrms. (⅓ grain to a grain).

There is also an =extract of St. Ignatius bean= which is used in the
United States; nearly the whole of its alkaloid may be referred to
strychnine.

=The tincture of nux vomica=, made according to the British
Pharmacopœia, contains in 1 fl. oz. 1 grain of alkaloids, or 0·21 part
by weight in 100 by volume, but the strength of commercial samples often
varies. Lieth found in one sample 0·122 per cent. of strychnine and 0·09
per cent. brucine; and two samples examined by Wissel consisted
respectively of 0·353 per cent. and 0·346 per cent. of total alkaloids.
Dragendorff found in two samples ·2624 per cent. and ·244 per cent. of
total alkaloids, about half of which was strychnine.

=Analysis.=--Either of the extracts may be treated for a few hours on
the water-bath, with water acidulated by sulphuric acid, filtered, the
residue well washed, the acid liquid shaken up with benzene to separate
impurities, and, on removal of the benzene, alkalised with ammonia, and
shaken up two or three times with chloroform; the chloroform is then
evaporated in a tared vessel, and the total alkaloids weighed. The
alkaloids can then be either (_a_) treated with 11 per cent. of nitric
acid on the water-bath until all the brucine is destroyed, and then (the
liquid being neutralised) precipitated by potassic chromate; or (_b_)
the alkaloids may be converted into picrates. Picrate of strychnine is
very insoluble in water, 1 part requiring no less than 10,000 of
water.[423] The tincture is analysed on precisely similar principles,
the spirit being got rid of by distillation, and the residue treated by
acidified water, &c.

[423] Dolzler, _Arch. Pharm._ [3], xxiv. 105-109.

The nux vomica powder itself may be valued as follows:--15 to 20 grms.,
pulverised as finely as possible, are treated three times with 150 to
300 c.c. of water, acidified with sulphuric acid, well boiled, and,
after each boiling, filtered and thoroughly pressed. The last exhaustion
must be destitute of all bitter taste. The united filtrates are then
evaporated to the consistence of a thick syrup, which is treated with
sufficient burnt magnesia to neutralise the acid. The extract is now
thoroughly exhausted with boiling alcohol of 90 per cent.; the alcoholic
extract, in its turn, is evaporated nearly to dryness, and treated with
acidulated water; this acid solution is freed from impurities by shaking
up with benzene, and lastly alkalised with ammonia, and the alkaloids
extracted by shaking up with successive portions of chloroform. The
chloroformic extract equals the total alkaloids, which may be separated
in the usual way.

In four samples of nux vomica examined by Dragendorff, the total
alkaloids ranged from 2·33 to 2·42 per cent. Grate found in two samples
2·88 per cent. and 2·86 per cent. respectively; while Karing from one
sample separated only 1·65 per cent. The strychnine and brucine are in
about equal proportions, Dragendorff[424] finding 1·187 per cent.
strychnine and 1·145 per cent. brucine.[425]

[424] Dragendorff, _Die chemische Werthbestimmung einiger starkwirkenden
Droguen_, St. Petersburg, 1874.

[425] These details are very necessary, as bearing on the question of
the fatal dose of nux vomica, which Taylor tells us (_Med. Jurisprud._,
i. 409) was of some importance in _Reg._ v. _Wren_, in which 47 grains
were attempted to be given in milk. The fatal dose of nux vomica must be
ruled by its alkaloidal content, which may be so low as 1 per cent., and
as high as nearly 3 per cent. 30 grains have proved fatal (_Taylor_); if
the powder in this instance was of the ordinary strength, the person
died from less than a grain (·0648 grm.) of the united alkaloids.

The =vermin-killers= in use in this country are those of Miller, Battle,
Butler, Clift, Craven, Floyd, Gibson, Hunter, Stenier, and Thurston. Ten
samples from these various makers were examined recently by Mr. Allen
(_Pharm. Journal_, vol. xii., 1889), and the results of the analyses are
embodied in the following table:--

  +-----+----------+------+-------------------+-------+--------------+
  |Name |Weight of |      |    Strychnine.    |Nature |              |
  | or  |  Powder  |Price.+---------+---------+  of   |  Colouring   |
  |Mark.|in Grains.|      |Weight in|   Per-  |Starch.|   Matter.    |
  |     |          |      |Grains.  |centage. |       |              |
  +-----+----------+------+---------+---------+-------+--------------+
  |     |          |      |         |         |       |              |
  |  1  |   5·6    | 3_d._|  0·61   |   10·9  | Wheat |      ?       |
  |  2  |  11·8    | 3_d._|  0·80   |    6·7  | Wheat | Ultramarine. |
  |  3  |  13·1    | 3_d._|  1·12   |    8·7  | Rice  | Ultramarine. |
  |  4  |  11·6    | 3_d._|  1·28   |   11·1  | Rice  | Ultramarine. |
  |  5  |  13·1    | 3_d._|  1·70   |   13·0  | Rice  | Ultramarine. |
  |  6  |  21·5    | 6_d._|  2·42   |   11·2  | Wheat |Prussian blue.|
  |  7  |  49·2    | 3_d._|  2·85   |    5·8  | Wheat |     Soot.    |
  |  8  |  30·5    | 3_d._|  3·45   |   11·3  | Wheat |Prussian blue.|
  |  9  |  16·6    | 3_d._|  3·81   |   19·4  | Rice  |   Carmine.   |
  | 10  |  10·0    | 3_d._|  4·18   |   41·8  | Rice  | Ultramarine. |
  +-----+----------+------+---------+---------+-------+--------------+

§ 389. =Statistics.=--In England, during the ten years 1883-92, out of
6666 total deaths from poison, strychnine, nux vomica, and vermin-killer
account for 325. Out of these deaths, 118 were ascribed to
“vermin-killer.” “Vermin-killer” may be presumed to include not only
strychnine mixtures, but also phosphorus and arsenic pastes and powders,
so that there are no means of ascertaining the number of strychnine
cases comprised under this heading. Taking the deaths actually
registered as due to strychnine or nux vomica, they are about 4·7 per
cent. of the deaths from all sorts of poison. Of these deaths, 268, or
82·4 per cent., were suicidal, 8 were homicidal, and 49 only were
accidental.

Schauenstein has collected from literature 130 cases of poisoning by
strychnine, but most of these occurred during the last twenty-five
years; 62 of the 130, or about one-half, were fatal, and 15 were
homicidal. It has been stated that strychnine is so very unsuitable for
the purpose of criminal poisoning as to render it unlikely to be often
used. Facts, however, do not bear out this view; for, allowing its
intensely bitter taste, yet it must be remembered that bitter liquids,
such as bitter ale, are in daily use, and a person accustomed to drink
any liquid rapidly might readily imbibe sufficient of a toxic liquid to
produce death before he was warned by its bitterness. It is, indeed,
capable of demonstration, that taste is more vivid _after_ a substance
has been taken than just in the act of swallowing, for the function of
taste is not a rapid process, and requires a very appreciable interval
of time.

The series of murders by Thomas Neill, or, more correctly, Thomas Neill
Cream, is an example of the use of strychnine for the purposes of
murder. Thomas Neill Cream was convicted, October 21, 1892, for the
murder of Matilda Clover on October 20, 1891; there was also good
evidence that the same criminal had murdered Ellen Dunworth, October 13,
1891; Alice Marsh, April 12, 1892; Emma Shrivell, April 12, 1892, and
had attempted the life of Louie Harvey. The agent in all these cases was
strychnine. There was no evidence as to what form of the poison was
administered in the case of Clover, but Ellen Dunworth, who was found
dying in the streets at 7.45 P.M., and died less than two hours
afterwards, stated that a gentleman gave her “two drops” of white stuff
to drink.

In the cases of Marsh and Shrivell, Neill Cream had tea with them on the
night of April 11, and gave them both “three long pills;” half an hour
after Neill Cream left them they were found to be dying, and died within
six hours. From Marsh 7 grains, from Shrivell nearly 2 grains of
strychnine were separated; the probability is that each pill contained
at least 3 grains of strychnine. The criminal met Louie Harvey on the
Embankment, and gave her “some pills” to take; she pretended to do so,
but threw them away. Hence it seems probable that Neill Cream took
advantage of the weakness that a large number of the population have for
taking pills, and mostly poisoned his victims in this manner. Clover’s
case was not diagnosed during life, but strychnine was found six or
seven months after burial in the body. It may be mentioned incidentally
that the accused himself furnished the clue which led to his arrest, by
writing letters charging certain members of the medical profession with
poisoning these poor young prostitutes with strychnine.

§ 390. =Fatal Dose.=--In a research, which may, from its painstaking
accuracy, be called classical, F. A. Falck has thrown much light upon
the minimum lethal dose of strychnine for various animals. It would seem
that, in relation to its size, the frog is by no means so sensible to
strychnine as was believed, and that animals such as cats and rabbits
take a smaller dose in proportion to their body-weight. The method used
by Falck was to inject subcutaneously a solution of known strength of
strychnine nitrate, and, beginning at first with a known lethal dose, a
second experiment was then made with a smaller dose, and if that proved
fatal, with a still smaller, and so on, until such a quantity was
arrived at, that the chances as determined by direct observation were as
great of recovery as of death. Operating in this way, and making no less
than 20 experiments on the rabbit, he found that the least fatal dose
for that animal was ·6 mgrm. of strychnine nitrate per kilogramme. Cats
were a little less susceptible, taking ·75 mgrm. Operating on fowls, he
found that strychnine taken into the crop in the usual way was very
uncertain; 50 mgrms. per kilo, taken with the food had no effect, but
results always followed if the poison was introduced into the
circulation by the subcutaneous needle--the lethal dose for fowls being,
under those circumstances, 1 to 2 mgrms. per kilo. He made 35
experiments on frogs, and found that to kill a frog by strychnine
nitrate, at least 2 mgrms. per kilo, must be injected. Mice take a
little more, from 2·3 to 2·4 mgrms. per kilo. In 2 experiments on the
ring adder, in one 62·5 mgrms. per kilo. of strychnine nitrate, injected
subcutaneously, caused death in seven hours; in the second, 23·1 mgrms.
per kilo. caused death in five days; hence the last quantity is probably
about the least fatal dose for this particular snake.

These observations may be conveniently thrown into the following table
(see next page), placing the animals in order according to their
relative sensitiveness.[426]

[426] According to Christison’s researches, 0·2 grm. (about ⅓ grain) is
fatal to swine; ·03 grm. (½ grain) to bears, if injected into the
pleura. 1 to 3 grains (·0648 to ·1944 grm.) is given to horses in cases
of paralysis, although 3 grains cannot but be considered a dangerous
dose, unless smaller doses have been previously administered without
effect; 10 grains would probably kill a horse, and 15 grains (·972 grm.)
have certainly done so.

Now, the important question arises, as to the place in this series
occupied by man--a question difficult to solve, because so few cases are
recorded in which strychnine has been administered by subcutaneous
injection with fatal result. Eulenberg has observed poisonous symptoms,
but not death, produced by 6 mgrms. (1/11 grain) and by 10 mgrms. (about
⅙ grain). Bois observed poisonous symptoms from the similar subcutaneous
administrations of 8 mgrms. to a child six years old, and 4 mgrms. to
another child four years old--the latter dose, in a case recorded by
Christison, actually killing a child of three years of age. On the other
hand, the smallest lethal dose taken by an adult was swallowed in
solution. Dr. Warner took 32 mgrms. (½ grain) of strychnine sulphate,
mistaking it for morphine sulphate, and died in twenty minutes. In other
cases 48 mgrms. (7/10 grain) have been fatal. It will be safe to
conclude that these doses by the stomach would have acted still more
surely and energetically if injected subcutaneously. The case of Warner
is exceptional, for he was in weak health; and, if calculated out
according to body-weight, presuming that Dr. Warner weighed 68 kilos.,
the relative dose as strychnine nitrate would be ·24 per kilo.--a
smaller dose than for any animal hitherto experimented upon. There is,
however, far more reason for believing that the degree of sensitiveness
in man is about the same as that of cats or dogs, and that the least
fatal dose for man is ·70 per kilo., the facts on record fairly bearing
out this view. It is, therefore, probable that death would follow if 38
mgrms. (7/10 grain) were injected subcutaneously into a man of the
average weight of 68 kilos. (150 lbs.). Taylor estimates the fatal dose
of strychnine for adults as from 32·4 to 129·6 mgrms. (·5 to 2 grains);
Guy puts the minimum at 16·2 mgrms. (·25 grain).

TABLE SHOWING THE ACTION OF STRYCHNINE ON ANIMALS.

  +------------+----------------------+--------------------------------+
  |            |                      |     Reckoned on 1 Kilo. of     |
  |            |                      |            Body-weight.        |
  |            |                      +-----------------|--------------+
  |            |      Manner of       |      Lowest     |  Highest     |
  |  Animal.   |     Application.     |    Experimental | Experimental |
  |            |                      |    Lethal Dose  | Lethal Dose. |
  |            |                      +-----------------+--------------+
  |            |                      | Dose of Strychnine Nitrate in  |
  |            |                      |              Mgrms.            |
  +------------+----------------------+-----------------+--------------+
  | Rabbit,    | Subcutaneous.        |      0·50       |    0·60      |
  | Cat,       |      „               |       ...       |    0·75      |
  | Dog,       |      „               |       ...       |    0·75      |
  |  „         | Taken by the Stomach.|       2·0       |    3·90      |
  |  „         |      „       Rectum. |       ...       |    2·00      |
  |  „         |      „       Bladder.|      5·50       |     ...      |
  | Fox,       | Subcutaneous.        |       ...       |    1·00      |
  | Hedgehog,  |      „               |      1·00       |    2·00      |
  | Fowl,      |      „               |       ...       |    2·00      |
  | Frog,      |      „               |      2·00       |    2·10      |
  | Mouse,     |      „               |      2·36       |    2·36      |
  | Ring Adder,|      „               |       ...       |   23·10      |
  +------------+----------------------+-----------------+--------------+

Large doses of strychnine may be recovered from if correct medical
treatment is sufficiently prompt. Witness the remarkable instances on
record of duplex poisonings, in which the would-be-suicide has
unwittingly defeated his object by taking strychnine simultaneously with
some narcotic, such as opium or chloral. In a case related by
Schauenstein,[427] a suicidal pharmacist took ·48 grm. or ·6 grm. (7·4
to 9·25 grains) of strychnine nitrate dissolved in about 30 c.c. of
bitter-almond water, and then, after half an hour, since no symptoms
were experienced, ·6 grm. (9·25 grains) of morphine acetate, which he
likewise dissolved in bitter-almond water and swallowed. After about ten
minutes, he still could walk with uncertain steps, and poured some
chloroform on the pillow-case of his bed, and lay on his face in order
to breathe it. In a short time he lost consciousness, but again awoke,
and lay in a half-dreamy state, incapable of motion, until some one
entered the room, and hearing him murmur, came to his bedside. At that
moment--two and a quarter hours after first taking the strychnine--the
pharmacist had a fearful convulsion, the breathing was suspended, and he
lost consciousness. Again coming to himself, he had several convulsions,
and a physician who was summoned found him in general tetanus. There
were first clonic, then tonic convulsions, and finally opisthotonus was
fully developed. The treatment consisted of emetics, and afterwards
tannin and codeine were given separately. The patient slept at short
intervals; in ten hours after the taking of the poison the seizures were
fewer in number and weaker in character, and by the third day recovery
was complete. Dr. Macredy[428] has also placed on record an interesting
case, in which the symptoms, from a not very large dose of strychnine,
were delayed by laudanum for eight hours. A young woman, twenty-three
years of age, pregnant, took at 10 A.M. a quantity of strychnine
estimated at 1·5 grain, in the form of Battle’s vermin-killer, and
immediately afterwards 2 ounces of laudanum. She was seen by Dr. Macredy
in four hours, and was then suffering from pronounced narcotic symptoms.
A sulphate of zinc emetic was administered. In eight hours after taking
the strychnine, there were first observed some clonic convulsive
movements of the hands, and, in a less degree, the legs. These
convulsions continued, at times severe, for several hours, and were
treated with chloral. Recovery was speedy and complete.

[427] Maschka’s _Handbuch_, from Tschepke, _Deutsche Klinik_, 1861.

[428] _Lancet_, November 28, 1882.

In a similar case related by Dr. Harrison,[429] a man, aged 54, took a
packet of Battle’s vermin-killer, mixed with about a drachm and a half
of laudanum and some rum. At the time he had eaten no food for days, and
had been drinking freely; yet fifty minutes elapsed before the usual
symptoms set in, and no medical treatment was obtained until four hours
after taking the dose. He was then given chloral and other remedies, and
made a rapid recovery.

[429] _Lancet_, May 13, 1882.

§ 391. =Action on Animals.=--The action of strychnine has been
experimentally studied on all classes of animals, from the infusoria
upwards. The effects produced on animal forms which possess a nervous
system are strikingly alike, and even in the cephalopoda, tetanic
muscular spasm may be readily observed. Of all animals the frog shows
the action of strychnine in its purest form, especially if a dose be
given of just sufficient magnitude to produce toxic effects. The frog
sits perfectly still and quiet, unless acted upon by some external
stimuli, such as a breath of air, a loud noise, or the shaking of the
vessel which contains it, then an immediate tetanic convulsion of all
the muscles is witnessed, lasting a few seconds only, when the animal
again resumes its former posture. This heightened state of reflex action
has its analogue in hydrophobia as well as in idiopathic tetanus. If the
frog thus poisoned by a weak dose is put under a glass shade, kept
moist, and sheltered from sound, or from other sources of irritation, no
convulsions occur, and after some days it is in its usual health. If, on
the other hand, by frequent stimuli, convulsions are excited, the animal
dies. M. Richet[430] has contributed a valuable memoir to the Academy of
Sciences on the toxic action of strychnine. He has confirmed the
statement of previous observers that, with artificial respiration, much
larger doses of strychnine may be taken without fatal result than under
normal conditions, and has also recorded some peculiar phenomena.
Operating on dogs and rabbits, after first securing a canula in the
trachea, and then injecting beneath the skin or into the saphena vein 10
mgrms. of strychnine hydrochlorate, the animal is immediately, or within
a few seconds, seized with tetanic convulsions, and this attack would be
mortal, were it not for artificial respiration. Directly this is
practised the attack ceases, and the heart, after a period of hurried
and spasmodic beats, takes again its regular rhythm. Stronger and
stronger doses may then be injected without causing death. As the dose
is thus augmented, the symptoms differ. M. Richet distinguishes the
following periods:--(1.) A period of tetanus. (2.) A period of
convulsion, characterised by spasmodic and incessant contraction of all
the muscles. (3.) A little later, when the quantity exceeds 10 mgrms.
per kilo., a choreic period, which is characterised by violent rhythmic
shocks, very sudden and short, repeated at intervals of about three to
four seconds; during these intervals there is almost complete
relaxation. (4.) A period of relaxation; this period is attained when
the dose exceeds 40 mgrms. per kilo. Reflex action is annihilated, the
spontaneous respiratory movements cease, the heart beats tumultuously
and regularly in the severe tetanic convulsions at first, and then
contracts with frequency but with regularity. The pupils, widely dilated
at first, become much contracted. The arterial pressure, enormously
raised at the commencement, diminishes gradually, in one case from 0·34
mm. to 0·05 mm. The temperature undergoes analogous changes, and during
the convulsions is extraordinarily elevated; it may even attain 41° or
42°, to sink in the period of relaxation to 36°. Dogs and rabbits which
have thus received enormous quantities of strychnine (_e.g._, 50 mgrms.
per kilo.), may, in this way, live for several hours, but the slightest
interruption to the artificial respiration, in the relaxed state, is
followed by syncope and death.

[430] _De l’Action de la Strychnine à très forte dose sur les
Mammifères. Comptes Rend._, t. xcl. p. 131.

§ 392. =Effects on Man: Symptoms.=--The commencement of symptoms may be
extremely rapid, the rapidity being mainly dependent on the form of the
poison and the manner of application. A soluble salt of strychnine
injected subcutaneously will act within a few seconds;[431] in a case of
amaurosis, related by Schuler,[432] 5·4 mgrms. of a soluble strychnine
salt were introduced into the punctum lachrymale;--in less than four
minutes there were violent tetanic convulsions. In a case related by
Barker, the symptoms commenced in three minutes from a dose of ·37 grm.
(5·71 grains).[433] Here the poison was not administered subcutaneously.
Such short periods, to a witness whose mind was occupied during the
time, might seem immediate. On the other hand, when nux vomica powder
has been taken, and when strychnine has been given in the form of pill,
no such rapid course has been observed, or is likely to occur, the usual
course being for the symptoms to commence within half an hour. It is,
however, also possible for them to be delayed from one to two hours, and
under certain circumstances (as in the case related by Macredy) for
eight hours. In a few cases, there is first a feeling of uneasiness and
heightened sensibility to external stimuli, a strange feeling in the
muscles of the jaw, and a catching of the respiration; but generally
the onset of the symptoms is as sudden as epilepsy, and previous to
their appearance the person may be pursuing his ordinary vocation, when,
without preliminary warning, there is a shuddering of the whole frame,
and a convulsive seizure. The convulsions take the form of violent
general tetanus; the limbs are stretched out involuntarily, the hands
are clenched, the soles of the feet incurved, and, in the height of the
paroxysm, the back may be arched and rigid as a board, the sufferer
resting on head and heels, and the abdomen tense. In the grasp of the
thoracic muscles the walls of the chest are set immovable, and from the
impending suffocation the face becomes congested, the eyes prominent and
staring. The muscles of the lower jaw--in “disease tetanus” the first to
be affected--are in “strychnos tetanus,” as a rule, the last; a
distinction, if it were more constant, of great clinical value. The
convulsions and remissions recur until death or recovery, and, as a
rule, within two hours from the commencement of the symptoms the case in
some way or other terminates. The number of the tetanic seizures noted
has varied--in a few cases the third spasm has passed into death, in
others there have been a great number. The duration of the spasm is also
very different, and varies from thirty seconds to five or even eight
minutes, the interval between lasting from forty-five seconds[434] to
one or even one and a half hours.[435]

[431] In one of M. Richet’s experiments, a soluble strychnine salt
injected into a dog subcutaneously acted in fourteen seconds.

[432] Quoted by Taylor from _Med. Times and Gazette_, July, 1861.

[433] A non-fatal dose may show its effects rapidly, _e.g._, there is a
curious case of symptoms of poisoning caused by the _last_ dose of a
mixture which is recorded in _Pharm. Journ._, 1893, 799. A medical
practitioner prescribed the following mixture:--

  ℞. Tr. strophanthi,                                  ʒi.
     Liq. strychni hydrochlorici,                      ʒiiss.
     Sol. bismuthi et pepsin. (Richardson’s),          ℥iss.
     Sp. ammon. aromat.,                                ...
     Sp. chloroformi,                              aa. ℥iss.
     Aquam ad,                                         ℥vi.
          ft. mist.
  Shake the bottle.
  Two teaspoonfuls when the attack threatens, and repeat in an hour if
  necessary.

Richardson’s liquor bismuth contains 1/20 grain of strychnine in each
drachm. The mixture was alkaline; it contained 1·7 grain of strychnine
and 38·25 minims of chloroform.

The patient, a woman, 54 years of age, had taken the previous doses with
considerable relief; but ten minutes after the last dose, which she
described as far more bitter than those she had taken previously, she
was seized with the usual symptoms of strychnine poisoning, but
recovered after five hours.

The explanation is pretty obvious; the mixture was alkaline, so that the
strychnine was not in the form of a salt, but in the free state, and was
therefore dissolved by the chloroform; the amount of strychnine taken in
each dose wholly depended on whether or not the mixture was shaken
violently and poured out into the teaspoon immediately after shaking; if
allowed to repose the globules of chloroform saturated with strychnine
would settle at the bottom, and there form a stratum rich in strychnine;
so that the last dose would certainly contain an excess.

[434] White, _Brit. Med. Journ._, 1867.

[435] Folkes, _Med. Times_, 1869.

§ 393. =Diagnosis of Strychnine Poisoning.=--However striking and well
defined the picture of strychnine tetanus may be, mistakes in diagnosis
are rather frequent, especially when a medical man is hastily summoned,
has never seen a case of similar poisoning, and has no suspicion of the
possible nature of the seizure. If a young woman, for instance, is the
subject, he may put it down to hysteria, and certainly hysteria not
unfrequently affects somewhat similar convulsions. In a painful case in
which the author was engaged, a young woman either took or was given
(for the mystery was never cleared up fully) a fatal dose of strychnine,
and though the symptoms were well marked, the medical attendant was so
possessed with the view that the case was due to hysteria, that, even
after making the _post-mortem_ examination, and finding no adequate
lesion, he theorised as to the possibility of some fatal hysteric spasm
of the glottis, while there was ample chemical evidence of strychnine,
and a weighable quantity of the alkaloid was actually separated from the
contents of the stomach. The medical attendant of Matilda Clover, one of
Neill’s victims, certified that the girl died from _delirium tremens_
and syncope, although the symptoms were typically those produced by
strychnine. Such cases are particularly sad, for we now know that, with
judicious treatment, a rather large dose may be recovered from.

If the case is a male, a confusion with epilepsy is possible, though
hardly to be explained or excused; while in both sexes idiopathic
tetanus is so extremely similar as to give rise to the idea that all
cases of idiopathic tetanus are produced by poison, perhaps secreted by
the body itself. As for the distinction between idiopathic and strychnic
tetanus, it is usually laid down (1) that the intervals in the former
are characterised by no relaxation of the muscles, but that they
continue contracted and hard; and (2) that there is a notable rise of
temperature in disease tetanus proper, and not in strychnine tetanus.
Both statements are misleading, and the latter is not true, for in
strychnic poisoning the relaxation is not constant, and very high
temperatures in animals have been observed.

§ 394. =Physiological Action.=--The tetanic convulsions are essentially
reflex, and to be ascribed to a central origin; the normal reflex
sensibility is exaggerated and unnaturally extended. If the ischiatic
plexus supplying the one leg of an animal is cut through, that leg takes
no part in the general convulsions, but if the artery of the leg alone
is tied, then the leg suffers from the muscular spasm, as well as the
limbs in which the circulation is unrestrained. In an experiment by Sir
B. W. Richardson, a healthy dog was killed, and, as soon as practicable,
a solution of strychnine was injected through the systemic vessels by
the aorta--the whole body became at once stiff and rigid as a board.
These facts point unmistakably to the spinal marrow as the seat of the
toxic influence. Strychnine is, _par excellence_, a spinal poison. On
physiological grounds the grey substance of the cord is considered to
have an inhibitory action upon reflex sensibility, and this inhibitory
power is paralysed by strychnine. The spinal cord, it would appear, has
the power of collecting strychnine from the circulation and storing it
up in its structure.[436]

[436] R. W. Lovett, _Journ. Physiol._, ix. 99-111.

Much light has been thrown upon the cause of death by Richet’s
experiments.[437] It would seem that, in some cases, death takes place
by a suffocation as complete as in drowning, the chest and diaphragm
being immovable, and the nervous respiratory centres exhausted. In such
a case, immediate death would be averted by a tracheal tube, by the aid
of which artificial respiration might be carried on; but there is
another asphyxia due to the enormous interstitial combustion carried on
by muscles violently tetanised. “If,” says Richet, “after having
injected into a dog a mortal dose of strychnine, and employed artificial
respiration according to the classic method twenty or thirty times a
minute, the animal dies (sometimes at the end of ten minutes, and in
every case at the end of an hour or two), and during life the arterial
blood is examined, it will be ascertained that it is black, absolutely
like venous blood.”

[437] _Op. cit._

This view is also supported by the considerable rise of temperature
noticed: the blood is excessively poor in oxygen, and loaded with carbon
dioxide. That this state of the blood is produced by tetanus, is proved
by the fact that an animal poisoned by strychnine, and then injected
subcutaneously with curare in quantity just sufficient to paralyse the
muscular system, does not exhibit these phenomena. By the aid of
artificial respiration, together with the administration of curare, an
animal may live after a prodigious dose of strychnine.

Meyer[438] has investigated carefully the action of strychnine on the
blood-pressure--through a strong excitement of the vaso-motor centre,
the arteries are narrowed in calibre, and the blood-pressure much
increased; the action of the heart in frogs is slowed, but in the
warm-blooded animals quickened.

[438] _Wiener Akad. Sitzungsber._, 1871.

§ 395. =Post-mortem Appearances.=--There is but little characteristic in
the _post-mortem_ appearances from strychnine poisoning. The body
becomes very stiff a short time after death, and this rigidity remains
generally a long time. In the notorious Palmer case, the body was rigid
two months after death, but, on the other hand, the _rigor mortis_ has
been known to disappear within twenty-four hours. If the convulsions
have been violent, there may be minute hæmorrhages in the brain and
other parts. I have seen considerable hæmorrhage in the trachea from
this cause. When death occurs from asphyxia, the ordinary signs of
asphyxia will be found in the lungs, &c. The heart mostly has its right
side gorged with blood, but in a few cases it is empty and contracted.

In a case which Schauenstein has recorded[439] he found strychnine still
undissolved, coating the stomach as a white powder; but this is very
unusual, and I believe unique. The bladder often contains urine, which,
it need scarcely be said, should be preserved for chemical
investigation.

[439] _Op. cit._

§ 396. =Treatment.=--From the cases detailed, and from the experiments
on animals, the direction which treatment should take is very clear. As
a matter of course, if there is the slightest probability of any of the
poison remaining in the stomach, it should be removed. It is doubtful
whether the stomach pump can be ever applied with benefit in strychnine
poisoning, the introduction of the tube is likely to aggravate the
tetanus, but apomorphine can be injected subcutaneously. Large and
frequent doses of chloral should be administered in order to lessen the
frequency of convulsions, or prevent their occurrence, and it may be
necessary in a few cases, where death threatens by suffocation, to
perform tracheotomy, and to use artificial respiration. Where chloral or
chloroform is not at hand, and in cases of emergency, where this may
easily happen, the medical man must administer in full doses the nearest
narcotic at hand.[440]

[440] It is certain that lutidine would be a valuable antidote for
strychnine. C. G. Williams found that lutidine injected into frogs
already under the influence of strychnine, arrested the convulsions, or
if given first, and then followed by a fatal dose of strychnine, it
prevented the appearance of the tetanus. (See _ante_, p. 276, footnote.)

§ 397. =Separation of Strychnine from Organic Matters.=--The separation
of strychnine from organic matters, &c., is undertaken strictly on the
general principles already detailed. It may happen, however, that in
cases of poisoning there is the strongest evidence from symptoms in the
person or animal that strychnine alone is to be sought for. In an
instance of the kind, if a complex organic liquid (such as the contents
of the stomach) is under examination, it is best to remove the solid
substances by filtration through glass, wool, or linen, and evaporate
nearly to dryness over the water-bath, acidifying with acetic acid, and
then exhausting the residue repeatedly with boiling alcohol of 80 per
cent. The alcoholic extract is in its turn evaporated to dryness, and
taken up with water; the aqueous solution is passed through a wet
filter, and then shaken up with the usual succession of fluids, viz.,
petroleum ether, benzene, chloroform, and amyl alcohol, which will
remove a great number of impurities, but will not dissolve the
strychnine from the acid solution. The amyl alcohol may lastly be
removed by petroleum ether; and on removal of the final extractive
(which should be done as thoroughly as possible) chloroform is added,
and the fluid is alkalised by ammonia, which precipitates the alkaloid
in the presence of the solvent. Should the reverse process be
employed--that is, ammonia added first, and then chloroform--the
strychnine is not so perfectly dissolved, since it has time to assume a
crystalline condition. On separation and evaporation of the chloroform,
the residue (if much discoloured, or evidently impure) may be dissolved
in alcohol or benzene, and recrystallised several times. Cushman has
published an improved method of separating strychnine, which, according
to test experiments, appears to give good results. He describes the
method as follows:[441]--

[441] “The _post-mortem_ Detection and Estimation of Strychnine,” by
Allerton S. Cushman--_Chem. News_, vol. lxx. 28.

    “The stomach contents or viscera properly comminuted are weighed,
    and an aliquot part taken for analysis. The mass is digested in a
    beaker over night, at a warm temperature, with water acidulated with
    acetic acid. The contents of the beaker are filtered by pressing
    through muslin, and then passing through paper. The clear filtrate
    is evaporated on the water-bath to soft dryness, an excess of
    ordinary 80 per cent. alcohol added, and boiled ten minutes with
    stirring, and allowed to stand one half hour at a warm temperature.
    This extraction is repeated, the alcohol extracts united, filtered,
    evaporated to soft dryness, and the residue taken up with a little
    water acidulated with acetic acid, and shaken out with pure acetic
    ether in a separating funnel. Successive fresh portions of acetic
    ether are used until the solvent shows by its colour, and by the
    evaporation of a few drops, that it does not contain extractive
    matter. As many as twelve extractions are sometimes necessary to
    accomplish this. Care should be taken in each case to allow time for
    as complete separation as possible between the two layers. The
    purified acid aqueous liquid, which need not exceed in bulk 50 c.c.,
    is now returned to the separator, an equal quantity of fresh acetic
    ether added, and enough sodic carbonate in solution to render the
    mixture slightly alkaline, and the separator is then thoroughly
    shaken for several minutes. All the alkaloid should now be in
    solution in the acetic ether, but a second shaking of the alkaline
    liquid, with acetic ether, is always made, the two extracts united,
    and evaporated in a glass dish over hot water to dryness. It will
    now be found that the residue shows the alkaloid fairly pure, but
    not pure enough for quantitative results. The residue is dissolved
    in a few drops of dilute acetic acid, warmed to complete solution,
    filtered if necessary, diluted to about 30 c.c., and the solution
    transferred to a small separating funnel; 30 c.c. of
    ether-chloroform (1-1) are now added, and the separator shaken.
    After separation the heavier ether-chloroform is allowed to run off,
    another lot of 30 c.c. of ether-chloroform is added, the separator
    shaken, and immediately enough ammonia-water added to render the
    mixture alkaline, and the whole vigorously agitated for several
    minutes. After separation is complete, the ether-chloroform layer is
    run out into a clean 50 c.c. glass-stoppered burette. The alkaline
    water solution is agitated with 20 c.c. more of the
    ether-chloroform, separated, and this extract added to that in the
    burette. The burette is now supported over a small weighed glass
    dish, which is kept warm on a water-bath, and the liquid allowed to
    evaporate gently, drop by drop, until a sufficient quantity of the
    pure alkaloid has collected in the centre of the dish to render an
    accurate weighing possible, or else all of the alkaloid may be
    collected and weighed at once. After all possible tests have been
    made upon the weighed alkaloid, the remainder is re-dissolved in a
    drop or two of acetic acid, a little water added, and the dish
    exposed under a bell-glass to the fumes of ammonia. After standing
    some time all the strychnine is found crystallised out in the
    beautiful characteristic needle-formed crystals. The mother-liquor
    is drawn off with a small fine-pointed tube and rubber bulb, the
    crystals carefully washed with a little water and dried over
    sulphuric acid. The glass dish containing these crystals is kept as
    the final exhibit, and is shown in evidence. Another convenient
    exhibit may be prepared by moistening a small filter-paper with a
    solution of the alkaloid in dilute acetic acid, then moistening with
    a solution of potassium dichromate: this paper, on being dried, may
    be kept indefinitely. On moistening it, and touching it at any time
    with a drop of strong sulphuric acid, a violet film, changing to
    cherry-red, is formed at the place of contact.”

Should search be made for minute portions of strychnine in the tissues,
considering the small amount of the poison which may produce death, it
is absolutely necessary to operate on a very large quantity of material.
It would be advisable to take the whole of the liver, the brain, spinal
cord, spleen, stomach, duodenum, kidneys, all the blood that can be
obtained, and a considerable quantity of muscular tissue, so as to make
in all about one-eighth to one-tenth of the whole body; this may be cut
up into small pieces, and boiled in capacious flasks with alcohol,
acidified with acetic acid. Evaporation must be controlled by adapting
to the cork an upright condenser.

Should the analyst not have apparatus of a size to undertake this at
one operation, it may be done in separate portions--the filtrate from
any single operation being collected in a flask, and the spirit
distilled off in order to be used for the next. In this way, a large
quantity of the organs and tissues can be exhausted by half a gallon of
alcohol. Finally, most of the alcohol is distilled off, and the
remainder evaporated at a gentle heat in a capacious dish, the final
extract being treated, evaporating to a syrup, and using Cushman’s
process (_ante_, p. 334) as just described. It is only by working on
this large scale that there is any probability of detecting absorbed
strychnine in those cases where only one or two grains have destroyed
life, and even then it is possible to miss the poison.

Strychnine is separated by the kidneys rapidly. In a suicidal case
recorded by Schauenstein,[442] death took place in an hour and a half
after taking strychnine, yet from 200 c.c. of the urine, Schauenstein
was able to separate nitrate of strychnine in well-formed crystals. Dr.
Kratter[443] has made some special researches on the times within which
strychnine is excreted by the kidneys. In two patients, who were being
treated by subcutaneous injection, half an hour after the injection of
7·5 mgrms. of strychnine nitrate the alkaloid was recognised in the
urine. The strychnine treatment was continued for eight to ten days, and
then stopped; two days after the cessation, strychnine was found in the
urine, but none on the third day, and the inference drawn is that the
elimination was complete within forty-eight hours.

[442] Maschka’s _Handbuch_, Band 2, p. 620.

[443] _Ibid._

Strychnine has been detected in the blood of dogs and cats in researches
specially undertaken for that purpose, but sometimes a negative result
has been obtained, without apparent cause. Dragendorff[444] gave dogs
the largest possible dose of strychnine daily. On the first few days no
strychnine was found in the urine, but later it was detected, especially
if food was withheld. M’Adam was the first who detected the absorbed
poison, recognising it in the muscles and urine of a poisoned horse, and
also in the urine of a hound. Dragendorff has found it in traces in the
kidneys, spleen, and pancreas; Gay, in different parts of the central
nervous system, and in the saliva. So far as the evidence goes, the
liver is the best organ to examine for strychnine; but all parts
supplied with blood, and most secretions, may contain small quantities
of the alkaloid. At one time it was believed that strychnine might be
destroyed by putrefaction, but the question of the decomposition of the
poison in putrid bodies may be said to be settled. So far as all
evidence goes, strychnine is an extremely stable substance, and no
amount of putrescence will destroy it. M’Adam found it in a horse a
month after death, and in a duck eight weeks after; Nunneley in 15
animals forty-three days after death, when the bodies were much
decomposed; Roger in a body after five weeks’ interment; Richter in
putrid tissues exposed for eleven years to decomposition in open
vessels; and, lastly, W. A. Noyes[445] in an exhumed body after it had
been buried 308 days.

[444] In an animal rapidly killed by a subcutaneous injection of acetate
of strychnine, no strychnine was detected either in the blood or
liver.--_Dragendorff._

[445] _Journ. Americ. Chem. Soc._, xvi. 2.

It would appear from Ibsen’s[446] experiments that strychnine gets
dissolved in the fluids of the dead body--so that whether strychnine
remains or not, greatly depends as to whether the fluids are retained or
are allowed to soak away; it is, therefore, most important in
exhumations to save as much of the fluid as possible.

[446] _Viertel. f. gericht. Med._, Bd. viii.

§ 398. =Identification of the Alkaloid.=--A residue containing
strychnine, or strychnine mixed with brucine, is identified--

(1.) By its alkaline reaction and its bitter taste. No substance can
possibly be strychnine unless it tastes remarkably bitter.

(2.) By the extremely insoluble chromate of strychnine, already
described.[447] A fluid containing 1 : 1000 of strychnine gives with
chromate of potash (if allowed to stand over-night) a marked
precipitate, dissimilar to all others, except those of lead and baryta
chromates, neither of which can possibly occur if any of the processes
described are followed.

[447] 1 grm. of strychnine gave 1·280 grms. of the chromate, = 78·1 per
cent. of strychnine; 3 gave 3·811 of the chromate, = 78·77 per cent. of
strychnine.--_Mohr._

(3.) If the chromate just described is treated on a porcelain plate with
a drop of pure strong sulphuric acid, a deep rich blue colour, passing
through purple into red, rapidly makes its appearance. This colour
possesses an absorption spectrum (figured at p. 55). Dr. Guy, neglecting
intermediate colours, aptly compares the succession--(1) to the rich
blue of the Orleans plum; (2) to the darker purple of the mulberry; and
(3) to the bright clear red of the sweet orange. These characters--viz.,
alkalinity, bitterness, and the property of precipitation by potassic
chromate in a definite crystalline form, the crystals giving the
colours detailed--belong to no other substance known save strychnine,
and for all purposes sufficiently identify the alkaloid. The same
colour is obtained by mixing a drop of sulphuric acid with
strychnine and a crystal, or speck, of any one of the following
substances:--Ferridcyanide of potash, permanganate of potash, peroxide
of lead, peroxide of manganese, and cerous hydroxide.

Potassic permanganate and sulphuric acid is the most delicate, and will
detect 0·001 mgrm. of strychnine; cerous hydroxide is, on the other
hand, most convenient, for cerous hydroxide is white; all the others
have colours of their own. Cerous hydroxide is prepared strychnine; 3
gave 3·811 of the chromate, = 78·77 per cent. of strychnine.--_Mohr._
by dissolving cerium oxalate in dilute sulphuric acid and precipitating
with ammonia, filtering and well washing the precipitate; and the latter
may be used while moist, and responds well to 1/100 mgrm. of strychnine.

The influence of mixtures on the colour reactions of strychnine have
been studied by Flückiger, who states:--

“No strychnine reaction appears with sulphuric acid containing chromic
acid (made by dissolving 0·02 grm. of pot. bichromate in 10 c.c. of
water, and then adding 30 grms. strong sulphuric acid) when brucine and
strychnine mixed in equal parts are submitted to the test; it succeeds,
however, in this proportion with sulphuric acid containing potassium
permanganate (·02 grm. pot. permanganate in 10 c.c. of water, and 30
grms. of strong sulphuric acid).

“If the brucine is only one-tenth of the mixture, the blue-violet colour
is obtained. A large excess of atropine does not prevent or obscure the
strychnine reaction. A solution of 1 milligrm. atropine sulphate
evaporated to dryness, together with 5 c.c. of a solution of strychnine
(1 : 100,000) has no influence on the reaction, neither in the
proportion of 1 mgrm. to 1 c.c. of the same solution; neither has
cinchonine nor quinine any effect.

“Morphine obscures the reaction in the following proportions:--

“A solution of 0·01 mgrm. strychnine evaporated with a solution of 1
mgrm. of morphine sulphate on a water-bath, yields a blurred strychnine
reaction when the residue is dissolved in sulphuric acid, and a crystal
of potassic permanganate added. But still there is evidence whereby to
_suspect_ the presence of strychnine.

“A solution of 2 mgrms. of morphine sulphate treated in like manner with
0·01 mgrm. of strychnine yields like results.

“A solution of 3 mgrms. of morphine sulphate evaporated to dryness, with
a solution of 0·01 mgrm. strychnine yielded results with the potassic
permanganate test the same as if no strychnine was present.

“A solution of 1 mgrm. of morphine sulphate, treated as above, with a
solution of 0·1 mgrm. strychnine, offered positive proof of the presence
of the latter.”[448]

[448] Flückiger’s _Reactions_, translated by Nagelvoort, Detroit, 1893.

Dragendorff was able to render evident ·025 mgrm. mixed with twenty
times its weight of quin. sulphate; the same observer likewise
recognised ·04 mgrm. of strychnine in thirty-three times its weight of
caffeine. Veratrine is likewise not injurious.

=The physiological test= consists in administering the substance to some
small animal (preferably to a frog), and inducing the ordinary tetanic
symptoms. It may be at once observed that if definite chemical evidence
of strychnine has been obtained, the physiological test is quite
unnecessary; and, on the other hand, should the application of a liquid
or substance to a frog induce tetanus, while chemical evidence of the
presence of strychnine was wanting, it would be hazardous to assert that
strychnine was present, seeing that caffeine, carbolic acid, picrotoxin,
certain of the opium alkaloids, hypaphorine, some of the ptomaines, and
many other substances induce similar symptoms. The best method (if the
test is used at all) is to take two frogs,[449] and insert under the
skin of the one the needle of a subcutaneous syringe, previously charged
with a solution of the substance, injecting a moderate quantity. The
other frog is treated similarly with a very dilute solution of
strychnine, and the two are then placed under small glass shades, and
the symptoms observed and compared. It is not absolutely necessary to
inject the solution under the skin, for if applied to the surface the
same effects are produced; but, if accustomed to manipulation, the
operator will find the subcutaneous application more certain, especially
in dealing with minute quantities of the alkaloid.[450]

[449] A very practical disadvantage of the physiological test is the
great difficulty of obtaining frogs exactly when wanted.

[450] Methyl strychnine, as well as methyl brucine, has been shown by
Brown and Fraser to have an effect exactly the opposite to that of
strychnine, paralysing the muscles like curare. In the case, therefore,
of the methyl compounds, a physiological test would be very valuable,
since these compounds do not respond to the ordinary tests.

    § 399. =Hypaphorine.=--One substance is known which neither
    physiological test nor the colour reactions suffice to distinguish
    from strychnine, viz., hypaphorine,[451] the active matter of a
    papilionaceous tree growing in Java--the _Hypaphorus subumbrans_; a
    small quantity of the alkaloid is in the bark, a larger quantity is
    in the seed.

[451] Dr. C. Plugge, _Arch. f. exp. Path. u. Ph._, Bd. xxxii. 313.

    Hypaphorine forms colourless crystals which brown, without melting,
    above 220°, and exhale a vapour smelling like napththylamine. The
    free alkaloid is soluble in water, but has no action on litmus. The
    salts are less soluble than the free alkaloid, so that acids, such
    as nitric or hydrochloric, produce in a short time precipitates on
    standing. Solutions of the salts are not precipitated by alkalies;
    chloroform, ether, benzene, all fail to extract it from either
    alkaline or acid solutions. It gives no precipitate with potassic
    chromate, but most general alkaloidal reagents precipitate.

    It gives a precipitate with iodine trichloride, and has therefore
    probably a pyridine nucleus, it may be an acid anilide.[452] It
    gives the same colours as strychnine with sulphuric acid and
    potassic permanganate or potassic chromate; it causes in frogs
    tetanus, but the dose has to be much larger than that of strychnine.
    The duration of life in doses of 15 mgrms. may extend to five days,
    and frogs may even recover after 50 mgrms.

[452] Julius Tafel (_Ber._, 1890, 412) has shown that the colour
reactions with H₂SO₄ and oxidising agents are the characteristic tests
of an acid anilide.

    The distinction between strychnine and hypaphorine is therefore
    easy; besides it will not occur in a chloroform extract, and it will
    not give a precipitate with potassic chromate.

    § 400. =Quantitative Estimation of Strychnine.=--The best process of
    estimating the proportion of each alkaloid in a mixture of
    strychnine and brucine, is to precipitate them as picrates, and to
    destroy the brucine picrate by nitric acid after obtaining the
    combined weight of the mixed picrates; then to weigh the undestroyed
    strychnine picrate.

    To carry out the process, the solution of the mixed alkaloids must
    be as neutral as possible. A saturated solution of picric acid is
    added drop by drop to complete precipitation. A filter paper is
    dried and weighed, and the precipitate collected on to this filter
    paper; the precipitate is washed with cold water, dried at 105°, and
    weighed. This weight gives the combined weight of both strychnine
    and brucine picrates.

    The precipitate is now detached from the filter, washed into a small
    flask, and heated on the water-bath for some time with nitric acid
    diluted to 1·056 gravity (about 11 per cent. HNO₃). This process
    destroys the brucine picrate, but leaves the strychnine picrate
    untouched. The acid liquid is now neutralised with ammonia or soda,
    and a trace of acetic acid added; the precipitate of strychnine
    picrate is now collected and weighed. The weight of this subtracted
    from the first weight, of course, gives that of the brucine picrate.

    One part of strychnine picrate is equal to 0·5932 strychnine; and
    one part of brucine picrate is equal to 0·6324 brucine.

    From the strychnine picrate the picric acid may be recovered and
    weighed by dissolving the picrate in a mineral acid and shaking out
    with ether; from the acid liquid thus deprived of picric acid the
    alkaloid may be separated by alkalising with ammonia and shaking out
    with chloroform.

§ 401. =Brucine= (C₂₃H₂₆N₂O₄ + 4H₂O)[453] occurs associated with
strychnine in the plants already mentioned; its best source is the
so-called _false angustura_ bark, which contains but little strychnine.
Its action is similar to that of strychnine. If crystallised out of
dilute alcohol it contains 4 atoms of water, easily expelled either in a
vacuum over sulphuric acid or by heat. Crystallised thus, it forms
transparent four-sided prisms, or arborescent forms, like boric acid. If
thrown down by ammonia from a solution of the acetate, it presents
itself in needles or in tufts.

[453] Sonnenschein has asserted that brucine may be changed into
strychnine by the action of NO₃. This statement has been investigated by
A. J. Cownley, but not confirmed.--_Pharm. Journ._ (3), vi. p. 841.

The recently-crystallised alkaloid has a solubility different from that
which has effloresced, the former dissolving in 320 parts of cold, and
150 parts of boiling water; whilst the latter (according to Pelletier
and Caventou) requires 500 of boiling, and 850 parts of cold water for
solution. Brucine is easily soluble in absolute, as well as in ordinary
alcohol; 1 part dissolves in 1·7 of chloroform, in 60·2 of benzene.
Petroleum ether, the volatile and fatty oils and glycerine, dissolve the
alkaloid slightly, amyl alcohol freely; it is insoluble in _anhydrous_
ether. The behaviour of brucine in the subliming cell is described at p.
260. Anhydrous brucine melts in a tube at 178°. The alcoholic solution
of brucine turns the plane of polarisation to the left [α]_r_ = -11·27°.
The taste is bitter and acrid. Soubeiran maintains that it can be
recognised if 1 part is dissolved in 500,000 parts of water. If nitric
trioxide be passed into an alcoholic solution of brucine, first brucine
nitrate is formed; but this passes again into solution, from which,
after a time, a heavy, granular, blood-red precipitate separates: it
consists of dinitro-brucine (C₂₃H₂₄(NO₂)₂N₂O₄). Brucine fully
neutralises acids, and forms salts, which are for the most part
crystalline. The neutral sulphate (C₂₃H₂₅N₂O₄SH₂O₄ + 3½H₂O) is in long
needles, easily soluble in water. The acetate is not crystalline, that
of strychnine is so (p. 321).

Brucine is precipitated by ammonia, by the caustic and carbonated
alkalies, and by most of the group reagents. Ammonia does not
precipitate brucine, if in excess; on the other hand, strychnine comes
down if excess of ammonia is added immediately. This has been proposed
as a method of separation; if the two alkaloids are present in acid
solution, ammonia in excess is added, and the solution is immediately
filtered; the quantitative results are, however, not good, the
strychnine precipitate being invariably contaminated by brucine.

Chromate and dichromate of potassium give no precipitate with neutral
salts of brucine; on the other hand, strychnine chromate is at once
formed if present. It might, therefore, be used to separate strychnine
from brucine. The author has attempted this method, but the results were
not satisfactory.

§ 402. =Physiological Action.=--The difference between the action of
strychnine and that of brucine on man or animals is not great. Mays
states that strychnine affects more the anterior, brucine the posterior
extremities. In strychnine poisoning, convulsions occur early, and
invariably take place before death; but death may occur from brucine
without any convulsions, and in any case they develop late. Brucine
diminishes local sensibility when applied to the skin; strychnine does
not.[454] In a physiological sense, brucine may be considered a diluted
strychnine. The lethality of brucine, especially as compared with
strychnine, has been investigated by F. A. Falck.[455] He experimented
on 11 rabbits, injecting subcutaneously brucine nitrate, in doses of
varying magnitude, from 100 mgrms. down to 20 mgrms. per kilogram of
body-weight. He found that brucine presented three stages of symptoms.
In the first, the respiration is quickened; in 3 of the 11 cases a
strange injection of the ear was noticed; during this period the pupils
may be dilated. In the second stage, there are tetanic convulsions,
trismus, opisthotonus, oppressed respiration, and dilated pupils. In the
third stage, the animal is moribund. Falck puts the minimum lethal dose
for rabbits at 23 mgrms. per kilo. Strychnine kills 3·06 times more
quickly than brucine, the intensity of the action of strychnine relative
to that of brucine being as 1 : 117·4. Falck has also compared the
minimum lethal dose of strychnine and brucine with the tetanising opium
alkaloids, as shown in the following table:--

[454] _Journ. Physiol._, viii. 391-403.

[455] _Brucin u. Strychnin; eine toxikologische Parallele_, von Dr. F.
A. Falck. _Vierteljahrsschr. f. gerichtl. Med._, Band xxiii. p. 78.

TABLE SHOWING THE LETHAL DOSES OF VARIOUS TETANISING POISONS.

  +-----------------------+---------------+------------+
  |                       |Minimum Lethal |            |
  |                       |Dose for every |Proportional|
  |                       |Kilogram Weight| Strength.  |
  |                       | of Rabbit.    |            |
  +-----------------------+---------------+------------+
  |                       |   Mgrms.      |            |
  |                       |               |            |
  |Strychnine nitrate,    |     0·6       |     ...    |
  |Thebaine nitrate,      |    14·4       |    24·0    |
  |Brucine nitrate,       |    23·0       |    38·33   |
  |Landanine nitrate,     |    29·6       |    49·33   |
  |Codeine nitrate,       |    51·2       |    85·33   |
  |Hydrocotarnine nitrate,|   203·8       |   339·66   |
  +-----------------------+---------------+------------+

If these views are correct, it follows that the least fatal dose for an
adult man would be 1·64 grm. (about 24·6 grains) of brucine nitrate.

[Illustration: Brucine Crystals. (_From a Photograph._)]

§ 403. Tests.--If to a solution of brucine in strong alcohol a little
methyl iodide is added, at the end of a few minutes circular rosettes of
crystal groups appear (see fig.): they are composed of methyl brucine
iodide (C₂₃H₂₅(CH₃)N₂O₄HI). Crystals identical in shape are also
obtained if an alcoholic solution of iodine, or hydriodic acid with
iodine, is added to an alcoholic solution of brucine. A solution of
strychnine gives with methyl iodide no similar reaction. Strychnine in
alcoholic solution, mixed with, brucine in no way interferes with the
test. The methyl iodide test may be confirmed by the action of nitric
acid. With that reagent it produces a scarlet colour, passing into
blood-red, into yellow-red, and finally ending in yellow. This can be
made something more than a mere colour test, for it is possible to
obtain a crystalline body from the action of nitric acid on brucine. If
a little of the latter be put in a test-tube, and treated with nitric
acid of 1·4 specific gravity (immersing the test-tube in cold water to
moderate the action), the red colour is produced. On spectroscopic
examination of the blood-red liquid a broad, well-marked absorption band
is seen, the centre of which (_see_ page 55) is between E. & F. [W. L.
about 500]. There is also a development of nitric oxide and carbon
dioxide, and the formation of methyl nitrite, oxalic acid, and kakotelin
(C₂₃H₂₆N₂O₄ + 5NHO₃ = C₂₀H₂₂N₄O₉ + N(CH₃)O₂ + C₂H₂O₄ + 2NO + 2H₂O). On
diluting abundantly with water, the kakotelin separates in yellow
flocks, and may be crystallised out of dilute hydrochloric or dilute
nitric acid in the form of yellow or orange-red crystals, very insoluble
in water, but dissolving readily in dilute acid. On removal by dilution
of the product just named, neutralisation with ammonia, and addition of
a solution of chloride of calcium, the oxalate of lime is thrown down.
The nitric acid test is, therefore, a combined test, consisting of--the
production by the action of nitric acid (1) of a red colour; (2) of
yellow scales or crystals insoluble in water; (3) of oxalic acid. No
alkaloid save brucine is known to give this reaction.

There are other methods of producing the colour test. If a few drops of
nitric acid are mixed with the substance in a test-tube, and then
sulphuric acid cautiously added, so as to form a layer at the bottom, at
the junction of the liquids a red zone, passing into yellow, is seen.

A solution of brucine is also coloured red by chlorine gas, ammonia
changing the colour into yellow.

Flückiger[456] has proposed as a test mercurous nitrate, in aqueous
solution with a little free nitric acid. On adding this reagent to a
solution of brucine salt, and gently warming, a fine carmine colour is
developed.

[456] _Archiv f. Pharm._ (3), vi. 404.

In regard to the separation of brucine from organic fluids or tissues,
the process already detailed for strychnine suffices. It is of very
great importance to ascertain whether both strychnine and brucine are
present or not--the presence of both pointing to nux vomica or one of
its preparations. The presence of brucine may, of course, be owing to
impure strychnine; but if found in the tissues, that solution of the
question is improbable, the commercial strychnine of the present day
being usually pure, or at the most containing so small a quantity of
brucine as would hardly be separated from the tissues.

    § 404. =Igasurine= is an alkaloid as yet but little studied; it
    appears that it can be obtained from the boiling-hot watery extract
    of nux vomica seeds, through precipitating the strychnine and
    brucine by lime, and evaporation of the filtrate. According to
    Desnoix,[457] it forms white crystals containing 10 per cent. of
    water of crystallisation.

[457] _Journ. Pharm._ (3), xxv. 202.

    It is said to be poisonous, its action being similar to that of
    strychnine and brucine, and in activity standing midway between the
    two.

    § 405. _Strychnic Acid._--Pelletier and Caventou obtained by boiling
    with spirit small, hard, warty crystals of an organic acid, from _S.
    ignatius_, as well as from nux vomica seeds. The seeds were first
    exhausted by ether, the alcohol solution was filtered and
    evaporated, and the extract treated with water and magnesia,
    filtered, and the residue first washed with cold water, then with
    hot spirit, and boiled lastly with a considerable quantity of water.
    The solution thus obtained was precipitated with acetate of lead,
    the lead thrown out by SH₂, and the solution evaporated, the acid
    crystallising out. It is a substance as yet imperfectly studied, and
    probably identical with malic acid.


2. THE QUEBRACHO GROUP OF ALKALOIDS.

    § 406. The bark of the _Quebracho Blanco_[458] (_Aspidosperma
    quebracho_) contains, according to Hesse’s researches, no fewer than
    six alkaloids--Quebrachine, Aspidospermine, Aspidospermatine,
    Aspidosamine, and Hypoquebrachine. The more important of these are
    _Aspidospermine_ and _Quebrachine_.

[458] See Liebig’s _Annal._, 211, 249-282; _Ber. der deutsch. Chem.
Gesellsch._, 11, 2189; 12, 1560.

    =Aspidospermine= (C₂₂H₃₀N₂O₂) forms colourless needles which melt at
    206°. They dissolve in about 6000 parts of water at 14°--48 parts of
    90 per cent. alcohol, and 106 parts of pure ether. The alkaloid
    gives a fine magenta colour with perchloric acid.

    =Quebrachine= (C₂₁H₂₆N₂O₃) crystallises in colourless needles,
    melting-point (with partial decomposition) 215°. The crystals are
    soluble in chloroform, with difficulty soluble in cold alcohol, but
    easily in hot. The alkaloid, treated with sulphuric acid, and
    peroxide of lead, strikes a beautiful blue colour. It also gives
    with sulphuric acid and potassic chromate the strychnine colours.
    Quebrachine, dissolved in sulphuric acid containing iron, becomes
    violet-blue, passing into brown. The alkaloid, treated with strong
    sulphuric acid, becomes brown; on adding a crystal of potassic
    nitrate, a blue colour is developed; on now neutralising with
    caustic soda no red coloration is perceived. Dragendorff has
    recently studied the best method of extracting these alkaloids for
    toxicological purposes. He recommends extraction of the substances
    with sulphuric acid holding water, and shaking up with solvents.
    Aspidospermine is not extracted by petroleum ether or benzene from
    an acid watery extract, but readily by chloroform or by amyl
    alcohol. It is also separated from the same solution, alkalised by
    ammonia, by either amyl alcohol or chloroform; with difficulty by
    petroleum ether; some is dissolved by benzene. Quebrachine may be
    extracted from an acid solution by chloroform, but not by petroleum
    ether. Alkalised by ammonia, it dissolves freely in chloroform and
    in amyl alcohol. Traces are taken up by petroleum, somewhat more by
    benzene. Aspidospermine is gradually decomposed in the body, but
    Quebrachine is more resistant, and has been found in the stomach,
    intestines, blood, and urine. The toxicological action of the bark
    ranks it with the tetanic class of poisons. In this country it does
    not seem likely to attain any importance as a poison.


3. PEREIRINE.

    § 407. =Pereirine=--an alkaloid from pereira bark--gives a play of
    colours with sulphuric acid and potassic bichromate similar to but
    not identical with that of strychnine. Fröhde’s reagent strikes
    with it a blue colour. On dissolving pereirine in dilute sulphuric
    acid, and precipitating by gold chloride, the precipitate is a
    beautiful red, which, on standing and warming, is deepened.
    Pereirine may be extracted from an acid solution, after alkalising
    with ammonia, by ether or benzene.


4. GELSEMINE.

    § 408. Gelsemine (C₂₂H₂₈N₂O₄) is an alkaloid[459] which has been
    separated from _Gelsemium sempervirens_, the Carolina jessamine, a
    plant having affinities with several natural orders, and placed by
    De Candolle among the _Loganiaceæ_, by Chapman among the _Rubiaceæ_
    and by Decaisne among the _Apocynaceæ_. It grows wild in Virginia
    and Florida.[460] Gelsemine is a strong base; it is yellowish when
    impure, but a white amorphous powder when pure. It fuses below 100°
    into a transparent vitreous mass, at higher temperatures it
    condenses on glass in minute drops; its taste is extremely bitter;
    it is soluble in 25 parts of ether, in chloroform, bisulphide of
    carbon, benzene, and in turpentine; it is not very soluble in
    alcohol, and still less soluble in water, but it freely dissolves in
    acidulated water. The caustic alkalies precipitate it, the
    precipitate being insoluble in excess; it is first white, but
    afterwards brick-red. Tannin, picric acid, iodised potassic iodide,
    platinic chloride, potassio-mercuric iodide, and mercuric chloride
    all give precipitates. Fröhde’s reagent gives with gelsemine a brown
    changing to green.

[459] Dr. T. G. Wormley separated, in 1870, a non-nitrogenised
remarkably fluorescent body, which he named gelsemic acid (_Amer. Journ.
of Pharm._, 1870), but Sonnenschein and C. Robbins afterwards found
gelsemic acid to be identical with æsculin (_Ber. der deutsch. Chem.
Ges._, 1876, 1182). Dr. Wormley has, however, contested this, stating
that there are differences. (_Amer. Journ. of Pharm._, 1882, p. 337.
_Yearbook of Pharmacy_, 1882, p. 169.)

[460] The following are its botanical characters:--Calyx five-parted,
corolla funnel-shaped, five-lobed, somewhat oblique, the lobes almost
equal, the posterior being innermost in bud; stamens five; anthers
oblong sagittate, style long and slender; stigmas two, each two-parted,
the divisions being linear; fruit elliptical, flattened contrary to the
narrow partition, two-celled, septicidally two-valved, the valves
keeled; seeds five to six in each cell, large, flat, and winged; embryo
straight in fleshy albumen; the ovate flat, cotyledons much shorter than
the slender radicle; stem smooth, twining and shrubby; leaves opposite,
entire, ovate, or lanceolate, shining on short petioles, nearly
persistent; flowers large, showy, very fragrant, yellow, one to five in
the axil of the leaves.

    Sulphuric acid dissolves gelsemine with a reddish or brownish
    colour; after a time it assumes a pinkish hue, and if warmed on the
    water-bath, a more or less purple colour; if a small crystal of
    potassic bichromate be slowly stirred in the sulphuric acid
    solution, reddish purple streaks are produced along the path of the
    crystal; ceric oxide exhibits this better and more promptly, so
    small a quantity as ·001 grain showing the reaction. This reaction
    is something like that of strychnine, but nitric acid causes
    gelsemine to assume a brownish-green, quickly changing to a deep
    green--a reaction which readily distinguishes gelsemine from
    strychnine and other alkaloids.

    § 409. =Fatal Dose.=--10 mgrms. killed a frog within four hours, and
    8 mgrms. a cat within fifteen minutes. A healthy woman took an
    amount of concentrated tincture, which was equivalent to 11 mgrms.
    (⅙ grain), and died in seven and a half hours.

    § 410. =Effects on Animals--Physiological Action.=--Gelsemine acts
    powerfully on the respiration; for example, Drs. Sydney Ringer and
    Murrell[461] found, on operating on the frog, that in two minutes
    the breathing had become distinctly slower; in three and a half
    minutes, it had been reduced by one-third; and in six minutes, by
    one-half; at the expiration of a quarter of an hour, it was only
    one-third of its original frequency; and in twenty minutes, it was
    so shallow and irregular that it could no longer be counted with
    accuracy. In all their experiments they found that the respiratory
    function was abolished before reflex and voluntary motion had become
    extinct. In several instances the animals could withdraw their legs
    when their toes were pinched, days after the most careful
    observations had failed to detect the existence of any respiratory
    movement. The heart was seen beating through the chest wall long
    after the complete abolition of respiration.

[461] _Lancet_, vol. i., 1876, p. 415.

    In their experiments on warm-blooded animals (cats), they noticed
    that in a few minutes the respirations were slowed down to 12 and
    even to 8, and there was loss of power of the posterior extremities,
    while at short intervals the upper half of the body was convulsed.
    In about half an hour paralysis of the hind limbs was almost
    complete, and the respiratory movements so shallow that they could
    not be counted. In the case of a dog, after all respiration had
    ceased tracheotomy was performed, and air pumped in: the animal
    recovered.

    Ringer and Murrell consider that gelsemine produces no primary
    quickening of the respiration, that it has no direct action on
    either the diaphragm or intercostal muscles, that it paralyses
    neither the phrenic nor the intercostal nerves, and that it
    diminishes the rate of respiration after both vagi have been
    divided. They do not consider that gelsemine acts on the cord
    through Setschenow’s inhibitory centre, but that it destroys reflex
    power by its direct action on the cord, and that probably it has no
    influence on the motor nerves. Dr. Burdon Sanderson has also
    investigated the action of gelsemine on the respiration, more
    especially in relation to the movements of the diaphragm. He
    operated upon rabbits; the animal being narcotised by chloral, a
    small spatula, shaped like a teaspoon, was introduced into the
    peritoneal cavity through an opening in the linea alba, and passed
    upwards in front of the liver until its convex surface rested
    against the under side of the centrum tendineum. The stem of the
    spatula was brought into connection with a lever, by means of which
    its to-and-fro movements (and consequently that of the diaphragm)
    were inscribed. The first effect is to augment the depth but not the
    frequency of the respiratory movements; the next is to diminish the
    action of the diaphragm both in extent and frequency. This happens
    in accordance with the general principle applicable to most cases of
    toxic action--viz., that paresis of a central organ is preceded by
    over-action. The diminution of movement upon the whole is
    progressive, but this progression is interrupted, because the blood
    is becoming more and more venous, and, therefore, the phenomena of
    asphyxia are mixed up with the toxical effects. Dr. Sanderson
    concludes that the drug acts by paralysing the automatic respiratory
    centre; the process of extinction, which might be otherwise expected
    to be gradual and progressive, is prevented from being so by the
    intervention of disturbances of which the explanation is to be found
    in the imperfect arterialisation of the circulating blood. Ringer
    and Murrell have also experimented upon the action of gelsemine on
    the frog’s heart. In all cases it decreased the number of beats; a
    small fatal dose produced a white contracted heart, a large fatal
    dose, a dark dilated heart; in either case arrest of the circulation
    of course followed.

    § 411. =Effects on Man.=--The preparations used in medicine are the
    fluid extract and the tincture of gelsemine; the latter appears to
    contain the resin of the root as well as the active principle. There
    are several cases on record of gelsemine, or the plant itself,
    having been taken with fatal effect.[462] Besides a marked effect on
    the respiration, there is an effect upon the eye, better seen in man
    than in the lower animals; the motor nerves of the eye are attacked
    first, objects cannot be fixed, apparently dodging their position,
    the eyelids become paralysed, droop, and cannot be raised by an
    effort of the will; the pupils are largely dilated, and at the same
    time a feeling of lightness has been complained of in the tongue; it
    ascends gradually to the roof of the mouth, and the pronunciation is
    slurred. There is some paresis of the extremities, and they refuse
    to support the body; the respiration becomes laboured, and the pulse
    rises in frequency to 120 or 130 beats per minute, but the mind
    remains clear. The symptoms occur in about an hour and a half after
    taking an overdose of the drug, and, if not excessive, soon
    disappear, leaving no unpleasantness behind. If, on the other hand,
    the case proceeds to a fatal end, the respiratory trouble increases,
    and there may be convulsions, and a course very similar to that seen
    in experimenting on animals. Large doses are especially likely to
    produce tetanus, which presents some clinical differences
    distinguishing it from strychnine tetanus. Gelsemine tetanus is
    always preceded by a loss of voluntary reflex power, respiration
    ceases before the onset of convulsions, the posterior extremities
    are most affected, and irritation fails to excite another paroxysm
    till the lapse of some seconds, as if the exhausted cord required
    time to renew its energy; finally, the convulsions only last a short
    time.

[462] See _Lancet_, 1873, vol. ii. p. 475; _Brit. Med. and Surg.
Journ._, April 1869; _Phil. Med. and Surg. Reporter_, 1861.

    § 412. _Extraction from Organic Matters, or the Tissues of the
    Body._--Dragendorff states that, from as little as half a grain of
    the root, both gelsemine and gelsemic acid may be extracted with
    acid water, and identified. On extracting with water acidified with
    sulphuric acid, and shaking up the acid liquid with chloroform, the
    gelsemic acid (æsculin?) is dissolved, and the gelsemine left in the
    liquid. The chloroform on evaporation leaves gelsemic acid in little
    micro-crystals; it may be identified by (1) its crystallising in
    little tufts of crystals; (2) its strong fluorescent properties, one
    part dissolved in 15,000,000 parts of water showing a marked
    fluorescence, which is increased by the addition of an alkali; and
    (3) by splitting up into sugar and another body on boiling with a
    mineral acid. After separation of gelsemic acid, the gelsemine is
    obtained by alkalising the liquid, and shaking up with fresh
    chloroform; on separation of the chloroform, gelsemine may be
    identified by means of the reaction with nitric acid, and also the
    reaction with potassic bichromate and sulphuric acid.


5. COCAINE.

    § 413. =Cocaine= (C₁₇H₂₁NO₄).--There are two cocaines--the one
    rotating a ray of polarised light to the left, the other to the
    right. The left cocaine is contained in the leaves of _Erythroxylon
    coca_ with other alkaloids, and is in commerce.

    Cocaine has been used most extensively in medicine since the year
    1884--its chief use being as a local anæsthetic. Chemically cocaine
    is a derivative of ecgonin, being ecgonin-methyl-ester. It has a
    pyridine nucleus, and may be written
    C₅H₄N(CH₃)--H₃CHO--(COC₆H₅)--CH₂COOCH₃, or expressed graphically as
    follows:--

     CH₂
      /\
  CH /  \CH₂
    ║   |
    ║Py |  H
    ║   | /
  CH \  /C--CHO(C₆H₅CO)--CH₂COOCH₃.
      \/
     NCH₃

    =Properties.=--Cocaine is in the form of four- to six-sided prisms
    of the monoclinic system. It is one of the few alkaloids which melt
    under the temperature of boiling water, the melting-point being as
    low as 85° in water. It readily furnishes a sublimate at 100°,
    partially decomposing. On boiling with hydrochloric acid cocaine is
    decomposed into methyl alcohol, ecgonin, and benzoic acid, according
    to the following reaction:--

                    Benzoic             Methyl
  Cocaine.           acid.   Ecgonin.  Alcohol.
  C₁₇H₂₁NO₄  + 2H₂O = C₆H₅COOH + C₉H₁₅NO₃  + CH₃OH.

    Cocaine is but little soluble in water, but easily dissolves in
    ether, alcohol, benzene, chloroform, and carbon disulphide; an
    aqueous solution is alkaline to methyl-orange, but not to
    phenol-phthalein. It can be made synthetically by the reaction of
    ecgonin-methyl-ester with benzoyl chloride.

§ 414. =Cocaine Hydrochlorate= (C₁₇H₂₁NO₄HCl).--Crystallised from
alcohol, cocaine hydrochlorate appears in prismatic crystals; these
crystals, according to Hesse,[463] when perfectly pure, should melt at
186°, although the melting-point is generally given as 200° or even
202°. Cocaine hydrochlorate is soluble in half its weight of water,
insoluble in dry ether, but readily soluble in alcohol, amyl alcohol, or
chloroform.

[463] O. Hesse, _Annalen_, 276, 342-344.

§415. =Pharmaceutical Preparations.=--Cocaine hydrochlorate is
officinal. Gelatine discs, weighing 1·31 mgrms. (1/50 grain), and each
containing 0·33 mgrm. (1/200 grain) of the salt are officinal, and used
by ophthalmic surgeons. A solution of the hydrochlorate, containing 10
per cent. of cocaine hydrochlorate and (for the purposes of preserving
the solution) 0·15 per cent. of salicylic acid is also officinal.
Stronger solutions may also be met with; for instance, a 20 per cent.
solution in oil of cloves for external application in cases of
neuralgia.

§416. =Separation of Cocaine and Tests.=--Cocaine may be shaken out of
solutions made slightly alkaline by ammonia by treatment with benzene;
it also passes into petroleum ether under the same circumstances. The
best method is to extract a solution, made feebly alkaline, thoroughly
by ether, and then shake it out by benzene and evaporate the separated
benzene at the ordinary air temperature. The property of the alkaloid to
melt at or below the temperature of boiling water, and the ready
decomposition into benzoic acid and other products, render cocaine easy
of identification. If, for instance, a small particle of cocaine is put
in a tube, a drop of strong sulphuric acid added and warmed by the
water-bath, colourless crystals of benzoic acid sublime along the tube,
and an aromatic odour is produced.

Flückiger has recommended the production of benzoate of iron as a useful
test both for cocaine and for cocaine hydrochlorate.

One drop of a dilute solution of ferric chloride added to a solution of
20 mgrms. of cocaine hydrochlorate in 2 c.c. of water, gives a yellow
fluid, which becomes red on boiling from the production of iron
benzoate. This reaction is of little use unless a solution of the same
strength of ferric chloride, but to which the substance to be tested has
not been added, is boiled at the same time for comparison, because all
solutions of ferric chloride deepen in colour on heating.

A solution of the alkaloid evaporated to dryness on the water-bath,
after being acidulated with nitric acid, and then a few drops of
alcoholic solution of potash or soda added, develops an odour of benzoic
ethyl-ester. Cocaine hydrochlorate, when triturated with calomel,
blackens by the slightest humidity or by moistening it with alcohol.
Cocaine in solution is precipitated by most of the group reagents, but
is not affected by mercuric chloride, picric acid, nor potassic
bichromate.

Added to the tests above mentioned, there is the physiological action;
cocaine dilates the pupil, tastes bitter, and, for the time, arrests
sensation; hence the after-effect on the tongue is a sensation of
numbness.

§ 417. =Symptoms.=--A large number of accidents occur each year from the
external application of cocaine; few, however, end fatally. Cocaine has
thus produced poisonous symptoms when applied to the eye, to the rectum,
to the gums, to the urethra, and to various other parts. There have been
a few fatal cases, both from its external and internal administration;
Mannheim, for example, has collected eleven of such instances.

The action of cocaine is twofold; there is an action on the central and
the peripheral nervous system. In small doses cocaine excites the spinal
cord and the brain; in large it may produce convulsions and then
paralysis. The peripheral action is seen in the numbing of sensation.
There is always interference with the accommodation of vision, and
dilatation of the pupil. The eyelids are wider apart than normal, and
there may be some protrusion of the eyeball.

The usual course of an acute case of poisoning is a feeling of dryness
in the nose and throat, difficulty of swallowing, faintness, and there
is often vomiting; the pulse is quickened; there is first cerebral
excitement, followed usually by great mental depression. Occasionally
there is an eruption on the skin. Hyperæsthesia of the skin is followed
by great diminution of sensation, the pupils, as before stated, are
dilated, the eyes protruding, the eyelids wide open, the face is pale,
and the perspiration profuse. Convulsions and paralysis may terminate
the scene. Death takes place from paralysis of the breathing centre;
therefore the heart beats after the cessation of respiration. As an
antidote, nitrite of amyl has apparently been used with success.

There is a form of chronic poisoning produced from the taking of small
doses of cocaine daily. The symptoms are very various, and are referable
to disturbance of the digestive organs, and to the effect on the nervous
system. The patients become extremely emaciated, and it seems to produce
a special form of mania.

§ 418. =Post-mortem Appearances.=--The appearances found in acute cases
of poisoning have been hyperæmia of the liver, spleen, and kidneys, as
well as of the brain and spinal cord.

In the experimental poisoning of mice with cocaine Ehrlich[464] found a
considerable enlargement of the liver.

[464] _Deutsche med. Wochens._, 1890, No. 32.

§ 419. =Fatal Dose.=--The fatal dose, according to Mannheim,[465] must
be considered as about 1 grm. (15·4 grains); the smallest dose known to
have been fatal is 0·08 grm. (1·2 grain) for an adult, and 0·05 grm.
(0·7 grain) for a child.

[465] _Deutsch. Arch. f. klin. Med._, Bd. viii., 1891, 380.


6. CORYDALINE.

    § 420. =Corydaline= (C₂₂H₂₈NO₄) is an alkaloid discovered by
    Wackenroder (1826) in the tubers of _Corydalis tuberosa_;
    crystallised in the cold and away from light, out of a mixture of
    absolute alcohol and ether, corydaline forms colourless, flat,
    prismatic crystals, which quickly turn yellow on exposure to light
    or heat. Pure corydaline changes colour at about 125°, softens at
    about 133°, and melts finally at 134° to 135°. It dissolves in
    ether, chloroform, carbon disulphide, and benzene, but not so
    readily in alcohol. It is almost insoluble in cold water, and but
    slightly soluble in boiling water. Water precipitates it from a
    solution in alcohol. It is also soluble in dilute hydrochloric and
    sulphuric acids. It gives a precipitate with potassium iodide if a
    solution of the hydrochloride be used. The precipitate crystallises
    out of hot water in clusters of short lemon-yellow prismatic
    crystals, and has the formula of C₂₂H₂₈NO₄HI. Corydaline
    platinochloride has the composition of (C₂₂H₂₈NO₄)₂H₂PtCl₆,
    containing Pt 16·94 per cent., and 2·44 per cent. of N.--Dobbie &
    Lauder, _Journ. Chem. Soc._, March 1892, 244.

    Corydaline in large doses causes epileptiform convulsions. Death
    takes place from respiratory paralysis.


V.--The Aconite Group of Alkaloids.

§ 421. The officinal aconite is the _Aconitum napellus_--monkshood or
wolfsbane--a very common garden plant in this country, and one
cultivated for medicinal purposes. Many varieties of aconite exist in
other regions, which either are, or could be, imported. Of these the
most important is the _Aconitum ferox_, a native of the Himalayan
mountains, imported from India.

All the aconites, so far as known, are extremely poisonous, and it
appears probable that different species contain different alkaloids. The
root of _A. napellus_ is from 2 to 4 inches long, conical in shape,
brown externally, and white internally. The leaves are completely
divided at the base into five wedge-shaped lobes, each of the five lobes
being again divided into three linear segments. The numerous seeds are
three-sided, irregularly twisted, wrinkled, of a dark-brown colour, in
length one-sixth of an inch, and weighing 25 to the grain (_Guy_). The
whole plant is one of great beauty, from 2 to 6 feet high, and having a
terminal spike of conspicuous blue flowers. The root has been fatally
mistaken for horse-radish, an error not easily accounted for, since no
similarity exists between them.

§ 422. =Pharmaceutical Preparations of Aconite.=--The preparations of
aconite used in medicine are--

=Aconitine=, officinal in all the pharmacopœias.

=Aconite liniment= (=linimentum aconiti=), made from the root with
spirit, and flavoured with camphor; officinal in the British
Pharmacopœia. It may contain about 2·0 per cent. of aconitine.

=Aconite tincture=, officinal in all the pharmacopœias.

=Aconite ointment=, 8 grains of aconitine to the oz. (_i.e._, 1·66 per
cent.); officinal in the British Pharmacopœia.

=Aconite extract=, the juice of the leaves evaporated; officinal in most
of the pharmacopœias. The strength in alkaloid of the extract varies; in
six samples examined by F. Casson, the least quantity was 0·16 per
cent., the maximum 0·28 per cent.[466]

[466] _Pharm. Journ._, 1894, 901.

=Fleming’s tincture of aconite= is not officinal, but is sold largely in
commerce. It is from three to four times stronger than the B.P.
tincture.

§ 423. =The Alkaloids of Aconite.=--The researches of Dr. Alder Wright
and Luff, and especially those of Professor Dunstan,[467] have
established that in the root of the true aconite there exist four
alkaloids, one only of which has been as yet crystallised.

[467] Various papers in _Journ. Chem. Soc._, 1892-1894.

Three of the alkaloids have been fairly well worked out; the fourth
homo-napelline has not yet been satisfactorily investigated.

The three alkaloids are aconitine, aconine and benzoyl-aconine; besides
which pyraconitine and pyraconine can be obtained by suitable treatment
from aconitine and aconine.

The formulæ of the alkaloids and their derivatives are as follows:--

  Aconitine (acetyl-benzoyl-aconine),         m.p., 188·60°, C₃₃H₄₅NO₁₂
  Benzoyl-aconine,                            m.p., 268·0°, C₃₁H₄₃NO₁₁
  Pyraconitine (anhydro-benzoyl-aconine),     m.p., 188-190°, C₃₁H₄₁NO₁₀
  Aconine,                                    m.p., 132°, C₂₄H₃₉NO₁₀
  Pyraconine (anhydro-aconine),                          C₂₄H₃₇NO₉

§ 424. =Aconitine=, C₃₃H₄₅NO₁₂.--This base has been shown by Dunstan to
be acetyl-benzoyl-aconine; one molecule of the base breaking up, on
complete hydrolysis, into one molecule of aconine, one of acetic acid,
and one of benzoic acid--

                  Acetic  Benzoic
                   Acid.   Acid.   Aconine.
  C₃₃H₄₅NO₁₂ + 2H₂O = C₂H₄O₂ + C₇H₆O₂ + C₂₄H₃₉NO₁₀.

That is to say that 100 parts of aconitine, according to theory, should
yield:--

Acetic acid, 9·37 per cent.; benzoic acid, 18·85 per cent.; and aconine,
77·52 per cent.

Pure aconitine has a tube melting-point of 188·6°. The behaviour of a
sample of Merck’s aconitine in the subliming cell, which had a
melting-point of 184°, was as described at page 259.

Aconitine dissolves in water at 22° in the proportion of 1 in 4431
(_Dunstan_); it is soluble in 37 of absolute alcohol, 64 of anhydrous
ether, 5·5 parts of chloroform and benzene (_A. Jurgens_); it has basic
properties, and a cold watery solution has an alkaline reaction to
cochineal, but not to litmus nor to phenol-phthalein. Aconitine is not
precipitated by mercuric potassium iodide, but gives a voluminous
precipitate with an aqueous solution of iodine in potassium iodide.

It gives a crystalline yellow gold compound with gold chloride, which
has a melting-point of 135·5°, and according to its composition,
C₃₃H₄₅NO₁₂HAuCl₄, should give 19·9 per cent. of gold.

Aconitine is best extracted from the plant, or from organic matters
generally, by a 1 per cent. sulphuric acid; this strength is stated not
to hydrolyse aconitine if acting in the cold; after purifying the acid
liquid by shaking it with amyl alcohol, and then with chloroform,
_always operating in the cold_, the liquid is precipitated by ammonia in
very slight excess, and the liquid shaken with ether; the ether is
removed, dehydrated by standing over calcium chloride, and then
evaporated spontaneously; should the aconitine be mixed with the other
alkaloids, advantage can be taken of the method of separating
aconitine by converting it into hydrobromide, as described under
“Benzoyl-aconine.”

§ 425. =Tests for Aconitine.=--The most satisfactory and the most
delicate is the physiological test; the minutest trace of an
aconite-holding liquid, applied to the tongue or lips, causes a peculiar
numbing, tingling sensation which, once felt, can readily be remembered.

An alkaloidal substance which, heated in a tube, melts approximately
near the melting-point of aconitine, and gives off an acid vapour, would
render one suspicious of aconitine, for most alkaloids give off alkaline
vapours. Aconitine also may, by heating with dilute acids, be made to
readily yield benzoic acid, an acid easy of identification. Aconitine
dissolved in nitric acid, evaporated to dryness, and then treated with
alcoholic potash, gives off an unmistakable odour of benzoic ester.

Should there be sufficient aconitine recovered to convert it into the
gold salt, the properties of the gold salt (that is, its melting-point,
and the percentage of gold left after burning) assist materially in the
identification.

A minute quantity of aconitine dissolved in water, acidified with
acetic acid, and a particle of KI added and the solution allowed to
evaporate, gives crystals of aconitine hydriodide, from which water will
dissolve out the KI. Iodine water gives a precipitate of a reddish-brown
colour in a solution of 1 : 2000.[468]

[468] A. Jurgens, _Arch. Pharm._ (3), xxiv. 127, 128.

The chemical tests are supplementary to the physiological; if the
alkaloidal extract does not give the tingling, numbing sensation,
aconitine cannot be present.

§ 426. =Benzoyl-aconine (“isaconitine”)=, C₃₁H₄₃NO₁₁, is obtained from
aconitine by heating an aqueous solution of the sulphate or
hydrochloride in a closed tube at 120°-130° for two or three hours, a
molecule of acetic acid (9·27 per cent.) being split off, and
benzoyl-aconine left.

It may be separated from the mixed alkaloids of the _Aconitum napellus_
by dissolving in a 5 per cent. solution of hydrobromic acid (excess of
acid being avoided), precipitating with a slight excess of ammonia, and
shaking out with ether. The residue left after the ether is evaporated
chiefly consists of aconitine; it is dissolved in just sufficient
hydrobromic acid and the exactly neutral hydrobromate solution allowed
to evaporate spontaneously in a desiccator; crystals of aconitine
hydrobromide separate out, the mother liquor containing some
benzoyl-aconine and “homonapelline.” The aqueous solution which has been
exhausted with ether is now shaken out with chloroform. This chloroform
solution contains most of the benzoyl-aconine, and on separation the
residue is dissolved in just sufficient hydrochloric acid to form a
neutral solution; this solution is concentrated on the water-bath with
constant stirring, crystals of the hydrochloride form, and are filtered
off from time to time and washed with a little cold water, the washings
being added to the original liquid; the different fractions are mixed
together, and the process repeated until they have a melting-point of
268°. Benzoyl-aconine is obtained from the hydrochloride by
precipitating the aqueous solution by the addition of dilute ammonia,
and extracting the solution with ether; the solution in ether is washed
with water, dried by means of calcium chloride, and then distilled off.
Benzoyl-aconine is left as a transparent colourless non-crystalline
varnish of a melting-point near 125°.

The solution in water is alkaline to litmus. The base is readily soluble
in alcohol, in chloroform, and in ether. The alcoholic solution is
dextrorotatory. The solutions are bitter, but do not give the tingling
sensation characteristic of aconitine. The hydrochloride, the
hydrobromide, the hydriodide, and the nitrate have been obtained in a
crystalline state. The most characteristic salt is, however, the
aurochlor derivative. When aqueous solutions of benzoyl-aconine chloride
and auric chloride are mixed, a yellow precipitate is thrown down,
which (dissolved in alcohol, after being dried over calcium chloride,
and slowly evaporated in a desiccator) deposits colourless crystals
entirely different from the yellow crystals of aconitine gold chloride.
These crystals have the composition C₃₁H₄₂(AuCl₂)NO₁₁, and therefore, by
theory, should yield 22·6 per cent. of gold, and 8·2 per cent. of
chlorine.

By hydrolysis benzoyl-aconine yields benzoic acid, which can be shaken
out of an acid solution by ether and identified; one molecule of benzoic
acid is formed from one molecule of benzoyl-aconine. Twenty per cent. of
benzoic acid should, according to the formula, be obtained; Professor
Dunstan found only 18·85 per cent.[469]

[469] Professor Dunstan found, as a means of two determinations, 21·6
per cent. of gold, and 7·8 per cent. of chlorine, which comes nearer his
old formula of C₃₃H₄₄(AuCl₂)NO₁₂.--_Journ. Chem. Soc._, April 1893.

Benzoic acid in the subliming cell begins to give a cloud at about
77°-80°, and at or near 100° sublimes most rapidly.

Benzoic acid, recovered from an acid solution by shaking out with ether,
may be recognised as follows:--To the film left on evaporating off the
ether add a drop of H₂SO₄, and a few crystals of sodic nitrate, and heat
gently for a short time; pour the clear liquid into ammonia water, and
add a drop of ammonium sulphide. A red-brown colour indicates benzoic
acid. The _rationale_ of the test is as follows:--Dinitro-benzoic acid
is first formed, and next, by the action of ammonium sulphide, this is
converted into the red-brown ammonium diamidobenzoate.--E. Mohler,
_Bull. Soc. Chem._ (3), iii. 414-416.

§ 427. =Pyraconitine=, C₃₁H₄₁NO₁₀, is anhydro-benzoyl-aconine; it
differs from benzoyl-aconine by a molecule of water; picraconitine is
obtained by keeping aconitine at its melting-point (188°-190°) for some
time, when acetic acid distils over and pyraconitine is left.
Pyraconitine is an amorphous varnish, sparingly soluble in water, but
readily dissolving in alcohol, chloroform, and ether; it gives a pale
yellow precipitate with gold chloride, and forms crystalline salts with
hydriodic, hydrobromic, and hydrochloric acids. Pyraconitine readily
undergoes hydrolysis by the action of dilute acids, or by potash or
soda, or with water in a closed tube; the products are benzoic acid and
an alkaloid, to which the name of pyraconine has been given.

§ 428. =Pyraconine=, C₂₄H₃₇NO₉.--This base is anhydro-aconine, the
formula differing from aconine by one atom of water. It is amorphous,
closely resembling aconine; it is soluble in water and ether; the
aqueous solution has a somewhat sweet taste, and is lævorotatory; it
combines with acids to form crystalline salts, which are very soluble in
water.

§ 429. =Aconine=, C₂₄H₃₉NO₁₀, m.p. 132°.--Aconine does not crystallise.
Its aqueous solution is decidedly alkaline, and, like aconitine, it is
lævorotatory, although to a less degree. Its taste is bitter, but causes
no tingling sensation. Aconine is very soluble in water or alcohol, and
slightly in chloroform, but insoluble in ether or in petroleum ether. It
does, however, dissolve, in the presence of aconitine, slightly in
ether. The aqueous solutions reduce the salts of gold and silver, and
also Fehling’s solution. A solution of aconine gives precipitates with
the general alkaloidal reagents; with mercuric chloride it gives a
copious yellow precipitate, which darkens on standing.

Aconine hydrochloride, the hydriodide, the hydrobromide, and the
sulphate, have all been crystallised; solutions of these salts are
lævorotatory.

§ 430. =Commercial Aconitine and the Lethal Dose of
Aconitine.=--Commercial aconitine has in the past varied in appearance
from that of a gummy amorphous mass up to a purer kind in white
crystals.

Professor Dunstan[470] has recently examined fourteen samples, some of
them of considerable age, and only found two samples (one of English,
another of German make) which approached in melting-point and
crystalline appearance pure aconitine; the one, the English, melted at
186°-187°, and contained about 3 per cent. of benzoyl-aconine; the
other, a German specimen, was almost pure; the melting-point was 187·5°.
At the present time it is, however, not difficult to obtain fairly pure
crystalline aconitine, and to assay it accurately by determining the
proportion of acetic and benzoic acids. The physiological action of
commercial aconitine is, however, in all cases the same, the difference
being in quantitative not qualitative action; in the small doses usually
administered, the physiological action depends wholly upon the true
aconitine present, the other bases being practically without toxic
action. Professor Plugge[471] has made some researches on the fatal dose
(for the lower animals) of Petit’s, Merck’s, and Friedländer’s aconitine
nitrate, which in 1882 were the purest in commerce. He administered the
following doses to the animals mentioned:--

[470] _Journ. Chem. Soc. Trans._, 1893, 491.

[471] _Archiv de Pharm._, Jan. 7, 1882.

TABLE SHOWING FATAL DOSES (FOR ANIMALS) OF ACONITINE.

PETIT’S CRYSTALLINE ACONITINE NITRATE.

  +--------------+------------+-----------+----------------------+
  |   Animals    |   Dose     |  Dose     |                      |
  |Experimented  |  Given.    |   per     |       Result.        |
  |    upon.     |            | Kilogrm.  |                      |
  +--------------+------------+-----------+----------------------+
  | A Frog,      |   ·4 mgrm. |   16·0    | Death in 60 Minutes. |
  | A Rabbit,    |   ·8  „    |  ·5-·6    |     „    30    „     |
  | A Dog,       |  1·6  „    |     ·21   |     „    20    „     |
  |   „          |   ·45 „    |     ·10   |     „   140    „     |
  |   „          |   ·50 „    |     ·054  | Recovered.           |
  |   „          |   ·60 „    |     ·075  | Recovered.           |
  | A Pigeon,    |   ·07 „    |     ·22   | Death in 21 Minutes. |
  +--------------+------------+-----------+----------------------+

MERCK’S ACONITINE NITRATE.

  +--------------+------------+-----------+----------------------+
  |   Animals    |   Dose     |  Dose     |                      |
  |Experimented  |  Given.    |   per     |       Result.        |
  |    upon.     |            | Kilogrm.  |                      |
  +--------------+------------+-----------+----------------------+
  | A Frog,      |   ·4 mgrm. |   16      | Recovered.           |
  |   „          |  1·0  „    |   40      | Died in 110-360 Min. |
  |   „          |  2·0  „    |   80      |     „    75-130  „   |
  |   „          |  4·0  „    |  160      |     „    50      „   |
  | A Rabbit,    |  3·5  „    |    2      |     „    75      „   |
  |   „          | 10    „    |    6·50   |     „    15      „   |
  | A Dog,       | 10    „    |    1·65   |     „    15      „   |
  | A Pigeon,    |   ...      |    1·65   | Recovered.           |
  +--------------+------------+-----------+----------------------+

FRIEDLÄNDER’S ACONITINE NITRATE.

  +--------------+------------+-----------+----------------------+
  |   Animals    |   Dose     |  Dose     |                      |
  |Experimented  |  Given.    |   per     |       Result.        |
  |    upon.     |            | Kilogrm.  |                      |
  +--------------+------------+-----------+----------------------+
  | A Frog,      |  4 mgrms.  |  160      | Recovered.           |
  |              |            |           |                      |
  |   „          | 10   „     |  400    } | Death in             |
  |   „          | 20   „     |  800    } | more than            |
  |   „          | 40   „     | 1600    } | 60 minutes.          |
  |              |            |           |                      |
  | A Rabbit,    |  6   „     |    4·11   | Recovered.           |
  |   „          | 24   „     |   18·00   |     „                |
  |   „          | 50   „     |   85·50   |     „                |
  | A Dog,       | 28   „     |    6·00   |     „                |
  | A Pigeon,    | 10   „     |   33·4    |     „                |
  +--------------+------------+-----------+----------------------+

The conclusions Plugge draws from his researches are that Petit’s
aconitine was at least eight times stronger than that of Merck, and
seventy times more toxic than that of Friedländer, while Merck’s
“aconitine again was twenty to thirty times stronger than
Friedländer’s.” He was inclined to put seven commercial samples which he
has examined in the following diminishing order of toxicity:--(1)
Petit’s crystalline aconitine nitrate; (2) Morson’s aconitine nitrate;
(3) Hottot’s aconitine nitrate; (4) Hopkins & Williams’ pseudaconitine;
(5) Merck’s aconitine nitrate; (6) Schuchart’s aconitine sulphate; and
(7) Friedländer’s aconitine nitrate.

From a study of Dr. Harley’s experiments,[472] however, made a few years
ago, there would appear to have been but little difference between the
activity of Petit’s and Morson’s aconitine. Dr. Harley experimented on a
young cat, 3 lbs. in weight, and nearly killed it with a 1/1000 of a
grain of Morson’s aconitine; two other cats, also weighing 3 lbs. each,
died in seven and a half hours and three-quarters of an hour
respectively, killed from a subcutaneous dose of of a grain. Reducing
these values to the ordinary equivalents, the dose, after which the cat
recovered with difficulty, is equal to about ·048 mgrm. per kilo.,
while a certainly fatal dose is ·092 mgrm. per kilo.; therefore, it
seems likely that the least fatal dose for Morson’s, as for Petit’s, is
some number between ·075 and ·09 mgrm. per kilo.

[472] “On the Action and Use of Aconitine,” _St. Thos. Hosp. Report_,
1874.

Man is evidently more sensitive to aconitine than any of the dogs or
cats experimented upon, since, in the German cases to be recorded, 1·6
mgrm. of Petit’s aconitine nitrate, taken by the mouth, gave rise to
symptoms so violent that it was evidently a dangerous dose, while 4
mgrms. were rapidly fatal; but if man took the same amount per kilo. as
dogs or cats, he would require a little over 6 mgrms. to be certainly
fatal. It seems, then, from the evidence obtainable, that ·03 grain (2
mgrms.) is about the least fatal dose for an adult man of standard
weight. This dose is equal to ·028 mgrm. per kilo., and, of course,
refers either to Morson’s aconitine or French aconitine, the alkaloid
being taken by the mouth. If given by subcutaneous injection, probably
1·5 mgrm. would kill, for the whole of the poison is then thrown on the
circulation at one time, and there is no chance of its elimination by
vomiting.

The lethal dose of the pure alkaloid being even approximately settled,
it is possible to get a more exact idea as to the suitable medicinal
dose of the tincture and extract, and also to study more profitably the
“quantitative toxicity.” The English officinal tincture, although
variable in strength, may for our purposes be regarded as averaging 1
per cent. of alkaloid--that is, in every 100 parts by volume there will
be 1 part of the alkaloid by weight, and Fleming’s tincture may be
considered as one-third stronger, containing in every 100 parts 1·3 part
of alkaloid. The medicinal dose of the P.B. tincture is laid down as
from 5 to 15 min.--equal to from ·005 to ·015 grain of aconitine. The
German pharmacopœia gives the maximum single dose as 1 c.c. (say 15
mins.), and the maximum quantity to be taken in the twenty-four hours as
four times that quantity. As before stated, 2 mgrms. (·030 grain) of
aconitine being considered a fatal dose, this is equivalent to about 2
c.c. (30 mins.) of the P.B. tincture, or to 1·2 c.c. (20 mins.) of
Fleming’s tincture in a single dose; and on these theoretical grounds I
should consider this dose dangerous, and in the absence of prompt
treatment likely to be fatal to an adult man. The usual least fatal dose
laid down in medical toxicological works, however, is greater than
this--viz., 3·75 c.c. (a drachm).

In 1863 a woman took 70 minims of Fleming’s tincture, and a grain of
acetate of morphine, and died in about four hours; but as this was a
complex case of poisoning, it is not of much value. Fifteen minims of
the tincture caused very serious symptoms in the case of a woman under
the care of Dr. Topham,[473] the effects lasting many hours. Probably
the smallest quantity of the tincture recorded as having destroyed life
is in the case of Dr. Male, of Birmingham.[474] He died from the
effects of 80 drops taken in ten doses, extending over a period of four
days--the largest dose at any one time being 10 drops, the total
quantity would perhaps equal ·08 grain of aconitine.

[473] _Lancet_, July 19, 1851, p. 56.

[474] _Med. Gaz._, vol. xxxvi. p. 861, quoted by Taylor, _Prin. of Med.
Juris._, vol. i. p. 426.

The P.B. extract is not a very satisfactory preparation, varying much in
strength. It may be taken to average about ·6 per cent., and if so,
applying the same reasoning as before, from ·26 to ·32 grm. (4 to 5
grains) would be a fatal dose.[475] On the other hand, there is an
alcoholic extract which is very powerful, and averages 5 per cent. of
aconitine: 40 mgrms. (·6 grain) of this extract would be likely to be
fatal. With regard to the root itself, 3·8 grms. (60 grains) have been
known to produce death, and from the average alkaloidal contents it is
probable that ·648 grm. (10 grains) would be a highly dangerous dose.
Dunstan’s researches will now alter probably the whole of the pharmacy
of aconite, and the tendency will be to make the preparations of greater
activity, and, consequently, to make the dangerous doses smaller than
formerly.

[475] But there is a case reported by Dr. Vachell, of Cardiff, in which
2 grains of extract of aconite taken in pills proved fatal. Now 2 grains
is the medicinal dose, laid down as a maximum in the pharmacopœia; a
complete revolution is, therefore, necessary in the use of these active
remedies. No extract or tincture should be used until its approximate
strength in active principles is determined.

§ 431. =Effects of Aconitine on Animal Life.=--There are few substances
which have been experimented upon in such a variety of ways and upon so
many classes of animals as aconitine in different forms; but there does
not seem to be any essential difference in the symptoms produced in
different animals save that which is explained by the organisation of
the life-form under experiment.

=Insects.=--The author has made experiments with the active principles
of aconite upon blow-flies. An extract was made by allowing the ordinary
tincture to evaporate spontaneously at the temperature of the
atmosphere. If a minute dot of this is placed upon the head of a
blow-fly, absorption of the active principle takes place in from fifteen
to thirty minutes, and marked symptoms result. The symptoms consist
essentially of muscular weakness, inability to fly, and to walk up
perpendicular surfaces; there is also, in all cases, a curious
entanglement of the legs, and very often extrusion of the proboscis;
trembling of the legs and muscular twitchings are frequent. A
progressive paralysis terminates in from four to five hours in death;
the death is generally so gradual that it is difficult to know when the
event occurs, but in one case there were violent movements of the body,
and sudden death.[476]

[476] It may be well to quote in full a typical experiment. Six P.M., a
little extract smeared on the head of a blow-fly. Forty-five minutes
after--makes no attempt to fly, great muscular weakness, no trembling or
convulsive movements. Fifty minutes after--partial paralysis of right
half of body, so that the fly, on moving, goes in a circular direction,
the second pair of legs are curiously bent forward and useless; the
wings seem fairly strong. Seventy-five minutes--fly very dull, always in
one spot, without movement; when placed on a horizontal glass surface,
and the glass then very slowly inclined, until it is at last quite
perpendicular, the fly falls. There is now a strange entanglement of the
legs. 125 minutes--perfectly paralysed; 145 minutes--dead.

=Fish.=--The action on fish has been studied by Schulz and Praag. There
is rapid loss of power and diminished breathing; the respiration seems
difficult, and the fish rapidly die.

=Reptiles--Frogs.=--The most recent experiments on frogs are those of
Plugge, and although his interpretation of the phenomena in some points
is different from that of previous observers, the symptoms themselves
are, as might have been expected, not different from those described by
Achscharumow, L. v. Praag, and others. Plugge found no qualitative
difference in the action of any of the commercial samples of aconitine.
This fact gives the necessary value to all the old experiments, for we
now know that, although they were performed with impure or weak
preparations, yet there is no reason to believe that the symptoms
described were due to any other but the alkaloid aconitine in varying
degrees of purity or dilution. Frogs show very quickly signs of weakness
in the muscular power; the respiration invariably becomes laboured, and
ceases after a few minutes; the heart’s action becomes slowed,
irregular, and then stops in diastole. The poisoned heart, while still
pulsating, cannot be arrested either by electrical stimulation of the
vagus or by irritation of the sinus, nor when once arrested can any
further contraction be excited in it. Opening of the mouth and apparent
efforts to vomit, Plugge observed both with _Rana esculenta_ and _Rana
temporaria_. He considers them almost invariable signs of aconitine
poisoning. A separation of mucus from the surface of the body of the
frog is also very constantly observed. Dilatation of the pupils is
frequent, but not constant; there may be convulsions, both of a clonic
and tonic character, before death, but fibrillar twitchings are seldom.
(With regard to the dose required to affect frogs, see _ante_, pp. 355
and 356.)

=Birds.=--There is a discrepancy in the descriptions of the action of
aconitine on birds. L. v. Praag thought the respiration and circulation
but little affected at first; while Achscharumow witnessed in pigeons
dyspnœa, dilatation of the pupils, vomiting, shivering, and paresis. It
may be taken that the usual symptoms observed are some difficulty in
breathing, a diminution of temperature, a loss of muscular power
generally (but not constantly), dilatation of the pupils, and
convulsions before death.

=Mammals.=--The effects vary somewhat, according to the dose. Very large
doses kill rabbits rapidly. They fall on their sides, are violently
convulsed, and die in an asphyxiated condition; but with smaller doses
the phenomena first observed are generally to be referred to the
respiration. Thus, in an experiment on the horse, Dr. Harley found that
the subcutaneous administration of ·6 mgrm. (·01 grain) caused in a
weakly colt some acceleration of the pulse and a partial paralysis of
the dilator narium. Double the quantity given to the same animal some
time after, caused, in six hours and a half, some muscular weakness, and
an evident respiratory trouble. The horse recovered in eighteen hours.
2·7 mgrms. (1/24 grain) given in the same way, after a long interval of
time, caused, at the end of an hour, more pronounced symptoms; the
pulse, at the commencement 50, rose in an hour and a half to 68, then
the respiration became audible and difficult. In an hour and
three-quarters there were great restlessness and diminution of muscular
power. Two hours after the injection the muscular weakness increased so
much that the horse fell down; he was also convulsed. After eight hours
he began to improve. In another experiment, 32·4 mgrms. (½ grain) killed
a sturdy entire horse in two hours and twenty minutes, the symptoms
commencing within the hour, and consisting of difficulty of breathing,
irregularity of the heart’s action, and convulsions.

The general picture of the effects of fatal, but not excessive, doses
given to dogs, cats, rabbits, &c., resembles closely that already
described. The heart’s action is at first slowed, then becomes quick and
irregular, there is dyspnœa, progressive paralysis of the muscular
power, convulsions, and death in asphyxia. Vomiting is frequently
observed, sometimes salivation, and very often dilatation of the pupil.
Sometimes the latter is abnormally active, dilating and contracting
alternately. Diarrhœa also occurs in a few cases. Vomiting is more
frequent when the poison is taken by the mouth than when administered
subcutaneously.[477]

[477] The more important physiological researches on the action of
aconite are contained in the following works and papers:--

    FLEMING, A.--_An Inquiry into the Physiological and Medicinal
    Properties of the Aconitum napellus_, to which are added
    observations on several other species of aconite, 8vo, Lond., 1845.

    SCHULZ, F. W.--_De Aconitini Effectu in Organismum Animalium._

    V. PRAAG.--_Arch. f. Path. Anat._, vii. p. 438, 1854.

    HOTTOT, E.--_De l’Aconitine et de ses Effets Physiologiques_, 4to,
    Paris, 1863.

    ACHSCHARUMOW.--_Arch. f. Anatom. u. Physiol._, 1866.

    BÖHN.--_Herzgifte_, 1871.

    EWERS, C.--_Ueber die physiologischen Wirkungen des aus Aconitum
    ferox dargestellten Aconitins_ (_Pseudoaconitin, Aconitinum
    anglicum, Nepalin_), 8vo, Dorpat, 1873.

    GUILAUD.--_De l’Aconite et de l’Aconitine_, 4to, Montpellier, 1874.

    FRANCHESCHINI, M. A.--_Contribution a l’Étude de l’Action
    Physiologique et Thérapeutique de l’Aconitine_, 4to, Paris, 1875.

    LEWIN.--_Exp. Untersuch. über die Wirkung d. Aconitins auf’s Herz.
    Diss._, Berlin, 1875.

    GIULINI, P.--_Experimentelle Untersuchungen ueber die Wirkung des
    Aconitins auf das Nervensystem, das Herz, u. die Athmung_, 8vo,
    Erlangen, 1876.

    HARLEY, DR. JOHN.--“On the Action and Uses of Aconitia,” _St. Thos.
    Hosp. Reports_, 1874.

    V. SCHROFF, C. Jr.--_Beitrag zur Kenntniss des Aconit._, 8vo, Wien,
    1876.

    PLUGGE, P. C.--“Untersuchungen ueber die physiologische Wirkung
    verschiedener Handelssorten von Aconitin, u. Pseudoaconitin auf
    Muskeln u. Nerven,” _Virch. Archiv_, Bd. 87, 1882, S. 410.


§ 432. =Statistics.=--During the ten years, 1883-92, there were recorded
in England and Wales, 40 accidental deaths from the various forms of
aconite (19 males, 21 females); and 19 suicidal deaths (9 males, 10
females) from the same cause, which makes a total of 59.

§ 433. =Effects on Man.=--I have collected from European medical
literature, 87 cases of poisoning by aconite in some form or other.
These comprise only 2 cases of murder, 7 of suicide, and 77 which were
more or less accidental. Six of the cases were from the use of the
alkaloid itself; 10 were from the root; in two cases children eat the
flowers; in 1, the leaves of the plant were cooked and eaten by mistake;
in 7, the tincture was mistaken for brandy, sherry, or liqueur; the
remainder were caused by the tincture, the liniment, or the extract.

§ 434. =Poisoning by the Root.=--A case of murder which occurred some
years ago in America, and also the Irish case which took place in 1841
(_Reg._ v. _M’Conkey_), were, until the recent trial of Lamson, the only
instances among English-speaking people of the use of aconite for
criminal purposes; but if we turn to the Indian records, we find that it
has been largely used from the earliest times as a destroyer of human
life. In 1842 a tank of water destined for the use of the British army
in pursuit of the retreating Burmese, was poisoned by intentional
contamination with the bruised root of _Aconitum ferox_; it was
fortunately discovered before any harm resulted. A preparation of the
root is used in all the hill districts of India to poison arrows for the
destruction of wild beasts. A Lepcha described the root to a British
officer as being “useful to sportsmen for destroying elephants and
tigers, useful to the rich for putting troublesome relations out of the
way, and useful to jealous husbands for the purpose of destroying
faithless wives.” From the recorded cases, the powdered root, mixed with
food, or the same substance steeped in spirituous liquor, is usually the
part chosen for administration. In M’Conkey’s case, the man’s wife
purchased powdered aconite root, mixed it with pepper, and strewed it
over some greens, which she cooked and gave to him. The man complained
of the sharp taste of the greens, and soon after the meal vomited, and
suffered from purging, became delirious with lock-jaw, and clenching of
the hands; he died in about three hours. The chief noticeable
_post-mortem_ appearance was a bright red colour of the mucous membrane
of the stomach.

The symptoms in this case were, in some respects, different from those
met with in other cases of poisoning by the root. A typical case is
given by Dr. Chevers (_op. cit._), in which a man had taken by mistake a
small portion of aconite root. Immediately after chewing it he felt a
sweetish taste, followed immediately by tingling of the lips and tongue,
numbness of the face, and severe vomiting. On admission to hospital he
was extremely restless, tossing his limbs about in all directions and
constantly changing his position. He complained of a burning sensation
in the stomach, and a tingling and numbness in every part of the body,
excepting his legs. The tingling was specially marked in the face and
tongue--so much so that he was constantly moving the latter to and fro
in order to scratch it against the teeth. Retching and vomiting occurred
almost incessantly, and he constantly placed his hand over the cardiac
region. His face was anxious, the eyes suffused, the lips pale and
exsanguine, the eyelids swollen, moderately dilated, and insensible to
the stimulus of light; the respiration was laboured, 64 in a minute; the
pulse 66, small and feeble. There was inability to walk from loss of
muscular power, but the man was perfectly conscious. The stomach-pump
was used, and albumen and milk administered. Three and three-quarter
hours after taking the root the symptoms were increased in severity. The
tongue was red and swollen, the pulse intermittent, feeble, and slower.
The tingling and numbness had extended to the legs. On examining the
condition of the external sensibility with a pair of scissors, it was
found that, on fully separating the blades and bringing the points in
contact with the skin over the arms and forearms, he felt them as one,
although they were 4 inches apart. But the sensibility of the thighs and
legs was less obtuse, for he could feel the two points distinctly when
they were 4 inches apart, and continued to do so until the distance
between the points fell short of 2¾ inches. He began to improve about
the ninth hour, and gradually recovered, although he suffered for one or
two days from a slight diarrhœa. As in the case detailed (p. 363), no
water was passed for a long time, as if the bladder early lost its
power.

§ 435. =Poisoning by the Alkaloid Aconitine.=--Probably the earliest
instance on record is the case related by Dr. Golding Bird in 1848.[478]
What kind of aconitine was then in commerce I know not, and since
apparently a person of considerable social rank was the subject of the
poisoning, the case has been imperfectly reported. It seems, however,
that, whether for purposes of suicide, or experiment, or as a medicine,
two grains and a half of aconitine were swallowed. The symptoms were
very violent, consisting of vomiting, collapse, and attacks of muscular
spasm; the narrator describes the vomiting as peculiar. “It, perhaps,
hardly deserved that title; the patient was seized with a kind of
general spasm, during which he convulsively turned upon his abdomen,
and with an intense contraction of the abdominal muscles, he jerked out,
as it were, with a loud shout the contents of his stomach, dependent
apparently on the sudden contraction of the diaphragm.” On attempting to
make him swallow any fluid, a fearful spasm of the throat was produced;
it reminded his medical attendants of hydrophobia. The patient recovered
completely within twenty-four hours.

[478] _Lancet_, vol. i. p. 14.

One of three cases reported by Dr. Albert Busscher,[479] of poisoning by
aconitine nitrate, possesses all the exact details of an intentional
experiment, and is of permanent value to toxicological literature.

[479] _Intoxicationsfälle durch Aconitin Nitricum Gallicum, nebst
Sections Bericht_, von Dr. Albert Busscher; _Berl. klinische
Wochenschrift_, 1880, No. 24, pp. 338, 356.

A labourer of Beerta, sixty-one years of age, thin, and of somewhat weak
constitution, suffered from neuralgia and a slight intermittent fever;
Dr. Carl Meyer prescribed for his ailment:--

  ℞. Aconiti Nitrici, 2 grm.
     Tr. Chenopodii Ambrosioid., 100 grms. M.D.S.

Twenty drops to be taken four times daily. The patient was instructed
verbally by Dr. Meyer to increase the dose until he attained a maximum
of sixty drops per day.

The doses which the man actually took, and the time of taking them, are
conveniently thrown into a tabular form as follows:--

  No. 1. March 14,  7 P.M.,  5 drops equal to aconitine nitrate,  ·4 mgrm.
   „  2.   „        9 P.M., 20   „        „            „         1·6  „
   „  3. March 15,  8 A.M., 20   „        „            „         1·6  „
   „  4.   „       11 A.M., 20   „        „            „         1·6  „
   „  5.   „        4 P.M., 20   „        „            „         1·6  „
   „  6.   „        9 P.M., 20   „        „            „         1·6  „
   „  7. March 16, 10 P.M., 10   „        „            „          ·8  „

In the whole seven doses, which were distributed over forty-eight hours,
he took 9·2 mgrms. (·14 grain) of aconitine nitrate.

On taking dose No. 1, he experienced a feeling of constriction
(_Zusammenziehung_), and burning spreading from the mouth to the
stomach, but this after a little while subsided. Two hours afterwards he
took No. 2, four times the quantity of No. 1. This produced the same
immediate symptoms, but soon he became cold, and felt very ill. He had
an anxious oppressive feeling about the chest, with a burning feeling
about the throat; the whole body was covered with a cold sweat, his
sight failed, he became giddy, there was excessive muscular weakness, he
felt as if he had lost power over his limbs, he had great difficulty in
breathing. During the night he passed no water, nor felt a desire to do
so. About half an hour after he had taken the medicine, he began to
vomit violently, which relieved him much; he then fell asleep.

Dose No. 3, equal as before to 1·6 mgrm., he took in the morning. He
experienced almost exactly the same symptoms as before, but convulsions
were added, especially of the face; the eyes were also prominent; twenty
minutes after he had taken the dose, vomiting came on, after which he
again felt better.

He took dose No. 4, and had the same repetition of symptoms, but in the
interval between the doses he felt weaker and weaker; he had no energy,
and felt as if paralysed. No. 5 was taken, and produced, like the
others, vomiting, after which he felt relieved. Neither he nor his wife
seemed all this time to have had any suspicion that the medicine was
really doing harm, but thought that the effects were due to its constant
rejection by vomiting, so, in order to prevent vomiting with No. 6, he
drank much cold water. After thus taking the medicine, the patient
seemed to fall into a kind of slumber, with great restlessness; about an
hour and a half afterwards he cried, “I am chilled; my heart, my heart
is terribly cold. I am dying; I am poisoned.” His whole body was covered
with perspiration; he was now convulsed, and lost sight and hearing; his
eyes were shut, his lips cracked and dry, he could scarcely open his
mouth, and he was extremely cold, and thought he was dying. The
breathing was difficult and rattling; from time to time the muscular
spasms came on. His wife now made a large quantity of hot strong black
tea, which she got him to drink with great difficulty; although it was
hot, he did not know whether it was hot or cold. About five minutes
afterwards he vomited, and did so several times; this apparently
relieved him, and he sank into a quiet sleep; during the night he did
not urinate. In the morning the wife went to Dr. Carl Meyer, described
the symptoms, and accused the medicine. So convinced was Dr. Meyer that
the medicine did not cause the symptoms, that he poured out a quantity
of the same, equal to 4 mgrms. of aconitine nitrate, and took it himself
in some wine, to show that it was harmless, and ordered them to go on
with it. The unhappy physician died of aconitine poisoning five hours
after taking the medicine.[480] In the meantime, the woman went home,
and her husband actually took a seventh, but smaller dose, which
produced similar symptoms to the former, but of little severity; no more
was taken.

[480] The symptoms suffered by Dr. Meyer are to be found in _Neder.
Tijdschrift van Geneeskunde_, 1880, No. 16.

The absence of diarrhœa, and of the pricking sensations so often
described, is in this case noteworthy. Both diarrhœa and formication
were also absent in a third case reported by Dr. Busscher in the same
paper.

§ 436. The most important criminal case is undoubtedly that of
Lamson:--At the Central Criminal Court, in March, 1882, George Henry
Lamson, surgeon, was convicted of the murder of his brother-in-law,
Percy Malcolm John. The victim was a weakly youth of eighteen years of
age, paralysed in his lower limbs from old standing spinal disease. The
motive for perpetrating the crime was that Lamson, through his wife
(Malcolm John’s sister), would receive, on the death of his
brother-in-law, a sum of £1500, and, according to the evidence, it is
probable that there had been one or more previous attempts by Lamson on
the life of the youth with aconitine given in pills and in powders.
However this may be, on November 24, 1880, Lamson purchased 2 grains of
aconitine, came down on Dec. 3 to the school where the lad was placed,
had an interview with his brother-in-law, and, in the presence of the
head-master, gave Malcolm John a capsule, which he filled then and there
with some white powder, presumed at the time to be sugar. Lamson only
stayed altogether twenty minutes in the house, and directly after he saw
his brother-in-law swallow the capsule, he left. Within fifteen minutes
Malcolm John became unwell, saying that he felt as if he had an attack
of heart-burn, and then that he felt the same as when his brother-in-law
had on a former occasion given him a quinine pill. Violent vomiting soon
set in, and he complained of pains in his stomach, a sense of
constriction in his throat, and of being unable to swallow. He was very
restless--so much so that he had to be restrained by force from injuring
himself. There was delirium a few minutes before death, which took place
about three hours and three-quarters after swallowing the fatal dose.
The _post-mortem_ appearances essentially consisted of redness of the
greater curvature of the stomach, and the posterior portion of the same
organ. In one part there was a little pit, as if a blister had broken;
the rest of the viscera were congested, and the brain also slightly
congested.[481]

[481] To these cases of poisoning by the alkaloid aconitine may be added
one recorded in Bouchardat’s _Annuaire de Thérapeutie_, 1881, p. 276.
The case in itself is of but little importance, save to illustrate the
great danger in permitting the dispensing of such active remedies of
varying strength. A gentleman suffering from “angina pectoris” was
prescribed “Hottot’s aconitine” in granules, and directed carefully to
increase the dose up to four granules, according to the effect produced.
The prescription was taken to a pharmacist, who, instead of supplying
Hottot’s aconitine, supplied some other of unknown origin. The medicine
was taken daily, and the dose raised to four granules, which were taken
with benefit until the whole was exhausted. He then went to Hottot’s
establishment, and had a fresh supply, presumably of the same substance,
but a very little time after he had taken his usual dose of four
granules, he suffered from symptoms of aconitine poisoning, headache,
vertigo, feebleness of the voice, and muscular weakness, and was
alarmingly ill. He recovered after some hours of medical treatment.

§ 437. The symptoms of poisoning by the tincture, extract, or other
preparation, do not differ from those detailed. As unusual effects,
occasionally seen, may be noted profound unconsciousness lasting for
two hours (Topham’s case), violent twitching of the muscles of the
face, opisthotonos, and violent convulsions. It is important to
distinguish the symptoms which are not constant from those which are
constant, or nearly so. The tingling and creeping sensations about the
tongue, throat, lips, &c., are not constant; they certainly were not
present in the remarkable German case cited at p. 363. Speaking
generally, they seem more likely to occur after taking the root or the
ordinary medicinal preparations. A dilated state of the pupil is by no
means constant, and not to be relied upon. Diarrhœa is seen after taking
the root or tincture by the stomach, but is often absent. In short, the
only constant symptoms are difficulty of breathing, progressive muscular
weakness, generally vomiting, and a weak intermittent pulse.

§ 438. =Physiological Action.=--Aconitine, according to Dr. S. Ringer,
is a protoplasmic poison, destroying the functions of all nitrogenous
tissue--first of the central nervous system, next of the nerves, and
last of the muscles. Aconitine without doubt acts powerfully on the
heart, ultimately paralysing it; there is first a slowing of the pulse,
ascribed to a central excitation of the vagus; then a quickening, due to
paralysis of the peripheral termination of the vagus in the heart;
lastly, the heart’s action becomes slow, irregular, and weak, and the
blood-pressure sinks. The dyspnœa and convulsions are the usual result,
seen among all warm-blooded animals, of the heart affection. Plugge
found that the motor nerves, and more especially their intra-muscular
terminations, were always paralysed; but if the dose was small the
paralysis might be incomplete. Bœhm and Wartmann, on the other hand,
considered that the motor paralysis had a central origin, a view not
supported by recent research. The action of aconitine in this way
resembles curare. The muscles themselves preserve their irritability,
even after doses of aconitine which are five to ten times larger than
those by which the nerve terminations are paralysed.

§ 439. =Post-mortem Appearances.=--Among animals (mammals) the
appearances most constantly observed have been hyperæmia of the cerebral
membranes and brain, a fulness of the large veins, the blood generally
fluid--sometimes hyperæmia of the liver, sometimes not. When aconitine
has been administered subcutaneously, there have been no inflammatory
appearances in the stomach and bowels.

In the case of Dr. Carl Meyer, who died in five hours from swallowing 4
mgrms. of aconitine nitrate, the corpse was of a marble paleness, the
pupils moderately dilated. The colour of the large intestine was pale;
the duodenum was much congested, the congestion being most intense the
nearer to the stomach; the mucous membrane of the stomach itself was
strongly hyperæmic, being of an intense red colour; the spleen was
enlarged, filled with much dark blood. The liver and kidneys were
deeply congested, the lungs also congested; the right ventricle of the
heart was distended with blood; in the pericardium there was a quantity
of bloody serum. The brain was generally blood-red; in the cerebral
hemispheres there were several large circumscribed subarachnoid
extravasations. The substance of the brain on section showed many red
bloody points.

In a case recorded by Taylor, in which a man died in three hours from
eating a small quantity of aconitine root, the only morbid appearance
found was a slight reddish-brown patch on the cardiac end of the
stomach, of the size of half a crown; all the other organs being
healthy.

§ 440. =Separation of Aconitine from the Contents of the Stomach or the
Organs.=--It would appear certain that in all operations for the
separation of aconite alkaloids (whether from the organic matters which
make up the plant, or from those constituting animal tissues), mineral
acids and a high heat should be avoided. A 1 per cent. sulphuric acid
does not, however, hydrolyse, if acting in the cold, so that the process
already given, p. 352, may be followed.

The chemical examination in the Lamson case was entrusted to Dr.
Stevenson, assisted by Dr. Dupré, and was conducted on the principles
detailed. The contents of the stomach were treated with alcohol, and
digested at the ordinary temperature of the atmosphere; the contents
were already acid, so no acid in this first operation was added. The
mixture stood for two days and was then filtered. The insoluble portion
was now exhausted by alcohol, faintly acidulated by tartaric acid, and
warmed to 60°; cooled and filtered, the insoluble part being washed
again with alcohol. The two portions--that is, the spirituous extract
acid from acids pre-existing in the contents of the stomach, and the
alcohol acidified by tartaric acid--were evaporated down separately,
exhausted by absolute alcohol, the solutions filtered, evaporated, and
the residue dissolved in water. The two aqueous solutions were now
mixed, and shaken up with ether, which, as the solution was acid, would
not remove any alkaloid, but might remove various impurities; the
residue, after being thus partially purified by ether, was alkalised by
sodic carbonate, and the alkaloid extracted by a mixture of chloroform
and ether. On evaporation of the chloroform and ether, the resulting
extract was tested physiologically by tasting, and also by injections
into mice. By means analogous to those detailed, the experts isolated
aconitine from the vomit, the stomach, liver, spleen, and urine, and
also a minute quantity of morphine, which had been administered to the
patient to subdue the pain during his fatal attack. When tasted, the
peculiar numbing, tingling sensation lasted many hours. These extracts
were relied upon as evidence, for their physiological effect was
identical with that produced by aconitine. For example, the extract
obtained from the urine caused symptoms to commence in a mouse in two
minutes, and death in thirty minutes, and the symptoms observed by
injecting a mouse with known aconitine coincided in every particular
with the symptoms produced by the extraction from the urine.

With regard to the manner of using “_life tests_,” since in most cases
extremely small quantities of the active principle will have to be
identified, the choice is limited to small animals, and it is better to
use mice or birds, rather than reptiles. In the Lamson case,
subcutaneous injections were employed, but it is a question whether
there is not less error in administering it by the mouth. If two healthy
mice are taken, and the one fed with a little meal, to which a weighed
quantity of the extract under experiment has been added, while to the
other some meal mixed with a supposed equal dose of aconitine is given,
then the symptoms may be compared; and several objections to any
operative proceeding on such small animals are obviated. It is certain
that any extract which causes distinct numbness of the lips will contain
enough of the poison to kill a small bird or a mouse, if administered in
the ordinary way.[482]

[482] Dr. A. Langaard has described a species of aconite root, named by
the Japanese _Kŭsa-ūsū_. From his experiments on frogs and rabbits, its
physiological action seems not to differ from that of aconitine
generally.--_Ueber eine Art Japanische Akonit-knollen, Kŭsa-ūsū genannt,
u. über das in denselben vorkommende Akonitin. Virchow’s Archiv_, B. 79,
1880, p. 229.


VI.--The Mydriatic Group of
Alkaloids--Atropine--Hyoscyamine--Solanine--Cytisine.


1. ATROPINE.

§ 441. =Atropine= (=Daturine=), C₁₇H₂₃NO₃.--This important alkaloid has
been found in all parts of the _Atropa belladonna_, or deadly
nightshade, and in all the species of _Datura_.

The _Atropa belladonna_ is indigenous, and may be found in some parts of
England, although it cannot be said to be very common. It belongs to the
_Solanaceæ_, and is a herbaceous plant with broadly ovate entire leaves,
and lurid-purple axillary flowers on short stalks; the berries are
violet-black, and the whole of the plant is highly poisonous. The juice
of the leaves stains paper a purple colour. The seeds are very small,
kidney-shaped, weighing about 90 to the grain; they are covered closely
with small, round projections, and are easily identified by an expert,
who may be supposed to have at hand (as is most essential) samples of
different poisonous seeds for comparison. The nightshade owes its
poisonous properties to _atropine_.

The yield of the different parts of belladonna, according to
Gunther,[483] is as follows:--

[483] _Pharm. Zeitschr. f. Russl._, Feb., 1869; Dragendorff, _Die
chemische Werthbestimmung einiger starkwirkenden Droguen_, St.
Petersburg, 1874.

TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE BELLADONNA
PLANT.

  +-------------+----------------------+----------------------+
  |             |Quantity of Alkaloids |Quantity of Alkaloids |
  |             |    in the Fresh      |      in the Dry      |
  |             | Substance, per cent. | Substance, per cent. |
  |             +-----------+----------+-----------+----------+
  |             | (_a._) By |(_b._) By | (_a._) By |(_b._) By |
  |             | Weighing. |Titration.| Weighing. |Titration.|
  +-------------+-----------+----------+-----------+----------+
  |Leaves,      |  0·2022   | 0·20072  |  0·838    | 0·828    |
  |Stalk,       |  0·0422   |    ...   |  0·146    |  ...     |
  |Ripe fruit,  |  0·2128   | 0·20258  |  0·821    | 0·805    |
  |Seed,        |  0·26676  |    ...   |  0·407    |  ...     |
  |Unripe fruit,|  0·1870   | 0·1930   |  0·955    | 0·955    |
  |Root,        |  0·0792   |    ...   |  0·210    |  ...     |
  +-------------+-----------+----------+-----------+----------+

Atropine appears to exist in the plant in combination with malic acid.
According to a research by Ladenburg, hyoscyamine is associated with
atropine, both in the Belladonna and Datura plants.[484]

[484] _Ber. der deutsch. Chem. Ges._, Bd. 13.

From a research by W. Schütte,[485] it appears that the younger roots of
wild belladonna contain hyoscyamine only, whilst the older roots contain
atropine as well as hyoscyamine, but only in small proportion; the same
was observed to be the case in the older cultivated roots.

[485] _Arch. Pharm._, ccxxix., 492-531; _Journ. Chem. Soc._ (abstract),
February 1892, 231.

The ripe berries of cultivated _Atropa belladonna nigra_ contain
atropine and hyoscyamine; those of the wild plant contain atropine only;
the ripe fruit of _Atropa belladonna lutea_ contains only atropine and
another base, perhaps identical with atropamine; the unripe fruit of
wild _Atropa belladonna nigra_ contains hyoscyamine, with only a small
quantity of atropine.

The leaves of the yellow and black-fruited wild _Atropa belladonna_
contain hyoscyamine and atropine, the latter being in small quantity
only.

Fresh and old seeds of _Datura Stramonium_ contain chiefly hyoscyamine;
small quantities of atropine and scopolamine are also present.

§ 442. =The Datura Stramonium or Thorn-apple= is also indigenous in the
British Islands, but, like belladonna, it cannot be considered a common
plant. Datura belongs to the Solanaceæ; it grows from 1 to 2 feet in
height, and is found in waste places. The leaves are smooth, the flowers
white; the fruit is densely spinous (hence the name thorn-apple), and is
divided into four dissepiments below, two at the top, and containing
many seeds.

The _Datura_, or the _Dhatura_-plants, of India have in that country a
great toxicological significance, the white-flowered datura, or _Datura
alba_, growing plentifully in waste places, especially about Madras. The
purple-coloured variety, or _Datura fastuosa_, is also common in certain
parts. There is a third variety, the _Datura atrox_, found about the
coast of Malabar. The seeds of the white datura have been mistaken in
India for those of capsicum. The following are some of the most marked
differences:--

  SEEDS OF THE COMMON OR WHITE        SEEDS OF CAPSICUM.
  DATURA.

  (1.) Outline angular.               Outline rounded.

  (2.) Attached to the placenta by a  Attached to the placenta by a
  large, white, fleshy mass separ-    cord from a prominence on the
  ating easily, leaving a deep        concave border of the seed.
  furrow along half the length of
  the seed’s concave border.

  (3.) Surface scabrous, almost re-   Uniformly scabrous, the sides
  ticulate, except on the two com-    being equally rough with the
  pressed sides, where it has         borders.
  become almost glaucous from
  pressure of the neighbouring
  seeds.

  (4.) Convex border thick and        Convex border thickened, but
  bulged with a longitudinal depres-  uniformly rounded.
  sion between the bulgings, caused
  by the compression of the two
  sides.

  (5.) A suitable section shows the   The embryo, exposed by a suitable
  embryo curved and twisted in the    section, is seen to resemble in
  fleshy albumen.                     outline very closely the figure
                                      6.

  (6.) The taste of the datura seeds  The taste of capsicum is pungent;
  is very feebly bitter. The watery   a decoction irritates the eye
  decoction causes dilatation of the  much, but does not cause dilata-
  pupil.                              tion of the pupil.

The identity of the active principle in both the datura and belladonna
tribes is now completely established.[486]

[486] See a research by Ernst Schmidt, “Ueber die Alkaloide der
Belladonna-Wurzel u. des Stechapfel-Samens,” _Lieb. Annl._, Bd. 208,
1881.

§ 443. =Pharmaceutical Preparations.=--(_a._) _Of the leaves. Extract
of Belladonna._--This contains, according to Squire,[487a] from 0·73 to
1·7 per cent. of total alkaloids. _Belladonna Juice_ (_succus
belladonnæ_).--Strength in alkaloid about 0·05 per cent. _Tincture of
Belladonna._--Half the strength of the juice, and therefore yielding
about 0·025 per cent. of alkaloid.

[487a] _Companion to the British Pharmacopœia_, 1894.

(_b._) _Belladonna Root.--Belladonna plaster_ contains 20 per
cent. of alcoholic extract of belladonna. _Alcoholic Extract of
Belladonna._--This extract, according to Squire,[487b] contains from 1·6
to 4·45 per cent. of alkaloid. _Belladonna liniment_ is an alcoholic
extract with the addition of camphor; its strength is about equal to 0·2
per cent. of alkaloid. _Belladonna ointment_ contains about 10 per cent.
of the alcoholic extract.

[487b] _Companion to the British Pharmacopœia_, 1894.

(_c._) _The Alkaloid.--Atropine Discs_ (_lamellæ atropinæ_).--These are
discs of gelatin, each weighing about 1/50 grain, and containing for
ophthalmic use 1/5000 grain of atropine sulphate. Similar discs are made
for hypodermic use, but stronger; each containing 1/120 grain. _Solution
of Atropine Sulphate._--Strength about 1 per cent. _Atropine
Ointment._--Strength about 1 in 60, or 1·60 per cent. of atropine.

(_d._) _Stramonium._--An extract of the seeds is officinal in Britain;
the alkaloidal content is from 1·6 to 1·8 per cent. There is also a
tincture which contains about 0·06 per cent. of alkaloid.

§ 444. =Properties of Atropine=, C₁₇H₂₃NO₃.--Atropine, hyoscyamine, and
hyoscine have all the same formula, but differ in their molecular
constitution. Atropine by hydrolysis, either by heating it with
hydrochloric acid or baryta water, is decomposed into tropine and tropic
acid:--

  C₁₇H₂₃NO₃ + H₂O = C₈H₁₅NO + C₉H₁₀O₃.
  Atropine.      Tropine. Tropic
                           acid.

On the other hand, by heating tropic acid and tropine together,
atropine is regenerated. Hence it is proved by analysis and
synthesis, that atropine is tropic acid-tropine, just as aconitine is
benzoyl-aconine. Tropic acid has been produced synthetically by
boiling β-chlorphenyl-propionic acid with potash, which at once shows
its constitutional formula, viz.:--

        CH₂OH
       /
  C₆H₅CH      .
       \
        COOH

Tropic acid has a melting-point of 117° to 118°. Tropine is a four-fold
hydrated oxethyl-methyl-pyridine, and has the constitutional formula of
C₅H₃(H₄)(C₂H₄OH)N(CH₃); hence the constitutional formula of atropine
is--

          CH₂(OH)
         /
  C₆H₅--CH                       .
         \
          CO--O(C₂H₄--C₅H₇==N--CH₃)

Tropine is a white, crystalline, strongly alkaline mass, melting at 60°,
and volatilising at 230° undecomposed. It is soluble in water, alcohol,
and ether, and gives precipitates with tannic acid, iodised hydriodic
acid, Mayer’s reagent, gold chloride, and mercuric chloride. Tropine
gold chloride melts at 210° to 212°. Atropic acid (C₉H₈O₂),
melting-point 198° to 200°, and isatropic acid (C₉H₈O₂), may also be
obtained by the action of hydrochloric acid--the first, in radiating
crystals, melting at 106°, and capable of distillation; the second, in
thin rhombic plates, melting about 200°, and not volatile. Picric acid
also gives a precipitate of beautiful plates. To obtain this the
carbazotic acid must be in excess, and time must be given for the
precipitate to form.

Atropine forms colourless crystals (mostly in groups or tufts of needles
and prisms), which are heavier than water, and possess no smell, but an
unpleasant, long-enduring, bitter taste. The experiments of E. Schmidt
place the melting-point between 115° and 115·5°. It is said to sublime
scantily in a crystalline form, but the writer has been unable to obtain
any crystals by sublimation; faint mists collect on the upper disc, at
about 123°, but they are perfectly amorphous.

Its reaction is alkaline; one part requires, of cold water, 300; of
boiling, 58; of ether, 30; of benzene, 40; and of chloroform, 3 parts
for solution. In alcohol and amyl alcohol it dissolves in almost every
proportion. It turns the plane of polarisation weakly to the left.

§ 445. =Tests.=--Atropine mixed with nitric acid exhibits no change of
colour. The same is the case with concentrated sulphuric acid in the
cold; but on heating, there ensues the common browning, with development
of a peculiar odour, likened by Gulielmo to orange flowers, by
Dragendorff to the flowers of the _Prunus padus_, and by Otto to the
_Spiræa ulmaria_--a sufficient evidence of the untrustworthiness of this
as a distinctive test. The odour, indeed, with small quantities, is
certainly not powerful, nor is it strongly suggestive of any of the
plants mentioned. A far more intense odour is given off if a speck of
atropine is evaporated to dryness with a few drops of strong solution of
baryta, and heated strongly; the scent is decidedly analogous to that of
hawthorn-blossom, and unmistakably agreeable.

By boiling a small quantity of atropine, say 1 mgrm., with 2 mgrms. of
calomel and a very little water, the calomel blackens, and crystals may
be obtained of a double salt; this reaction is, however, given also by
hyoscyamine and homatropine. Mercuric potassium iodide solution, and
mercuric bromide solution give amorphous precipitates, which, after a
time, become crystalline, and have characteristic forms.

A solution of iodine in potassium iodide gives a precipitate with
acidulated solutions of atropine in even a dilution of 1 : 10,000.
Tannin precipitates, and the precipitate is soluble in excess of the
reagent. If atropine be dissolved in dilute hydrochloric acid, and a 5
per cent. of gold chloride solution be added, a precipitate of a gold
compound (C₁₇H₂₃NO₃HClAuCl₃) separates. The precipitate is in the form
of rosettes or needles; melting-point 137°. On boiling it with water,
however, it melts into oily drops, and this peculiar behaviour
distinguishes it from the analogous salt of hyoscyamine, which does not
melt in boiling water. The percentage of gold left on a combustion of
atropine gold chloride is 31·35 per cent. 100 parts of the gold salt are
equal to 46·2 of atropine. A platinum salt may also be obtained,
(C₁₇H₂₃NO₃HCl)₂,PtCl₄, containing 29·5 per cent. of platinum.

Vitali’s test is important; it consists in the production of a violet
colour with alcoholic potash after oxidation.

The test may be applied as follows:--Equal parts, say 1 mgrm., of
nitrate of sodium and of the substance to be tested, are rubbed together
with a glass rod on a porcelain slab, and to this mixture 1 drop of
sulphuric acid is added; the mixture is spread out in a thin film; upon
this is strewn a little powdered potassium hydrate, and finally 1 drop
of alcohol added; a violet colour is produced which passes into a fine
red; according to the author of the test, 0·001 mgrm. of atropine
sulphate can by this test be detected. Strychnine obscures this
reaction.

Atropine, homatropine, and hyoscyamine show an alkaline reaction with
phenolphthalein: atropine and homatropine give a precipitate with HgCl₂.
Hyoscyamine, not cocaine, precipitates HgCl₂, and is alkaline to litmus,
but not to phenolphthalein. Atropine behaves as follows:--(1) Sodium
nitrate, sulphuric acid, and afterwards sodium hydroxide, gives a violet
colour; (2) the test as before, but with nitrite instead of nitrate,
gives orange colour, which, on dilution with sodium hydroxide solution,
changes to red, violet, or lilac; (3) when heated with glacial acetic
acid and sulphuric acid for a sufficient time, a greenish-yellow
fluorescence is produced.--_Flückiger, Pharm. Journ. Trans._ (3), vol.
xvi. p. 601-602.

The two alkaloids, strychnine and atropine, are not likely to be often
together in the human body, but that it may sometimes occur is shown by
a case recorded by L. Fabris.[488] A patient in the hospital at Padua
had for some time been treated with daily injections of 3 mgrms. of
strychnine nitrate; unfortunately, one day, instead of the 3 mgrms. of
strychnine, the same quantity of atropine sulphate was injected, and the
patient died after a few hours, with symptoms of atropine poisoning.

[488] _Gazzetta_, xxii., i. 347-350.

On chemical treatment of the viscera, a mixture of alkaloids was
obtained which did not give either the reactions of strychnine or of
atropine. To test the possibility of these alkaloids obscuring each
other’s reactions, mixtures of 3 per cent. solutions (the strength of
the injections) of atropine sulphate and strychnine nitrate were mixed
together, and strychnine tested for by the dichromate and sulphuric acid
test.

A mixture of equal parts gave the strychnine reaction very clearly, but
the atropine reaction not at all; 1 strychnine with 3 of atropine gave
strychnine reaction, but not that of atropine; 1 strychnine with 4
atropine gave indistinct reaction for both alkaloids; 1 of strychnine
with 5 of atropine gave a momentary atropine reaction, the violet was,
however, almost immediately replaced by a red colour. Vitali’s reaction
was not clearly shown until the mixture was in the proportion of 9 of
atropine to 1 of strychnine, but mixtures in the proportion of 3
strychnine and 1 atropine will give distinct mydriasis.

In such a case, of course, the strychnine should be separated from the
atropine; this can be effected by precipitating the strychnine as
chromate, filtering and recovering from the filter the atropine by
alkalising and shaking it out with ether.

The atropine may be farther purified by converting it into oxalate,
dissolving the oxalate in as small a quantity of alcohol as possible,
and precipitating the oxalate out with ether; the precipitate is
collected, dissolved in as small a quantity of water as possible, the
water made alkaline, and the base shaken out with ether.

The most reliable test for atropine, or one of the mydriatic alkaloids,
is its action on the iris; a solution of atropine, even so weak as 1 :
130,000, causing dilatation.[489] This action on the iris has been
studied by Ruyter,[490] Donders, and von Graefe.

[489] _De Actione Atropæ Belladonnæ in Iridem_, Traj. ad Rhen., 1852.

[490] _Arch. Ophthal._, ix. 262, 1864.

The action is local, taking effect when in dilute solution only on the
eye to which it has been applied; and it has been produced on the eyes
of frogs, not only in the living subject, but after the head has been
severed from the body and deprived of brain. The thinner the cornea, the
quicker the dilatation; therefore, the younger the person or animal, the
more suitable for experiment. In frogs, with a solution of 1 : 250,
dilatation commences in about five minutes; in pigeons, seven minutes;
and in rabbits, ten minutes. In man, a solution of 1 : 120 commences to
act in about six to seven minutes, reaches its highest point in from ten
to fifteen minutes, and persists more or less for six to eight days. A
solution of 1 : 480 acts first in fifteen to twenty minutes, and reaches
its greatest point in twenty minutes; a solution of 1 : 48,000 requires
from three-quarters of an hour to an hour to show its effect. Dogs and
cats are far more sensible to its influence than man, and therefore more
suitable for experiment. If the expert chooses, he may essay the proof
upon himself, controlling the dilatation by Calabar bean; but it is
seldom necessary or advisable to make personal trials of this
nature.[491]

[491] A. Ladenburg (_Compt. Rend._, xc. 92), having succeeded in
reproducing atropine by heating tropine and tropic acid with
hydrochloric acid, by substituting various organic acids for the tropic
acid, has obtained a whole series of compounds to which he has given the
name of _tropeines_. One of these, hydroxytoluol (amygdalic) tropeine,
he has named _homatropine_. It dilates the pupil, but is less poisonous
than atropine.

§ 446. =Statistics of Atropine Poisoning.=--Since atropine is the active
principle of belladonna and datura plants, and every portion of
these--root, seeds, leaves, and fruit--has caused toxic symptoms,
poisoning by any part of these plants, or by their pharmaceutical or
other preparations, may be considered with strict propriety as atropine
poisoning. Our English death statistics for the ten years ending 1892,
record 79 deaths (50 males and 29 females) from atropine (for the most
part registered under the head of belladonna); 29 (or 36·7 per cent.)
were suicidal, the rest accidental.

The greatest number of the accidental cases arise from mistakes in
pharmacy; thus, belladonna leaves have been supplied for ash leaves; the
extract of belladonna has been given instead of extract of juniper; the
alkaloid itself has been dispensed in mistake for theine;[492] a more
curious and marvellously stupid mistake is one in which it was dispensed
instead of assafœtida (Schauenstein, _op. cit._, p. 652). Further,
valerianate of atropine has been accidentally substituted for quinine
valerianate, and Schauenstein relates a case in which atropine sulphate
was administered subcutaneously instead of morphine sulphate; but the
result was not lethal. Many other instances might be cited. The extended
use of atropine as an external application to the eye naturally gives
rise to a few direct and indirect accidents. Serious symptoms have
arisen from the solution reaching the pharynx through the lachrymal duct
and nose. A curious indirect poisoning, caused by the use of atropine as
a collyrium, is related by Schauenstein.[493] A person suffered from all
the symptoms of atropine poisoning; but the channel by which it had
obtained access to the system was a great mystery, until it was traced
to some coffee, and it was then found that the cook had strained this
coffee through a certain piece of linen, which had been used months
before, soaked in atropine solution, as a collyrium, and had been cast
aside as of no value.

[492] Hohl, _De Effectu Atropini. Diss. Halle_, 1863.

[493] Maschka’s _Handbuch_.

§ 447. =Accidental and Criminal Poisoning by Atropine.=--External
applications of atropine are rapidly absorbed, _e.g._, if the foot of a
rat be steeped for a little while in a solution of the alkaloid, and the
eyes watched, dilatation of the pupils will soon be observed. If the
skin is broken, enough may be absorbed to cause death. A case is on
record in which ·21 grm. of atropine sulphate, applied as an ointment to
the abraded skin, was fatal.[494] Atropine has also been absorbed from
the bowel; in one case, a clyster containing the active principles of
5·2 grms. (80 grains) of belladonna root was administered to a woman
twenty-seven years of age, and caused death. Allowing the root to have
been carefully dried, and to contain ·21 per cent. of alkaloid, it would
seem that so little as 10·9 mgrms. (·16 grain) may even prove fatal, if
left in contact with the intestinal mucous membrane. Belladonna berries
and stramonium leaves and seeds are eaten occasionally by children. A
remarkable series of poisonings by belladonna berries occurred in London
during the autumn of 1846.

[494] Ploss, _Zeitschr. f. Chir._, 1863.

Criminal poisoning by atropine in any form is of excessive rarity in
Europe and America, but in India it has been frightfully prevalent. In
all the Asiatic cases the substance used has been one of the various
species of datura, and mostly the bruised or ground seeds, or a
decoction of the seeds. In 120 cases recorded in papers and works on
Indian toxicology, I find no less than 63 per cent. of the cases
criminal, 19 per cent. suicidal, and 18 per cent. accidental. In noting
these figures, however, it must be borne in mind that known criminal
cases are more certain to be recorded than any other cases. The drug has
been known under the Sanscrit name of _dhatoora_ by the Hindoos from
most remote times. It was largely used by the Thugs, either for the
purpose of stupefying their victim or for killing him; by loose wives to
ensure for a time the fatuity of their husbands; and, lastly, it seems
in Indian history to have played the peculiar _rôle_ of a state agent,
and to have been used to induce the idiocy or insanity of persons of
high rank, whose mental integrity was considered dangerous by the despot
in power. The Hindoos, by centuries of practice, have attained such
dexterity in the use of the “datura” as to raise that kind of poisoning
to an art, so that Dr. Chevers, in his _Medical Jurisprudence for
India_,[495] declares that “there appears to be no drug known in the
present day which represents in its effects so close an approach to the
system of slow poisoning, believed by many to have been practised in the
Middle Ages, as does the datura.”

[495] Dr. Chevers’s work contains a very good history of datura criminal
poisoning.

§ 448. =Fatal Dose.=--It is impossible to state with precision the exact
quantity which may cause death, atropine being one of those substances
whose effect, varying in different cases, seems to depend on special
constitutional tendencies or idiosyncracies of the individual. Some
persons take a comparatively large amount with impunity, while others
scarcely bear a very moderate dose without exhibiting unpleasant
symptoms. Eight mgrms. (⅛ grain) have been known to produce poisonous
symptoms, and ·129 grm. (2 grains) death. We may, therefore, infer that
about ·0648 grm. (1 grain) would, unchecked by remedies, probably act
fatally; but very large doses have been recovered from, especially when
treatment has been prompt.

Atropine is used in veterinary practice, from 32·4 to 64·8 mgrms. (½ to
1 grain) and more being administered subcutaneously to horses; but the
extent to which this may be done with safety is not yet established.

§ 449. =Action on Animals.=--The action of atropine has been studied on
certain beetles, on reptiles (such as the salamander, triton, frogs, and
others), on guinea-pigs, hedgehogs, rats, rabbits, fowls, pigeons, dogs,
and cats. Among the mammalia there is no essential difference in the
symptoms, but great variation in the relative sensibility; man seems the
most sensitive of all, next to man come the carnivora, while the
herbivora, and especially the rodents, offer a considerable resistance.
According to Falck the lethal dose for a rabbit is at least ·79 mgrm.
per kilo. It is the general opinion that rabbits may eat sufficient of
the belladonna plant to render their flesh poisonous, and yet the
animals themselves may show no disturbance in health; but this must not
be considered adequately established. Speaking very generally, the
higher the animal organisation the greater the sensibility to atropine.
Frogs are affected in a peculiar manner. According to the researches of
Fraser,[496] the animal is first paralysed, and some hours after the
administration of the poison lies motionless, the only signs of life
being the existence of a slight movement of the heart and muscular
irritability. After a period of from forty-eight to seventy-two hours,
the fore limbs are seized with tetanic spasms, which develop into a
strychnine-like tetanus.

[496] _Transact. of Edin. Roy. Soc._, vol. xxv. p. 449. _Journ. of Anat.
and Physiol._, May 1869, p. 357.

§ 450. =Action on Man.=--When atropine is injected subcutaneously, the
symptoms, as is usually the case with drugs administered in this manner,
may come on immediately, the pupil not unfrequently dilating almost
before the injection is finished. This is in no way surprising; but
there are instances in which decoctions of datura seeds have been
administered by the stomach, and the commencement of symptoms has been
as rapid as in poisoning by oxalic or even prussic acid. In a case tried
in India in July 1852, the prosecutor declared that, while a person was
handing him a _lota_ of water, the prisoner snatched it away on pretence
of freeing the water from dirt or straws, and then gave it to him. He
then drank only two mouthfuls, and, complaining of the bitter taste,
fell down insensible within forty yards of the spot where he had drunk,
and did not recover his senses until the third day after. In another
case, a man was struck down so suddenly that his feet were scalded by
some hot water which he was carrying.--_Chevers._

When the seeds, leaves, or fruit of atropine-holding plants are eaten,
there is, however, a very appreciable period before the symptoms
commence, and, as in the case of opium poisoning, no very definite rule
can be laid down, but usually the effects are experienced within half
an hour. The first sensation is dryness of the mouth and throat; this
continues increasing, and may rise to such a degree that the swallowing
of liquids is an impossibility. The difficulty in swallowing does not
seem to be entirely dependent on the dry state of the throat, but is
also due to a spasmodic contraction of the pharyngeal muscles.
Tissore[497] found in one case such constriction that he could only
introduce emetics by passing a catheter of small diameter. The mucous
membrane is reddened, and the voice hoarse.[498] The inability to
swallow, and the changed voice, bear some little resemblance to
hydrophobia--a resemblance heightened to the popular mind by an
inclination to bite, which seems to have been occasionally observed; the
pupils are early dilated, and the dilatation may be marked and extreme;
the vision is deranged, letters and figures often appear duplicated; the
eyeballs are occasionally remarkably prominent, and generally congested;
the skin is dry, even very small quantities of atropine arresting the
cutaneous secretion; in this respect atropine and pilocarpine are
perfect examples of antagonism. With the dryness of skin, in a large
percentage of cases, occurs a scarlet rash over most of the body. This
is generally the case after large doses, but Stadler saw the rash
produced on a child three months old by ·3 mgrm. of atropine sulphate.
It appeared three minutes after the dose, lasted five hours, and was
reproduced by a renewed dose.[499] The temperature of the body with
large doses is raised; with small, somewhat lowered. The pulse is
increased in frequency, and is always above 100--mostly from 115 to 120,
or even 150, in the minute. The breathing is at first a little slowed,
and then very rapid. Vomiting is not common; the sphincters may be
paralysed so that the evacuations are involuntary, and there may be also
spasmodic contractions of the urinary bladder. The nervous system is
profoundly affected; in one case there were clonic spasms,[500] in
another,[501] such muscular rigidity, that the patient could with
difficulty be placed on a chair. The lower extremities are often partly
paralysed, there is a want of co-ordination, the person reels like a
drunken man, or there may be general jactitation. The disturbance of
the brain functions is very marked; in about 4 per cent. only of the
recorded cases has there been no delirium, or very little--in the
majority delirium is present. In adults this generally takes a
garrulous, pleasing form, but every variety has been witnessed. Dr. H.
Giraud describes the delirium from datura (which it may be necessary to
again repeat is _atropine_ delirium) as follows:--“He either vociferates
loudly or is garrulous, and talks incoherently; sometimes he is
mirthful, and laughs wildly, or is sad and moans, as if in great
distress; generally he is observed to be very timid, and, when most
troublesome and unruly, can always be cowed by an angry word, frequently
putting up his hands in a supplicating posture. When approached he
suddenly shrinks back as if apprehensive of being struck, and frequently
he moves about as if to avoid spectra. But the most invariable
accompaniment of the final stage of delirium, and frequently also that
of _sopor_, is in the incessant picking at real or imaginary objects. At
one time the patient seizes hold of parts of his clothes or bedding,
pulls at his fingers and toes, takes up dirt and stones from the ground,
or as often snatches at imaginary objects in the air, on his body, or
anything near him. Very frequently he appears as if amusing himself by
drawing out imaginary threads from the ends of his fingers, and
occasionally his antics are so varied and ridiculous, that I have seen
his near relatives, although apprehensive of danger, unable to restrain
their laughter.”[502] This active delirium passes into a somnolent state
with muttering, catching at the bedclothes, or at floating spectra, and
in fatal cases the patient dies in this stage. As a rule, the sleep is
not like opium coma; there is complete insensibility in both, but in the
one the sleep is deep, without muttering, in the other, from atropine,
it is more like the stupor of a fever. The course in fatal cases is
rapid, death generally taking place within six hours. If a person live
over seven or eight hours, he usually recovers, however serious the
symptoms may appear. On waking, the patient remembers nothing of his
illness; mydriasis remains some time, and there may be abnormality of
speech and weakness of the limbs, but within four days health is
re-established. In cases where the seeds have been swallowed, the
symptoms may be much prolonged, and they seem to continue until all the
seeds have been voided--perhaps this is due to the imperfect but
continuous extraction of atropine by the intestinal juices.

[497] _Gaz. hebd._, 1856.

[498] A friend of the author’s was given, by a mistake in dispensing, 16
minims of a solution of atropine sulphate, equivalent to 1/7 grain of
atropine (or 9·3 mgrms). Ten minutes after taking the dose there was
dilatation of the pupil, indistinctness of vision, with great dryness of
the throat and difficulty in swallowing; he attempted to eat a biscuit,
but, after chewing it, he was obliged to spit it out, as it was not
possible to swallow; the throat was excessively sore, and there was a
desire to pass urine, but only a few drops could be voided. In
forty-five minutes he was unable to stand or walk. There was a bright
rash on the chest. In two hours he became insensible, and was taken to
the Middlesex Hospital, recovering under treatment in about eight hours.

[499] _Med. Times_, 1868.

[500] _Lancet_, vol. i., 1881, p. 414.

[501] _Ibid._, vol. i., 1876, p. 346.

[502] In an English case of belladonna poisoning, the patient, a tailor,
sat for four hours, moving his hands and arms as if sewing, and his lips
as if talking, but without uttering a word.

Chronic poisoning by atropine may, from what has been stated, be of
great importance in India. It is probable that its continuous effect
would tend to weaken the intellect, and there is no reason for any
incredulity with regard to its power as a factor of insanity. Rossbach
has ascertained that if dogs are, day after day, dosed with atropine,
they become emaciated; but a certain tolerance is established, and the
dose has to be raised considerably after a time to produce any marked
physiological effect.

§ 451. =Physiological Action of Atropine.=--From the numerous
experiments on animals which have been performed for the purpose of
elucidating the action of atropine, it is clear that the terminations of
the vagus in the heart muscle are first excited, and then paralysed. The
excitor-motor ganglion is also paralysed, and finally the heart itself;
death resulting from heart paralysis. The respiratory disturbance is
also to be ascribed to the vagus; the terminations in the lung are
paralysed, and, at the same time, the poison circulating through the
respiratory nervous centre stimulates it first, and then it also becomes
finally paralysed. The small vessels are generally widened after a
previous transitory narrowing. Organs containing unstriped muscular
fibre are generally paralysed, as well as the ends of the nerves
regulating secretion--hence the dryness of the skin. The action on the
iris is not thoroughly elucidated.

§ 452. The _diagnosis_ of atropine poisoning may be very difficult
unless the attention of the medical man be excited by some suspicious
circumstance. A child suffering from belladonna rash, with hot dry skin,
quick pulse, and reddened fauces, looks not unlike one under an attack
of scarlet fever. Further, as before mentioned, some cases are similar
to rabies; and again, the garrulous delirium and the hallucinations of
an adult are often very similar to those of _delirium tremens_, as well
as tomania.

§ 453. =Post-mortem Appearances.=--The _post-mortem_ appearances do not
seem to be characteristic, save in the fact that the pupils remain
dilated. The brain is usually hyperæmic, and in one case the absence of
moisture seems to have been remarkable. The stomach and intestines may
be somewhat irritated if the seeds, leaves, or other parts of the plant
have been eaten; but the irritation is not constant if the poisoning has
been by pure atropine, and still less is it likely to be present if
atropine has been administered subcutaneously.

§ 454. =Treatment.=--The great majority of cases recover under
treatment. In 112 cases collected by F. A. Falck, 13 only were fatal
(11·6 per cent.). The greater portion of the deaths in India are those
of children and old people--persons of feeble vitality. The Asiatic
treatment, which has been handed down by tradition, is the application
of cold water to the feet; but the method which has found most favour in
England is treatment by pilocarpine, a fifth of a grain or more being
injected from time to time. Pilocarpine shows as perfect antagonism as
possible; atropine dries, pilocarpine moistens the skin; atropine
accelerates, pilocarpine slows the respiration. Dr. Sydney Ringer and
others have published a remarkable series of cases showing the efficacy
of this treatment, which, of course, is to be combined where necessary
with emetics, the use of the stomach-pump, &c.[503]

[503] See, for Dr. Ringer’s cases, _Lancet_, vol. i., 1876, p. 346.
Refer also to _Brit. Med. Journ._, vol. i., 1881, p. 594; _ib._, p. 659.

§ 455. =Separation of Atropine from Organic Tissues, &c.=--From the
contents of the stomach, atropine may be separated by acidulating
strongly with sulphuric acid (15 to 20 c.c. of dilute H₂SO₄ to 100
c.c.), digesting for some time at a temperature not exceeding 70°, and
then reducing any solid matter to a pulp by friction, and filtering,
which can generally be effected by the aid of a filter-pump. The liver,
muscles,[504] and coagulated blood, &c., may also be treated in a
precisely similar way. The acid liquid thus obtained, is first, to
remove impurities, shaken up with amyl alcohol, and after the separation
of the latter in the usual manner, it is agitated with chloroform, which
will take up any of the remaining amyl alcohol,[505] and also serve to
purify further. The chloroform is then removed by a pipette (or the
separating flask before described), and the fluid made alkaline, and
shaken up with ether, which, on removal, is allowed to evaporate
spontaneously. The residue will contain atropine, and this may be
farther purified by converting it into oxalate, as suggested, page 374.

[504] Neither amyl alcohol nor chloroform removes atropine from an
_acid_ solution.

[505] Atropine goes into the blood, and appears to be present in the
different organs in direct proportion to the quantity of blood they
contain. Dragendorff has found in the muscles of rabbits fed upon
belladonna sufficient atropine for quantitative estimation.

From the urine,[506] atropine may be extracted by acidifying with
sulphuric acid, and agitation with the same series of solvents. Atropine
has been separated from putrid matters long after death, nor does it
appear to suffer any decomposition by the ordinary analytical operations
of evaporating solutions to dryness at 100°. In other words, there seems
to be no necessity for operations _in vacuo_, in attempts at separating
atropine.

[506] Dragendorff has found atropine in the urine of rabbits fed with
belladonna; the separation by the poison is so rapid that it often can
only be recognised in the urine during the first hour after the poison
has been taken.

TABLE SHOWING THE ALKALOIDAL CONTENT OF VARIOUS PARTS OF THE HENBANE
PLANT.

  +----------------------------+-------+-------+-------+-------+
  |                            | Seeds,|Leaves,| Stalk,| Root, |
  +----------+---------+-------+-------+-------+-------+-------+
  | Plant    | Hyosc.- | 1868. |  ...  | 0·588 | 0·012 | 0·128 |
  | Desti-   | Albus.  | 1869. |  ...  | 0·469 |  ...  | 0·176 |
  | tute     +---------+-------+-------+-------+-------+-------+
  | of       | Hyosc.- | 1868. |  ...  | 0·154 | 0·070 | 0·027 |
  | Flowers. | Niger.  | 1869. |  ...  | 0·192 | 0·017 | 0·080 |
  +----------+---------+-------+-------+-------+-------+-------+
  |          | Hyosc.- | 1868. |  ...  | 0·359 | 0·036 | 0·146 |
  | Plant    | Albus.  | 1869. |  ...  | 0·329 | 0·048 | 0·262 |
  | in       +---------+-------+-------+-------+-------+-------+
  | Flower.  | Hyosc.- | 1868. |  ...  | 0·147 | 0·032 | 0·127 |
  |          | Niger.  | 1869. |  ...  | 0·206 | 0·030 | 0·138 |
  +----------+---------+-------+-------+-------+-------+-------+
  |          | Hyosc.- | 1868. | 0·162 | 0·211 | 0·027 | 0·106 |
  | Plant    | Albus.  | 1869. | 0·172 | 0·153 | 0·029 | 0·086 |
  | in       +---------+-------+-------+-------+-------+-------+
  | Fruit.   | Hyosc.- | 1868. | 0·075 | 0·065 | 0·009 | 0·028 |
  |          | Niger.  | 1869. | 0·118 | 0·110 | 0·010 | 0·056 |
  +----------+---------+-------+-------+-------+-------+-------+


2. HYOSCYAMINE.

§ 456. This powerful alkaloid is contained in small quantities in datura
and belladonna, and also is found in the common lettuce (·001 per
cent.),[507] and in _Scopola carmolica_, a solanaceous plant
indigenous to Austria and Hungary[508]; but its chief source is the
_Hyoscyamus niger_ and _Hyoscyamus alba_ (black and white henbane): it
is also found in the _Duboisia myoporoides_. The latter plant was
considered to contain a new alkaloid, “_Duboisine_,” but duboisine is a
mixture of hyoscyamine and hyoscine. Ladenburg’s hyoscine accompanies
hyoscyamine, and is an isomeride of both atropine and hyoscyamine; its
chemical reactions are similar to those of hyoscyamine, as well as its
physiological effects.[509]

[507] T. S. Dymond, _Journ. Chem. Soc. Trans._, 1892, 90.

[508] W. R. Dunstan and A. E. Chaston. _Pharm. Journ. Trans._ (3), xx.
461-464.

[509] See _Ber. der deutsch. Chem. Gesell._, 13, 1549 to 1554. By
boiling hyoscine hydrochloride with animal charcoal, and then
precipitating with auric chloride, a good crystalline compound, melting
at 198°, can be obtained.

=Hyoscyamine= (C₁₇H₂₃NO₃), as separated in the course of analysis, is a
resinoid, sticky, amorphous mass, difficult to dry, and possessing a
tobacco-like odour. It can, however, be obtained in well-marked
odourless crystals, which melt at 108°-109°, a portion subliming
unchanged. It liquefies under boiling water without crystallisation.
According to Thorey,[510] hyoscyamine crystallises out of chloroform in
rhombic tables, and out of benzene in fine needles; but out of ether or
amyl alcohol it remains amorphous. When perfectly pure, it dissolves
with difficulty in cold, but more readily in hot, water; if impure, it
is hygroscopic, and its solubility is much increased. In any case, it
dissolves easily in alcohol, ether, chloroform, amyl alcohol, benzene,
and dilute acids. Hyoscyamine neutralises acids fully, and forms
crystallisable salts, which assume for the most part the form of
needles. It is isomeric with atropine, and is converted into atropine by
heating to 110°, or warming with alcoholic potash. The gold salt melts
at 159°, and does not melt in boiling water like the atropine gold salt.

[510] _Pharm. Zeitschr. f. Russl._, 1869.

§ 457. =Pharmaceutical and other Preparations of Henbane.=--The leaves
are alone officinal in the European pharmacopœias; but the seeds and the
root, or the flowers, may be met with occasionally, especially among
herbalists. The table[511] (p. 382) will give an idea of the alkaloidal
content of the different parts of the plant.

[511] This table, taken from Dragendorff’s _Chemische Werthbestimmung
einiger starkwirkenden Droguen_, embodies the researches of Thorey.

In order to ascertain the percentage of the alkaloid in any part of the
plant, the process followed by Thorey has the merit of simplicity. The
substance is first exhausted by petroleum ether, which frees it from
fat; after drying, it is extracted with 85 per cent. alcohol at a
temperature not exceeding 40°. The alcoholic extracts are then united,
the alcohol distilled off, and the residue filtered. The filtrate is now
first purified by agitation with petroleum ether, then saturated by
ammonia, and shaken up with chloroform. The latter, on evaporation,
leaves the alkaloid only slightly impure, and, after washing with
distilled water, if dissolved in dilute sulphuric acid, a crystalline
sulphate may be readily obtained.

=A tincture and an extract of henbane leaves and flowering tops= are
officinal in most pharmacopœias; an extract of the seeds in that of
France.

=An oil of hyoscyamus= is officinal in all the Continental
pharmacopœias, but not in the British.

=Henbane juice= is recognised by the British pharmacopœia; it is about
the same strength as the tincture.

=An ointment=, made of one part of the extract to nine of simple
ointment, is officinal in the German pharmacopœia.

The tincture (after distilling off the spirit) and the extracts (on
proper solution) may be conveniently titrated by Mayer’s reagent (p.
263), which, for this purpose, should be diluted one-half; each c.c.
then, according to Dragendorff, equalling 6·98 mgrms. of hyoscyamine.
Kruse found 0·042 per cent. of hyoscyamine in a Russian tincture, and
·28 per cent. in a Russian extract. Any preparation made with extract of
henbane will be found to contain nitrate of potash, for Attfield has
shown the extract to be rich in this substance. The ointment will
require extraction of the fat by petroleum ether; this accomplished, the
determination of its strength is easy.

=The oil of hyoscyamus= is poisonous, and contains the alkaloid. An
exact quantitative research is difficult; but if 20 grms. of the oil are
shaken up for some time with water acidified by sulphuric acid, the
fluid separated from the oil, made alkaline, shaken up with chloroform,
and the latter removed and evaporated, sufficient will be obtained to
test successfully for the presence of the alkaloid, by its action on the
pupil of the eye.

§ 458. =Dose and Effects.=--The dose of the uncrystalline hyoscyamine is
6 mgrms. (1/10 grain), carefully increased. I have seen it extensively
used in asylums to calm violent or troublesome maniacs. Thirty-two
mgrms. (½ grain) begin to act within a quarter of an hour; the face
flushes, the pupils dilate, there is no excitement, all muscular motion
is enfeebled, and the patient remains quiet for many hours, the effects
from a single dose not uncommonly lasting two days. 64·8 mgrms. (1
grain) would be a very large, and possibly fatal, dose. The absence of
delirium or excitement, with full doses of hyoscyamine, is a striking
contrast to the action of atropine, in every other respect so closely
allied; yet there are cases on record showing that the henbane root
itself has an action similar to that of belladonna, unless indeed one
root has been mistaken for another; _e.g._, Sonnenschein relates the
following ancient case of poisoning:--In a certain cloister the monks
ate by error the root of henbane. In the night they were all taken with
hallucinations, so that the pious convent was like a madhouse. One monk
sounded at midnight the matins, some who thereupon came into chapel
could not read, others read what was not in the book, others sang
drinking songs--in short, there was the greatest disturbance.

§ 459. =Separation of Hyoscyamine from Organic Matters.=--The isolation
of the alkaloid from organic tissues or fluids, in cases where a
medicinal preparation of henbane, or of the leaves, root, &c., has been
taken, is possible, and should be carried out on the principles already
detailed. Hyoscyamine is mainly identified by its power of dilating the
pupil of the eye. It is said that so small a quantity as ·0083 mgrm.
(1/4000 grain) will in fifteen minutes dilate the eye of a rabbit. It is
true that atropine also dilates the pupil; but if sufficient of the
substance should have been isolated to apply other tests, it can be
distinguished from atropine by the fact that the latter gives no
immediate precipitate with platinic chloride, whilst hyoscyamine is
precipitated by a small quantity of platinic chloride, and dissolved by
a larger amount, and also by the characters of the gold salt.


3. HYOSCINE.

    § 460. =Hyoscine=, C₁₇H₂₃NO₃.--According to E. Schmidt[512] the
    formula is C₁₇H₂₁NO₄ + H₂O, and the alkaloid is identical with
    scopolamine. Scopolamine has a m.p. of 59°, gives an aurochloride,
    crystallising in needles, the m.p. of which is 212° to 214°; when
    boiled with baryta water, it splits up into atropic acid and
    scopoline, a base (C₈H₁₃NO), m.p. 110°, boiling-point, 241° to 243°;
    scopoline forms an aurochloride, m.p. 223°-225°; and a
    platinochloride, m.p. 228°-230°; but Ladenburg,[513] in answer to
    Schmidt, asserts that hyoscine exists, and is not identical with
    scopolamine. A sample of commercial hyoscine hydrobromide Nagelvoort
    found to melt, water-free, at 198°; other commercial samples of
    hydrobromide melted at 179° and 186°; the latter sample giving an
    aurochloride which melted at 192°. Pure hyoscine gold chloride is
    stated to melt at 198°. Its reactions are much the same as those of
    atropine, but it does not blacken calomel. It is very poisonous.

[512] _Arch. Pharm._, ccxxx. 207-231.

[513] _Ber._, xxv. 2388-2394.

    According to experiments on animals, the heart is first slowed, then
    quickened; the first effect being due to a stimulation of the
    inhibitory nervous apparatus, the second to a paralysing action on
    the same. The temperature is not altered. The pupils are dilated,
    the saliva diminished. The irritability of the brain is
    lessened.[514]

[514] Parloff, _St Petersburg Med. Chem. Acad._, Dissert. No. 9,
1889-90.


4. SOLANINE.

    § 461. =Distribution of Solanine.=--Solanine is a poisonous
    nitrogenised glucoside found in all parts of the plants belonging to
    the nightshade order. The English common plants in which solanine
    occurs are the edible potato plant (_Solanum tuberosum_), the
    nightshade (_Solanum nigrum_), and the _Solanum dulcamara_, or
    bitter-sweet. The berries of the _Solanum nigrum_ and those of _S.
    dulcamara_ contain about 0·3 per cent. Mature healthy potatoes
    appear to contain no solanine, but from 150 grms. of diseased
    potatoes G. Kassner[515] separated 30 to 50 mgrms.

[515] _Arch. Pharm._ (3), xxv. 402, 403.

    R. Firbas,[516] in a research on the active substances or young
    shoots of the _S. tuberosum_ found two products--one crystalline,
    _Solanine_; the other amorphous, _Solaneine_. He gives the following
    formula to solanine--C₅₂H₉₃NO₁₈4½H₂O; when dried at 100° it becomes
    anhydrous. From a solution in 85 per cent. alcohol it crystallises
    in colourless needles, m.p. 244°; these are almost insoluble in
    ether and alcohol, but are readily dissolved in dilute hydrochloric
    acid. On hydrolysis solanine breaks up into solanidine and a sugar,
    according to the equation--

[516] _Monatsh._, x. 541-560; _Journ. Chem. Soc._ (Abst.), Jan. 1890.

  C₅₂H₉₃NO₁₈ = C₄₀H₆₁NO₂ + 2C₆H₁₂O₆ + 4H₂O.

    § 462. =Properties of Solanine.=--The reaction of the crystals is
    weakly alkaline; the taste is somewhat bitter and pungent. Solanine
    is soluble in 8000 parts of boiling water, 4000 parts of ether, 500
    parts of cold, and 125 of boiling alcohol. It dissolves well in hot
    amyl alcohol, but is scarcely soluble in benzene. An aqueous
    solution froths on shaking, but not to the degree possessed by
    saponine solutions.

    The amyl alcohol solution has the property of gelatinising when
    cold. It does this if even so little as 1 part of solanine is
    dissolved in 2000 of hot amyl alcohol. The jelly is so firm that the
    vessel may be inverted without any loss. This peculiar property is
    one of the most important tests for the presence of solanine. The
    hot ethylic alcohol solution will, on cooling, also gelatinise, but
    a stronger solution is required. From very dilute alcoholic
    solutions (and especially with slow cooling) solanine may be
    obtained in crystals. In dilute mineral acids solanine dissolves
    freely, and forms salts, which for the most part have an acid
    reaction and are soluble in alcohol and in water, but with
    difficulty in ether. The compounds with the acids are not very
    stable, and several of them are broken up on warming the solution,
    solanine separating out from the aqueous solutions of the solanine
    salts. The alkaloid may be precipitated by the fixed and volatile
    alkalies, and by the alkaline earths. Solanine will stand boiling
    with strongly alkaline solutions without decomposition; but dilute
    acids, on warming, hydrolyse. By heating solanine in alcoholic
    solution with ethyl iodide in closed tubes, and then treating the
    liquid with ammonia, ethyl solanine in well-formed crystals can be
    obtained. Solanine is precipitated by phosphomolybdic acid, but by
    very few other substances. It gives, for example, no precipitate
    with the following reagents:--Platinic chloride, gold chloride,
    mercuric chloride, potassic bichromate, and picric acid. Tannin
    precipitates it only after a time. Sodic phosphate gives a
    crystalline precipitate of solanine phosphate, if added to a
    solution of solanine sulphate. Both solanine and solanidine give
    with nitric acid at first a colourless solution, which, on gentle
    warming, passes into blue, then into light red, and lastly becomes
    weakly yellow. Solanine, dissolved in strong sulphuric acid, to
    which a little Fröhde’s reagent is added, at first colours the fluid
    light brown; after standing some time the edges of the drop becomes
    reddish-yellow, and finally the whole a beautiful cherry-red, which
    gradually passes into dark violet when violet-coloured flocks
    separate.

    § 463. =Solanidine.=--Solanidine has stronger basic properties than
    solanine. Its formula is C₄₀H₆₁NO₂. It is obtained from an alcoholic
    solution in amorphous masses interspersed with needles; m.p. 191°.
    It dissolves readily in hot alcohol, with difficulty in ether. With
    hydrochloric acid it forms a hydrochloride--3(C₄₀H₆₁NO₂HCl)HCl + H₂O
    or 1½H₂O. This hydrochloride is a slightly yellow powder, only
    sparingly soluble in water, and carbonising without melting when
    heated to 287°. Solanidine also forms a sulphate,
    3(C₄₀H₆₁NO₂H₂SO₄)H₂SO₄ + 8H₂O; this salt is in the form of scaly
    plates, melting at 247°; it dissolves readily in water.

    The sugar obtained from the hydrolysis of solanidine is a yellow
    amorphous mass dissolving readily in water and wood spirit, and has
    a specific rotatory power of [α]_{D} = + 28·623. With
    Phenylhydrazine hydrochloride and sodium acetate in aqueous solution
    it forms a glucosazone, melting at 199°. It is probably a mixture of
    sugars.

    Solaneine is the name that has been given to the amorphous substance
    accompanying solanine; on hydrolysis it yields solanidine and the
    same sugar as solanine. Its formula is C₅₂H₈₂NO₁₃ with 4H₂O.

    § 464. =Poisoning from Solanine.=--Poisoning from solanine has been,
    in all recorded cases, induced, not by the pure alkaloid (which is
    scarcely met with out of the laboratory of the scientific chemist),
    but by the berries of the different species of _Solanum_, and has
    for the most part been confined to children. The symptoms in about
    twenty cases,[517] which may be found detailed in the medical
    literature of this century, have varied so greatly that the most
    opposite phenomena have been witnessed as effects of poisoning by
    the same substance. The most constant phenomena are a quick pulse,
    laboured respiration, great restlessness, and hyperæsthesia of the
    skin. Albumen in the urine is common. Nervous symptoms, such as
    convulsions, aphasia, delirium, and even catalepsy, have been
    witnessed. In some cases there have been the symptoms of an irritant
    poison--diarrhœa, vomiting, and pain in the bowels: in many cases
    dilatation of the pupil has been observed.

[517] See “Death of Three Children by _S. nigrum_”; Hirtz., _Gaz. Med.
de Strasbourg_, 1842; Maury, _Gaz. des Hôp._, 1864; J. B. Montane,
_Chim. Med._, 1862; Magne, _Gaz. des Hôp._, 1869; Manners, _Edin. Med.
Journ._, 1867. Cases of poisoning by bitter-sweet berries are recorded
in _Lancet_, 1856; C. Bourdin, _Gaz des Hôpitaux_, 1864; Bourneville,
the berries of _S. tuberosum_, _Brit. Med. Journ._, 1859.

    Rabbits are killed by doses of ·1 grm. per kilo. The symptoms
    commence in about ten minutes after the administration, and consist
    of apathy and a low temperature; the breathing is much slowed.
    Convulsions set in suddenly before death, and the pupils become
    dilated. The _post-mortem_ appearances in animals are intense
    redness and injection of the meninges of the cerebellum, of the
    medulla oblongata, and the spinal cord. Dark red blood is found in
    the heart, and the kidneys are hyperæmic. The intestinal mucous
    membrane is normal.

    § 465. =Separation of Solanine from the Tissues of the
    Body.=--Dragendorff has proved the possibility of separating
    solanine from animal tissues by extracting it from a poisoned pig.
    The best plan seems to be to extract with cold dilute sulphuric acid
    water, which is then made alkaline by ammonia, and shaken up with
    warm amyl alcohol. This readily dissolves any solanine. The peculiar
    property possessed by the alkaloid of gelatinising, and the play of
    colours with Fröhde’s reagent, may then be essayed on the solanine
    thus separated.


5. CYTISINE.

§466. =The Cytisus Laburnum.=--The laburnum tree, _Cytisus laburnum_, so
common in shrubberies, is intensely poisonous. The flowers, bark, wood,
seeds, and the root have all caused serious symptoms. The active
principle is an alkaloid, to which the name of Cytisine has been given.
The best source is the seeds. The seeds are powdered and extracted with
alcohol containing hydrochloric acid, the alcohol distilled off, the
residue treated with water and filtered through a wet filter to remove
any fatty oil, the filtrate treated with lead acetate; and, after
separating the precipitated colouring matter, made alkaline with caustic
potash, and shaken with amyl alcohol. The amyl alcohol is shaken with
dilute hydrochloric acid, the solution evaporated, the crude crystals
of hydrochloride thus obtained treated with alcohol to remove colouring
matters, and recrystallised several times from water; it then forms
well-developed, colourless, transparent prisms. From the hydrochloride
the free base is readily obtained.

=Cytisine=, C₁₁H₁₄N₂O.--To cytisine used to be ascribed the formula
C₂₀H₂₇N₃O, but a study of the salt and new determinations appear to
prove that it is identical with ulexine.[518] Cytisine is in the form of
white radiating crystals, consisting, when deposited from absolute
alcohol, of anhydrous prisms, which melt at from 152° to 153°. Cytisine
has a strong alkaline reaction; it is soluble in water, alcohol, and
chloroform, less so in benzene and amyl alcohol, almost insoluble in
cold light petroleum, and insoluble in pure ether. The specific rotatory
power in solution is [α]_{D}17° = -119·57.

[518] A. W. Gerrard and W. H. Symons dispute this; they ascribe to
ulexine the formula of C₁₁H₁₄N₂O, to cytisine C₂₀H₂₇N₃O. Ulexine is very
hygroscopic, cannot be sublimed, even in a vacuum, without
decomposition, and dissolves readily in chloroform; on the contrary,
cytisine is not hygroscopic, sublimes completely, and is almost
insoluble in chloroform, _Pharm. J._ (3), xx. 1017.

A. Partheil, _Ber._, xxiii. 3201-3203; _Arch. Pharm._, ccxxx. 448-498.

It is capable of sublimation in a current of hydrogen at 154·5°; the
sublimate is in the form of very long needles and small leaflets; at
higher temperatures it melts to a yellow oily fluid, again becoming
crystalline on cooling. Cytisine is a strong base; it precipitates the
earths and oxides of the heavy metals from solutions of the chlorides,
and, even in the cold, expels ammonia from its combinations.

Cytisine forms numerous crystalline salts, among which may be mentioned
two platinochlorides, C₁₁H₁₄N₂OH₂PtCl₆ + 2½H₂O and (C₁₁H₁₄N₂O)₂H₂PtCl₆,
crystallising in golden yellow needles, which are tolerably soluble in
water; and the aurochloride, C₁₁H₁₄N₂OHAuCl₄, crystallising in short,
red-brown, hook-shaped needles; m.p. 212° to 213°, without evolution of
gas.

§ 467. =Reactions of Cytisine.=--Concentrated sulphuric acid dissolves
cytisine without colour; if to the solution is added a drop of nitric
acid, it becomes orange-yellow, and on addition of a crystal of potassic
bichromate, first yellow, then dirty brown, and lastly green.
Concentrated nitric acid dissolves the base in the cold without colour,
but, on warming, it becomes orange-yellow. Picric, tannic, and
phosphomolybdic acids, potassic, mercuric, and potass. cadmium iodides,
and iodine with potassic iodide, all give precipitates. Neither potassic
bichromate nor mercuric chloride precipitates cytisine, even though the
solution be concentrated. The best single test appears to be the
reaction discovered by Magelhaes; this consists in adding thymol to a
solution of cytisine in concentrated sulphuric acid, when a yellow
colour, finally passing into an intense red, is produced.

§ 468. =Effects on Animals.=--W. Marmé found subcutaneous doses of from
30 to 40 mgrms. fatal to cats; death was from paralysis of the
respiration, and could be avoided by artificial respiration. Cattle are
sometimes accidentally poisoned by laburnum. An instance of this is
recorded in the _Veterinarian_ (vol. lv. p. 92). In Lanark a storm had
blown a large laburnum tree down to the ground; it fell into a field in
which some young heifers were grazing, and they began to feed on the
leaves and pods. Two or three died, and three more were ill for some
time, but ultimately recovered.

The laburnum, however, does not always have this effect, for there is a
case related in the _Gardeners’ Chronicle_, in which five cows browsed
for some time on the branches and pods of an old laburnum tree that had
been thrown aside. Rabbits and hares are said to feed eagerly, and
without injury, on the pods and branches.

§ 469. =Effects on Man.=--The sweet taste of many portions of the
laburnum tree, as well as its attractive appearance, has been the cause
of many accidents. F. A. Falck has been able to collect from medical
literature no less than 155 cases--120 of which were those of the
accidental poisoning of children: only 4 (or 2·6 per cent.), however,
died, so that the poison is not of a very deadly character.

One of the earliest recorded cases is by Christison.[519] A servant-girl
of Inverness, in order to excite vomiting in her fellow-servant (the
cook), boiled some laburnum bark in soup; very soon after partaking of
this soup, the cook experienced violent vomiting, which lasted for
thirty-six hours; she had intense pain in the stomach, much diarrhœa,
and great muscular weakness; she appears to have suffered from
gastro-intestinal catarrh for some time, but ultimately recovered.

[519] _Ed. Med. Journ._, 1843.

Vallance[520] has described the symptoms observed in the poisoning of
fifty-eight boys, who ate the root of an old laburnum tree, being
allured by its sweet taste. All were taken ill with similar symptoms,
differing only in severity; two who had eaten half an ounce (nearly 8
grms.) suffered with especial severity. The symptoms were first
vomiting, then narcosis, with convulsive movements of the legs and
strange movements of the arms: the pupils were dilated. This dilatation
of the pupil Sedgwick also saw in the poisoning of two children who ate
the root. On the other hand, when the flower, seeds, or other portions
of the laburnum have been eaten, the symptoms are mainly referable to
the gastro-intestinal tract, consisting of acute pain in the stomach,
vomiting, and diarrhœa. On these grounds it is therefore more than
probable that there is another active principle in the root, differing
from that which is in those portions of the tree exposed to the
influence of sunlight.[521]

[520] _Brit. Med. Journ._, 1875.

[521] See also a case related by Dr. Popham, in which ten children ate
laburnum seeds; the pupils were dilated. They all recovered. _B. and F.
Med. Chir. Review_, Ap. 1863; also a case reported by H. Usher, _Med.
Times and Gazette_, Sept. 15, 1862.

The _post-mortem_ appearances are, so far as known, in no way
characteristic.


VII.--The Alkaloids of the Veratrums.

§ 470. The alkaloids of the veratrums have been investigated by Dr.
Alder Wright, Dr. A. P. Luff, and several other chemists.[522]

[522] “The Alkaloids of the Veratrums,” by C. R. Alder Wright, D.Sc.,
and A. P. Luff, _Journ. Chem. Soc._, July 1879; “The Alkaloids of
_Veratrum viride_,” by C. Alder Wright, D.Sc., _ib._, 1879.

The method which Wright and Luff adopted to extract and separate these
alkaloids from the root of _V. album_ and _V. viride_, essentially
consisted in exhausting with alcohol, to which a little tartaric acid
has been added, filtering, distilling off the alcohol, dissolving the
residue in water, alkalising with caustic soda, and shaking up with
ether. The ethereal solution was next separated, and then washed with
water containing tartaric acid, so as to obtain a solution of the bases
as tartrates: in this way the same ether could be used over and over
again. Ultimately a rough separation was made by means of the different
solubilities in ether, pseudo-jervine being scarcely soluble in this
medium, whilst jervine, veratralbine, veratrine, and cevadine are very
soluble in it.

The yield of Wright and Luff’s alkaloids was as follows:--

TABLE SHOWING THE ALKALOIDS IN THE VERATRUMS.

  +---------------+------------+---------------------+
  |               | V. album.  |    V. viride.       |
  |               | Per Kilo.  |     Per Kilo.       |
  |               +------------+---------------------+
  |Jervine,       |  1·3 grm.  |    ·2  grm.         |
  |Pseudo-jervine,|   ·4  „    |    ·15  „           |
  |Rubi-jervine,  |   ·25 „    |    ·02  „           |
  |Veratralbine,  |  2·2  „    |    Traces.          |
  |Veratrine,     |   ·05 „    | Less than ·004 grm. |
  |Cevadine,      |  Absent.   |     „     ·43   „   |
  +---------------+------------+---------------------+

From whence it appears that _V. album_ has only a very small quantity of
veratrine, that it is almost absent in _V. viride_; on the other hand,
_V. viride_ contains a fair quantity of cevadine, an alkaloid absent in
_V. album_.

Besides the six principles enumerated, G. Salzberger has recently
separated two other crystalline substances, to which he has given the
names of _protoveratrine_ and _protoveratridine_, and Pehkschen has also
separated a ninth substance, to which he has given the name of
_veratroidine_.

The formulæ of the nine bodies which have been separated from hellebore
root are as follows:--

                                                 Melting-point.
  1. Veratrine, C₃₇H₅₃NO₁₁,                              ...
  2. Cevadine, C₃₂H₄₉NO₉,                             205°-206°
  3. Protoveratrine, C₃₂H₅₁NO₁₁,                      245°-250°
  4. Pseudo-jervine, { C₂₉H₄₃NO₇  (_Wright_),          299°-300°
                     { C₂₉H₄₉NO₁₂ (_Pehkschen_),         ...
  5. Veratralbine, C₂₈H₄₃NO₅,                            ...
  6. Protoveratridine, C₂₆H₄₅NO₈,                        265°
  7. Rubi-jervine, { C₂₆H₄₃NO₂ (_Wright_ and _Luff_),    236°
                   {           (_Salzberger_),        240°-245°
  8. Jervine, C₂₆H₃₇NO₃2H₂O,                           237°-239°
  9. Veratroidine, C₃₂H₅₃NO₉,                            149°

Three of these alkaloids possess powerful sternutatory properties, the
least quantity applied to the nostrils exciting sneezing; the three are
veratrine, cevadine, and protoveratrine.

Protoveratrine, C₃₂H₅₁NO₁₁, has been obtained by G. Salzberger[523] from
powdered hellebore root, by the following process:--

[523] _Arch. Pharm._, ccxxviii. 462-483.

The powdered root is first freed from fatty and resinous matters by
treatment with ether, and then the fat-free powder is exhausted with
alcohol. The alcohol is evaporated off in a vacuum, the extract mixed
with much acetic acid water, filtered from the insoluble residue, and
treated with metaphosphoric acid; the voluminous precipitate contains
much amorphous matter, with insoluble compounds of jervine and
rubi-jervine. The precipitate is filtered off, and the filtrate treated
with excess of ammonia and shaken up with ether. On separating the ether
and distilling, protoveratrine crystallises out, and can be obtained
pure by recrystallisation from strong alcohol.

Protoveratrine crystallises in four-sided plates, which melt with
charring at 245° to 250°. The base is insoluble in water, benzene, and
light petroleum; chloroform and boiling 96 per cent. alcohol dissolve it
somewhat; cold ether scarcely touches it, boiling ether dissolves it a
little.

Concentrated sulphuric acid dissolves the alkaloid slowly with the
production of a greenish colour, which passes to cornflower blue, and,
after some hours, becomes violet. Sulphuric acid and sugar gives a
different colour to that produced by commercial veratrine. There is
first a green colour which darkens into olive green, then becomes dirty
green, and finally dark brown. When warmed with strong sulphuric,
hydrochloric, or phosphoric acids, there is a strong odour of
isobutyric acid developed. Dilute solutions of the salts are
precipitated by ammonia, Nessler’s reagent, gold chloride, potassium
mercury iodide, cadmium iodide, phosphotungstic acid, and picric acid;
no precipitate is produced by tannin, platinum chloride, or mercuric
chloride.

§ 471. =Veratrine= (C₃₇H₅₃NO₁₁) is a crystallisable alkaloid, which is a
powerful irritant of the sensory nerves of the mucous membrane, and
excites violent sneezing. Treated with concentrated sulphuric acid, it
dissolves with a yellow colour, deepening into orange, then into
blood-red, and finally passing into carmine-red. If the freshly-prepared
sulphuric acid solution is now treated with bromine water, a beautiful
purple colour is produced. Concentrated hydrochloric acid dissolves
veratrine without the production of colour, but, with careful warming,
it becomes beautifully red. This reaction is very delicate, occurring
with ·17 mgrm. On saponification veratrine yields veratric acid.

Veratric acid is procatechu-dimethylether acid, and has the
constitutional formula,

       COOH
      /
  C₆H₃
      \
       (OCH₃)₂

Veratric acid forms colourless needles and four-sided prisms which have
a marked acid reaction; it melts on heating to a colourless fluid, and
sublimes without decomposition; it is easily soluble in hot alcohol, but
insoluble in ether. If dissolved in nitric acid, water separates
nitro-veratric acid, C₉H₉(NO₂)O₄ which crystallises out of alcohol in
small yellow scales. Veratric acid unites with bases forming crystalline
salts; the silver salt has the composition of C₉H₉AgO₄ = 37·37 per cent.
silver, and may assist in identification. It is crystalline with a
melting point of 205° to 206°.

=Cevadine=, C₃₂H₄₉NO₉ (Merck’s veratrine).--It has powerful sternutatory
properties, and, under the influence of alcoholic potash, yields
tiglic[524] acid and cevine, C₂₇H₄₃NO₈.

[524] Tiglic acid, C₅H₈O₂, is a volatile acid, m.p. 64°, boiling point,
198·5°; it forms a soluble barium salt, and an insoluble silver salt.

According to Ahrens, angelic acid is first formed, and then converted
into tiglic acid. When the alkaloid is boiled with hydrochloric acid,
tiglic acid is formed, and a ruby red mass. Nitric acid oxidises
cevadine completely; with potassic permanganate it yields acetic and
oxalic acids; with chromic acid it forms acetaldehyde and carbon
dioxide.[525]

[525] _Ber._, xxiii. 2700-2707.

The Continental authorities always give to cevadine the name of
veratrine. Cevadine forms a crystalline aurochloride, a crystalline
mercurochloride, C₃₂H₄₉NO₉HHgCl₃, and a crystalline picrate,
C₃₂H₄₉NO₉C₆H₃N₈O₇. The mercury salt crystallises in small silvery
plates, and melts with decomposition at 172°. The picrate forms stable
crystals blackening at 225°; both of the latter salts are but little
soluble in water, but are soluble in alcohol. Cevadine also unites with
bromine, forming a tetrabromide, an amorphous yellow powder insoluble in
water, but readily soluble in alcohol, ether, and chloroform.

§ 472. =Jervine=, (C₂₆H₃₇NO₃2H₂O) (_Wright_ and _Luff_), C₁₄H₂₂NO₂
(_Pehkschen_),[526] crystallises in white needles, and, when anhydrous,
melts at 237·7°. It is slightly lævorotatory. At 25° one part of the
base dissolves in 1658 benzene, 268 ether, 60 chloroform, and 16·8
absolute alcohol. It is insoluble in light petroleum, and but slightly
soluble in ethyl acetate, water, or carbon bisulphide. It forms a very
insoluble sulphate, and a sparingly soluble nitrate and hydrochloride.
Jervine gives, with sulphuric acid and sugar, a violet colour, passing
to blue. Treated with strong sulphuric acid it dissolves to a yellow
fluid, which becomes successively dark yellow, brownish yellow, and then
greenish. The green shade is immediately developed by diluting with
water. Jervine does not produce sneezing.

[526] _Jour. Pharm._ (5), xxii. 265-269.

§ 473. =Pseudo-jervine=, C₂₉H₄₃NO₇ (_Wright_), m.p. 299°; C₂₉H₄₉NO₁₂,
m.p. 259° (_Pehkschen_), may be obtained in a crystalline state. One
part is soluble in 10·9 parts of light petroleum, 372 parts of benzene,
1021 parts of ether, 4 of chloroform, and 185 of absolute alcohol. The
pure base gives no colour with sulphuric, nitric, or hydrochloric acids.
It does not produce sneezing.

§ 474. =Protoveratridine=, C₂₆H₄₅NO₈, is probably derived from
protoveratrine. Salzberger[527] isolated it from powdered hellebore
roots by treating the powder with barium hydroxide and water, and
extracting with ether. The ether extract was separated and freed from
ether in a current of hydrogen at a low temperature.

[527] _Arch. Pharm._, ccxxviii. 462-483.

From the dark green syrup obtained jervine crystallised out, and from
the mother liquor ultimately protoveratridine was separated.

Protoveratridine crystallises in colourless four-sided plates, which
melt at 265°. It is almost insoluble in alcohol, chloroform, methyl
alcohol, and acetone, and insoluble in benzene, light petroleum, and
ether. Concentrated sulphuric acid gives a violet, then a cherry-red
colour. Its solution in concentrated hydrochloric acid becomes light red
on warming, and there is an odour of isobutyric acid. It is readily
soluble in dilute mineral acids, and the solution, on the addition of
ammonia, yields the alkaloid in a crystalline condition. The sulphuric
acid solution gives precipitates with phosphotungstic, picric, and
tannic acids, and with potassium mercury iodide; but gives no
precipitate with platinum chloride, potassium-cadmium iodide, or with
Millon’s reagent.

It forms a platinum salt, (C₂₆H₄₅NO₈)₂H₂PtCl₆ + 6H₂O, which is
precipitated in large six-sided plates on adding alcohol to a mixed
solution of platinum chloride and a salt of the base.

Protoveratridine is not poisonous, and does not cause sneezing. Its
solutions are very bitter.

§ 475. =Rubi-jervine=, C₂₆H₄₃NO₂, is a crystallisable base wholly
different from jervine, yet probably closely allied to it. It forms a
light yellow, indistinctly crystalline gold salt (C₂₆H₄₃NO₂,HCl,AuCl₃):
it gives a different play of colours from jervine with sulphuric acid.
The concentrated acid dissolves rubi-jervine to a clear yellow fluid,
becoming successively dark yellow, brownish yellow, and brownish
blood-red, changing after several hours to a brownish purple. On
diluting slightly with water the brownish-red liquid, it becomes
successively crimson, purple, dark lavender, dark violet, and ultimately
light indigo. Its hydrochloride and sulphate are both more soluble than
either of the corresponding salts of jervine or pseudo-jervine.

§ 476. =Veratralbine=, C₂₈H₄₃NO₅, an amorphous non-sternutatory base,
gives, when a speck of the substance is dissolved in sulphuric acid, a
play of colours, becoming successively yellow, dark yellow, brownish
orange, and brownish blood-red, with a strong green fluorescence. It
yields no acid on saponification.

§ 477. =Veratroidine=, C₃₂H₅₃NO₉, is another base which has been
separated by C. Pehkschen.[528] Its melting point is 149°. One part
dissolves in 13 of benzene, 59 of chloroform, and 9 of ether. It yields
amorphous salts with the mineral acids, and with oxalic and acetic
acids. It is precipitated by most of the group reagents. With 11 per
cent. solution of hydrochloric acid it gives a beautiful rose colour.

[528] _Op. cit._

§ 478. =Commercial Veratrine.=--Commercial veratrine is a mixture of
alkaloids, and has usually fairly constant properties, one of which is
its intense irritant action on the nostrils. Placed on moist blue-red
litmus paper it gives a blue spot. It is but little soluble in water,
1 : 1500; but readily dissolves in alcohol and chloroform; it is but
little soluble in amyl alcohol, benzene, and carbon disulphide.

When a very small quantity is treated with a drop of sulphuric acid, the
acid in the cold strikes a yellow colour; on warming, the colour becomes
violet, slowly changing to orange and cherry red. Sensible to 100th of
mgrm. If this test is performed in a test-tube, a green-yellow
fluorescence is also seen on the sides of the test-tube.

Commercial veratrine strikes a pink-red colour with hydrochloric acid in
the cold if a long time is allowed to elapse, but it at once appears if
the acid is warmed, and is permanent. The solution becomes fluorescent
if two drops of acetic acid are added.

If a small quantity of commercial veratrine is added to melted oxalic
acid and the warming continued, a blood-red colour is obtained.

Veratrine, warmed with syrupy phosphoric acid, develops an odour of
butyric acid.

A dark green colour, followed by reddish purple and blue colours, is
obtained by adding a sprinkling of finely-powdered sugar to a solution
of veratrine in sulphuric acid. This is best seen with a solution of 1
to 10,000; if in dilution of 1 to 100,000 a grass-green colour is
produced, followed by purple and blue colours, quickly changing to brown
or black.[529]

[529] _Flückiger’s Reactions_, 1893.

When two or three drops of sulphuric acid and furfur aldehyde (5 drops
to 10 c.c. of acid) are added to minute particles of alkaloids, a more
or less characteristic colour makes its appearance; this is particularly
the case with veratrine. A few particles rubbed with a glass rod, and
moistened with the reagent, gives first a yellowish-green, then an
olive-green mixture, the edges afterwards becoming a beautiful blue. On
warming, the mixture gradually acquires a purple-violet colour. The blue
substance obtained in the cold is insoluble in alcohol, ether, or
chloroform. The least amount of water decolorises the solution, and, on
adding much water, a fairly permanent yellow solution is obtained.[530]

[530] A. Wender, _Chem. Zeitung_, xvii. 950, 951.

§ 479. =Pharmaceutical Preparations.=--The alkaloid is officinal in the
English, American, and Continental pharmacopœias. There is also an
_unguentum veratrinæ_--strength about 1·8 per cent. In the London
pharmacopœia of 1851 there used to be a wine of white hellebore, the
active principle of 20 parts of the root by weight being contained in
100 parts by measure of the wine. Such a wine would contain about 0·084
per cent. of total alkaloids. Of the green hellebore there is a tincture
(_tinctura veratri viridis_), to make which four parts by weight of the
root are exhausted by 20 parts by measure of spirits; the strength
varies, but the average is 0·02 per cent. of total alkaloids.

§ 480. =Fatal Dose.=--The maximum dose of the commercial alkaloid is
laid down as 10 mgrms. (·15 grain), which can be taken safely in a
single dose, but nothing sufficiently definite is known as to what is a
lethal dose. 1·3 grm. of the powdered rhizome has caused death, and, on
the other hand, ten times that quantity has been taken with impunity, so
that at present it is quite an open question.

§ 481. =Effects on Animals--Physiological Action.=--Experiments on
animals have proved that the veratrums act on the sensory nerves of the
skin, and those of the mucous membranes of the nose and intestinal
canal; they are first excited, afterwards paralysed. When administered
to frogs, sugar and lactic acid appear in the urinary excretion.[531]
It exercises a peculiar influence on voluntary muscle; the
contractility is changed, so that, when excited, there is a
long-continuing contraction, and from a single stimulus more heat is
disengaged than with healthy muscle; the motor nerves are also affected.
The respiration, at first quickened, is then slowed, and finally
paralysed. The heart’s action is also first quickened, the
blood-pressure at the same time is raised, and the small arteries
narrowed in calibre; later follow sinking of the pressure, slowing of
the heart, and dilatation of the vessels, and the heart becomes finally
paralysed.

[531] _Zeit. Phys. Chem._, xvi. 453-459.

§ 482. =Effects on Man.=--Poisoning by veratrum, sabadilla, or
pharmaceutical preparations containing veratrine, is not common. Plenk
witnessed a case in which the external application of sabadilla powder
to the head caused delirium, and Lentin also relates a case in which an
infant at the breast seems to have died from an external application
made for the purpose of destroying lice. In both instances, however,
there is a possibility that some of the medicament was swallowed.

Blas recorded, in 1861, the case of two children who drank a decoction
of white hellebore, the liquid being intended as an external application
to an animal. They showed serious symptoms, but ultimately recovered.

A scientific chemist took 3·8 grms. (58 grains) of the tincture of green
hellebore for the purpose of experiment. There followed violent symptoms
of gastric irritation, vomiting, and diarrhœa, but he also
recovered.[532]

[532] _Med. Times and Gazette_, Jan. 3, 1863.

Casper relates the poisoning of a whole family by veratrum; from the
stomach of the mother (who died) and the remains of the repast (a
porridge of lentils) veratrine was separated.

Faber[533] recorded the poisoning of thirty cows by veratrum; eight
died, and it is noteworthy that violent poisonous symptoms were produced
in animals partaking of their flesh and milk.

[533] _Zeitschr. f. Staatsarzneik._, 1862.

§ 483. The symptoms appear soon after the ingestion, and consist of a
feeling of burning in the mouth, spreading downwards to the stomach,
increased secretion of saliva, and difficulty of swallowing; then follow
violent vomiting and diarrhœa, with great pain in the bowels, often
tenesmus; there is also headache, giddiness, a feeling of anxiety, and
the pupils are dilated. The consciousness is ordinarily intact; the
pulse is weak and slow, and the breathing embarrassed; the skin is
benumbed. There may be also formicating feelings, and twitchings in the
muscles with occasionally the tetanic cramps, which are constantly seen
in frogs. In cases which end fatally, the disturbance of the breathing
and circulation increases, and death takes place in collapse.

An important case of slow poisoning is on record,[534] in which two
brothers, aged twenty-one and twenty-two years, died after nine and
eleven weeks of illness, evidently from repeated small doses of the
powder of _Veratrum album_. They became very weak and thin, suffered
from diarrhœa and bloody stools, sleeplessness, disturbance of the
intellect, and delirium.

[534] Nivet and Géraud, _Gaz. Hebdom._, 1861.

§ 484. The _post-mortem_ signs do not appear distinctive; even in the
case just mentioned--in which one would expect to find, at all events,
an extensive catarrh of the intestinal canal--the results seem to have
been negative.

§ 485. =Separation from Organic Matters.=--The method of Stas (by which
the organic matters, whether the contents of the stomach or the tissues,
are treated with alcohol, weakly acidified by tartaric acid) is to be
recommended. After filtering, the alcoholic extract may be freed from
alcohol by careful distillation, and the extract taken up with water. By
now acidifying gently the watery extract, and shaking it up with ether
and chloroform, fatty matters, resinous substances, and other
impurities, are removed, and it may then be alkalised by soda or potash,
and the veratrine extracted by ether. The residue should be identified
by the hydrochloric acid and by the sulphuric acid and bromine
reactions; care should also be taken to ascertain whether it excites
sneezing.

A ptomaine, discovered by Brouardel,[535] was described by him as both
chemically and physiologically analogous to veratrine. A. M.
Deleziniere[536] has since investigated this substance. Only when in
contact with air does the analogy to veratrine obtain, and Deleziniere,
to ascertain its reactions, studied it when in an atmosphere of
nitrogen. It appears to be a secondary monamine, C₃₂H₃₁N, and is in the
form of a colourless, oily liquid, with an odour like that of the
hawthorn. It is insoluble in water, but alcohol, ether, toluene, and
benzene dissolve it readily. It oxidises in the presence of air. The
salts are deliquescent.

[535] _Moniteur Scient._ (3), 10, 1140.

[536] _Bull. Soc. Chim._ (3), 1, 178-180.


VIII.--Physostigmine.

§ 486. The ordeal bean of Calabar (_Physostigma faba_) is a large, all
but tasteless, kidney-shaped bean, about an inch in length, and half an
inch thick; its convex edge has a furrow with elevated ridges, and is
pierced by a small hole at one extremity. The integuments are
coffee-brown in colour, thin, hard, and brittle; they enclose two white
cotyledons, easily pulverisable, and weighing on an average 3·98 grms.
(61 grains). The seed contains at least one alkaloid, termed
_Physostigmine_ (first separated in 1864 by Jobst and Hesse), and
possibly a second, according to Harnack and Witkowsky, who have
discovered in association with physostigmine a new alkaloid, which they
call _Calabarine_, and which differs from physostigmine in being
insoluble in ether and soluble in water. It is also soluble in alcohol;
and further, the precipitate produced by potassium iodo-hydrargyrate in
calabarine solutions is insoluble in alcohol.

§ 487. =Physostigmine=, or =eserine=, is not easily obtained in a
crystalline state, being most frequently extracted as a colourless
varnish, drying into brittle masses. It is, however, quite possible to
obtain it in the form of partially-crystalline crusts, or even rhombic
plates, by care being taken to perform the evaporation, and all the
operations, at as low a temperature as possible, and preferably in a
dimly-lit room; for, if the temperature rises to 40°, much of the
alkaloid will be decomposed. Hesse recommends that the beans be
extracted, alcohol by the alcoholic solution alkalised by sodic
carbonate, and the liquid shaken up with ether, which will retain the
alkaloid. The ether solution is now separated, and acidified slightly
with very dilute sulphuric acid; the fluid, of course, separates into
two layers, the lower of which contains the alkaloid as a sulphate, the
upper is the ether, which is withdrawn, and the acid fluid passed
through a moist filter. The whole process is then repeated as a
purification.

Again, Vee, who has repeatedly obtained the alkaloid in a crystalline
condition, directs the extraction of the beans by alcohol, the alcoholic
solution to be treated as before with sodic carbonate, and then with
ether; the ethereal solution to be evaporated to dryness, dissolved in
dilute acid, precipitated by sugar of lead, and the filtrate from this
precipitate alkalised by potassic bicarbonate, and then shaken up with
ether. The ethereal solution is permitted to evaporate spontaneously,
the crystalline crusts are dissolved in a little dilute acid, and the
solution is lastly alkalised by potassic bicarbonate, when, after a few
minutes, crystalline plates are formed.

The formula ascribed to physostigmine is C₁₅H₂₁N₃O₂. It is strongly
alkaline, fully neutralising acids and forming tasteless salts. It is
easily melted, and perhaps partly decomposed, at a temperature of 45°;
at 100° it is certainly changed, becoming of a red colour, and forming
with acids a red solution. It dissolves easily in alcohol, ether,
chloroform, and bisulphide of carbon, but is not easily soluble in
water.

The salts formed by the alkaloid with the acids are generally
hygroscopic and uncrystallisable, but an exception is met with in the
hydrobromide, which crystallises in stellate groups.[537] If CO₂ is
passed into water containing the alkaloid in suspension, a clear
solution is obtained; but the slightest warmth decomposes the soluble
salt and reprecipitates the alkaloid. The hydrarg-hydroiodide
(C₁₅H₂₁N₃O₂,HI,2HgI) is a white precipitate, insoluble in water,
becoming yellow on drying, soluble in ether and alcohol, and from such
solutions obtained in crystalline prismatic groups. A heat of 70° melts
the crystals, and they solidify again in the amorphous condition.

[537] M. Duquesnel, _Pharm. J. Trans._ (3), v. 847.

It gives a precipitate with gold chloride, reducing the gold; also one
with mercuric chloride easily soluble in hydrochloric acid. It gives no
precipitate with platinum chloride.

§ 488. =Tests.=--Da Silva’s[538] test for eserine is as follows:--A
minute fragment of eserine or one of its salts is dissolved in a few
drops of fuming nitric acid; this makes a yellow solution, but
evaporated to complete dryness it is pure green. The green substance,
called by others chloreserine, dissolves to a non-fluorescent green
solution; in water and also in strong alcohol it shows a band in the red
between λ670 and λ688, a broader but more nebulous band in the blue and
violet between λ400 and λ418, and a very feeble band in the orange.

[538] S. J. Ferreira da Silva, _Compt. Rend._, cxvii. 330, 331.

J. B. Nagelvoort[539] has recommended the following tests:--(_a_) An
amorphous residue of a permanent blue colour is obtained if a trace of
the alkaloid, or one of its salts, is evaporated in the presence of an
excess of ammonia; this blue alkaloid dissolves in dilute acids with a
red colour; sensitiveness 0·00001 gm. (1 : 100000). The solution has
beautiful red fluorescence in reflected light; when evaporated, it
leaves a residue that is green at first, changing to blue afterwards,
the blue residue being soluble in water, alcohol, and chloroform, but
not in ether. Chloroform extracts the blue colour from the watery
ammoniacal solution only partially. The blue solutions are reddened at
first by H₂S, and discoloured afterwards. The blue colour is restored by
expelling the H₂S on the water-bath. (_b_) A red fluid is obtained when
0·010 gm. eserine or its salicylate, 0·050 gm. of slacked lime, and 1
c.c. of water are added together. Warmed in a water-bath, it turns
green, and a piece of red litmus-paper suspended in the test-tube turns
blue; a glass rod moistened with HCl gives off the well-known white
clouds characteristic of an ammonia reaction. The green solution does
not lose its colour by evaporation. Baryta water, added to an eserine
solution, gives a white precipitate that turns red when strongly
agitated, sensitive to 0·01 mgrm. (1 : 100000).

[539] _Flückiger’s Reactions_, 1893.

§ 489. =Pharmaceutical Preparations.=--The only preparations officinal
in this country are a spirituous extract (_Extractum physostigmatis_),
used principally for external application, the dose of which is not more
than 18·1 mgrms. (·18 grain), and gelatine discs for the purpose of the
ophthalmic surgeon, each disc weighing about 1/50th grain, and
containing 1/1000 gr. of the alkaloid.

§ 490. =Effects on Animals.=--A large number of experiments have been
made upon animals with physostigmine, most of them with the impure
alkaloid, which is a mixture of calabarine and physostigmine. Now, the
action of calabarine seems to be the opposite to that of
physostigmine--that is, it causes tetanus. Hence, these experiments are
not of much value, unless the different proportions of the alkaloids
were known. Harnack and Witkowsky[540] made, however, some researches
with pure physostigmine, of which the following are the main
results:--The smallest fatal dose for rabbits is 3 mgrms. per kilo.;
cats about the same; while dogs take from 4 to 5 mgrms. per kilo. Frogs,
under the influence of the alkaloid, lie paralysed without the power of
spontaneous movement, and the sensibility is diminished; later, the
breathing ceases, and the reflex irritability becomes extinguished. The
activity of the heart is through ·5 mgrm. slowed, but at the same time
strengthened.

[540] _Arch. f. Pathol. u. Pharm._, 1876, Bd. v.

The warm-blooded animals experimented upon show rapid paralysis of the
respiratory centre, but the animal by artificial respiration can be
saved. Fibrillar muscular twitching of all the muscles of the body are
observed. Death follows in all cases from paralysis of the respiration.
Experiments (first by Bexold, then by Fraser and Bartholow, and lastly
by Schroff) have amply shown that atropine is, to a certain extent, an
antidote for physostigmine poisoning. Fraser also maintains an
antagonism between strychnine and physostigmine, and Bennet that chloral
hydrate is antagonistic to physostigmine.

=Effects on Man.=--The bean has long been used by the superstitious
tribes of the West Coast of Africa as an ordeal, and is so implicitly
believed in that the innocent, when accused of theft, will swallow it,
in the full conviction that their innocency will protect them, and that
they will vomit up the bean and live. In this way, no doubt, life has
often been sacrificed. Christison experimented upon himself with the
bean, and nearly lost his life. He took 12 grains, and was then seized
with giddiness and a general feeling of torpor. Being alarmed at the
symptoms, he took an emetic, which acted. He was giddy, faint, and
seemed to have lost all muscular power; the heart and pulse were
extremely feeble, and beat irregularly. He afterwards fell into a sleep,
and the next day he was quite well.

In August 1864 forty-six children were poisoned at Liverpool by eating
some of the beans, which had been thrown on a rubbish heap, being part
of the cargo of a ship from the West Coast of Africa. A boy, aged six,
ate six beans, and died. In April of the same year, two children, aged
six and three years, chewed and ate the broken fragments of one bean;
the usual symptoms of gastric irritation and muscular weakness followed,
but both recovered. Physostigmine contracts the iris to a point; the
action is quite local, and is confined to the eye to which it is
applied. When administered internally, according to some, it has no
effect on the eyes, but according to others, it has a weak effect in
contracting the pupil. In any case, the difference of opinion shows that
the effect, when internally administered, is not one of a marked
character.

§ 491. =Physiological Action.=--The physiological action of
physostigmine is strikingly like that of nicotine, which it resembles in
being a respiratory poison, first exciting, afterwards paralysing the
vagus. Like nicotine, also, it produces a great loss of muscular power;
it first excites, and then paralyses the intra-muscular terminations of
the nerves; and, again, like nicotine, it induces a tetanus of the
intestine. A difference between physostigmine and nicotine exists in the
constant convulsive effects of the former, and in the greater influence
on the heart of the latter.

§ 492. =Post-mortem Appearances.=--But little is known relative to the
_post-mortem_ appearances likely to be found in human poisoning; redness
of the stomach and intestines is probably the chief sign.

§ 493. =Separation of Physostigmine.=--For the extraction of
physostigmine from the fluids of the body, Dragendorff recommends
benzene: the alcoholic filtered extract (first acidified) may be
agitated with such solvents as petroleum and benzene, in order to remove
colouring matter; then alkalised and shaken up with benzene, and the
latter allowed to evaporate spontaneously--all the operations being, as
before stated, carried on under 40°. If much coloured, it may be
purified according to the principles before mentioned. In cases where
enough of the extract (or other medicinal preparation) has been taken to
destroy life, the analyst, with proper care, would probably not have
much difficulty in separating a small quantity of the active principle.
It is rapidly eliminated by the saliva and other secretions. In most
cases it will be necessary to identify physostigmine by its
physiological activity, as well as by its chemical characters. For this
purpose a small quantity of the substance should be inserted in the eye
of a rabbit; if it contains the alkaloid in question, in twenty minutes,
at the very latest, there will be a strong contraction of the pupil, and
a congested state of the conjunctival vessels. Further researches may be
made with a small quantity on a bird or frog. The chief symptoms
observed will be those of paralysis of the respiratory and voluntary
muscles, followed by death. If a solution is applied to the web of a
frog’s foot, the blood-vessels become dilated. Physostigmine appears,
according to Dragendorff and Pander, to act as an irritant, for they
always observed gastro-enteritis as a result of the poison, even when
injected subcutaneously. The enhanced secretion from all mucous
surfaces, and the enlargement of the blood-vessels, are also very
constant symptoms. But of all these characteristics, the contraction of
the pupil is, for the purposes of identification, the principal. A
substance extracted from the tissue or other organic matters, in the
manner mentioned, strongly contracting the pupil and giving the bromine
reaction, would, in the present state of our knowledge, be indicative of
physostigmine, and of that alone.

§ 494. =Fatal Dose of Physostigmine.=--One mgrm. (·015 grain) as
sulphate, given by Vee to a woman subcutaneously, caused vomiting, &c.,
after half an hour. A disciple of Gubler’s took 2 mgrms. without
apparent effect; but another mgrm., a little time after, caused great
contraction of the pupil and very serious symptoms, which entirely
passed off in four hours. It would thus seem that three times this
(_i.e._, 6 mgrms.) would be likely to be dangerous. If so, man is far
more sensitive to physostigmine than dogs or cats; and 3 mgrms. per
kilo.--that is, about 205 mgrms. (3 grains)--would be much beyond the
least fatal dose.


IX.--Pilocarpine.

§ 495. From the leaves of the jaborandi, _Pilocarpus pennatafolius_
(Nat. Ord. _Rutaceæ_), two alkaloids have been separated--_jaborandi_
and _pilocarpine_.

=Jaborandi= (C₁₀H₁₂N₂O₃) is a strong base, differing from pilocarpine in
its sparing solubility in water, and more ready solubility in ether; its
salts are soluble in water and alcohol, but do not crystallise. P.
Ghastaing,[541] by treating pilocarpine with a large quantity of nitric
acid, obtained nitrate of jaborandi, and operating in the same way with
hydrochloric acid, obtained the hydrochlorate of jaborandi; hence, it
seems that jaborandi is derived from pilocarpine.

[541] _Compt. Rend._, vol. xciv. p. 223.

§ 496. =Pilocarpine= (C₁₁H₁₆N₂O₂) is a soft gelatinous mass, but it
forms with the mineral acids crystallisable salts. The solutions are
dextra-rotatory. On boiling with water, it decomposes into
trimethylamine and m-pyridine lactic acid,

                                    CH₃
                                  /
  C₁₁H₁₆N₂O₂ + H₂O = N(CH₃)₃ + C₅H₄NCHO      :
                                  \
                                    COOH

hence it is a pyridine derivative, and its graphic formula probably

        CO--O
        |
  C₅H₄N--C--N(CH₃)₃
        |
        CH₃

The nitrate and hydrochloride are at present much used in pharmacy.
Pilocarpine gives a precipitate with phosphomolybdic acid,
potassio-mercuric iodide, and most general alkaloidal reagents, but none
that are very distinctive. When a solution of gold chloride is added to
one of pilocarpine, a salt falls, having the composition C₁₁H₁₆N₂O₂,HCl
+ AuCl₃. It is not very soluble in water (about 1 in 4600), and has been
utilised for the estimation of pilocarpine. Pilocarpine fused with
potash yields trimethylamine, carbon dioxide, butyric, and traces of
acetic acid. Pilocarpine dissolves without the production of colour in
sulphuric acid; but, with bichromate of potash and sulphuric acid, a
green colour is produced. It may be extracted from an aqueous solution
made alkaline by ammonia, by shaking up with chloroform or benzene.

§ 497. =Tests.=--When a little of the alkaloid is mixed with ten times
its weight of calomel, and rubbed, and moistened by the breath, the
calomel is blackened; cocaine also acts similarly; but the two could not
be mistaken for each other. If a solution of mercur-potassium iodide is
added to a solution of the hydrochloride, the amorphous precipitate
becomes, in the course of a day or two, oily drops. “A solution of
iodine in potassium iodide gives in pilocarpine solutions a brown
precipitate that often crystallises to feathery brown crystals
(microscopically), and of serrated form, something like the blade of a
scroll-saw, when the crystallisation is incomplete.”--_Flückiger’s
Reactions._

§ 498. =Effects.=--Pilocarpine, given subcutaneously in doses of about
32 mgrms. (½ grain), causes within five minutes a profuse perspiration
and salivation, the face becomes flushed, and the whole body sweats; at
the same time, the buccal secretion is so much increased that in a few
hours over a pint may be secreted. The tears, the bronchial secretion,
and the intestinal secretions are also augmented; there are generally
headache and a frequent desire to pass water; the pulse is much
quickened, and the temperature falls from 1°·4 to 4°: the symptoms last
from two to five hours. Langley has shown that the over-action of the
submaxillary gland is not affected by section either of the _chorda
tympani_ or of the sympathetic supplying the gland. Although pilocarpine
quickens the pulse of man, it slows, according to Langley,[542] the
heart of the warm-blooded animals, and that of the frog. With regard to
the frog, Dr. S. Ringer’s researches are confirmatory. With large doses
the heart stops in diastole. If to the heart thus slowed, or even when
recently stopped, a minute quantity of atropine be applied, it begins to
beat again. There is also a most complete antagonism between atropine
and pilocarpine in other respects, atropine stopping the excessive
perspiration, and relieving the headache and pain about the pubes, &c.
Pilocarpine, given internally, does not alter the size of the pupil,
but the sight may, with large doses, be affected. If a solution is
applied direct to the eye, then the pupil contracts. No fatal case of
its administration has occurred in man. The probable dangerous dose
would be about 130 mgrms. (2 grains) administered subcutaneously.
Pilocarpine must be classed among the heart poisons.

[542] “The Action of Jaborandi on the Heart,” by J. N. Langley, B.A.,
_Journ. Anat. and Physiol._, vol. x. p. 187.


X.--Taxine.

§ 499. =Properties of Taxine.=--The leaves and berries, and probably
other portions of the yew tree (_Taxus baccata_), are poisonous. The
poison is alkaloidal, and was first separated by Marmé.

=Taxine= (C₃₇H₅₂O₁₀N).--Taxine cannot be obtained in crystals, but as a
snow-white amorphous powder, scarcely soluble in water, but dissolving
in alcohol, in ether, and in chloroform; insoluble in benzene. It melts
at 82°, gives an intense purple-red, with sulphuric acid, and colours
Fröhde’s reagent reddish-violet.

A slightly acid aqueous solution of the alkaloid gives precipitates with
all the group reagents and with picric acid.

The salts are soluble in water; the hydrochloride may be obtained by
passing gaseous HCl into anhydrous ether. The platinichloride forms a
yellow micro-crystalline powder (C₃₇H₅₂O₁₀N)₂H₂PtCl₆. The salts are
generally difficult to crystallise.[543]

[543] A. Hilger and F. Brande, _Ber._, xxiii. 464-468.

§ 500. =Poisoning by Yew.=--Falck has been able to collect no less than
32 cases of poisoning by different parts of the yew--9 were from the
berries, and the rest from the leaves. They were all accidental; 20
persons died, or 62·5 per cent.

§ 501. =Effects on Animals--Physiological Action.=--From the researches
of Marmé-Borchers, it appears that taxine acts upon the nervous
centres--the nervous trunks themselves and the muscles remaining with
their excitability unimpaired, even some time after death. Taxine kills
through paralysis of the respiration, the heart beating after the
breathing has stopped. The leaves contain much formic acid, and their
irritant action on the intestine is referred to this cause.

§ 502. =Effects on Man.=--Several deaths from yew have resulted in
lunatic asylums from the patients chewing the leaves. For example, a few
years ago, at the Cheshire County Asylum, a female, aged 41, was
suddenly taken ill, apparently fainting, her face pale, her eyes shut,
and pulse almost imperceptible. Upon the administration of stimulants,
she somewhat revived, but in a little while became quite unconscious.
The pupils were contracted, and there were epileptiform convulsions,
succeeded by stertorous breathing. These convulsions returned from time
to time, the action of the heart became weaker, and there was a
remarkable slowing of the respirations, with long intervals between the
breathing. The woman died within an hour from the time when her illness
was first observed, and within two hours of eating the leaves. Yew
leaves were found in her stomach. In another case that occurred at the
Parkside Asylum,[544] the patient died suddenly in a sort of epileptic
fit. Yew leaves were again found in the stomach. In a case quoted by
Taylor, in which a decoction of the leaves was drunk by a girl, aged 15,
for the purpose of exciting menstruation, she took the decoction on four
successive mornings. Severe vomiting followed, and she died eight hours
after taking the last dose. In another case there were also no symptoms
except vomiting, followed by rapid death. Mr. Hurt, of Mansfield, has
recorded a case of poisoning by the berries. The child died in
convulsions before it was seen by any medical man.

[544] _Pharm. Journ._ (3), No. 294.

From these and other recorded cases, the symptoms seem generally to be a
quick pulse, fainting or collapse, nausea, vomiting, convulsions, slow
respiration, and death, as a rule sudden and unexpected. We may suppose
that the sudden death is really due to a rapid paralysis of the
respiration, and suffocation.

§ 503. =Post-Mortem Appearances.=--In the case of the girl who drank the
decoction, nothing unusual was observed in the stomach or organs of the
body; but when the leaves have been eaten, usually more or less
congestion of the mucous membrane of the stomach, as well as of the
bowels, is apparent. In the case of the child who ate the berries
(Hurt’s case), the stomach was filled with mucous and half-digested pulp
of the berries and seeds. The mucous membrane was red in patches and
softened, and the small intestines were also inflamed.


XI.--Curarine.

§ 504. Commercial curare is a black, shining, resinoid mass, about 83
per cent. of which is soluble in water, and 79 in weak spirit. It is a
complicated mixture of vegetable extracts, from which, however, a
definite principle possessing basic characters (_curarine_) has been
separated.

The extract is an arrow poison[545] prepared by different tribes of
Indians in South America, between the Amazon and the Orinoco;
therefore, samples are found to vary much in their poisoning properties,
although it is noticeable that qualitatively they are the same, and
produce closely analogous symptoms. It is supposed that some of the
curare is derived from different species of strychnos. This is the more
probable, because, as before stated, the South American strychnines
paralyse, and do not tetanise. It is not unlikely that the active
principles of curare (or woorari) may be methyl compounds similar to
those which have been artificially prepared, such as methyl strychnine
and methyl brucine, both of which have a curare-like action.

[545] A constituent of the Borneo arrow poison is “derrid,” a toxic
principle obtained from a leguminous plant, the _Derris elliptica_; it
is a resinous substance, which has not yet been obtained in the pure
state. It is said not to be a glucoside, nor to contain any nitrogen
(Greshoff, _Ber._, xxiii. 3537-3550).

The Comalis on the east coast of Africa prepare an arrow poison from the
aqueous extract of the root of Oubaion, a tree closely related to
_Carissa Schimperii_.

Oubain is prepared by treating the aqueous extract with lead acetate,
getting rid of excess of lead by SH₂, and concentrating in a vacuum. The
syrup is boiled with six times its volume of alcohol of 85°, and allowed
to cool in shallow vessels; crystals are obtained which are
recrystallised, first from alcohol, and afterwards from water.

Oubain, C₃₀H₄₆O₁₂, forms thin white nacreous lamellæ. It is tasteless,
odourless, and neutral, almost insoluble in cold water, and soluble in
boiling water; it dissolves readily in moderately concentrated alcohol,
is almost insoluble in absolute alcohol, and insoluble in ether and
chloroform. Its melting-point is 200°. The solution of oubain in water
is lævorotatory [α]_{D} = -340. It is a glucoside, yielding on boiling
with dilute acids a sugar. It is very poisonous; 2 mgrms. will kill a
dog of 12 kilos. weight in a few minutes, if subcutaneously injected;
but, taken by the stomach, it produces no effect.--Arnaud, _Compt.
Rend._, cvi. 1011-1014.

=Curarine= was first separated by Preyer in a crystalline form in 1865.
He extracted curare with boiling alcohol, to which a few drops of soda
solution had been added, evaporated off the alcohol, took up the extract
with water, and, after filtration, precipitated by phosphomolybdic acid,
which had been acidified with nitric acid. The precipitate was dried up
with baryta water, exhausted with boiling alcohol, and curarine
precipitated from the alcoholic solution by anhydrous ether. It may also
be obtained by precipitating with mercuric chloride solution, and
throwing out the mercury afterwards by means of hydric sulphide, &c.

Curarine, when pure, forms colourless, four-sided, very hygroscopic
prisms of bitter taste, and weakly alkaline reaction; soluble in water
and alcohol in all proportions, but with difficulty soluble in amyl
alcohol and chloroform, and not at all in anhydrous ether, bisulphide of
carbon, or benzene. The base forms crystallisable salts with
hydrochloric, nitric, and acetic acids. Curarine strikes a purple colour
with strong nitric acid. Concentrated solutions of curarine mixed with
dilute glycerin, give an amorphous precipitate with potassic bichromate,
and the precipitate treated with sulphuric acid strikes a beautiful blue
colour. Curarine chromate is distinguished from strychnine chromate by
its amorphous character, and by its comparatively easy solubility. If
the chromates of strychnine and curarine be mixed, and the mixed
chromates be treated with ammonia, strychnine will be precipitated, and
curarine pass into solution, thus forming a ready method of separating
them.

§ 505. =Physiological Effects.=--According to Voisin and Liouville’s
experiments, subcutaneous injections of curare on man cause, in small
doses, strong irritation at the place of application, swelling, and
pain. The temperature of the body is raised from 1° to 2°, and the
number of respirations increased from 4 to 8 per minute. The pulse
becomes somewhat stronger and more powerful. The urine is increased, and
contains sugar. Large doses administered to warm-blooded animals cause,
after a short time, complete paralysis of voluntary motion and of reflex
excitability, and the animal dies in asphyxia, the heart continuing to
beat.

This state is best produced for the purpose of experiment on frogs, and,
indeed, is the best test for the poison. A very minute dose injected
beneath the skin of a frog soon paralyses both the voluntary and
respiratory muscles; the animal continues to breathe by the skin; the
heart beats normally, or, perhaps, a little weakly, and the frog may
remain in this motionless condition for days and yet recover. Only
curare and its congeners have this effect. By tying the femoral artery
of one of the frog’s legs before administering the poison, an insight
into the true action of the drug is obtained. It is then found that the
reflex excitability and power of motion in the leg are retained,
although all the rest of the body is paralysed. The only explanation of
this is that curare does not act centrally, but paralyses the
intramuscular ends of the motor nerves. Curare is eliminated partly
through the liver and partly through the kidneys. Dragendorff found it
in the fæces, while a striking proof that it is excreted by the kidneys
is given by the experiment of Bidder,[546] in which the urine of a frog
poisoned by curare was made to poison a second, and the urine of the
second, a third. The easy excretion of curare through the kidneys
furnishes an explanation of the relatively large dose of curare which
can be taken by the stomach without injury. A dose which, given by
subcutaneous injection, would produce violent symptoms, perhaps death,
may yet be swallowed, and no ill effects follow. It is hence presumed
that, in the first case, the poison is, comparatively speaking, slowly
absorbed, and almost as fast separated, and put, as it were, outside the
body by going into the urine; while, in the other case, the whole dose
is thrown suddenly into the circulation.

[546] _Arch. f. Anat. u. Physiol._, 1879, p. 598.

§ 506. =Separation of Curarine.=--It is hardly probable that the
toxicologist will have to look for curarine, unless it has entered the
body by means of a wound or by subcutaneous injection; so that in all
cases the absorbed poison alone must be sought for. The seat of entry,
the liver, the kidneys, and the urine are the only parts likely to be of
any use. Dragendorff recommends the extraction of the tissues with water
feebly acidulated with a mineral acid, to precipitate albuminous
matters, &c., by strong alcohol, and separate, by means of benzene,
fatty matters. The liquid is then made alkaline, and shaken up with
petroleum ether, which removes certain alkaloidal matters. It is now
evaporated to dryness, mixed with finely-powdered glass, and extracted
with absolute alcohol. The alcohol is evaporated to dryness, and any
curarine extracted from this residue with water. By very careful drying
up of this last extract, and taking it up in alcohol, the alkaloid is
said to be obtained so pure as to respond to chemical tests. The
identification may be by the colour reaction of sulphuric acid described
_ante_, in all cases supplemented by its physiological action on
frogs.[547]

[547] It is known that curare may cause slight symptoms of excitation
before the paralysis comes on. M. Couty has succeeded in isolating these
symptoms by employing feeble extracts of _Strychnos triplinervia_, or
small doses of certain native preparations. By these means, in dogs, a
new phase of intoxication may be present for ten or even twenty minutes.
In the first instance the animal is agitated, jumping, scratching,
barking, as if in a state of general hyperæsthesia. Then it presents
half choreic shocks or tremors; the pupils dilate, and are alternately
dilated and contracted. The heart’s action is increased or diminished in
frequency; sometimes there is vomiting, micturition, or defecation; and
there is always salivation. Finally, the central and peripheral
temperature are raised, and the excitability of the muscles and nerves
becomes highly increased. With the native preparation of curare, it is
impossible to prolong this stage, and symptoms of paralysis soon become
associated with those of excitement. The choreic shocks were found to be
arrested by section of the sciatic nerve. Other experiments proved that
the spasms originated from the spinal cord, and were influenced by its
preceding functional condition. If the cord was tied in the mid-dorsal
region, and the curare injected, the spasms were still produced in the
hind legs; but if, after the operation, the excitability of the
posterior segment became lowered, the spasm was no longer produced in
the hind legs. This dependence on a perfect functional activity is a
point of difference of these spasms from those produced by strychnine,
and by asphyxia. The action of small doses of curare is not, however,
limited to the spinal cord. The diminished frequency of the heart
continues after section of the pneumogastrics, and will even occur if
the pneumogastrics have been previously divided. From these facts M.
Couty considers that curare must not be regarded as entirely destitute
of a “convulsant” action, nor of an action on the central nervous
system.


XII.--Colchicine.

§ 507. The whole of the _Colchicum autumnale_, or common meadow-saffron,
is poisonous, owing to the presence of an alkaloid (discovered by
Pelletier and Caventou) called _Colchicine_.

According to Johannson’s experiments, the dried colchicum seeds contain
1·15 per cent. of colchicine; the leaves, 1·459 per cent.; the bulbs,
from 1·4 to 1·58 per cent.; and the roots, 0·634 per cent. The frequent
poisoning of cattle in the autumn by colchicum, its use in quack pills
for rheumatism, and its supposed occasional presence in beer, give it
an analytical importance.

§ 508. =Colchicine= (C₂₂H₂₅NO₆) may be extracted from the seeds, &c., in
the manner recommended by Hübler:--The seeds are treated, without
crushing, by hot 90 per cent. alcohol, and the alcoholic solution
evaporated to a syrup, which is diluted with twenty times its bulk of
water and filtered; the liquid is next treated with acetate of lead,
again filtered, and the lead thrown out by phosphate of soda. Colchicine
is now precipitated as a tannate.[548] The precipitation is best
fractional, the first and last portions being rejected as containing
impurities. The tannate is decomposed in the usual way with litharge and
extracted by alcohol.

[548] The purest tannic acid must be used. The commercial tannin may be
purified by evaporating to dryness with litharge, exhausting the tannate
of lead repeatedly with boiling alcohol and water, and, lastly,
suspending in water, and separating the lead by SH₂.

A simpler method is, however, extraction by chloroform from an aqueous
solution, feebly acidified, as recommended by Dragendorff. The parts of
the plant are digested in very dilute acid water, and the resulting
solution concentrated and shaken up with chloroform, which is best done
in a separating tube.

Colchicine contains four methoxyl groups, and its constitutional formula
is considered to be C₁₅H₉[NH(CH₃CO)](COOCH₃)(OCH₃)₃.

Its melting-point is 143°-147°. It is usually a white, gummy mass. It is
easily soluble in cold water, in alcohol, and in chloroform. The
solutions are lævorotatory. It is hardly soluble in ether. Boiling with
dilute acids or alkalies in closed tubes yields colchiceine.

Colchiceine contains three methoxyl groups. It melts at 150°, dissolves
but little in cold, copiously in boiling water. Colchiceine appears to
be an acid, forming salts with the alkalies.

Zeisel[549] has formed acetotrimethylcolchicinamide
(NHAcC₁₅H₉(OMe)₃CONH₃) by heating colchicine with alcoholic ammonia in
closed tubes for four hours at 100°. The amide is crystallised from hot
alcohol; it is readily soluble in dilute HCl, almost insoluble in water;
when a strong hydrochloric acid solution of the amide is treated with a
small amount of potassium nitrite a splendid violet colour is produced.

[549] _Monatsh._, ix. 1-30.

§ 509. =Tests.=--Ferric chloride, if added to an alcoholic solution of
the alkaloid, strikes a garnet red; if to an aqueous solution a green or
brownish-green; nitric acid added to the solid substance gives a violet
colour. Erdmann’s reagent (nitrosulphuric acid) gives in succession
green, dark blue, and violet colours, ultimately turning yellow,
changed, on addition of an alkali, to raspberry-red. Mandelin’s reagent
(1 grm. of ammonium vanadate in 200 grms. of sulphuric acid) gives a
green colour.

§ 510. =Pharmaceutical Preparations.=--Colchicine itself is officinal in
Austria--the wine in the British, French, and Dutch, and the seeds
themselves in all the pharmacopœias. The wine of colchicum, officinal in
nearly all the pharmacopœias, is made with very different proportions of
seeds or bulbs.

The tincture of colchicum is officinal in our own and in all the
Continental pharmacopœias; in the British, one part of seeds is
exhausted by eight parts of proof spirit.

A tincture of colchicum seeds, examined by Johannson, contained ·18 per
cent. of colchicine, and a tincture prepared from the bulbs ·14 per
cent.

Colchicum vinegar is not officinal in Britain, but one containing 5·4
per cent. of acetic acid is so in the Netherlands, Germany, and France;
the strength appears to be about ·095 per cent. of colchicine.

An extract of colchicum is officinal in Britain and France; and an
acetic extract in Britain. The latter is the most active of all the
pharmaceutical preparations of colchicum.

Lastly, an oxymel of colchicum is in use in Germany, France, and the
Netherlands.

=Quack and Patent Medicines.=--In all specifics for gout the analyst
will naturally search for colchicum. Most gout pills contain the
extracts; and liquids, such as “Reynolds’ gout specific,” the wine or
the tincture, variously flavoured and disguised.

The strength of the different pharmaceutical preparations may be
ascertained by dissolving in chloroform, evaporating off the chloroform,
dissolving in water (which is finally acidified by from 7 to 10 per
cent. of sulphuric acid), and titrating with Mayer’s reagent (see p.
263). If the solution is diluted so that there is about one part of
colchicine in 600 of the solution, then each c.c. of Mayer’s reagent
equals 31·7 mgrms. colchicine.

§ 511. =Fatal Dose.=--In Taylor’s _Principles of Medical Jurisprudence_
is mentioned an instance in which 3½ drachms of colchicum wine, taken in
divided doses, caused death on the fourth day. The quantity of the
active principle in the colchicum wine, as found by Johannson
(_Dragendorff_), being 0·18 per cent., it follows that 24·4 mgrms. (·378
grain) were fatal, though not given as one dose, so that this quantity
may be considered as the least fatal one. Casper puts the lethal dose of
colchicine at from 25 to 30 mgrms. (·385 to ·463 grain). It is, however,
incontestable that there are cases of recovery from as much as 70 mgrms.
(1·08 grain). The lethal dose of the pharmaceutical preparations of
colchicum may, on these grounds, be predicted from their alkaloidal
contents, and, since the latter is not constant, in any medico-legal
inquiry, it may be necessary, where facility is given, to ascertain the
strength of the preparation administered.

§ 512. =Effects of Colchicine on Animals.=--The researches of Rossbach
show that the carnivoræ are more sensitive to colchicine than any other
order of mammals. Frogs show a transitory excitement of the nervous
system, then there is loss of sensation, paralysis of motion, and of the
respiratory apparatus; the heart beats after the respiration has ceased.
Death follows from paralysis of the respiration. The mucous membrane of
the intestine is much congested and swollen.

I have seen cattle die from the effects of eating the meadow-saffron;
the animals rapidly lose condition, suffer great abdominal pain, and are
generally purged. The farmers, in certain parts of the country, have had
extensive losses from want of care and knowledge with regard to
colchicum poisoning.

§ 513. =Effects of Colchicum on Man.=--Colchicum poisoning in man[550]
is not very common: 2 deaths (accidental) are recorded in England and
Wales during the ten years ending 1892. F. A. Falck was able to collect
from medical literature, prior to 1880, 55 cases, and he gives the
following analysis of the cases:--In 2, colchicum was taken for suicidal
purposes; of the unintentional poisonings, 5 were from too large a
medicinal dose of colchicum wine, syrup, or extract, given in cases of
rheumatism; in 13 cases, colchicum was used as a purgative; 42 cases
were owing to mistaking different preparations for drinks, or
cordials--the tincture in 5, and the wine in 14, being taken instead of
orange tincture, quinine wine, schnapps or Madeira; in 1 case the corms
were added to mulled wine, in another, the leaves consumed with salad;
in 16 cases (all children), the seeds of colchicum were eaten. Forty-six
of the 55 died--that is, 83·7 per cent.

[550] For the curious epidemic of diarrhœa which broke out in the Rhone
Gorge in 1785, and was referred to colchicine, see “Foods,” p. 287.

In the remarkable trial at the Central Criminal Court, in 1862, of
Margaret Wilson (_Reg._ v. _Marg. Wilson_), who was convicted of the
murder of a Mrs. Somers, the evidence given rendered it fairly probable
that the prisoner had destroyed four people at different dates by
colchicum. The symptoms in all four cases were--burning pain in the
throat and stomach, intense thirst, violent vomiting and purging,
coldness and clamminess of the skin, excessive depression, and great
weakness. One victim died on the second day, another on the fifth, a
third on the eighth, and the fourth on the fourteenth day. Schroff
witnessed a case in which a man took 2 grms. (nearly 31 grains) of the
corms; in one and a half hours he experienced general _malaise_; on the
next day there were flying muscular pains, which at length were
concentrated in the diaphragm, and the breathing became oppressed;
there was also pain in the neighbourhood of the duodenum, the abdomen
was inflated with gas; there was a sickly feeling and faintness. Then
came on a sleepy condition, lasting several hours, followed by fever,
with excessive pain in the head, noises in the ears, and delirium; there
was complete recovery, but the abdomen continued painful until the fifth
day.

In another instance, a gentleman, aged 50,[551] had taken twenty-eight
of Blair’s gout-pills in four and a half days for the relief of a
rheumatic affection. He suffered from nausea, griping pains in the
belly, considerable diarrhœa, vomiting, and hiccough; towards the end
there was stupor, convulsive twitchings of the muscles, paralysis, and
death. The fatal illness lasted fourteen days; he was seen by three
medical men at different dates--the first seems to have considered the
case one of diarrhœa, the second one of suppressed gout; but Dr. C. Budd
was struck with the similarity of the symptoms to those from an acrid
poison, and discovered the fact that the pills had been taken. These
pills I examined; they were excessively hard, and practically consisted
of nothing else than the finely-ground colchicum corms; six pills
yielded 8 mgrms. of colchicine, so that the whole twenty-eight would
contain 39 mgrms. (⅗ grain). Dr. Budd considered that the whole of the
pills, which were of a stony hardness, remained in the bowels for some
time undigested, so that the ultimate result was the same as if the
whole had been taken in one dose.

[551] See _Lancet_, vol. i., 1881, p. 368.

§ 514. The general symptoms produced by colchicum are--more or less
burning pain in the whole intestinal tract, vomiting, diarrhœa, with not
unfrequently bloody stools; but sometimes diarrhœa is absent. In single
cases tenesmus, dysuria, and, in one case, hæmaturia have been noted.
The respiration is usually troubled, the heart’s action slowed, the
pulse small and weak, and the temperature sinks. In a few cases there
have been pains in the limbs; cerebral disturbance is rare; but in two
cases (one described _ante_) there was stupor. Muscular weakness has
been observed generally. In a few cases there have been cramps in the
calves and in the foot, with early collapse and death.

=Post-mortem Appearances.=--Schroff found in rabbits poisoned with from
·1 to 1·0 grm. of colchicine, tolerably constantly enteritis and
gastritis, and always a thick, pitch-like blood in the heart and veins.
Casper has carefully recorded the _post-mortem_ appearances in four
labourers, ages ranging from fifteen to forty years, who, finding a
bottle of colchicum-wine, and supposing it to be some kind of brandy,
each drank a wine-glassful. They all died from its effects. In all four
there was great hyperæmia of the brain membranes and of the kidneys. The
large veins were filled with thick, dark, cherry-red blood, very similar
to that seen in sulphuric acid poisoning. There was an acid reaction of
the contents of the stomach. The lungs were moderately congested. The
mucous membrane of the stomach of the one who died first was swollen and
scarlet with congestion; with the second there was some filling of the
vessels at the small curvature; while the stomachs of the third and
fourth were quite normal. In 5 cases described by Roux there was also
hyperæmia of the brain and kidneys, but no gastritis or enteritis. It
is, therefore, evident that there are in man no constant pathological
changes from colchicine poisoning.

§ 515. =Separation of Colchicine from Organic Matters.=--W.
Obolonski[552] has recommended the following process:--The finely
divided viscera are triturated with powdered glass and digested for
twelve hours with alcohol. The liquid is squeezed out and the dry
residue washed with alcohol. The extract is concentrated at a
temperature not exceeding 80°, and the cooled residue made up to the
original volume with alcohol. The filtered liquid is evaporated as
before, and this operation repeated until no more clots separate on
addition of water. The residue is then dissolved in water, the solution
purified by shaking with light petroleum, and the colchicine finally
extracted with chloroform.

[552] _Zeit. anal. Chem._, xxix. 493.

In cases of poisoning by colchicum at Berlin, Wittstock used the
following process:--The contents of the stomach were mixed with a large
amount of alcohol, a few drops of HCl added, and the whole well shaken;
the fluid was then filtered, and the filtrate evaporated to a syrupy
consistence at 37°. The resulting residue was dissolved in distilled
water, the fat, &c., filtered off, and the liquid carefully evaporated.
From the extract foreign matter was again separated by treatment with
alcohol and filtration, and the last filtrate was evaporated to a syrupy
consistence. The syrupy fluid was taken up by distilled water, filtered,
evaporated to 30 grms., and 2 grms. of calcined magnesia with 90 grms.
of ether were added. After a time, the ether was removed, and allowed to
evaporate spontaneously. The residue was once more taken up with water,
filtered from fat, &c., and evaporated. This final residue gave all the
reactions of colchicine. In medico-legal researches, it must be
remembered that colchicine is absorbed but slowly, a not insignificant
portion remaining in the bowels, with the fæces.


XIII.--Muscarine and the Active Principles of Certain Fungi.

§ 516. =The Amanita Muscaria=, or fly-blown agaric, is a very
conspicuous fungus, common in fir-plantations, about the size and shape
of the common mushroom; but the external surface of the pileus is of a
bright red, or sometimes of a yellowish cast, and studded over with
warts. The common name of the fungus denotes that it was used in former
times as a popular insecticide; the fungus was bruised, steeped in milk,
and the milk exposed, in the same way as we now expose arsenical
fly-papers.

Some peculiar properties of the agaric have long been known to the
natives of Kamschatka, and of the north-eastern part of Asia generally.
They collect the fungi in the hottest months, and hang them up to dry.
The fungus is then rolled up in a kind of bolus, and swallowed without
chewing. One large, or two small, fungi will produce a kind of
intoxication, which lasts a whole day. It comes on in about two hours’
time, and is very similar to that of alcohol. There is a giddy feeling,
the spirits are exalted, the countenance becomes flushed, involuntary
actions and words follow, and sometimes loss of consciousness. It
renders some persons remarkably active, and proves highly stimulant to
muscular exertion; by too large a dose violent spasmodic effects are
produced. “So very exciting to the nervous system in many individuals is
this fungus, that the effects are often very ludicrous. If a person
under its influence wishes to step over a straw or small stick, he takes
a stride or a jump sufficient to clear the trunk of a tree. A talkative
person cannot keep silence or secrets, and one fond of music is
perpetually singing. The most singular effect of the amanita is the
influence which it has over the urine. It is said that from time
immemorial the inhabitants have known that the fungus imparts an
intoxicating quality to that secretion, which continues for a
considerable time after taking it. For instance, a man moderately
intoxicated to-day will, by the next morning, have slept himself sober,
but (as is the custom) by taking a teacup of his urine he will be more
powerfully intoxicated than he was the preceding day. It is, therefore,
not uncommon for confirmed drunkards to preserve their urine as a
precious liquor against a scarcity of the fungus. The intoxicating
property of the urine is capable of being propagated; for every one who
partakes of it has his urine similarly affected. Thus, with a very few
amanitas, a party of drunkards may keep up their debauch for a week. Dr.
Langsdorf mentions that by means of the second person taking the urine
of the first, the third of the second, and so on, the intoxication may
be propagated through five individuals.”[553]

[553] Lindley’s _Vegetable Kingdom_.

§ 517. A few cases of poisoning by the fly-blown agaric from time to
time have occurred in Europe, where it has been eaten in mistake for the
edible fungi, or taken by children allured by the bright attractive
colours. In these cases the poisonous symptoms noticed have been those
of gastro-intestinal irritation, as shown by vomiting and diarrhœa,
_dilated_[554] pupils, delirium, tetanic convulsions, slow pulse,
stertorous breathing, collapse, and death. In a few cases epileptic
attacks and trismus have been observed. The course is usually a rapid
one, the death occurring within twelve hours. In cases of recovery,
convalescence has been prolonged.

[554] This is the more curious, for muscarine strongly contracts the
pupil. It, however, tends to prove what is stated in the text--viz.,
that there is more than one poisonous substance in _Amanita_.

=The post-mortem characteristics are not distinctive=, a fluid condition
of the blood, hyperæmia of the brain, liver, and kidneys has been
noticed.

§ 518. =Muscarine.=--These effects are partly due to an undiscovered,
toxic substance--which seems to be destroyed at the temperature of
boiling water, and is probably of rather easy destructibility--and of a
very definite poisonous alkaloid (_muscarine_) first separated by a
complex process by Schmiedeberg and Koppe in 1869.[555] It is a
trimethylammonium base, and has lately been formed synthetically by
Schmiedeberg and Harnack,[556] by treating cholin with nitric acid.
Muscarine is isomeric with betain and oxycholin, from which it is
separated by its fluorescence and poisonous properties.

[555] _Das Muscarin, das giftige Alkaloid des Fliegenpilzes._ Leipzig,
1869.

[556] _Arch. f. exper. Path._, Bd. 4 u. 5.

The structural formula of muscarine, and its connection with choline, is
as follows:--

  CH₂OH
  |
  CH₂
  |
  N(CH₃)₃OH

  _Choline._

  CH₂OH
  |
  CHOH
  |
  N(CH₃)₃OH

  _Muscarine._


An atom of hydrogen from the choline, CH₂, group, being replaced by
hydroxyl.

Muscarine is a colourless, strongly alkaline, syrupy fluid, which, if
allowed to stand over sulphuric acid, becomes gradually crystalline, but
liquefies again on exposure to the atmosphere. It dissolves in water in
every proportion, and also in alcohol, but is very little soluble in
chloroform, and insoluble in ether. It is not precipitated by tannin: it
forms salts with acids, and gives precipitates with auric chloride,
phosphotungstic, and phosphomolybdic acids, and also with
potassio-mercuric iodide. The last precipitate is at first amorphous,
but it gradually becomes crystalline. This was the compound used by the
discoverers to separate the base. With many other general alkaloidal
reagents muscarine forms no compound that is insoluble, and therefore
gives no precipitate, such, _e.g._, as iodine with potassic iodide,
picric acid, and platinic chloride. Muscarine is a stronger base than
ammonia, and precipitates copper and iron oxides from solutions of
their salts. Muscarine is very poisonous; 2 to 4 mgrms. are sufficient
in subcutaneous injection to kill cats in from two to twelve
hours--larger doses in a few minutes; but with rabbits the action is
less intense. Cats become salivated, their pupils contract, they vomit,
and are purged, the breathing becomes frequent, and there is marked
dyspnœa. At a later stage the respirations are slower, and there are
convulsions, and death.

The alkaloid has also been tried on man. Doses of from 3 to 5 mgrms.,
injected subcutaneously, cause, after a few minutes’ profuse salivation,
increased frequency of the pulse, nausea, giddiness, confusion of
thought and myosis, but no vomiting, and no diarrhœa. Small quantities
applied to the eye cause, after a few minutes, a derangement of the
accommodation, but no change in the size, of the pupil; larger
quantities cause also myosis, which depends upon an excitement of the
sphincter iridis, or of the oculomotorius.

§ 519. The actions of muscarine and atropine are to a great extent
antagonistic. This is especially and beautifully demonstrated by the
effects of the two substances on the frog’s heart. The action of
muscarine upon the heart is to excite the inhibitory nerve apparatus,
while the action of atropine is to paralyse the same system. One mgrm.
of muscarine, injected subcutaneously into a frog, arrests the heart _in
diastole_, but if a suitable dose of atropine is applied to the heart
thus arrested, it begins to beat again; or, if atropine is first given,
and then muscarine, the heart does not stop. The muscarine heart, when
it has ceased to beat, may be successfully stimulated by galvanism.
Muscarine at first excites the respiratory centre, and then paralyses
it.

§ 520. =Detection of Muscarine in the Body.=--Muscarine itself is not
likely to be taken as a poison or administered; but if it is sought for
in the fly-blown agaric, or in the tissues or organs of persons who have
been poisoned by the fungus, the process of Brieger appears the best.
The process depends upon the fact that muscarine gives a soluble
mercuric chloride compound, and is not precipitated by chloride of
platinum, whilst most other substances accompanying it give more or less
insoluble precipitates. The substances are treated with water acidulated
with hydrochloric acid, and the acidulated extract concentrated (best in
a vacuum) to a syrup. The syrupy residue is now treated with water, and
the solution precipitated by means of mercuric chloride solution and any
precipitate filtered off; the filtrate is freed from mercury by SH₂, and
evaporated to a syrup; the syrup is repeatedly extracted with alcohol,
and the alcoholic solution precipitated with platinum chloride and any
precipitate filtered off. The filtrate is freed from alcohol, and all
the platinum thrown out of solution by SH₂; the aqueous filtrate is now
concentrated to a small volume, and again platinum chloride added, any
precipitate which forms is filtered off, and the final filtrate allowed
to crystallise. If muscarine be present, a crystalline compound of
muscarine platinum chloride will form.

The crystals are usually octahedral in form, and have the composition
(C₅H₁₄NO₂Cl)₂PtCl₄; the percentage of platinum is 30·41.

It would probably be necessary to identify farther, by the action of the
poison on a frog.

§ 521. =The Agaricus phalloides=, a common autumn fungus, has been
several times mistaken for mushrooms, and has proved fatal; of some 53
cases collected by Falck, no less than 40, or 75 per cent., were fatal;
the real mortality is much lower than this, for it is only such cases
that are pronounced and severe which are likely to be recorded. The
fungus contains a toxalbumin which has been named “phallin.” The action
of this toxalbumin is to dissolve the blood corpuscles; according to
Kobert, even one 250,000th dilution produces “polycholie,” with all its
consequences, such as the escape of hæmoglobin and its decomposition
products in the blood and urine, multiple blood coagulation through the
fibrin ferment becoming free, and serious cerebral disturbance. If into
a dog, cat, or rabbit, only 0·5 mgrm. of phallin be injected
intravenously, within from twenty to thirty minutes blood from a vein
shows that the serum has a red colour.

The symptoms in man first appear in from three to forty-eight hours;
there is mostly diarrhœa, violent vomiting, with cramp in the legs,
cyanosis, and collapse. There are also nervous phenomena, convulsions,
trismus, and, in a few cases, tetanic spasms. The pulse, in seven cases
described by Maschka, was very small, thready, and quick, but in others,
again, small and slow. The pupils have in some cases been dilated, in
others unchanged. Death is generally rapid. In two of Maschka’s cases
from sixty to sixty-eight hours after the investigation, but in the rest
from twelve to eighteen hours. Life may, however, be prolonged for
several days. In a case recorded by Plowright,[557] in which a boy had
eaten a piece of the pileus, death occurred on the fourth day.

[557] _Lancet_, 1879.

§ 522. =The post-mortem appearances= observed in Maschka’s seven cases
were--absence of cadaveric rigidity, dilatation of the pupil, a dark red
fluid condition of the blood, numerous ecchymoses in the pleura, in the
substance of the lungs, the pericardium, the substance of the heart, the
liver, kidneys, and spleen. The mucous membrane of the digestive canal
presented nothing characteristic. In two cases there were a few
ecchymoses, and in one the mucous membrane of the stomach was softened,
red, and easily detached. In one case only were any remnants of the
fungus found, by which the nature of the substance eaten could be
determined. The bladder in each case was full. In three cases a fatty
degeneration of the liver had commenced. The same appearance was met
with in some of the older cases related by Orfila.

§ 523. =The Agaricus pantherinus= is said to be poisonous, although
Hertwig found it to have no action when given to dogs.

=The Agaricus ruber=, a bright-hued fungus, growing profusely on the
Hampshire coast, of a purple-red colour--the colouring-matter not only
covering the pileus, but also extending down the stipe--is poisonous,
and has recently been chemically investigated by Phipson,[558] who has
identified a colouring-matter _ruberine_, and an alkaloid _agarythrine_.
Agarythrine is separated by macerating the fungus (from which the skin
containing the colouring-matter has been removed) as completely as
possible in water acidulated with 8 per cent. of hydrochloric acid. The
filtered solution is neutralised by sodic carbonate, and the alkaloid
shaken up with ether. On evaporation the ether leaves a white, somewhat
greasy-looking substance, having a bitter burning taste, and easily
fusible into yellow globules, giving forth an odour like quinoleine; it
is soluble in alcohol and ether. From Phipson’s observations it would
appear probable that the red colouring-matter is derived from a
decomposition of this alkaloidal substance. A rose-red colour is
produced by the action of nitric acid, and chlorinated lime first
reddens and then bleaches it. Buchwald[559] has recorded three cases of
poisoning by this fungus; the patients were labourers, who, after eating
the fungus, suffered from vomiting, thirst, a “drunken” condition,
cramp, albuminuria, and disturbance of the sensory functions. The fungus
causes in cats myosis, but is said not to affect rabbits.

[558] _Chem. News_, p. 199, 1882.

[559] _Industr. Bl._, 1876.

§ 524. =The Soletus satanas, or luridus= (=Lenz=), is poisonous; very
small quantities of the uncooked fungus caused in Lenz, who experimented
upon its properties, violent vomiting. In cases in which this fungus has
been eaten accidentally, the symptoms have been very similar to cholera.

§ 525. =The Common Morelle= seems under certain conditions to be
poisonous. From six to ten hours after ingestion there have appeared
depression, nausea, jaundice, dilated pupils, and in the worst cases at
the end of the first day, delirium, somnolence, and muscular cramps,
followed by collapse and death. In a case observed by Kromholz, the
_post-mortem_ appearances were jaundice, a dark fluid state of the
blood, and hyperæmia of the brain and liver. Boström fed a dog with 100
grms. of the fresh young morelle; the animal died on the third day, and
the canaliculi of the kidney were found filled with hæmoglobin, partly
amorphous, and partly crystalline.[560]

[560] See Casper’s _Viertelj._, 1844; Keber, _Preuss. Vereinszeitg._
1846; Boström, _Ber. d. Phys. Med. Soc._, Erlangen, 1880; Schauenstein,
“Giftige Schwämme” in Maschka’s _Handbuch_, &c.


DIVISION II.--GLUCOSIDES.


I.--Digitalis Group.

§ 526. =The Digitalis purpurea=, or foxglove, is a plant extremely
common in most parts of England, and poisoning may occur from the
accidental use of the root, leaves, or seeds. The seeds are very small
and pitted; they weigh 1126 to a grain (_Guy_), are of a light brown
colour, and in form somewhat egg-shaped. The leaves are large, ovate,
crenate, narrowed at the base, rugous, veined, and downy, especially on
the under surface. Their colour is a dull green, and they have a faint
odour and a bitter, nauseous taste. The leaf is best examined in
section. Its epidermis, when fresh, is seen to consist of transparent,
hexagonal, colourless cells, beneath which, either singly or in groups,
there are round cells of a magenta tint, and beneath these again a layer
of columnar cells, and near the lower surface a loose parenchyma. The
hairs are simple, appearing scantily on the upper, but profusely on the
lower, surface; each is composed of from four to five joints or cells,
and has at its base a magenta-coloured cell. The small leaves just below
the seed-case, and the latter itself, are studded with glandular hairs.
The root consists of numerous long slender fibres.

§ 527. =Chemical Composition.=--It is now generally accepted that there
exist in the foxglove, at least, four distinct principles--_digitalin_,
_digitonin_, _digitoxin_, and _digitalein_. Besides these there are
several others of more or less definite composition, which are all
closely related, and may be derived from a complex glucoside by
successive removals of hydrogen in the form of water.

The following is the theoretical percentage composition of the
digitalins, the identity of which has been fairly established. They are
arranged according to their percentage in carbon:--

TABLE SHOWING THE COMPOSITION OF THE DIGITALINS.

  +------------------+--------+-------------------------------------+
  |      Name.       |Formula.|    Percentage Composition.          |
  +------------------+--------+-------------------------------------+
  | Digitalein,      | C₂₁H₄₆O₁₁ | C. 53·16 per cent. H. 8·08 per cent.|
  | Digitonin,[561]  | C₃₁H₅₂O₁₇ | C. 53·44  „        H. 7·46     „    |
  | Digitalin,       | C₅₄H₈₄O₂₇ | C. 58·16  „        H. 3·65     „    |
  | Digitaletin,     | C₄₄H₃₀O₁₈ | C. 62·41  „        H. 3·54     „    |
  | Digitoxin,       | C₂₁H₃₂O₇  | C. 63·63  „        H. 8·08     „    |
  | Digitaleretin,   | C₄₄H₃₈O₁₈ | C. 66·05  „        H. 4·58     „    |
  | Paradigitaletin, | C₄₄H₃₄O₁₄ | C. 67·17  „        H. 4·3      „    |
  +------------------+--------+-------------------------------------+

[561] According to Kiliani, digitonin has the composition of C₂₇H₄₄O₁₃,
and it breaks up, when heated with hydrochloric acid, as follows:--

    C₂₇H₄₄O₁₃   + 2H₂O =    C₁₆H₂₄O₃    + 2C₆H₁₂O₆.
  Digitonin.          Digitogenin.   Dextrose.

--_Ber._, xxiii. 1555-1568.

    § 528. =Digitalein= is a colourless, amorphous body, easily soluble
    in water and in cold absolute alcohol. It may be precipitated from
    an alcoholic solution by the addition of much ether. It is with
    difficulty soluble in chloroform, and insoluble in ether. It is
    precipitated from a watery solution by tannin, or by basic lead
    acetate; saponification by dilute acids splits it up into glucose
    and digitaleretin. It has a sharp, acrid taste, and the watery
    solution froths on shaking.

    § 529, =Digitonin=, a white amorphous body, has many of the
    characters of saponin. Like saponin, it is easily soluble in water,
    and the solution froths, and, like saponin again, it is precipitated
    by absolute alcohol, by baryta water, and by basic lead acetate. It
    may be readily distinguished from saponin by treating a watery
    solution with sulphuric or hydrochloric acid. On saponifying, it is
    split up into digitogenin, galactose, and dextrose. On heating, a
    beautiful red colour develops. It does not give the bromine
    reaction.

=Digitogenin= is insoluble in water and aqueous alkalies; it is somewhat
soluble in alcohol, chloroform, and glacial acetic acid; it forms a
crystalline compound with alcoholic potash, which is strongly alkaline,
and not very soluble in alcohol.

§ 530. =Digitalin=, when perfectly pure, forms fine, white, glittering,
hygroscopic needles, or groups of crystalline tufts; it is without
smell, but possesses a bitter taste, which is at once of slow
development and of long endurance. On warming, it becomes soft under
100°, and, above that temperature, is readily decomposed with evolution
of white vapours. It is insoluble in water, in dilute soda solution, in
ether, and in benzene. It is soluble in chloroform, especially in
chloroform and alcohol, and dissolves easily in warm acetic acid; twelve
parts of cold and six of boiling alcohol of 90 per cent. dissolve one of
digitalin. Dilute hydrochloric or sulphuric acid decompose it into
glucose and digitaletin (C₄₄H₃₀O₁₈); if the action is prolonged,
digitaleretin (C₄₄H₃₈O₁₈), and finally dehydrated digitaleretin, are
formed. Concentrated sulphuric acid dissolves it with the production of
a green colour, which by bromine passes into violet-red, but on the
addition of water becomes green again. Hydrochloric acid dissolves it
with the production of a greyish-yellow colour, passing gradually into
emerald green; water precipitates from this solution a resinous mass.

    § 531. =Digitaletin.=--A substance obtained by Walz on treating his
    digitalin by dilute acids. It is crystalline, and its watery
    solution tastes bitter. It melts at 175°, and decomposes, evolving
    an acid vapour at about 206°. It dissolves in 848 parts of cold, and
    222 of boiling, water; in 3·5 parts of cold, and in from 2 to 4 of
    boiling, alcohol. It is with difficulty soluble in ether. It
    dissolves in concentrated sulphuric acid, developing a red-brown
    colour, which, on the addition of water, changes to olive-green. On
    boiling with dilute acids, it splits up into sugar and
    digitaleretin.

§ 532. =Digitoxin= always accompanies digitalin in the plant, and may by
suitable treatment be obtained in glittering needles and tabular
crystals. It is insoluble in water and in benzene. It dissolves with
some difficulty in ether, and is readily dissolved by alcohol or by
chloroform. On boiling with dilute acids, it is decomposed into an
amorphous, readily soluble body,--_Toxiresin_. Digitoxin, according to
Schmiedeberg, only exists in the leaves of the digitalis plant, and that
in the proportion of 1 part in 10,000. Digitalin and digitoxin are _par
excellence_ the poisonous principles of the plant. Toxiresin is also
intensely poisonous. It may be obtained in crystals by extracting the
dry exhausted leaves with alcohol of 50 per cent., precipitating with
lead acetate, and washing the precipitate first with a dilute solution
of sodium carbonate (to remove colouring-matter), and then with ether,
benzene, and carbon disulphide, in all of which it is insoluble; on
decomposing the lead compound, digitoxin may be obtained in colourless
scales or needle-shaped crystals.

    § 533. =Digitaleretin=, the origin of which has been already alluded
    to, is a yellowish-white, amorphous powder, possessing no bitter
    taste, melting at 60°, soluble in ether or in alcohol, but insoluble
    in water.

    =Paradigitaletin= is very similar to the above, but it melts at
    100°, and is insoluble in ether.

§ 534. Several other derivatives have been obtained and described, such
as the inert _digitin_, _digitalacrin_, _digitalein_, and others, but
their properties are, as yet, insufficiently studied. Digitalin, as well
as digitoxin, may now be obtained pure from certain firms, but the
ordinary digitalin of commerce is, for the most part, of two kinds,
which may be distinguished as French and German digitalin. The French
digitalin, or the digitalin of Homolle, is prepared by treating an
aqueous extract of the digitalis plant with lead acetate, and freeing
the filtrate from lead, lime, and magnesia, by successive additions of
alkaline carbonate, oxalate, and phosphate, and then precipitating with
tannin. The tannin precipitate is treated with litharge, and the
digitalins boiled and extracted from the mass by means of alcohol, and
lastly, purifying with animal charcoal. Crystals are in this way
obtained, and by removing all substances soluble in ether by that
solvent, digitalin may be separated. The German digitalin is prepared
according to the process of Walz, and is extracted from the plant by
treatment with alcohol of ·852. The alcohol is removed by evaporation,
and the alcoholic extract taken up with water; the watery extract is
treated with lead acetate and litharge, filtered, the filtrate freed
from lead by hydric sulphate, and the excess of acid neutralised by
ammonia, and then tannin added to complete precipitation. The
precipitate is collected and rubbed with hydrated oxide of lead, and the
raw digitalin extracted by hot alcohol. The alcohol, on evaporation,
leaves a mixture of digitalin mixed with other principles and fatty
matter. If sold in this state, it may contain from 2 to 3 per cent. of
digitalein and digitonin. On treating the mixture with ether, digitalin
with some digitaletin is left behind, being almost insoluble in ether.
Since, however, digitaletin is very insoluble in cold water, by
treating the mixture with eight parts of its weight of cold water,
digitalin is dissolved out in nearly a pure state. It may be further
purified by treating the solution with animal charcoal,
recrystallisation from spirit, &c.

§ 535. =Reactions of the Digitalins.=--Digitonin is dissolved by dilute
sulphuric acid (1 : 3) without colour, and the same remark applies to
hydrochloric acid; on warming with either of these acids, a violet-red
colour appears; this reaction thus serves to distinguish digitonin from
the three other constituents, as well as from saponin.

Sulphuric and gallic acids colour the glucosides of digitalin,
digitalein, and digitonin, red, but not digitoxin, which can be
identified in this way.

Sulphuric acid and bromine give with digitalin a red, and with
digitalein a violet coloration, which, on the addition of water, change
respectively into emerald and light green. This, the most important
chemical test we possess, is sometimes called _Grandeau’s test_; it is
not of great delicacy, the limit being about ·1 mgrm.

§ 536. =Pharmaceutical Preparations of Digitalin.=--Digitalin itself is
officinal in the French, Belgium, Portuguese, Russian, Spanish, and
Austrian pharmacopœias. It is prepared in our own by making a strong
tincture of the leaves at 120° F.; the spirit is then evaporated off,
and the extract heated with acetic acid, decolorised by animal charcoal,
and filtered. After neutralisation with ammonia, the digitalin is
precipitated with tannin, and the tannate of digitalin resolved into
tannate of lead and free digitalin, by rubbing it with oxide of lead and
spirit.

Digitalis leaf is officinal in most of the pharmacopœias.

Tincture of digitalis is officinal in our own and all the Continental
pharmacopœias, and an ethereal tincture is used in France and Germany.

An _Acetum digitalis_ is officinal in the Netherlands and Germany; an
extract and infusion are also used to some extent.

With regard to the nature of the active principle in these different
preparations, according to Dragendorff, digitonin and digitalein are
most plentiful in the acetic and aqueous preparations; whilst in the
alcoholic, digitalin, digitoxin, and digitalein are present.

According to Schmiedeberg, commercial digitalin contains, in addition to
digitoxin, digitonin, digitalin, and digitalein; of these, digitonin is
greatest in amount.[562]

[562] H. Kiliani, _Ber._, xxiii.

§ 537. =Fatal Dose.=--The circumstance of commercial digitalin
consisting of varying mixtures of digitoxin, digitalin, and digitalein,
renders it difficult to be dogmatic about the dose likely to destroy
life. Besides, with all heart-poisons, surprises take place; and very
minute quantities have a fatal result when administered to persons with
disease of the heart, or to such as, owing to some constitutional
peculiarity, have a heart easily affected by toxic agents. Digitoxin,
according to Kopp’s[563] experiments, is from six to ten times stronger
than digitalin or digitalein. Two mgrms. caused intense poisonous
symptoms. Digitoxin is contained in larger proportions in Nativelle’s
digitalin than in Homolle’s, or in the German digitalin. The digitalin
of Homolle is prescribed in 1 mgrm. (·015 grain) doses, and it is
thought dangerous to exceed 6 mgrms.

[563] _Archiv f. exp. Pathol. u. Pharm._, vol. iii. p. 284, 1875.

Lemaistre has, indeed, seen dangerous symptoms arise from 2 mgrms. (·03
grain), when administered to a boy fifteen years old. It may be
predicated from recorded cases and from experiment, that digitoxin would
probably be fatal to an adult man in doses of 4 mgrms. (1/16 grain), and
digitalin, or digitalein, in doses of 20 mgrms. (·3 grain). With regard
to commercial digitalin, as much as from 10 to 12 mgrms. (·15 to ·18
grain) have been taken without a fatal result; on the other hand, 2
mgrms. gave rise to poisonous symptoms in a woman (Battaille). Such
discrepancies are to be explained on the grounds already mentioned. It
is, however, probable that 4 mgrms. (or 1/16 grain) of ordinary
commercial digitalin would be very dangerous to an adult.

It must also, in considering the dose of digitalin, be ever remembered
that it is a cumulative poison, and that the same dose--harmless if
taken once--yet, frequently repeated, becomes deadly: this peculiarity
is shared by all poisons affecting the heart. When it is desired to
settle the maximum safe dose for the various tinctures, extracts, and
infusions of digitalis used in pharmacy, there is still greater
difficulty, a difficulty not arising merely from the varying strength of
the preparations, but also from the fact of the vomiting almost
invariably excited by large doses. Individuals swallow quantities
without death resulting, simply because the poison is rapidly expelled;
whereas, if the œsophagus was ligatured (as in the experiments on the
lower animals formerly favoured by the French school of toxicologists),
death must rapidly ensue. The following table is a guide to the maximum
single dose, and also the amount safe to administer in the twenty-four
hours in divided doses. As a general rule, it may be laid down that
double the maximum dose is likely to be dangerous:--

TABLE SHOWING THE MAXIMUM SINGLE DOSE, AND MAXIMUM QUANTITY OF THE
DIFFERENT PREPARATIONS OF DIGITALIS, WHICH CAN BE ADMINISTERED IN A DAY.

  +----------------+----------------------+--------------------------+
  |                |     Single Dose.     |         Per Day.         |
  |                +----------+-----------+-------------+------------+
  |                | Grains or|  Grammes  | Grains or   |Grammes     |
  |                |  Minims. | or c.c’s. |  Minims.    |or c.c’s.   |
  +----------------+----------+-----------+-------------+------------+
  |Powdered Leaves,| 4½ grns. |  ·3 grm.  |  15·4 grns. |  1·0 grm.  |
  |Infusion,       | 480 m.   |28·3 c.c.  | 1440 m.     | 84·9 c.c.  |
  |Tincture,       |  45 m.   |   3 c.c.  |  135 m.     |    9 c.c.  |
  |Digitalin,      | ·03 grn. |  ·002 grm.|   ·09 grn.  |  ·006 grm. |
  |Extract,        |3·0   „   |  ·2    „  | 12·0 „      |  ·8    „   |
  +----------------+----------+-----------+-------------+------------+

§ 538. =Statistics.=--The main knowledge which we possess of the action
of digitalis is derived from experiments on animals, and from occasional
accidents in the taking of medicines; but in comparison with certain
toxic agents more commonly known, the number of cases of death from
digitalis is very insignificant. Of 42 cases of digitalis-poisoning
collected by Husemann, 1 was criminal (murder); 1 the result of
mistaking the leaves for those of borage; 42 were caused in medicinal
use--in 33 of these last too large a dose had been given, in 3 the drug
was used as a domestic remedy, in 2 of the cases the prescription was
wrongly read, and in 1 digitalis was used as a secret remedy. Twenty-two
per cent. of the 45 were fatal.

§ 539. =Effects on Man.=--It was first distinctly pointed out by Tardieu
that toxic doses of digitalis, or its active principles, produced not
only symptoms referable to an action on the heart, but also, in no small
degree, gastric and intestinal irritation, similar to that produced by
arsenic. Tardieu also attempted to distinguish the symptoms produced by
the pharmaceutical preparations of digitalis (the tincture, extract,
&c.), and the glucoside digitalin; but there does not appear a
sufficient basis for this distinction. The symptoms vary in a
considerable degree in different persons, and are more or less tardy or
rapid in their development, according to the dose. Moderate doses
continued for some time (as, for example, in the persistent use of a
digitalis medicine) may produce their first toxic effects even at the
end of many days; but when a single large dose is taken, the symptoms
are rarely delayed more than three hours. They may commence, indeed, in
half an hour, but have been known to be retarded for more than
twenty-four hours, and the longer periods may be expected if digitalis
is given in hard, not easily soluble pills. There is commonly a feeling
of general _malaise_, and then violent retching and vomiting. The pulse
at first may be accelerated, but it soon is remarkably slowed--it sinks
commonly down to 50, to 40, and has even been known as low as 25. To
these symptoms, referable to the heart and to the digestive tract, are
added nervous troubles; there are noises in the ears, and disturbances
of vision. In a case related by Taylor, a red-coal fire seemed to the
patient to be of a blue colour; in another, related by Lersch,[564]
there was blindness for eighteen hours, and for some time a confusion in
the discrimination in colours; quiet delirium has also been noticed. As
the case proceeds, the gastric symptoms also increase in severity; the
tongue Christison, in one case, noticed to be enormously swollen, and
the breath fœtid. Diarrhœa is commonly present, although also sometimes
absent. The action of the kidneys is suppressed. Hiccough and
convulsions close the scene.

[564] _Rhen. West. Corr. Bl._, 15, 1848; Husemann in Maschka’s
_Handbuch_.

In the cumulative form, the symptoms may suddenly burst out, and the
person pass into death in a fainting-fit without any warning. As a rare
effect, hemiplegia may be mentioned.

This brief _résumé_ of the symptoms may be further illustrated by the
following typical cases:--A recruit, aged 22, desiring to escape from
military service, went to a so-called “_Freimacher_” who gave him 100
pills, of which he was to take eight in two doses daily. Eleven days
after the use of the pills, he became ill, and was received into
hospital, where he suddenly died after three weeks’ treatment. His
malady was at first ascribed to gastric catarrh; for he suffered from
loss of appetite, nausea, and constipation. He complained of pain in the
head, and giddiness. His breath smelled badly, and the region of the
stomach was painful on pressure. The pulse was slow (56), the
temperature of the body normal. Towards the end, the pulse sank to 52;
he suffered from vomiting, noise in the ears, troubles of vision, great
weakness, and later, hiccough and swelling in the neck. The mere act of
standing up in order to show his throat caused him to faint; on the same
day on which this occurrence took place, he suddenly died on the way to
the nightstool. Thirteen of the pills were found in the patient’s
clothes, and from a chemical and microscopical examination it was found
that they contained digitalis leaf in fine powder. The quantity which
the unfortunate man took in the four weeks was estimated at 13·7 grms.
(= about 211 grains).

Two of his comrades had also been to the “_Freimacher_,” and had
suffered from the same symptoms, but they had left off the use of the
medicine before any very serious effect was produced.[565][566]

[565] Köhnhorn, _Vierteljahrsschr. f. ger. Med._, 1876, n. F. xxiv. p.
402.

[566] There is an interesting case on record, in which a woman died from
the expressed juice of digitalis. She was twenty-seven years of age, and
took a large unknown quantity of the freshly expressed juice for the
purpose of relieving a swelling of the limbs. The symptoms came on
almost immediately, she was very sick, and was attacked by a
menorrhagia. These symptoms continued for several days with increasing
severity, but it was not until the fifth day that she obtained medical
assistance. She was then found semi-comatose, the face pale, pulse slow,
epigastrium painful on pressure, diarrhœa, and hiccough were frequent.
She died on the twelfth day. The _post-mortem_ appearances showed
nothing referable to digitalis save a few spots of inflammation on the
stomach.--Caussé, _Bull. de Thérapeutique_, vol. lvi. p. 100; _Brit. and
For. Med. Chir. Review_, vol. xxvi., 1860, p. 523.

An instructive case of poisoning by digitoxin occurred in the person of
Dr. Koppe, in the course of some experiments on the drug. He had taken
1·5 mgrm. in alcohol without result; on the following day (May 14) he
took 1 mgrm. at 9 A.M., but again without appreciable symptoms. Four
days later he took 2 mgrms. in alcoholic solution, and an hour
afterwards felt faint and ill, with a feeling of giddiness; the pulse
was irregular, of normal frequency, 80 to 84. About three hours after
taking the digitoxin, Dr. Koppe attempted to take a walk, but the
nausea, accompanied with a feeling of weakness, became so intense that
he was obliged to return to the house. Five hours after the dose, his
pulse was 58, intermittent after about every 30 to 50 beats. Vomiting
set in, the matters he threw up were of a dark green colour; after
vomiting he felt better for a quarter of an hour, then he again vomited
much bilious matter; the pulse sank to 40, and was very intermittent,
stopping after every 2 or 3 beats. Every time there was an intermission,
he felt a feeling of constriction and uneasiness in the chest. Six and a
quarter hours after the dose there was again violent vomiting and
retching, with paleness of the face. The muscular weakness was so great
that he could not go to bed without assistance. He had a disorder of
vision, so that the traits of persons well-known to him were changed,
and objects had a yellow tint. He had a sleepless night, the nausea and
vomiting continuing. During the following day the symptoms were very
similar, and the pulse intermittent, 54 per minute. He passed another
restless night, his short sleep being disturbed by terrible dreams. On
the third day he was somewhat better, the pulse was 60, but irregular
and still intermittent; the nausea was also a little abated. The night
was similar in its disturbed sleep to the preceding. He did not regain
his full health for several days.[567]

[567] _Arch. f. exp. Path. u. Pharm._, vol. iii. p. 289, 1875.

A third case may be quoted, which differs very markedly from the
preceding, and shows what a protean aspect digitalin poisoning may
assume. A woman, twenty-three years old, took on June 26th, at 7 A.M.,
for the purpose of suicide, 16 granules of digitalin. Two hours later
there was shivering and giddiness, so that she was obliged to go to bed.
In the course of the day she had hallucinations. In the evening at 8
P.M., after eating a little food, she had a shivering fit so violent
that her teeth chattered; there was cold sweat, and difficulty in
breathing; she became gradually again warm, but could not sleep. At 1
A.M. the difficulty of breathing was so great that she dragged herself
to the window, and there remained until 3 A.M., when she again went back
to bed, slept until 7 A.M., and woke tolerably well. Since this attempt
of self-destruction had failed, she took 40 granules. After one hour she
became giddy, had hallucinations, chilliness, cold sweats, copious
vomiting, and colicky pains; there was great muscular weakness, but no
diarrhœa. Towards evening the vomiting became worse. There was no action
of the bowels, nor was any urine passed; she felt as if her eyes were
prominent and large. The sufferings described lasted during the whole
night until five o’clock the following day, when the vomiting ceased,
whilst the hallucinations, chilliness, and cold sweat continued; and the
thirst, sick feeling, and weakness increased. The next morning, a
physician found her motionless in bed, with pale face, notable double
exophthalmus, dilated pupils, and cold skin, covered with sweat; the
pulse was small and intermittent, sometimes scarcely to be felt (46 to
48 per minute); the epigastrium was painful on pressure. She passed this
second night without sleep, and in the morning the pulse had risen from
56 to 58 beats, but was not quite so intermittent. There was some action
of the bowels, but no urine was passed, nor had any been voided from the
commencement; the bladder was not distended. The following (third) day
some red-coloured, offensive urine was passed; the skin was warmer, and
the pulse from 60 to 64, still somewhat intermittent--from this time she
began to improve, and made a good recovery.[568]

[568] Related by Ducroix: _De l’Empoisonnement par la Digitale et la
Digitaline._ Paris, 1864.

§ 540. =Physiological Action of the Digitalins.=--Whatever other
physiological action this group may have, its effect on the heart’s
action is so prominent and decided, that the digitalins stand as a type
of _heart poisons_. The group of heart poisons has been much extended of
late years, and has been found to include the following:--Antiarin, an
arrow poison; helleborin, a glucoside contained in the hellebore family;
a glucoside found in the _Apocynaceæ_, _Thevatii neriifolia_, and
_Thevatia iccotli_; the poisonous principle of the _Nerium oleander_ and
_N. odorum_; the glucoside of _Tanghinia venenifera_; convallamarin,
derived from the species of _Convallaria_; scillotoxin, from the squill;
superbin, from the Indian lily; and the alkaloid erythrophlœin from the
_Erythrophlœum judiciale_ (see p. 432 _et seq._). This list is yearly
increasing.

§ 541. =Local Action.=--The digitalins have an exciting or stimulating
action if applied to mucous membranes--_e.g._, if laid upon the nasal
mucous surface, sneezing is excited; if applied to the eye, there is
redness of the conjunctivæ with smarting; if to the tongue, there is
much irritation and a bitter taste. The leaves, the extract, and the
tincture all have this directly irritating action, for they all redden
and inflame mucous membranes.

§ 542. =Action on the Heart.=--The earlier experimenters on the
influence of digitalis on the heart were Stannius and Traube.
Stannius[569] experimented on cats, and found strong irregularity, and,
lastly, cessation in diastole, in which state it responded no longer to
stimuli. Rabbits and birds--especially those birds which lived on
plants--were not so susceptible, nor were frogs.

[569] _Arch. f. Physiol._

Traube[570] made his researches on dogs, using an extract, and
administering doses which corresponded to from ·5 to 4·0 grms. He
divided the symptoms witnessed into four stages:--

[570] _Ann. d. Charité-Krankenhauses_, vol. ii. p. 785.

_1st Stage._--The pulse frequently diminishes, while the pressure of the
blood rises.

_2nd Stage._--Not seen when large doses are employed; pulse frequency,
as well as blood pressure, abnormally low.

_3rd Stage._--Pressure low, pulse beats above the normal frequency.

The slowing of the heart[571] is attributed to the stimulus of the
inhibitory nerves, but the later condition of frequency to their
paralysis. After the section of the vagi the slow pulse frequently
remains, and this is explained by the inhibitory action of the cardiac
centre. The vagus, in point of time, is paralysed earlier than the
muscular substance of the heart.

[571] Slowing of the pulse was mentioned first by Withering (_An Account
of the Foxglove_, Lond., 1785). Beddoes afterwards observed that
digitalis increased the force of the circulation, the slowing of the
pulse not being always observed; according to Ackermann, if the
inhibitory apparatus is affected by atropine, or if the patient is under
deep narcosis, the slowing is absent.

The increased blood pressure Traube attributed to increased energy of
the heart’s contraction, through the motor centre being stimulated
later; the commencing paralysis explains the abnormally low pressure.

There is, however, also an influence on vaso-motor nerves. What Dr.
Johnson has described as the “stop-cock” action of the small arteries
comes into play, the small arteries contract and attempt, as it were, to
limit the supply of poisoned blood. Ackermann,[572] indeed, witnessed
this phenomenon in a rabbit’s mesentery, distinctly seeing the arteries
contract, and the blood pressure rise after section of the spinal cord.
This observation, therefore, of Ackermann’s (together with experiments
of Böhm[573] and L. Brunton[574]) somewhat modifies Traube’s
explanation, and the views generally accepted respecting the cause of
the increased blood pressure may be stated thus:--The pressure is due to
prolongation of the systolic stroke of the cardiac pump, and to the
“stop-cock” action of the arteries; in other words, there is an increase
of force from behind (_vis a tergo_), and an increased resistance in
front (_vis a fronte_).

[572] _Deutsch. Arch. f. klin. Med._, vol. xix. p. 125.

[573] _Archiv f. d. Ges. Phys._, vol. v. p. 153.

[574] _On Digitalis, with Some Observations on the Urine_, Lond., 1868.

§ 543. =Action of the Digitalins on the Muco-Intestinal Tract and other
Organs.=--In addition to that on the heart, there are other actions of
the digitalins; for example, by whatever channel the poison is
introduced, vomiting has been observed. Even in frogs this, in a
rudimentary manner, occurs. The diuretic action which has been noticed
in man is wanting in animals, nor has a lessened diminution of urea been
confirmed.

Ackermann found the temperature during the period of increased blood
pressure raised superficially, but lowered internally. According to
Boeck[575] there is no increase in the decomposition of the albuminoids.

[575] _Intoxication_, p. 404.

    § 544. =The Action of Digitalin on the Common Blow-fly.=--The author
    has studied the effects of digitalin, made up into a thin paste with
    water, and applied to the head of the common blow-fly. There are at
    once great signs of irritation, the sucker is extruded to its full
    length, and the fly works its fore feet, attempting to brush or
    remove the irritating agent. The next symptom is a difficulty in
    walking up a perpendicular glass surface. This difficulty increases,
    but it is distinctly observed that weakness and paralysis occur in
    the legs before they are seen in the wings. Within an hour the wings
    become paralysed also, and the fly, if jerked from its support,
    falls like a stone. The insect becomes dull and motionless, and
    ultimately dies in from ten to twenty-four hours. A dose, in itself
    insufficient to destroy life, does so on repetition at intervals of
    a couple of hours. The observation is not without interest, inasmuch
    as it shows that the digitalins are toxic substances to the muscular
    substance of even those life-forms which do not possess a heart.

§ 545. =Action of the Digitalins on the Frog’s Heart.=--The general
action of the digitalins is best studied on the heart of the frog. Drs.
Fagge and Stevenson have shown[576] that, under the influence of
digitalin, there is a peculiar form of irregularity in the beats of the
heart of the frog; the ventricle ultimately stops in the white
contracted state, the voluntary power being retained for fifteen to
twenty minutes afterwards; in very large doses there is, however, at
once paralysis. Lauder Brunton[577] considers the action on the heart to
essentially consist in the prolongation of the systole.

[576] _Guy’s Hospl. Reports_, 3rd ver., vol. xii. p. 37.

[577] _On Digitalis, with Some Observations on the Urine_, Lond., 1868.

Atropine or curare have no influence on the heart thus poisoned. If the
animal under the influence of digitalin be treated with muscarine, it
stops in diastole instead of systole. On the other hand, the heart
poisoned by muscarine is relieved by digitalin, and a similar influence
appears to be exercised by atropine. The systolic stillness of the
heart is also removed by substances which paralyse the heart, as
delphinin, saponin, and apomorphin.

Large doses of digitalin, thrown suddenly on the circulation by
intravenous injection, cause convulsions and sudden death, from quick
palsy of the heart. With frogs under these circumstances there are no
convulsions, but a reflex depression, which, according to Weil[578] and
Meihuizen,[579] disappears on decapitation. The central cerebral
symptoms are without doubt partly due to the disturbance of the
circulation, and there is good ground for attributing them also to a
toxic action on the nervous substance. The arteries are affected as well
as the heart, and are reduced in calibre; the blood pressure is also
increased.[580] This is essentially due to the firm, strong contraction
of the heart, and also to the “stop-cock” action of the small
arteries.[581]

[578] _Archiv f. Anat. u. Physiol._, 1871, p. 282.

[579] _Archiv f. d. Ges. Physiol._, vol. vii. p. 201.

[580] The following is a brief summary of observations on the blood
pressure; four stages may be noticed--(1) Rise of normal blood pressure,
not necessarily accompanied with a diminution of pulse frequency; (2)
continuation of heightened blood pressure, the pulse being raised beyond
the normal rate; (3) continued high pressure, with great irregularity of
the heart and intermittent pulse; (4) quick depression of pressure,
sudden stopping of the heart, and death.

[581] According to Boehm (_Arch. f. d. Ges. Physiol._, Bd. v. S. 189)
and to Williams (_Arch. f. exper. Pathol._, Bd. xiii. S. 2), the rise of
pressure is due entirely to the heart, and not to the contractions of
the small arteries; but I fail to see how the small arteries can
contract, and yet not heighten the pressure.

§ 546. =Post-mortem Appearances.=--In the case of the recruit poisoned
by digitalis leaf (p. 425), the blood was found dark and fluid; the
right ventricle and auricle of the heart were filled with blood, the
left empty; the brain and its membranes were anæmic; the stomach and
mucous membrane of the intestines were in parts ecchymosed, and there
were patches of injection. In the case of the widow De Pauw, poisoned
with digitalin by the homœopath (Conty de la Pommerais), the only
abnormality discovered was a few hyperæmic points in the mucous membrane
of the stomach and small intestines. It is then certain that although
more or less redness of the lining membrane of the intestine track may
be present, yet, on the other hand, the active principle of the
digitalis may destroy life, and leave no appreciable sign.

§ 547. =Separation of the Digitalins from Animal Tissues, &c.=--It is
best to make an alcoholic extract after the method of Stas, the alcohol
being feebly acidulated by acetic acid, and all operations being carried
on at a temperature below 60°. The alcoholic extract is dissolved in
water feebly acidulated by acetic acid, and shaken up, first with
petroleum ether to remove impurities (the ether will not dissolve any of
the digitalins), then with benzene, and, lastly, with chloroform. The
benzene dissolves digitalein, and the chloroform, digitalin and
digitoxin. On allowing these solvents to evaporate spontaneously,
residues are obtained which will give the reactions already detailed.
Neither the bromine nor any other chemical test is sufficient to
identify the digitalins; it is absolutely necessary to have resource to
physiological experiment. The method used by Tardieu in the classical
Pommerais case may serve as a model, more especially the experiments on
frogs. Three frogs were properly secured, the hearts exposed, and the
beats counted. The number of beats was found to be fairly equal. Frog
No. 1 was placed under such conditions that the heart was constantly
moist. Frog No. 2 was poisoned by injecting into the pleura 6 drops of a
solution in which 10 mgrms. of digitalin were dissolved in 5 c.c. of
water. The third frog was poisoned by a solution of the suspected
extract. The number of beats per minute were now counted at definite
intervals of time as follows:--

TABLE SHOWING THE ACTION OF DIGITALIN ON THE FROG’S HEART.

  +----------------------+--------------------+----------------------+
  |     Frog No. 1.      |    Frog No. 2.     |     Frog No. 3.      |
  |     Unpoisoned.      |   Poisoned by a    |   Poisoned by the    |
  |                      |   known quantity   |     suspected        |
  |                      |   of digitalin.    |      extract.        |
  +----------------------+--------------------+----------------------+
  |    No. of beats      |   No. of beats     |   No. of beats       |
  |     per minute.      |    per minute.     |    per minute.       |
  +----------------------+--------------------+----------------------+
  | After 6 minutes, 42  |    20              |   26                 |
  |   „  10    „     40  |    16 irregular.   |   24 irregular.      |
  |   „  20    „     40  |    15              |   20     „           |
  |   „  28    „     38  |     0              |   12 very irregular. |
  |   „  31    „     36  |     0              |    0                 |
  +----------------------+--------------------+----------------------+

In operating in this way--which is strictly comparative, and, with care,
has few sources of error--if the heart of the frog poisoned with the
unknown extract behaves in the number and irregularity of its
contractions similarly to that of the digitalin-poisoned heart, it is a
fair inference that, at all events, a “heart-poison” has been separated;
but it is, of course, open to question whether this is a digitalin or
one of the numerous groups of glucosides acting in the same way. If
sufficient quantity has been separated, chemical reactions, especially
the bromine test (Grandeau’s test), may decide, but with the larger
number (yearly increasing) of substances acting similarly on the heart,
great caution in giving an opinion will be necessary.


II.--Other Poisonous Glucosides Acting on the Heart.

§ 548. Several members of these glucosides have been studied by
Schmiedeberg,[582] and his convenient divisions will be followed here:--

[582] _Beiträge zur Kentniss der pharmakol. Gruppe des Digitalins._


1. CRYSTALLISABLE GLUCOSIDES.

    =Antiarin= (C₁₄H₂₀O₅).--Antiarin is an arrow poison obtained from
    the milky juice of the _Antiaris toxicaria_ growing in Java.
    Antiarin is obtained in crystals, by first treating the inspissated
    milky juice with petroleum ether to remove fatty and other matters,
    and then dissolving the active principle out with absolute alcohol.
    The alcoholic extract is taken up with water, precipitated with lead
    acetate, filtered, and from the filtrate antiarin obtained by
    freeing the solution from lead, and then evaporating. De Vry and
    Ludwig obtained about 4 per cent. from the juice. Antiarin is
    crystalline, the crystals containing 2 atoms of water. Its
    melting-point is given as 220·6°; the crystals are soluble in water
    (254 parts cold, 27·4 parts boiling), they are not soluble in
    benzene, and with difficulty in ether; 1 part of antiarin requiring
    2792 parts of ether.

    The watery solution is not precipitated by metallic salts. On
    warming with dilute mineral acids, antiarin splits up into a resin
    and sugar. Concentrated sulphuric acid gives with antiarin a
    yellow-brown solution, hydrochloric and nitric acids strike no
    distinctive colours.

    § 549. =Effects.=--Antiarin is essentially a muscular and a heart
    poison. When given in a sufficient dose, it kills a frog in from
    half an hour to an hour. Its most marked effect is on the cardiac
    muscle, the heart beats more and more slowly, and at last stops, the
    ventricle being firmly contracted. As with digitalin, there is a
    very marked prolongation of the systole, and as with digitalin,
    after the beats have ceased, a forcible dilatation of the ventricle
    will restore them (Schmiedeberg). It is doubtful whether by
    physiological experiment antiarin could be differentiated from
    digitalin.

    § 550. =Separation of Antiarin.=--In any case of poisoning by
    antiarin, it would be best to extract with alcohol, evaporate,
    dissolve the alcoholic extract in water, precipitate with lead
    acetate, filter, free the filtrate from lead, and then, after
    alkalising with ammonia, shake the filtrate successively with
    petroleum ether, benzene, and a small quantity of ether in the
    manner recommended at page 247, _et seq._ The liquid, now freed from
    all fatty, resinous, and alkaloidal bodies, is neutralised and
    evaporated to dryness in a vacuum, and the dry residue taken up with
    absolute alcohol, filtered, the alcohol evaporated at a very low
    temperature, and finally the extract dissolved in a small quantity
    of water, and submitted to physiological tests.

§ 551. =The Active Principles of the Hellebores.=--The Christmas rose
(_Helleborus niger_), as well as _H. viridis_, _H. fœtidus_, and, in
short, all the species of hellebore, are poisonous, and if the root is
treated with alcohol, from the alcoholic extract may be separated two
glucosides, _helleborin_ and _helleborein_.

=Helleborin= is in the form of white, glittering needles, which, if
placed on the tongue, are almost tasteless, but if dissolved in alcohol,
and then tasted, give a burning, numbing sensation. By boiling with zinc
chloride, helleborin splits up into sugar and a resin--_helleboresin_.
Concentrated sulphuric acid dissolves the crystals with the production
of a beautiful red colour; on standing, the solution after a while
becomes colourless, and a white powder separates.

=Helleborein= forms colourless crystals, mostly consisting of fine
needles; they have a bitter taste, excite sneezing, and are very
hygroscopic. The crystals easily dissolve in water and dilute alcohol,
but are with difficulty soluble in absolute alcohol, and not soluble in
ether. They dissolve in fatty oils. Helleborein splits by the action of
mineral acids into sugar and amorphous _helleboretin_.

=Helleboretin= is in the moist condition of a beautiful violet-blue
colour, becoming, when dried at 100°, dirty green. Concentrated
sulphuric acid dissolves it with the production of a brown-yellow
colour, which on standing passes into violet and then into brown.

Marmé separated from _H. fœtidus_, in addition, a white, intensely
odorous substance, but too small in quantity to thoroughly investigate
its properties.

§ 552. There is little doubt that hellebore owes its properties to the
glucosides just described. There are several instances of poisoning by
hellebore root,[583] and by the pharmaceutical preparations, but none of
poisoning by the pure active principles. Morgagni mentions a case in
which 2 grms. (nearly 31 grains) of the watery extract of _H. Niger_
caused death within eight hours; and Ferrari saw, after the use of the
wine in which the root had been boiled, two persons poisoned with a like
result. A more recent case was recorded by Felletar, in 1875, in which a
person died from an infusion of hellebore; there was, however, old
standing heart-disease, so that there may be a doubt as to the real
cause of death in this instance. Schauenstein mentions a case in which
the roots of hellebore were accidentally used in soup, but the bitter
taste prevented any quantity being eaten. The physiological action,
especially of helleborein, is that of an intense heart poison, and the
symptoms produced by the hellebores are so strikingly like those of the
digitalins that it might be difficult to distinguish clinically between
them. In any case of poisoning, the active principle must be separated
in the form of an alcoholic extract, and identified as a heart poison by
physiological experiment.

[583] There used to be a tincture officinal in our pharmacopœia; the
root of _H. viridis_ is officinal in the German pharmacopœia, maximum
single dose, ·3 grm.; maximum total quantity in twenty-four hours, 1·2
grm. The tincture is also officinal on the Continent.

    § 553. =Euonymin= is found in a resin obtained from the _Euonymus
    atropurpureus_; it is crystalline, crystallising in colourless,
    cauliflower-like masses consisting of groups of stellate needles,
    which are soluble in water, but with difficulty in alcohol. It is a
    glucoside, and a powerful heart poison, 1 mgrm. causing the heart of
    a frog to cease in diastole.[584]

[584] Schmiedeberg, _op. cit._, from unpublished researches of Professor
H. Meyer, Dorpat.

    § 554. =Thevetin= (C₅₄H₄₈O₂).--A glucoside which has been separated
    from the Thevetia nereifolia, and perhaps also from the _Cerbera
    Odallam_. It is soluble in 124 parts of water at 14°, and is easily
    soluble in spirit, but not in ether. It is coloured by sulphuric
    acid red-brown, passing into cherry-red, and then, in a few hours,
    into violet. On boiling with diluted acids, it splits up into sugar
    and theveresin. Both thevetin and theveresin are powerful heart
    poisons.[585]

[585] Husemann, _Archiv f. exper. Path. u. Pharmakol._, Bd. v., S. 228,
1876.


2. SUBSTANCES PARTLY CRYSTALLISABLE BUT WHICH ARE NOT GLUCOSIDES.

    § 555. =Strophantin= is a very poisonous substance which belongs
    physiologically to this group, but does not seem to be a glucoside.
    It is soluble in water and in alcohol, less so in ether and
    chloroform. It is found in the _kombé_, _manganja_, _inée_, or
    _onaje_, a West African poison derived from the _Strophanthus
    hispidus_ of the family of _Apocynaceæ_. The poison has been
    investigated by several observers.[586]

[586] _Digitoxin_ (see _ante_, p. 420) belongs to this group.

    Dr. Fraser considers, from his experiments, (1) That strophantin
    acts primarily on the heart, producing, as an end result, heart
    paralysis, with permanence of the ventricular systole. (2) He found
    the pulmonary respiration to continue in cold-blooded animals many
    minutes after the heart was paralysed. (3) The striped muscles of
    the body are affected, and twitches occur in them; their tonicity is
    exaggerated, and finally their functional activity is destroyed.
    This change is referred to an action on the muscular structure
    itself, independent of that upon the heart, and also independent of
    the cerebro-spinal nervous system. (4) The reflex action of the
    spinal cord is suspended after the heart is paralysed, but the motor
    conductivity of the spinal cord and of the nerve trunks continue
    after the striped muscles of the body are paralysed. (5) The
    lymph-hearts of the frog continue to contract for many minutes after
    the blood-heart has been paralysed.

    § 556. =Apocynin.=--In the root of _Apocynum cannabinum_ a
    non-crystallisable substance, soluble in alcohol and ether, but not
    soluble easily in water, has been separated and found to have a
    physiological activity similar to that of the digitalins.[587]

[587] Hardy et Callois, “_Sur la matière active du Strophanthus Hispidus
ou Inée_,” _Gaz. Med. de Paris_; Pelikan, _Compt. Rend._, t. 60, p.
1209, 1815; Sharpey,_ Proc. Roy. Soc._, May, 1865; Fagge and Stevenson,
_Pharm. Journ._, p. 11, 1865-66; Fraser, _Journ. of Anatom. and Phys._,
also _Proc. of Roy. Soc. of Edin._; Poillo and Carville, _Arch. de
Physiol. Norm. et Pathol._, 1872; G. Valentin, _Zeitschr. et.
Biologie._, x. 133, 1874.


3. NON-CRYSTALLISABLE GLUCOSIDES ALMOST INSOLUBLE IN WATER.

    § 557. =Scillain, or Scillitin=, a glucoside which has been
    separated from the bulbs of the common squill. It is insoluble or
    nearly so in water, but easily dissolves in alcohol. It is little
    soluble in ether. It acts upon the heart, and is poisonous.

    =Adonidin=, a very similar substance, has been separated from the
    root of the _Adonis vernalis_ (Nat. Ord. _Ranunculaceæ_), to which
    the name of adonidin has been given.[588] It is an amorphous,
    colourless substance, without odour; soluble in alcohol, but with
    difficulty soluble in ether and water. It is precipitated by tannin,
    and on saponification by mineral acids, splits up into sugar and a
    substance soluble in ether. The effects on animals are identical
    with those of digitalin. The root has been used recently in
    medicine, and found to slow the heart and increase the urinary
    secretion; in this also it is like digitalis.

[588] Cervello, _Archiv für exp. Path. Pharm._, 1882, p. 338.

    § 558. =Oleandrin.=--Oleander leaves contain two
    chemically-different, nitrogen-free substances. The one is probably
    identical with digitalein; but as this is not certain, Schmiedeberg
    proposes to call it provisionally _neriin_. The other active
    substance is essentially the same as the oleandrin of Lukomske[589]
    and Betelli.[590] Oleandrin has basic properties, and is separated
    in the form of an amorphous mass, soluble in alcohol, ether, and
    chloroform, and slightly soluble in water. Schmiedeberg obtained a
    third product from African leaves, which he calls _nerianthin_.
    This, on treatment with sulphuric acid and bromine, gives a
    beautiful colour peculiar to oleander leaves. It is very similar in
    physiological and chemical properties to digitalin, and is probably
    derived by decomposition from one of the principles already
    described. There is also a product similar to digitaliresin.

[589] _Repert. de Chimie de Wurtz et Bareswill_, t. iii. p. 77, 1861.

[590] _Bull. Med. di Bologna_, t. xix. p. 321, 1865.

    The active principles of the oleander are separated by digestion of
    the leaves with alcohol of 50 per cent., and precipitating the
    alcoholic extract with lead acetate and ammonia. The first
    precipitate is yellow, and is probably composed of a tannin-like
    substance; the next precipitate is white, consisting of the lead
    compound of neriin. The precipitates are filtered off, and the
    filtrate concentrated; nerianthin, after a while, separates in light
    flocks, and the filtrate from this contains some of the other
    products.

    § 559. =Neriin or Oleander Digitalin.=--Neriin is, in the presence
    of much free mineral acid, precipitated by potass-bismuth iodide, a
    reaction first pointed out by Marmé,[591] as useful in the isolation
    of the helleborins; or it may be precipitated by tannin, and then
    the precipitate decomposed by dissolving in alcohol, and evaporating
    it to dryness with zinc oxide on the water-bath. It is next
    extracted by absolute alcohol, and precipitated by the addition of
    much ether. The further purification consists of resolution in
    alcohol, and fractional precipitation by ether. If, however, the
    potass-bismuth iodide process is used, the liquid must be acidified
    strongly with sulphuric acid, and the precipitate washed with
    diluted sulphuric acid. The precipitate may be decomposed by baryta,
    filtered, and the filtrate freed from baryta by carbon dioxide; the
    filtrate from this contains neriin with baric iodide; it is
    therefore treated with silver sulphate, then again with baryta, next
    with carbon dioxide, and also with SH₂ to get rid of the last trace
    of silver.

    The filtrate will also contain some oleandrin which, by evaporating
    slowly in a vacuum, separates gradually in the form of a clear,
    resinous mass. It can be filtered off, and the neriin then may be
    precipitated pure by fractional precipitation. Its physiological
    action is the same as that of digitalein.

[591] _Zeitschr. f. rat. Med._ (3 R.), Bd. xxvi., S. 1, 1866.

    § 560. The nerium oleander has several times caused grave symptoms
    of poisoning, and they have usually fairly agreed with those
    produced by foxglove. For example, Maschka[592] relates the case of
    a boy, two years old, who ate two handfuls of the nerium oleander.
    The effects commenced in ten minutes, the child was uneasy, and
    vomited. In six hours a sleepy condition came on; the face was pale,
    the skin cold, the pupils contracted, and the pulse slow and
    irregular. After the sickness the boy woke up, but again fell
    asleep, and this occurred frequently; coffee was given, which
    appeared to do good. The pulse was intermittent. On the following
    day the child was still ill, with an intermittent pulse, frequent
    vomiting, feebleness, sleeplessness, and dilatation of the pupil;
    there was no diarrhœa, on the contrary, the bowels were confined. On
    the third day recovery followed.

[592] _Vierteljahrsschrift f. gericht. Med._, Bd. ii., No. 17, 1860.
_Brit. and For. Med. Chir. Review_, vol. xxvi. p. 523, 1860.

    In an Indian case,[593] the symptoms were altogether peculiar, and
    belonged rather to the convulsive order. A wood-cutter, aged
    thirty-five, near Kholapore, took, for the purpose of suicide, a
    little over an ounce of the expressed juice of the oleander. The
    symptoms began so rapidly that he had not time to walk five yards
    before he fell insensible; he was brought to the hospital in this
    state; the face on his arrival was noticed to be flushed, the
    breathing stertorous, there were violent spasmodic contractions of
    the whole body, more marked on the left than on the right side. The
    effect of this was remarkable. During the intervals of the spasm,
    the patient lay evenly on his back, and when the convulsions
    commenced the superior contraction of the left side threw him on to
    the right, in which position he remained during the paroxysm, after
    the subsidence of which he fell back into his old position. The
    evacuations were involuntary and watery; the man was insensible,
    with frequent convulsions of the kind described, for two days, but
    on the third day became conscious, and made a good recovery.

[593] _Transac. of Med. and Phys. Soc. of Bombay_, 1859.

    In any case of poisoning, the methods by which neriin and oleandrin
    are separated from the plant can be applied to separate them from
    the tissues with more or less success. Here, as in all the other
    digitalin-like glucosides, physiological tests are alone of value in
    the final identification.

    § 561. =The Madagascar Ordeal Poison.=--To this group may also
    belong the poison of the _Tanghinia venenifera_, a tree in the
    Island of Madagascar, the fruit of which is used as an ordeal
    poison. It may be obtained in crystals; it is insoluble in water,
    and very poisonous. The upas of Singapore is also said to contain
    with strychnine a glucoside similar to antiarin.


4. SUBSTANCES WHICH, WITH OTHER TOXIC EFFECTS, BEHAVE LIKE THE
DIGITALIS.

    § 562. =Erythrophlein= is an alkaloid, not a glucoside, and is
    obtained from the bark of the _Erythrophlœum guineense_ (West
    Africa). It acts on the heart like digitalis, and has also effects
    similar to picrotoxin.


III.--Saponin--Saponin Substances.

§ 563. The term “saponin” of late years has been applied to a class of
glucosides which possess the common property of being poisonous, and,
when dissolved in water, forming solutions which froth on shaking like
soap-suds.

The substances which have these properties are not all of the same
series chemically, but those of the general formula, C_{n}H_{2n-8}O₁₀,
are most numerous, and the following is a list:--

         Name.                                       Formula.

  Saponin, senegin,      }
  Quillaja-sapotoxin,    }
  Sapindus-sapotoxin,    }                           C₁₇H₂₆O₁₀.
  Grypsophila-sapotoxin, }
  Agrostemma-sapotoxin,  }
  Saponin II., digitonin, saporubrin, assamin,       C₁₈H₂₈O₁₀.
  Saponin III., quillajic acid, polygalic acid, }    C₁₉H₃₀O₁₀.
  Herniari-saponin,                             }
  Cyclamin, sarsaparilla-saponin,                    C₂₀H₃₂O₁₀.
  Sarsa-saponin,                                     C₂₂H₃₆O₁₀.
  Parillin,                                          C₂₆H₄₄O₁₀.
  Melanthin,                                         C₂₉H₅₀O₁₀.

Possibly also dulcamarin C₂₂H₃₄O₁₀ and syringen C₁₇H₂₆O₁₀ may belong to
this series.

There are some 150 distinct plants which thus yield saponins; a few of
these plants are as follows:--_Saponaria officinalis_, _Gypsophila
struthium_, _Agrostemma githago_ (corn cockle), _Polygala senega_,
_Monimia polystachia_, the bark of _Quillaja saponaria_, and
_Chrysophyllum glycyphleum_.

The saponin separated from _Saponaria_, and from the corn cockle will be
here described.

§ 564. =Properties.=--Saponin is a white amorphous powder, very soluble
in water, to which it gives the curious property of frothing just like
soap solution. To obtain this effect there must be at least 1 mgrm. in 1
c.c. of liquid. Saponin is neutral in reaction, it has no odour, but
causes sneezing if applied to the mucous membrane of the nose; the taste
is at first sweet, and then sharp and acrid. It is almost entirely
insoluble in absolute alcohol, but dissolves in hot alcohol of 83° to
separate again nearly completely on cooling. It is precipitated by basic
lead acetate, and also by baryta water, but in each case it is advisable
to operate on concentrated solutions. Picric acid, mercuric chloride,
and alkaloidal “group reagents” give no precipitate. When a little of
the solid substance is treated with “Nessler” reagent, there is a
greenish or yellow colour produced. A drop of strong sulphuric acid,
mixed with a minute quantity of saponin, strikes slowly a bright red
colour, which, on heating, deepens to maroon-brown. Nordhausen sulphuric
acid shows this better and more rapidly. If saponin is boiled with
dilute acid it breaks up into sapogenin and sugar, and therefore the
liquid after neutralisation reduces “Fehling.” This reaction is probably
after the following equation:--

  2C₁₇H₂₆O₁₀ + 2H₂O = 2C₈H₁₁O₂ + 3C₆H₁₂O₆.

Sapogenin may be separated by evaporating the neutralised liquid to
dryness, treating the dry residue with ether, which dissolves out the
sapogenin, and finally recovering the substance from the ethereal
solution, and crystallising it from hot alcohol. Crystals are readily
obtained if the alcoholic solution is allowed to evaporate
spontaneously. A solution of saponin exposed to the air gets turbid, and
develops carbon dioxide; not unfrequently the solution becomes mouldy.

§ 565. =Effects.=--Pelikan[594] has studied the effects of various
saponins on frogs. One to two drops of a saturated watery solution of
saponin applied subcutaneously to the leg, caused, in from five to six
minutes, great weakness, accompanied by a loss of sensibility; but
strong mechanical, chemical, or electrical stimuli applied to the foot
excited reflex action, for the ischiatic nerve still retained its
functions. Nevertheless, from the commencement, the excitability of the
poisoned muscles was much weakened, and just before death quite
disappeared. Section of the ischiatic nerve delayed the phenomena.
Curarine did not seem to have any effect on the poisonous action. A
concentrated solution applied to the heart of a frog soon arrests its
beats, but weaker doses first excite, and then retard.[595]

[594] _Berl. klin. Wochschr._, 36, 186.

[595] J. Hoppe, _Nervenwirkung der Heilmittel_, H. 4, 37.

The author has studied the general action of saponin on kittens,
insects, and infusoria. Small doses, such as from 13 to 32 mgrms. (⅕ to
½ grain), were injected beneath the loose skin of the back of the neck
of a kitten, when there were immediate symptoms of local pain. In from
five to ten minutes the respiration notably quickened, and the animal
fell into a lethargic state, with signs of general muscular weakness;
just before death the breathing became very rapid, and there were all
the signs of asphyxia. The pathological appearances after death were
fulness in the right side of the heart, and intense congestion of the
intestinal canal, the stomach generally being perfectly normal in
appearance, and the kidneys and other organs healthy. The least fatal
dose for a kitten seems to be 13 mgrms., or ·04 grm. to a kilogram.[596]

[596] The action of saponin when applied in concentrated solution to
flies is that of an intense irritant. There is protrusion of the sucker,
and progressive paralysis. The common infusoria live for some time in
dilute solutions of saponin--this is also true of some of the higher
forms; for example, a _Cyclops quadricornis_ seemed in no way affected
by a 2 per cent. solution.

§ 566. =Action on Man.=--The effects of saponin on man have been but
little studied; it has been administered by the mouth in doses of from
·1 to ·2 grm., and in those doses seems to have distinct physiological
effects. There is increased mucous secretion, and a feeling of nausea;
but neither diaphoresis nor diuresis has been observed. From the
foregoing study it may be predicated that 2·6 grms. (40 grains), if
administered subcutaneously to an adult, would endanger life. The
symptoms would be great muscular prostration, weakness of the heart’s
action, and probably diarrhœa. In fatal cases, some signs of an irritant
or inflammatory action on the mucous membranes of the stomach and
intestines would be probable.

§ 567. =Separation of Saponin.=--Saponin is separated from bread, flour,
and similar substances by the process given at p. 153, “Foods.” The
process essentially consists in extracting with hot spirit, allowing the
saponin to separate as the spirit cools, collecting the precipitate on
a filter, drying, dissolving in cold water, and precipitating with
absolute alcohol. In operating on animal tissues, a more elaborate
process is necessary. The author has successfully proceeded as
follows:--The finely divided organ is digested in alcohol of 80 to 90
per cent. strength, and boiled for a quarter of an hour; the alcohol is
filtered hot and allowed to cool, when a deposit forms, consisting of
fatty matters, and containing any saponin present. The deposit is
filtered off, dried, and treated with ether to remove fat. The insoluble
saponin remaining is dissolved in the least possible quantity of water,
and precipitated with absolute alcohol. It is also open to the analyst
to purify it by precipitating with baryta water, the baryta compound
being subsequently decomposed by carbon dioxide. Basic lead acetate may
also be used as a precipitant, the lead compound being, as usual,
decomposed by hydric sulphide; lastly, a watery solution may be shaken
up with chloroform, which will extract saponin. By some one of these
methods, selected according to the exigencies of the case, there will be
no difficulty in separating the glucoside in a fairly pure state. The
organ best to examine for saponin is the kidney. In one of my own
experiments, in a cat poisoned with a subcutaneous dose of saponin (·2
grm.), evidence of the glucoside was obtained from the kidney alone. The
time after death at which it is probable that saponin could be detected
is unknown; it is a substance easily decomposed, and, therefore, success
in separating it from highly putrid matters is not probable.

§ 568. =Identification of Saponin.=--An amorphous white powder, very
soluble in water, insoluble in cold alcohol or ether, having glucosidal
reactions, striking a red colour with sulphuric acid, imparting a
soap-like condition to water, and poisonous to animals, is most probably
a saponin.


DIVISION III.--CERTAIN POISONOUS ANHYDRIDES OF ORGANIC ACIDS.


I.--Santonin.

§ 569. Santonin (C₁₅H₁₈O₃) is a neutral principle extracted from the
unexpanded heads of various species of _Artemisia_ (Nat. Ord.
_Compositæ_). The seeds contain, according to Dragendorff, 2·03 to 2·13
per cent. of santonin, and about 2·25 per cent. of volatile oil, with 3
per cent. of fat and resin. Santonin forms brilliant, white, four-sided,
flat prisms, in taste feebly bitter. The crystals become yellow through
age and exposure to light; they melt at 169°, and are capable of being
sublimed; they are scarcely soluble in cold water, but dissolve in 250
parts of boiling water, freely in alkaline water, in 3 parts of boiling
alcohol, and in 42 parts of boiling ether. Santonin is the anhydride of
santonic acid (C₁₅H₂₀O₄). Santonin unites with alkalies to form
santonates. Sodic santonate (C₁₅H₁₉NaO₄ + 3½H₂O) is officinal on the
Continent; it forms colourless rhombic crystals, soluble in 3 parts of
cold water.

§ 570. =Poisoning by Santonin.=--Eighteen cases of poisoning, either by
santonin or santonin-holding substances, which F. A. Falck has been able
to collect, were nearly all occasioned by its use as a remedy for worms.
A few were poisonings of children who had swallowed it by accident. With
one exception those poisoned were children of from two to twelve years
of age; in five the flower heads, and in thirteen santonin itself was
taken. Of the eighteen cases, two only died (about 11 per cent.).

§ 571. =Fatal Dose.=--So small a number of children have died from
santonin, that data are not present for fixing the minimum fatal dose.
·12 grm. of santonin killed a boy of five and a half years of age in
fifteen hours; a girl, ten years old, died from a quantity of flower
heads, equal to ·2 grm. of santonin. The maximum dose for children is
from 65 to 194 mgrms. (1 to 3 grains), and twice the quantity for
adults.

§ 572. =Effects on Animals.=--Experiments on animals with santonin have
been numerous. It has first an exciting action on the centres of nerves
from the second to the seventh pairs, and then follows decrease of
excitability. The medulla is later affected. There are tetanic
convulsions, and death follows through asphyxia. Artificial respiration
lessens the number and activity of the convulsions, and chloroform,
chloral hydrate, or ether, also either prevent or shorten the attacks.

§ 573. =Effects on Man.=--One of the most constant effects of santonin
is a peculiar aberration of the colour-sense, first observed by Hufeland
in 1806. All things seem yellow, and this may last for twenty-four
hours, seldom longer. According to Rose, this apparent yellowness is
often preceded by a violet hue over all objects. If the lids are closed
while the “yellow sight” is present, the whole field is momentarily
violet. De Martiny,[597] in a few cases, found the “yellow sight”
intermit and pass into other colours, _e.g._, after ·3 grm. there was
first the yellow perception, then giving the same individual ·6 grm.,
all objects seemed coloured red, after half an hour orange, and then
again yellow. In another patient the effect of the drug was to give
“green vision,” and in a third blue.

[597] _Gaz. des Hôpit._, 1860.

Hufner and Helmholtz explain this curious effect as a direct action on
the nervous elements of the retina, causing them to give the perception
of violet; they are first excited, then exhausted, and the eye is
“violet blind.” On the other hand, it has been suggested that santonin
either colours the media of the eye yellow, or that there is an increase
in the pigment of the _macula lutea_. I, however, cannot comprehend how
the two last theories will account for the intermittency and the play of
colours observed in a few cases. To the affections of vision are also
often added hallucinations of taste and smell; there is headache and
giddiness, and in fourteen out of thirty of Rose’s observations vomiting
occurred. The urinary secretion is increased. In large and fatal doses
there are shivering of the body, clonic, and often tetanic convulsions;
the consciousness is lost, the skin is cool, but covered with sweat, the
pupils dilated, the breathing becomes stertorous, the heart’s action
weak and slow, and death occurs in collapse--in the case observed by
Grimm in fifteen hours, in one observed by Linstow in forty-eight hours.
In those patients who have recovered, there have also been noticed
convulsions and loss of consciousness. Sieveking[598] has recorded the
case of a child who took ·12 grm. (1·7 grain) santonin; an eruption of
nettle rash showed itself, but disappeared within an hour.

[598] _Brit. Med. Journ._, 1871.

§ 574. =Post-mortem Appearances.=--The _post-mortem_ appearances are not
characteristic.

§ 575. =Separation of Santonin from the Contents of the Stomach,
&c.=--It is specially important to analyse the fæces, for it has been
observed that some portion goes unchanged into the intestinal canal. The
urine, also, of persons who have taken santonin, possesses some
important peculiarities. It becomes of a peculiar yellow-green, the
colour appearing soon after the ingestion of the drug, and lasting even
sixty hours. The colour may be imitated, and therefore confused with
that which is produced by the bile acids; a similar colour is also seen
after persons have been taking rhubarb. Alkalies added to urine coloured
by santonin or rhubarb strike a red colour. If the urine thus reddened
is digested on zinc dust, santonin urine fades, rhubarb urine remains
red. Further, if the reddened urine is precipitated by excess of milk of
lime or baryta water and filtered, the filtrate from the urine reddened
by rhubarb is colourless, in that reddened by santonin the colour
remains. Santonin may be isolated by treating substances containing it
with warm alkaline water. The water may now be acidified and shaken up
with chloroform, which will dissolve out any santonin. On driving off
the chloroform, the residue should be again alkalised, dissolved in
water, and acidified with hydrochloric acid, and shaken up with
chloroform. In this way, by operating several times, it may be obtained
very pure. Santonin may be identified by its dissolving in alcoholic
potash to a transitory carmine-red, but the best reaction is to dissolve
it in concentrated sulphuric acid, to which a very little water has
been added, to warm on the water-bath, and then to add a few drops of
ferric chloride solution to the warm acid; a ring of a beautiful red
colour passing into purple surrounds each drop, and after a little time,
on continuing the heat, the purple passes into brown. A distinctive
reaction is also the production of “iso-santonin”; this substance is
produced by warming santonin on the water-bath with sulphuric acid for a
few hours, and then diluting with water; iso-santonin is precipitated,
and may be crystallised from boiling alcohol. Iso-santonin melts at
138°; it has the same composition as santonin. It is distinguished from
santonin by giving no red colour when treated with sulphuric or
phosphoric acids.


II.--Mezereon.

    § 576. =The Daphne Mezereum= (L.).--Mezereon, an indigenous shrub
    belonging to the _Thymeleaceæ_, is rather rare in the wild state,
    but very frequent in gardens. The flowers are purple and the berries
    red. Buckheim isolated by means of ether an acrid resin, which was
    converted by saponifying agents into _mezereic acid_; the acrid
    resin is the anhydride of the acid. The resin is presumed to be the
    active poisonous constituent of the plant, but the subject awaits
    further investigation. There are a few cases of poisoning on record,
    and they have been mostly from the berries. Thus, Linné has recorded
    an instance in which a little girl died after eating twelve berries.
    The symptoms observed in the recorded cases have been burning in the
    mouth, gastroenteritis, vomiting, giddiness, narcosis, and
    convulsions, ending in death. The lethal dose for a horse is about
    30 grms. of powdered bark; for a dog, the œsophagus being tied, 12
    grms.; but smaller doses of the fresh leaves may be deadly.


DIVISION IV.--VARIOUS VEGETABLE POISONOUS PRINCIPLES--NOT ADMITTING OF
CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS.


I.--Ergot of Rye.

§ 577. Ergot is a peculiar fungus attacking the rye and other
graminaceous plants;[599] it has received various names, _Claviceps
purpurea_ (Tulasne), _Spermœdia clavus_ (Fries), _Sclerotium clavus_
(D.C.), &c. The peculiar train of symptoms arising from the eating of
ergotised grain (culminating occasionally in gangrene of the lower
limbs), its powerful action on the pregnant uterus, and its styptic
effects, are well known.

[599] Some of the _Cyperaceæ_ are also attacked.

The very general use of the drug by accoucheurs has, so to speak,
popularised a knowledge of its action among all classes of society, and
its criminal employment as an abortive appears to be on the
increase.[600]

[600] The Russian peasantry use the drug for the same purpose. _Vide_
Mackenzie Wallace’s “Russia,” i. p. 117.

The healthy grain of rye, if examined microscopically in thin sections,
is seen to be composed of the seed-coating, made up of two layers,
beneath which are the gluten-cells, whilst the great bulk of the seed is
composed of cells containing starch. In the ergotised grain, dark
(almost black) cells replace the seed-coat and the gluten-cells, whilst
the large starch-containing cells are filled with the small cells of the
fungus and numerous drops of oil.

§ 578. =The chemical constituents of ergot= are a fixed oil,
trimethylamine, certain active principles, and colouring-matters.

The =fixed oil= is of a brownish-yellow colour, of aromatic flavour and
acrid taste; its specific gravity is 0·924, and it consists chiefly of
palmitin and olein; it has no physiological action.

=Trimethylamine= is always present ready formed in ergot; it can also be
produced by the action of potash on ergot.

With regard to the =active principles of ergot= considerable confusion
still exists, and no one has hitherto isolated any single substance in
such a state of purity as to inspire confidence as to its formula or
other chemical characters. They may, however, be briefly described.

C. Tamet[601] has separated an alkaloid, which appears identical with
Wenzel’s _ergotinine_. To obtain this the ergot is extracted by alcohol
of 86°, the spirit removed by distillation, and the residue cooled; a
resin (which is deposited) and a fatty layer (which floats on the
surface) are separated from the extractive liquor and washed with ether;
the ethereal solution is filtered and shaken with dilute sulphuric acid,
which takes up the alkaloid; the aqueous solution of the substance is
then filtered, rendered alkaline by KHO, and agitated with chloroform.
The ergotinine is now obtained by evaporating the chloroform solution,
care being taken to protect it from contact with the air. It gives
precipitates with chloride of gold, potassium iodohydrargyrate,
phosphomolybdic acid, tannin, bromine water, and the chlorides of gold
and platinum. With moderately concentrated SO₄H₂, it gives a
yellowish-red coloration, changing to an intense violet, a reaction
which does not occur if the alkaloid has been exposed to the air. The
composition of the base is represented by the formula C₇₀H₄₀N₄O₁₂, and a
crystalline sulphate and lactate have been obtained.[602]

[601] _Compt. Rendus_, vol. xxxi. p. 896.

[602] _Compt. Rendus_, April 1878.

Wenzel’s =Ecboline= is prepared by precipitating the cold watery extract
of ergot with sugar of lead, throwing out the lead in the usual way by
hydric sulphide, concentrating the liquid, and adding mercuric chloride,
which only precipitates the ecboline. The mercury salt is now decomposed
with hydric sulphide, and after the mercury precipitate has been
filtered off, the filtrate is treated with freshly precipitated
phosphate of silver, and refiltered; lastly, the liquid is shaken up
with milk of lime, again filtered, and the lime thrown out by CO₂. The
last filtrate contains ecboline only, and is obtained by evaporation at
a gentle heat. It is an amorphous, feebly bitter substance, with an
alkaline reaction, forming only amorphous salts.

The most recent research by Dragendorff on ergot tends to show that
Wenzel’s alkaloids, ergotinine and ecboline, are inactive. Dragendorff
describes also (_a._) _Scleromucin_, a slimy substance which goes into
solution upon extraction of the ergot with water, and which is again
precipitated by 40 to 45 per cent. alcohol. It is colloidal and soluble
with difficulty in water. It contains nitrogen, but gives no albuminoid
reaction, nor any reaction of an alkaloidal or glucosidal body; it
yields to analysis--

   8·26 per cent. Water.
  26·8     „      Ash.
  39·0     „      Carbon.
   6·44    „      Hydrogen.
   6·41    „      Nitrogen.

(_b._) =Sclerotic Acid.=--A feebly-acid substance, easily soluble in
water and dilute and moderately concentrated alcohol. It passes, in
association with other constituents of the ergot extract, into the
diffusate, when the extract is submitted to dialysis; but after its
separation in a pure state it is, like scleromucin, colloidal. It is
precipitated by 85 to 90 per cent. alcohol, together with lime, potash,
soda, silica, and manganese; but after maceration with hydrochloric
acid, the greater part of the ash constituents can be separated by a
fresh precipitation with absolute alcohol. The sample gave 40·0 per
cent. of carbon, 5·2 per cent. hydrogen, 4·2 per cent. nitrogen, 50.6
per cent. oxygen, with 3·4 per cent. of ash. Sclerotic acid forms with
lime a compound that is not decomposed by carbonic acid, and which upon
combustion leaves from 19 to 20 per cent. of calcium carbonate. Both
these substances are active, although evidently impure. Sclerotic acid
is sold in commerce, and has been employed subcutaneously in midwifery
practice in Russia and Germany for some time.

The inert principles of ergot are--(1.) A red colouring matter,
_Sclererythrin_, insoluble in water, but soluble in dilute and strong
alcohol, ether, chloroform, dilute solutions of potash, ammonia, &c. It
can be obtained by dissolving in an alkali, neutralising with an acid,
and shaking up with ether. Alcoholic solution of sclererythrin gives
with aluminium sulphate, and with zinc chloride, a splendid red mixture;
with salts of calcium, barium, and many of the heavy metals, it gives a
blue precipitate; the yield is only ·1 to ·05 in a thousand parts.

(2.) Another colouring-matter, dissolving in concentrated sulphuric acid
with the production of a fine blue violet colour, the discoverer has
named _Scleroidin_. This is not soluble in alcohol, ether, chloroform,
or water, but dissolves in alkaline solutions, potash producing a
splendid violet colour; yield about 1 per 1000.

(3, 4.) Two crystalline substances, which may be obtained from ergot
powder, first treated with an aqueous solution of tartaric acid, and the
colouring-matters extracted by ether. One Dragendorff names
_Sclerocrystallin_ (C₁₀H₁₀O₄); it is in colourless needles, insoluble in
alcohol and water, with difficulty soluble in ether, but dissolving in
ammonia and potash solutions. The other crystalline substance is thought
to be merely a hydrated compound of sclerocrystallin. Both are without
physiological action.

Kobert recognises two active substances in ergot, and two alone; the one
he calls _sphacelic acid_, the other _cornutin_.

§ 579. =Detection of Ergot in Flour= (see “Foods”).--The best process is
to exhaust the flour with boiling alcohol. The alcoholic solution is
acidified with dilute sulphuric acid, and the coloured liquid examined
by the spectroscope in thicker or thinner layers, according to the depth
of colour. A similar alcoholic solution of ergot should be made, and the
spectrum compared. If the flour is ergotised, the solution will be more
or less red, and show two absorption bands, one in the green, and a
broader and stronger one in the blue. On mixing the original solution
with twice its volume of water, and shaking successive portions of this
liquid with ether, amyl alcohol, benzene, and chloroform, the red
colour, if derived from ergot, will impart its colour to each and all of
these solvents.

§ 580. =Pharmaceutical Preparations.=--Ergot itself is officinal in all
the pharmacopœias, and occurs in grains from ⅓ to 1 inch in length, and
about the same breadth, triangular, curved, obtuse at the ends, of a
purple colour, covered with a bloom, and brittle, exhibiting a pinkish
interior, and the microscopical appearances already detailed. Ergot may
also occur as a brown powder, possessing the unmistakable odour of the
drug. A liquid extract of the B.P. is prepared by digesting 16 parts of
ergot in 80 parts of water for twelve hours, the infusion is decanted or
filtered off, and the digestion repeated with 40 parts of water; this is
also filtered off, and the residue pressed, and the whole filtrate
united and evaporated down to 11 parts; when cold, 6 parts of rectified
spirit are added, and, after standing, the liquid is filtered and made
up to measure 16. A tincture and an infusion are also officinal; the
latter is very frequently used, but seldom sold, for it is preferable to
prepare it on the spot. The tincture experience has shown to be far
inferior in power to the extract, and it is not much used. Ergotin is a
purified extract of uncertain strength; it is used for hypodermic
injection; it should be about five times more active than the liquid
extract.

§ 581. =Dose.=--The main difficulties in the statement of the medicinal
dose, and of the minimum quantity which will destroy life, are the
extreme variability of different samples of ergot, and its readiness to
decompose. A full medicinal dose of ergot itself, as given to a woman in
labour, is 4 grms. (61·7 grains), repeated every half hour. In this way
enormous doses may be given in some cases without much effect. On the
other hand, single doses of from 1 to 4 grms. have caused serious
poisonous symptoms. The extract and the tincture are seldom given in
larger doses than that of a drachm as a first dose, to excite uterine
contraction. In fact, the medical practitioner has in many cases to
experiment on his patient with the drug, in order to discover, not only
the individual susceptibility, but the activity of the particular
preparation used. From the experiments of Nikitin, it is probable that
the least fatal dose of sclerotic acid for an adult man is 20 mgrms. per
kilogrm.

§ 582. =Ergotism.=--Ergotised cereals have played a great part in
various epidemics, probably from very early times, but the only accurate
records respecting them date from the sixteenth century. According to
Dr. Tissot,[603] the first recorded epidemic was in 1596, when a
strange, spasmodic, convulsive disease broke out in Hessia and the
neighbouring regions. It was probably due to spurred rye. In
Voigtländer, the same disease appeared in 1648, 1649, and 1675; in 1702
the whole of Freiberg was attacked. In Germany and in France successive
epidemics are described throughout the eighteenth century. In France, in
1710, Ch. Noel, physician at the _Hôtel Dieu_, had no less than fifty
cases under treatment at the same time.

[603] Dr. Tissot in _Phil. Trans._, vol. lv. p. 106, 1765. This is a
Latin letter by Dr. Baker, and gives a good history of the various
epidemics of ergotism.

It is generally said that in 1630, Thuillier, in describing an ergot
epidemic which broke out in Cologne, first referred the cause of the
disease to spurred rye.

It is interesting to inquire into the mortality from this disease. In
1770, in an epidemic described by Taube, in which 600 were affected, 16
per cent. died. In a nineteenth-century epidemic (1855), in which,
according to Husemann, 30 were ill, 23·3 per cent. died. In other
epidemics, according to Heusinger, out of 102, 12 per cent. died;
according to Griepenkerl, out of 155, 25 or 16 per cent. died; and,
according to Meyer, of 283 cases, 6 per cent. died.

There are two forms of chronic poisoning by ergot--one a spasmodic form,
the other the gangrenous form.

§ 583. =The convulsive form of ergotism= mostly begins with some
cerebral disturbance. There are sparks before the eyes, giddiness,
noises in the ears, and a creeping feeling about the body. There is also
very commonly anæsthesia of the fingers and toes, and later of the
extremities, of the back, and even of the tongue. Diarrhœa, vomiting,
colic, and other signs of intestinal irritation seldom fail to be
present; there are also tetanic spasms of the muscles, rising in some
cases to well-marked tetanus; epilepsy, faintings, aberrations of
vision, amaurosis, and amblyopia are frequent; the skin becomes of a
yellow or earthy colour, and is covered with a cold sweat; boils and
other eruptions may break out; blebs, like those caused by burns or
scalds, have in a few cases been noticed. Death may occur in from four
to twelve weeks after the eating of the spurred grain from exhaustion.
In those individuals who recover, there remain for some time weakness,
contractions of groups of muscles, anæmia, or affections of vision.

§ 584. =The Gangrenous Form of Ergotism.=--In this form there is
generally acute pain in the limb or limbs which are to mortify; and
there may be prodromata, similar to those already described. The limb
swells, is covered with an erysipelatous blush, but at the same time
feels icy cold; the gangrene is generally dry, occasionally moist; the
mummified parts separate from the healthy by a moist, ulcerative
process; and in this way the toes, fingers, legs, and even the nose, may
be lost. During the process of separation there is some fever, and
pyæmia may occur with a fatal result.

Fontenelle described a case in which a rustic lost all the toes of one
foot, then those of the other; after that, the remnant of the first
foot, and lastly the leg. But probably the most extraordinary case of
gangrene caused by the use of ergot is that which occurred at Wattisham,
Suffolk, in the family of a labouring man named John Downing. He had a
wife and six children of various ages, from fifteen years to four
months. On Monday, January 10, 1762, the eldest girl complained of a
pain in the calf of her left leg; in the evening, her sister, aged 10,
also experienced the same symptoms. On the following Monday, the mother
and another child, and on Tuesday, all the rest of the family except the
father became affected. The pain was very violent. The baby at the
breast lived a few weeks, and died of mortification of the extremities.
The limbs of the family now began to slough off, and the following are
the notes on their condition made by an observer, Dr. C. Wollaston,
F.R.S., on April 13:--

“The mother, aged 40. Right foot off at the ankle, the left leg
mortified; a mere bone left, but not off.

“Elizabeth, aged 13. Both legs off below the knees.

“Sarah, aged 10. One foot off at the ankle.

“Robert, aged 8. Both legs off below the knees.

“Richard, aged 4. Both feet off at the ankle.

“Infant, four months old, dead.”

The father was also attacked a fortnight after the rest of the family,
and in a slighter degree--the pain being confined to the fingers of his
right hand, which turned a blackish colour, and were withered for some
time, but ultimately got better.

As a remarkable fact, it is specially noted that the family were in
other respects well. They ate heartily, and slept soundly when the pain
began to abate. The mother looked emaciated. “The poor boy in particular
looked as healthy and florid as possible, and was sitting on the bed,
quite jolly, drumming with his stumps.” They lived as the country people
at the time usually lived, on dried peas, pickled pork, bread and
cheese, milk, and small beer. Dr. Wollaston strictly examined the corn
with which they made the bread, and he found it “very bad; it was wheat
that had been cut in a rainy season, and had lain in the ground till
many of the grains were black and totally decayed.”[604]

[604] In the _Phil. Trans._ for 1762 there are two strictly concordant
accounts of this case; and in the parish church of Wattisham, there is
said to be a memorial tablet, which runs as follows:--“This inscription
serves to authenticate the truth of a singular calamity which suddenly
happened to a poor family in this parish, of which six persons lost
their feet by a mortification not to be accounted for. A full narrative
of their case is recorded in the Parish Register and _Philosophical
Transactions_ for 1762.”

§ 585. =Symptoms of Acute Poisoning by Ergot.=--In a fatal case of
poisoning by ergot of rye, recorded by Dr. Davidson,[605] in which a
hospital nurse, aged 28, took ergot, the symptoms were mainly vomiting
of blood, the passing of bloody urine, intense jaundice, and stupor. But
in other cases, jaundice and vomiting of blood have not been recorded,
and the general course of acute poisoning shows, on the one hand,
symptoms of intense gastro-intestinal irritation, as vomiting, colicky
pains, and diarrhœa; and, on the other, of a secondary affection of the
nervous system, weakness of the limbs, aberrations of vision, delirium,
retention of urine, coma, and death.

[605] _Lancet_, Sept. 30, 1882.

§ 586. =Physiological Action as shown by Experiments on Animals.=--In
spite of numerous experiments on animals and man, the action of the
ergot principles remains obscure. It has been found in medicine to exert
a specific action on the uterus,[606] causing powerful contractions of
that organ, especially in labour. It is also a hæmostatic, and is used
to check bleeding from the lungs and other internal organs of the body.
This hæmostatic action, as well as the extraordinary property possessed
by ergot, of producing an arrest or disturbance of the circulation
inducing gangrene has naturally led to the belief that ergot causes a
narrowing in the calibre of the small arteries, but this has not
received the necessary experimental sanction. Holmes,[607] Eberty,
Köhler,[608] and Wernick,[609] all observed a contraction in the part to
which the ergot was applied, both in frogs and in warm-blooded animals;
but L. Hermann,[610] although he made many experiments, and used the
most different preparations, never succeeded in observing a contraction.
It would also seem reasonable to expect that with a narrowing of the
vessels, which means a peripheral obstruction, the blood-pressure would
rise, but on the contrary the pressure sinks, a fact on which there is
no division of opinion.

[606] In a case in which the author was engaged, a dabbler in drugs,
having seduced a young woman, administered to her a dose of ergot which
produced a miscarriage, and for this offence he was convicted. The
defence raised was that ergot is a common medicine used by physicians in
the treatment of amenorrhœa, and other uterine affections. Although in
itself this statement was perfectly true, as a defence it was
invalidated by the large dose given, the fact of the seduction, and the
other circumstances of the case.

[607] _Archiv d. Physiol. Norm. u. Pathol._, iii. p. 384.

[608] _Ueber die Wirkungen des Secale Cornutum_, Dissert. Halle, 1873.

[609] _Arch. f. pathol. Anat._, lvi. p 505.

[610] _Lehrbuch der exper. Toxicologie_, Berlin, 1874, p. 386.

Nikitin has made some researches with pure sclerotic acid, which
certainly possesses the most prominent therapeutic effects of ergot; but
since it is not the only _toxic_ substance, it may not represent the
collective action of the drug, just in the same way that morphine is not
equivalent in action to opium. Cold-blooded animals are very sensitive
to sclerotic acid; of the warm-blooded the carnivoræ are more sensitive
than the herbivoræ. The toxic action is specially directed to the
central nervous system--with frogs, the reflex excitability is
diminished to full paralysis; with warm-blooded animals reflex
excitability is only diminished, and continues to exist even to death.

The temperature falls, the breathing is slowed, and the respiration
stops before the heart ceases to beat; the peristaltic action of the
intestines is quickened, and the uterus (even of non-pregnant animals)
is thrown into contraction. The terminations of the sensory nerves are
paralysed by the direct action of sclerotic acid, but they remain intact
with general poisoning. The heart of frogs is slowed by sclerotic acid.
Eberty observed that this slowing of the heart (he used ergotin) was
produced even after destruction of the spinal cord; he therefore
considered it as acting on the inhibitory nerve apparatus of the heart
itself. Rossbach, using Wenzel’s ecbolin, has also studied its action on
the heart of the frog, and observed that the slowing affected the
ventricles rather than the auricles, so that for one ventricle-systole
there were two contractions of the auricles; besides which, the
contractions themselves were peculiar and abnormal in character. The
cause of death from sclerotic acid seems to be paralysis of the
respiration. It is said not to affect animal fœtal life. With regard to
the effects produced by feeding animals with ergotised grain,
experiments made during the last century have proved that it produces a
gangrenous disease, _e.g._, C. Salerné mixed one part of spurred rye
with two of good barley, and fed pigs with the mixture; a few days
afterwards the pigs perished with dilated, hard, and black bellies, and
offensively ulcerated legs; another pig fed entirely on the rye, lost
its four feet and both ears.

Kobert[611] has investigated the effects produced on animals by
“sphacelic acid,” and by “cornutin.” Sphacelic acid appears to cause
gangrene, like ergot, and Kobert believes that in “sphacelic acid” is to
be found the gangrene-producing substance. In cases of death
putrefaction is rapid, the mucous membrane of the intestine is swollen,
and the spleen enlarged. If the mucous membrane of the intestine is
examined microscopically, a large quantity of micro-organisms are found
in the vessels, in the villi, between the muscular bundles and in the
deeper layers of the intestinal walls; this is evidence that the
protective epithelial cells have been destroyed. The mesentery of cats,
pigs, and fowls, contains numerous small extravasations of blood. The
organs generally, and especially the subcutaneous cellular tissue, are
tinged with the colouring matters of the bile; this Kobert considers as
evidence of weakened vitality of the red blood corpuscles. The walls of
the blood-vessels show hyaline degeneration, and give with iodine a
quasi-amyloid reaction. The vessels are often partly filled with a
hyaline mass, in which, at a later date, a fine black pigment appears.
These pigmented hyaline masses probably occlude the vessels, and hence
cause gangrene.

[611] _Lehrbuch der Intoxicationen_, by Dr. Rudolph Kobert, Stuttgart,
1893.

Cornutin, according to Kobert, first excites the vagus; consequently
there is slow pulse and heightened blood pressure; then it paralyses the
vaso-motor centre, and the pulse is accelerated. Severe convulsions,
preceded by formication, follow. Paralysis of the extensor muscles, with
permanent deformity, may result. Cornutin stimulates the uterus to
contraction, but it does not act so well in this respect alone as when
given with sphacelic acid. In animals poisoned with cornutin, no special
pathological changes of a distinctive nature have been described.

§ 587. =Separation of the Active Principles of Ergot from Animal
Tissues.=--There has been no experience in the separation of the
constituents of ergot from the organs of the body; an attempt might be
made on the principles detailed in page 425, but success is doubtful.


II.--Picrotoxin, the Active Principle of the Cocculus indicus (Indian
Berry, Levant Nut).

§ 588. The berries of the _Menispermum cocculus_ comprise at least three
definite crystalline principles: _menispermine_,[612] _paramenispermine_
(nitrogen containing bases), and _picrotoxin_, which possesses some of
the characters of an acid.

[612] _Menispermine_ (C₁₈H₂₄N₂O₂?), discovered in 1834 by Pelletier and
Courbe, is associated with a second named _paramenispermine_. The
powdered berries are extracted by alcohol of 36°; the picrotoxin removed
by hot water from the alcoholic extract; the menispermine and
paramenispermine dissolved out together by acidulated water, and from
this solution precipitated by ammonia. The brown precipitate is
dissolved by acetic acid, filtered, and again precipitated by ammonia.
This precipitate is dried, treated with cold alcohol, to separate a
yellow resinous substance, and lastly with ether, which dissolves out
the menispermine, but leaves the paramenispermine.

Menispermine forms white semi-transparent, four-sided, truncated prisms,
melting at 120°, decomposed at a higher temperature, insoluble in water,
but dissolving in warm alcohol and ether. Combined with 8 atoms of water
it crystallises in needles and prisms. The crystals are without any
taste; in combination with acids, salts may be formed.

_Paramenispermine_ forms four-sided prisms, or radiating crystalline
masses, melting at 250°, and subliming undecomposed. The crystals are
soluble in absolute ether, insoluble in water, and scarcely soluble in
ether.

_Paramenispermine_ dissolves in acids, but apparently without forming
definite salts.

§ 589. =Picrotoxin= (C₃₀H₃₄O₁₃) was discovered in 1820 by Boullay. It is
usually prepared by extracting the berries with boiling alcohol,
distilling the alcohol off, boiling the alcoholic residue with a large
quantity of water, purifying the watery extract with sugar of lead,
concentrating the colourless filtrate by evaporation, and crystallising
the picrotoxin out of water.

Picrotoxin crystallises out of water, and also out of alcohol, in
colourless, flexible, four-sided prisms, often arborescent, and
possessing a silky lustre. They are unalterable in the air, soluble in
150 parts of cold, and 25 parts of boiling water, dissolving easily in
acidified water, in spirit, in ether, in amyl alcohol, and chloroform.
They are without smell, but have an extremely bitter taste. Caustic
ammonia is also a solvent.

The crystals are neutral in reaction. They melt at 192°-200° C. to a
yellow mass; at higher temperatures giving off an acid vapour, with a
caramel-like odour, and lastly carbonising. Picrotoxin in cold
concentrated sulphuric acid dissolves with the production of a beautiful
gold-yellow to saffron-yellow colour, which becomes on the addition of a
trace of potassic bichromate, violet passing into brown. An alcoholic
solution turns a ray of polarised light to the left [α]_{D} = -28·1°.

Picrotoxin behaves towards strong bases like a weak acid. Its compounds
with the alkalies and alkaline earths are gummy and not easily obtained
pure. Compounds with quinine, cinchonine, morphine, strychnine, and
brucine can be obtained in the crystalline condition. Dilute sulphuric
acid transforms it, with assimilation of water, into a weak gummy-like
acid, which corresponds to the formula C₁₂H₁₆O₆. Nitric acid oxidises it
to oxalic acid. Nitropicrotoxin and bromopicrotoxin, C₃₀H₃₃(NO₂)O₁₃, and
C₃₀H₃₂Br₂O₁₃, can by appropriate treatment be obtained.

Concentrated aqueous solutions of alkalies and ammonia decompose
picrotoxin fully on warming. It reduces alkaline copper solution, and
colours bichromate of potash a beautiful green. The best test for its
presence is, however, as follows:--The supposed picrotoxin is carefully
dried, and mixed with thrice its bulk of saltpetre, the mixture
moistened with sulphuric acid, and then decomposed with soda-lye in
excess, when there is produced a transitory brick-red colour. For the
reaction to succeed, the picrotoxin should be tolerably pure.

Solutions of picrotoxin are not precipitated by the chlorides of
platinum, mercury, and gold, iodide of potassium, ferro- and
ferri-cyanides of potassium, nor by picric nor tannic acids.

§ 590. =Fatal Dose.=--Vossler killed a cat in two hours with a dose of
·12 grm. (1·8 grain); and another cat, with the same dose, died in 45
minutes. Falck destroyed a young hound with ·06 grm. (·92 grain) in 24
to 26 minutes. Given by subcutaneous or intravenous injection, it is, as
might be expected, still more lethal and rapid in its effects. In an
experiment of Falck’s, ·03 grm. (·46 grain), injected into a vein,
destroyed a strong hound within 20 minutes; ·016 grm. (·24 grain)
injected under the skin, killed a guinea-pig in 22 minutes; and ·012
grm. (·18 grain) a hare in 40 minutes. Hence it may be inferred that
from 2 to 3 grains (12·9 to 19·4 centigrms.) would in all probability,
be a dangerous dose for an adult person.

§ 591. =Effects on Animals.=--The toxic action of picrotoxin on fish and
frogs has been proposed as a test. The symptoms observed in fish are
mainly as follows:--The fish, according to the dose, show uncertain
motions of the body, lose their balance, and finally float to the
surface, lying on one side, with frequent opening of the mouth and
gill-covers. These symptoms are, however, in no way distinguishable from
those induced by any poisonous substance in the water, or by many
diseases to which fish are liable. Nevertheless, it may be conceded that
in certain cases the test may be valuable--if, _e.g._, beer be the
matter of research, none of the methods used for the extraction of
picrotoxin will be likely to extract any other substance having the
poisonous action described on fish, so that, as a confirmatory test,
this may be of use.

Frogs, under the influence of picrotoxin, become first uneasy and
restless, and then somewhat somnolent; but after a short time tetanic
convulsions set in, which might lead the inexperienced to imagine that
the animal was poisoned by strychnine. There is, however, one marked
distinction between the two--viz., that in picrotoxin poisoning an
extraordinary swelling of the abdomen has been observed, a symptom
which, so far as known, is due to picrotoxin alone. The frog is,
therefore, in this instance, the most suitable object for physiological
tests.

Beer extract containing picrotoxin is fatal to flies; but no definite
conclusion can be drawn from this, since many bitter principles (notably
quassia) are in a similar manner fatal to insect life.

§ 592. =Effects on Man.=--Only two fatal cases of poisoning by
picrotoxin are on record. In 1829 several men suffered from drinking rum
which had been impregnated with _Cocculus indicus_; one died, the rest
recovered. In the second case, a boy, aged 12, swallowed some of a
composition which was used for poisoning fish, the active principle of
which was _Cocculus indicus_; in a few minutes the boy experienced a
burning taste, he had pains in the gullet and stomach, with frequent
vomiting, and diarrhœa. A violent attack of gastro-enteritis supervened,
with fever and delirium; he died on the nineteenth day. The
_post-mortem_ signs were those usual in peritonitis: the stomach was
discoloured, and its coats thinner and softer than was natural; there
were also other changes, but it is obvious that, as the death took place
so long after the event, any pathological signs found are scarcely a
guide for future cases.

§ 593. =Physiological Action.=--The convulsions are considered to arise
from an excitation of the medulla oblongata; the vagus centre is
stimulated, and causes spasm of the glottis and slowing of the heart’s
action during the attack. Röhrig also saw strong contraction of the
uterus produced by _picrotoxin_. According to the researches of Crichton
Browne, _chloral hydrate_ acts in antagonism to picrotoxin, and prevents
the convulsions in animals if the dose of picrotoxin is not too large.

§ 594. =Separation from Organic Matters.=--Picrotoxin is extracted from
aqueous acid solutions by either chloroform, amyl alcohol, or ether; the
first is the most convenient. Benzene does not extract it, if employed
in the same manner. On evaporation of the solvent the crude picrotoxin
can be crystallised out of water, and its properties examined.

R. Palm[613] has taken advantage of the fact that picrotoxin forms a
stable compound with freshly precipitated lead hydroxide, by applying
this property as follows:--the solution supposed to contain picrotoxin
is evaporated to dryness, and the extract then taken up in a very little
water, acidified and shaken out with ether. The ether is evaporated,
the ethereal extract dissolved in a little water, the aqueous solution
filtered through animal charcoal, and precipitated by means of lead
acetate, avoiding excess. The solution is filtered and shaken with
freshly prepared lead hydroxide. The lead hydroxide is dried and tested
direct for picrotoxin; if it does contain picrotoxin then on adding to
it concentrated H₂SO₄ a beautiful saffron yellow is produced as bright
as if the substance was pure picrotoxin.

[613] _J. Pharm._, (5), xvii. 19-20.


III.--The Poison of Illicium Religiosum--A Japanese Plant.

    § 595. A new poison belonging to the picrotoxin class has been
    described by Dr. A. Langaard. In 1880, 5 children in Japan were
    poisoned by the seeds of the _Illicium religiosum_; 3 of the
    children died. Dr. Langaard then made various experiments on animals
    with an active extract prepared by exhaustion with spirit, and
    ultimate solution of the extract in water. Eykmann has also
    imperfectly examined the chemistry of the plant, and has succeeded
    in isolating a crystalline body which is not a glucoside; it is
    soluble in hot water, in chloroform, ether, alcohol, and acetic
    acid, but it is insoluble in petroleum ether; it melts at 175°, and
    above that temperature gives an oily sublimate. Langaard’s
    conclusions are that all parts of the plant are poisonous. The
    poison produces excitation of the central apparatus of the medulla
    oblongata and clonic convulsions analogous to those produced by
    picrotoxin, toxiresin, and cicutoxin. Before the occurrence of
    convulsions, the reflex excitability of frogs is diminished, the
    respiratory centre is stimulated, hence frequency of the
    respiration. Small doses cause slowing of the pulse through
    stimulation of the vagus and of the peripheral terminations of the
    vagus; in the heart the functional activity is later diminished.
    Small doses kill by paralysing the respiratory centre, large by
    heart paralysis. The proper treatment seems to be by chloral
    hydrate, for when animals are poisoned by small lethal doses it
    appears to save life, although when the dose is large it has no
    effect.--_Ueber die Giftwirkung von Japanischem Sternanis_
    (_Illicium religiosum_, Sieb.), _Virch. Archiv_, Bd. lxxxvi., 1881,
    S. 222.


IV.--Picric Acid and Picrates.

§ 596. =Picric Acid=,

                  OH
                 /
  C₆H₃N₃O₇, or C₆H₂
                \\\
                 (NO₂)₃

is trinitrophenol; it forms a number of salts, all of which are more or
less poisonous. Picric acid is much used in the arts, especially as a
dye. The pure substance is in the form of pale yellow crystals, not very
soluble in cold water, but readily soluble in hot water, and readily
soluble in benzene, ether, and petroleum ether. The solution is yellow,
tastes bitter, and dyes animal fibres, such as wool; but it can be
washed out of plant fibres such as cotton.

§ 597. =Effects of Picric Acid.=--Picric acid and its salts have a
tendency to decompose the elements of the blood, and to produce
methæmoglobin; picric acid is also an excitor of the nervous system,
producing convulsions. To these two effects must be added a third; in
acid solution it has a strong affinity for albumin, so that if it meets
with an acid tissue it combines with the tissue, and in this way local
necroses are set up. The action on albumin is somewhat weakened by the
reduction in the body of part of the picric acid to picraminic acid
C₆H₂(NO₂)₂NH₂OH, a substance that does not so readily form compounds
with albuminous matters. Doses of 0·5 to 0·9 grm. (about 8 to 14 grains)
may be taken several days in succession without marked symptoms.
Ultimately, however, what is known as “picric jaundice” appears, the
conjunctiva and the whole skin being stained more or less yellow. The
urine, at first of a dark yellow, is later of a red brown colour.
Dyspepsia, with flatulence and an inclination to diarrhœa have been
noticed. A single dose of a gramme (15·4 grains) caused in a case
described by Adler[614] pain in the stomach, headache, weakness,
diarrhœa, vomiting of yellow matters, quickening and afterwards slowing
of the pulse; the skin was of a brown yellow colour, and there were
nervous symptoms. The urine was ruby red. In both fæces and urine picric
acid could be recognised. The excretion of picric acid continued for six
days. A microscopical examination of the blood showed a diminution of
the red blood corpuscles, an increase in the white. Chéron[615] has
described a case in which the application of 0·45 grm. (6·9 grains) to
the vagina produced yellowness of the skin in an hour, and the urine was
also coloured red. Erythema, somnolence, burning and smarting in the
stomach and in the kidneys were also noticed.

[614] _Wiener. med. Woch._, 1880, 819.

[615] J. Chéron, _Journ. de Thêr._, 1880, 121.

§ 598. =Tests.=--Picric acid is easily separated from either tissues or
other organic matters. These are acidified with sulphuric acid and then
treated with 95 per cent. alcohol; the alcohol is filtered off,
distilled, and the residue treated with ether; this last ethereal
extract will contain any picric acid that may be present.

If the ether extract contains much impurity, it may be necessary to
drive off the ether, and to take up the residue with a little warm
water, then to cool, filter through a moistened filter paper, and test
the aqueous solution. Picric acid, warmed with KCN and KHO gives a
blood-red colour, from the production of iso-purpurate of potash.
Ammoniacal copper sulphate forms with picric acid yellow-green crystals
which strongly refract the light. If a solution of picric acid be
reduced by the addition of a hydrochloric acid solution of stannous
chloride, the subsequent addition of ferric chloride produces a blue
colour, due to the formation of amidoimidophenol hydrochloride
C₆H₂OH(NH₂)(NH)₂HCl.


V.--Cicutoxin.

§ 599. The _Cicuta virosa_, a not very common umbelliferous plant
growing in moist places, is extremely poisonous. It is from 3 to 4 feet
in height, with white flowers; the umbels are large, the leaves are
tripartite, the leaflets linear lanceolate acute, serrate decurrent; the
calyx has five leaf-like teeth, the petals are obcordate with an inflex
point; the carpels have five equal broad flattened ridges with solitary
stripes. Böhm[616] succeeded, in 1876, in separating an active principle
from this plant. The root was dried, powdered, and exhausted with ether;
on evaporation of the ether the extract was taken up with alcohol, and
after several days standing the filtrate was treated with petroleum
ether; after removing the petroleum, the solution was evaporated to
dryness in a vacuum; it was found to be a resinous mass, to which was
given the name _cicutoxin_. It was fully soluble in alcohol, ether, or
chloroform, and was very poisonous, but what its exact chemical nature
may be is still unknown.

[616] _Arch. f. exp. Path._, Bd. v., 1876.

§ 600. =Effects on Animals.=--Subcutaneously injected into frogs,
cicutoxin acts something like picrotoxin, and something like the barium
compounds. Ten to fifteen minutes after the injection the animal assumes
a peculiar posture, holding the legs so that the thigh is stretched out
far from the trunk, and the leg at right angles with the thigh;
voluntary motion is only induced by the strongest stimuli, and when the
frog springs, he falls down plump with stiffly stretched-out limbs. The
frequency of breathing is increased, the muscles of the abdomen are
thrown into contraction, and the lungs being full of air, on mechanical
irritation there is a peculiar loud cry, depending upon the air being
forced under the conditions detailed through the narrow glottis. Tetanic
convulsions follow, gradually paresis of the extremities appears, and,
lastly, full paralysis and death; these symptoms are seen after doses of
from 1 to 2 mgrms. The lethal dose for cats is about 1 centigrm. per
kilo. Diarrhœa, salivation, and frequent breathing are first seen, and
are followed by tonic and clonic convulsions, then there is an interval,
during which there is heightened excitability of reflex action, so that
noises will excite convulsions. Small doses by exciting the vagus slow
the pulse; larger doses quicken the pulse, and raise the arterial
pressure. Cicutoxin is supposed to act specially on the medulla
oblongata, while the spinal cord and the brain are only secondarily
affected.

§ 601. =Effects on Man.=--F. A. Falck was able to collect thirty-one
cases of poisoning by cicuta; of these 14 or 45·2 per cent. died. The
symptoms are not dissimilar to those described in animals. There are
pain and burning in the stomach, nausea, vomiting, headache, and then
tetanic convulsions. These, in some cases, are very severe, and resemble
those induced by strychnine; but in a few cases there is early coma
without convulsions. There is also difficulty or absolute impossibility
of swallowing. In fatal cases the respiration becomes stertorous, the
pulse small, the pupils dilated, and the face cyanotic, and death occurs
within some four hours, and in a few cases later. The _fatal dose_ is
unknown.

§ 602. =Separation of Cicutoxin from the Body.=--An attempt might be
made to extract cicutoxin from the tissues on the same principles as
those by which it has been separated from the plant, and identified by
physiological experiments. In all recorded cases, identification has
been neither by chemical nor physiological aids, but by the recognition
of portions of the plant.


VI.--Æthusa Cynapium (Fool’s Parsley).

§ 603. This plant has long been considered poisonous, and a number of
cases are on record in which it is alleged that death or illness
resulted from its use. Dr. John Harley,[617] however, in an elaborate
paper, has satisfactorily proved the innocence of this plant, and has
analysed the cases on record. He has experimented on himself, on
animals, and on men, with the expressed juice and with the tincture. The
results were entirely negative: some of the published cases he refers to
conium, and others to aconite.

[617] _St. Thomas’ Hospital Reports_, N.S., 1875.


VII.--Œnanthe Crocata.

§ 604. =The Water Hemlock.=[618]--This, a poisonous umbelliferous plant,
indigenous to England, and growing in moist places such as ditches, &c.,
is in flower in the month of August. It resembles somewhat celery, and
the root is something like the parsnip, for which it has been eaten. All
parts of the plant are said to be poisonous, but the leaves and stalks
only slightly so, while the root is very deadly. We unfortunately know
nothing whatever about the active principles of the plant, its
chemistry has yet to be worked out. M. Toulmouche (_Gaz. Méd._, 1846)
has recorded, as the expert employed in the case, an attempt to murder
by using the _œnanthe_ as a poison; a woman scraped the root into her
husband’s soup with evil intent, but the taste was unpleasant, and led
to the detection of the crime. The root has been mistaken several times
for parsnip and other edible roots, and has thus led to poisonings. The
case of 36 soldiers poisoned in this way, in 1758, has been recorded by
Orfila; there was one death. In 1803 three soldiers were poisoned at
Brest--1 died. In Woolwich Bossey witnessed the poisoning of 21 convicts
who ate the roots and leaves of the plant--6 died. In 1858 there were
several sailors poisoned in a similar way--2 died; while there have been
numerous cases in which the plant has been partaken of by children.

[618] The earliest treatise on poisoning by the water-hemlock is by
Wepfer. _Cicutæ Aquat. Historia et Noxæ_, 1679; for cases see
Trojanowsky, _Dorp. med. Ztg._, 1875; Meyer, _Med. Zeitg. f. Preussen_,
1842; Schlesier in Casper’s _Wochenschrift_, 1843; Maly, _Œster. med
Wochenschr._, 1844; Badgeley, _Montreal med. Gaz._, 1844; Lender,
_Viertelj. f. ger. Med._, 1865; Gampf, _Cöln. Pharm. Zeitg._, 1875; and
the treatises of Taylor and others.

§ 605. The effects of the poison may be gathered from a case of
poisoning[619] which occurred in 1882 at Plymouth; a Greek sailor, aged
thirty, found on the coast what he considered “wild celery,” and ate
part of the root and some of the stem. Two hours after this he ate a
good meal and felt perfectly well, but fifteen minutes later he suddenly
and violently vomited; the whole contents of the stomach were completely
evacuated. In five minutes he was completely unconscious, and had
muscular twitchings about the limbs and face. There was a copious flow
of a thick tenacious mucus from the mouth which hung about the lips and
clothing in viscid strings. Twenty-four hours after the poisoning he was
admitted into the South Devon Hospital apparently semi-comatose; his
legs dragged, and he had only feeble control of them; the extremities
were cold, but there was general free sweating. He could be roused only
with difficulty. There were no spasms, the pupils were dilated and
sluggish, the respiration only 14 per minute. Twelve hours after
admission he became warmer, and perspired freely; he slept continuously,
but could easily be roused. On the following day he was quite conscious,
and made a good recovery. Two companions who had also eaten a smaller
quantity of the hemlock dropwort, escaped with some numbing sensations,
and imperfect control over the extremities. In the Woolwich cases the
symptoms seem to have been something similar; in about twenty minutes,
one man, without any apparent warning, fell down in strong convulsions,
which soon ceased, although he looked wild; a little while afterwards
his face became bloated and livid, his breathing stertorous and
convulsive, and he died in five minutes after the first symptoms had set
in. A second died with similar symptoms in a quarter of an hour; a third
died in about an hour, a fourth in a little more than an hour; two other
cases also proved fatal, one in nine days, the other in eleven. In the
two last cases there were signs of intestinal irritation. The majority
of the others fell down in a state of insensibility with convulsions,
the after-symptoms being more or less irritation of the intestinal
canal.

[619] _Lancet_, Dec. 18, 1882.

§ 606. =Post-mortem Appearances.=--It was noticed in the Woolwich cases
that those who died quickly had congestion of the cerebral vessels, and,
in one instance, there was even extravasation of blood, but the man who
died first of all had no congestion of the cerebral vessels. The lining
membrane of the wind-pipe and air tubes was intensely injected with
blood, and the lungs were gorged with fluid blood; the blood in the
heart was black and fluid. The stomach and intestines were externally of
a pink colour. The mucous membrane of the stomach was much corrugated,
and the follicles particularly enlarged. In the two protracted cases the
stomach was not reddened internally, but the vessels of the brain were
congested.


VIII.--Oil of Savin.

§ 607. The leaves of the _Sabina communis_ (_Juniperus Sabina_), or
common savin, an evergreen shrub to be found in many gardens, contains a
volatile oil, which has highly irritant properties. Savin leaves are
occasionally used in medicine, maximum dose 1 grm. (15·4 grains). There
is also a tincture--maximum dose 3 c.c. (about 45 mins.)--and an
ointment made by mixing eight parts of savin tops with three of yellow
wax and sixteen parts of lard, melting and digesting for twenty minutes,
and then straining through calico. The oil, a tincture, and an ointment,
are officinal pharmaceutical preparations.

The oil of savin is contained to the extent of about 2 per cent. in the
leaves and 10 per cent. in the fruit. It has a peculiar odour, its
specific gravity is ·89 to ·94, and it boils at 155° to 160°. An
infusion of savin leaves (the leaves being drunk with the liquid) is a
popular and very dangerous abortive.

It is stated by Taylor that oil of savin has no abortive effect, save
that which is to be attributed to its general effect upon the system,
but this is erroneous. Röhrig found that, when administered to rabbits,
it had a very evident effect upon the pregnant uterus, throwing it into
a tetanic contraction. The action was evident after destruction of the
spinal cord. The plant causes great irritation and inflammation, whether
applied to the skin or taken internally. The symptoms are excruciating
pain, vomiting, and diarrhœa, and the person dies in a kind of collapse.

In a case in which the author was engaged some years ago, a woman,
pregnant by a married man, took an unknown quantity of infusion of savin
tops. She was violently sick, suffered great pain, with diarrhœa, and
died in about 26 hours. The pharynx was much reddened, and the gullet
even congested; the stomach was inflamed, and contained some greenish
matter, in which the author was able to detect savin tops, as well as to
separate by distillation a few drops of a strong savin-like smelling
oil. The time which would elapse between the swallowing of the poison
and the commencement of the pain was an important factor in this case,
for the man was accused of having supplied her with the infusion. From
the redness of the pharynx, and, generally, the rapid irritation caused
by ethereal oils, the author was of opinion that but a few minutes must
have passed between the taking of the liquid and the sensation of
considerable burning pain, although it is laid down in some works, as
for example Falck’s _Toxicologie_, that commonly the symptoms do not
commence for several hours. Symptoms which have been noticed in many
cases are--some considerable irritation of the urinary organs, such as
strangury, bloody urine, &c.; in a few cases vomiting of blood, in
others anæsthesia, convulsions, and coma. Death may occur within 12
hours, or may be postponed for two or three days.

§ 608. =Post-mortem Appearances.=--More or less inflammation of the
bowels, stomach, and intestinal tract, with considerable congestion of
the kidneys, are the signs usually found.

§ 609. =Separation of the Poison and Identification.=--Hitherto reliance
has been placed entirely on the finding of the savin tops, or on the
odour of the oil. There is no reliable chemical test.


IX.--Croton Oil.

§ 610. Croton oil is an oil expressed from the seeds of _Croton
tiglium_, a plant belonging to the natural order _Euphorbiaceæ_, growing
in the West Indies. The seeds are oval in shape, not unlike castor-oil
seeds, and about three-eighths of an inch in length. Both the seeds and
the oil are very poisonous. The chemical composition of croton oil can
scarcely be considered adequately settled. The most recent view,
however, seems to be that it contains a fixed oil (C₉H₁₄O₂) with certain
glycerides.[620] On saponifying and decomposing the soap a series of
volatile fatty acids can be distilled over, the principal of which are
methyl crotonic acid, with small quantities of formic, acetic,
iso-butyric, valeric, and perhaps propionic, and other acids.[621] The
peculiar properties of croton are due rather to the fixed oil than to
the volatile principles. The only officinal preparation in the British
pharmacopœia is a “_croton oil liniment_,” containing one part of croton
oil to seven of equal parts of oil of cajuput and rectified spirit.

[620] G. Schmidt, _Arch. Pharm._ [3] 13, 213-229. Schlippe, Liebig’s
_Annalen_, 105, 1. Geuther and Fröhlich, _Zeitschrift f. Chem._, 1870,
26 and 549; _Journ. Chem. Society_, March 1879, p. 221.

[621] Benedikt has found 0·55 per cent. of unsaponifiable matter in
croton oil. Lewkowitsch gives the iodine value 101·7 to 104·7, and
solidifying point as 18·6°-19·0°. (_Cheml. Analysis of the Oils, Fats,
and Waxes_, by R. Benedikt, translated and enlarged by J. Lewkowitsch,
London, 1895.)

§ 611. =Dose.=--The oil is given medicinally as a powerful purgative in
doses up to 65 mgrms. (about a grain). It is used externally as an
irritant or vesicant to the skin. A very dangerous dose would be from
fifteen to twenty times the medicinal dose.

=Effects.=--Numerous cases of poisoning from large doses of croton oil
are recorded in medical literature, but the sufferers have mostly
recovered. The symptoms are pain, and excessive purging and vomiting.

In the case of a chemist,[622] who took half an ounce of impure croton
oil instead of cod-liver oil, the purging was very violent, and he had
more than a hundred stools in a few hours; there was a burning pain in
the gullet and stomach, the skin was cyanosed, the pupils dilated, and
great faintness and weakness were felt, yet the man recovered. A child,
aged four, recovered from a teaspoonful of the oil given by mistake
directly after a full meal of bread and milk. In five minutes there were
vomiting and violent purging, but the child was well in two days. A
death occurred in Paris, in 1839, in four hours after taking two and a
half drachms of the oil. The symptoms of the sufferer, a man, were those
just detailed, namely, burning pain in the stomach, vomiting, and
purging. Singularly enough, no marked change was noticed in the mucous
membrane of the stomach when examined after death. An aged woman died in
3 days from a teaspoonful of croton-oil embrocation; in this case there
were convulsions.

[622] _Revue de Thérapeut._, May 1881.

In the case of _Reg._ v. _Massey and Ferraud_,[623] the prisoners were
charged with causing the death of a man, by poisoning his food with
jalap and six drops of croton oil. The victim, with others who had
partaken of the food, suffered from vomiting and purging; he became
better, but was subsequently affected with inflammation and ulceration
of the bowels, of which he died. In this case it was not clear whether
the inflammation had anything to do with the jalap and croton oil or
not, and the prisoners were acquitted. In a criminal case in the United
States, a man, addicted to drink, was given, when intoxicated, 2 drachms
of croton oil in a glass of whisky. He vomited, but was not purged, and
in about twelve hours was found dead. The mucous membrane of the stomach
and small intestines proved to be much inflamed, and in some parts
eroded, and croton oil was separated from the stomach.

[623] _Orfila_, t. i. p. 108.

§ 612. =Post-mortem Appearances.=--Inflammation of the stomach and
intestines are the signs usually found in man and animals.

§ 613. =Chemical Analysis.=--The oil may be separated from the contents
of the stomach by ether. After evaporation of the ether, the blistering
or irritant properties of the oil should be essayed by placing a droplet
on the inside of the arm.


X.--The Toxalbumins of Castor-Oil Seeds and of Abrus.

§ 614. =The Toxalbumin of Castor-Oil Seeds.=--In castor-oil seeds,
besides the well-known purgative oil, there exists an albuminous body
intensely poisonous, which has been carefully investigated by
Stillmark,[624] under the direction of Kobert.[625] Injected into the
circulation it is more poisonous than strychnine, prussic acid, or
arsenic; and since the pressed seeds are without taste or smell, this
poison has peculiar dangers of its own.

[624] H. Stillmark, _Dorp. Arb._, Bd. iii., 1889.

[625] Kobert’s _Lehrbuch_, 453-456.

It is essentially a blood poison, coagulating the blood.

The blood, if carefully freed from all fibrin, is yet again brought to
coagulation by a small amount of this body.

If castor-oil seeds are eaten, a portion of the poison is destroyed by
the digestive processes; a part is not thus destroyed, but is absorbed,
and produces in the blood-vessels its coagulating property. Where this
takes place, ulcers naturally form, because isolated small areas are
deprived of their blood supply. These areas thus becoming dead, may be
digested by the gastric or intestinal fluids, and thus, weeks after,
death may be produced. The symptoms noted are nausea, vomiting, colic,
diarrhœa, tenesmus, thirst, hot skin, frequent pulse, sweats, headache,
jaundice, and death in convulsions or from exhaustion. Animals may be
made immune by feeding them carefully with small doses, gradually
increased.

The _post-mortem_ appearances are ulceration in the stomach and
intestines. In animals the appearances of hæmorrhagic gastro-enteritis,
with diffuse nephritis, hæmorrhages in the mesentery and so forth have
been found.

§ 615. =Toxalbumin of Abrus.=--A toxalbumin is found in the _Abrus
precatorius_ (Jequirity) which causes quite similar effects and
symptoms. That it is not identical is proved by the fact that, though
animals may become immune by repeated doses of Jequirity against
“Abrin,” the similar substance from castor-oil seeds only confers
immunity against the toxalbumin of those seeds, and not against abrin;
and similarly abrin confers no immunity against the castor albumin.
Either of these substances applied to the conjunctiva produces
coagulation in the vessels and a secondary inflammation, to
which in the case of jequirity has been given the name of
“jequirity-ophthalmia.”[626]

[626] Heinr. Hellin, _Der giftige Eiweisskorper-Abrin u. seine Wirkung
auf das Blut. Inaug.-Diss._, Dorpat., 1891.

The general effect of these substances, and, above all, the curious fact
that a person may acquire by use a certain immunity from otherwise fatal
doses is so similar to poisonous products evolved in the system of
persons suffering from infectious fevers, that they have excited of late
years much interest, and a study of their methods of action will throw
light upon many diseased processes.

At present there are no chemical means of detecting the presence of the
toxalbumins mentioned. Should they be ever used for criminal purposes,
other evidence will have to be obtained.


XI.--Ictrogen.

§ 616. =Ictrogen.=--Various lupins, _e.g._, _Lupinus luteus_, _L.
angustifolius_, _L. thermis_, _L. linifolius_, _L. hirsutus_, contain a
substance of which nothing chemically is known, save that it may be
extracted by weakly alkaline water, and which has been named “ictrogen”;
this must not be confused with the alkaloid of lupins named “lupinine,”
a bitter tasting substance. In large doses a nerve poison. Ictrogen has
the unusual property of acting much like phosphorus. It causes yellow
atrophy of the liver, and produces the following symptoms:--Intense
jaundice; at first enlargement of the liver, afterwards contraction;
somnolence, fever, paralysis. The urine contains albumen and the
constituents of the bile. After death there is found to be
parenchymatous degeneration of the heart, kidneys, muscles, and liver.
If the animal has suffered for some time the liver may be cirrhotic.

Hitherto the cases of poisoning have been confined to animals. Many
thousands of sheep and a few horses and deer have, according to Kobert,
died in Germany from eating lupin seeds. Further information upon the
active principles of lupins may be obtained by referring to the
following treatises:--G. Schneidemuhl, _Die lupinen Krankheit der
Schafe_; _Vorträge f. Thierärzte_. Ser. 6, Heft. 4, Leipzig, 1883. C.
Arnold and G. Schneidemuhl, _Vierter Beitrag zur Klarstellung der
Ursache u. des Wesens der Lupinose_, Luneburg, 1883; Julius Löwenthal,
_Ueber die physiol. u. toxicol. Wirkungen der Lupinenalkaloide,
Inaug.-Diss._, Königsberg, 1888.


XII.--Cotton Seeds.

§ 617. Cotton seeds, used as an adulterant to linseed cake, &c., have
caused the death of sheep and calves. Cotton seeds contain a poison of
which nothing is chemically known, save that it is poisonous. It
produces anæmia and cachexia in animals when given in small repeated
doses.

After death the changes are, under these circumstances, confined to the
kidney; these organs showing all the signs of nephritis. If, however,
the animal has eaten a large quantity of cotton seeds, then there is
gastro-enteritis, as well as inflammation of the kidneys.


XIII.--Lathyrus Sativus.

§ 618. Various species of vetchlings, such as _L. sativus_, _L. cicera_,
_L. clymenum_, are poisonous, and have caused an epidemic malady in
parts of Spain, Africa, France, and Italy, among people who have eaten
the seeds. The symptoms are mainly referable to the nervous system,
causing a transverse myelitis and paraplegia. In this country it is
chiefly known as a poisonous food for horses; the last instance of
horse-poisoning by lathyrus was that of horses belonging to the Bristol
Tramways and Carriage Company.[627] The company bought some Indian peas;
these peas were found afterwards to consist mainly of the seeds of
_Lathyrus sativus_, for out of 335 peas no fewer than 325 were the seeds
of _Lathyrus_. The new peas were substituted for the beans the horses
had been having previously on the 2nd November, and the horses ate them
up to the 2nd December. Soon after the new food had been given, the
horses began to stumble and fall about, not only when at work, but also
in their stalls; to these symptoms succeeded a paralysis of the larynx;
this paralysis was in some cases accompanied by a curious weird
screaming, which once having been heard could never be forgotten; there
was also gasping for breath and symptoms of impending suffocation. A few
of the horses were saved by tracheotomy. Some died of suffocation; one
horse beat its brains out in its struggles for breath; 127 horses were
affected; 12 died.

[627] Bristol Tramways and Carriage Company _v._ Weston & Co., _Times_,
July 17, 1894.

The above train of symptoms has also been recorded in similar cases;
added to which paralysis of the lower extremities is frequent. After
death atrophy of the laryngeal muscles, wasting of the nervus recurrens,
and atrophy of the ganglion cells of the vagus nucleus as also of the
multipolar ganglion cells in the anterior horns of the spinal cord have
been found.

The active principle of the seeds has not been satisfactorily isolated.
The symptoms suggest the action of a toxalbumin. Teilleux found a resin
acid; Louis Astier a volatile alkaloid, and he explains the fact that
the seeds, after being heated, are no longer poisonous by the
dissipation of this alkaloid.


XIV.--Arum--Bryony--Locust Tree--Male Fern.

§ 619. =Arum maculatum=, the common cuckoo-pint, flowering in April and
May, and frequent in the hedges of this country, is extremely poisonous.
Bright red succulent attractive berries are seen on a single stalk, the
rest of the plant having rotted away, and these berries are frequently
gathered by children and eaten. The poison belongs to the class of acrid
irritants, but its real nature remains for investigation.

Some of the species of the same natural order growing in the tropics are
far more intensely poisonous.

§ 620. =The Black Bryony.=--_Tamus communis_, the black bryony, a common
plant by the wayside, flowering in May and June, possesses poisonous
berries, which have been known to produce death, with symptoms of
gastro-enteritis. In smaller doses the berries are stated to produce
paralysis of the lower extremities.[628]

[628] Contagne, _Lyon med._, xlvi., 1884, 239.

§ 621. =The Locust Tree.=--The _Robinia pseudo-acacia_, a papilionaceous
tree, contains a poison in the leaves and in the bark. R. Coltmann [629]
has recorded a case in China of a woman, twenty-four years of age, who,
at a time of famine, driven by hunger, ate the leaves of this tree. She
became ill within forty-eight hours, with high fever; the tongue swelled
and there was much erysipelatous-like infiltration of the tissues of the
mouth; later the whole body became swollen. There was constipation and
so much œdema of the eyelids that the eyeballs were no longer visible.
Recovery took place without special treatment. Power and Cambier[630]
have separated from the bark an albumose, which is intensely poisonous,
and is probably the cause of the symptoms detailed.

[629] _Medical and Surgical Reporter_, lxi., 1889.

[630] _Pharm. Journ._, 1890, 711.

§ 622. =Male Fern.=--An ethereal extract of _Aspidium Filix mas_ is used
as a remedy against tape worm.

Poullson[631] has collected up to the year 1891 sixteen cases of
poisoning by male fern; from which it would appear that 7 to 10 grms.
(103 to 154 grains) of the extract may be fatal to a child, and 45 grms.
(rather more than 1½ oz.) to an adult. The active principle seems to be
filicic acid and the ethereal oil. Filicic acid, under the influence of
saponifying agencies, breaks up into butyric acid and phloroglucin.

[631] _Arch. exp. P._, Bd. 29.

The symptoms produced are pain, heaviness of the limbs, faintness,
somnolence, dilatation of the pupil, albuminuria, convulsions, lock-jaw,
and collapse. In animals there have also been noticed salivation,
amaurosis, unsteady gait, dragging of the hind legs, dyspnœa, and
paralysis of the breathing centres. The _post-mortem_ appearances which
have been found are as follows:--Redness and swelling with hæmorrhagic
spots of the mucous membranes of the stomach and intestines; acute œdema
of the brain and spinal cord with petechia in the meninges; the kidneys
inflamed, the liver and spleen congested, and the lungs œdematous.

There is no characteristic reaction for male fern; the research most
likely to be successful is to attempt to separate from an ethereal
extract filicic acid, and to decompose it into butyric acid and
phloroglucin; the latter tinges red a pine splinter moistened with
hydrochloric acid.




PART VII.--POISONS DERIVED FROM LIVING OR DEAD ANIMAL SUBSTANCES.


DIVISION I.--POISONS SECRETED BY LIVING ANIMALS.


I.--Poisonous Amphibia.

§ 623. The glands of the skin of certain amphibia possess a secretion
that is poisonous; the animal is unable to empty the poison glands by
any voluntary act, but the secretion can readily be obtained by
pressure. Zalesky found the juice in the skin glands of the _Salamandra
maculosa_, milky, alkaline in reaction, and bitter in taste. He isolated
from it an organic base, which he named _Salamandrine_ (C₃₄H₆₀N₂O₅), it
is soluble in water and in alcohol, and forms salts. Salamandrine is a
strong poison; injected subcutaneously into rabbits it causes shivering,
epileptiform convulsions, and salivation; then tetanus, followed by
oppressed respiration, dilated pupils, and anæsthesia. Death occurs
after a kind of paralytic state. When given to dogs, it causes vomiting.
In frogs, tetanus occurs first and then paralysis--the result of all the
experiments being that salamandrine acts on the brain and spinal cord,
leaving the heart and muscular substance unaffected. A similar secretion
obtained from the water salamander (_Triton cristatus_), causes,
according to Vulpian, the death of dogs in from three to eighteen hours;
the symptoms being progressive weakness, slowing of the respiration, and
depression of the heart’s action.

§ 624. The secretion of the skin of the common toad contains
methylcarbylaminic acid, carbylamine, and, according to Fornara, an
alkaloid which is soluble in alcohol, and to which the name of
_phrynine_ has been applied; its action is toxic on all animals
experimented upon, save toads. Administered subcutaneously to frogs, it
has a digitalis-like action, causing rapid paralysis of the heart, and
the breathing soon after ceases; the muscles become early rigid.


II.--The Poison of the Scorpion.

§ 625. There are several species of scorpions. The small European
variety (_Scorpio europæus_) is found in Italy, the south of France, and
the Tyrol; the African scorpion (_Bothus afer_, L.), which attains the
length of 16 cm., is found in Africa and the East Indies; _Androctonus
bicolor_ in Egypt; and the _Androctonus occitanus_ in Spain, Italy,
Greece, and North Africa.

In the last joint of the tail the scorpion is provided with a poisonous
apparatus, consisting of two oval glands, the canal of which leads into
a round bladder, and this last is connected with a sting. When the sting
is inserted, the bladder contracts, and expels the poison through the
hollow sting into the wound. The smaller kinds of scorpion sting with as
little general effect as a hornet, but the large scorpion of Africa is
capable of producing death. There is first irritation about the wound,
and an erysipelatous inflammation, which may lead to gangrene. Vomiting
and diarrhœa then set in, with general weakness and a fever, which may
last from one to one and a half days; in the more serious cases there
are fainting, delirium, coma, convulsions, and death. According to G.
Sanarelli[632] the blood corpuscles of birds, fishes, frogs, and
salamanders are dissolved by the poison; only the nucleus remaining
intact; the blood corpuscles of warm-blooded animals are not affected.

[632] G. Sanarelli, _Bollet. della Soc. della sez. dei cult. delle
Scienze med._, v., 1888, 202.

Valentin made some experiments on frogs with the _Androctonus
occitanus_. He found that soon after the sting the animal remains quiet,
but on irritation it moves, and is thrown into a transitory convulsion;
to this follow twitchings of single muscular bundles. The frog is
progressively paralysed, and the reflex irritability is gradually
extinguished from behind forwards; at first the muscles may be excited
by electrical stimuli to the nerves, but later they are only capable of
contraction by direct stimuli.


III.--Poisonous Fish.

§ 626. A large number of fish possess poisonous properties; in some
cases the poison is local; in others the poison is in all parts of the
body.

Many fish are provided with poison glands in connection with the fins or
special weapons, and such are used for purposes of defence; for example,
_Synanceia brachio_ is provided with a back fin consisting of 13 spines,
each of which has two poison reservoirs; the reservoirs are connected
with 10 to 12 tubular glands which secrete the poison, a clear feebly
acid bluish fluid, exciting in a concentrated condition, local gangrene;
in a diluted one, paralysis of the nervous centres.

Another kind of localisation is the localisation in certain of the
internal organs. Remy states, that there are twelve varieties of
_Tetrodon_ in Japanese waters, all of which are poisonous. M. Minra and
K. Takesaki[633] find that the poison of the _Tetrodon_ is confined to
the sexual organs of the female, and at the time of activity of these
glands, the poisonous properties are most intense; but, even in winter,
when the glands are atrophied, Remy found the glands were so poisonous
that he could prepare from them a fluid, which, administered
subcutaneously, killed dogs within two hours. The symptoms in the dog
are restlessness, salivation, vomiting of slimy masses, dilatation of
the pupil, paralysis and great dyspnœa. Death occurs by the lung. After
death the appearances are similar to those from asphyxia; in addition to
which there are small ecchymoses in the stomach and intestines; the
salivary glands and pancreas are also injected. The symptoms observed in
man are similar, there is headache, dilated pupils, vomiting, sometimes
hæmatamesis, convulsions, paralysis, dyspnœa and death.

[633] Virchow’s _Archiv_, 1890, Bd. 122.

Some fishes are poisonous on account of the food they live upon; the
_Meletta venenosa_ is only poisonous when it feeds upon a certain green
monad; _Clupea thrissa_, _C. venenosa_ and certain species of _Scarus_,
neither possess poison glands nor poisonous ovaries; but also derive
their poisonous properties from their food. In the West Indies it is
well-known that fish caught off certain coral banks are unwholesome,
while the same species caught elsewhere may be eaten with safety.

A good many shell-fish, especially mussels, occasionally cause intense
poisonous symptoms; those usually noticed are high fever, nettle rash,
dilated pupils, and diarrhœa. It may be that in these cases a ptomaine,
the product of bacterial action, has been ingested. To the agency of
bacteria has been ascribed illness produced in Russia by a good many
fish of the sturgeon species. The symptoms are those of cerebro-spinal
paralysis. The “Icthyismus gastricus” of Germany may belong to the same
type. Prochorow[634] has described illness from ingestion of _Petromyzon
fluviatilis_ in Russia. Whether the fish was eaten raw or cooked, the
effect was the same, producing a violent diarrhœa, dysenteric in
character. Even the broth in which the fish had been boiled produced
symptoms. Fresh blood of the eel is stated to be intensely poisonous;
this property is apparently due to a toxalbumin; Pennavaria[635] relates
the case of a man who took, in 200 c.c. of wine, 0·64 kilo. of fresh eel
blood and suffered from diarrhœa with symptoms of collapse.

[634] _Pharmac. Ztg._, 1885.

[635] _Il Farmacista Italiano_, xii., 1888.

In the _Linnean Transactions_ for November, 1860, is recorded a fatal
accident, which took place on board the Dutch ship “Postillion” at
Simon’s Bay, Cape of Good Hope. The boatswain and purser’s steward
partook of the liver of the _toad_ or _ball-bladder_ (_Diodon_); within
twenty minutes the steward died; in ten minutes the boatswain was
violently ill; the face flushed, the eyes glistening, and the pupils
contracted; there was cyanosis of the face, the pulse was weak and
intermittent, and swallowing was difficult, the breathing became
embarrassed, and the body generally paralysed. Death took place in
seventeen minutes. The liver of one fish only is said to have been
eaten. This might weigh 4 drachms. If the account given is literally
correct, the intensity of the poison equals that of any known substance.

The poisonous nature of the goby has also led to several accidents, and
we possess a few experiments made by Dr. Collas,[636] who fed chickens
with different parts of the fish, and proved that all parts were alike
poisonous. The effects were slow in developing; they commenced in about
an hour or an hour and a half, and were well developed in five hours,
mainly consisting of progressive muscular weakness and prostration.
Death occurred without convulsions.

[636] _Soc. Sci. Rev._, July 19, 1862; _Brit. and For. Med. Chir. Rev._,
Oct. 1862, p. 536.


IV.--Poisonous Spiders and Other Insects.

§ 627. It is probable that all spiders are poisonous; the only species,
however, of which we have any definite information relative to their
poisonous properties, are _Lycosa tarantula_ and the _Latrodectus
malmignatus_, to which may be added the New Zealand _katipo_. These
spiders possess a poisonous gland connected with their masticatory
apparatus, which secretes a clear, oily, bitter acid-reacting fluid; the
acidity seems due to formic acid.

Zangrilli has observed several cases of tarantula bite; soon after the
occurrence the part bitten is anæsthetic, after a few hours there are
convulsive shiverings of the legs, cramps of the muscles, inability to
stand, spasm of the pharyngeal muscles, quickening of the pulse, and a
three days’ fever, with vomiting of yellow, bilious matter; recovery
follows after copious perspiration. In one case there was tetanus, and
death on the fourth day. The extraordinary effects attributed to the
bite of the tarantula, called _tarantism_ in the Middle Ages, are well
detailed by Hecker;[637] this excitement was partly hysterical and
partly delirious, and has not been observed in modern times.

[637] “The Epidemics of the Middle Ages,” by J. F. C. Hecker, translated
by B. G. Babington, M.D., F.R.S. (_The Dancing Mania_, chap, ii., &c.)

Dax has described the effects of the bite of the _L. malmignatus_; it
occasioned headache, muscular weakness, pain in the back, cramps, and
dyspnœa; the symptoms disappeared after several days.

§ 628. The _katipo_ is a small poisonous spider confined to New Zealand.
Mr. W. H. Wright has recorded the case of a person who, in 1865, was
bitten by this spider on the shoulder. The part rapidly became swollen,
and looked like a large nettle-rash wheal; in an hour the patient could
hardly walk, the respiration and circulation were both affected, and
there was great muscular prostration; but he recovered in a few hours.
In other cases, if the accounts given are to be relied upon, the bite of
the spider has produced a chronic illness, accompanied by wasting of the
body, followed by death after periods varying from six weeks to three
months.[638]

[638] _Transac. of the New Zealand Inst._, vol. ii., 1869; _Brit. and
For. Med. Chir. Review_, July 1871, p. 230.

§ 629. =Ants.=--The various species of ants possess at the tail special
glands which secrete _formic acid_. Certain exotic species of ants are
provided with a sting, but the common ant of this country has no special
piercing apparatus. The insect bites, and then squirts the irritating
secretion into the wound, causing local symptoms of swelling and
inflammation.

§ 630. =Wasps, &c.=--Wasps, bees, and hornets all possess a poison-bag
and sting. The fluid secreted is as clear as water, and of an acid
reaction; it certainly contains formic acid, with some other poisonous
constituent. An erysipelatous inflammation generally arises round the
sting, and in those cases in which persons have been attacked by a swarm
of bees, signs of general poisoning, such as vomiting, fainting,
delirium, and stupor, have been noticed. Death has occasionally
resulted.

§ 631. =Cantharides.=--Commercial cantharides is either the dried
entire, or the dried and powdered blister-beetle, or Spanish fly
(_Cantharis vesicatoria_). The most common appearance is that of a
greyish-brown powder, containing shining green particles, from which
cantharidin is readily extracted by exhausting with chloroform, driving
off the chloroform by distillation or evaporation, and subsequently
treating the extract with bisulphide of carbon, which dissolves the
fatty matters only. Finally, the cantharidin may be recrystallised from
chloroform, the yield being ·380 to ·570 per cent. Ferrer found in the
wings and their cases, ·082 per cent.; in the head and antennæ, ·088; in
the legs, ·091; in the thorax and abdomen, ·240; in the whole insect,
·278 per cent. Wolff found in the _Lytta aspera_, ·815 per cent.; Ferrer
in _Mylabris cichorei_, ·1 per cent.; in _M. punctum_, ·193; and in _M.
pustulata_, ·33 per cent. of _cantharidin_.

§ 632. =Cantharidin= (C₁₀H₁₂O₄) has two crystalline forms--(1)
Right-angled four-sided columns with four surfaces, each surface being
beset with needles; and (2) flat tables. It is the anhydride of a ketone
acid (cantharidic acid), C₈H₁₃O₂-CO-COOH. It is soluble in alkaline
liquids, and can be recovered from them by acidifying and shaking up
with _ether_, _chloroform_, or _benzene_; it is almost completely
insoluble in water. 100 parts of alcohol (99 per cent.) dissolve at 18°
0·125 part; 100 of bisulphide of carbon, at the same temperature, 0·06
part; ether, ·11 part; chloroform, 1·2 part; and benzene, ·2 part.
Cantharidin can be completely sublimed, if placed in the subliming cell
(described at p. 258), floating on mercury; a scanty sublimate of
crystals may be obtained at so low a temperature as 82·5°; at 85°, and
above, the sublimation is rapid. If the cantharidin is suddenly heated,
it melts; but this is not the case if the temperature is raised
gradually. The tube melting-point is as high as 218°. Potassic chromate
with sulphuric acid decomposes cantharidin with the production of the
green oxide of chromium. An alkaline solution of permanganate, iodic
acid, and sodium amalgam, are all without influence on an alcoholic
solution of cantharidin. With bases, cantharidin forms crystallisable
salts, and, speaking generally, if the base is soluble in water, the
“_cantharidate_” is also soluble; the lime and magnesic salts dissolve
readily. From the soda or potash salt, mineral acid will precipitate
crystals of cantharidin; on heating with pentasulphide of phosphorus,
o-xylol is produced.

§ 633. =Pharmaceutical Preparations of Cantharides.=--The P.B.
preparations of cantharides are--_Acetum cantharides_, or vinegar of
cantharides, containing about ·04 per cent. of cantharidin.

_Tincture of cantharides_, containing about ·005 per cent. of
cantharidin.

A solution of cantharides for blistering purposes, _Liquor
epispasticus_, a strong solution of the active principle in ether and
acetic acid, containing about ·16 per cent. of cantharidin.

There are also--An _ointment_; a blistering paper, _Charta epispastica_;
a blistering plaster, _Emplastrum cantharides_; and a warm plaster,
_Emplastrum calefaciens_.

§ 634. =Fatal Dose.=--It is difficult to state the fatal dose of
cantharidin, the unassayed powder or tincture having mostly been taken.
A young woman died from 1·62 grm. (25 grains) of the powder, which is
perhaps equivalent to 6·4 mgrms. (1 grain) of cantharidin, whilst the
smallest dose of the tincture known to have been fatal is (according to
Taylor) an ounce. This would be generally equivalent to 15 mgrms. (·24
grain). Hence the fatal dose of cantharidin may be approximately stated
as from 6 mgrms. upwards. But, on the other hand, recovery has taken
place from very large doses.

§ 635. =Effects on Animals.=--Certain animals do not appear susceptible
to the action of cantharidin. For example, hedgehogs and swallows are
said to be able to take it with impunity. Radecki[639] found that
cantharidin might even be injected into the blood of fowls without any
injury, and frogs also seem to enjoy the same impunity; while dogs,
cats, and other animals are sensitive to the poison. Galippe ascertained
that after the injection of 5 mgrms. into the veins of a dog, there was
exaltation of the sexual desire; the pupils quickly dilated, the dog
sought a dark place, and became sleepy. Animals when poisoned die in
asphyxia from paralysis of the respiratory centre. Schachowa[640] made
some observations on the effect of cantharides on the renal excretion of
a dog fed daily with 1 grm. in powder. On the third day, pus corpuscles
were noticed; on the fifth, bacteria; on the thirteenth, the urine
contained a large quantity of fatty matters, and several casts; and on
the seventeenth, red shrivelled blood corpuscles were observed.

[639] _Die Cantharidin Vergift._, Diss., Dorpat, 1806.

[640] _Unters. über die Nieren_, Diss., Bern, 1877; Cornil, _Gaz. Méd._,
1880.

=Effects on Man.=--Heinrich[641] made the following experiments upon
himself:--Thirty living blister-beetles were killed, and digested,
without drying, in 35 grms. of alcohol for fourteen days, of this
tincture ten drops were taken. There ensued immediately a feeling of
warmth in the mouth and stomach, salivation, the pulse was more frequent
than in health, there was a pleasant feeling of warmth about the body,
and some sexual excitement lasting three hours. In half an hour there
was abdominal pain, diarrhœa, and tenesmus, and frequent painful
micturition. These symptoms subsided in a few hours, but there was a
want of appetite, and pain about the kidneys lasting until the following
day. In the second experiment, on taking 1 cgrm. of cantharidin, there
were very serious symptoms of poisoning. Blisters formed on the tongue,
and there was salivation, with great difficulty in swallowing, and a
general feeling of illness. Seven hours after taking the poison, there
were frequent micturitions of bloody urine, diarrhœa, and vomiting.
Twenty hours after the ingestion the face was red, the skin hot, the
pulse twenty beats beyond the normal pulsation, the tongue was denuded
to two-thirds of its extent of its epithelium, and the lips and mucous
membrane were red and swollen; there was great pain in the stomach,
intestines, and in the neighbourhood of the kidneys, continuous desire
to micturate, burning of the urethra, and swelling of the glands. There
was no sexual excitement whatever; the urine was ammoniacal, and
contained blood and pus; the symptoms gradually subsided, but recovery
was not complete for fourteen days.

[641] Schroff, _Zeitschrift d. Ges. d. Aerzte in Wien_, 13, 56.

§ 636. The foregoing is a fair picture of what may be expected in
cantharides poisoning. It is remarkable that the popular idea as to the
influence of cantharidin in exciting the sexual passion, holds good only
as to the entire cantharides, and not with cantharidin. It is very
possible that cantharidin is not the only poisonous principle in the
insect. The symptoms in other cases, fatal or not, have been as
follows:--Immediate burning in the mouth and throat, extending to the
stomach and alimentary canal, and increasing in intensity until there is
considerable pain. Then follow salivation, difficulty in swallowing, and
vomiting, and generally diarrhœa, pain in the kidneys, irritation of the
bladder, priapism, and strangury, are all present. The pulse is
accelerated, the breathing disturbed, there are pains in the head, and
often mydriasis, giddiness, insensibility, delirium, and convulsions;
trismus has been noticed. The desire to micturate frequently is urgent,
the urine is generally bloody, and contains pus. Pregnant women have
been known to abort. In a few of the cases in which a different course
has been run, the nervous symptoms have predominated over those of
gastro-intestinal irritation, and the patient has sunk in a kind of
collapse. In a case of chronic poisoning by cantharides, extending over
three months, and recorded by Tarchioni Bonfanti,[642] after the first
dose appeared tetanic convulsions, which subsided in twenty-four hours,
there was later cystitis, and from time to time the tetanic convulsions
returned; gastro-enteritis followed with frequent vomiting, when,
cantharides being found in the matters ejected, the otherwise obscure
nature of the illness was shown.

[642] _Gaz. Med. Ital. Lomb._, 1863.

In a case recorded by Sedgwick,[643] following the gastro-enteric
symptoms, there were epileptic convulsions; in this instance also was
noticed an unpleasant smell, recalling the notion formerly held that
cantharides imparted a peculiar odour to the breath and urine. In a case
of chronic poisoning related by Tardieu, six students, during several
months, used what they thought was pepper with their food, but the
substance proved to be really powdered cantharides. The quantity taken
each day was probably small, but they suffered from pain about the
loins, and also irritation of the bladder. There was no sexual
excitement.

[643] _Med. Times_, 1864.

§ 637. =Post-mortem Appearances.=--In a French criminal case, in which a
man poisoned his step-brother by giving cantharides in soup, the
pathological signs of inflammation of the gastro-intestinal tract were
specially evident, the mouth was swollen, the tonsils ulcerated, the
gullet, stomach, and intestines were inflamed, and the mucous membrane
of the intestines covered with purulent matter. In another case there
was an actual perforation 3 inches from the pylorus. The inflammatory
appearances, however, are not always so severe, being confined to
swelling and inflammation without ulceration. In all cases there has
been noted inflammation of the kidneys and urinary passages, and this is
seen even when cantharidin is administered to animals by subcutaneous
injection. In the urine will be found blood and fatty epithelial casts,
as well as pus. The contents of the stomach or the intestines will
probably contain some remnants of powdered cantharides, if the powder
itself has been taken.

§ 638. =Tests for Cantharidin, and its Detection in the Tissues,
&c.=--The tests for cantharidin are--(1.) Its form, (2.) its action in
the subliming cell, and (3.) its power of raising a blister.

The most convenient method of testing its vesicating properties, is to
allow a chloroformic solution of the substance supposed to be
cantharidin to evaporate to dryness, to add to this a drop of olive oil
(or almond oil), and to take a drop up on the smallest possible quantity
of cotton wool, and apply the wool to the inside of the arm, covering it
with good oilskin, and strapping the whole on by the aid of
sticking-plaster. In about an hour or more the effect is examined. The
thin skin of the lips is far more easily blistered than that of the arm,
but the application there is inconvenient.

Dragendorff has ascertained that cantharidin is not present in the
contents of a blister raised by a cantharides plaster, although it has
been found in the urine of a person treated by one; and Pettenkofer has
also discovered cantharidin in the blood of a boy to whose spine a
blister had been applied.

The great insolubility of cantharidin in water has led to various
hypotheses as to its absorption into the system. It is tolerably easily
dissolved by potash, soda, and ammonia solutions, and is also taken up
in small proportion by sulphuric, phosphoric, and lactic acids. The
resulting compounds quickly diffuse themselves through animal membranes.
Even the salts with lime, magnesia, alumina, and the heavy metals, are
not quite insoluble. A solution of salt with cantharidin, put in a
dialysing apparatus, separates in twenty-four hours enough cantharidin
to raise a blister.

Cantharidin has actually been discovered in the heart, brain, muscles,
contents of the stomach, intestines, and fæces (as well as in the blood
and urine) of animals poisoned by the substance. A urine containing
cantharidin is alkaline and albuminous. Cantharidin, although readily
decomposed by chemical agents, is so permanent in the body that it has
been detected in the corpse of a cat eighty-four days after death.

In any forensic case, the defence will not improbably be set up that
some animal (_e.g._, a fowl poisoned by cantharides) has been eaten and
caused the toxic symptoms, for cantharides is an interesting example of
a substance which, as before stated, for certain animals (such as
rabbits, dogs, cats, and ducks), is a strong poison, whilst in others
(_e.g._, hedgehogs, fowls, turkeys, and frogs), although absorbed and
excreted, it appears inert. Experiment has shown that a cat may be
readily poisoned by a fowl saturated with cantharides; and in Algeria
the military surgeons meet with cystitis among the soldiers, caused by
eating frogs in the months of May and June, the frogs living in these
months almost exclusively on a species of cantharides.

Dragendorff recommends the following process:--The finely-pulped
substance is boiled in a porcelain dish with potash-lye (1 part of
potash and 12 to 18 of water) until the fluid is of a uniform
consistence. The fluid, after cooling, is (if necessary) diluted with an
equal bulk of water, for it must not be too thick; then shaken with
chloroform in order to remove impurities; and after separation of the
chloroform, strongly acidified with sulphuric acid, and mixed with about
four times its volume of alcohol of 90 to 95 per cent. The mixture is
kept for some time at a boiling temperature, filtered hot, and the
alcohol distilled from the filtrate. The watery fluid is now again
treated with chloroform, as above described. The chloroform extract is
washed with water, the residue taken up on some hot almond oil, and its
blistering properties investigated. The mass, heated with potash in the
above way, can also be submitted to dialysis, the diffusate
supersaturated with sulphuric acid, and shaken up with chloroform.

In order to test further for cantharidin, it can be dissolved in the
least possible potash or soda-lye. The solution, on evaporation in the
water-bath, leaves crystals of a salt not easily soluble in alcohol, and
the watery solution of which gives with chloride of calcium and baryta a
white precipitate; with sulphate of copper and sulphate of protoxide of
nickel, a green; with cobaltous sulphate, a red; with sugar of lead,
mercury chloride and argentic nitrate, a white crystalline precipitate.
With palladium chloride there occurs a yellow, hair-like, crystalline
precipitate; later crystals, which are isomorphous with the nickel and
copper salts.

If the tincture of cantharides has been used in considerable quantity,
the urine may be examined; in such a case there will collect on the
surface drops of a green oil, which may be extracted by petroleum ether;
this oil is not blister-raising. Cantharides in powder may, of course,
be detected by its appearance.

To the question whether the method proposed would extract any other
blister-producing substance, the answer is negative, since ethereal oil
of mustard would be decomposed, and the active constituents of the
_Euphorbias_ do not withstand the treatment with KHO. Oils of anemone
and anemonin are dissolved by KHO, and again separated out of their
solutions, but their blistering property is destroyed. They are
volatile, and found in anemone and some of the _Ranunculaceæ_. In the
_Aqua pulsatilla_ there is an oil of anemone, which may be obtained by
shaking with ether; but this oil is not permanent, and if the _Aqua
pulsatilla_ stand for a little time, it splits up into anemonic acid and
anemonin, and then cannot be reobtained. A blistering substance,
obtained from the _Anacardia orientalia_ and the fruit of the
_Anacardium occidentale_ and _Semecarpus anacardium_, is not quite
destroyed by a short action with potash, but is by one of long duration;
this substance, however, cannot be confused with cantharidin, for it is
oily, yellow, easily soluble in alcohol and ether, and differs in other
respects.


V.--Snake Poison.

§ 639. The poisonous snakes belong chiefly to two classes, the
_Proteroglypha_ and the _Solenoglypha_.

Weir Mitchell and Ed. T. Reichert[644] have made some important
experiments on snake poison, using the venom of some 200 snakes. Most of
the snakes were rattlesnakes, a few were cobras and other species. They
came to the conclusion that the active constituents are contained in the
fluid part alone, the solid particles suspended in the fluid having no
action. The poison they considered to consist of two toxalbumins, one a
globulin, acting more particularly on the blood, the other, a peptone
(albumose?), acting more particularly on the tissues. Differences in
snake venom depend on the relative proportions of these two substances.
The peptone, which acts more especially locally on the tissues,
determines an inflammatory action, with much swelling and multiple
extravasation of blood, which may proceed to a moist gangrene. The
globulin has a paralysing influence on the heart, the vasomotor centres,
the peripheral ends of the splanchnic nerves, as well as on the
respiratory centres of both warm and cold-blooded animals.
Feoktisow’s[645] researches show that although the heart continues to
beat after the respiration has ceased for a few minutes, it has no
force. The blood pressure sinks immediately after the injection. Whether
the globulin is injected subcutaneously or direct into the veins, there
is commonly considerable extravasation of blood in the chest and
abdomen; the intestine is often filled with blood as well as the
pericardium; and the urine is bloody. The poison of _Vipera ammodytes_
in watery solution may be boiled for six minutes, and yet is as active
as before. According to Lewin, snake poison generally can be heated to
125° and yet preserve its poisonous properties. These last observations
are not in accordance with the belief of some that the active principle
of snake venom is a ferment, or, indeed, in harmony with the idea that
it is a globulin or toxalbumin; for such bodies have not, so far as we
know, the stability to withstand so high a degree of heat.

[644] _Smithsonian Contributions to Knowledge_, Washington, 1886.

[645] _Exp. Unters. über Schlangengift. Inaug. Diss._, Dorpat, 1888.

§ 640. =The Poison of the Cobra.=--The poison excreted from the salivary
glands of the cobra di capello is the most deadly animal fluid known.
When first ejected, it is an amber-coloured, rather syrupy, frothy
liquid, of specific gravity 1·046, and of feeble acid reaction; it dries
rapidly on exposure to air to a yellow film, which readily breaks up
into brilliant yellow granules, closely imitating crystals. The yellow
powder is very acrid and pungent to the nostrils, and excites a painful
(though transitory) inflammation, if applied to the mucous membrane of
the eye; the taste is bitter, and it raises little blisters on the
tongue. It is perfectly stable, and preserves its activity for an
indefinite time. The dried poison as described is perfectly soluble in
water, and if the water is added in proper proportions, the original
fluid is without doubt reproduced, the solution usually depositing a
sediment of epithelial _débris_, and often containing little white
threads.

The poison has been examined by several chemists, but until of late
years with a negative result. The writer was the first to isolate, in
1876, a crystalline principle, which appears to be the sole acting
ingredient; the yellow granules were dissolved in water, the albumen
which the venom so copiously contains coagulated by alcohol, and
separated by filtration; the alcohol was then driven off at a gentle
heat, the liquid concentrated to a small bulk, and precipitated with
basic acetate of lead. The precipitate was separated, washed, and
decomposed in the usual way by SH₂, and on removing the lead sulphide,
crystals having toxic properties were obtained.

Pedler,[646] precipitating the albumen by alcohol, and then to the
alcoholic solution adding platinic chloride, obtained a semi-crystalline
precipitate, which from an imperfect combustion he thinks may have
something like the composition PtCl₄(C₁₇H₂₅N₄O₇HCl)₂. I have examined
the platinum compound, and made several combustions of different
fractions, but was unable to obtain the compound in a sufficient state
of purity to deduce a formula. My analysis agreed with those of Pedler
for nitrogen--viz., 9·93 per cent. (Pedler, 9·69); hydrogen 4·17
(Pedler, 4·28); but were higher for carbon, 41·8 per cent. (Pedler,
33·42 per cent.); one fraction gave 7·3 per cent. of platinum, another
double that amount. Material was insufficient to thoroughly investigate
the compound, but it was evident that several double salts were formed.
The blood of the cobra is also poisonous. A. Calmette[647] has found
that 2 c.c. of fresh cobra blood, injected into the peritoneum of a
rabbit weighing 1·5 kilo., causes death in six hours; the same dose of
the defibrinated blood injected into the veins is fatal in three
minutes.

[646] _Proc. Roy. Soc._, vol. xxvii. p. 17.

[647] _Compt. Rend., Soc. de Biol._, 1894.

§ 641. =Fatal Dose.=--From my experiments on cats, rabbits, and birds,
it seems probable that the least fatal dose for cats and rabbits, lies
between ·7 and ·9 mgrm. per kilo., and for birds somewhere about ·7
mgrm. per kilo. of the dried poison; the venom contains about 60 per
cent. of albuminous matter, and about 10 per cent. of poisonous
substance; therefore, the lethal power is represented by something like
·07 to ·09 mgrm. per kilo., if the pure toxic principle free from
albumen and diluting impurities be considered.

§ 642. =Effects on Animals.=--Almost immediately local pain or signs of
uneasiness at the seat of injection are observed. There is then a
variable interval, seldom exceeding 20 minutes (and generally much
less), but in one of my experiments half an hour elapsed after the
injection of a fatal dose before any effect was evident. The symptoms
once produced, the course is rapid, and consists, first, of acceleration
of the respirations, and then a progressive slowing, soon followed by
convulsions. The convulsions are probably produced by the interference
with the respiration and the deficient oxidation of the blood, and are
therefore, the so-called “carbonic acid convulsions.” There is paresis
or paralysis of the limbs. Death seems to occur from asphyxia, and the
heart beats for one or more minutes after the respirations have ceased.
If the dose is so small as not to produce death, no after-effects have
been observed; recovery is complete.

Sir J. Fayrer, and Dr. Lauder Brunton consider that the terminations of
the motor nerves suffer; on the other hand, Dr. Wall would explain the
phenomena by referring the action entirely to the central nervous
system, and concludes that the effects of the cobra poison consist in
the extinction of function extending from below upwards of the various
nerve centres constituting the cerebro-spinal system. In addition to
this, there is a special and rapid action on the respiratory and allied
nuclei, and this it is that causes death.

§ 643. =Effects on Man.=--By far the best account hitherto published of
the effects of the cobra poison is a paper by Dr. Wall,[648] in which he
points out the very close similarity between the symptoms produced and
those of glosso-pharyngeal paralysis. This is well shown in the
following typical case:--A coolie was bitten on the shoulder about
twelve at midnight by a cobra; he immediately felt burning pain at the
spot bitten, which increased. In fifteen minutes afterwards he began, he
said, to feel intoxicated, but he seemed rational, and answered
questions intelligently. The pupils were natural, and the pulse normal;
the respirations were also not accelerated. He next began to lose power
over his legs, and staggered. In thirty minutes after the bite his lower
jaw began to fall, and frothy viscid mucous saliva ran from his mouth;
he spoke indistinctly, like a man under the influence of liquor, and the
paralysis of the legs increased. Forty minutes after the bite, he began
to moan and shake his head from side to side, and the pulse and
respirations were somewhat accelerated; but he was still able to answer
questions, and seemed conscious. There was no paralysis of the arms. The
breathing became slower and slower, and at length ceased one hour and
ten minutes after the bite, the heart beating for about one minute after
the respiration had stopped.

[648] “On the Difference of the Physiological Effects Produced by the
Poison of Indian Venomous Snakes,” by A. T. Wall, M.D., _Proc. Roy.
Soc._, 1881, vol. xxxii. p. 333.

There is often very little sign of external injury, merely a scratch or
puncture being apparent, but the areolar tissue lying beneath is of a
purple colour, and infiltrated with a large quantity of coagulable,
purple, blood-like fluid. In addition, the whole of the neighbouring
vessels are intensely injected, the injection gradually diminishing as
the site of the poisoned part is receded from, so that a bright scarlet
ring surrounds a purple area, and this in its turn fades into the normal
colour of the neighbouring tissues. At the margin is also a purple
blood-like fluid, replaced by a pinkish serum, which may often be traced
up in the tissues surrounding the vessels that convey the poison to the
system, and may extend a considerable distance. These appearances are to
be accounted for in great part by the irritant properties of the cobra
venom. The local hyperæmia and the local pain are the first symptoms. In
man there follows an interval (which may be so short as a few minutes,
or so long as four hours) before any fresh symptoms appear; the average
duration of the interval is, according to Dr. Wall, about an hour. When
once the symptoms are developed, then the course is rapid, and, as in
the case quoted, a feeling like that of intoxication is first produced,
and then loss of power over the legs. This is followed by a loss of
power over the speech, over swallowing, and the movement of the lips;
the tongue becomes motionless, and hangs out of the mouth; the saliva is
secreted in large quantities, and runs down the face, the patient being
equally unable to swallow it or to eject it, and the glosso-pharyngeal
paralysis is complete.

§ 644. =Antidotes and Treatment.=--Professor Halford some years ago
proposed ammonia, and M. Lacerda in recent times has declared potassic
permanganate an antidote to the cobra poison. The ammonia theory has
been long disproved, and before Lacerda had made his experiments I had
published the chemical aspect of some researches,[649] which showed that
mixing the cobra venom with an alkaline solution of potassic
permanganate destroyed its poisonous properties. Other experiments were
also made in every conceivable way with potassic permanganate, injecting
it separately, yet simultaneously, into different parts of the same
animal’s body, but so long as it does not come into actual contact with
the poison it has no antidotal power whatever over the living subject.
Other observers, previous to the researches mentioned and since, all
agree that permanganate is no true antidote.[650] It only acts when it
comes directly into contact with the venom, but when the venom is once
absorbed into the circulation potassic permanganate, whether acid,
alkaline, or neutral, is powerless. That it is of great use when applied
to a bite is unquestionable, for it neutralises or changes any of the
venom hanging about the wound, and which, if allowed to remain, might
yet be absorbed; but here it is obvious that the venom is, so to speak,
outside the body. A. Galmette (_Annales de l’Institut Pasteur_, 25th
March 1892) has found that gold chloride forms an insoluble compound
with the cobra poison, which is not poisonous, and that animal living
tissues impregnated with gold chloride will not absorb the poison. He
even advances some evidence tending to show that gold chloride may
overtake, as it were, the venom in the circulation, and thus act as a
true antidote. This is improbable, and, until confirmed, the general
treatment most likely to be successful is the immediate sucking of the
wound, followed by the application of an alkaline solution of
permanganate; and lastly, if the symptoms should nevertheless develop,
an attempt should be made to maintain the breathing by galvanism and
artificial respiration.[651]

[649] _Analyst_, Feb. 28, 1877.

[650] See Note on the effect of various substances in destroying the
activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer,
_Proc. Roy. Soc._, vol. xxvii. p. 17.

[651] Some of my experiments on the cobra poison may be briefly
detailed, illustrating the general statement in the text:--

1. A quantity equal to 1 mgrm. of the dried venom was injected
subcutaneously into a chicken. The symptoms began in two minutes with
loss of power over both legs. In eight minutes the legs were perfectly
paralysed. There were convulsive movements of the head and wings,
slowing of the respiration, and death in ten minutes. The same quantity
of poison was treated with a little tannin, and the clear liquid which
separated from the precipitate injected into another chicken. The
respiration became affected in ten minutes; in eighteen minutes the bird
had become very quiet, and lay insensible; in twenty minutes it was
dead, the respiration ceasing before the heart.

2. In seven experiments with cobra poison, first rendered feebly
alkaline with an alkaline solution of potassic permanganate, no effect
followed. Three of the experiments were on chickens, four on rabbits.

3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and
in the other simultaneously with a solution of potassic permanganate.
Death followed in sixteen minutes. Another chicken was treated in the
same way, but with injections of potassic permanganate solution every
few minutes. Death resulted in thirty-seven minutes. Four other similar
experiments were made--two with feebly alkaline permanganate, two with
permanganate made feebly acid with sulphuric acid--but death occurred
with the usual symptoms.

4. Cobra poison was mixed with a weak solution of iodine, and a quantity
equal to half a mgrm. was injected into a chicken. The symptoms began
directly, were fully developed in ten minutes, and death took place in
twenty-one minutes.

5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity
equivalent to 1 mgrm. of the cobra poison injected. The symptoms were
immediate paralysis and insensibility, and the respiration rapidly fell.
Death occurred in four minutes without convulsions.

6. The cobra venom was mixed with a feebly alkaline solution of
pyrogallic acid, and injected subcutaneously into a chicken. In six
minutes the usual symptoms commenced, followed in thirteen minutes by
death.

7. One mgrm. was injected into a chicken. The respirations at the
commencement were 120; in twenty-two minutes they sank to 96, in
twenty-five minutes to 84, in twenty-seven minutes to 18, and then to
occasional gasps, with slight movement of the wings and toes. There was
death in thirty-two minutes after the injection.

8. A young rabbit was injected with ·5 mg. (equal to 1 mgrm. per kilo.)
of cobra poison. In two hours it was apparently moribund, with
occasional short gasps. Artificial respiration was now attempted. There
was considerable improvement, but it was intermitted during the night,
and the animal was found dead in the morning, having certainly lived six
hours.

9. A strong healthy kitten was injected with 1 mgrm. of cobra venom
(equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well
developed, and in an hour the animal was gasping--about twelve short
respirations per minute. Artificial respiration was kept up for two
hours, and the animal recovered, but there was great muscular weakness
lasting for more than twenty-four hours.

10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms.
(6 per kilo.) of the cobra poison. The symptoms developed within ten
minutes; ammonia was injected, and also given by the nostril. The
heart’s action, which, previous to the administration of the ammonia,
had been beating feebly, became accelerated, but death followed within
the hour, the heart beating two minutes after the respiration had
ceased.

11. A brown rabbit, about 2 kilos. in weight, was injected with 1·5
mgrms. of cobra poison (·75 per kilo.). There were no symptoms for
nearly an hour, then sudden convulsions, and death.

12. Another rabbit of the same size was treated similarly, but
immediately after the injection made to breathe nitrous oxide; death
took place in thirty minutes. A rabbit, a little over 2 kilos. in
weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10
mgrms. of monobromated camphor were administered. In fifteen minutes
there was general paralysis of the limbs, from which in a few minutes
the animal seemed to recover; thirty minutes after the injection there
were no very evident symptoms, but within forty minutes there was a
sudden accession of convulsions, and death. Experiments were also made
with chloroform, morphine, and many other substances, but none seemed to
exercise any true antidotal effect.

§ 645. =Detection of the Cobra Venom.=--In an experiment on a rabbit,
the animal was killed by the subcutaneous injection of 8 mgrms. per
kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood
were injected into a small rabbit; in fifteen minutes there was slow
respiration with pains in the limbs; in thirty minutes this had, in a
great measure, passed off, and in a little time the animal was well. In
any case in which it is necessary to attempt to separate the cobra
venom, the most likely method of succeeding would be to make a cold
alcoholic extract, evaporate in a vacuum, take up the residue in a
little water, and test its effect on small animals.

§ 646. =Duboia Russellii.=--The _Duboia russellii_ or _Russell’s viper_
is one of the best known and most deadly of the Indian vipers. The
effects of the poison of this viper are altogether different from those
of the cobra. The action commences by violent general convulsions, which
are often at once fatal, or may be followed by rapid paralysis and
death; or these symptoms, again, may be recovered from, and death follow
at a later period. The convulsions do not depend on asphyxia, and with a
small dose may be absent. The paralysis is general, and may precede for
some time the extinction of the respiration, the pupils are widely
dilated, there are bloody discharges, and the urine is albuminous.
Should the victim survive the first effects, then blood-poisoning may
follow, and a dangerous illness result, often attended with copious
hæmorrhages. A striking example of this course is recorded in the
_Indian Med. Gaz._, June 1, 1872.

A Mahommedan, aged 40, was bitten on the finger by Russell’s viper; the
bitten part was soon after excised, and stimulants given. The hand and
arm became much swollen, and on the same day he passed blood by the
rectum, and also bloody urine. The next day he was sick, and still
passing blood from all the channels; in this state he remained eight
days, losing blood constantly, and died on the ninth day. Nothing
definite is known of the chemical composition of the poison; it is
probably qualitatively identical with “viperin.”

§ 647. =The Poison of the Common Viper.=--The common viper still abounds
in certain parts of Great Britain, as, for example, on Dartmoor. The
venom was analysed in a partial manner by Valentin. In 1843 Prince
Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and
transparent, which he called _echidnin_ or _viperin_; it was a neutral
nitrogenous body without taste, it arrested the coagulation of the
blood, and, injected into animals, produced all the effects of the bite
of the viper. Phisalix and G. Bertrand have studied the symptoms
produced in small animals after injection. A guinea-pig, weighing 500
grms., was killed by 0·3 grm. of the dried venom dissolved in 5000 parts
of saline water; the symptoms were nausea, quickly passing into stupor.
The temperature of the body fell. The autopsy showed the left auricle
full of blood, the intestine, lungs, liver, and kidneys injected. The
blood of the viper is also poisonous, and produces the same symptoms as
the venom.[652] The same observers have shown (_Compt. rend._, cxviii.,
Jan. 1894) that the blood of the water-snake (_Tropidonotus natrix_) and
of the Thuringian adder (_Tropidonotus viperinus_) is poisonous,
producing the same symptoms as that of the viper.

[652] _Compt. rend. Soc. de Biol._, t. v. 997.

=The Venom of Naja Haje= (=Cleopatra’s Asp=).--It has been stated that
20,000 persons annually die in Ceylon from the bite of Cleopatra’s asp.
Graziani (_Rif. Med._, October 7, 1893) has undertaken a physiological
study of the venom, which has already received attention at the hands of
Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The
venom, when dried, appears as transparent scales, easily soluble in
water, very slightly so in alcohol, ether, or chloroform; its aqueous
solution has an unpleasant odour, and is neutral to test paper.
Chemically it gives all the tests described by Weir Mitchell and others
as characteristic of the venom of _Naja tripudians_. The physiological
effects of this dried venom were tried on guinea-pigs, rabbits, and
frogs, to all of which it proved fatal in extremely minute doses. The
guinea-pig, a few seconds after injection, becomes paralysed in its hind
limbs, it foams at the mouth, and makes violent attempts at vomiting.
The eyes are half closed, but occasionally for short periods there is a
partial disappearance of the paralysis, and the animal makes feeble
attempts to support itself. Respiratory embarrassment is soon added to
the foregoing symptoms, and the animal lies perfectly prone, devoting
all its attention to breathing, which is rendered still more difficult
by the vomiting and frothy saliva which is secreted in abundance.
Finally death ensues from asphyxia. The _post-mortem_ examination
reveals the heart still feebly beating, the lungs pallid, and the blood
in the organs very dark. The liver and kidneys are hyperæmic, but the
brain and cord, with their coverings, are anæmic. In the rabbit the
course of the poisoning is practically identical with that described
above. Histologically, the following facts are made out in addition to
the foregoing. The red blood-corpuscles are in great measure broken
down, and there are also effusions into the muscular tissues. The
kidneys are very hyperæmic, and there is marked degeneration of the
epithelium lining the glomeruli and convoluted tubules. The glomerular
capsules are much distended, and numerous leucocytes are discernible
throughout the organ. The liver, also, is hyperæmic, and shows numerous
broken-down blood-corpuscles, and partial necrosis of many of the liver
cells. Examination of the central nervous system reveals no particular
changes.


DIVISION II.--PTOMAINES--TOXINES.

§ 648. =Definition of a Ptomaine.=--A ptomaine may be considered as a
basic chemical substance derived from the action of bacteria on
nitrogenous substances. If this definition is accepted, a ptomaine is
not necessarily formed in the dead animal tissue; it may be produced by
the living, and, in all cases, it is the product of bacterial life. A
ptomaine is not necessarily poisonous; many are known which are, in
moderate doses, quite innocuous.

When Selmi’s researches were first published there was some anxiety lest
the existence of ptomaines would seriously interfere with the detection
of poison generally, because some were said to be like strychnine,
others like colchicine, and so forth. Farther research has conclusively
shown that at present no ptomaine is known which so closely resembles a
vegetable poison as to be likely in skilled hands to cause confusion.


Isolation of Ptomaines.

§ 649. =Gautier’s[653] Process.=--The liquid is acidified with oxalic
acid, warmed, filtered, and distilled in a vacuum.

[653] _Ptomaines et Leucomaines_, E. J. A. Gautier, Paris, 1886.

In this way pyrrol, skatol, phenol, indol, and volatile fatty acids are
separated and will be found in the distillate. The residue in the retort
is treated with lime, filtered from the precipitate that forms, and
distilled in a vacuum, the distillate being received in weak sulphuric
acid. The bases accompanied with ammonia distil over. The distillate is
now neutralised by sulphuric acid[654] and evaporated nearly to dryness,
separating the mother liquid from sulphate of ammonia, which
crystallises out. The mother liquids are treated with absolute alcohol,
which dissolves the sulphates of the ptomaines. The alcohol is got rid
of by evaporation, the residue treated with caustic soda, and the bases
shaken out by successive treatment with ether, petroleum ether, and
chloroform. The residue remaining in the retort with the excess of lime
is dried, powdered, and exhausted with ether; the ethereal extract is
separated, evaporated to dryness, the dry residue taken up in a little
water, slightly acidulated, and the bases precipitated by an alkali.

[654] The first acid apparently is so dilute that the distillate more
than neutralises it, hence more sulphuric acid is added to complete
neutralisation.

§ 650. =Brieger’s Process.=--Brieger[655] thus describes his process:--

[655] _Untersuchungen über Ptomaine_, Theil iii., Berlin, 1886.

“The matters are finely divided and boiled with water feebly acidulated
with hydrochloric acid.

“Care must be taken that on boiling, the weak acid reaction must be
retained, and that this manipulation only lasts a few minutes.

[Illustration]

“The insoluble portion is filtered off, and the filtrate evaporated,
either in the gas-oven or on the water-bath, to syrupy consistency. If
the substances are offensive, as alcoholic and watery extracts of flesh
usually are, the use of Bocklisch’s simple apparatus (see diagram) is to
be recommended. The filtrate to be evaporated is placed in a flask
provided with a doubly perforated caoutchouc cork carrying two bent
tubes; the tube _b_ terminates near the bottom of the flask, while the
tube _a_ terminates a little above the level of the fluid to be
evaporated. The tube _a_ is connected with a water pump which sucks away
the escaping steam. In order to avoid the running back of the condensed
water forming in the cooler part of the tube, the end of the tube _a_ is
twisted into a circular form. Through the tube _b_, which has a fine
capillary bore, a stream of air is allowed to enter, which keeps the
fluid in constant agitation, continually destroying the scum on the
surface, and avoiding sediments collecting at the bottom, which may
cause fracture of the flask. According to the regulation of the air
current, a greater or smaller vacuum can be produced. The fluid,
evaporated to the consistency of a syrup, is treated with 96 per cent.
alcohol, filtered, and the filtrate precipitated with lead acetate.

“The lead precipitate is filtered off, the filtrate evaporated to a
syrup, and the syrup again treated with 96 per cent. alcohol. This is
again filtered, the alcohol got rid of by evaporation, water added, the
lead thrown down by SH₂, and the fluid, after the addition of a little
hydrochloric acid, evaporated to the consistence of a syrup; this syrup
is exhausted with 96 per cent. alcohol, and precipitated with an
alcoholic solution of mercury chloride. The mercury precipitate is
boiled with water, and by the different solubility of the mercury salts
of certain ptomaines some separation takes place. If it is suspected
that some of the ptomaines may have been separated with the lead
precipitate, this lead precipitate can be decomposed by SH₂ and
investigated. I have only (says Brieger) in the case of mussels been
able to extract from the lead precipitate small quantities of ptomaines.

“The mercury filtrate is freed from mercury and evaporated, the excess
of hydrochloric acid being carefully neutralised by means of soda (for
it must only be slightly acid); then it is again treated with alcohol,
so as to separate as much as possible the inorganic constituents. The
alcoholic extract is evaporated, dissolved in a little water,
neutralised with soda, acidulated with nitric acid, and precipitated
with phospho-molybdic acid. The phospho-molybdic acid precipitate is
decomposed with neutral lead acetate, which process may be facilitated
by heating on the water-bath. After getting rid of the lead by treatment
with SH₂, the fluid is evaporated to a syrup and alcohol added, by which
process many ptomaines may be eliminated as hydrochlorates; or they can
be converted into double salts (of platinum or gold) for the purpose of
separation. In the filtrate from phospho-molybdate, ptomaines may also
be found by treating with lead acetate to get rid of the
phospho-molybdic acid, and then adding certain reactives. Since it is
but seldom that the hydrochlorates are obtained in a state of purity, it
is preferable to convert the substance separated into a gold or platinum
salt or a picrate, since the greater or less solubility of these
compounds facilitates the purification of individual members; but which
reagent is best to add, must be learned from experience. The
melting-point of these salts must always be taken, so that an idea of
their purity may be obtained. It is also to be noted that many gold
salts decompose on warming the aqueous solution; this may be avoided by
the addition of hydrochloric acid. The hydrochlorates of the ptomaines
are obtained by decomposing the mercury, gold, or platinum combinations
by the aid of SH₂, while the picrates can be treated with hydrochloric
acid and shaken up with ether, which latter solvent dissolves the picric
acid.

“Considerable difficulty in the purification of the ptomaines is caused
by a nitrogenous, amorphous, non-poisonous, albumin-like substance,
which passes into all solutions, and can only be got rid of by careful
precipitation with an alcoholic solution of lead acetate, in which it is
soluble in excess. This albuminoid forms an amorphous compound with
platinum, and acts as a strongly reducing agent (the platinum compound
contains 29 per cent. platinum). When this albuminoid is eliminated,
then the hydrochlorates or the double salts of the ptomaines
crystallise.”

§ 651. =The Benzoyl Chloride Method.=--The fatty diamines in dilute
aqueous solutions, shaken with benzoyl chloride and soda, are converted
into insoluble dibenzoyl derivatives; these may be separated from
benzamide and other nitrogenous products by dissolving the precipitate
in alcohol, and pouring the solution into a large quantity of
water.[656] Compounds which contain two amido groups combined with one
and the same carbon atom, do not yield benzoyl derivatives when shaken
with benzoyl chloride and soda. Hence this reaction can be utilised for
certain of the ptomaines only. The solution must be dilute, because
concentrated solutions of creatine, creatinine, and similar bodies also
give precipitates with benzoyl chloride; no separation, however, occurs
unless these bodies are in the proportion of five per thousand.

[656] L. V. Udrànsky and Baumann, _Ber._, xxi. 2744.

The process is specially applicable for the separation of
ethylenediamine, pentamethylenediamine (cadaverine), and
tetramethylenediamine (putrescine) from urine. In a case of
cystinuria Udrànsky and E. Baumann[657] have found 0·24 grm. of
benzoyltetramethylenediamine, 0·42 grm. of benzoylpentamethylenediamine
in a day. Diamines are absent in normal fæces and urine. Stadthagen and
Brieger[658] have also found, in a case of cystinuria diamines, chiefly
pentamethylenediamine.

[657] L. V. Udrànsky and Baumann, _Zeit. f. physiol. Chem._, xiii. 562.

[658] _Arch. pathol. Anatom._, cxv. p. 3.

The operation is performed by making the liquid alkaline with soda, so
that the alkalinity is equal to about 10 per cent., adding benzoyl
chloride, shaking until the odour of benzoyl chloride disappears, and
then filtering; to the filtrate more benzoyl chloride is added, the
liquid shaken, and, if a precipitate appears, this is also filtered off,
and the process repeated until all diamines are separated.

The precipitate thus obtained is dissolved in alcohol, and the alcoholic
solution poured into a considerable volume of water and allowed to stand
over night; the dibenzoyl compound is then usually found to be in a
crystalline condition. The compound is crystallised once or twice from
alcohol or ether, and its melting-point and properties studied. Mixtures
of diamines may be separated by their different solubilities in ether
and alcohol.

A solution of 0·00788 grm. of pentamethylenediamine in 100 c.c. of water
gave 0·0218 grm. of the dibenzoyl-derivative when shaken with benzoyl
chloride (5 c.c.) and 40 c.c. of soda (10 per cent.) and kept for
twenty-four hours. In a second experiment with a similar solution only
0·0142 grm. of dibenzoyl-derivative was obtained;[659] hence the process
is not a good quantitative process, and, although convenient for
isolation, gives, so far as the total amount recovered is concerned,
varying results.

[659] _Ber._, xxi. 2744.

§ 652. =The Amines.=--The amines are bases originating from ammonia and
built on the same type. Those that are interesting as poisons are
monamines, diamines, and the quaternary ammonium bases.

Considered as compound ammonias, the amines are divided into primary or
amide bases, secondary or imid bases, and tertiary or nitrile bases,
according as to whether one, two, or three atoms of hydrogen have been
displaced from the ammonia molecule by an alkyl; for instance,
methylamine NH₂CH₃ is a primary or amide base, because only one of the
three atoms of H in NH₃ has been replaced by methyl; similarly,
dimethylamine is a secondary or imid base, and trimethylamine is a
tertiary or nitrile base.

The quaternary bases are derived from the hypothetical ammonium
hydroxide NH₄OH, as, for example, tetraethyl ammonium hydroxide
(C₂H₅)₄N,OH.

The diamines are derived from two molecules of NH, and therefore
contain, instead of one molecule of nitrogen, two molecules of nitrogen;
in two molecules of ammonia there are six atoms of hydrogen, two, four,
or six of which may be replaced by alkyls; as, for example,

    C₂H₄
    /  \
   /    \
  N--HH--N
   \    /
    \  /
     HH

  Ethylenediamine.

     C₂H₄
    /   \
   /     \
  N--C₂H₄--N
   \     /
    \   /
     HH

  Diethylenediamine.

     C₂H₄
    /   \
   /     \
  N--C₂H₄--N
   \     /
    \   /
     C₂H₄

  Triethylenediamine.

The monamines are similar to ammonia in their reactions; some of them
are stronger bases; for instance, ethylamine expels ammonia from its
salts. The first members of the series are combustible gases of pungent
odour, and easily soluble in water; the higher homologues are fluids;
and the still higher members solids.

The hydrochlorides are soluble in absolute alcohol, while chloride of
ammonium is insoluble; this property is taken advantage of for
separating amines from ammonia. The amines form double salts with
platinic chloride; this is also utilised for recognition, for the
purpose of separation, and for purification; for instance,
ammonium-platinum-chloride on ignition yields 43·99 per cent. of
platinum, and methylamine-platinum-chloride yields 47·4 of platinum. It
is comparatively easy to ascertain whether an amine is primary,
secondary, or tertiary.

The primary and secondary amines react with nitrous acid, but not the
tertiary; the primary amines, for instance, are converted into alcohols,
and there is an evolution of nitrogen gas; thus methylamine is
decomposed into methyl alcohol, nitrogen, and water.

  CH₃NH₂ + (OH)NO = CH₃(OH) + N₂ + H₂O.

The secondary amines, treated in the same way, evolve no nitrogen, but
are converted into nitrosamines; thus dimethylamine, when treated with
nitrous acid, yields nitrosodimethylamine,

  (CH₃)₂NH + (OH)NO = (CH₃)₂(NO)N + H₂O;

and the nitrosamines respond to the test known as Lieberman’s
nitroso-reaction, which is thus performed:--The substance is dissolved
in phenol and a few drops of concentrated sulphuric acid added. The
yellow colour at first produced changes into blue by adding to the acid
liquid a solution of potash.

The primary amines, and the primary amines alone, treated with
chloroform and alcoholic potash, yield the peculiarly offensive smelling
carbylamine or isonitrile (Hofmann’s test),

                             V
  NH₂(CH₃) + CHCl₃ + 3KOH = C≣N-CH₃ + 3KCl + 3H₂O.

Again the primary bases, when treated with corrosive sublimate and
carbon disulphide, evolve sulphuretted hydrogen, and mustard oil is
produced, _e.g._,

   NH₂(C₂H₅)   + CS₂ =  CS=N-C₂H₅   + H₂S.
  Ethylamine.        Ethylmustard
                         oil.

Where a sufficient quantity of an amine is obtained, the primary,
secondary, or tertiary character of the amine may be deduced with
certainty by treating it with methyl or ethyl iodide.

A molecule of the base is digested with a molecule of methyl iodide and
distilled with potash; the distillate is in the same manner again
treated with methyl iodide and again distilled; and the process is
repeated until an ammonium base is obtained, which will take up no more
iodide. If three methyl groups were in this way introduced, the original
substance was primary, if two, secondary, if one, tertiary.

The quaternary bases, such as tetraethyl ammoniumoxhydrate, decompose,
on heating, into triethylamine and ethylene; the corresponding methyl
compound in like manner yields trimethylamine and methyl-alcohol.

On the other hand, the primary, secondary, and tertiary bases do not
decompose on heating, but volatilise without decomposition.

The chief distinctions between these various amines are conveniently put
into a tabular form as follows:--

  +--------------------+-----------+-----------+-----------+-----------+
  |                    |  Primary, |Secondary, | Tertiary, |Quaternary,|
  |                    |   NH₂R.   |   NHR₂.   |    NR₃.   |  NR₄(OH). |
  +--------------------+-----------+-----------+-----------+-----------+
  |On treating with    |      3    |     2     |     1     |   ...     |
  |methyl iodide it    |           |           |           |           |
  |takes up the follow-|           |           |           |           |
  |ing number of methyl|           |           |           |           |
  |groups,             |           |           |           |           |
  |                    |           |           |           |           |
  |Reaction with       |Decomposes |Formation  |           |           |
  |nitrous acid,       |with evolu-|of nitro-  |   ...     |   ...     |
  |                    |tion of    |samine.    |           |           |
  |                    |nitrogen   |           |           |           |
  |                    |gas.       |           |           |           |
  |                    |           |           |           |           |
  |Mustard oil, &c., on|Mustard oil|           |           |           |
  |treatment with CS₂  |formed.    |   ...     |   ...     |   ...     |
  |and sublimate,      |           |           |           |           |
  |                    |           |           |           |           |
  |Chloroform and      |Formation  |   ...     |   ...     |   ...     |
  |alcoholic potash,   |of carbyl- |           |           |           |
  |                    |amine.     |           |           |           |
  |                    |           |           |           |           |
  |Effect of strong    |Sublimes.  |Sublimes.  |Sublimes.  |Decomposes.|
  |heat,               |           |           |           |           |
  |                    |           |           |           |           |
  |On addition of      |Combines to|Combines to|Combines to|   ...     |
  |acids,              |form salts.|form salts.|form salts.|           |
  +--------------------+-----------+-----------+-----------+-----------+

    § 653. =Methylamine,= CH₃NH₂.--This is a gas at ordinary
    temperatures; it is inflammable, and possesses a strong ammoniacal
    odour. It has been found in herring brine, and is present in
    cultures of the comma bacillus; it has also been found in poisonous
    sausages, but it is not in itself toxic.

    It forms crystalline salts, such as, for example, the hydrochloride,
    the platinochloride (Pt = 41·4 per cent.), and the aurochloride (Au
    = 53·3 per cent. when anhydrous). The best salt for estimation is
    the platinochloride, insoluble in absolute alcohol and ether.

    § 654. =Dimethylamine=, (CH₃)₂NH.--Dimethylamine is also a gas; it
    has been found in various putrefying substances. It forms
    crystalline salts, such as the hydrochloride, the platinochloride
    (Pt = 39·1 per cent.), and an aurochloride (Au = 51·35 per cent.).
    It is not poisonous.

    In Brieger’s process it may occur in both the mercuric chloride
    precipitate and filtrate. From cadaverine it may be separated by
    platinum chloride; cadaverine platinochloride is with difficulty
    soluble in cold water and crystallises from hot water, while
    dimethylamine remains in the mother liquor. From choline it may be
    separated by recrystallising the mercuric precipitate from hot
    water. From methylamine it may be separated by converting into
    chloride and extracting with chloroform; dimethylamine chloride is
    soluble, methylamine chloride insoluble in chloroform.

    § 655. =Trimethylamine=, (CH₃)₃N.--Trimethylamine in the free state
    is an alkaline liquid with a fishy odour, boiling at 9·3°; it is not
    toxic save in large doses.

    It occurs in a great variety of plants, and is also found in
    putrefying substances. It is a product of the decomposition of
    choline, betaine, and neuridine, when these substances are distilled
    with potash.

    In Brieger’s process, if an aqueous solution of mercuric chloride is
    used as the precipitant, trimethylamine (if present) will be almost
    entirely in the filtrate, from which it can be obtained by getting
    rid of the mercury by SH₂, filtering, evaporating to dryness,
    extracting with alcohol, and precipitating the alcoholic solution
    with platinic chloride. It forms crystalline salts with hydrochloric
    acid, platinum chloride, and gold chloride; the platinum double salt
    yields 37 per cent. of platinum, the gold salt 49·4 per cent. gold.
    The gold salt is easily soluble, and this property permits its
    separation from choline, which forms a compound with gold chloride
    soluble with difficulty.

    § 656. =Ethylamine=, C₂H₅NH₂.--Ethylamine is in the free state an
    ammoniacal liquid boiling at 18·7°. It is a strong base, miscible
    with water in every proportion. It has been found in putrefying
    yeast, in wheat flour, and in the distillation of beet sugar
    residues. It is not poisonous; the hydrochloride forms deliquescent
    plates melting at 76°-80°; the platinochloride contains 39·1 per
    cent. of platinum, and the gold salt 51·35 per cent. of gold. In
    other words, the same percentages as the corresponding salts of
    dimethylamine, with which, however, it cannot be confused.

    § 657. =Diethylamine=, (C₂H₅)₂NH, is an inflammable liquid boiling
    at 57·5°; it forms salts with hydrochloric acid, platinum and gold,
    &c.; the gold salt contains 47·71 per cent. of gold, and its
    melting-point is about 165°.

    § 658. =Triethylamine=, (C₂H₅)₃N, is an oily base but slightly
    soluble in water, and boiling at 89°-89·5°. It gives no precipitate
    with mercuric chloride in aqueous solution; it forms a
    platinochloride containing 31·8 per cent. of platinum. It has been
    found in putrid fish.

    § 659. =Propylamine.=--There are two propylamines; one, normal
    propylamine, CH₃CH₂.CH₂.NH₂, boiling at 47°-48°, and
    iso-propylamine, (CH₃)₂CH.NH₂, boiling at 31·5°; both are ammoniacal
    fish-like smelling liquids. The hydrochloride of normal propylamine
    melts at 155°-158°, and iso-propylamine chloride melts at 139·5°.

    It has been found in cultures of human fæces on gelatin. None of the
    above amines are sufficiently active in properties to be poisonous
    in the small quantities they are likely to be produced in
    decomposing foods.

    § 660. =Iso-amylamine=, (CH₃)₂CH.CH₂.CH₂.NH₂, is a colourless
    alkaline liquid, possessing a peculiar odour. It boils at 97°-98°.
    It forms a deliquescent hydrochloride. The platinochloride
    crystallises in golden yellow plates.

    Iso-amylamine occurs in the putrefaction of yeast, and is a normal
    constituent of cod-liver oil. It is intensely poisonous, producing
    convulsions.


Diamines.

§ 661. =Rate of Formation of Diamines.=--Diamines are formed in
putrefactive processes, generally where there is abundance of nitrogen.
Garcia[660] has attempted to trace the rates at which they are formed by
allowing meat extracts to decompose, precipitating by benzoyl chloride
(see p. 487) the dibenzoyl compound, and weighing; the following were
the results obtained:--

[660] _Zeit. f. physiol. Chemie_, xvii. 6. 571.

    Time.        Weight of benzoyl compound.
  24 hours,              0·56 grm.
   2 days,               0·75  „
   3 days,               0·82  „
   4 days,               0·73  „
   5 days,               0·57  „
   6 days,               0·58  „

    § 662. =Ethylidenediamine.=--Brieger found in putrid haddock, in the
    filtrate from the mercury chloride precipitate:--gadinine,
    neuridine, a base isomeric with ethylenediamine C₂H₈N₂ (but which
    Brieger subsequently more or less satisfactorily identified with
    ethylidenediamine), muscarine, and triethylamine; these bases were
    separated as follows:--

    The filtrate from the mercury chloride solution was freed from
    mercury by SH₂, evaporated to a syrup, and then extracted with
    alcohol. From the alcoholic solution platinum chloride precipitated
    neuridine, this was filtered off, the filtrate freed from alcohol
    and platinum, and the aqueous solution concentrated to a small
    volume and precipitated with an aqueous solution of platinum
    chloride; this precipitated ethylidene platinum chloride. The mother
    liquor from this precipitate was concentrated on the water-bath,
    and, on cooling, the platinochloride of muscarine crystallised out.
    From the mother liquor (freed from the crystals), on standing in a
    desiccator, the gadinine double salt crystallised out, and from the
    mother liquor (freed from gadinine after removal of the platinum by
    SH₂) distillation with KHO recovered trimethylamine.

    From the platinochloride of ethylenediamine, the chloride can be
    obtained by treating with SH₂, filtering, and evaporating; by
    distilling the chloride with a caustic alkali, the free base can be
    obtained by distillation.

    Ethylidenediamine is isomeric with ethylenediamine, but differs from
    it in the following properties:--ethylidenediamine is poisonous,
    ethylenediamine is non-poisonous.

    Ethylenediamine forms a platinochloride almost insoluble in hot
    water, while the ethylidene salt is more easily soluble. The
    properties of the gold salts are similar, ethylenediamine forming a
    difficultly soluble gold salt, ethylidene a rather soluble gold
    salt.

    Ethylidenediamine forms a hydrochloride, C₂H₈N₂2HCl, crystallising
    in long glistening needles, insoluble in absolute alcohol, rather
    soluble in water. The hydrochloride gives precipitates in aqueous
    solution with phospho-molybdic acid, phospho-antimonic acid, and
    potassium bismuth iodide; the latter is in the form of red plates.

    The platinochloride, C₂H₈N₂2HCl.PtCl (Pt = 41·5 per cent.), is in
    the form of yellow plates, not very soluble in cold water.

Ethylidenediamine, when subcutaneously injected into guinea-pigs,
produces an abundant secretion from the mucous membranes of the nose,
mouth, and eyes. The pupils dilate, and the eyeballs project. There is
acute dyspnœa; death takes place after some twenty-four hours, and the
heart is stopped in diastole.

Trimethylenediamine is believed to have been isolated by Brieger from
cultivations in beef broth of the comma bacillus.

It occurs in small quantity in the mercuric chloride precipitate, and is
isolated by decomposing the precipitate with SH₂, evaporating the
filtrate from the mercury sulphide to dryness, taking up the residue
with absolute alcohol, and precipitating by an alcoholic solution of
sodium picrate. The precipitate contains the picrate of
trimethylenediamine, mixed with the picrates of cadaverine and
creatinine. Cadaverine picrate is insoluble in boiling absolute alcohol,
the other picrates soluble; so the mixed picrates are boiled with
absolute alcohol, and the insoluble cadaverine filtered off. Next, the
picrates of creatinine and trimethylenediamine are freed from alcohol,
the solution in water acidified with hydrochloric acid, the picric acid
shaken out by treatment with ether, and then the solution precipitated
with platinum chloride; the platinochloride of trimethylenediamine is
not very soluble, while creatinine easily dissolves; so that separation
is by this means fairly easy.

It also gives a difficultly soluble salt with gold chloride.

The picrate consists of felted needles, melting-point 198°.
Phospho-molybdic acid gives a precipitate crystallising in plates;
potassium bismuth iodide gives dark coloured needles.

It produces in animals violent convulsions and muscular tremors; but the
substance has hitherto been obtained in too small a quantity to be
certain as to its identification and properties.

§ 663. =Neuridine=, C₅H₁₄N₂.--Neuridine is a diamine, and is apparently
the most common basic product of putrefaction; it has been obtained from
the putrefaction of gelatin, of horseflesh, of fish, and from the yelk
of eggs. It is usually accompanied by choline, from which it can be
separated by converting the bases into hydrochlorides, choline
hydrochloride being soluble in absolute alcohol, neuridine scarcely so.
Brieger isolated neuridine from putrid flesh by precipitating the watery
extract with mercuric chloride. He decomposed the mercury precipitate
with SH₂, and, after having got rid of the sulphide of mercury by
filtration, he concentrated the liquid to a small bulk, when a substance
separated in crystals similar in form to urea; this was purified by
recrystallisation from absolute alcohol, and converted into the platinum
salt.

Another method which may be used for the separation and purification of
neuridine is to dissolve it in alcohol and precipitate with an alcoholic
solution of picric acid; the picrate may be decomposed by treatment with
dilute mineral acid, and the picric acid removed by shaking with ether.

The free base has a strong seminal odour. It is gelatinous, and has not
been crystallised. It is insoluble in ether and in absolute alcohol, and
not readily soluble in amyl alcohol. It gives white precipitates with
mercuric chloride, neutral and basic lead acetates. It does not give
Hofmann’s isonitrile reaction. When distilled with a fixed alkali, it
yields di- and trimethylamine.

The hydrochloride, C₅H₁₄N₂2HCl, crystallises in long needles, which are
insoluble in absolute alcohol, ether, benzol, chloroform, petroleum
ether, and amyl alcohol; but the hydrochloride is very soluble in water
and in dilute alcohol.

The hydrochloride gives no precipitate with mercuric chloride,
potass-mercuric iodide, potass-cadmium iodide, iodine and iodide of
potassium, tannic acid, ferricyanide of potassium, ferric chloride, and
it does not give any colour with Fröhde’s reagent.

On the other hand, phosphotungstic acid, phospho-molybdic acid, picric
acid, potass-bismuth iodide, platinum chloride, and gold chloride all
give precipitates.

Neuridine hydrochloride is capable of sublimation, and at the same time
it is decomposed, for the sublimed needles show red or blue colours.

Neuridine platinochloride, C₅H₁₄N₂2HCl.PtCl₄, yields 38·14 per cent. of
platinum; it crystallises in flat needles, soluble in water, from which
it is precipitated on the addition of alcohol.

The aurochloride has the formula C₅H₁₄N₂2HCl2AuCl₃; it is rather
insoluble in cold water, and crystallises in bunches of yellow needles.
On ignition, it should yield 41·19 per cent. of gold.

The picrate, C₅H₁₄N₂,2C₆H₂(NO₂)₃OH, is almost insoluble in cold water,
and crystallises in needles. It is not fusible, but decomposes at about
230°.

Neuridine is not poisonous.

§ 664. =Cadaverine= (Pentamethylenediamine, C₅H₁₄N₂ =
NH₂CH₂--CH₂--CH₂--CH₂CH₂NH₂) is formed in putrid animal matters, and in
cultures of the genus _Vibrio_. It has been found in the urine and fæces
in cases of cystinuria, and Roos[661] has separated it by the
benzoyl-chloride method from the fæces of a patient suffering from
tertian ague. It may be formed synthetically by dissolving
trimethylcyanide in absolute alcohol, and then reducing by sodium
(Mendius’ reaction).

[661] _Zeit. f. physiol. Chemie_, xvi., 1892.

Cadaverine is a thick, clear, syrupy liquid, with a peculiar coniine- as
well as a semen-like odour. It absorbs eagerly CO₂ from the air, and
ultimately is converted into a solid crystalline mass. It volatilises
with the steam when boiled with water, and may be distilled in the
presence even of the caustic alkalies and the alkaline earths without
decomposition. It does not give oil of mustard when treated with CS₂ and
mercuric chloride, nor does it give with chloroform and alcoholic
potash, carbylamine (isonitrile). If dehydrated by KHO, it boils at from
115°-120° (_Brieger_).[662]

[662] Brieger has also given to the pure base a boiling-point of 175°.

When cadaverine is treated with methyl iodide, two atoms of hydrogen may
be replaced with methyl, forming the base C₅H₁₂(CH₃)₂N₂; the
platinochloride of this last base crystallises in long red needles.

Cadaverine forms well-defined crystalline salts as well as compounds
with metals.

Cadaverine hydrochloride, C₅H₁₄N₂2HCl, crystallises in needles which are
deliquescent, or it may be obtained from an alcoholic solution in
plates. The crystals are insoluble in absolute alcohol, but readily
soluble in 96 per cent. alcohol. Putrescine hydrochloride, on the other
hand, is with difficulty soluble in alcohol of that strength; hence the
two hydrochlorides can be separated by taking advantage of their
difference in solubility in 96 per cent. alcohol; but the better
method for separation is the benzoyl-chloride process (p. 487). On
dry distillation, cadaverine hydrochloride decomposes into
NH₃,HCl and piperidine C₅H₁₁N. The compound with mercury
chloride--C₅H₁₄N₂2HCl,4HgCl₂ (Hg = 63·54 per cent.); melting-point,
214°-216°--is insoluble in alcohol and in cold water; this property is
also useful to separate it from putrescine, the mercury compound of
which is soluble in cold water. The platinochloride, C₅H₁₄N₂2HCl,PtCl₄
(Pt = 38·08 per cent.), crystallises in dirty red needles; but, by
repeated crystallisation, it may be obtained in clear chrome yellow,
short, octahedral prisms; it is soluble with difficulty in hot water,
insoluble in cold water. The salt decomposes at 235°-236°.

The aurochloride--C₅H₁₄N₂2HCl2AuCl (Au = 50·41 per cent.), melting-point
188°--crystallises partly in cubes and partly in needles, and is easily
soluble in water.

Other salts are the picrate, C₅H₁₄N₂2C₆H₂(NO₂)₃OH, melting-point 221°
with decomposition; with difficulty soluble in cold, but dissolving in
hot water, and insoluble in absolute alcohol. There are also a neutral
oxalate, C₅H₁₄N₂,H₂C₂O₄ + 2H₂O, melting-point 160°; and an acid oxalate,
C₅H₁₄N₂2H₂C₂O₄ + H₂O, melting-point 143° with decomposition; both these
oxalates are insoluble in absolute alcohol.

Cadaverine dibenzoyl--C₅H₁₀(NHCOC₆H₅)₂, melting-point
129°-130°--crystallises in needles and plates, soluble in alcohol and
slightly soluble in ether, insoluble in water.

It is not acted on by hot dilute acids or alkalis, and when dissolved in
concentrated hydrochloric acid and alcohol it is, only after prolonged
boiling, decomposed into benzoic acid and the free base. The benzoic
acid after getting rid of the alcohol by evaporation, can be removed by
shaking up with ether; then the hydrochloride can be decomposed by an
alkali and the free base obtained, or the platinum salt of cadaverine
may be formed by precipitation with platinum chloride. Should cadaverine
and putrescine be in the same liquid, the dibenzoyl compounds may be
separated as follows:--the crystalline precipitate is collected on a
filter, washed with water until the filtrate runs clear, and then
dissolved in warm alcohol; this solution is poured into twenty times its
volume of ether and allowed to stand; after a short time crystals form
of the putrescine compound, which are far less soluble in alcohol than
those of cadaverine dibenzoyl; these crystals are filtered off and
repeatedly crystallised from alcohol until the melting-point is about
175°-176°. The filtrate contains the cadaverine compound; this latter is
recovered by evaporating off the ether-alcohol.

§ 665. =Putrescine--Tetramethylenediamine=,

  C₄H₁₂N₂=NH₂CH₂CH₂CH₂CH₂NH₂.

The free base is a clear liquid, with a semen-like odour, boiling-point
135°. It is a common base in putrefying animal substances, and also
occurs in the urine in cases of cystinuria. It can be obtained
synthetically by reducing ethylene cyanide by the action of sodium in
absolute alcohol.

The best method of separating putrescine is the benzoyl chloride method
already given.

Putrescine forms crystalline salts, of which the following are the most
important:--

Putrescine hydrochloride, C₄H₁₂N₂2HCl, forms long colourless needles,
insoluble in absolute alcohol, easily soluble in water.

The platinochloride, C₄H₁₂N₂2HCl.PtCl₄ (Pt = 39·2 per cent.), is with
difficulty soluble in cold water. When pure, the salt is in the form of
six-sided plates.

The aurochloride, C₄H₁₂N₂2HCl.2AuCl₃ + 2H₂O (Au = 51·3 per cent.), is
insoluble in cold water, in contradistinction to cadaverine
aurochloride, which easily dissolves.

The picrate, C₄H₁₂N₂2C₆H₂(NO₂)₃OH, is a salt of difficult solubility. It
crystallises in yellow plates. It browns at 230°, and melts with
evolution of gas at 250°.

Dibenzoylputrescine, C₄H₈(NHCOC₆H₅)₂, forms silky plates or long
needles, melting-point 175°-176°. By boiling it for twelve hours with
alcohol and strong hydrochloric acid the compound may be broken up into
hydrochloride of putrescine and free benzoic acid. As stated before, it
is less soluble in alcohol than the corresponding compound of
cadaverine.

Putrescine is not poisonous. On the other hand, by repeated treatment
with methyl iodide, it takes up four methyl radicals, and the
tetramethyl compound, C₄H₈(CH₃)₄N₂, produces symptoms similar to those
of muscarine poisoning.

§ 666. =Metaphenylenediamine=,

      NH₂¹
     /
  C₆H₄    ,
     \
      NH₂³

is a crystalline substance, melting-point 63°, boiling-point 276°-277°.
The crystals are easily soluble in alcohol or ether, with difficulty in
water. The least trace of nitrous acid strikes a yellow colour from the
formation of triamidobenzol.

§ 667. =Paraphenylenediamine=,

      NH₂¹
     /
  C₆H₄    ,
     \
      NH₂⁴

is in the form of tabular crystals, melting-point 140°, boiling-point
267°. If this substance is oxidised with ferric chloride or manganese
binoxide and sulphuric acid, chinone is produced; if treated with SH₂
and ferric chloride, a violet sulphur-holding colouring matter, allied
to methylene blue, is formed; these reactions are tests for the presence
of the para-compound.

Both these diamines are poisonous. Metaphenylenediamine produces, in the
dog, the symptoms of an aggravated influenza with continual sneezing and
hoarse cough, which, if the dose is large enough, ends in coma and
death. Paraphenylenediamine produces exophthalmia, the tissues of the
eye undergoing complete alteration.[663]

[663] _Comptes Rend._, cvii. 533-535.

Both compounds, in doses of 100 mgrms. per kilo., cause more or less
salivation, with diarrhœa. The para-compound is more poisonous than the
meta-compound. So far as the author is aware, neither of these diamines
have been separated with certainty from the urine of sick persons, nor
from products of decomposition.

§ 668. =Hexamethylenediamine=, C₆H₁₆N₂.--Hexamethylenediamine has been
found by A. Garcia[664] in a putrefying mixture of horse-flesh and
pancreas.

[664] _Zeit. f. physiol. Chemie_, xvii. 543-555.

§ 669. =Diethylenediamine=, C₄H₁₀N₂, is a crystalline substance,
melting-point 104°, boiling-point 145°-146°. After melting, it
solidifies on cooling, forming a hard crystalline mass. It is extremely
soluble in water, and is deposited from alcohol in large transparent
crystals. A technical product called “spermin piperazidin” or
“piperazine” has been found by A. W. v. Hoffmann[665] to be identical
with diethylenediamine. The hydrochloride crystallises in colourless
needles, insoluble in alcohol, readily soluble in water. The
platinochloride, C₄H₁₀N₂H₂PtCl₆, is in small yellow needles, and is
fairly easily soluble in hot water, but dissolves but slightly in hot
alcohol. The mercuro-chloride, C₄H₁₀N₂H₂HgCl₄, crystallises in
concentrically grouped needles, and is readily soluble in hot water, but
is reprecipitated on adding alcohol. The picrate, C₄H₁₀N₂,C₆H₂(NO₂)₃OH,
crystallises from water in yellow needles, almost insoluble in
alcohol.[666]

[665] _Ber._, xxiii. 3297-3303.

[666] Sieber, J., _Ber._, xxiii. 326-327.

§ 670. =Mydaleine= is a poisonous base discovered by Brieger in putrid
animal matters. It is probably a diamine, but has not been obtained in
sufficient quantity for accurate chemical study. The platinochloride is
extremely soluble in water, and only comes down from an absolute alcohol
solution. It has been obtained in a crystalline form, giving on analysis
38·74 per cent. of platinum, C. 10·83 per cent., H. 3·23 per cent.

Mydaleine is very poisonous. Small quantities injected into guinea-pigs
cause dilatation of the pupil, an abundant secretion from the nose and
eyes, and a rise of temperature. Fifty mgrms. cause death. The
_post-mortem_ appearances are not distinctive; the heart is arrested in
diastole; the intestines and bladder are contracted. In cats it causes
profuse diarrhœa and vomiting.

§ 671. =Guanidine.=--Guanidine may be considered to have a relation to
urea; for, if the oxygen of urea is replaced by the imide group NH,
guanidine originates thus:--

             NH₂
            /
  Urea = O=C
            \
             NH₂

                  NH₂
                 /
  Guanidine = NHC
                 \
                  NH₂

Hence guanidine from its structural formula is a carbodiamidimide.
Guanidine may be formed by the action of oxidising agents, such as
potassic chlorate and hydrochloric acid, on guanine; or by heating amide
cyanide with ammonium chloride, and so forming guanidine chloride. It is
also produced from the oxidation of albumin. When boiled with
baryta-water it decomposes into urea and ammonia. It combines with acids
to form salts; the gold salt, CH₅N₃HCl,AuCl₃, is in the form of long
yellow needles, with difficulty soluble in water. Guanidine nitrate,
CH₅N₃HNO₃, is also almost insoluble in cold water and similar to urea
nitrate. By dissolving equivalent parts of phenol and guanidine in hot
alcohol, triphenylguanidine is formed; on adding picric acid to a
solution of triphenylguanidine, phenylguanidine picrate,
CH₂Ph₃N₃C₆H₂(NO₂)₃OH, is formed, and falls as a precipitate of slender
needles, melting-point 208°; this picrate is very slightly soluble, 1
part dissolving in 12,220 parts of water at 15°. Guanidine is
poisonous.[667]

[667] O. Prelinger, _Monatsb._, xiii. 97-100.

A method of separating guanidine from urine has been worked out by
Gergers and Baumann.[668] The principle of the method is based upon the
fact that guanidine is precipitated by mercurous oxide. The urine is
precipitated by hydrate of baryta, the precipitate filtered off, the
alkaline filtrate neutralised by hydrochloric acid, and the neutral
filtrate evaporated to a syrup on the water-bath; the syrup is exhausted
by absolute alcohol, and the alcoholic solution filtered; this filtrate
is freed from alcohol by distillation, the alcohol-free residue
dissolved in a little water, shaken up with freshly precipitated mercury
oxide, and allowed to stand for two days in a warm place; the
precipitate formed is collected, acidulated with HCl and treated with
SH₂; the mercury sulphide thus obtained is separated by filtration, the
filtrate evaporated, and the residue dissolved in absolute alcohol. This
solution is precipitated by platinum chloride, filtered, separated from
any platinum ammonium salt, and evaporated to a small volume. After long
standing the guanidine salt crystallises out. The best method to
identify it appears to be, to ascertain the absence of ammonia and of
urea, and then to gently warm the supposed guanidine with an alkali,
which breaks guanidine up into ammonia and urea, according to the
following equation:--

  NH=C(NH₂)₂ + H₂O = NH₃ + CO(NH₂)₂.

[668] Pflüger’s _Archiv_, xii. 205.

The physiological effects of guanidine are as follows:--

A centigrm. of guanidine salt injected into the lymph sac in the back of
frogs produces, after a few minutes, muscular convulsions: first, there
are fibrillar twitchings of the muscles of the back; next, these spread
generally so that the whole surface of the frog seems to be in a
wave-like motion. Irritation of the limbs produces tetanus. There is, at
the same time, increased secretion from the skin. The breathing is
irregular. In large doses there is paralysis and death. The heart is
found arrested in diastole. The fatal dose for a frog is 50 mgrms.; but
1 mgrm. will produce symptoms of illness. In dogs there is paralysis,
convulsions, vomiting, and difficult breathing.

§ 672. =Methylguanidine=,

       NH.CH₃
      /
  NH=C      .
      \
       NH₂

--Methylguanidine has been isolated by Brieger from putrefying
horse-flesh; it has also been found in impure cultures in beef broth of
Finkler and Prior’s _Vibrio proteus_. Bocklisch isolated it, working
with Brieger’s process, from the mercuric chloride precipitate, after
removal of the mercury and concentration of the filtrate, by adding a
solution of sodium picrate. The precipitate contained the picrates of
cadaverine, creatinine, and methylguanidine; cadaverine picrate,
insoluble in boiling absolute alcohol, was separated by filtering from a
solution of the picrates of the bases in boiling absolute alcohol; the
alcohol was evaporated from the filtrate and the residue taken up with
water. From this aqueous solution the picric acid was removed and then
the solution precipitated with gold chloride; methylguanidine was
precipitated, while creatinine remained in solution.

Methylguanidine aurochloride, C₂H₇N₃HCl.AuCl₃ (Au = 47·7 per cent.),
forms rhombic crystals easily soluble in alcohol and ether;
melting-point 198°. The hydrochloride, C₂H₇N₃HCl, crystallises in
needles insoluble in alcohol. The picrate, C₂H₇N₃C₆H₂(NO₂)₃OH, comes
down at first as a resinous mass, but, after boiling in water, is found
to be in the form of needles soluble in hot absolute alcohol;
melting-point 192°. The symptoms produced by methylguanidine are rapid
respiration, dilatation of the pupils, paralysis, and death, preceded by
convulsions. The heart is found arrested in diastole.

§ 673. =Saprine=, C₅H₁₄N₂.--Saprine is isomeric with cadaverine and
neuridine; it was found by Brieger in human livers and spleens after
three weeks’ putrefaction. Saprine occurs, in Brieger’s process, in the
mercury precipitate. Its reactions are very similar to those of
cadaverine; the main difference being that cadaverine hydrochloride
gives a crystalline aurochloride, saprine does not; the platinum salt is
also more soluble in water than the cadaverine salt. It is not
poisonous.

§ 674. =The Choline Group.=--The choline group consists of choline,
neurine, betaine, and muscarine.

All these bodies can be prepared from choline; their relationship to
choline can be readily gathered from the following structural formulæ:--

  CH₂OH
  |
  CH₂
  |
  N(CH₃)₃.OH

  Choline.

  CH₂
  ║
  CH
  |
  N(CH₃)₃.OH

  Neurine.

  CO₂H
  |
  CH₂
  |
  N(CH₃)₃.OH

  Betaine.

  CH₂OH
  |
  CHOH
  |
  N(CH₃)₃.OH

  Muscarine.

Choline is a syrup with an alkaline reaction. On boiling with water, it
decomposes into glycol and trimethylamine. It gives, when oxidised,
muscarine. It forms salts. The hydrochloride is soluble in water and
absolute alcohol; neurine hydrochloride and betaine hydrochloride are
but little soluble in absolute alcohol, therefore this property can be
utilised for their separation from choline. The platinochloride is
insoluble in absolute alcohol; it melts at 225° with effervescence, and
contains 31·6 per cent. of platinum. The mercurochloride is soluble with
difficulty even in hot water. The aurochloride (Au = 44·5 per cent.) is
crystalline, and with difficulty soluble in cold water; but is soluble
in hot water and in alcohol; melting-point 264° with decomposition.

Choline is only poisonous in large doses.

§ 675. =Neurine= (Trimethyl-vinyl-ammonium hydrate),
C₂H₃N(CH₃)₃OH.--Neurine is one of the products of decomposition of
choline. It is poisonous, and has been separated by Brieger and others
from decomposing animal matters. In Brieger’s process, neurine, if
present, will be for the most part in the mercuric chloride precipitate,
and some portion will also be in the filtrate. The mercury precipitate
is decomposed by SH₂, the mercury sulphide filtered off, and the
filtrate, concentrated, treated with absolute alcohol and then
precipitated by platinum chloride. It is usually accompanied by choline;
the platinochloride of choline is readily soluble in water, neurine
platinochloride is soluble with difficulty; this property is taken
advantage of, and the platinochloride crystallised from water until
pure. Neurine has a strong alkaline reaction.

Neurine chloride, C₅H₁₂N.Cl, crystallises in fine needles. The
platinochloride, (C₅H₁₂NCl)₂PtCl₄ (Pt = 33·6 per cent.), crystallises in
octahedra. The salt is soluble with difficulty in hot water.

The aurochloride, C₅H₁₂NClAuCl₃ (Au = 46·37 per cent.), forms flat
prisms, which, according to Brieger, are soluble with difficulty in hot
water.

Neurine is intensely poisonous, the symptoms being similar to those
produced by muscarine.

Atropine is an antidote to neurine, relieving in suitable doses the
effects, and even rendering animals temporarily immune against the toxic
action of neurine.

When a fatal dose of neurine is injected into a frog there is in a short
time paralysis of the extremities. The respiration stops first, and
afterwards the heart, the latter in diastole.

The symptoms in rabbits are profuse nasal secretion and salivation with
paralysis, as in frogs. Applied to the eye, neurine causes contraction
of the pupil; to a less degree the same effect is produced by the
ingestion of neurine.

=Trimethyloxyammonium= hydrochloride causes similar symptoms to neurine,
but the action is less powerful.--V. Cervello, _Arch. Ital. Biol._, vii.
232-233.

§ 676. =Betaine.=--Betaine may be separated from a solution in alcohol
as large deliquescent crystals; the reaction of the crystals is neutral.
Distilled with potash, trimethylamine and other bases are formed.

Betaine chloride, C₅H₁₂NO₂Cl, forms plates permanent in the air and
insoluble in absolute alcohol. A solution of the chloride in water
gives, with potassium mercuric iodide, a light yellow or whitish yellow
precipitate, soluble in excess; but, on rubbing the sides of the tube
with a glass rod, the oily precipitate crystallises as yellow needles;
probably this is characteristic.

The aurochloride (Au = 43·1 percent.) forms fine cholesterine plates,
soluble in water; melting-point 209°. Betaine is not poisonous.

§ 677. =Peptotoxine.=--Brieger submitted to the action of fresh gastric
juice moist fibrin for twenty-four hours at blood heat. The liquid was
evaporated to a syrup and boiled with ethylic alcohol, the ethylic
alcohol was evaporated, the residue digested with amylic alcohol, and
the amyl alcohol in its turn evaporated to dryness; the residue was a
brown amorphous mass that was poisonous. It was farther purified by
treating the extract with neutral lead acetate and then filtered; the
filtrate was freed from lead by SH₂ and treated with ether, the ethereal
extract being then separated and evaporated to dryness; this last
residue was taken up with amyl alcohol, the alcohol evaporated to
dryness, and the residue finally taken up with water and filtered. The
filtrate is poisonous. The poisonous substance, to which Brieger gave
the provisional name of peptotoxine, is a very stable substance,
resisting the action of a boiling temperature, and even the action of
strong alkalies. It gives precipitates with alkaloidal group reagents,
and strikes a blue colour with ferric chloride and ferricyanide of
potassium. The most characteristic test seems to be its action with
Millon’s reagent (a solution of mercury nitrate in nitric acid
containing nitrous acid); this gives a white precipitate which, on
boiling, becomes intensely red.

It is poisonous, killing rabbits in doses of 0·5 grm. per kilogrm., with
symptoms of paralysis and coma. The nature of this substance requires
further elucidation.

§ 678. =Pyridine Alkaloid from the Cuttle Fish.=--O. de Coninck[669] has
obtained, by Gautier’s process, an alkaloid from the cuttle fish, of the
formula C₈H₁₁N, in the form of a yellow, mobile, strongly odorous
liquid, very soluble in alcohol, ether, and acetone, boiling-point 202°.
It quickly absorbs moisture from the air. It forms two mercuric
chlorides, one of which has the formula (C₈H₁₁N,HCl)₂HgCl₂; this
compound crystallises in small white needles, slightly soluble in water
and dilute alcohol, but insoluble in absolute alcohol, and decomposing
when exposed to moist air. The other salt is a sesqui-salt, forming long
yellowish needles, insoluble in ordinary solvents, and decomposing when
exposed to moist air. The alkaloid also forms deliquescent very soluble
salts with hydrochloric and hydrobromic acids. A platinum salt is also
formed, (C₈H₁₁N)₂H₂PtCl₆; it is of a deep yellow colour, almost
insoluble in cold, but soluble in hot water; it is decomposed by boiling
water, with the formation of a very insoluble compound in the shape of a
brown powder, (C₈H₁₁N)₂PtCl₄. Coninck’s alkaloid, on oxidation with
potassic permanganate, yields a gummy acid; this acid, on purifying it
by conversion into a potassium salt and then into a cupric salt, was
found to be nicotinic acid; so that the alkaloid is undoubtedly a
pyridine compound; indeed, the acid, distilled with lime, yields
pyridine.

[669] _Comptes Rend._, cvi. 858, 861; cviii. 58-59, 809-810; cvi.
1604-1605.

§ 679. =Poisons connected with Tetanus.=--Brieger, in 1887, isolated a
base of unknown composition, to which he gave the name of
“spasmotoxine.” It was produced in cultures of the tetanus bacillus in
beef broth.

Two more definite substances have also been discovered, viz., tetanine
and tetanotoxine.

=Tetanine=, C₁₃H₃₀N₂O₄, is best isolated by the method of Kitasato and
Weyl.[670] Their method of treating broth cultures of the tetanus
bacillus is as follows:--

[670] _Zeit. f. Hygiene_, viii. 404.

The broth is digested with 0·25 per cent. HCl for some hours at 460°,
then rendered feebly alkaline, and distilled in a vacuum. The residue in
the retort is then worked up for tetanine by Brieger’s method; the
distillate contains tetanotoxine, ammonia, indol, hydrogen sulphide,
phenol, and butyric acid. On treating the contents of the retort by
Brieger’s mercury chloride method, the filtrate contains most of the
poison. The mercury is removed by SH₂, the filtered solution evaporated
and exhausted by absolute alcohol, in which the tetanine dissolves. Any
ammonium chloride is thus separated, ammonium chloride being insoluble
in absolute alcohol. The alcoholic solution, filtered from any insoluble
substance, is next treated with an alcoholic solution of platinum
chloride, which precipitates creatinine (and any ammonium salts), but
does not precipitate tetanine. The platinum salt of tetanine may,
however, be precipitated by the addition of ether to the alcoholic
solution. The platinum salt, as obtained by precipitation from ether, is
very deliquescent; it has, therefore, to be rapidly filtered off and
dried in a vacuum. It can then be recrystallised from hot 96 per cent.
alcohol, forming clear yellow plates; these plates, if dried in a
vacuum, become with difficulty soluble in water.

Tetanine may be obtained as a free base by treating the hydrochloride
with freshly precipitated moist silver oxide. It forms a strongly
alkaline yellow syrup, and is easily decomposed in acid solution, but is
permanent in alkaline solutions.

The platinochloride, as before observed, is precipitable by ether from
alcoholic solution; it contains 28·3 per cent. of platinum, and
decomposes at 197°.

The base produces tetanus.

§ 680. =Tetanotoxine= may be distilled, and be found in the distillate
with other matters. It forms an easily soluble gold salt, melting-point
130°. The platinochloride is soluble with difficulty, and decomposes at
240°. The hydrochloride is soluble in alcohol and in water,
melting-point about 205°.

Tetanotoxine produces tremor, then paralysis, and lastly, violent
convulsions.

§ 681. =Mydatoxine=, C₆H₁₃NO₂.--A base obtained by Brieger from
horse-flesh in a putrefactive condition and other substances. It is
found in the mercury chloride precipitate. The free base is an alkaline
syrup, isomeric with the base separated by Brieger from tetanus
cultures. The hydrochloride is a deliquescent syrup, not forming any
compound with gold chloride, but uniting with phospho-molybdic acid in
forming a compound crystallising in cubes. It forms a double salt with
gold chloride, sparingly soluble in water. The platinochloride (Pt = 29
per cent.) is very soluble in water, but not soluble in alcohol;
melting-point 193° with decomposition.

The base in large doses is poisonous, causing lachrymation, diarrhœa,
and convulsions.

§ 682. =Mytilotoxine=, C₆H₁₅NO₂.--This is believed to be the poison of
mussels. Brieger isolated it as follows:--

The mussels were boiled with water acidified by hydrochloric acid; the
liquid was filtered, and the filtrate evaporated to a syrup, and the
syrup was repeatedly extracted with alcohol. It was found advisable to
exhaust thoroughly with alcohol, otherwise much poison remained behind.
The alcoholic solution was treated with an alcoholic solution of lead
acetate. The filtrate was evaporated and the residue extracted with
alcohol. The lead was removed by SH₂, the alcohol distilled off, water
added to the remaining syrup, and the solution decolorised by boiling
with animal charcoal. The solution was neutralised by sodium carbonate,
acidulated with nitric acid, and precipitated with phosphomolybdic acid.
The precipitate was then decomposed by warming with a neutral solution
of lead acetate, and the filtrate (after the removal of the lead by the
action of SH₂) was acidulated with HCl and evaporated to dryness. The
residue was then extracted with absolute alcohol, filtered from any
insoluble chloride, _e.g._, betaine chloride, and precipitated by
mercury chloride in alcohol.

The free base has a most peculiar odour, which disappears on exposure to
air; at the same time, the poisonous properties also diminish. The base
is destroyed by boiling with sodium carbonate; on the other hand, the
hydrochloride may be evaporated to dryness or be boiled without
decomposing.

The hydrochloride crystallises in tetrahedra; the aurochloride
crystallises in cubes (Au=41·66 per cent.). Its melting-point is 182°.

§ 683. =Tyrotoxicon= (Diazobenzol, C₆H₅N₂(OH)).--It appears, from the
researches of Vaughan and others, that diazobenzol is liable to be
formed in milk and milk products, especially in summer time. It is
confidently asserted by many that the summer diarrhœa of infants is due
to this toxine; however that may be, it is well established that
diazobenzol is a violent poison, causing sickness, diarrhœa, and, in
large doses, an acute malady scarcely distinguishable from cholera, and
which may end fatally. There will always be difficulty in detecting it,
because of its instability. The following is the best process of
extraction from milk. The milk will probably be acid from decomposition;
if so, the whey must be separated by dilution and filtration; without
dilution it may be found impracticable to get a clear filtrate. In order
to keep the bulk down, 25 c.c. of the milk may be diluted up to 100
c.c., and, having obtained a clear filtrate from this 25 c.c. thus
diluted, the filtrate is used to dilute another 25 c.c. of milk and so
on. The acid filtrate is neutralised by sodium carbonate, agitated with
an equal volume of ether, allowed to stand in a stoppered vessel for
twenty-four hours, and the ether then separated and allowed to evaporate
spontaneously. The residue is acidified with nitric acid and then
treated with a saturated solution of potash, which forms a stable
compound with diazobenzol, and the whole concentrated on the water-bath.
On cooling, the tyrotoxicon compound forms six-sided plates. Before the
whole of this process is undertaken, it is well to make a preliminary
test of the milk as follows:--A little of the ether is allowed to
evaporate spontaneously. Place on a porcelain slab two or three drops of
a mixture of equal parts of sulphuric and carbolic acids, and add a few
drops of the aqueous solution; if tyrotoxicon be present, a yellow to
orange-red colour is produced. A similar colour is also produced by
nitrates or nitrites, which are not likely to be present under the
circumstances, milk having mere traces only of nitrates or nitrites; it
may also be due to butyric acid, which, in a decomposed milk, may
frequently be in solution. Therefore, if a colour occurs, this is not
absolutely conclusive; if, however, no colour is produced, then it is
certain that no diazobenzol has been separated. That is all that can be
said, for the process itself is faulty, and only separates a fractional
part of the whole.

§ 684. =Toxines of Hog Cholera.=--Toxines have been isolated by F. G.
Novy[671] from a cultivation of Salmon’s bacillus in pork broth. The
fluid possessed a strong alkaline reaction. For the isolation, Brieger’s
method was used. The mercury chloride precipitate was amorphous and was
converted into a chlorine-free platinum compound, to which was assigned
the composition of C₈H₁₄N₄PtO₈. After separation of this compound, the
mother liquor still contained a platinum salt crystallising in needles,
and from this was obtained the chlorhydrate of a new base, to which was
given the name of _susotoxine_; it had the composition of
C₁₀H₂₆N₂2HCl,PtCl₄. Susotoxine gives general alkaloidal reactions, and
is very poisonous.

[671] _Med. News_, September 1890.

§ 685. =Other Ptomaines.=--Besides the ptomaines which have been already
described, there are a number of others; the following may be mentioned:
isoamylamine,[672] (CH₃)₂CH.CH₂.CH₂NH₂; butylamine, CH₃CH₂CH₂CH₂NH₂;
dihydrolutidine,[673] C₇H₁₁N; hydrocollidine,[674] C₈H₁₃N; C₁₀H₁₅N (a
base isolated by Guareschi and Mosso[675] from ox-fibrin in a state of
putrefaction by Gautier’s method; it forms a crystalline hydrochloride
and an insoluble platinochloride; its action is like that of curare but
weaker); aselline,[676] C₂₅H₃₂N₄, isolated from cod-liver oil;
typhotoxine,[677] C₇H₁₇NO₂, isolated from cultures of Eberth’s bacillus.
So far as the published researches go, it would appear that other
crystalline substances have been isolated from the urine, from the
tissues, and from the secretions of patients suffering from various
diseases; the quantity obtained in each case has, however, been, under
the most favourable circumstances, less than a gramme; often only a few
milligrms. To specifically declare that a few milligrms. of a substance
is a new body, requires immense experience and great skill; and, even
where those qualifications are present, this is too often impossible.
This being so, the long list of named ptomaines, such as erysipeline,
varioline, and others, must have their existence more fully confirmed by
more than one observer before they can be accepted as separate entities.

[672] Hesse, _Chem. Jahresb._, 1857, 403.

[673] Gautier, A., and Morgues, _Compt. Rend._, 1888.

[674] Gautier et Etard, _Bull. Soc. Chim._, xxxvii., 1882.

[675] Guareschi et Mosso, _Les ptomaines_, 1883.

[676] Gautier, A., et Morgues, _Compt. Rend._, 1888.

[677] Brieger, 1885, _Ptomaines_, iii.


DIVISION III.--FOOD POISONING.

§ 686. A large number of cases of poisoning by food occur yearly; some
are detailed in the daily press; the great majority are neither recorded
in any journal, scientific or otherwise; nor, on account of their slight
and passing character, is medical aid sought. The greatest portion of
these cases are probably due to ptomaines existing in the food before
being consumed; others may be due to the action of unhealthy
fermentation in the intestinal canal itself; in a third class of cases,
it is probable that a true zymotic infection is conveyed and develops in
the sufferer; the latter class of cases, as, for instance, the
Middlesborough epidemic of pleuro-pneumonia, is outside the scope of
this treatise.

Confining the attention to cases of food poisoning in which the symptoms
have been closely analysed and described, the reader is referred to
thirteen cases of food poisoning, investigated by the medical officers
of the Local Government Board between the years 1878 and 1891, as
follows:--

1878. =A Case of Poisoning at Whitchurch from eating Roast Pork.=--Only
the leg of pork was poisonous, other parts eaten without injury. Two
persons died after about thirty hours’ illness. The pork itself, on a
particular Sunday, was innocuous; it became poisonous between the Sunday
and the Monday; the toxicity appeared to gradually increase, for those
who ate it for dinner on the Monday were not taken ill for periods of
from seven to nineteen hours, while two persons who ate of it in the
evening were attacked four hours after eating.

1880. =The Welbeck Epidemic=, due to eating cold boiled ham. Over fifty
persons affected. Symptoms commenced in from twelve to forty-eight
hours.

1881. =A Series of Poisoning from eating Baked Pork,
Nottingham.=--Probably the gravy was the cause and not the pork itself.
Many persons seriously ill. One died.

1881. =Tinned American Sausage.=--A man in Chester died from eating
tinned American sausage. Poison found to be unequally distributed in the
sausage.

1882. =Poisoning at Oldham by Tinned Pigs’ Tongues.=--Two families
affected. Symptoms commenced in about four hours. All recovered. After a
few days’ keeping it would appear that the poison had been decomposed.

1882. =A Family Poisoned by Roast Beef at Bishop Stortford.=--Only a
particular piece of the ribs seemed to be poisonous, the rest of the
carcase being innocuous. Symptoms did not commence until several hours
after ingestion.

1882. =Ten different Families at Whitchurch Poisoned by eating
Brawn.=--First symptoms after about four hours.

1884. =Tinned Salmon at Wolverhampton.=--Five persons, two being
children, ate of tinned salmon at Wolverhampton. All suffered more or
less. The mother’s symptoms began after twelve hours, and she died in
five days; the son died in three days, the symptoms commencing in ten
hours. The _post-mortem_ signs were similar to those from phosphorus
poisoning, viz., fatty degeneration. Mice fed on the material also
suffered, and their organs showed a similar degeneration.

1886. =The Carlisle A Case.=--At a wedding breakfast in Carlisle
twenty-four persons were poisoned by food which had been kept in an
ill-ventilated cellar. The articles suspected were an American ham, an
open game pie, and certain jellies. The bride died. Symptoms commenced
in from six to forty-three hours.

1886. =Poisoning by Veal Pie at Iron Bridge.=--Twelve out of fifteen ate
of the pie; all were taken ill in from six to twelve hours.

1887. =Poisoning at Retford of Eighty Persons from eating Pork Pie or
Brawn.=--Symptoms commenced at various intervals, from eight to
thirty-six hours.

1889. =The Carlisle B Case.=--Poisoning by pork pies or boiled salt
pork. Number of persons attacked, about twenty-five.

1891. =Poisoning by a Meat Pie at Portsmouth.=--Thirteen persons
suffered from serious illness. Portions of the pies were poisonous to
mice.

The symptoms in all these cases were not precisely alike; but they were
so far identical as to show as great a similarity as in cases when a
number of persons are poisoned by the same chemical substance. Arsenic,
for instance, produces several types of poisoning; so does phosphorus.

Severe gastro-enteric disturbance, with more or less affection of the
nervous system, were the main characteristics. These symptoms commenced,
as before stated, at various intervals after ingestion of the food; but
they came on with extreme suddenness. Rigors, prostration, giddiness,
offensive diarrhœa, followed by muscular twitchings, dilatation of the
pupil, drowsiness, deepening in bad cases to coma, were commonly
observed. The _post-mortem_ appearances were those of enteritis, with
inflammatory changes in the kidney and liver. Convalescence was slow;
sometimes there was desquamation of the skin.

In many of these cases Dr. Klein found bacteria which, under certain
conditions, were capable of becoming pathogenic; but in no case does
there seem to have been at the same time an exhaustive chemical inquiry;
so that, although there was evidence of a poison passing through the
kidney, the nature of the poison still remains obscure.

The deaths in England and Wales from unwholesome food during ten years
were as follows:--

DEATHS IN ENGLAND AND WALES FROM UNWHOLESOME FOOD DURING THE TEN YEARS
1883-1892.

  +----------+-----+---+-----+---+-----+---+-----+---+-----+----+----+
  |          |1883.|   |1885.|   |1887.|   |1889.|   |1891.|    |To- |
  |           |   |1884.|   |1886.|   |1888.|   |1890.|   |1892.|tal.|
  +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+
  |Diseased   | 1 | ... |...| ... |...| ... |...| ... |...| ... |  1 |
  |meat,      |   |     |   |     |   |     |   |     |   |     |    |
  |Poisonous  | 2 |  3  | 2 |  1  | 1 |  4  | 3 |  2  | 9 |  6  | 33 |
  |fish,      |   |     |   |     |   |     |   |     |   |     |    |
  |Unwholesome|...|  1  |...| ... |...| ... |...| ... |...| ... |  1 |
  |brawn,     |   |     |   |     |   |     |   |     |   |     |    |
  |Tinned     |...|  2  |...| ... |...| ... |...| ... |...| ... |  2 |
  |salmon,    |   |     |   |     |   |     |   |     |   |     |    |
  |Putrid     |...|  1  | 1 |  1  |...| ... | 1 | ... |...| ... |  4 |
  |meat,      |   |     |   |     |   |     |   |     |   |     |    |
  |Diseased   |...|  1  |...| ... |...| ... |...| ... |...| ... |  1 |
  |food,      |   |     |   |     |   |     |   |     |   |     |    |
  |Mussels,   |...|  1  |...| ... |...| ... | 1 | ... |...| ... |  2 |
  |Tinned     |...| ... |...| ... | 2 | ... |...| ... |...| ... |  2 |
  |foods,     |   |     |   |     |   |     |   |     |   |     |    |
  |Whelks,    |...| ... |...| ... | 1 | ... |...| ... |...| ... |  1 |
  |Winkles,   |...| ... |...| ... |...| ... |...|  1  |...| ... |  1 |
  |Ptomaines, |...| ... |...| ... |...| ... |...| ... | 1 | ... |  1 |
  |           +---+-----+---+-----+---+-----+---+-----+---+-----+----+
  |           | 3 |  9  | 3 |  2  | 4 |  4  | 5 |  3  |10 |  6  | 49 |
  +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+

§ 687. =German Sausage Poisoning.=--A series of cases may be picked out
from the accounts of sausage poisoning in Germany, all of which
evidently depend upon a poison producing the same symptoms, and the
essentially distinctive mark of which is extreme dryness of the skin and
mucous membranes, dilatation of the pupil, and paralysis of the upper
eyelids (ptosis). In an uncertain time after eating sausages or some
form of meat, from one to twenty-four hours, there is a general feeling
of uneasiness, a sense of weight about the stomach, nausea, and soon
afterwards vomiting, and very often diarrhœa. The diarrhœa is not
severe, never assumes a choleraic form, and is unaccompanied by cramps
in the muscles. After a considerable interval there is marked dryness of
the mucous membrane (a symptom which never fails), the tongue, pharynx,
and the mouth generally seem actually destitute of secretion; there is
also an absence of perspiration, the nasal mucous membrane participates
in this unnatural want of secretion, the very tears are dried up. In a
case related by Kraatzer,[678] the patient, losing a son, was much
troubled, but wept no tear. This dryness leads to changes in the mucous
membrane, it shrivels, and partly desquamates, aphthous swellings may
occur, and a diffuse redness and diphtheritic-like patches have been
noticed. There is obstinate constipation, probably from a dryness of the
mucous lining of the intestines. The breath has an unpleasant odour,
there is often a croupy cough, the urinary secretion alone is not
decreased but rather augmented. Swallowing may be so difficult as to
rise to the grade of aphagia, and the tongue cannot be manipulated
properly, so that the speech may be almost unintelligible. At the same
time, marked symptoms of the motor nerves of the face are present, the
patient’s sight is disturbed, he sees colours or sparks before his eyes;
in a few cases there has been transitory blindness, in others diplopia.
The pupil in nearly all the cases has been dilated, also in exceptional
instances it has been contracted. The _levator palpebrae superioris_ is
paralysed, and the resulting ptosis completes the picture. Consciousness
remains intact almost to death, there is excessive weakness of the
muscles, perhaps from a general paresis. If the patient lives long
enough, he gets wretchedly thin, and dies from marasmus. In more rapidly
fatal cases, death follows from respiratory paralysis, with or without
convulsions.

[678] Quoted by Husemann, _Vergiftung durch Wurstgift_ (Maschka’s
_Handbook_).

=The post-mortem appearances= which have been observed are--the mucous
membranes of the mouth, gullet, and throat are white, hard, and
parchment-like; that of the stomach is more or less injected with
numerous hæmorrhages: the kidneys are somewhat congested, with some
effusion of blood in the tubuli; the spleen is large and very full of
blood, and the lungs are often œdematous, pneumonic, or bronchitic.




PART VIII.--THE OXALIC ACID GROUP OF POISONS.

§ 688. Oxalic acid is widely distributed both in the free state and in
combination with bases throughout the vegetable kingdom, and it also
occurs in the animal kingdom. In combination with potash it is found in
the _Geranium acetosum_ (L.), _Spinacia oleracea_ (L.), _Phytolacca
decandra_ (L.), _Rheum palmatum_ (L.), _Rumex acetosa_, _Atropa
belladonna_, and several others; in combination with soda in different
species of _Salsola_ and _Salicornia_; and in combination with lime in
most plants, especially in the roots and bark. Many lichens contain half
their weight of calcic oxalate, and oxalic acid, either free or
combined, is (according to the observations of Hamlet and
Plowright[679]) present in all mature non-microscopic fungi. Crystals of
oxalate of lime may be frequently seen by the aid of the microscope in
the cells of plants. According to Schmidt,[680] this crystallisation
only takes place in the fully mature cell, for in actively growing cells
the oxalate of lime is entirely dissolved by the albumen of the plant.

[679] _Chem. News_, vol. xxxvi. p. 93.

[680] _Ann. Chem. Pharm._, vol. lxi. p. 297.

In the animal kingdom oxalic acid is always present in the intestinal
contents of the caterpillar. In combination with lime, it is constantly
found in the allantois liquor of the cow, the urine of man, swine,
horses, and cats. With regard to human urine, the presence or absence of
oxalate of lime greatly depends upon the diet, and also upon the
individual, some persons almost invariably secreting oxalates, whatever
their food may be.

§ 689. =Oxalic Acid=, H₂C₂O₄2H₂O (90 + 36), specific gravity 1·64,
occurs in commerce in prismatic crystals, very similar to, and liable to
be mistaken for, either magnesic or zincic sulphates. The crystals are
intensely acid, easily soluble in water (1 part requiring at 14·5° 10·46
parts of water); they are also soluble in parts of cold, and readily in
boiling, alcohol. Oxalic acid is slightly soluble in cold absolute
ether; but ether, although extracting most organic acids from an aqueous
solution, will not extract oxalic acid.

Oxalic acid sublimes slowly at 100°, but rapidly and completely at
150°; the best means of obtaining the pure anhydride is to put a
sufficient quantity of the acid into a strong flask, clamp it by
suitable connections to a mercury pump, and sublime in a vacuum; in this
way a sufficient quantity may be sublimed a little above 100°. It is
well to remember, not only its low subliming temperature, but also that
an aqueous solution, if kept at 100°, loses acid; hence all evaporating
or heating operations must not exceed 98°, or there will be some loss.
The effect of heat is first to drive off water, then, if continued up to
about 190°, there is decomposition into carbon monoxide, carbon dioxide,
water, and formic acid; the two reactions occurring simultaneously--

  C₂H₂O₄ = CO₂ + CO + H₂O.

  C₂H₂O₄ = CO₂ + CH₂O₂.

Heated with sulphuric acid to 110°, the following decomposition takes
place:--

  H₂C₂O₄ = H₂O + CO₂ + CO.

Oxalic acid decomposes fluor spar, the phosphates of iron, silver, zinc,
copper, and the arseniates of iron, silver, and copper. It may be used
to separate the sulphides of iron and manganese from the sulphides of
zinc, cadmium, uranium, cobalt, mercury, and copper--dissolving the
former, not the latter. Many minerals and other substances are also
attacked by this acid.

If a solution of oxalic acid in water is boiled with ammonio or sodio
terchloride of gold (avoiding direct exposure to light) the gold is
precipitated--

  2AuCl₃ + 3H₂C₂O₄ = 6CO₂ + 6HCl + Au₂.

When black oxide of manganese (free from carbonate) is mixed with an
oxalate, and treated with dilute sulphuric acid, the oxalic acid is
decomposed, and carbon dioxide evolved--

  MnO₂ + H₂C₂O₄ + H₂SO₄ = MnSO₄ + 2H₂O + 2CO₂.

A similar reaction occurs with permanganate of potash.

If to a solution of oxalic acid, which may be neutralised with an
alkali, or may contain free acetic acid, a solution of acetate of lime
be added, oxalate of lime is thrown down. This salt, important in an
analytical point of view, it will be well to describe.

§ 690. =Oxalate of Lime= (CaC₂O₄H₂O), 1 part ·863 crystallised oxalic
acid. This is the salt which the analyst obtains for the quantitative
estimation of lime or oxalic acid; it is not identical with that
occurring in the vegetable kingdom, the latter containing 3H₂O. Oxalate
of lime cannot be precipitated for quantitative purposes from solutions
containing chromium, aluminium, or ferric iron, since somewhat soluble
salts are formed. It dissolves in solutions of magnesium and
manganese,[681] and citrate of soda, and is also decomposed by boiling
with solutions of copper, silver, lead, cadmium, zinc, nickel, cobalt,
strontium, or barium. It is insoluble in solutions of chlorides of the
alkalies and alkaline earths, and in water, in alkaline solutions, or in
acetic acid; and is soluble in mineral acid only when the acid is strong
and in considerable excess. It is unalterable in the air, and at 100°.
When carefully and slowly ignited it may be wholly converted into
carbonate of lime; if the heat is not properly managed (that is, if
excessive), caustic lime may be formed in greater or smaller quantity.

[681] But it is reprecipitated unaltered by excess of alkaline oxalate.

§ 691. =Use in the Arts.=--Oxalic acid is chiefly used by dyers and
calico-printers, but also by curriers and harness-makers for cleaning
leather, by marble masons for removing iron stains, by workers in straw
for bleaching, and it is applied to various household purposes,[682]
such as the whitening of boards, the removing of iron-mould from linen,
&c. The hydropotassic oxalate (binoxalate of potash), under the popular
names of “_essential salt of lemons_” and salts of sorrel, is used for
scouring metals and for removing ink-stains from linen.

[682] A “Liquid Blue,” used for laundry purposes, contains much free
oxalic acid.

§ 692. =Hydropotassic Oxalate, Binoxalate of Potash=, KHC₂O₄(H₂O), is a
white salt, acid in reaction, soluble in water, and insoluble in
alcohol. Heated on platinum foil it leaves potassic carbonate, which may
be recognised by the usual tests. Its aqueous solution gives, with a
solution of acetate or sulphate of lime, a precipitate of calcic oxalate
insoluble in acetic acid.

§ 693. =Statistics.=--Poisoning by oxalic acid is more frequent in
England than in any other European country. In the ten years 1883-92,
there were registered in England and Wales 222 deaths from oxalic
acid--of these 199, or 89·6 per cent., were suicidal, the remainder
accidental. The age and sex distribution of these cases is set out in
the following table:--

POISONING BY OXALIC ACID IN ENGLAND AND WALES DURING THE TEN YEARS
1883-1892.

                       ACCIDENT OR NEGLIGENCE.

  Ages,          0-1  1-5  5-15  15-25  25-65  65 and  Total
                                               above
  Males,          1   ...   ...     2    ...     14      17
  Females,      ...   ...   ...     1      5    ...       6
               ---------------------------------------------
    Total,        1   ...   ...     3      5     14      23
               ---------------------------------------------

                              SUICIDE.

  Ages,                          15-25  25-65  65 and  Total
                                               above
  Males,                            9    102      3     114
  Females,                         21     62      2      85
                                ----------------------------
    Total,                         30    164      5     199
                                ----------------------------

§ 694. =Fatal Dose.=--The smallest dose of oxalic acid known to have
destroyed life is, according to Dr. Taylor, 3·88 grms. (60 grains); but
recovery has taken place, on prompt administration of remedies, after
eight times this quantity has been swallowed.

With regard to oxalate of soda, or binoxalate of potash, 14·2 grms.
(half an ounce) have been taken without fatal result, although the
symptoms were very serious; and it may be held that about that quantity
would usually cause death. Oxalic acid is not used in medicine, save as
a salt, _e.g._, oxalate of cerium.

§ 695. =Effects of Oxalic Acid and Oxalates on Animals.=--The first
cases of poisoning by oxalic acid occurred early in the nineteenth
century, a little more than fifty years after its discovery.
Thompson[683] was the first who attempted, by experiment on animal life,
to elucidate the action of the poison; he noted the caustic action on
the stomach, and the effects on the heart and nervous system, which he
attributed simply to the local injury through the sympathetic nerves.
Orfila[684] was the next who took the matter up, and he made several
experiments; but it was Robert Christison[685] who distinctly recognised
the important fact that oxalic acid was toxic, quite apart from any
local effects, and that the soluble oxalates, such as sodic and potassic
oxalates, were violent poisons.

[683] _Lond. Med. Rep._, vol. iii. p. 382.

[684] _Traité de Toxicologie._

[685] _Edin. Med. and Surg. Journ._, 1823.

§ 696. Kobert and Küssner[686] have made some extended researches on the
effects of sodic oxalate on rabbits, cats, dogs, guinea-pigs, hedgehogs,
frogs, &c.--the chief results of which are as follows:--On injection of
sodic oxalate solution in moderate doses into the circulation, the
heart’s action, and, therefore, the pulse, become arhythmic; and a
dicrotic or tricrotic condition of the pulse may last even half a day,
while at the same time the frequency may be uninfluenced. The
blood-pressure also with moderate doses is normal, and with small atoxic
doses there is no slowing of the respiration. On the other hand, toxic
doses paralyse the respiratory apparatus, and the animal dies
asphyxiated. With chronic and subacute poisoning the respiration becomes
slower and slower, and then ceases from paralysis of the respiratory
muscles. The first sign of poisoning, whether acute or chronic, is a
sleepy condition; dogs lie quiet, making now and then a noise as if
dreaming, mechanical irritations are responded to with dulness. The hind
extremities become weak, and then the fore. This paresis of the hind
extremities, deepening into complete paralysis, was very constant and
striking. Take, for example, from the paper (_op. cit._) the experiment
in which a large cat received in six days five subcutaneous injections
of 5 c.c. of a solution of sodic oxalate (strength 1 : 30), equalling
·16 grm.; the cat died, as it were, gradually from behind forwards, so
that on the sixth day the hinder extremities were fully motionless and
without feeling. The heart beat strongly. The temperature of the
poisoned animal always sinks below the normal condition. Convulsions in
acute poisoning are common, in chronic quite absent; when present in
acute poisoning, they are tetanic or strychnic-like. In all the
experiments of Kobert and Küssner, lethal doses of soluble oxalates
caused the appearance of sugar in the urine.

[686] _Exper. Wirkungen der Oxalsäure, Virch. Archiv_, Bd. lxxvii. S.
209.

J. Uppmann[687] made forty-nine experiments on dogs, in which he
administered relatively large doses by the stomach; no poisonous effect
followed. Emil Pfeiffer[688] gave a dog in three successive days ·2, ·5,
and lastly 1 grm. oxalic acid with meat, but no symptoms resulted. Yet
that oxalic acid, as sodic oxalate, is poisonous to dogs, if it once
gets into the circulation, cannot be disputed. The accepted explanation
is that the large amount of lime phosphates in the digestive canal of
dogs is decomposed by oxalic acid, and the harmless lime oxalate formed.

[687] _Allg. Med. central Ztg._, 1877.

[688] _Archiv der Pharm._ (3 R.), Bd. xiii. S. 544, 1878.

Oxalic acid is absorbed into the blood, and leeches have been known to
die after their application to a person who had taken a large dose. Thus
Christison[689] quotes a case related by Dr. Arrowsmith, in which this
occurred:--“They were healthy, and fastened immediately; on looking at
them a few minutes after, I remarked that they did not seem to fill, and
on touching one it felt hard, and instantly fell off motionless and
dead; the others were in the same state. They had all bitten, and the
marks were conspicuous, but they had drawn scarcely any blood. They were
applied about six hours after the acid had been taken.”

[689] _Treatise on Poisons._

§ 697. =Effects of Vaporised Oxalic Acid.=--Eulenberg has experimented
on pigeons on the action of oxalic acid when breathed. In one of his
experiments, ·75 grm. of the acid was volatilised into a glass shade, in
which a pigeon had been placed; after this had been done five times in
two minutes, there was uneasiness, shaking of the head, and cough, with
increased mucous secretion of the nasal membrane. On continuing the
transmission of the vapour, after eight minutes there was again
restlessness, shaking of the head, and cough; after eleven minutes the
bird fell and was convulsed. On discontinuing the sublimation, it got up
and moved freely, but showed respiratory irritation. On the second day
after the experiment, it was observed that the bird’s note was hoarse,
on the fourth day there was slowness of the heart’s action and refusal
of food, and on the sixth day the bird was found dead. Examination after
death showed slight injection of the cerebral membranes; the cellular
tissue in the neighbourhood of the trachea contained in certain places
extravasations of blood, varying from the size of a pea to that of a
penny; the mucous membrane of the larynx and trachea was swollen and
covered with a thick croupous layer; the lungs were partially hepatised,
and the pleura thickened; the crop as well as the true intestines still
contained some food.[690]

[690] _Gewerbe Hygiene_, p. 423.

§ 698. =The Effects of Oxalic Acid and Hydropotassic Oxalate on
Man.=--The cases of oxalic poisoning have been invariably due to either
oxalic acid or hydropotassic oxalate, the neutral sodic or potassic
oxalates having hitherto in no instance been taken. The symptoms, and
even the locally destructive action of oxalic acid and the acid oxalate,
are so similar that neither from clinical nor _post-mortem_ signs could
they be differentiated by anyone not having a previous knowledge of the
case.

The external application of oxalic acid does not appear to cause
illness; workmen engaged in trades requiring the constant use of the
acid often have the nails white, opaque, and brittle; but no direct
injury to health is on record.

A large dose of either causes a local and a remote effect; the local is
very similar to that already described as belonging to the mineral
acids, i.e., more or less destructive of the mucous membranes with which
the acid comes in contact. The remote effects may only be developed
after a little; they consist essentially of a profound influence on the
nervous system. Though more than 120 cases of oxalic acid poisoning have
occurred since Christison wrote his treatise, his graphic description
still holds good. “If,” says he, “a person immediately after swallowing
a solution of a crystalline salt, which tasted purely and strongly acid,
is attacked with burning in the throat, then with burning in the
stomach, vomiting, particularly of bloody matter, imperceptible pulse,
and excessive languor, and dies in half an hour, or still more, in
twenty, fifteen, or ten minutes, I do not know any fallacy which can
interfere with the conclusion that oxalic acid was the cause of death.
No parallel disease begins so abruptly, and terminates so soon; and no
other crystalline poison has the same effect.” The local action is that
of a solvent on the mucous tissues. If from 10 to 30 grms. are
swallowed, dissolved in water, there is an immediate sour taste, pain,
burning in the stomach, and vomiting. The vomit may be colourless,
greenish, or black, and very acid; but there is a considerable variety
in the symptoms. The variations may be partly explained by saying that,
in one class of cases, the remote or true toxic effects of the poison
predominate; in a second, the local and the nervous are equally divided;
while in a third, the local effects seem alone to give rise to symptoms.

In a case at Guy’s Hospital, in 1842, there was no pain, but vomiting
and collapse. In another case which occurred in 1870, a male (aged 48)
took 10·4 grms. (162 grains); he had threatening collapse, cold sweats,
white and red patches on the tongue and pharynx, difficulty in
swallowing, and contracted pupils. Blood was effused from the mouth and
anus; on the following day there were convulsions, coma, and death
thirty-six hours after taking the poison. In another case, there was
rapid loss of consciousness and coma, followed by death in five hours.
Death may be very rapid, _e.g._, in one case (_Med. Times and Gaz._,
1868) it took place in ten minutes; there was bleeding from the stomach,
which doubtless accelerated the fatal result. Orfila has recorded a
death almost as rapid from the acid oxalate of potash; a woman took 15
grms.; there was no vomiting, but she suffered from fearful cramps, and
death ensued in fifteen minutes. In another case, also recorded by
Orfila, there was marked slowing of the pulse, and soporific tendencies.
With both oxalic acid and the acid oxalate of potash, certain nervous
and other sequelæ are more or less constant, always provided time is
given for their development. From the experiments already detailed on
animals, one would expect some paresis of the lower extremities, but
this has not been observed in man. There is more or less inflammation of
the stomach, and often peritonitis; in one case (_Brit. Med. Journal_,
1873) there were cystitis and acute congestion of the kidneys with
albuminuria.

In two cases quoted by Taylor, there was a temporary loss or
enfeeblement of voice; in one of the two, the aphonia lasted for eight
days. In the other, that of a man who had swallowed about 7 grms. (¼
oz.) of oxalic acid, his voice, naturally deep, became in nine hours low
and feeble, and continued so for more than a month, during the whole of
which time he suffered in addition from numbness and tingling of the
legs. As a case of extreme rarity may be mentioned that of a young
woman,[691] who took 12 grms. (185 grains) of the acid oxalate of
potash, and on the third day died; before death exhibiting delirium so
active and intense that it was described as “madness.”

[691] _Journ. de Chim. Méd._, 1839, p. 564.

§ 699. =Physiological Action.=--Putting on one side the _local_ effects
of oxalic acid, and regarding only its true toxic effects, there is some
difference of opinion as to its action. L. Hermann considers it one of
the heart poisons, having seen the frog’s heart arrested by subcutaneous
doses of sodic oxalate, an observation which is borne out by the
experiments of Cyon,[692] and not negatived by those of Kobert and
Küssner. The poison is believed to act on the extracardial ganglia.
Onsum[693] held at one time a peculiar theory of the action of oxalic
acid, believing that it precipitated as oxalate of lime in the lung
capillaries, causing embolic obstruction; but this view is not now
accepted--there are too many obvious objections to it. Kobert and
Küssner do not consider oxalic acid a heart poison, but believe that its
action is directed to the central nervous system, as attested by sinking
of the blood-pressure, the arhythm and retardation of the pulse, the
slow breathing, the paralytic symptoms, and the fibrillary muscular
contraction; but, with regard to the latter, Locke[694] has observed
that a frog’s sartorius, immersed in 0·75 sodium oxalate solution,
becomes in a few seconds violently active, much more so than in
Biederman’s normal saline solution. After thirty to forty-five minutes
it loses its irritability, which, however, it partially recovers by
immersion in 0·6 sodium chloride solution. He thinks this may explain
the symptoms of fibrillary muscular contraction observed by Kobert and
Küssner, which they ascribe to an action on the central nervous system.

[692] _Virch. Archiv_, Bd. xx. S. 233.

[693] Almen afterwards supported Onsum’s view; he made a number of
microscopical observations, and appears to have been the first who
identified oxalate of lime in the kidneys (Upsala, _Läkareförenings
förhandl._, Bd. ii. Hft. iv. S. 265).

[694] F. S. Locke, _J. Phys._, xv. 119; _Journ. Chem. Soc._, 1893, 480.

§ 700. =Pathological Changes.=--Kobert and Küssner observed that when
oxalate of soda was subcutaneously injected into animals, there was
often abscess, and even gangrene, at the seat of the injection. If the
poison were injected into the peritoneal cavity, death was so rapid as
to leave little time for any coarse lesions to manifest themselves. They
were not able to observe a cherry-red colour of the blood, nor did they
find oxalate of lime crystals in the lung capillaries; there were often
embolic processes in the lung, but nothing typical. They came,
therefore, to the conclusion that the state of the kidneys and the urine
was the only typical sign. The kidneys were dark, full of blood, but did
not show any microscopic hæmorrhages. Twelve hours after taking the
poison there is observed in the cortical substance a fine striping
corresponding to the canaliculi; in certain cases the whole boundary
layer is coloured white. If the poisoning lasts a longer time, the
kidneys become less blood-rich, and show the described white striping
very beautifully; this change persists several weeks. The cause of this
strange appearance is at once revealed by a microscopical examination;
it is due to a deposition of oxalate of lime; no crystals are met with
in the glomerules. Both by the microscope and by chemical means it may
be shown that the content of the kidney in oxalates is large.[695] So
far as the tissues generally are concerned, free oxalic acid is not
likely to be met with; there is always present sufficient lime to form
lime oxalate. The urine was always albuminous and contained a reducing
substance, which vanished about the second day after the dose. Hyaline
casts and deposits of oxalates in the urine never failed.[696]

[695] The important fact of the oxalate-content of kidneys and urine,
and the expulsion of casts, was first observed by Mitscherlich in 1854.
He noticed in a rabbit, to which had been given 7·5 grms. of oxalic
acid, and which had died in thirteen minutes, “_renes paululum magis
sanguine replete videbantur, in urina multa corpora inveniebantur, quæ
tubulos Bellenianos explese videntur_” (_De acidi acetici, oxalici,
tartarici, citrici, formici, et boracici, &c., Berlin_).

[696] Rabuteau has discovered by experiment that even the oxalates of
iron and copper are decomposed and separated by the kidneys. _Gaz. Méd.
de Paris_, 1874.

§ 701. Observations of the pathological effects of the oxalates on man
have been confined to cases of death from the corrosive substances
mentioned, and hence the intestinal tract has been profoundly affected.

In the museum of St. Thomas’ Hospital is a good example of the effects
produced. The case was that of a woman who had taken a large, unknown
quantity of oxalic acid, and was brought to the hospital dead. The
mucous membrane of the gullet is much corrugated and divided into
numerous parallel grooves, these again by little transverse grooves, so
that the intersection of the two systems makes a sort of raised pattern.
It is noted that in the recent state the mucous membrane could be
removed in flakes; in the upper part it was whitish, in the lower
slate-coloured. The stomach has a large perforation, but placing the
specimen beside another in the same museum which illustrates the effect
of the gastric juice, in causing an after-death solution of a portion of
the stomach, I was unable to differentiate between the two. The mucous
membrane had the same shreddy flocculent appearance, and is soft and
pale. The pyloric end is said to have been of a blackish colour, and no
lymph was exuded.

§ 702. The pathological changes by the acid oxalate of potash are
identical with those of oxalic acid, in both the gullet and stomach
being nearly always more or less inflamed or corroded; the inflammation
in a few cases has extended right through into the intestinal canal;
there are venous hyperæmia, hæmorrhages, and swelling of the mucous
membrane of the stomach. The hæmorrhages are often punctiform, but
occasionally larger, arranged in rows on the summits of the rugæ;
sometimes there is considerable bleeding. In the greater number of cases
there is no actual erosion of the stomach, but the inner layer appears
abnormally transparent. On examining the mucous membrane under the
microscope, Lesser[697] has described it as covered with a layer which
strongly reflects light, and is to be considered as caused by a fine
precipitate of calcic oxalate. Lesser was unable to find in any case
oxalic acid crystals, or those of the acid oxalate of potash. There are
many cases of perforation on record, but it is questionable whether they
are not all to be regarded as _post-mortem_ effects, and not
life-changes; at all events, there is little clinical evidence to
support the view that these perforations occur during life. In the case
(mentioned _ante_) in which death took place by coma, the brain was
hyperæmic. The kidneys, as in the case of animals, show the white zone,
and are congested, and can be proved by microscopical and chemical
means to be rich in oxalates.

[697] Virchow’s _Archiv_, Bd. lxxxiii. S. 218, 1881.

§ 703. =Separation of Oxalic Acid from Organic Substances, the Tissues
of the Body, &c.=--From what has been stated, no investigation as to the
cause of poison, when oxalic acid is suspected, can be considered
complete unless the analyst has an opportunity of examining both the
urine and the kidneys; for although, in most cases--when the acid
itself, or the acid potassic salt has been taken--there may be ample
evidence, both chemical and pathological, it is entirely different if a
case of poisoning with the neutral sodic salt should occur. In this
event, there may be no congested appearance of any portion of the
intestinal canal, and the evidence must mainly rest on the urine and
kidneys.

Oxalic acid being so widely distributed in the vegetable kingdom, the
expert must expect, in any criminal case, to be cross-examined by
ingenious counsel as to whether or not it was possible that the acid
could have entered the body in a rhubarb-pie, or accidentally through
sorrel mixed with greens, &c. To meet these and similar questions it is
important to identify, if possible, any green matters found in the
stomach. In any case, it must be remembered, that although rhubarb has
been eaten for centuries, and every schoolboy has occasionally chewed
small portions of sorrel, no poisoning has resulted from these
practices. When oxalic acid has been taken into the stomach, it will
invariably be found partly in combination with lime, soda, ammonia, &c.,
and partly free; or if such antidotes as chalk has been administered, it
may be wholly combined. Vomiting is nearly always present, and valuable
evidence of oxalic acid may be obtained from stains on sheets, carpets,
&c. In a recent case of probably suicidal poisoning, the writer found no
oxalic acid in the contents of the stomach, but some was detected in the
copious vomit which had stained the bed-clothes. The urine also
contained a great excess of oxalate of lime--a circumstance of little
value taken by itself, but confirmatory with other evidence. If a liquid
is strongly acid, oxalic acid may be separated by dialysis from organic
matters, and the clear fluid thus obtained precipitated by sulphate of
lime, the oxalate of lime being identified by its microscopic form and
other characters.

The usual general method for the separation of oxalic acid from organic
substances or mixtures is the following:--Extract with boiling water,
filter (which in some cases must be difficult or even impossible), and
then precipitate with acetate of lead. The lead precipitate may contain,
besides oxalate of lead, phosphate, chloride, sulphate, and various
organic substances and acids. This is to be decomposed by sulphuretted
hydrogen, and on filtering off the sulphide of lead, oxalic acid is to
be tested for in the filtrate. This process can only be adopted with
advantage in a few cases, and is by no means to be recommended as
generally applicable. The best general method, and one which insures
the separation of oxalic acid, whether present as a free acid, as an
alkaline, or a calcic oxalate, is perhaps the following:--The substance
or fluid under examination is digested with hydrochloric acid until a
fluid capable of filtration is obtained; the free acid is neutralised by
ammonia in very slight excess, and permitted to deposit, and the fluid
is then carefully decanted, and the deposit thrown on a filter. The
filtrate is added to the decanted fluid, and precipitated with a slight
excess of acetate of lime--this precipitate, like the first, being
collected on a filter. The first precipitate contains all the oxalic
acid which was in combination with lime; the second, all that which was
in the free condition. Both precipitates should be washed with acetic
acid. The next step is to identify the precipitate which is supposed to
be oxalate of lime. The precipitate is washed into a beaker, and
dissolved with the aid of heat by adding, drop by drop, pure
hydrochloric acid; it is then reprecipitated by ammonia, and allowed to
subside completely, which may take some time. The supernatant fluid is
decanted, and the precipitate washed by subsidence; it is lastly dried
over the water-bath in a tared porcelain dish, and its weight taken. The
substance is then identified by testing the dried powder as follows:--

(_a_) It is whitish in colour, and on ignition in a platinum dish leaves
a grey carbonate of lime. All other organic salts of lime--viz.,
citrate, tartrate, &c.--on ignition become coal-black.

(_b_) A portion suspended in water, to which is added some sulphuric
acid, destroys the colour of permanganate of potash--the reaction being
similar to that on p. 511--a reaction by which, as is well known, oxalic
acid or an oxalate may be conveniently titrated. This reaction is so
peculiar to oxalic acid, that there is no substance with which it can be
confounded. It is true that uric acid in an acid solution equally
decolorises permanganate, but it does so in a different way; the
reaction between oxalic acid and permanganate being at first slow, and
afterwards rapid, while the reaction with uric acid is just the
reverse--at first quick, and towards the end of the process extremely
slow.

(_c_) A portion placed in a test-tube, and warmed with concentrated
sulphuric acid, develops on warming carbon oxide and carbon dioxide; the
presence of the latter is easily shown by adapting a cork and bent tube
to the test-tube, and leading the evolved gases through baryta water.

Alexander Gunn[698] has described a new method of both detecting and
estimating oxalic acid; it is based on the fact that a small trace of
oxalic acid, added to an acid solution of ferrous phosphate, strikes a
persistent lemon-yellow colour; the depth of colour being proportionate
to the amount of oxalic acid.

[698] _Pharm. Journal_, 1893, 408.

The reagents necessary for both quantitative and qualitative testing are
as follows:--A standard solution of oxalic acid, of which 100 c.c. equal
1 grm., and a solution of ferrous phosphate, containing about 12·5 per
cent. of Fe₃2PO₄, with excess of phosphoric acid.

Into each of two Nessler graduated glasses 7·5 c.c. of the ferrous
phosphate solution are run and made up to 50 c.c. with distilled water;
both solutions should be colourless; 1, 2, or more c.c. of the solution
to be tested are then run into one of the Nessler glasses; if oxalic
acid be present, a more or less deep tint is produced; this must be
imitated by running the standard solution of oxalic acid into the second
Nessler cylinder--the calculation is the same as in other colorimetric
estimations. It does not appear to be reliable quantitatively, if alum
is present; and it is self-evident that the solution to be tested must
be fairly free from colour.

§ 704. =Oxalate of Lime in the Urine.=--This well-known urinary sediment
occurs chiefly as octahedra, but hour-glass, contracted or dumbbell-like
bodies, compound octahedra, and small, flattened, bright discs, not
unlike blood discs, are frequently seen. It may be usually identified
under the field of the microscope by its insolubility in acetic acid,
whilst the ammonio mag. phosphate, as well as the carbonate of lime, are
both soluble in that acid. From urates it is distinguished by its
insolubility in warm water. A chemical method of separation is as
follows:--The deposit is freed by subsidence as much as possible from
urine, washed with hot water, and then dissolved in hydrochloric acid
and filtered; to the filtrate ammonia is added in excess. The
precipitate may contain phosphates of iron, magnesia, lime, and oxalate
of lime. On treatment of the precipitate by acetic acid, the phosphates
of the alkaline earths (if present) dissolve; the insoluble portion will
be either phosphate of iron, or oxalate of lime, or both. On igniting
the residue in a platinum dish, any oxalate will be changed to
carbonate, and the carbonate of lime may be titrated with d. n. HCl acid
and cochineal solution, and from the data thus obtained the oxalate
estimated. The iron can be tested qualitatively in the acid solution by
ferrocyanide of potassium, or it can be determined by the ordinary
methods. If the qualitative detection of oxalate of lime in the deposit
is alone required, it is quite sufficient evidence should the portion
insoluble in acetic acid, on ignition in a platinum dish, give a residue
effervescing on the addition of an acid.

§ 705. =Estimation of Oxalic Acid.=--Oxalic acid is estimated in the
free state by direct weighing, or by titration either with alkali or by
potassic permanganate, the latter being standardised by oxalic acid. If
(as is commonly the case) oxalic acid is precipitated as oxalate of
lime, the oxalate may be--

(_a_) Dried at 100° and weighed directly, having the properties already
described.

(_b_) Titrated with dilate sulphuric acid and permanganate.

(_c_) Ignited, and the resulting carbonate of lime weighed; or dissolved
in standard acid and titrated back--one part of calcic carbonate
corresponds to 1·26 part of crystallised oxalic acid, or 0·90 part of
H₂C₂O₄; similarly, 1 c.c. of standard acid equals ·05 of calcic
carbonate (or ·063 of crystallised oxalic acid).

(_d_) The oxalate may be dissolved in the smallest possible amount of
hydrochloric acid, and boiled with ammonio chloride of gold, avoiding
exposure to light; every part of gold precipitated corresponds to ·961
part of crystallised oxalic acid.

(_e_) The oxalate may be placed in Geissler’s carbonic acid apparatus,
with peroxide of manganese and diluted sulphuric acid. The weight of the
gas which at the end of the operation has escaped, will have a definite
relation to that of the oxalate, and if multiplied by 1·4318 will give
the amount of crystallised oxalic acid.


CERTAIN OXALIC BASES--OXALMETHYLINE--OXALPROPYLINE.

    § 706. Hugh Schulz[699] and Mayer have contributed the results of
    some important researches bearing upon a more exact knowledge of the
    effects of the oxalic group of poisons, and upon the relation
    between chemical constitution and physiological effects. They
    experimented upon _oxalmethyline_, _chloroxalmethyline_, and
    _oxalpropyline_.

[699] _Beitrag zur Kenntniss der Wirkung der Oxalbasen auf den
Thierkörper. Arch. f. exper. Path. u Pharm._, 1882.

    =Chloroxalmethyline= (C₆H₅ClN₂) is a liquid, boiling at 205°, with a
    weakly narcotic smell. A solution of the hydrochlorate of the base
    was employed. Subcutaneous injections of ·05 grm. into frogs caused
    narcosis, and both this and the ethylic compound deranged the
    heart’s action, decreasing the number of beats. Thus ·05 grm.
    decreased the number of the beats of the heart of a frog in the
    course of one and three-quarter hours as follows: 72, 60, 56, 50,
    44, 40, 35, 0.

    =Oxalmethyline= produces somewhat similar symptoms, but the nervous
    system is more affected than in that which contains chlorine.

    =Oxalpropyline= also causes narcosis, and afterwards paralysis of
    the hinder extremities and slowing of the heart.

    The difference between the chlorine-free and the chlorine-containing
    oxalic bases are summarised as follows:--

                                 FROGS.

  CHLORINE-HOLDING BASES.             CHLORINE-FREE BASES.

  Notable narcosis; no heightened     Narcosis occurs late, and is
  reflex action, muscular cramps,     little pronounced; a notable in-
  nor spontaneous convulsions.        crease of reflex  excitability;
                                      more and more muscular paralysis;
                                      between times, muscular cramps.

                                   CATS.

  Notable narcosis and salivation;    Great excitement; general
  no mydriasis; convulsions and       shivering, rising to pure clonic
  paralysis; no change in the         convulsions; paralysis of the
  respirations.                       hind legs; notable mydriasis,
                                      jerking, and superficial res-
                                      piration; weak narcosis.

                                   DOGS.

  Notable narcosis; occasional        Narcosis evident; the rest as in
  vomiting; the rest as in cats.      cats.




PART IX.--INORGANIC POISONS.


I.--PRECIPITATED FROM A HYDROCHLORIC ACID SOLUTION BY HYDRIC
SULPHIDE--PRECIPITATE YELLOW OR ORANGE.[700]

Arsenic--Antimony--Cadmium.

[700] Fresenius has pointed out that sulphur may mask small quantities
of arsenic, antimony, tin, &c., and he recommends that the turbid liquid
in which apparently nothing but sulphur has separated should be treated
as follows:--A test-tube is half filled with the liquid, and then a
couple of c.c. of petroleum ether or of benzene added, the tube closed
by the thumb, and the contents well shaken. The sulphur dissolves, and
is held in solution by the solvent, which latter forms a clear upper
layer. If traces of a metallic sulphide were mixed with the sulphur,
thin coloured films are seen at the junction of the two layers, and the
sulphides may also coat the tube above the level of the liquid with a
slight faintly-coloured pellicle (_Chem. News_, Jan. 4, 1895).


1. ARSENIC.

§ 707. =Metallic Arsenic=, at. wt. 75, specific gravity of solid 5·62 to
5·96, sublimes without fusion in small quantities at 110° (230° F.)
_Guy_. It occurs in commerce in whitish-grey, somewhat brittle,
crystalline masses, and is obtained by subjecting arsenical pyrites to
sublimation in earthen retorts, the arsenic being deposited in suitable
receivers on sheet iron. Metallic arsenic is probably not poisonous, but
may be changed by the animal fluids into soluble compounds, and then
exert toxic effects--volatilised metallic arsenic is easily transformed
in the presence of air into arsenious acid, and is therefore intensely
poisonous.

§ 708. =Arsenious Anhydride--Arsenious Acid--White Arsenic--Arsenic=,
As₂O₃ = 198; specific gravity of vapour, 13·85; specific gravity of
opaque variety, 3·699; specific gravity of transparent variety, 3·7385.
Composition in 100 parts, As 75·75, O 24·25; therefore one part of
metallic arsenic equals 1·32 of As₂O₃. It is entirely volatilised at a
temperature of 204·4°.

In analysis it is obtained in brilliant octahedral crystals as a
sublimate on discs of glass, or within tubes, the result of heating a
film of metallic arsenic with access of air. It is obtained in commerce
on a very large scale from the roasting of arsenical pyrites. As thus
derived, it is usually in the form of a white cake, the arsenious acid
existing in two forms--an amorphous and a crystalline--the cake being
generally opaque externally, whilst in the centre it is transparent.
According to Kruger, this change from the crystalline to the amorphous
condition is dependent upon the absorption of moisture, no alteration
taking place in dry air. Both varieties of arsenious anhydride are acid
to test-paper.

The solubility of arsenious acid is often a question involving chemical
legal matters of great moment. Unfortunately, however, no precisely
definite statement can be made on this point, the reason being that the
two varieties of arsenic occur in very different proportions in
different samples. Both the amorphous and crystalline varieties having
very unequal solubilities, every experimenter in succession has given a
different series of figures, the only agreement amid the general
discrepancy being that arsenic is very sparingly soluble in water.

The statement of Taylor may, however, be accepted as very near the
truth, viz., that an ounce of cold water dissolves from half a grain to
a grain. According to M. L. A. Buchner,[701] one part of crystalline
arsenious acid dissolves after twenty-four hours’ digestion in 355 parts
of water at 15°; and the amorphous, under the same condition, in 108 of
water. A boiling solution of the crystalline acid, left to stand for
twenty-four hours, retains one part of acid in 46 of water; a similar
solution of the amorphous retains one of arsenic in 30 parts of water,
_i.e._, 100 parts of water dissolve from 2·01 to 3·3 parts of As₂O₃.

[701] _Bull. de la Société Chem. de Paris_, t. xx. 10, 1873.

Boiling water poured on the powdered substance retains in cooling a
grain and a quarter to the ounce; in other words, 100 parts of water
retain ·10. Lastly, arsenious acid boiled in water for an hour is
dissolved in the proportion of 12 grains to the ounce, _i.e._, 100 parts
of water retain 2·5.

K. Chodomisky[702] has investigated the solubility of recrystallised
arsenious acid in dilute acids, and his results are as follows:--100
c.c. of 1·32 per cent. hydrochloric acid dissolves 1·15 grm. As₂O₃ at
18·5°. 100 c.c. of 6 per cent. hydrochloric acid dissolves 1·27 grm. at
18·5°. 100 c.c. of pure hydrochloric acid of the ordinary commercial
strength dissolves 1·45 grm. As₂O₃. 100 c.c. of dilute sulphuric acid at
18° dissolves about 0·54 grm.; at 18·5° from 0·65 to 0·72 grm.; and at
80° from 1·09 to 1·19 grm.

[702] _Chem. Centrbl._, 1889, 569.

§ 709. =Arsine--Arseniuretted Hydrogen=, H₃As.--Mol. weight, 78; vol.
weight, 39; specific gravity, 2·702; weight of a litre, 3·4944 grammes;
percentage composition, 95·69 As, 4·31 H; volumetric composition, 2 vol.
H₃As = half vol. As + 3 vol. H. A colourless inflammable gas, of a
fœtid alliaceous odour, coercible into a limpid colourless liquid at a
temperature of from -30° to -40°. The products of the combustion of
arseniuretted hydrogen are water and arsenious acid; thus, 2H₃As + 6O =
3H₂O + As₂O₃. If supplied with air in insufficient quantity, if the
flame itself be cooled by (for example) a cold porcelain plate, or if
the gas pass through a tube any portion of which is heated to redness,
the gas is decomposed and the metal separated. Such a decomposition may
be compared to the deposit of carbon from ordinary flames, when made to
play upon a cooled surface. It may also be decomposed by the electric
spark,[703] _e.g._, if the gas is passed slowly through a narrow tube
0·7 to 0·8 mm. internal diameter, provided with wires 0·5 to 0·6 mm.
apart, and a small induction coil used connected with two large Bunsen’s
cells, then, under these conditions, arsenic as a metal is deposited in
the neighbourhood of the sparks. For the decomposition to be complete,
the gas should not be delivered at a greater speed than from 10 to 15
c.c. per minute. The gas burns with a blue-white flame, which is very
characteristic, and was first observed by Wackenroder. It cannot,
however, be properly seen by using the ordinary apparatus of Marsh, for
the flame is always coloured from the glass; but if the gas is made to
stream through a platinum jet, and then ignited, the characters
mentioned are very noteworthy.

[703] N. Klobrikow, _Zeit. Anal. Chem._, xxix. 129-133.

Oxygen or air, and arsine, make an explosive mixture. Chlorine
decomposes the gas with great energy, combining with the hydrogen, and
setting free arsenic as a brown cloud; any excess of chlorine combines
with the arsenic as a chloride. Sulphur, submitted to arseniuretted
hydrogen, forms sulphuretted hydrogen, whilst first arsenic and then
sulphide of arsenic separate. Phosphorus acts in a similar way.
Arseniuretted and sulphuretted hydrogen may be evolved at ordinary
temperatures without decomposition; at the boiling-point of mercury
(350°) they are decomposed, sulphide of arsenic and hydrogen being
formed; thus, 3H₂S + 2AsH₃ = As₂S₃ + 6H₂, a reaction which is of some
importance from a practical point of view. Many metals have also the
property of decomposing the gas at high temperatures, and setting
hydrogen free. Metallic oxides, again, in like manner combine with
arsenic, and set water free, _e.g._, 3CuO + 2H₃As = Cu₃As₂ + 3H₂O.

Arsine acts on solutions of the noble metals like phosphuretted
hydrogen, precipitating the metal and setting free arsenious acid; for
example, nitrate of silver is decomposed thus--

  12AgNO₃ + 2H₃As + 3H₂O = As₂O₃ + 12HNO₃ + 12Ag.

Vitali[704] thinks the reaction is in two stages, thus:--

[704] _L’Orosi_, 1892, 397-411.

  (1) 2AsH₃ + 12AgNO₃ = 2(Ag₃As3AgNO₃) + 6HNO₃.

  (2) 2(Ag₃As,3AgNO₃) + 6H₂O = 6HNO₃ + 6Ag₂ + 2H₃AsO₃.

This reaction admits of valuable practical application to the estimation
of arsenic; for the precipitated silver is perfectly arsenic-free; the
excess of nitrate of silver is easily got rid of by a chloride of sodium
solution, and the absorption and decomposition of the gas are complete.

In cases of poisoning by arsine, the blood, when examined by the
spectroscope (a process the analyst should never omit where it is
possible), is of a peculiar inky colour, and the bands between D and C
are melted together, and have almost vanished. Such blood, exposed to
oxygen remains unaltered.

§ 710. =Arsine in the Arts, &c.=--In the bronzing of brass, in the
desilverising of lead by zinc, and subsequent treatment of the silver
zinc with hydrochloric acid, in the tinning of sheet iron, and similar
processes, either from the use of acids containing arsenic as an
impurity, or from the application of arsenic itself, arsine is evolved.

§ 711. =Effects on Animals and Man of Breathing Arsine.=--The most
general effect on mammals is to produce jaundice, bloody urine, and
bile. In the course of numerous experiments on dogs, Stadelmann[705]
found that by making them breathe a dose of arsine, which would not be
immediately fatal, icterus was always produced under these
circumstances, and could be always detected by the appearance of the
tissues. The bile is remarkably thickened, and the theory is, that in
such cases the jaundice is purely mechanical, the gall-duct being
occluded by the inspissated bile. Rabbits experimented upon similarly
showed increased biliary secretion, but no jaundice; while it was proved
that cats are not so sensitive to arsine as either rabbits or dogs.
There are not wanting instances of arsine having been breathed by
man--the discoverer of the gas, Gehlen, was in fact the first victim on
record. In order to discover a flaw in his apparatus he smelt strongly
at the joints, and died in eight days from the effects of the
inhalation.

[705] _Die Arsenwasserstoff-Vergiftung, Archiv f. exper. Path. u.
Pharm._, Leipzig, 1882.

Nine persons, workmen in a factory, were poisoned by arsine being
evolved during the treatment by hydrochloric acid of silver-lead
containing arsenic. Three of the nine died; their symptoms were briefly
as follows:--

(1) H. K., 22 years old; his duty was to pour hydrochloric acid on the
metal. Towards mid-day, after this operation, he complained of nausea,
giddiness, and _malaise_. In the afternoon he felt an uncommon weight of
the limbs, and an oppression in breathing. His fellow-workmen thought
that he looked yellow. On going home he lay down and passed into a
narcotic sleep. Next morning he went to his work as usual, but was not
capable of doing anything; he passed bloody urine several times
throughout the day, and fell into a deep sleep, from which he could
scarcely be roused. On the third day after the accident, a physician
called in found him in a deep sleep, with well-developed jaundice, the
temperature moderately high, pulse 100. On the fifth day the jaundice
diminished, but it was several months before he could resume his work.

(2) J. T., aged 19, suffered from similar symptoms after five and a half
hours’ exposure to the gas. He went home, vomited, was jaundiced, and
suffered from bloody urine; in six days became convalescent, but could
not go to work for many months.

(3) C. E. was very little exposed, but was unwell for a few days.

(4) L. M., 37 years old, was exposed two days to the gas; he vomited,
had bloody urine, passed into a narcotic sleep, and died in three days
from the date of the first exposure.

(5) J. S., aged 40, was exposed for two days to the gas; the symptoms
were similar to No. 4, there was suppression of urine, the catheter
drawing blood only, and death in eight days.

(6) M. E., 36 years old; death in three days with similar symptoms.

(7), (8), and (9) suffered like Nos. 1 and 2, and recovered after
several months.

The chief _post-mortem_ appearance was a dirty green colour of the
mucous membrane of the intestines, and congestion of the kidneys.
Arsenic was detected in all parts of the body.[706]

[706] Trost, _Vergiftung durch Arsenwasserstoff bei der technischen
Gewinnung des Silbers, Vierteljahrsschrift f. gericht. Med._, xviii.
Bd., 2 Heft, S. 6, 1873.

Two cases are detailed by Dr. Valette in Tardieu’s _Étude_.[707] A
mistake occurred in a laboratory, by which a solution of arsenic
(instead of sulphuric acid) was poured on zinc to develop hydrogen. Of
the two sufferers, the one recovered after an illness of about a week or
ten days, the other died at the end of twenty-eight days. The main
symptoms were yellowness of skin, vomiting, bloody urine, great
depression, slight diarrhœa, headache, and in the fatal case a
morbiliform eruption. In a case recorded in the _British Medical
Journal_, November 4, 1876, there were none of the usual symptoms of
gastric irritation, but loss of memory of recent acts, drowsiness, and
giddiness.

[707] Ambroise Tardieu, _Étude Médico-légale sur l’Empoisonnement_, Obs.
xxv. p. 449.

§ 712. =The Sulphides of Arsenic.=--Of the sulphides of arsenic, two
only, realgar and orpiment, are of any practical importance. _Realgar_,
As₂S₂ = 214; specific gravity, 3·356; composition in 100 parts, As
70·01, S 29·91; average composition of commercial product, As 75, S 25.
Realgar is found native in ruby-red crystals, and is also prepared
artificially by heating together 9 parts of arsenic and 4 of sulphur, or
198 parts of arsenious anhydride with 112 parts of sulphur, 2As₂O₃ + 7S
= 2As₂S₂ + 3SO₂. It is insoluble in water and in hydrochloric acid, but
is readily dissolved by potassic disulphide, by nitric acid, and by
aqua regia. It is decomposed by caustic potash, leaving undissolved a
brown sediment (As₁₂S), which contains 96·5 per cent. of arsenic. The
dissolved portion is readily converted into arsine by aluminium.

§ 713. =Orpiment, or Arsenic Trisulphide.=--As₂S₃ = 246; specific
gravity, 3·48; composition in 100 parts, As 60·98, S 39·02; found native
in crystals, presents itself in the laboratory usually as a brilliant
yellow amorphous powder, on passing sulphuretted hydrogen through an
acid solution of arsenious acid or an arsenite. It is very insoluble in
water (about one in a million, _Fresenius_), scarcely soluble in boiling
concentrated hydrochloric acid, and insoluble generally in dilute acids.
Red fuming nitric acid dissolves it, converting it into arsenic and
sulphuric acids; ammonia and other alkaline sulphides, the alkalies
themselves, alkaline carbonates, bisulphide of potassium, and aqua
regia, all dissolve it readily. In the arts it is used as King’s yellow
(see p. 532). Tanners also formerly employed a mixture of 90 parts of
orpiment and 10 of quicklime, under the name of _Rusma_, as a
depilatory; but the alkaline sulphides from gas-works are replacing this
to a great extent.

§ 714. =Haloid Arsenical Compounds.--The Chloride of Arsenic=, AsCl₃ =
181·5; specific gravity liquid, 0° 2·205; boiling-point 134° (273·2°F.),
is a heavy, colourless, oily liquid, which has been used as an
escharotic in cancerous affections (principally by quacks). In one
process of detecting and estimating arsenic, the properties of this
substance are utilised (see p. 575). It is immediately decomposed by
water into arsenious and hydrochloric acids.

=The Iodide of Arsenic= (AsI₃) is used occasionally in skin diseases,
but is of little interest to the analyst; it is commonly seen in the
form of brick-red brilliant flakes.

§ 715. =Arsenic in the Arts.=--The metal is used in various alloys; for
example, speculum metal is made of tin, copper, and a little arsenic;
white copper is an alloy of copper and arsenic; shot is composed of 1000
parts of lead mixed with 3 of arsenic; the common Britannia metal used
for tea-pots, spoons, &c., often contains arsenic; and brass is bronzed
with a thin film of arsenic. It was formerly much employed in the
manufacture of glass, but is being gradually superseded. It is also now
used to some extent in the reduction of indigo blue, and in that of
nitro-benzole in the manufacture of aniline.

In cases of suspected poisoning, therefore, and the finding of arsenic
in the stomach, or elsewhere, it may be set up as a defence that the
arsenic was derived from shot used in the cleansing of bottles, from the
bottles themselves, or from metal vessels, such as tea-pots, &c.

The arsenic in all these alloys being extremely insoluble, any solution
to a poisonous extent is in the highest degree improbable. It may,
however, be necessary to treat the vessels with the fluid or fluids
which have been supposed to exert this prejudicial action, and test
them for arsenic. The treatment should, of course, be of a severe and
exhaustive character, and the fluids should be allowed to stand cold in
the vessels for twenty-four hours; then the effect of a gentle heat
should be studied, and, lastly, that of boiling temperatures. The
analysis of the alloy itself, or of the glass, it would seldom be of
value to undertake, for the crushed and finely divided substance is in a
condition very different from that of the article when entire, and
inferences drawn from such analytical data would be fallacious.

Arsenious anhydride is also used for the preservation of wood, and is
thrown occasionally into the holds of vessels in large quantities to
prevent vegetable decomposition. In India, again, a solution of arsenic
is applied to the walls as a wash, in order to prevent the attacks of
insects.

§ 716. =Pharmaceutical, Non-officinal, and other Preparations of
Arsenic.=--(1) =Pharmaceutical Preparations.=--The Liquor arsenicalis
(Fowler’s solution), or solution of arsenic of the pharmacopœia, is
composed of:--

  Carbonate of Potash,              87 grains  (5·64 grms.)
  Arsenious Acid,                   87   „     (5·64   „  )
  Compound Tincture of Lavender,     5 drachms (17·72 c.c.)

dissolved in 1 pint (567·9 c.c.) of water; every ounce, therefore,
contains 4·3 grains of arsenious acid (or 100 c.c. = ·9As₂O₃); the
strength is therefore nearly 1 per cent.

=Liquor Ammonii Arsenitis= (not officinal) is made of the same strength,
ammonium carbonate being substituted for potassic carbonate.

The _hydrochloric solution of arsenic_ is simply arsenious acid
dissolved in hydrochloric acid; its strength should be exactly the same
as that of Fowler’s solution.

A solution of _arseniate of soda_[708] contains the _anhydrous_ salt in
the proportion of 4 grains to the ounce (·9 in 100 c.c.) of water.

[708] The formula for arseniate of soda is Na₂HAsO₄7H₂O, but it
sometimes contains more water.

=Liquor Arsenii et Hydrargyri Iodidi= (Donovan’s Solution of
Arsenic).--This is not officinal, but is used to some extent in skin
diseases; it is a solution of the iodides of mercury and arsenic;
strength about 1 per cent. of each of the iodides.

=Arseniate of Iron=, Fe₃As₂O₈, is an amorphous green powder, used to
some extent in medicine. It should contain 33·6 per cent. of metallic
arsenic.

=Clemen’s Solution.=--A solution of the bromide and arseniate of
potassium; strength equal to 1 per cent. arsenious acid. Officinal in
U.S., France, and Norway.

=Pilula Asiatica= (not officinal) is composed of arsenious acid, extract
of gentian, and black pepper. There is 1/12th of a grain (5·4
milligrams) of arsenious acid in each pill.

=Dr. De Valanguis’ Solutio solventes mineralis= is composed of 30 grains
of As₂O₃ dissolved by 90 minims of HCl in 20 oz. of water; strength =
0·034 per cent. As₂O₃.

(2) =Veterinary Arsenical Medicine.=--Common veterinary preparations
containing arsenic are:--A ball for worms, containing in parts--

  Calomel,                   1·3 per cent.
  Arsenious Acid,            1·3    „
  Tin Filings,              77·9    „
  Venice Turpentine,[709]   19·5    „

[709] The Venice turpentine is rarely found in ordinary commerce, what
is sold under that name consisting of black resin and oil of turpentine.

A common tonic ball:[710]--

[710] A similar preparation in common use has the addition of sulphate
of zinc.

  Arsenious Acid,        5 to 10 grains (·324 to ·648 grm.)
  Aniseed,                 ½ oz.        (14·1744 grms.)
  Opium,                 30 grains      ( 1·94     „  )
  Treacle,               q. s.

An arsenical ball, often given by grooms to horses for the purpose of
improving their coats, contains in 100 parts:--

  Arsenious Acid,          2·5 per cent.
  Pimento,                19·2    „
  Extract of Gentian,     78·3    „

Another ball in use is composed of arsenic and verdigris (acetate of
copper), of each 8 grains (·518 grm.); cupric sulphate, 20 grains (1·3
grm.); q. s. of linseed meal and treacle.

(3) =Rat and Fly Poisons, &c.=--An arsenical paste sold for rats has the
following composition:--

  Arsenious Acid,                       5·0 per cent.
  Lampblack,                             ·6    „
  Wheat Flour,                         46·3    „
  Suet,                                46·3    „
  Oil of Aniseed, a small quantity.

Another rat poison is composed as follows:--

  White Arsenic,                    46·8 per cent.
  Carbonate of Baryta,              46·8    „
  Rose-pink,[711]                    5·8    „
  Oil of Aniseed,                     ·2    „
  Oil of Rhodium,                     ·2    „

[711] Alum and carbonate of lead coloured with Brazil and peach woods.

Various arsenical preparations are used to kill flies; the active
principle of the brown “_papier moure_” is arsenious acid. A dark grey
powder, which used to be sold under the name of fly-powder, consisted of
metallic arsenic that had been exposed some time to the air.

=Fly-water= is a strong solution of arsenious acid of uncertain
strength, sweetened with sugar, treacle, or honey. Another fly-poison
consists of a mixture of arsenious acid, tersulphide of arsenic,
treacle, and honey.

(4) =Quack and other Nostrums.=--The analyst may meet with several quack
preparations for external use in cancer. A celebrated arsenical paste
for this purpose is composed of:--

  Arsenious Acid,              8 per cent.
  Cinnabar,                   70    „
  Dragon’s Blood,             22    „

=Frères Come’s Cancer Paste= is composed of arsenious acid, 1; charcoal,
1; red mercury sulphide, 4; water, q. s.

The tasteless “_ague drops_” used in the fen countries are simply a
solution of arsenite of potash.

=Davidson’s Cancer Remedy= consists, according to Dr. Paris, of equal
parts of arsenious acid and powdered hemlock.

In India, arsenic given as a medicine by native practitioners, or
administered as a poison, may be found coloured and impure, from having
been mixed either with cow’s urine, or with the juice of leaves,
&c.[712]

[712] Chevers, _Med. Jurisprudence for India_, p. 116.

Arsenious acid is used by dentists to destroy the nervous pulp of
decayed and painful teeth, about the twenty-fifth of a grain (2·5
mgrms.) being placed in the cavity. A common formula is arsenious acid,
2; sulphate of morphine, 1; creasote, q. s. to make a stiff paste. There
is no record of any accident having resulted from this practice
hitherto; but since the dentist seldom weighs the arsenic, it is not
altogether free from danger.

(5) =Pigments, &c.=--_King’s yellow_ should be As₂S₃, the trisulphide of
arsenic or orpiment. It is frequently adulterated with 80 to 90 per
cent. of arsenious acid, and in such a case is, of course, more
poisonous. King’s yellow, if pure, yields to water nothing which gives
any arsenical reaction.

A blue pigment, termed _mineral blue_, consists of about equal parts of
arsenite of copper and potash, and should contain 38·7 per cent. of
metallic arsenic (= to 51·084 As₂O₃H) and 15·6 of copper.

=Schweinfurt green= (Syn. _Emerald-green_), (CuAs₂O₄)₃Cu(C₂H₃O₂)₂ is a
cupric arsenite and acetate, and should contain 25 per cent. of copper
and 58·4 per cent. of arsenious acid. In analysis, the copper in this
compound is readily separated from the arsenic by first oxidising with
nitric acid, and then adding to the nitric acid solution ammonia, until
the blue colour remains undissolved. At this point ammonium oxalate is
added in excess, the solution is first acidified by hydrochloric or
nitric acid, and, on standing, the copper separates completely (or
almost so) as Oxalate, the arsenic remaining in solution.

Another method is to pass SH₂ to saturation, collect the sulphides on a
filter, and, after washing and drying the mixed sulphides, oxidise with
fuming nitric acid, evaporate to dryness, and again treat with nitric
acid. The residue is fused with soda and potassic nitrate, the fused
mass is dissolved in water, acidulated with nitric acid, and the copper
is precipitated by potash; the solution is filtered, and in the filtrate
the arsenic is precipitated as ammonio-magnesian arseniate or as
trisulphide.[713]

[713] P. Gucci, _Chem. Centrbl._, 1887, 1528.

=Scheele’s green= (CuHAsO₃) is a hydrocupric arsenite, and contains 52·8
per cent. of arsenious anhydride and 33·8 per cent. of copper.

(6) =External Application of Arsenic for Sheep, &c.=--Many of these are
simply solutions of arsenic, the solution being made by the farmer. Most
of the yellow sheep-dipping compounds of commerce are made up either of
impure carbonate of potash, or of soda ash, arsenic, soft soap, and
sulphur. The French _bain de Tessier_ is composed of:--

  Arsenious Acid,        1·00 kgrm.
  Ferrous Sulphate,     10·00  „
  Peroxide of Iron,      0·40  „
  Gentian Powder,        0·20  „

This is to be added to 100 kgrms. of water. Another common application
consists of alum and arsenic (10 or 12 to 1), dissolved in two or three
hundred parts of water.

(7) =Arsenical Soaps, &c.=--Arsenic is used in preserving the skins of
animals. One of the compounds for this purpose, known under the name of
_Bécoeur’s arsenical soap_, has the following composition:--

  Camphor,                 3·4 per cent.
  Arsenic,                20·2    „
  Carbonate of Potash,    56·2    „
  Lime,[714]              20·2    „

[714] The dust from the preserved skins of animals has caused, at least,
one case of poisoning. _Ann. d’Hyg. Pub. et de Méd. Lég._, 2 sér., 1870,
t. xxxiii, p. 314.

(8) =Arsenical compounds= used in pyrotechny:--

                                              Parts.
    Blue fires--(1) Realgar,                     2
                    Charcoal,                    3
                    Potassic Chlorate,           5
                    Sulphur,                    13
                    Nitrate of Baryta,          77
                                               -----
                (2) Sulphur,                    40·9
                    Nitre,                      36·8
                    Sulphide of Antimony,       12·3
                       „        Arsenic,         5
                    Charcoal,                    5
                                               -----
       Green fires--Metallic Arsenic,            2
                    Charcoal,                    3
                    Chlorate of Potash,          5
                    Sulphur,                    13
                    Nitrate of Baryta,           7
                                               ------
  Light green fire--Charcoal,                    1·75
                    Sulphide of Arsenic,         1·75
                    Sulphur,                    10·50
                    Chlorate of Potash,         23·25
                    Nitrate of Baryta,          62·50
                                               ------
    White fire--(1) Arsenious Acid,               ·76
                    Charcoal,                    1·63
                    Sulphide of Antimony,       12·27
                    Nitrate of Potash,          36·59
                    Sulphur,                    48·75
                                               ------
                (2) Realgar,                     6·1
                    Sulphur,                    21·2
                    Nitrate of Potash,          72·7
                                               ------

§ 717. =Statistics.=--During the ten years 1883-92 there were registered
in England and Wales 113 deaths from arsenic; of these 57, or about
half, were suicidal deaths, and 5 were classed under the head of
“murder”; the rest were due to accident. The age and sex distribution of
persons dying from accidental or suicidal arsenical poisoning are
detailed in the following table:--

DEATHS FROM ARSENIC DURING THE TEN YEARS 1883-1892.

                   ACCIDENT OR NEGLIGENCE.

  Ages,         1-5  5-15  15-25  25-65  65 and  Total
                                         above
  Males,         1     4      3     23      6      37
  Females,       4   ...      3      4      3      14
               ---------------------------------------
    Total,       5     4      6     27      9      51
               ---------------------------------------

                           SUICIDE.

  Ages,                    15-25  25-65  65 and  Total
                                         above
  Males,                      3     32      2      37
  Females,                    5     12      3      20
                          ----------------------------
    Total,                    8     44      5      57
                          ----------------------------

§ 718. =Law Relative to the Sale of Arsenic.=--By the 14th of Vict. c.
12, every person selling arsenic is bound to keep a written record of
every particular relative to each transaction, such as the name, abode,
and calling of the purchaser, the purpose for which the poison is
required, and the quantity sold, &c. These particulars are to be signed
also by the purchaser. No person (sec. 2) is allowed to sell arsenic to
any one unknown to the seller, unless in the presence of a witness whom
the seller is acquainted with. The arsenic sold (sec. 3) is to be mixed
with soot or indigo in the proportion of half an ounce of indigo to a
pound of arsenic. It, therefore, follows that the coloured substance
should not contain more than 70 per cent. of arsenious acid. The Act
applies to all the colourless preparations of arsenic: but it is not to
affect chemists in making up prescriptions for medical men, or in
supplying medical men; nor is it to affect the wholesale dealers in
supplying arsenic to retail shops, &c. The penalty for conviction is
£20, or less.[715]

[715] Commercial arsenic is often much adulterated, especially with
gypsum, chalk, &c. These are most readily detected by subliming the
arsenic. The sublimed arsenic itself may not be entirely pure, sometimes
containing arsenical sulphides and antimonious oxide.

§ 719. =Dose.=--The smallest dose of arsenic known to have proved fatal
to a human being is ·16 grm. (2½ grains). Farriers and grooms are in the
habit of giving as much as l·3 grm. (20 grains) a day to a horse, so
that the poisonous dose for this animal must be very large.

The maximum dose for the horned cattle appears to be from ·32 to ·38
grm. (5 to 6 grains); that for a dog is 16 mgrms. (¼ grain), and even
this may, in the smaller kinds, cause illness.

The following may be considered as _dangerous doses_ of arsenic:--·13
grm. (2 grains) for an adult; 1·9 grm. (30 grains) for a horse; ·64 grm.
(10 grains) for a cow; and 32 to 64 mgrms. (½ to 1 grain) for a dog.

§ 720. =Effects of Arsenious Acid on Plants.=--If the root or stem of a
plant is immersed in a solution of arsenious acid, the hue of the leaves
soon alters in appearance, the green colour becomes of a whitish or
brownish hue, and the plant withers; the effect being very similar to
that produced by hot water. The toxic action may be traced from below
upwards, and analysis will detect minute quantities of arsenic in all
portions of the plant.

It has, however, been shown by Gorup-Besanez,[716] that if arsenious
acid be mixed with earth, and plants grown in such earth, they only take
up infinitesimal quantities of arsenic. Hence, in cases of cattle
poisoning, any defence based upon the alleged presence of arsenic in the
pasture will be more ingenious than just.

[716] _Annal. d. Chemie u. Pharmacie_, Bd. cxxvii., H. 2, 243.

The influence of arsenical fumes as evolved from manufactories upon
shrubs and trees is in general insignificant. Pines and firs, five to
six years old, have been known to suffer from a disease in which there
is a shedding of the leaves, the more tender herbage being at the same
time affected. Whatever dangers the practice of steeping corn intended
for seed in a solution of arsenious acid, as a preventive of “smut,” may
possess, it does not appear to influence deleteriously the growth of the
future plant.

Superphosphate of manure is frequently rich in arsenic. Dr. Edmund Davy
asserts that plants to which such manure is applied take up arsenic in
their tissues, and M. Andonard has made a similar statement. Tuson[717]
has also undertaken some experiments, which confirm Andonard and Davy’s
researches. The bearing of this with relation to the detection of
arsenic in the stomachs of the herbivora needs no comment.

[717] Cooley’s _Dictionary_, Art. “Arsenic.”

§ 721. =Effects on Animal Life--Animalcules.=--All infusoria and forms
of animalcule-life hitherto observed perish rapidly if a minute quantity
of arsenious acid is dissolved in the water in which they exist.

=Insects.=--The common arsenical fly-papers afford numerous
opportunities for observing the action of arsenic on ordinary flies;
within a few minutes (five to ten after taking the poison into their
digestive organs) they fall, apparently from paralysis of the wings, and
die. Spiders and all insects into which the poison has been introduced
exhibit a similar sudden death. It is said that in the neighbourhood of
arsenical manufactories there is much destruction among bees and other
forms of insect life.

=Annelids.=--If arsenious acid is applied to the external surface of
worms or leeches, the part which it touches perishes first, and life is
extinguished successively in the others. If a wound is made first, and
the arsenious acid then applied to it, the effects are only intensified
and hastened. There is always noticed an augmentation of the excretions;
the vermicular movements are at first made more lively, they then become
languid, and death is very gradual.

=Birds.=--The symptoms with birds are somewhat different, and vary
according to the form in which the poison is administered, viz., whether
as a vapour or in solution. In several experiments made by Eulenberg on
pigeons, the birds were secured under glass shades, and exposed to the
vapour of metallic arsenic vaporised by heat. It is scarcely necessary
to remark that in operating in this way, the poisoning was not by
metallic arsenic vapour, but by that of arsenious acid. One of these
experiments may be cited:--A pigeon was made to breathe an atmosphere
charged with vapour from the volatilisation of metallic arsenic. The
bird was immediately restless; in thirty minutes it vomited repeatedly,
and the nasal apertures were noticed to be moist; after a little while,
the bird, still breathing the arsenious acid atmosphere, was much
distressed, shook its head repeatedly, and yawned; in fifty minutes the
respiration was laboured, and in fifty-nine minutes there was much
vomiting. On removing the bird, after it had been exposed an hour to the
vapour (·16 grm. of metallic arsenic having been evaporated in all), it
rapidly recovered.

Six days after, the pigeon was again exposed in the same way to the
vapour, but this time ·56 grm. of metallic arsenic was volatilised. In
fifteen minutes there was retching, followed by vomiting. On taking it
out after an hour it remained very quiet, ate nothing, and often puffed
itself out; the breathing was normal, movements free, but it had unusual
thirst. On the second and third day the excretions were frequent and
fluid; the cardiac pulsations were slowed, and the bird was disinclined
to move. On the fourth day it continued in one place, puffing itself
out; towards evening the respirations slowed, the beak gaping at every
inspiration. On attempting flight, the wings fluttered and the bird fell
on its head. After this it lay on its side, with slow, laboured
respiration, the heart-beats scarcely to be felt, and death took place
without convulsions, and very quietly. On examining the organs after
death, the brain and spinal cord were very bloodless; there were
ecchymoses in the lungs; but little else characteristic. The experiment
quoted has a direct bearing upon the breathing of arsenical dust; as,
for example, that which floats in the air of a room papered with an
easily detached arsenical pigment. Other experiments on birds generally
have shown that the symptoms produced by arsenious acid in solution, or
in the solid form, in a dose insufficient to destroy life, are languor,
loss of appetite, and the voidance of large quantities of liquid excreta
like verdigris. With fatal doses, the bird remains quiet; there are
fluid, sometimes bloody, excretions; spasmodic movements of the pharynx,
anti-peristaltic contraction of the œsophagus, vomiting, general
trembling of the body, thirst, erection of the feathers, and laboured
respiration. The bird becomes very feeble, and the scene mostly closes
with insensibility and convulsions.

=Mammals=, such as cats, dogs, &c., suffer from symptoms fairly
identical with those observed in man; but the nervous symptoms
(according to P. Hugo) do not predominate, while with rabbits and
guinea-pigs, nervous symptoms are more marked and constant.[718] There
are vomiting, purging, and often convulsions and paralysis before death.
It has been noticed that the muscles after death are in a great state of
contraction. The slow poisoning of a dog, according to Lolliot,[719]
produced an erythematous eruption in the vicinity of the joints, ears,
and other parts of the body; there were conjunctivitis, increased
lachrymal secretion, and photophobia; the hair fell off.

[718] _Archiv f. exper. Path. u. Pharmakol_, Leipzig, 1882.

[719] _Étude Physiol. d’Arsène_, Thèse, Paris, 1868.

§ 722. =Effects of Arsenious Acid on Man.=--The symptoms produced by
arsenious acid vary according to the form of the poison--whether solid,
vaporous, or soluble--according to the condition of bodily health of the
person taking it, and according to the manner in which it is introduced
into the animal economy, while they are also in no small degree modified
by individual peculiarities of organisation and by habit, as, for
instance, in the arsenic-eaters.

=Arsenic-Eaters.=--In all European countries grooms and horse-dealers
are acquainted with the fact that a little arsenic given daily in the
corn improves the coat, increases, probably, the assimilation of the
food, and renders the horse plump and fat. On the Continent grooms have
been known to put a piece of arsenic, the size of a pea, in a little
oatmeal, make it into a ball, tie it up in a linen rag, and attach it to
the bit; the saliva dissolves, little by little, the poison, while both
the gentle irritation and physiological action excite a certain amount
of salivation, and the white foam at the mouth, and the champing of the
horse, are thought vastly to improve the appearance. Shot, which
contains a small quantity of arsenic, have been used for the same
purpose, and from half a pound to a pound of small shot has been given
to horses. When a horse has been for a long time dosed with arsenic, it
seems necessary to continue the practice; if this is not done, the
animal rapidly loses his condition. The explanation probably is, that
the arsenic stimulates the various cells and glands of the intestinal
tract to a superaction, the natural termination of which is an
enfeeblement of their secreting power--this especially in the absence of
the stimulus. Turning from equine involuntary arsenic-eaters, we find
the strange custom of arsenic-eating voluntarily pursued by the races of
lower Austria and Styria, especially by those dwelling on the mountains
separating Styria from Hungary. In India also (and especially in the
Punjaub) the same practice prevails, and here it is often taken as an
aphrodisiac. The mountaineers imagine that it increases the respiratory
power, nor is there wanting some evidence to show that this is actually
the fact, and medicinal doses of arsenic have been in use for some time
in cases of asthma and other diseases of the chest. The arsenic-eaters
begin with a very small dose, which is continued for several weeks or
months, until the system gets accustomed to it. The amount is then
slightly augmented until relatively large doses are taken with impunity.
In one case[720] it appears that a countryman, in good health, and sixty
years of age, took daily 4 grains of arsenious acid, a habit which he
had inherited from his father, and which he in turn bequeathed to his
son.

[720] Tardieu, _op. cit._

The existence of such a custom as arsenic-eating, in its literal sense,
has more than once been doubted, but all who have travelled over Styria
and other places where the habit prevails have convinced themselves that
the facts have not been overstated. For example, Dr. Maclagan, in
company with Dr. J. T. Rutter,[721] visited Styria in 1865, and having
carefully weighed 5 or 6 grains of arsenic, saw these doses actually
swallowed by two men. On collecting their urine, about two hours
afterwards, abundant quantitative evidence of its presence was found;
but in neither of the men were there the slightest symptoms of
poisoning. It is obvious that the existence of such a habit might
seriously complicate any inquiry into arsenical poisoning in these
regions.

[721] _Edin. Med. Journ._, April 1865; _Brit. and For. Med. Chir.
Journ._, Oct. 1865.

§ 723. =Manner of Introduction of Arsenic.=--Arsenious acid exerts a
poisonous action, whether it is taken by the stomach, or introduced into
the system by any other channel whatever. The differences in the
symptoms produced by external application (as through a wound), and by
swallowing arsenious acid in substance or in solution, are not so marked
as might be expected. It was probably Hunter who first distinctly
recognised the fact that arsenic, even when introduced outwardly by
application to an abraded surface, exerts a specific effect on the
mucous membrane of the stomach. Brodie[722] states, “Mr. Home informed
me that in an experiment made by Mr. Hunter himself, in which arsenic
was applied to a wound in a dog, the animal died in twenty-four hours,
and the stomach was found to be considerably inflamed. I repeated this
experiment several times, taking the precaution of always applying a
bandage to prevent the animal licking the wound. The result was that the
inflammation of the stomach was commonly more violent and more immediate
than when the poison was administered internally, and that it preceded
in appearance the inflammation of the wound.”

[722] _Phil. Trans._, 1812.

§ 724. =Cases of Poisoning by the External Application of Arsenic.=--A
mass-poisoning by the external use of arsenical violet powder to infants
occurred in England some years ago. Two deaths from this cause were
established by coroners’ inquests.[723] Dr. Tidy found the violet
powders used in the two cases to have the following composition:--

[723] “Gleanings in Toxicology,” by C. Meymott Tidy, M.B.--_Lancet_,
Aug. 21, 1878.

                             1.         2.
                          Per cent.  Per cent.
  Arsenious Acid,           38·5       38·3
  Starch (Potato),          54·8       55·4
  Magnesia, &c.              6·7        6·3[724]

[724] Two recipes were handed in at the coroner’s inquest which pretty
fairly represent the composition of ordinary commercial violet powder:--

  _First Quality, sold at 7s. per gross._

  Starch Powder,                      28  lbs.
  Magnesia,                            1½ lb.
  Orris-root,                          1  lb.
  Violet Perfume,                      1  oz.
  Essence of Roses,                    5  drops.

  _Second Quality, sold at 6s. per gross._

  Terra Alba (Sulphate of Lime),      14  lbs.
  Potato Starch,                      21  lbs.
  Magnesia,                            3  lbs.
  Orris-root,                          1½ lb.
  Violet Perfume,                      1½ oz.
  Essence of Roses,                    5  drops.


Although the children were poisoned by absorption through the skin
(unless it is allowed that some may have found its way in the form of
arsenical dust into the throat, or, what is still more probable, that
the infants may from time to time have seized the puff-ball and _sucked_
it), the large quantity of ·421 grm. (6·5 grains) of arsenious acid was
separated in the one case, and ·194 grm. (3 grains) in the other. In
these cases arose the question which is sure to recur in legal inquiries
into poisoning by absorption, viz., whether the poison lying on the
surface and folds of the skin could not have been mixed during the
_post-mortem_ examination with the organs of the body? In these
particular cases special care appears to have been taken, and the answer
was satisfactory. It is not amiss, however, to call attention to the
extreme precaution which such instances necessitate.

A woman, aged 51, had used a solution of arsenious acid to cure the
itch; erysipelas of the body, however, followed, and she died after a
long illness--one of the symptoms noted being trembling and paresis of
the limbs.[725] In a case recorded by Desgranges,[726] a young
chambermaid had applied to the unwounded scalp an arsenical ointment for
the purpose of destroying vermin. She also suffered from a severe
erysipelas, and the hair fell off. Quacks have frequently applied
various arsenical pastes to ulcers and cancerous breasts with a fatal
result. Instances of this abound; in one, a charlatan applied to a
chronic ulcer of the leg an arsenical caustic; the patient showed
symptoms of violent poisoning, and died on the sixth day.[727] In
another, a lady suffering from some form of tumour of the breast,
applied to an unqualified practitioner, who made from fifteen to twenty
punctures with a lancet in the swelling, covered a piece of bread with
an arsenical compound, and applied the bread thus prepared to the
breast. Twelve hours afterwards symptoms of violent gastric irritation
commenced; and vomiting and a sanguinolent diarrhœa followed, with death
on the fifth day. Arsenic was found in all the organs.[728] Such
examples might be multiplied. Arsenic has been in more than one case
introduced criminally into the vagina with a fatal result.[729] Foderé,
_e.g._, has recorded the case of a maid-servant who poisoned her
mistress by intentionally administering several arsenical enemata.[730]
Arsenious acid again has been respired in the form of vapour. One of the
best instances of this is recorded by Taylor, and was the subject of a
trial at the York Lent Assizes, 1864. The prisoner placed some burning
pyrites at the doorway of a small room, in which there were eight
children, including an infant in the cradle. The other children were
removed speedily, but the infant was exposed to the vapour for an hour;
it suffered from vomiting and diarrhœa, and died in twenty-four hours.
There was slight inflammation of the stomach and intestines, the brain
and lungs were congested, and the lining membrane of the trachea of a
bright red colour. Arsenic was detected in the stomach, in the lungs,
and spleen. The pyrites contained arsenic, and the fatal fumes were in
effect composed of sulphurous and arsenious acids.

[725] Belloc, _Méd. Lég._, t. iv. p. 124.

[726] _Recueil de la Soc. de Méd. de Paris_, t. vi. p. 22, An. vii.;
also Tardieu, _Étude Méd. Légale, sur l’Empoisonnement_, Obs. xxvii. p.
457.

[727] Mean, _Bibliothèque Méd._, t. lxxiv., 1821, p. 401.

[728] Tardieu, _op. cit._, Obs. xxix.; Dr. Vernois, _Ann. d’Hyg. et de
Méd. Lég._, t. xxxvi., 1st ser., p. 141, 1846.

[729] Ansiaulx, _Clinique Chirurgicale_. Mangor (_Acta. Societ. Reg.
Hafniens_, iii. p. 178) gives the case of a man who poisoned his three
wives successively with arsenic--the two last by introducing into the
vagina a powder composed of flour and arsenic. Another similar case is
related by Brisken. Mangor made experiments on mares, showing that when
arsenic is applied to the vagina, death may result from inflammation.

[730] _Méd. Légale_, iv.

§ 725. =Arsenic in Wall-Papers.=--It is now an accepted fact that
arsenical colours on wall-papers cause illness. The symptoms are those
of chronic poisoning, and present nothing distinctive from the effects
produced from small doses of arsenic.

Kirschgasser[731] has described the symptoms in detail of twenty-six
cases. That arsenic is actually present in patients suffering is often
susceptible of proof, by examining skilfully and carefully a
considerable volume (from one to two days’ collection) of the urine; in
most of the cases thus examined arsenic has been discovered. This
poisoning is produced, sometimes from the dust, at others from a
volatile compound of arsenic, which has the following properties:--It is
very volatile (perhaps a gas), it has a strong alliaceous odour, it is
not entirely decomposed by a solution of silver nitrate, but is
apparently decomposed by a boiling acid solution of potassic
permanganate. The author suggests that it may be a compound of CO and
As, but this is only a supposition. The existence of this volatile
substance has been settled beyond all question by the experiments of
Gosio,[732] confirmed by those of Charles Robert Sanger.[733]

[731] _Vierteljahr. f. gericht Med._, N. F., ix. 96.

[732] _Azione di alcune Muffe sui Compositi fissi d’Arsenico. Ministero
dell’ Interno, Laboratori Scientifici della Direzione di Sanita_, Roma,
1892.

[733] “On the Formation of Volatile Compounds of Arsenic from Arsenical
Wall-Papers,” _American Academy of Arts and Sciences_, vol. xxix.

This substance appears to be readily enough produced by the action of
the common moulds upon organic matter in the presence of small amounts
of arsenic; the moulds vary in this property: _Mucor_, _Mucedo_, and
_Aspergillum glaucum_ react well; on the contrary, _Penicillium
glaucum_, _Mucor ramosus_, and several others have either no action, or
the action is but slight. One mould, the _Penicillium brevicaule_, has
quite a special endowment in forming this peculiar arsenical compound;
so much so, that Gosio has proposed its use as a reagent for arsenic,
the garlic odour being perceived when the fungus is made to grow in
solutions containing organic matter and only traces of arsenic.

§ 726. =Forms of Arsenical Poisoning.=--There are at least four distinct
forms of arsenical poisoning, viz., an acute, subacute, a nervous, and a
chronic form.

=Acute Form.=--All those cases in which the inflammatory symptoms are
severe from the commencement, and in which the sufferer dies within
twenty-four hours, may be called acute. The commencement of the symptoms
in these cases is always within the hour; they have been known, indeed,
to occur within eight minutes, but the most usual time is from twenty
minutes to half an hour. There is an acrid feeling in the throat, with
nausea; vomiting soon sets in, the ejected matters being at first
composed of the substances eaten; later they may be bilious or even
bloody, or composed of a whitish liquid. Diarrhœa follows and
accompanies the vomiting, the motions are sometimes like those met with
in ordinary diarrhœa and English cholera, and sometimes bloody. There is
coldness of the extremities, with great feebleness, and the pulse is
small and difficult to feel. The face, at first very pale, takes a
bluish tint, the temperature falls still lower; the patient sinks in
collapse, and death takes place in from five to twenty hours after the
taking of the poison.

There can scarcely be said to be any clinical feature which
distinguishes the above description from that of cholera; and supposing
that cholera were epidemic, and no suspicious circumstance apparently
present, there can be little doubt that a most experienced physician
might mistake the cause of the malady, unless surrounding circumstances
give some hint or clue to it. In the acute form diarrhœa may be absent,
and the patient die, as it were, from “shock.” This was probably the
cause of death in a case related by Casper,[734] that of Julius Bolle,
poisoned by his wife. He took an unknown quantity of arsenic in
solution at seven in the morning, and in about three-quarters of an hour
afterwards suffered from pain and vomiting, and died in little more than
three hours. There were no signs of inflammation in the stomach and
intestines, but from the contents of the stomach were separated ·0132
grm. of arsenious acid, and ·00513 grm. from pieces of the liver,
spleen, kidneys, lung, and blood. The dose actually taken is supposed
not to have been less than ·388 grm. (6 grains).

[734] Case 188 in Casper’s _Handbuch_.

§ 727. =The Subacute Form.=--The subacute form is that which is most
common; it exhibits some variety of phenomena, and individual cases vary
much in the matter of time. The commencement of symptoms is, as in the
most acute form, usually within the hour, but exceptions to this rule
occur. In a case quoted by Taylor,[735] and recorded by M. Tonnelier,
the poison did not cause any marked illness for eight hours; it was
found, on _post-mortem_ examination, that a cyst had been formed in the
stomach which sheathed the arsenic over, and in some degree explained
this delay. In another case, again, ten hours elapsed, and this is
considered to be the maximum period yet observed. As with the acute
form, there is a feeling of nausea, followed by vomiting, which
continues although the stomach is quite empty; at first the ejected
matter is a watery fluid, but later it may be streaked with blood. The
tongue is thickly coated; there is great thirst, but the drinking of any
liquid (even of ice-cold water) increases the vomiting. Nearly always
pain is felt in the epigastrium, spreading all over the abdomen, and
extending to the loin (which is tense and tender on pressure).
Deglutition is often painful, and is accompanied by a sort of spasmodic
constriction of the pharyngeal muscles. Diarrhœa follows the vomiting,
and has the same characters as that previously described; occasionally,
however, this feature is absent. In the case recorded by Martineau,[736]
a man, aged 25, was seized at 10 A.M. suddenly with vomiting, which
persisted all that day and the next, during which time the bowels were
obstinately confined. On the second day a purgative was administered,
whereupon diarrhœa set in, and continued until his death, which occurred
in about two days and sixteen hours from the commencement of the
symptoms. This case is also remarkable from the absence of pain or
tenderness of the abdomen.

[735] Taylor’s _Principles and Practice of Jurisprudence_, vol. i. p.
251; Flandin, vol. i. p. 535.

[736] Tardieu, _op. cit._, Obs. xix.

In subacute cases the urine has several times been suppressed, and it is
generally scanty and red in colour. Irregularity of the heart’s action
and feebleness are tolerably constant phenomena. As the end approaches,
there is excessive muscular weakness, the face is pale, the eyes hollow;
the mucous membranes first, and then the skin, take a bluish tint; the
skin itself is covered with perspiration, and there has been noticed a
peculiar odour, which has been likened to arsine (arseniuretted
hydrogen). The respiration is troubled, convulsive movements of the
limbs have been observed, and cramps in the calves of the legs; death
follows in a variable time--from twenty-four hours to several days. In
certain cases there is a curious remission after violent symptoms, the
patient rallies and seems to have recovered; but the appearance is
deceptive, for the symptoms recur, and death follows. Recovery may also
take place partially from the primary effects, and then inflammatory
changes in the stomach, &c., set in, with fever and the ordinary
symptoms which are common in all internal inflammation.

A single dose of arsenious acid may cause a prolonged and fatal illness,
one of the best known examples being that of the suicide of the Duc de
Praslin,[737] who took, with suicidal intent, on Wednesday, August 18,
1847, a dose of arsenious acid. The exact time of the act could not be
ascertained, but the first effects appeared at 10 P.M.; there were the
usual signs of vomiting, followed on the next day by diarrhœa, fainting,
and extreme feebleness of the pulse. On Friday there was a remission of
the symptoms, but great coldness of the limbs, intermittency and
feebleness of the heart’s action, and depression. On Saturday there was
slight fever, but no pain or tenderness in the abdomen, vomiting, or
diarrhœa; on this day no urine was passed. On the Sunday he complained
of a severe constriction of the throat, and deglutition was extremely
painful; thirst was extreme, the tongue intensely red, as well as the
mucous membrane of the mouth and pharynx, and the patient had a
sensation of burning from the mouth to the anus. The abdomen was painful
and distended, the heat of the skin was pronounced, the pulse frequent
and irregular,--sometimes strong, at others feeble,--the bowels had to
be relieved by injections, the urine was in very small quantity; during
the night there was no sleep. The duke died at 4.35 A.M. on Tuesday the
24th, the sixth day; intelligence was retained to the last. As the end
approached, the respiration became embarrassed, the body extremely cold,
and the pulse very frequent.

[737] Tardieu, “Relation Médico-Légale de l’Assassinat de la Duchesse de
Praslin,” _Ann. d’Hyg. Pub. et de Médico-Lég._, 1847, t. xxxviii. p.
390; also _op. cit._, Obs. xi.

§ 728. =In the nervous form= the ordinary vomiting and purging are
either entirely suppressed, or present in but feeble degree; and under
this heading are classed the rare cases in which, in place of the
ordinary symptoms, affections of the nervous system predominate.
Narcotism, paresis, deepening into paralysis, delirium, and even acute
mania, as well as epileptiform convulsions, have all been recorded. In
short, the symptoms show so much variety, that an idea of the malady
produced in this very rare form can only be obtained by studying the
clinical history of cases which have presented this aspect. In a case
recorded by Guilbert,[738] a man, thirty-five years of age, had
swallowed a solution of arsenic, half of which was immediately rejected
by vomiting. A little while afterwards his respiration became laborious;
the eyes were bathed with tears, which were so acrid as to inflame the
eyelids and the cheeks; the muscles of the face were from time to time
convulsed; he perspired much, and the perspiration had a fœtid odour;
there was some diarrhœa, the urine was suppressed, and from time to time
he was delirious. Afterwards the convulsions became general, and the
symptoms continued with more or less severity for five days. On the
sixth a copious miliary eruption broke out, and the symptoms became less
severe. The eruption during fifteen days every now and again reappeared,
and at the end of that time the patient was convalescent, but weak,
liable to ophthalmia, and had a universal trembling of the limbs.

[738] _Journal de Van der Monde_, 1756, t. iv. p. 353; Tardieu, _op.
cit._, Obs. xiii. p. 430.

In one of Brodie’s[739] experiments on rabbits, 7 grains of arsenious
acid were inserted in a wound in the back; the effect of which was to
paralyse the hind legs. In other experiments on animals, paralysis of
the hind legs has been frequently noticed, but paralysis certainly is
rare in man; in the case, however, recorded by Barrier,[740] of the five
men who took by mistake a solution of arsenious acid, one of them was
found stretched on the ground with the inferior extremities paralysed.

[739] “The Action of Poisons,” _Phil. Trans._, 1812.

[740] _Journ. de Médecine_, 1783, p. 353; Tardieu, _op. cit._, Obs. xiv.
p. 431.

In a case of “mass” poisoning reported by Dr. Coqueret,[741] three
persons ate by mistake an unknown quantity of arsenious acid--two of
them only suffered slightly, but the third severely, vomiting occurring
almost immediately, and continuing with frequency until the end of the
fourth day. Two hours after swallowing the poison, the patient took the
hydrated oxide of iron as an antidote. On the sixth day there was stupor
and a semi-delirious state, with an eruption of a pustular character
compared to that of the small-pox. These symptoms continued more or less
until the fifteenth day, when they diminished, and ultimately the
patient recovered. In a case related by Tardieu,[742] in which a person
died on the eleventh day from the effects of the poison, towards the
end, as a specially marked symptom, there was noted hyperæsthesia of the
inferior extremities, so that the least touch was painful.

[741] _Journ. de Connaiss. Méd. Chirurg._, 1839, p. 155; Tardieu, _op.
cit._, Obs. xv. p. 482.

[742] _Op. cit._, Obs. xvii. p. 434.

§ 729. =Absence of Symptoms.=--In a few cases there have been a
remarkable absence of symptoms, and this both in man and animals. Seven
horses were fed with oats accidentally mixed with arseniate of soda.
The first succumbed three hours after taking the poison, without having
presented any symptom whatever; he fell suddenly, and in a short time
expired.[743] It is related by Orfila,[744] that a woman, aged 27,
expired in about twelve hours from a large dose of arsenious acid; there
were the usual _post-mortem_ appearances, but in life no sign of pain,
no vomiting, and but little thirst.

[743] Bouley (Jeune), _Ann. d’Hyg. et de Médico-Lég._, 1834, t. xii. p.
393.

[744] Tome i. Obs. iv. p. 314.

§ 730. =Slow Poisoning.=--Slow poisoning has been caused accidentally by
arsenical wall-paper, in the manufacture of arsenical pigments, by the
admixture of small quantities of arsenic with salt or other condiments,
and repeated small doses have been used for criminally producing a fatal
illness intended to simulate disease from natural causes. The illness
produced by small intermittent doses may closely resemble in miniature,
as it were, those produced by large amounts; but, on the other hand,
they may be different and scarcely to be described otherwise than as a
general condition of ill-health and _malaise_. In such cases there is
loss of appetite, feebleness, and not unfrequently a slight yellowness
of the skin. A fairly constant effect seen, when a solution of arsenious
acid is given continuously for a long time, is an inflammation of the
conjunctivæ, as well as of the nasal mucous membrane--the patient
complains of “always having a cold.” This inflammatory action also
affects the pharynx, and may extend to the air-passages, and even to the
lung-tissue. At the same time there is often seen an exanthem, which has
received a specific name--“_eczema arsenicale_.” Salivation is present,
the gums are sore, at times lacerated. In chronic poisoning by arsenic,
nervous symptoms are almost constant, and exhibit great variety; there
may be numbness, or the opposite condition, hyperæsthesia, in the
extremities. In certain cases fainting, paresis, paralysis, and
sometimes convulsions occur; towards the end a sort of hectic fever
supervenes, and the patient dies of exhaustion.

    § 731. =The Maybrick Case.=[745]--The Maybrick case may be
    considered an example of poisoning extending over a considerable
    period of time:--Mr. James Maybrick, a Liverpool cotton-broker, aged
    49, married Florence Elizabeth, an American lady, aged 21. They had
    two children. The marriage proved an unhappy one. Some two years
    before his death in May 1889 they had occupied two separate rooms.
    Seven weeks before the husband’s death, Mrs. Maybrick went to London
    on a false pretext, and lived for some days at an hotel, ostensibly
    the wife of another man. Two days after her return, Mr. and Mrs.
    Maybrick attended the Grand National race meeting, and there a
    serious quarrel arose between them respecting the man with whom she
    had cohabited in London; they returned from the race, each
    separately, and she slept apart. Next day an apparent reconciliation
    took place through the intervention of Dr. Fuller, the family
    medical attendant.

[745] “The Maybrick Trial and Arsenical Poisoning,” by Thos. Stevenson,
M.D., _Guy’s Hosp. Rep._, 1889.

    On or about April 12-19th, 1889, Mrs. Maybrick purchased arsenical
    fly-papers. On April 13-20th Mr. Maybrick visited London, and
    consulted Dr. Fuller for dyspepsia, who prescribed nux vomica,
    acids, and mild remedies (but no arsenic); in one bottle of
    medicine, ostensibly made according to Dr. Fuller’s prescription,
    arsenic was subsequently found.

    Up to Saturday, April 27th, Mr. Maybrick was in his usual health; he
    was then sick, numbed, and in pain, and had cramps; he told his
    clerk he had been an hour in the water-closet, but whether for
    diarrhœa or constipation does not appear; he ascribed the symptoms
    to an overdose of Fuller’s medicine. About this date fly-papers were
    found by the servants soaking in Mrs. Maybrick’s bedroom in a
    sponge-basin, carefully covered up. On the 29th she again purchased
    two dozen fly-papers from another chemist. On April 28th Mr.
    Maybrick was sick and ill; at 11 A.M. Dr. R. Humphreys was called
    in; Mr. Maybrick complained of a peculiar sensation about his heart,
    and said he was in dread of paralysis. He attributed his illness to
    a strong cup of tea taken before breakfast. On the following day he
    was better, and on the 30th still improving. On May 1st and 2nd Mr.
    Maybrick went to his office and lunched, both days, off revalenta
    food, prepared at home and warmed at his office in a new saucepan
    purchased for the occasion; on one of these days the lunch was
    forgotten, and was sent to Mr. Maybrick by his wife; and on one of
    the two days, it is not clear which, Mr. Maybrick complained that
    his lunch did not agree with him, and he attributed it to inferior
    sherry put into his food.

    In a jug found at the office, and in which food had been taken
    there, a trace of the food still remained after Mr. Maybrick’s
    death, and arsenic was found therein.

    On May 3rd the last fatal illness set in. It is uncertain what food
    he had after breakfast; he went to the office, and returned home
    between 5 and 6 P.M. He had been seen by Dr. Humphreys in the
    morning, and appeared then not quite so well; he found him at
    midnight suffering from what he thought was severe sciatica; the
    patient said he had been sick from revalenta. On May 4th he was
    continually sick, nothing could be retained on the stomach, but the
    sciatic pain was gone; on May 5th the vomiting continued, the
    patient complained of the sensation of a hair sticking in the
    throat, and of a filthy taste in the mouth. The throat and fauces
    were only slightly reddened, the tongue was furred.

    On May 6th there was less vomiting, but otherwise the condition was
    the same, and Fowler’s solution ordered, but only a quantity equal
    to 1/300 grain was actually taken.

    May 7th the condition was improved, but there was no increase of
    power. Dr. W. Carter was called in consultation. The vomiting was
    passing away, and diarrhœa commencing. The throat was red, dry, and
    glazed; there were incessant attempts to cough up an imaginary hair.
    No cramps, no pain in the stomach or intestines, nor conjunctivitis.
    On this day the first direct evidence of diarrhœa is recorded, the
    medical men actually seeing a loose motion. The result of the
    consultation was that Mr. Maybrick must have taken some irritant in
    his food or drink.

    On the 8th a professional nurse took charge. During the 8th and 9th
    severe tenesmus set in with diarrhœa, and blood was observed in the
    fæces. Now arsenic was suspected, the urine was examined by Dr.
    Humphreys, and a rough analysis was made of some Neaves’ food which
    the patient had been taking.

    The patient died on the 10th, at 8.30 P.M.

    The _post-mortem_ appearances were as follows:--

    The tongue was dark, the top of the gullet slightly red, but
    otherwise healthy, save at the lower end, where the mucous membrane
    was gelatinous, and was dotted over with black dots, like frogs’
    spawn.

    There was a small shallow ulcer in the mucous membrane of the larynx
    at the back of the epiglottis. The free margin of the epiglottis was
    rough and eroded; and on the posterior aspect of the ericoid
    cartilage there were two small red patches. In the stomach were
    from 5-6 ozs. of brownish fluid. At the cardiac end there was a
    large vermilion-red patch, interspersed here and there with small
    dark ecchymoses (spoken of by Dr. Humphreys as a flea-bitten
    appearance); to this followed a non-inflamed space, and near the
    pyloric orifice, and extending 2 inches from it, was another red
    inflamed portion of mucous membrane. In the small intestine the
    mucous membrane was red and inflamed, from 3 inches below the
    pylorus to about 3 feet downwards. About 18 or 20 feet lower down,
    _i.e._, a little below the ileo-cæcal valve, the mucous membrane was
    again inflamed to a lesser extent over a space of about 2 feet; the
    lower end of the rectum was also red and inflamed. No arsenic was
    found in the stomach or its contents, or in the spleen. Arsenic was
    present in the liver, in the intestines, and in the kidneys. The
    quantity separated altogether amounted to over 0·1 grain. The liver
    weighed 48 ozs., and from 12 ozs. of the liver 0·076 grain of
    arsenic, reckoned as As₂O₃, was separated.

    The whole course of the symptoms and the _post-mortem_ examination
    showed that the deceased died from an irritant poison; and from the
    fact of a small quantity of arsenic having been found in the body,
    there can be little doubt but that the poison was arsenic. The
    symptoms were somewhat anomalous, but not more so than in other
    recorded cases of undoubted arsenical poisoning. The facts that
    tended to connect the accused with the death were as follows:--On
    the night of either May 9th or the 10th Mrs. Maybrick was observed
    to remove from the table an opened bottle of Valentine’s meat juice,
    and take it into an inner dressing-room, and then replace it--the
    acts being surreptitious. In replacing it, she was observed to take
    it either from the pocket of her dressing-gown or from an inner
    pocket. The lining of this pocket was found to be impregnated with
    As₂O₃. The juice was found to contain 0·5 grain As₂O₃, and the
    liquid was of lower gravity than commercial juice; it had probably,
    therefore, been diluted.

    The following is a list of things containing arsenic:--

   1. Mrs. Maybrick’s dressing-gown.
   2.       „         apron.
   3. A handkerchief wrapped around a bottle.
   4. Packet of arsenic “for cats.” (Arsenious acid mixed with char-
      coal.) Tumbler containing milk, with handkerchief soaking in it;
      at least 20 grains of As₂O₃ in the tumbler mixed with charcoal.
   5. A portion of a handkerchief.
   6. A bottle containing a strong solution of arsenious acid and
      several grains of undissolved arsenious acid.
   7. A bottle containing from 15-20 grains of solid arsenic and a few
      drops of solution.
   8. A saturated solution of arsenious acid and some solid arsenious
      acid.
   9. Valentine’s meat juice.
  10. Price’s glycerin; ⅔ grain in the whole bottle.
  11. A bottle containing 0·1 grain of arsenious acid.
  12. A bottle from Mr. Maybrick’s office containing a few drops of
      medicine prescribed by Dr. Fuller (decidedly arsenical).
  13. Jug from the office with remains of food.
  14. Sediment from trap of w.c. and lavatory drain containing As₂O₃.

    Mrs. Maybrick was convicted, but afterwards the sentence was
    commuted to penal servitude for life.

§ 732. =Post-mortem Appearances in Animals.=--P. Hugo[746] has made some
minute researches as to the pathological appearances met with in
animals. His experiments were made on seven dogs, eight guinea-pigs,
five rabbits, two pigeons, and five cats--all poisoned by arsenious
acid. According to Hugo, so far as these animals were concerned, changes
were more constant in the intestine than in the stomach.

[746] _Beiträge zur Pathologie der acuten Arsenikvergiftung., Archiv für
exper. Pathol. u. Pharmakol._, Leipzig, 1882.

=Stomach.=--Changes in the mucous membrane were especially noticed in
the great curvature and towards the pylorus; the pylorus itself, and a
part of the cardiac portion, remained unchanged. The mucous membrane in
dogs and cats was red, with a tinge of blue--in many cases the redness
was in streaks, with injection of the capillaries. The stomach of
plant-eaters was less altered, and a microscopical examination of the
mucous tissues did not show any fatty change.

=The Intestines.=--In dogs and cats changes were evident; in rabbits and
guinea-pigs they were not so marked, but the intestines of the last were
extremely tender and brittle, very moist, and filled with a slimy,
serous, grey-white fluid; nevertheless, the changes in all these animals
appear to be of essentially the same nature. The most striking effect is
the shedding of a pseudo-membrane; in quite recent cases there is a
layer of from 1 to 1½ mm. wide of a transparent, frog-spawn-like jelly
streaking the intestine. In later stages it becomes thicker, while
occasionally it resembles a diphtheritic exudation. The mucous membrane
itself is deep purple-red, showing up by the side of the
pseudo-membrane. With regard to the villi, the epithelial layer is
detached, and the capillary network filled with blood and enlarged.

=The Liver.=--Hugo met only occasionally with fatty degeneration of the
liver, but there was marked steatosis of the epithelium of the
gall-bladder of dogs. A fact not prominently noticed before, is (at all
events, in dogs) a serous transudation into the pleural sac and acute
œdema of the lungs; the exudation may be excessive, so that more than
100 c.c. of serous fluid can be obtained from the thorax; there is also
usually much fluid in the pericardium. In two of Hugo’s experiments
there was fluid in the cerebral ventricles; and in all there was
increased moisture of the brain substance with injection of the
capillary vessels, especially of the pia.

§ 733. =Post-mortem Appearances.=--A remarkable preservation of the body
is commonly, but not constantly, observed. When it does occur it may
have great significance, particularly when the body is placed under
conditions in which it might be expected to decompose rapidly. In the
celebrated Continental case of the apothecary Speichert (1876),
Speichert’s wife was exhumed eleven months after death. The coffin stood
partly in water, the corpse was mummified. The organs contained arsenic,
the churchyard earth no arsenic. R. Koch was unable to explain the
preservation of the body, under these conditions, in no other way than
from the effect of arsenic; and this circumstance, with others, was an
important element which led to the conviction of Speichert.

When arsenious acid is swallowed in substance or solution, the most
marked change is that in the mucous membrane of the stomach and
intestines; and, even when the poison has been absorbed by the skin, or
taken in any other way, there may be a very pronounced inflammatory
action. On the other hand, this is occasionally absent. Orfila[747]
relates a case in which a man died in thirteen hours after having taken
12 grms. of arsenious acid:--“The mucous membrane of the stomach
presented in its whole extent no trace of inflammation, no redness, and
no alteration of texture.” Many other similar cases are on record; and,
according to Harvey’s statistics, in 197 cases, 36 (about 18·2 per
cent.) presented no lesion of the stomach.

[747] Tome i. Obs. v.

The usual changes produced by arsenious acid may be studied in the
museums of the London hospitals. In Guy’s Hospital Museum there are
three preparations. In preparation 1798³² is seen a large stomach with
the mucous membrane at certain points abraded, and at the great
curvature the whole coats are thinned; it is also somewhat congested. In
preparation 1798⁶⁴ is a portion of coagulated lymph, from the stomach of
a lad, aged 14, who had taken accidentally a piece of cheese charged
with arsenious acid, prepared for the purpose of destroying rats. He
lived twenty-eight hours, and presented the ordinary symptoms. The lymph
has a membranous appearance, and the rugæ of the stomach are impressed
upon it. It is said when recent to have presented numerous bright bloody
spots, although there was no visible breach of substance on the surface
of the stomach. The mucous membrane of the stomach is stated to have
been injected, and there was also diffuse injection of the duodenum.
Preparation 1798⁸⁰ is the stomach of a person who survived thirteen
hours after taking a fatal dose of arsenious acid; and in the same
museum there is a wax model of the appearances which the fresh
preparation exhibited, showing a large oval patch coated with mucus and
the poison. The stomach was intensely inflamed, the cæcum injected. The
rest of the intestine was healthy.

In the museum of University College there are two preparations, one[748]
exhibiting intense swelling and congestion of the gastric mucous
membrane, which is of a perfectly vermilion colour. Another preparation
(No. 2868) shows the effect of a small dose of arsenic on the stomach;
there are spots of arborescent extravasation, and slight congestion of
the summits of the rugæ, but in other respects it is normal. There is
also a cast of Peyer’s patches from the same case, showing great
prominence of the glands, with some injection of the intestinal mucous
membrane.

[748] This preparation at the time of my visit had no number.

In St. Thomas’ Hospital there is an interesting preparation (No. 8)
showing the gastric mucous membrane dotted all over with minute ulcers,
none of which have an inflammatory zone.[749] I have not, however, seen
in any museum a preparation of the curious emphysematous condition of
the mucous membrane, which has more than once been met with. For
example, in a case related by Tardieu,[750] Schwann, a labourer, died
from the effects of arsenic in thirty-six hours. The autopsy showed that
the mucous membrane of the stomach and small intestine was covered with
a pasty coating, and was elevated in nearly its whole extent by bullæ
filled with gas, forming true emphysematous swellings which encroached
upon the diameter of the intestine. There was neither redness nor
ulceration, but the mucous membrane was softened.

[749] In a case related by Orfila, t. i. Obs. xv., death resulted from
the outward application of arsenic; the mucous membrane of the stomach
was natural in colour, but there were four ulcers, one of which was 50
centimetres in diameter.

[750] _Op. cit._, Obs. i. p. 468.

The author saw, many years ago, at Barnard Castle, an autopsy made on a
gentleman who died from arsenic. In this case the mucous membrane of the
stomach presented a peculiar appearance, being raised here and there by
little blebs, and very slightly reddened.

§ 734. The inflammatory and other changes rarely affect the gullet.
Brodie[751] never observed inflammation of the œsophagus as an effect of
arsenic; but, when arsenic is swallowed in the solid state, as in the
suicide of Soufflard, graphically described by Orfila,[752] it may be
affected. In Soufflard’s case there was a vivid injection of the pharynx
and gullet.

[751] _Phil. Trans._, 1812.

[752] T. i. p. 319.

In many instances, when the arsenic has been taken in the solid form,
the crystals with mucus and other matters adhere to the lining membrane.
I have seen in the stomach of a horse, poisoned by an ounce of arsenic,
an exquisite example of this. The inflammatory changes may be recognised
many months after death owing to the antiseptic properties of arsenic;
nevertheless, great caution is necessary in giving an opinion, for there
is often a remarkable redness induced by putrefactive changes in healthy
stomachs. Casper,[753] on this point, very justly observes:--“If Orfila
quotes a case from Lepelletier, in which the inflammatory redness of the
mucous membrane of the stomach was to be recognised after nine months’
interment, and if Taylor cites two cases in which it was observed
nineteen and twenty-one months after death respectively, this is in
contradiction of all that I, on my part, have seen in the very numerous
exhumed corpses examined by me in relation to the gradual progress of
putrefaction and of saponification, and I cannot help here suspecting a
confusion with the putrefactive imbibition redness of the mucous
membrane.”

[753] _Handbuch_, vol. ii. p. 420.

If examined microscopically, the liver and kidneys show no change, save
a fatty degeneration and infiltration of the epithelial cells. In the
muscular substance of the heart, under the endocardium, there is almost
constantly noticed ecchymosis. In the most acute cases, in which a
cholera-like diarrhœa has exhausted the sufferer, the blood may be
thickened from loss of its aqueous constituents, and the whole of the
organs will present that singularly dry appearance found in all cases in
which there has been a copious draining away of the body fluids. In the
narcotic form of arsenical poisoning, the vessels of the brain have been
noted as congested, but this congestion is neither marked nor
pathognomonic. Among the rare pathological changes may be classed
glossitis, in which the whole tongue has swollen, and is found so large
as almost to fill the mouth. This has been explained, in one case, as
caused by solid arsenious acid having been left a little time in the
mouth before swallowing it. On the other hand, it has also been observed
when the poison has been absorbed from a cutaneous application. When
arsenic has been introduced into the vagina, the ordinary traces of
inflammatory action have been seen, and, even without direct contact, an
inflammation of the male and female sexual organs has been recorded,
extending so far as gangrene. As a rule, putrefaction is remarkably
retarded, and is especially slow in those organs which contain arsenic;
so that, if the poison has been swallowed, the stomach will retain its
form, and, even to a certain extent, its natural appearance, for an
indefinite period. In corpses long buried of persons dying from
arsenical poisoning, the ordinary process of decay gives place to a
saponification, and such bodies present a striking contrast to others
buried in the same graveyard. This retardation of putrefaction is what
might, _à priori_, be expected, for arsenic has been long in use as a
preservative of organic tissues.

§ 735. =Physiological Action of Arsenic.=--The older view with regard to
the essential action of arsenic was, without doubt, that the effects
were mainly local, and that death ensued from the corrosive action on
the stomach and other tissues--a view which is in its entirety no longer
accepted; nevertheless, it is perfectly true that arsenic has a
corrosive local action; it will raise blisters on the skin, will inflame
the tongue or mucous membranes with which it comes in contact; and, in
those rapid cases in which extensive lesions have been found in the
alimentary canal, it can hardly be denied that instances of death have
occurred more from the local than the constitutional action. In the vast
majority of cases, however, there is certainly insufficient local action
to account for death, and we must refer the lethal result to a more
profound and intimate effect on the nervous centres. The curious fact,
that, when arsenic is absorbed from a cutaneous surface or from a
wound, the mucous membrane of the stomach inflames, is explained by the
absorption of the arsenic into the blood and its separation by the
mucous membrane, in its passage exerting an irritant action. The
diarrhœa and hyperæmia of the internal abdominal organs have been
referred to a paralysis of the splanchnic nerves, but Esser considers
them due to an irritation of the ganglia in the intestinal walls. Binz
has advanced a new and original theory as to the action of arsenious
acid; he considers that the protoplasm of the cells of many tissues
possess the power of oxidising arsenious acid to arsenic acid, and this
arsenic acid is again, by the same agency, reduced to arsenious acid, in
this way, by the alternate oxidation and reduction of the arsenious
acid, the cells are decomposed, and a fatty degeneration takes place.
Thus arsenic causes fatty changes in the liver, kidney, and other cells
by a process analogous to the action of phosphorus. T. Araki[754] also
considers that both arsenic and phosphorus lessen oxidation, and points
out that lactic acid appears in the urine when either of these poisons
are taken, such acid being the result of insufficient oxidation. A
notable diminution of arterial pressure has been observed. In an
experiment by Hugo[755] ·03 grm. of As₂O₃ was injected intravenously,
the normal arterial pressure being 178 mm. Ten minutes after injection
the pressure sank to 47 mm.; in sixteen minutes it again rose to 127 mm.
Accumulative action of arsenic does not occur. Hebra has given, in skin
diseases, during many months, a total quantity of 12 grms. without evil
result.

[754] _Zeit. physiol. Chem._, xvii. 311-339.

[755] _Op. cit._

§ 736. =Elimination of Arsenic.=--Arsenic is separated especially by the
urine,[756] then through the bile, and by the perspiration. The eruption
often observed on the skin has been referred to the local action of
small quantities of arsenic in this way eliminated. It is found in the
urine first after from five to six hours, but the elimination from a
single dose is not finished till a period of from five to eight days; it
has often been looked for twelve days after taking it, but very seldom
found. According to Vitali, the arsenic in the urine is not free, but
probably displaces phosphorus in phospho-glyceric acid; possibly it may
also replace phosphorus in lecithin.

[756] An old experiment of Orfila’s has some practical bearings, and may
be cited here. A dog was treated by ·12 grm. of arsenious acid, and
supplied plentifully with liquid to drink; his urine, analysed from time
to time during ten days, gave abundant evidences of arsenic. On killing
the animal by hanging on the tenth day, no arsenic could be detected in
any of the organs of the body; it had been, as it were, washed out.

§ 737. =Antidote and Treatment.=--In any case in which there is
opportunity for _immediate_ treatment, ferric hydrate should be
administered as an antidote. Ferric hydrate converts the soluble
arsenious acid into the insoluble ferric arseniate, the ferric oxide
being reduced to ferrous oxide. It is necessary to use ferric hydrate
recently prepared, for if dried it changes into an oxyhydrate, or even
if kept under water the same change occurs, so that (according to the
experiments of Messrs. T. & H. Smith) after four months the power of the
moist mass is reduced to one-half, and after five months to one-fourth.

It is obvious that ferric hydrate is not in the true sense of the word
an antidote, for it will only act when it comes in contact with the
arsenious acid; and, when once the poison has been removed from the
stomach by absorption into the tissues, the administration of the
hydrate is absolutely useless. Ferric hydrate may be readily prepared by
adding strong ammonia to the solution or tincture of ferric chloride,
found in every medical man’s surgery and in every chemist’s shop, care
being taken to add no caustic excess of ammonia; the liquid need not be
filtered, but should be at once administered. With regard to other
methods of medical treatment, they are simply those suggested by the
symptoms and well-known effects of the poison. When absorbed, the
drinking of water in excess cannot but assist its elimination by the
kidneys.

§ 738. =Detection of Arsenic.=--The analyst may have to identify arsenic
in substance, in solution, in alloys, in wall-papers, in earth, and in
various animal, fatty, resinous, or other organic matters.

=Arsenious Acid in Substance.=--The general characters of arsenious acid
have been already described, and are themselves so marked as to be
unmistakable. The following are the most conclusive tests:--

(1) A small fragment placed in the subliming cell (p. 258), and heated
to about the temperature of 137·7° (286° F.), at once sublimes in the
form of an amorphous powder, if the upper glass disc is cool; but if
heated (as it should be) to nearly the same temperature as the lower,
characteristic crystals are obtained, remarkable for their brilliancy
and permanency, and almost always distinct and separate. The prevailing
form is the regular octahedron, but the rhombic dodecahedron, the
rectangular prism, superimposed crystals, half crystals, deep triangular
plates like tetrahedra, and irregular and confused forms, all
occasionally occur.

[Illustration]

(2) A beautiful and well-known test is that of Berzelius:--A small
hard-glass tube is taken, and the closed end drawn out to the size of a
knitting needle. Within the extreme point of this fine part is placed
the fragment (which may be no more than a milligramme) and a splinter of
charcoal, fine enough to enter freely the narrow part, as shown in the
figure. The portion of the tube containing the charcoal (_e_) is first
heated until it glows, and then the extreme end; if arsenic is present,
a mirror-like coating is easily obtained in the broader portion of the
tube (_d_). That this coating is really arsenical can be established by
the behaviour of metallic crusts of arsenic towards solvents (as given
at p. 557). The portion of the tube containing the crust may also be
broken up, put in a very short, wide test-tube (the mouth of which is
occupied by a circle of thin microscopic glass) and heated, when the
arsenic will sublime on to the glass disc, partly as a metal and partly
as crystalline arsenious acid.

(3) Arsenious acid, itself inodorous, when heated on coal, after mixing
it with moist oxalate of potash, evolves a peculiar garlic-like odour.
To this test oxide of antimony adulterated with arsenic will respond, if
there is only a thousandth part present. Simply projecting arsenious
acid on either red-hot charcoal or iron produces the same odour.

(4) A little bit of arsenious acid, heated in a matrass with two or
three times its weight of acetate of potash, evolves the unsupportable
odour of kakodyl.

=Arsenites and Arseniates=, mixed with oxalate of soda and heated in a
matrass, afford distinct mirrors, especially the arsenites of the earths
and silver; those of copper and iron are rather less distinct.

=Sulphides of Arsenic= are reduced by any of the processes described on
p. 573 _et seq._

=In Solution.=--An acid solution of arsenious acid gives, when treated
with SH₂, a canary-yellow precipitate, soluble in ammonia, carbonate of
ammonia, and bisulphite of potash, and also a metallic sublimate when
heated in a tube with the reducing agents in the manner described at p.
575. By these properties the sulphide is distinguished and, indeed,
separated from antimony, tin, and cadmium.

The sulphides of tin and cadmium are certainly also yellow, but the
latter is quite insoluble in ammonia, while the former gives no metallic
sublimate when heated with reducing substances.

The sulphide of antimony, again, is orange, and quite insoluble in
potassic bisulphite, and scarcely dissolves in ammonia.

A small piece of sodium amalgam placed in a test-tube or flask
containing an arsenic-holding liquid, or the liquid made alkaline with
soda or potash and a little bit of aluminium added, produces in a short
time arsine, which will blacken a piece of paper, soaked in nitrate of
silver, and inserted in the mouth of the flask. This is certainly the
most convenient test for arsenic. No antimoniuretted hydrogen
(_stibine_) is given off from an alkaline solution and no SH₂.

=Marsh’s Original Test for Arsenic= consisted in evolving nascent
hydrogen by zinc and sulphuric acid, and then adding the liquid to be
tested. The apparatus for Marsh’s test, in its simplest form, consists
of a flask provided with a cork conveying two tubes, one a funnel
reaching nearly to the bottom of the flask; the other, a delivery tube,
which is of some length, is provided with a chloride of calcium
bulb,[757] and towards the end is turned up at right angles, the end
being narrowed. By evolving hydrogen from zinc and sulphuric acid, and
then adding portions of the liquid through the funnel, arseniuretted
hydrogen in a dry state is driven along the leading tube, can be ignited
on its issue, and on depressing a piece of cold porcelain, a dark
metallic spot of arsenic is obtained.[758] Or, if any portion of the
tube be made red-hot, the metal is deposited in the same way as a ring.
The apparatus admits of much complication and variety. One of the most
useful additions is, perhaps, the interposition of a small gasometer.
This consists of a cylindrical glass vessel with entrance and exit
tubes, open at the bottom, immersed in water in a larger vessel, and
counterpoised by weights and rollers, exactly like the large gasometers
used at gasworks; the exit tube must have a stop-cock, and the gas must
pass over calcic chloride in order to dry it thoroughly.

[757] Otto recommends the first half of the drying tube connected with
the development flask to be filled with caustic potash, the latter half
with chloride of calcium (_Ausmittelung der Gifte_). Dragendorff
approves of this, but remarks that it should be used when arsenic alone
is searched for, since caustic potash decomposes stibine. The potash
fixes SH₂, and prevents the formation of chloride of arsenic; on the
other hand, it absorbs some little AsH₃.

[758] For identification of arsenical films, see p. 557.

M. Blondlot has observed[759] that if pure zinc, a weak solution of
arsenious acid, and a sulphuric acid containing nitric acid or nitrous
compounds, be mixed together, the arsenic passes into a solid hydrate,
which is deposited on the surface of the zinc; this is, however,
prevented by the addition of a little stannous chloride dissolved in
hydrochloric acid.

[759] Blondlot, “Transformation de l’arsenic en hydrure solide par
l’hydrogène aissant sous l’influence des composés nitreux.”--_Jour. de
Pharm. et de Chim._, 3e sér., t. xliv. p. 486.

The precautions to be observed in Marsh’s test are:--

(1) Absolute freedom of the reagents used from arsenic, antimony,[760]
and other impurities.

[760] With regard to purity of reagents, Sonnenschein states that he has
once found chlorate of potash contaminated with arsenic.--Sonnenschein,
_Gericht. Chemie_, p. 139.

(2) The sulphuric acid should be diluted with five times its weight of
water, and if freshly prepared should be cooled before use. Strong acid
must not be employed.[761]

[761] M. A. Gautier uses sulphuric acid diluted with five times its
weight of water; when the hydrogen has displaced the air, he adds to the
arsenical matter 45 grms. of this acid and 5 grms. of pure sulphuric
acid.--_Bull. de la Société Chim. de Paris_, 1875, t. xxiv.

(3) The fluid to be tested should be poured in little by little.

(4) Nitrous compounds, nitric acid, hydrochloric acid, chlorides, are
all more or less prejudicial.

(5) The gas should come off regularly in not too strong a stream, nor
out of too small an opening.

(6) The gas should pass through the red-hot tube at least one hour, if
no stain is at once detected.

(7) Towards the end of the operation, a solution of stannous chloride in
hydrochloric acid is to be added to the contents of the flask. This
addition precipitates any arsenic present in a finely divided state, in
which it is readily attacked by nascent hydrogen.[762]

[762] F. W. Schmidt, _Zeit. anorg. Chem._, i. 353-359.

The characteristics of the metallic stains which may occur either on
glass or porcelain in the use of Marsh’s test, may be noted as under:--

  MIRROR OR CRUST OF ARSENIC          MIRROR OR CRUST OF ANTIMONY

  Is deposited at a little distance   Is deposited close to the flame,
  from the flame.                     and on both sides of it, and is
                                      therefore notched.

  An arsenical stain is in two        The stain is tolerably homo-
  portions, the one brownish, the     geneous, and usually has a tin-
  other a glittering black.           like lustre.

  On heating, it is rapidly           Volatilisation very slow; no
  volatilised as arsenious acid.      crystalline sublimate obtainable.

  On transmission of a stream of      The same process applied in the
  SH₂, whilst immediately behind the  case of antimony produces the
  stain a gentle heat is applied,     orange or black sulphide; and on
  the arsenic is changed to yellow    passing dry ClH, chloride of
  sulphide;[763] if dry ClH is now    antimony volatilises without the
  transmitted, the arsenical          application of heat.
  sulphide is unchanged.

  Chloride of lime dissolves the      Antimony not affected. Dissolves
  arsenic completely.                 slowly but completely the
                                      antimony stain.

  Protochloride of tin has no action  No precipitate with antimony.
  on metallic arsenic.

  The arsenic stain, dissolved in
  _aqua regia_, or ClH and chlorate
  of potash, and then treated with
  tartaric acid, ammonia, and
  magnesia mixture, gives a
  precipitate of ammonia magnesian
  arseniate.[764]

[763] It is desirable to dissolve away the free sulphur often deposited
with the arsenical sulphide by bisulphide of carbon.

[764] Schönbein has proposed ozone as an oxidiser of arsenical stains.
The substance containing the stain, together with a piece of moist
phosphorus, is placed under a shade, and left there for some time; the
oxidisation product is, of course, coloured yellow by SH₂ if it is
arsenious acid, orange if antimony. The vapour of iodine colours
metallic arsenic pale yellow, and later a brownish hue; on exposure to
the air it loses its colour. Iodine, on the other hand, gives with
antimony a carmelite brown, changing to orange.

An arsenical ring may be also treated as follows:--Precipitated zinc
sulphide is made into a paste with a little water, and introduced into
the end of the tube; the same end is then plunged into dilute sulphuric
acid, and the ring heated, when the arsenical sulphide will be
produced.

The mirror or crust of arsenic is usually described and weighed as being
composed of the pure metal, but J. W. Rettgers has investigated the
matter, and the following is an abstract of his results:--

There is no amorphous form of arsenic, the variety generally thus called
being crystalline. Two modifications can be distinguished: the one being
a hexagonal silver-white variety possessed of metallic lustre,
specifically heavier and less volatile than the second kind, which is
black in colour, crystallises apparently in the regular system, and
constitutes the true arsenic mirror. The former modification corresponds
to red hexagonal phosphorus (red phosphorus having been recently proved
by the author to be crystalline), and the latter to yellow phosphorus,
which crystallises in the regular system. Both modifications of arsenic
are perfectly opaque; deposits which are yellow or brown, and more or
less transparent, consist of the suboxide and hydride, As₂O and AsH. The
brown spot on porcelain produced by contact with a flame of
arseniuretted hydrogen is not a thin film of As, but one of the brown
solid hydride AsH, formed by the decomposition of AsH₃. This view is
confirmed by the fact that arsenic sublimed in an indifferent gas
(_e.g._, CO₂) is deposited in one or other of the modifications
described above, the brown transparent product being obtained only in
the presence of H or O. Moreover, pure arsenic is insoluble in all
solvents, whereas the film on porcelain (AsH) is soluble in many
solvents, including hydrocarbons of the benzene series (_e.g._, xylene),
warm methylene iodide, and hot caustic potash.

Hence quantitative results from weighing arsenical mirrors can never be
accurate, because the mirrors consist of mixtures of hydride and
suboxide.

=Reinsch’s Test.=--A piece of bright copper foil, boiled in an acid
liquid containing either arsenic or antimony, or both, becomes coated
with a dark deposit of antimony or arsenic, as the case may be. The
arsenical stain, according to Lippert, is a true alloy, consisting of 1
arsenic to 5 copper.[765] Properly applied, the copper will withdraw
every trace of arsenic or antimony from a solution. Dr. John Clark[766]
has lately introduced some improvements in Reinsch’s process. His
experiments have been directed to the means of proving the presence of
arsenic or antimony in the stain on the copper with greater certainty,
and at the same time estimating the amount when they occur together.

[765] _Journ. f. pract. Chem._, xiii. 168.

[766] _Journ. Chem. Soc._, June 1893, 886.

The material to be tested is boiled gently in a porcelain vessel with
dilute hydrochloric acid and a small strip of copper about 1 inch long
by ¼ inch broad, till the absence of arsenic or antimony has been
ascertained, or a coating has been produced. When the coating is
decided, the piece of copper is taken out, washed first with water, then
with a little alcohol to get rid of fatty matter, and finally with
water. It is then placed in a mixture of dilute caustic potash and
peroxide of hydrogen, and allowed to digest in the cold. At the same
time a second piece of copper is introduced into the material which has
given a deposit on the first piece, the washings of the first piece
being added, and the boiling continued.

The treatment of the first piece of copper by caustic potash and
peroxide of hydrogen dissolves any antimony or arsenic and restores the
copper to its original brightness; when this is accomplished, the second
piece of copper is taken out and replaced by the first, and this second
piece, if stained, is digested with potash, peroxide of hydrogen, and
washed as in the former case. The process is repeated until the slips of
copper cease to be stained in the slightest degree--until, in short, the
whole arsenic or antimony has been withdrawn.

The alkaline liquid contains the arsenic, as arsenate of potassium; the
antimony, if present, as antimonate; and the solution is also
contaminated by a little hydrated copper oxide; this latter separates on
boiling, and can be filtered off, and the filtrate is boiled down to a
small bulk. The liquid is washed into a small distillation-flask with
strong hydrochloric acid, ferrous chloride is added, the flask, fitted
with a safety tube, is connected with a condenser, and the arsenic
distilled into water. To obtain the last traces of arsenic it may be
necessary to distil it twice in this way, adding, each time, fresh
strong acid and distilling to dryness. The distillate is then tested for
arsenic by adding an equal bulk of saturated SH₂ water. The sulphide of
arsenic may be dealt with as described (p. 573).

The residue in the flask is now tested for antimony by saturating with
SH₂; should antimony be present, the precipitate by SH₂ will probably be
dark coloured, because of a small quantity of copper. The precipitate is
collected, dissolved in dilute caustic soda, boiled, filtered to remove
copper sulphide, the filtrate acidified by hydrochloric acid, and
sulphuretted hydrogen water added. If antimony was present, this time
the precipitate will be of an orange colour, and may be dealt with as
described (p. 589).

The test experiments with regard to this combined process appear
satisfactory.

§ 739. =Arsenic in Glycerin.=--Arsenic has been frequently found in
commercial glycerin, the quantity varying from 0·1 to 1 mgrm. in 100
c.c. The best method to detect the presence of arsenic in glycerin is as
follows:--A mixture of 5 c.c. of hydrochloric acid (1 : 7) and 1 grm. of
pure zinc is placed in a long test-tube, the mouth of which is covered
with a disc of filter-paper previously moistened with one or two drops
of mercuric chloride solution, and dried. If arsenic is present, a
yellow stain is produced upon the filter-paper within fifteen minutes,
and it subsequently becomes darker.[767]

[767] “Arsenic in Glycerin,” by Dr. H. B. H. Paul and A. J. Cownley,
_Pharm. Journ._, Feb. 24, 1894.

§ 740. =Arsenic in Organic Matters.=--Orfila and the older school of
chemists took the greatest care, in searching for arsenic, to destroy
the last trace of organic matter. Orfila’s practice was to chop up the
substance and make it into a paste with 400 to 700 grms. of water; to
this ·010 grm. KHO in alcohol was added, and ·020 grm. of potassic
nitrate. The substances were heated up to from 80° to 90° for some time,
until they were pretty well dissolved; the organic matter was then burnt
off in a Hessian crucible heated to redness, on which small quantities
of the matters were placed at a time. When the whole had thus been
submitted to red heat, the melted mass was run into an almost red-hot
porcelain basin, and allowed to cool. Afterwards, it was again heated
with concentrated sulphuric acid, until all nitric and nitrous fumes
were dissipated; on dissolving and filtering in water, the liquid was
introduced into a Marsh’s apparatus. Orfila never seems to have failed
in detecting arsenic by this process. For an organ like the liver, he
considered that 100 grms. of potash and 86 of strong sulphuric acid were
necessary in order to destroy the organic matters.

The liability of the various reagents used to impurity, and the
probability of loss in these operations, have tended to discredit
destruction of the organic matter by a red heat, and chemists generally
have preferred to oxidise animal matters by a moist process. The organic
substance is divided finely and digested with dilute hydrochloric acid,
and from time to time crystals of potassic chlorate are thrown in until
all the fluid is very thin and capable of passing through a filter. The
filtrate must now be submitted to the prolonged action of sulphuretted
hydrogen,[768] and the sulphide of arsenic separated from free sulphur
by dissolving in sodic sulphide. After filtering, the arsenic sulphide
may be again thrown down by the addition of hydrochloric acid,
collected on a filter, and still further purified by solution in ammonic
carbonate; once more precipitated by hydrochloric acid, and lastly
identified by conversion into magnesia pyro-arseniate (see p. 572). The
above process is a general and safe way of detecting arsenic in almost
any organic tissue, but the author prefers the distillation process
described p. 575 _et seq._

[768] The SH₂ should be washed by passing it through two or more washing
bottles supplied with warm dilute HCl--a few samples of sulphide of iron
give off an arseniferous gas, so that this precaution is necessary.

From ordinary pills, quack extracts, and similar preparations, drying,
powdering, and exhaustion with boiling dilute HCl, will remove the whole
of the arsenic, if in a soluble state.

Oils and matters consisting almost entirely of fat, suspected of
containing arsenic, are gently heated, and allowed to deposit any
insoluble matter they may contain; the oil is then decanted, and, if
necessary, filtered from any deposit; saponified by alcoholic potash,
the soap decomposed by HCl, the fatty acids separated, and the arsenic
looked for both in the first deposit and in the solution, now fairly
free from fat, and easy to treat.

In searching for arsenic in the fluids or tissues of the body, the
analyst is generally at the mercy of the pathologist, and sometimes the
work of the chemist leads to a negative result, solely from not having
the proper organ sent to him.[769]

[769] For example, in cases of poisoning by external application, more
than once merely the empty stomach and a piece of intestine have been
forwarded to the writer.

Brodie long ago stated that when arsenious acid had been given in
solution to any animal capable of vomiting, no arsenic could be detected
in the stomach; this statement is too absolute, but in the majority of
cases true.

In all cases the chemist should have portions of the brain, spinal cord,
liver, kidneys, lungs, and muscular tissue, as well as the stomach and
its contents.

According to the experiments of Scolosuboff,[770] arsenic is generally
greatest in the marrow, then in the brain, next in the liver, and least
in the muscles, and the following may be taken as a fairly accurate
statement of the relative proportion in which arsenic is likely to be
found in the body, 100 grms. being taken of each:--

[770] _Bull. Soc. Chim._ (2), xxiv. p. 124.

  Muscles,           1
  Liver,            10·8
  Brain,            36·5
  Spinal Marrow,    37·3

But Ludwig’s[771] experiments and conclusions are entirely opposed to
this, since both in acute and chronic cases he found as follows (per
cent. As₂O₃):--

[771] _Ueber die Verhaltung des Arsens im thierischen Organismus nach
Einverleibung von Arseniger Säure. Med. Jahrbuch_, 1880.

  Brain,      ·0002
  Liver,      ·001
  Kidney,     ·0004
  Muscle,     ·00025

So that he detected in the liver five times more than in the brain. M.
P. Hamberg has also confirmed the fact, that more is found in the liver
and kidneys than in the nervous tissues.

Chittenden[772] found in a body the following quantities of arsenic
estimated as arsenious acid:--

[772] _American Chemical Journal_, v. 8.

                           Grain.
  Stomach and gullet,      0·158
  Intestines,              0·314
  Liver,                   0·218
  Kidney,                  0·029
  Lungs and spleen,        0·172
  Heart,                   0·112
  Brain,                   0·075
  Diaphragm,               0·010

The whole arsenic present was estimated as equal to 3·1 grains of
arsenious acid, viz., 2·628 grains absorbed, and 0·472 unabsorbed; of
the absorbed portion 8·3 per cent. was found in the liver.

With regard to the preliminary treatment of the stomach and fluids
submitted to the analyst, the careful noting of appearances, the
decantation, washing, and examination[773] (microscopical and chemical)
of any deposit, are precautions so obviously dictated by common sense,
that they need only be alluded to in passing. Of some considerable
moment is the question which may be put to the analyst in court, in
reference to the possible entrance of arsenic into the living body, by
accidental and, so to speak, _subtle_ means. Such are the inhaling of
the fumes from the burning of arsenical candles,[774] and of emanations
from papers (see p. 541),[775] as well as the possible entrance of
arsenic into the body after death from various sources, such as
arsenical earth, &c.[776]

[773] From some observations of Fresenius in a recent number of the
_Zeitschrift f. anal. Chem._, it would seem necessary to test all glass
vessels used; for it is difficult at present to purchase arsenic-free
glass.

[774] See a case of poisoning (non-fatal) of a lady by the use of
arsenical candles, _Med. Times and Gazette_, vol. iii., 1876, p. 367.

[775] To solve this question, it has been at times considered necessary
to analyse an extraordinary number of things. In the “affaire Danval”
(_Journ. d’Hygiène_, 2e sér., No. 108, July 1878), more than sixty
different articles, comprising drugs, drinks, perfumes, bed-curtains,
wall-paper, and other matters, were submitted to the experts.

[776] The following important case is related by Sonnenschein:--

Nicholas Nobel and his wife, Jerome, were buried two metres from each
other in the churchyard at Spinal, the earth of which notoriously
contained arsenic. A suspicion of poisoning arose. The bodies were
exhumed, and arsenic was found in the stomach and intestines of Nobel,
but not the slightest trace in the corpse of the wife. The remains of
the bodies were reinterred, and after six months, on a fresh suspicion
of poisoning arising, again exhumed. The corpse of the woman had been
put naked in the moist earth during a heavy shower, but this time also
no arsenic was detected in it.

§ 741. =Imbibition of Arsenic after Death.=--The arguments which are
likely to be used, in favour of a corpse having become arsenical may be
gathered from a case related by Sonnenschein:--Certain bodies were
exhumed in two churchyards; the evidence went to show that they had been
poisoned by arsenic, and this substance was actually found in the
bodies, while at the same time it was discovered to exist also in traces
in the earth of the churchyard. The theory for the defence was, that
although the arsenic in the earth was in an insoluble state, yet that it
might combine with lime as an arsenite of lime; this arsenite would
become soluble by the action of carbonic acid set free by vegetation,
and filter down to the corpse. Sonnenschein suspended a quantity of this
earth in water, and passed CO₂ through it for twelve hours; on
filtering, the liquid gave no evidence of arsenic. A similar result was
obtained when an artificial mixture of 1 grm. of arsenious acid and 1
pound of earth were submitted to the same process.

The fact would appear to stand thus: oxide of iron in ordinary earth
retains arsenic, and requires treatment with a concentrated acid to
dissolve it. It therefore follows that, if a defence of arsenical earth
is likely to be set up, and the analyst finds that by mere extraction of
the tissues by _water_ he can detect arsenic, the defence is in all
probability unsound. The expert should, of course, deal with this
question on its merits, and without prejudice. According to
Eulenberg,[777] in arsenical earth--if, after having been crushed and
washed, it lies for some time exposed to the disintegrating action of
the air--soluble arsenical salts are formed, which may find their way
into brooks and supplies of drinking water. We may infer that it is
hardly probable (except under very peculiar circumstances) for a corpse
to be contaminated internally with an estimable quantity of arsenic from
the traces of arsenic met with in a few churchyards.

[777] _Gewerbe Hygiene_, p. 234.

It occasionally happens that an exhumation is ordered a very long time
after death, when no organs or parts (save the bones) are to be
distinguished. In the case of a man long dead, the widow confessing that
she had administered poison, the bones were analysed by Sonnenschein,
and a small quantity of arsenic found. Conièrbe and Orfila have both
asserted that arsenic is a normal constituent of the bones--a statement
which has been repeatedly disproved. Sonnenschein relates:[778]--“I
procured from a churchyard of this place (Berlin) the remnants of the
body of a person killed twenty-five years previously, and investigated
several others in a similar way, without finding the least trace of
arsenic. Similar experiments in great number were repeated in my
laboratory, but in no case was arsenic recognised.” The opinion of the
expert, should he find arsenic in the bones, must be formed from the
amount discovered, and other circumstances.

[778] _Gerichtl. Chem._, p. 212.

A difficult case on which to form an opinion is one recorded by William
P. Mason,[779] as follows:--

[779] _Chem. News_, Feb. 23, 1894.

    The deceased, a farmer, bachelor, sixty-five years of age, and in
    good health, was taken violently sick shortly after breakfast, with
    vomiting and distress in the stomach. Although a physician was
    summoned, the symptoms increased in severity, and a little after
    midnight death ensued. The funeral took place three days later.
    Certain very damaging pieces of circumstantial evidence having been
    collected, the housekeeper was arrested on the charge of murder, it
    having been shown, among other things, that on the day preceding the
    death she had purchased an ounce of white arsenic.

    Thirty-five days after death (from March 20 to April 25) the body
    was exhumed, and found in a state of remarkable preservation, and
    free from cadaveric smell. The stomach presented evidences of
    inflammation.

    Portions sent for analysis were the stomach, portion of intestine,
    portion of liver, one kidney, and the heart. Arsenic was found in
    all these parts. White octahedral crystals were found in the
    contents of the stomach, which on separation gave arsenical
    reaction.

    The arsenic found was:--

  Stomach and intestine,                 0·2376 grm.
  Liver and kidney,                      0·0032  „
  Heart,                                 0·0007  „
                                         ------
            Total as metallic arsenic,   0·2415  „

    The amount of arsenic recovered and produced in court was in
    quantity sufficient to produce death. Some time after the analytical
    report was made to the coroner, it was learned that an embalming
    fluid, highly arsenical in character, had been used upon the body by
    the undertaker at the time of preparation for burial. No injection
    of this embalming fluid was practised, but cloths wrung out in the
    fluid were laid upon the face and chest, and were kept constantly
    wet therewith during a period of many hours. In all about two quarts
    of embalming fluid were so used. Its composition appeared to be a
    strongly acidified solution of sodium arsenite and zinc sulphate.
    Only the arsenic and zinc were determined quantitatively, and they
    were found to be, zinc (metallic), 1·978 per cent., and arsenic
    (metallic), 1·365 per cent. by weight. An amount of this fluid
    measuring 15·7 c.c. would thus contain a weight of arsenic equal to
    that actually recovered from the body.

    Extended medical testimony was offered by the prosecution, tending
    to show that, under the given circumstances, no fluid of any kind
    could have reached the stomach through the nose or mouth after
    death, thus anticipating what the defence afterwards claimed, that
    the undertaker was responsible for the arsenic discovered in the
    remains.

    In order to gather further light upon the possibility of cadaveric
    imbibition of embalming fluid through the unbroken skin, test was
    made for zinc in the heart and stomach, and distinct traces of the
    metal were found in each instance. That at least a portion of the
    arsenic found in the body was due to _post-mortem_ causes was thus
    distinctly proven. A weighed portion (62 grms.) of the stomach and
    contents was then most carefully analysed quantitatively for both
    zinc and arsenic with the following results:--Arsenic, 0·0648 grm.,
    and zinc, 0·0079 grm. Bearing in mind the relative quantities of the
    two metals in the embalming fluid, it will be seen that the arsenic
    found in the 62 grms. of the stomach was nearly twelve times larger
    than it should have been to have balanced the zinc which was also
    present. This fact, together with the discovery of crystals of white
    arsenic in the stomach, constituted the case for the prosecution, so
    far as the chemical evidence was concerned.

    The defence made an unsuccessful effort to show that the crystals of
    the tri-oxide originated from the spontaneous evaporation of the
    embalming fluid. The prosecution met this point by proving that such
    fluid had been abundantly experimented upon by exposure to a very
    low temperature during an interval of several months, and also by
    spontaneous evaporation with a view of testing that very question,
    and that the results had in every case been negative. Special
    importance was given these experiments, because of the well-known
    separation of octahedral crystals during the spontaneous evaporation
    of a hydrochloric acid solution of the white oxide, it having also
    appeared that, in the manufacture of the embalming fluid, the
    arsenic was used as white arsenic.

    A very strong point was finally raised for the defence by the
    inability of the expert on the side of the prosecution to state
    positively whether or not an embalming fluid of the above
    composition would diffuse as a whole through dead tissue, or its
    several parts would be imbibed at different rates of speed, the zinc
    portion becoming arrested by albuminoid material and being therefore
    outstripped by the arsenic, or _vice versa_. The prisoner was
    ultimately acquitted.

In a case which occurred in the Western States of America, there was
good reason for believing that arsenic had been introduced into the
corpse of a man _after_ his decease. With regard to the imbibition of
arsenic thus introduced, Orfila[780] says:--“I have often introduced
into the stomach (as well as the rectum) of the corpses of men and dogs
2 to 3 grms. of arsenious acid, dissolved in from 400 to 500 grms. of
water, and have examined the different viscera at the end of eight, ten,
or twenty days. Constantly I have recognised the effects of cadaveric
imbibition. Sections of the liver or other organs which touch the
digestive canal, carefully cut and analysed, furnished arsenic, which
could not be obtained sensibly (or not at all) from sections which had
not been in contact with this canal. If the corpse remained long on the
back after arsenious acid had been introduced into the stomach, I could
obtain this metal from the left half of the diaphragm and from the
inferior lobe of the left lung, whilst I did not obtain it from other
portions of the diaphragm nor from the right lung.” Dr. Reece has also
made some experiments on the imbibition of arsenic after death. He
injected solutions of arsenious acid into the stomach of various
warm-blooded animals, and found at various periods arsenic, not alone in
the intestinal canal, but also in the spleen, liver, and kidneys.

[780] _Op. cit._, t. i. p. 309.

§ 742. =Analysis of Wall-Paper for Arsenic.=--The separation of arsenic
from paper admits of great variety of manipulation. A quick special
method is as follows:--The paper is saturated with chlorate of potash
solution, dried, set on fire in a suitable plate, and instantly covered
with a bell-glass. The ash is collected, pulverised, and exhausted with
cold water, which has previously thoroughly cleansed the plate and
bell-glass; the arsenic in combination with the potash is dissolved,
whilst oxides of chromium, copper, aluminium, tin, and lead remain in
the insoluble portion.[781]

[781] Kapferschlaeger: _Rev. Universelle des Mines_, 1876.

Fresenius and Hintz[782] have elaborated a method for the examination of
wall-papers, fabrics, yarns, and similar substances, which, provided the
reagents are pure, is accurate and easy. Twenty-five grms. of the
substance are placed in a half-litre distilling flask or retort, and 250
c.c. of HCl, specific gravity 1·19, added; after digestion for an hour,
5 c.c. of a saturated solution of ferrous chloride are added, and the
liquid slowly distilled until frothing stops any farther distillation. A
further quantity of 100 c.c. HCl is then added, and distilled over. The
receiver, in each case, contains water, and must be kept cool. The
united distillates are diluted to 800 c.c. and saturated with SH₂. The
arsenious sulphide is collected on an asbestos filter. After partial
washing, it is heated with bromine in HCl of 1·9 specific gravity, and
the solution again distilled with ferrous chloride. The distillate, on
now being treated with SH₂, gives arsenious sulphide free from organic
matter.

[782] _Zeit. anal. Chem._, xxvii. 179-182.

§ 743. =Estimation of Arsenic.=--Most of the methods for the
quantitative determination of arsenic are also excellent tests for its
presence. It may be regarded, indeed, as an axiom in legal chemistry,
that the precise amount of every substance detected, if it can be
weighed or estimated by any process whatever, should be accurately
stated. Indefinite expressions, such as “a small quantity was found,”
“traces were detected,” &c., are most objectionable. The more perfect of
the methods of evolving arsenic can be made quantitative. For example,
the galvanic process introduced by Bloxam may be utilised as follows:--A
fractional part of the arsenical solution is taken for the experiment;
the bottom of a narrow-necked bottle of about 100 c.c. capacity is
removed, and replaced by a piece of vegetable parchment. The neck of the
bottle carries a cork, which is pierced by (1) a platinum wire, which is
attached to a platinum electrode; (2) a short tube, bent at right
angles, and connected by piping with a longer tube, which has also a
rectangular bend, and dips into a solution of silver nitrate; (3) an
ordinary funnel-tube, reaching nearly to the bottom. The bottle is
placed in a beaker of such a size as to leave a small interval between
the two, and the whole apparatus stands in a large vessel of cold water.
Dilute sulphuric acid is now put into the bottle, and also into the
beaker, so that the fluid reaches exactly the same level in each. The
positive platinum electrode of a battery of six of Grove’s cells, or
other efficient combination, is immersed in the liquid outside the
bottle, connection with the negative plate is established, and hydrogen
very soon comes off, and passes over into the nitrate of silver
solution. When all the air is expelled, a portion of the rectangular
tube is heated to redness, and if there is no stain nor any reduction of
the silver, the acid is pure. If the gas is passed for a long time into
the silver solution, the silver will be reduced to some extent by the
hydrogen, although arsenic-free;[783] so that it is better to rely upon
the metallic ring or stain, which is certain to be formed on heating a
portion of the tube red-hot, and keeping it at that temperature for _at
least ten minutes_. The liquid is then passed through the funnel in
successive portions; if arsenic is present, there will be a decided
metallic ring on heating the tube as before, and if antimony is present,
there will also be a stain; the distinctions between these stains have
been described at p. 557.

[783] Nitrate of silver solution is reduced by H₂, CH₃, PH₃, and SbH₃;
hence it is absolutely necessary in any qualitative examination to prove
that arsenious acid has actually been produced in the silver solution.

The tube is kept red-hot until the stain is very distinct; then the
source of heat is removed, and the gas allowed to bubble through the
argentic nitrate solution, which it decomposes, as before detailed (p.
526). This process is continued until, on placing the delivery tube in a
sample of clear nitrate of silver solution, there is no darkening of
colour. In certain cases this may take a long time, but the apparatus,
once set to work, requires little superintendence. At the conclusion,
the whole of the arsenic is separated,--part is in the silver solution
as arsenious acid, part in the tube as a ring of metallic arsenic. The
portion of the tube containing the metallic arsenic should be cut off
with a file and weighed, the arsenic then removed and re-weighed; the
loss is the metal approximately. Or, the weight of the film may be
estimated by having a set of similar deposits of known weight or
quantities, in tubes exactly corresponding to those used in the
analysis, and comparing or matching them.

The arsenious acid in the nitrate of silver may be dealt with in several
ways. The equation given (p. 526) shows clearly that pure arsine, passed
into nitrate of silver solution, decomposes it in such a manner that, if
either the silver deposited or the free acid is estimated, the quantity
of arsenic can from such data be deduced. In operating on organic
liquids, ammonia and other products may be given off, rendering either
of the indirect processes inadvisable. A very convenient method,
applicable in many cases, is to throw out the silver by hydrochloric
acid, alkalise the filtrate by bicarbonate of soda, and titrate with
iodine solution. The latter is made by dissolving exactly 12·7 grms. of
pure dry iodine by the aid of 18 grms. of potassic iodide in one litre
of water, observing that the solution must take place in the cold,
without the application of heat. The principle of the titration is, that
arsenious acid, in the presence of water and free alkali, is converted
into arsenic acid--

  As₂O₃ + 4I + 2Na₂O = As₂O₅ + 4NaI.

The end of the reaction is known by adding a little starch-paste to the
solution; as soon as a blue colour appears, the process is finished.

Another convenient way by which (in very dilute solutions of arsenious
acid) the arsenic may be determined, is a colorimetric method, which
depends on the fact that sulphuretted hydrogen, when arsenious acid is
present in small quantity, produces no precipitate at first, but a
yellow colour, proportionate to the amount of arsenic present. The
silver solution containing arsenious acid is freed from silver by
hydrochloric acid; a measured quantity of saturated SH₂ water is added
to a fractional and, if necessary, diluted portion, in a Nessler
cylinder or colorimetric apparatus, and the colour produced exactly
imitated, by the aid of a dilute solution of arsenious acid, added from
a burette to a similar quantity of SH₂ water in another cylinder, the
fluid being acidified with HCl.

§ 744. =Destruction of the Organic Matter by Nitric Acid, and Subsequent
Reduction of the Arsenic Acid to Arsine (Arseniuretted Hydrogen), and
final Estimation as Metallic Arsenic.=--This process, which is
essentially a combination of several, has been much improved in its
details by R. H. Chittenden and H. H. Donaldson.[784] 100 grms. of the
suspected matters, cut up into small pieces, are heated in a porcelain
dish of suitable size, stirred by means of a glass rod with 23 c.c. of
pure concentrated nitric acid, and heated up to from 150° to 160°. When
the matters assume a yellow or orange colour, the bath is removed from
the source of heat, and 3 c.c. of pure concentrated sulphuric acid
added, and the mixture stirred, when the mass becomes brown, swells up,
and evolves dense nitrous and other fumes. The vessel is again heated to
180°, and while hot 8 c.c. of pure concentrated nitric acid are added,
drop by drop, with continual stirring. After this addition, it is heated
to 200° for fifteen minutes, and the result on cooling is a hard
carbonaceous residue wholly free from nitric acid. The arsenic is in
this way oxidised into arsenic acid, which is easily soluble in water.
The contents of the dish are, therefore, perfectly extracted by boiling
water, the aqueous extract filtered, and evaporated to dryness. The next
process is to obtain the arsenic in a metallic state:--

[784] _American Chem. Journ._, vol. ii., No. 4; _Chem. News_, Jan. 1881,
p. 21.

The flask, a Bunsen’s wash-bottle of 200 c.c. capacity, is provided with
a small separating funnel of 65 c.c. capacity, with glass stop-cock.
This is a very material aid to the obtaining of a slow and even
evolution of gas, an important desideratum when all loss is to be
avoided; for with only a funnel tube, every time a small portion of
fluid is added, a sudden rush of gas takes place, with probably a small,
but still more or less appreciable, loss. But the separating funnel,
filled with the acid mixture, can be so arranged as to give a constant
and regular supply of fluid at the rate of two or three drops per
minute, more or less. The gas generated is dried by a calcic chloride
tube, and then passes through a tube of hard glass, heated to a red heat
by a miniature furnace of three Bunsen lamps with spread burners, so
that a continuous flame of 6 inches is obtained, and with a proper
length of cooled tube not a trace of arsenic passes by. The glass tube
where heated is wound with a strip of wire gauze, both ends being
supported upon the edges of the lamp frame, so that the tube does not
sink down when heated. The small furnace is provided with two
appropriate side pieces of sheet metal, so that a steady flame is always
obtained. When the quantity of arsenic is very small, the tube is
naturally so placed that the mirror is deposited in the narrow portion;
but when the arsenic is present to the extent of 0·005 grm., the tube
should be 6 mm. in inner diameter, and so arranged that fully 2 inches
of this large tube are between the flame and the narrow portion. When
the quantity of arsenic is less, the tube can naturally be smaller.

Acids of different strengths are made as follows:--

  Acid No. 1.

   545 c.c. pure conc. H₂SO₄.
  5000 c.c. H₂O.

  Acid No. 2.

   109 c.c. pure conc. H₂SO₄.
  1640 c.c. Acid No. 1.

  Acid No. 3.

   218 c.c. pure conc. H₂SO₄.
  1640 c.c. Acid No. 1.

  Acid No. 4.

   530 c.c. pure conc. H₂SO₄.
  1248 c.c. H₂O.

25 to 35 grms. of granulated zinc, previously alloyed with a small
quantity of platinum, are placed in the generator, and everything being
in position, the apparatus is filled with hydrogen by the use of a small
quantity of acid No. 2. After a sufficient time has elapsed, the gas is
lighted at the jet, and the glass tube heated to a bright redness.

The arsenical solution in concentrated form is mixed with 45 c.c. of
acid No. 2, and the mixture passed into the separating funnel, from
which it is allowed to flow into the generator at such a rate that the
entire fluid is introduced in one hour or one and a half; 40 c.c. of
acid No. 3 are then added and allowed to flow slowly into the generator,
and, lastly, 45 c.c. of acid No. 4. The amount of time required will
vary with the amount of arsenic: 2 to 3 mgrms. of arsenic will require
about two to three hours for the entire decomposition, while 4 to 5
mgrms. will need perhaps three to four hours. Where the amount of
arsenic is small, only 25 grms. of zinc are needed, and but 45 c.c. of
acid No. 2, 30 c.c. of acid No. 3, and 30 c.c. of acid No. 4; but when
4 to 5 mgrms. of arsenic are present, it is better to take the first
mentioned quantities of zinc and acids.

The arsenic being thus collected as a large or small mirror of metal,
the tube is cut at a safe distance from the mirror, so that a tube of
perhaps 2 to 6 grms. weight is obtained. This is carefully weighed, and
then the arsenic removed by simple heating; or, if the arsenic is to be
saved (as in a toxicological case), dissolved out with strong nitric
acid. The tube is then cleaned, dried, and again weighed, the difference
giving the weight of metallic arsenic, from which, by a simple
calculation, the amount of arsenious oxide can be obtained. Some test
results are given as follows; they were obtained by introducing definite
quantities of arsenious oxide in the form of a solution mixed with 45
c.c. of No. 2 acid, &c.:--

  Quantity of           Wt. of Metallic   Theoretical Wt. of
  Arsenic introduced.   Arsenic found.    Metallic Arsenic.

  0·005 grm.  As₂O₃         0·00373            0·00378
  0·005  „      „          0·00370            0·00378
  0·004  „      „          0·00300            0·00303
  0·002  „      „          0·00151            0·00151

Sanger estimates and tests for minute quantities of arsenic by the
Marsh-Berzelius process, and uses a generator of hydrogen; that is to
say, the hydrogen is evolved in the ordinary way from zinc and sulphuric
acid, and the issuing gas dried by calcic chloride; but into this flask
is also delivered from another flask, charged with sulphuric acid and
zinc, pure hydrogen, so that into the second flask, little by little,
may be added the solution to be tested; and, owing to the generating
flask, the gas may be made to give a uniform current, and at the end of
the operation all arsine swept out. To estimate the quantities of
arsenic in the gas, the reduction tube is heated, and a mirror or
mirrors obtained, and compared with a set of standard mirrors. The
standard mirrors are made as follows:--One grm. of arsenious oxide,
purified by repeated sublimation, is dissolved with the aid of a little
sodic bicarbonate, and, after acidification with dilute sulphuric acid,
made up to 1 litre. This standard solution contains 1 mgrm. of As₂O₃ in
every c.c., and is used to make a second standard solution, containing
0·01 mgrm., to every c.c., by diluting 10 c.c. to a litre. Of this last
solution, 1 c.c., 2 c.c., 3 c.c., and so on, are measured and introduced
into the reduction flask, and the standard mirrors obtained. It is
recommended, for obvious reasons, to make more than one standard for
each quantity, for the appearance of the mirrors from the same amount of
arsenic varies. The tubes are hermetically sealed, and, when not in use,
kept in the dark.

This process is convenient for small amounts of arsenic; but, as stated
before, the results are given as metallic arsenic, whereas the films
appear never to be composed of pure metallic arsenic, but a mixture of
hydride and suboxide. Test experiments give, however, fair results.[785]

[785] _Proc. American Academy of Arts and Sciences_, vol. xxvi.

§ 745. =Arsine Developed from an Alkaline Solution.=--Fleitmann
discovered in 1851 that arsenic, mixed with finely divided zinc, and
excess of soda or potash added, evolved arsine; but no stibine was
evolved under the same conditions. In 1873 J. W. Gatehouse suggested the
use of aluminium and sodic hydrate as a modification of Fleitmann’s
test, for the purpose of distinguishing between arsenic and antimony;
and this is now the usual process adopted. The hydrogen comes off
regularly even in the cold, but it is best to apply a little heat. This
test will evolve arsine from arsenious acid, and also from arsenic
trisulphide; but it is not available for the detection of arsenic, when
the arsenic is in the form of arsenic acid. According to Clark,[786] it
is not adapted for quantitative purposes, because, owing to the
formation of solid hydride, about one-fifth remains behind.

[786] _Journ. Chem. Soc._, 1893, 884.

E. W. Davy, in 1876, proposed the use of sodium amalgam for the
generation of arsine; on the whole, it is, however, not so convenient as
the aluminium process.

The liquid to be tested is made strongly alkaline with pure sodic or
potassic hydrate placed in a flask connected with a tube dipping into a
4 per cent. solution of silver nitrate, a few pieces of sheet aluminium
added, and the flask gently heated; any arsine present will reduce the
silver. The silver solution thus blackened may be treated in the manner
described (p. 567).

§ 746. =Precipitation as Tersulphide.=--Despite the advantages of some
of the processes described, which are (to a certain extent) easy and
accurate, not a few chemists still prefer the old method of
precipitation with hydric sulphide SH₂, because, although tedious, it
has stood the test of experience. If this be used, it is well in most
cases to pass sulphurous anhydride through the liquid until it smells
strongly of the gas, for by this means any arsenic acid present is
reduced, the sulphurous anhydride is quickly got rid of by a current of
carbonic anhydride, and then the liquid is saturated with hydric
sulphide. In the ordinary way, much time is often wasted in saturating
the liquid with this gas. Those, however, who have large laboratories,
and daily employ hydric sulphide, possess (or should possess) a water
saturated with the gas under pressure; such a liquid, added in equal
volume to an arsenical solution, is able to convert the whole of the
arsenic into sulphide in a very few minutes. Those who do not possess
this hydric sulphide water can saturate in an hour the liquid to be
tested, by passing the gas in under pressure.[787] A convenient method
is to evolve SH₂ from sulphide of antimony and ClH; the gas passes first
into a wash-bottle, and then into a strong flask containing the solution
under trial. This flask is furnished with a safety-valve, proportioned
to the strength of the apparatus; the two tubes dipping into the
wash-bottle and the last flask are provided with Bunsen’s valves, which
only allow the gas to pass in one direction. The hydric sulphide is then
driven over by heat, and when sufficient gas has in this way passed into
the liquid, the flame is withdrawn, and the apparatus allowed to stand
for some hours, the valves preventing any backward flow of the liquid or
gas. When the precipitate has settled to the bottom, the supernatant
fluid is carefully passed through a filter, and the precipitate washed
by decantation in the flask, without transference to the filter, if it
can be avoided.

[787] Hydric sulphide gas has been liquefied, and is now an article of
commerce, being sold in iron bottles.

The impure sulphide is washed with water, then with alcohol, then with
carbon disulphide, then, after having got rid of the lead, again with
alcohol, and finally with water; it is then dissolved in ammonia, the
ammonia solution filtered, and the filtrate evaporated to dryness on a
sand-bath, at a somewhat high temperature; in this way it is freed from
sulphur and, to a great extent, from organic matter; after weighing, it
may be purified or identified by some of the following methods:--

(_a_) =Solution in Ammonia and Estimation by Iodine.=[788]--The filter
is pierced, the sulphide washed into a flask by ammonia water (which
need not be concentrated), and dissolved by warming, filtered from any
insoluble matter, and estimated by iodine and starch.

[788] P. Champion and H. Pellett, _Bull. Soc. Chim._ (2), xxvj. pp.
541-544.

(_b_) =Oxidation of the Sulphide and Precipitation as Ammonia Magnesian
Arseniate, or Magnesia Pyro-Arseniate.=--The tersulphide, as before, is
dissolved in ammonia (not omitting the filter-paper, which should be
soaked in this reagent), the solution filtered, and evaporated to
dryness. The dry residue is now oxidised by fuming nitric acid, taking
care to protect the dish with a large watch-glass (or other cover)
during the first violent action; the dish is then heated in the
water-bath until all the sulphur has disappeared, and only a small bulk
of the liquid remains; it is then diluted and precipitated by “magnesia
mixture.”[789] The fluid must stand for several hours, and, if the
arsenic is to be determined as the usual ammoniacal salt, it must be
passed through a weighed filter, and washed with a little ammoniacal
water (1 : 3). The solubility of the precipitate is considerable, and
for every 16 c.c. of the filtrate (not the washings) 1 mgrm. must be
allowed. The precipitate, dried at 100°, 2(NH₄MgAsO₄)H₂O, represents
39·47 per cent. metallic arsenic.

[789] Magnesia Mixture:--

  Sulphate of magnesia,       1
  Chloride of ammonium,       1
  Solution of ammonia,        4
  Water,                      8

Dissolve; then allow to stand for several days; finally filter, and keep
for use.

The solubility of the magnesium arseniate itself, and the general
dislike which chemists have to weighing in such hygroscopic material as
a filter, are, perhaps, the main reasons for the variation of this old
method, which has lately come into notice. Rose proposed some time ago
the conversion of the double salt into the pyro-arseniate--a method
condemned by Fresenius and Parnell, but examined and pronounced a
practicable and accurate process by Remol, Rammelsberg, Thorpe, Fuller,
Wittstein, Emerson, Macivor, Wood, and Brauner. The modification of
Rose’s process, recommended by Wood,[790] and still further improved by
Brauner,[791] may be accepted.

[790] _Zeitschrift für anal. Chem._, vol. xiv. p. 356.

[791] _Ibid._, xvj. pp. 57, 58.

The precipitation is effected by magnesia mixture, with the addition of
half its bulk of alcohol. The solution is allowed to stand for several
hours, until it is possible to decant the clear liquid from the
precipitate; the latter is now dissolved in ClH, reprecipitated as
before, thrown on a small filter, and washed with a mixture of one
volume of ammonia, two volumes of alcohol, and three of water.

The precipitate is now dried, and transferred as completely as possible
from the filter into a small porcelain crucible, included in a larger
one made of platinum, moistened with nitric acid, covered and heated at
first gently, lastly to a bright redness; the filter is then treated
similarly, and the crucible with its contents weighed. Pyro-arseniate of
arsenic (Mg₂As₂O₇) contains 48·29 per cent. of metallic arsenic.

(_c_) =Conversion of the Trisulphide of Arsenic into the Arsenomolybdate
of Ammonia.=--The purified sulphide is oxidised by nitric acid, the acid
solution is rendered alkaline by ammonia, and then precipitated by a
molybdenum solution, made as follows:--100 grms. of molybdic acid are
dissolved in 150 c.c. of ordinary ammonia and 80 of water; this solution
is poured drop by drop into 500 c.c. of pure nitric acid and 300 c.c. of
water; it is allowed to settle, and, if necessary, filtered. The
molybdic solution must be mixed in excess with the liquid under
treatment, the temperature raised to 70° or 80°, and nitric acid added
in excess until a yellow coloration appears; the liquid is then passed
through a tared filter, and dried at 100°. It contains 5·1 per cent. of
arsenic acid [3·3 As].[792]

[792] Champion and Pellett, _Bull. Soc. Chim._, Jan. 7, 1877.

(_d_) =Conversion of the Sulphide into Metallic Arsenic.=--If there
should be any doubt as to the nature of the precipitated substances, the
very best way of resolving this doubt is to reduce the sulphide to
metal; the easiest method of proving this is to dissolve in potash and
obtain arsine by the action of aluminium; or if it is desired to evolve
arsine from an acid solution with zinc in the usual way, then by
dissolving a slight excess of zinc oxide in potash or soda, and
dissolving in this the arsenic sulphide; the zinc combines with all the
sulphur, and converts the sulpharsenite into arsenite; the zinc sulphide
is filtered off, and the filtrate acidified and introduced into Marsh’s
apparatus. The original process of Fresenius was to mix the sulphide
with carbonate of soda and cyanide of potassium, and place the mixture
in the wide part of a tube of hard German glass, drawn out at one end to
a capillary fineness. Carbonic anhydride, properly dried, was passed
through the tube, and the portion containing the mixture heated to
redness; in this way the arsenical sulphide was reduced, and the metal
condensed in the capillary portion, where the smallest quantity could be
recognised. A more elaborate and accurate process, based on the same
principles, has been advocated by Mohr.[793]

[793] Mohr’s _Toxicologie_, p. 57.

A convenient quantity of carbonate of soda is added to the sulphide, and
the whole mixed with a very little water, and gently warmed. The yellow
precipitate is very soon dissolved, and then the whole is evaporated
carefully, until it is in a granular, somewhat moist, adhesive state. It
is now transferred to a glass tube, open at top and bottom, but the top
widened into a funnel; this tube is firmly held perpendicularly on a
glass plate, and the prepared sulphide hammered into a compact cylinder
by the aid of a glass rod, which just fits the tube. The cylinder is now
dried over a flame, until no more moisture is to be detected, and then
transferred into a glass tube 4 or 5 inches long, and with one end drawn
to a point (the weight of this tube should be first accurately taken).
The tube is connected with the following series:--(1) A chloride of
calcium tube; (2) a small bottle containing nitrate of silver solution;
(3) a hydrogen-generating bottle containing zinc and sulphuric acid. The
hydrogen goes through the argentic nitrate solution, leaving behind any
sulphur and arsenic it may contain; it is then dried by chloride of
calcium, and streams in a pure dry state over the cylinder of prepared
sulphide (no error with regard to impurities in the gas is likely to
occur; but in rigid inquiries it is advisable to heat a portion of the
tube, previous to the insertion of the cylinder, for some time, in order
to prove the absence of any external arsenical source); when it is
certain that pure hydrogen, unmixed with air, is being evolved, the
portion of the tube in which the cylinder rests is heated slowly to
redness, and the metallic arsenic sublimes at a little distance from the
source of heat. Loss is inevitable if the tube is too short, or the
stream of hydrogen too powerful.

The tube after the operation is divided, the portion soiled by the soda
thoroughly cleansed, and then both parts weighed; the difference between
the weight of the empty tube and the tube + arsenic gives the metallic
arsenic. This is the process as recommended by Mohr; it may, however, be
pointed out that the glass tube itself loses weight when any portion of
it is kept red-hot for some little time; and, therefore, unless the
crust is required in the original tube, it is better to divide it,
carefully weigh the arsenical portion, remove the crust, and then
re-weigh. The method is not perfectly accurate. The mirror is not pure
metallic arsenic (see p. 571), and if the white alkaline residue be
examined, arsenic will be detected in it, the reason being that the
arsenical sulphide generally contains pentasulphide of arsenic as well
as free sulphur. Now the pentasulphide does not give up metallic arsenic
when treated as before detailed; nor, indeed, does the trisulphide, if
mixed with much sulphur, yield an arsenical crust. It is, therefore, of
great moment to free the precipitate as much as possible from sulphur,
before attempting the reduction.

The development of a reducing gas from a special and somewhat
complicated apparatus is not absolutely necessary. The whole process of
reduction, from beginning to end, may take place in a single tube by any
of the following processes:--(1) The sulphide is mixed with oxalate of
soda (a salt which contains no water of crystallisation), and the dry
mixture is transferred to a suitable tube, sealed at one end. An
arsenical mirror is readily obtained, and, if the heat is continued long
enough, no arsenic remains behind--an excellent and easy method, in
which the reducing gas is carbonic oxide, in an atmosphere of carbonic
anhydride. (2) The sulphide is oxidised by _aqua regia_, and the
solution evaporated to complete dryness. The residue is then dissolved
in a few drops of water, with the addition of some largish grains of
good wood charcoal (which absorb most of the solution), and the whole
carefully dried. The mass is now transferred to a tube closed at one
end, a little charcoal added in the form of an upper layer, and heat
applied first to this upper layer, so as to replace the air with CO₂,
and then to bring the whole tube gradually to redness from above
downwards. In this case also the whole of the arsenic sublimes as a
metallic mirror.

There are various other modifications, but the above are trustworthy,
and quite sufficient. Brugelmann’s method of determining arsenic,
elsewhere described, would appear to possess some advantages, and to
promise well; but the writer has had no personal experience of it with
regard to arsenic.

§ 747. =Conversion of Arsenic into Arsenious Chloride= (AsCl₃).--This
process, first employed by Schneider and Fyfe, and afterwards modified
by Taylor, differs from all the preceding, since an attempt is made to
separate by one operation volatile metallic chlorides, and to
destroy the organic matter, and thus obtain two liquids--one a
distillate--tolerably clear and free from solid particles, whilst the
mass in the retort retains such metals as copper, and is in every way
easy to deal with.

Schneider and Fyfe employed sulphuric acid and common salt; but Taylor
recommends hydrochloric acid, which is in every respect preferable. As
recommended by Taylor, all matters, organic or otherwise, are to be
completely desiccated before their introduction into a retort, and on
these dried substances sufficient pure hydrochloric acid poured, and the
distillation pushed to dryness. Every one is well aware how tedious is
the attempt to dry perfectly the organs of the body (such as liver, &c.)
at any temperature low enough to ensure against volatilisation of such a
substance as, _e.g._, calomel. This drying has, therefore, been the
great stumbling-block which has prevented the general application of the
process. It will be found, however, that drying in the ordinary way is
by no means necessary. The writer cuts up the solid organ (such as
liver, brain, &c.) with scissors into small pieces, and transfers them
to a retort fitted by an air-tight joint to a Liebig condenser; the
condenser in its turn being connected with a flask by a tube passing
through an india-rubber stopper dipping into a little water. Another
tube from the same flask is connected with india-rubber piping, which is
connected with a water-pump, the fall tube of which terminates in the
basement of a house over a gully. The distillation is now carried on to
carbonisation; on cooling, a second quantity of hydrochloric acid is
added, and the last fraction of the distillate examined for arsenic. If
any is found, a third distillation is necessary. At the termination of
the operation the retort is washed with water, the solution filtered,
and this solution and the distillate are each separately examined for
arsenic. If properly performed, however, the second distillation brings
over the whole of the arsenical chloride,[794] and none will be found in
the retort. With the above arrangement there can be no odour, nor is
there any loss of substance. In the distillate the arsenic can hardly be
in the form of arsenious chloride, but rather arsenious acid and
hydrochloric acid; for the chloride easily splits up in the presence of
water into these substances. It is best to convert it into the
trisulphide. Taylor[795] recommends evolving arsine in the usual way,
and passing the arsine (AsH₃) into solution of silver nitrate, finally
estimating it as an arseniate of silver. Objections with regard to the
impurity of reagents should be met by blank experiments. Kaiser[796]
has proposed and practised a modification of this method, which
essentially consists in the use of sulphuric acid and sodic chloride (as
in Schneider and Fyfe’s original process), and in passing the distillate
first into a flask containing a crystal or two of potassium chlorate,
and thence into an absorption bulb; in the latter most of the arsenic is
found in the form of arsenic acid, the chloride having been oxidised in
its passage. The apparatus is, however, complicated in this way without
a corresponding advantage.[797] Lastly, E. Fischer[798] has shown that
it is a considerable advantage to add from 10 to 20 c.c. of a saturated
solution of ferrous chloride before distilling with HCl. In this way all
the arsenic, whether as arsenic or arsenious acids, is easily converted
into chloride.

[794] Dragendorff asserts to the contrary; but we may quote the
authority of Taylor, who has made several experiments, in which he
obtained all the arsenic as chloride. The writer has performed the
process many times, each time carefully testing the mass in the retort
for arsenic; but the result proved that it had entirely passed over.

[795] _Principles of Medical Jurisprudence_, vol. i. p. 267.

[796] _Zeitschr. f. anal. Chem._, xiv. pp. 250-281.

[797] Selmi (_Atti dell. Accademia dei Lincei_, Fasc. ii., 1879)
proposed a modification of Schneider’s process. The substances are
treated with hot, pure sulphuric acid, and at the same time the liquid
is traversed by a stream of hydrochloric acid gas. The resulting
distillate is tested for arsenic by Marsh’s process. Selmi states that,
operating in this way, he has detected 1/400 of a mgrm. of As₂O₃ in 100
grms. of animal matter.

[798] _Scheidung u. Bestimmung d. Arsens_; Liebig’s _Annalen d. Chemie_,
Bd. ccvii. p. 182.


2. ANTIMONY.

§ 748. =Metallic Antimony.=--Atomic weight, 120·3 (R. Schneider), 120·14
(Cook[799]); specific gravity, 6·715; fusing-point about 621° (1150°
F.). In the course of analysis, metallic antimony may be seen as a black
powder thrown down from solutions; as a film deposited on copper or
platinum; and, lastly, as a ring on the inside of a tube from the
decomposition of stibine. At a bright red-heat it is volatilised slowly,
even when hydrogen is passed over it; chlorine, bromine, and iodine
combine with it directly. It may be boiled in concentrated ClH without
solution; but _aqua regia_, sulphides of potassium and sodium readily
dissolve it. The distinction between thin films of this metal and of
arsenic on copper and glass are pointed out at pp. 557 and 559. It is
chiefly used in the arts for purposes of alloy, and enters to a small
extent into the composition of fireworks (_vide_ pp. 534 and 581).

[799] _Ann. Phys. Chem._ (2), v. pp. 255-281.

§ 749. =Antimonious Sulphide.=--Sulphide of antimony = 336; composition
in 100 parts, Sb 71·76, S 28·24. The commercial article, known under the
name of black antimony, is the native sulphide, freed from silicious
matter by fusion, and afterwards pulverised. It is a crystalline
metallic-looking powder, of a steel-grey colour, and is often much
contaminated with iron, lead, copper, and arsenic.

The amorphous sulphide (as obtained by saturating a solution of tartar
emetic with SH₂) is an orange-red powder, soluble in potash and in
ammonic, sodic, and potassic sulphides; and dissolving also in
concentrated hydrochloric acid with evolution of SH₂. It is insoluble in
water and dilute acid, scarcely dissolves in carbonate of ammonia, and
is quite insoluble in potassic bisulphite. If ignited gently in a stream
of carbonic acid gas, the weight remains constant. To render it
anhydrous, a heat of 200° is required.

The recognition of arsenic in the commercial sulphide is most easily
effected by placing 2 grms. or more in a suitable retort (with
condenser), adding hydrochloric acid, and distilling. The chloride of
arsenic passes over before the chloride of antimony; and by not raising
the heat too high, very little antimony will come over, even if the
distillation be carried almost to dryness. The arsenic is detected in
the distillate by the ordinary methods.

Several lamentable accidents have happened through mistaking the
sulphide of antimony for oxide of manganese, and using it with potassic
chlorate for the production of oxygen. The addition of a drop of
hydrochloric acid, it is scarcely necessary to say, will distinguish
between the two.

Antimony is frequently estimated as sulphide. An amorphous tersulphide
of mercury, containing a small admixture of antimonious oxide and
sulphide of potassium, is known under the name of _Kermes mineral_, and
has lately been employed in the vulcanising of india-rubber. Prepared in
this way, the latter may be used for various purposes, and thus become a
source of danger. It behoves the analyst, therefore, in searching for
antimony, to take special care not to use any india-rubber fittings
which might contain the preparation.

A _pentasulphide of antimony_ (from the decomposition of Schleppe’s salt
[Na₃Sb₆S₄ + 9H₂O], when heated with an acid) is used in calico-printing.

§ 750. =Tartarated Antimony, Tartrate of Potash and Antimony, or Tartar
Emetic=, is, in a medico-legal sense, the most important of the
antimonial salts. Its formula is KSbC₄H₄O₇H₂O, and 100 parts,
theoretically, should contain 35·2 per cent. of metallic antimony. The
B.P. gives a method of estimation of tartar emetic not free from error,
and Professor Dunstan has proposed the following:--Dissolve 0·3 grm. of
tartar emetic in 80 c.c. of water, add to this 10 c.c. of a 5 per cent.
solution of sodium bicarbonate, and immediately titrate with a
decinormal solution of iodine, using starch as an indicator. One c.c. of
_n_/10 iodine = 0·0166 grm. tartar emetic; therefore, if pure, the
quantity used by 0·3 grm. should be 18 c.c. Tartar emetic occurs in
commerce in colourless, transparent, rhombic, octahedral crystals,
slightly efflorescing in dry air.

A crystal, placed in the subliming cell (p. 258), decrepitates at 193·3°
(380° F.), sublimes at 248·8° (480° F.) very slowly and scantily, and
chars at a still higher temperature, 287·7° (550° F.). On evaporating a
few drops of a solution of tartar emetic, and examining the residue by
the microscope, the crystals are either tetrahedra, cubes, or branched
figures. 100 parts of cold water dissolve 5 of tartar emetic, whilst the
same quantity of boiling water dissolves ten times as much, viz., 50.
The watery solution decomposes readily with the formation of algæ; it
gives no precipitate with ferrocyanide of potassium, chloride of barium,
or nitrate of silver, unless concentrated.

§ 751. =Metantimonic Acid=, so familiar to the practical chemist from
its insoluble sodium salt, is technically applied in the painting of
glass, porcelain, and enamels; and in an impure condition, as antimony
ash, to the glazing of earthenware.

§ 752. =Pharmaceutical, Veterinary, and Quack Preparations of
Antimony.=[800]

[800] The history of antimony as a drug is curious. Its use was
prohibited in France in 1566, because it was considered poisonous, one
Besnier being actually expelled from the faculty for transgressing the
law on this point. The edict was repealed in 1650; but in 1668 there was
a fresh enactment, confining its use to the doctors of the faculty.

(1) =Pharmaceutical Preparations=:--

=Oxide of Antimony= (Sb₂O₃) is a white powder, fusible at a low red
heat, and soluble without effervescence in hydrochloric acid, the
solution responding to the ordinary tests for antimony. Arsenic may be
present in it as an impurity; the readiest means of detection is to
throw small portions at a time on glowing charcoal, when very small
quantities of arsenic will, under such conditions, emit the peculiar
odour. Carbonate of lime appears also to have been found in the oxide of
commerce.

=Antimonial Powder= is composed of one part of oxide of antimony and two
parts of phosphate of lime; in other words, it ought to give 33·3 per
cent. of Sb₂O₃.

=Tartar Emetic= itself has been already described. The preparations used
in medicine are--

=The Wine of Antimony= (=Vinum antimoniale=), which is a solution of
tartar emetic in sherry wine, and should contain 2 grains of the salt in
each ounce of the wine (0·45 grm. in 100 c.c.).

=Antimony Ointment= (=Unguentum antimonii tartarati=) is a mechanical
mixture of tartar emetic and lard, or simple ointment;[801] strength 20
per cent. There is no recorded case of conviction for the adulteration
of tartar emetic; cream of tartar is the only probable addition. In such
a case the mixture is less soluble than tartar emetic itself, and on
adding a small quantity of carbonate of soda to a boiling solution of
the suspected salt, the precipitated oxide at first thrown down, becomes
redissolved.

[801] Simple ointment is composed of white wax 2, lard 3, almond oil 3
parts.

=Solution of Chloride of Antimony= is a solution of the terchloride in
hydrochloric acid; it is a heavy liquid of a yellowish-red colour,
powerfully escharotic; its specific gravity is 1·47; on dilution with
water, the whitish-yellow oxychloride of antimony is precipitated. One
drachm (3·549 c.c.) mixed with 4 ounces (112 c.c.) of a solution of
tartaric acid (·25 : 4) gives a precipitate with SH₂, which weighs _at
least_ 22 grains (1·425 grm.). This liquid is used on very rare
occasions as an outward application by medical men; farriers sometimes
employ it in the foot-rot of sheep.

=Purified Black Antimony= (=Antimonium nigrum purificatum=) is the
purified native sulphide Sb₂S₃; it should be absolutely free from
arsenic.

=Sulphurated Antimony= (=Antimonium sulphuratum=) is a mixture of
sulphide of antimony, Sb₂S₃, with a small and variable amount of oxide,
Sb₂O₃. The P.B. states that 60 grains (3·888 grms.) dissolved in ClH,
and poured into water, should give a white precipitate of oxychloride of
antimony, which (properly washed and dried) weighs about 53 grains
(3·444 grms.). The officinal compound pill of subchloride of mercury
(_Pilula hydrargyri subchloridi composita_) contains 1 grain (·0648
grm.) of sulphurated antimony in every 5 grains (·324 grm.), _i.e._, 20
per cent.

(2) =Patent and Quack Pills=:--

    =Dr. J. Johnson’s Pills.=--From the formula each pill should
    contain:--

                                      Grains.    Grms.
  Compound Extract of Colocynth,        2·5   =  ·162
  Calomel,                               ·62  =  ·039
  Tartar Emetic,                         ·04  =  ·002
  Oil of Cassia,                         ·12  =  ·007
                                        ----     ----
                                        3·28  =  ·210

    The oil of cassia can be extracted by petroleum ether; the calomel
    sublimed and identified by the methods given in the article on
    “Mercury”; the antimony deposited in the metallic state on platinum
    or tin; and the colocynth extracted by dissolving in water,
    acidifying, and shaking up with chloroform. On evaporating the
    chloroform the residue should taste extremely bitter; dissolved in
    sulphuric acid it changes to a red colour, and dissolved in Fröhde’s
    reagent to a cherry-red. It should also have the ordinary reactions
    of a glucoside.

    =Mitchell’s Pills= contain in each pill:--

                        Grains.    Grms.
  Aloes,                  1·1   =  ·070
  Rhubarb,                1·6   =  ·103
  Calomel,                 ·16  =  ·010
  Tartar Emetic,           ·05  =  ·003
                          ----     ----
                          2·91  =  ·186

    The mineral substances in this are easy of detection by the methods
    already given; the aloes by the formation of chrysammic acid, and
    the rhubarb by its microscopical characters.

    =Dixon’s Pills= probably contain the following in each pill:--

                                   Grains.    Grms.
  Compound Extract of Colocynth,    2·0   =  ·1296
  Rhubarb,                          1·0   =  ·0648
  Tartar Emetic,                     ·06  =  ·0038
                                    ----     -----
                                    3·06  =  ·1982


(3) =Antimonial Medicines, chiefly Veterinary=:[802]--

[802] There has long prevailed an idea (the truth of which is doubtful)
that antimony given to animals improves their condition; thus, the
_Encyclop. Brit._, 5th ed., art. “Antimony”:--“A horse that is lean and
scrubby, and not to be fatted by any means, will become fat on taking a
dose of antimony every morning for two months together. A boar fed for
brawn, and having an ounce of antimony given him every morning, will
become fat a fortnight sooner than others put into the stye at the same
time, and fed in the same manner, but without the antimony.” Probably
the writer means by the term _antimony_ the impure sulphide. To this may
be added the undoubted fact, that in Brunswick the breeders of fat geese
add a small quantity of antimonious oxide to the food, as a traditional
custom.

    =Liver of Antimony= is a preparation formerly much used by farriers.
    It is a mixture of antimonious oxide, sulphide of potassium,
    carbonate of potassium, and undecomposed trisulphide of antimony
    (and may also contain sulphate of potassium), all in very
    undetermined proportions. When deprived of the soluble potash salts,
    it becomes the _washed saffron of antimony_ of the old pharmacists.
    A receipt for a grease-ball, in a modern veterinary work, gives,
    with liver of antimony, cream of tartar and guaiacum as ingredients.

    =Hind’s Sweating-ball= is composed of 60 grains (3·888 grms.) of
    tartar emetic and an equal portion of assafœtida, made up into a
    ball with liquorice-powder and syrup. The assafœtida will be readily
    detected by the odour, and the antimony by the methods already
    recommended.

    =Ethiops of Antimony=, very rarely used now, is the mechanical
    mixture of the sulphides of antimony and mercury--proportions, 3 of
    the former to 2 of the latter.

    =The Flowers of Antimony= is an impure oxysulphide of antimony, with
    variable proportions of trioxide and undecomposed trisulphide.

    =Diaphoretic Antimony= (=calcined antimony=) is simply antimoniate
    of potash.

    =Glass of Antimony= is a mixture of sulphide and oxide of antimony,
    contaminated with a small quantity of silica and iron.

    A quack pill, by name, =Ward’s Red Pill=, is said to contain glass
    of antimony and dragon’s blood.

    =Antimonial Compounds used in Pyrotechny=:--

  Blue Fire:--

  Antimonious sulphide,      1
  Sulphur,                   2
  Nitre,                     6

    This composition is used for the blue or Bengal signal-light at sea.
    Bisulphide of carbon and water are solvents which will easily
    separate the powder into its three constituents.

  Crimson Fire:--

  Potassic Chlorate,            17·25
  Alder or Willow Charcoal,      4·5
  Sulphur,                      18·
  Nitrate of Strontia,          55·
  Antimonious Sulphide,          5·5

    The spectroscope will readily detect strontia and potassium, and the
    analysis presents no difficulty. In addition to these a very great
    number of other pyrotechnical preparations contain antimony.

    § 753. =Alloys.=--Antimony is much used in alloys. The ancient
    _Pocula emetica_, or everlasting emetic cups, were made of antimony,
    and with wine standing in them for a day or two, they acquired
    emetic properties. The principal antimonial alloys are Britannia and
    type metal, the composition of which is as follows:--

                                  Tin,       Copper,    Antimony,
                                per cent.   per cent.   per cent.
  Britannia Metal, Best,          92·0        1·8         6·2
                   Common,        92·1        2·0         5·9
                   For Castings,  92·9        1·8         5·3
                   For Lamps,     94·0        1·3         4·7

                                Tea Lead,  Antimony,   Block Tin,
                                per cent.  per cent.   per cent.
  Type Metal,            { (1.)   75         20           5
                         { (2.)   70         25           5
  Metal for Stereotype,           84·2       13·5         2·3

    There is also antimony in brass, concave mirrors, bell-metal, &c.

    § 754. =Pigments.=--Cassella and Naples yellow are principally
    composed of the antimoniate of lead.

    =Antimony Yellow= is a mixture of antimoniate of lead with basic
    chloride of lead.

§ 755. =Dose.=--A medicinal dose of a soluble antimonial salt should not
exceed 97·2 mgrms. (1½ grain). With circumstances favouring its action,
a dose of 129·6 mgrms. (2 grains) has proved fatal;[803] but this is
quite exceptional, and few medical men would consider so small a
quantity dangerous for a healthy adult, especially since most
posological tables prescribe tartar emetic as an emetic in doses from
64·8 to 194·4 mgrms. (1 to 3 grains). The smallest dose which has killed
a child appears to be 48·5 mgrms. (¾ grain).[804] The dose of tartar
emetic for horses and cattle is very large, as much as 5·832 grms. (90
grains) being often given to a horse in his gruel three times a day. 3·8
grms. (60 grains) are considered a full, but not an excessive, dose for
cattle; ·38 grm. (6 grains) is used as an emetic for pigs, and half this
quantity for dogs.

[803] Taylor, Guy’s Hosp. Reports, Oct. 1857.

[804] Op. cit.

§ 756. =Effects of Tartar Emetic and of Antimony Oxide on
Animals.=--Large doses of tartar emetic act on the warm-blooded animals
as on man; whether the poison is taken by the mouth, or injected
subcutaneously, all animals able to vomit[805] do so. The heart’s
action, at first quickened, is afterwards slowed, weakened, and lastly
paralysed. This action is noticed in cold as well as in warm-blooded
animals. It is to be ascribed to a direct action on the heart; for if
the brain and spinal cord of the frog be destroyed--or even if a
solution of the salt be applied direct to the frog’s heart separated
from the body--the effect is the same. The weak action of the heart, of
course, causes the blood-pressure to diminish, and the heart stops in
diastole. The voluntary muscles of the body are also weakened; the
breathing is affected, partly from the action on the muscles. The
temperature of the body is depressed (according to F. A. Falck’s
researches) from 4·4° to 6·2°.

[805] L. Hermann (_Lehrbuch der experimentellen Toxicologie_) remarks
that the vomiting must be considered as a reflex action from the
inflammatory excitement of the digestive apparatus, especially of the
stomach. It is witnessed if the poison is administered subcutaneously or
injected into the brain. Indeed, it is established that (at least, so
far as the muscles are concerned) the co-ordinated movements producing
vomiting are caused by excitement of the medulla oblongata. Giannussi
and others found that after section between the first and third vertebræ
of dogs, and subsequent administration of tartar emetic, no vomiting
took place; and Grimm’s researches seem to show that the suspected
_vomit-centre_ is identical with the respiratory centre, so that the
vomiting movement is only an abnormal respiratory movement. L. Hermann,
however, considers the theory that when tartar emetic is introduced into
the vessels the _vomit-centre_ is directly excited, erroneous, for (1)
in introducing it by the veins much larger doses are required to excite
vomiting than by the stomach; and (2), after subcutaneous injection of
the salt, antimony is found in the first vomit. His explanation,
therefore, is that antimony is excreted by the intestinal tract, and in
its passage excites this action. Majendie’s well-known
experiment--demonstrating that, after extirpation of the stomach,
vomiting movements were noticed--is not considered opposed to this view.

The effect of small doses given repeatedly to animals has been several
times investigated. Dr. Nevin[806] experimented upon eleven rabbits,
giving them tartar emetic four times a day in doses of 32·4 mgrms. (½
grain), 64·8 mgrms. (1 grain), and 129·6 mgrms. (2 grains). Five died,
the first after four, the last after seventeen days; three were killed
after one, three, and four days respectively, two after an interval of
fourteen days, and one thirty-one days after taking the last dose. There
was no vomiting; diarrhœa was present in about half the number; one of
the rabbits, being with young, aborted. The chief symptoms were general
dulness, loss of appetite, and in a few days great emaciation. Four of
the five that died were convulsed before death, and several of the
animals exhibited ulcers of the mucous membrane of the mouth, in places
with which the powder had come in contact. Caillol and Livon have also
studied the action of small doses of the white oxide of antimony given
in milk to cats. A cat took in this way in 109 days ·628 grm. The animal
passed gradually into a cachectic state, diarrhœa supervened, and it
died miserably thin and exhausted.

[806] Lever, _Med. Chir. Journ._, No. 1.

§ 757. =Effects of Tartar Emetic on Man.=[807]--The analogy between the
symptoms produced by arsenic and antimony is striking, and in some acute
cases of poisoning by tartar emetic, there is but little (if any)
clinical difference. If the dose of tartar emetic is very large, there
may be complete absence of vomiting, or only a single evacuation of the
stomach. Thus, in a case mentioned by Taylor, in which a veterinary
surgeon swallowed by mistake 13 grms. (200 grains) of tartar emetic,
vomiting after fifteen minutes could only be induced by tickling the
throat. So, again, in the case reported by Mr. Freer, a man, aged 28,
took 7·77 grms. (120 grains) of tartar emetic by mistake for Epsom
salts; he vomited only once; half an hour after taking the poison he had
violent pain in the stomach and abdomen, and spasmodic contraction of
the abdomen and arms; the fingers were firmly contracted, the muscles
quite rigid, and there was involuntary aqueous purging. After six hours,
during which he was treated with green tea, brandy, and decoction of
oak-bark, he began to recover, but suffered for many nights from profuse
perspirations.

[807] Antimony occasionally finds its way into articles of food through
obscure channels. Dr. Page has recorded the fact of antimonial lozenges
having been sold openly by an itinerant vendor of confectionery. Each
lozenge contained nearly a quarter of a grain (·16 mgrms.), and they
caused well-marked symptoms of poisoning in the case of a servant and
two children. How the antimony got in was unknown. In this case it
appears to have existed not as tartar emetic, but as an insoluble oxide,
for it would not dialyse in aqueous solution.--“On a remarkable instance
of Poisoning by means of Lozenges containing Antimony,” by David Page,
M.D., Medical Officer of Health, _Lancet_, vol. i., 1879, p. 699.

With more moderate and yet large doses, nausea and vomiting are very
prominent symptoms, and are seldom delayed more than half an hour. The
regular course of symptoms may therefore be summed up thus:--A metallic
taste in the mouth, repeated vomitings, which are sometimes bloody,
great faintness and depression, pains in the abdomen and stomach, and
diarrhœa, which may be involuntary. If the case is to terminate fatally,
the urine is suppressed, the temperature falls, the face becomes
cyanotic, delirium and convulsions supervene, and death occurs in from
two to six days. Antimony, like arsenic, often produces a pustular
eruption. Solitary cases deviate more or less from the course described,
_i.e._, severe cramps affecting all the muscles, hæmorrhage from the
stomach, kidney, or bowel, and death from collapse in a few hours, have
all been noticed. In a case recorded by Mr. Morley,[808] a surgeon’s
daughter, aged 18, took by mistake an unknown quantity of antimonial
wine; she soon felt sleepy and powerless, and suffered from the usual
symptoms in combination with tetanic spasms of the legs. She afterwards
had enteritis for three weeks, and on recovery her hair fell off. Orfila
relates a curious case of intense spasm of the gullet from a large dose
of tartar emetic.

[808] _Brit. Med. Journ._, Oct. 14, p. 70.

§ 758. =Chronic Antimonial Poisoning.=--The cases of Palmer and J. P.
Cook, M. Mullen, Freeman, Winslow, Pritchard, and the remarkable Bravo
case have, in late years, given the subject of chronic antimonial
poisoning a considerable prominence. In the trials referred to, it was
shown that medical men might easily mistake the effects of small doses
of antimony given at intervals for the action of disease--the symptoms
being great nausea, followed by vomiting, chronic diarrhœa, alternating
with constipation, small frequent pulse, loss of voice, great muscular
weakness, depression, with coldness of the skin and a clammy
perspiration. In the case of Mrs. Pritchard,[809] her face was flushed,
and her manner so excited as to give an ordinary observer the idea that
she had been drinking; and with the usual symptoms of vomiting and
purging, she suffered from cramps in the hands. Dr. Pritchard tried to
make it appear that she was suffering from typhoid fever, which the
symptoms in a few respects only resembled.

[809] _Edin. Med. Journ._, 1865.

According to Eulenberg, workmen, exposed for a long period to the vapour
of the oxide of antimony, suffer pain in the bladder and a burning
sensation in the urethra, and continued inhalation even leads to
impotence and wasting of the testicles.[810]

[810] In the first operations of finishing printers’ types, the workmen
inhale a metallic dust, which gives rise to effects similar to lead
colic; and probably in this case the lead is more active than the
associated antimony.

§ 759. =Post-mortem Appearances.=--The effect of large doses of tartar
emetic is mainly concentrated upon the gastro-intestinal mucous
membrane. There is an example in the museum of University College
Hospital of the changes which resulted from the administration of tartar
emetic in the treatment of pneumonia. These are ascribed in the
catalogue, in part to the local action of the medicine, and in part to
the extreme prostration of the patient. In the preparation (No. 1052)
the mucous membrane over the fore border of the epiglottis and adjacent
part of the pharynx has been destroyed by sloughing; the ulceration
extends into the upper part of the œsophagus. About an inch below its
commencement, the mucous membrane has been entirely removed by sloughing
and ulceration, the circular muscular fibres being exposed. Above the
upper limit of this ulcer, the mucous membrane presents several oval,
elongated, and ulcerated areas, occupied by strips of mucous membrane
which have sloughed. In other places, irregular portions of the mucous
membrane, of a dull ashen-gray colour, have undergone sloughing; the
edges of the sloughing portion are of colours varying from brown to
black.

It is seldom that so much change is seen in the gullet and pharynx as
this museum preparation exhibits; but redness, swelling, and the
general signs of inflammation are seldom absent from the stomach and
some parts of the intestines. On the lining membrane of the mouth,
ulcers and pustules have been observed.

In Dr. Nevin’s experiments on the chronic poisoning of rabbits already
referred to, the _post-mortem_ appearances consisted in congestion of
the liver in all the rabbits; in nearly all there was vivid redness of
the stomach; in two cases there was ulceration; in some, cartilaginous
hardness of the pylorus; while, in others, the small intestines
presented patches of inflammation. In two of the rabbits the solitary
glands throughout the intestines were prominent, yellow in colour, and
loaded with antimony. The colon and rectum were healthy, the kidneys
congested; the lungs were in most congested, in some actually inflamed,
or hepatised and gorged with blood. Bloody extravasations in the chest
and abdomen were frequent.

Saikowsky,[811] in feeding animals daily with antimony, found invariably
in the course of fourteen to nineteen days fatty degeneration of the
liver, and sometimes of the kidney and heart. In the experiment of
Caillol and Livon also all the organs were pale, the liver had undergone
fatty degeneration, and the lung had its alveoli filled with large
degenerated cells, consisting almost entirely of fat. The mesenteric
glands also formed large caseous masses, yellowish-white in colour,
which, under the microscope, were seen to be composed of fatty cells, so
that there is a complete analogy between the action of arsenic and
antimony on the body tissues.

[811] Virchow’s _Arch. f. path. Anat._, Bd. xxv.; also, _Centralblatt f.
Med. Wissen._, No. 23, 1865.

§ 760. =Elimination of Antimony.=--Antimony is mainly eliminated by the
urine. In 1840, Orfila showed to the _Académie de Médecine_ metallic
antimony, which he had extracted from a patient who had taken ·12 grm.
of tartar emetic in twenty-four hours. He also obtained antimony from an
old woman, aged 80, who twelve hours before had taken ·6 grm. (9¼
grains)--a large dose, which had neither produced vomiting nor purging.
In Dr. Kevin’s experiments on rabbits, antimony was discovered in the
urine after the twelfth dose, and even in the urine of an animal
twenty-one days after the administration of the poison had been
suspended.

§ 761. =Antidotes for Tartar Emetic.=--Any infusion containing tannin or
allied astringent principles, such as decoctions of tea, oak-bark, &c.,
may be given with advantage in cases of recent poisoning by tartar
emetic, for any of the salt which has been expelled by vomiting may in
this way be decomposed and rendered harmless. The treatment of acute
poisoning which has proved most successful, has been the encouraging of
vomiting by tickling the fauces, giving strong green tea and stimulants.
(See Appendix.)

§ 762. =Effects of Chloride or Butter of Antimony.=--Only a few cases of
poisoning by butter of antimony are on record: its action, generally
speaking, on the tissues is like that of an acid, but there has been
considerable variety in the symptoms. Five cases are recorded by Taylor;
three of the number recovered after taking respectively doses of 7·7
grms. (2 drachms) and 15·5 grms. (4 drachms), and two died after taking
from 56·6 to 113 grms. (2 to 4 ounces). In one of these cases the
symptoms were more like those of a narcotic poison, in the other fatal
case there was abundant vomiting with purging. The autopsy in the first
case showed a black appearance from the mouth to the jejunum, as if the
parts had been charred, and extensive destruction of the mucous
membrane. In the other case there were similar changes in the stomach
and the upper part of the intestines, but neither the lips nor the lower
end of the gullet were eroded. In a case recorded by Mr. Barrington
Cooke,[812] a farmer’s wife, aged 40, of unsound mind, managed to elude
the watchfulness of her friends, and swallowed an unknown quantity of
antimony chloride about 1.30 P.M. Shortly afterwards she vomited several
times, and had diarrhœa; at 2.30 a medical man found her lying on her
back insensible, and very livid in the face and neck. She was retching,
and emitting from her mouth a frothy mucous fluid, mixed with ejected
matter of a grumous colour; the breathing was laboured and spasmodic;
the pulse could not be felt, and the body was cold and clammy. She
expired at 3.30, about one hour and a half from the commencement of
symptoms, and probably within two hours from the taking of the poison.
The autopsy showed no corrugation of the tongue or inner surface of the
lining membrane of the mouth, and no appearance of the action of a
corrosive upon the lips, fauces, or mucous membrane of the œsophagus.
The whole of the mucous membrane of the stomach was intensely congested,
of a dark and almost black colour, the rest of the viscera were healthy.
Chemical analysis separated antimony equivalent to nearly a grm. (15
grains) of the chloride, with a small quantity of arsenic, from the
contents of the stomach.

[812] _Lancet_, May 19, 1883.

§ 763. =Detection of Antimony in Organic Matters.=--In acute poisoning
by tartar emetic it is not impossible to find a mere trace only in the
stomach, the greater part having been expelled by vomiting, which nearly
always occurs early, so that the most certain method is, where possible,
to analyse the ejected matters. If it should be suspected that a living
person is being slowly poisoned by antimony, it must be remembered that
the poison is mainly excreted by the kidneys, and the urine should
afford some indication. The readiest way to test is to collect a
considerable quantity of the urine (if necessary, two or three days’
excretion), concentrate by evaporation, acidify, and then transfer the
liquid to a platinum dish, in which is placed a slip of zinc. The whole
of the antimony is in time deposited on the platinum dish, and being
thus concentrated, may be subsequently identified in any way thought
fit.

Organic liquids are boiled with hydrochloric acid; organic solids are
extracted with the same acid in the manner described (p. 51); or, if the
distillation process given at p. 576 be employed, the antimony may be
found partly in the distillate, and partly in the retort. In any case,
antimony in solution may be readily detected in a variety of ways--one
of the most convenient being to concentrate on tin or platinum, to
dissolve out the antimonial film by sulphide of ammonium, and thus
produce the very characteristic orange sulphide.

If a slip of pure tinfoil be suspended for six hours in a solution,
which should not contain more than one-tenth of its bulk of ClH, and
exhibit no stain or deposit, it is certain that antimony cannot be
present. It may also conveniently be deposited on a platinum dish,[813]
by filling the same with the liquid properly acidulated, and inserting a
rod of zinc; the metallic antimony can afterwards be washed, dried, and
weighed.

[813] According to Fresenius (_Zeitschr. f. anal. Chem._, i. 445), a
solution which contains 1/10000 of its weight of antimony, treated in
this way, gives in two minutes a brown stain, and in ten a very notable
and strong dark brown film. When in the proportion of 1 to 20,000, the
reaction begins to be certain after a quarter of an hour; with greater
dilution it requires longer time, 1 to 40,000 giving a doubtful
reaction, and 1 to 50,000 not responding at all to this test.

Reinsch’s and Marsh’s tests have been already described (pp. 558 and
559), and require no further notice. There is, however, a very beautiful
and delicate means of detecting antimony, which should not be omitted.
It is based upon the action of stibine (SbH₃) on sulphur.[814] When this
gas is passed over sulphur, it is decomposed according to equation,
2SbH₃ + 6S = Sb₂S₃ + 3SH₂, the action taking place slowly in diffused
daylight, but very rapidly in sunshine. An ordinary flask for the
evolution of hydrogen (either by galvanic processes or from zinc and
sulphuric acid), with its funnel and drying-tubes, is connected with a
narrow tube having a few fragments of sulphur, kept in place by plugs of
cotton wool. The whole apparatus is placed in sunshine; if no orange
colour is produced when the hydrogen has been passing for some time, the
liquid to be tested is poured in gradually through the funnel, and if
antimony should be present, the sulphur acquires a deep orange colour.
This is distinct even when so small a quantity as ·0001 grain has been
added through the funnel. The sulphide of antimony thus mixed with
sulphur can, if it is thought necessary, be freed from the sulphur by
repeated exhaustion with bisulphide of carbon. The stibine does not,
however, represent all the antimony introduced, a very large proportion
remaining in the evolution flask;[815] hence it cannot be employed for
quantitative purposes. Moreover, the test can, of course, only be
conveniently applied on sunny days, and is, therefore, in England more
adapted for summer.[816] Often, however, as mentioned elsewhere, when
the analyst has no clue whatever to the nature of the poison, it is
convenient to pass SH₂ in the liquid to saturation.[817] In such a case,
if antimony is present (either alone or in combination with other
sulphides), it remains on the filter, and must be separated and
identified as follows:--The sulphides are first treated with a solution
of carbonate of ammonia, which will dissolve arsenic, if present, and
next saturated _in situ_ with pure sulphide of sodium, which will
dissolve out sulphide of antimony, if present. The sulphide of antimony
will present the chemical characters already described, more
particularly--

[814] See Ernest Jones on “Stibine,” _Journ. Chem. Soc._, vol. i., 1876.

[815] Rieckter, _Jahresbericht_, 1865, p. 255.

[816] The action of salts of cæsium with chloride of antimony might be
used as a test for the latter. A salt of cæsium gives a white
precipitate with chloride of antimony in concentrated ClH; it contains
30·531 per cent. of antimony, and corresponds to the formula SbCl₃CsCl.
Chloride of tin acts similarly.--E. Godeffroy, _Berichte der deutschen
Chem. Gesellschaft_, Berlin, 1874.

[817] The solution must not be too acid.

(1) It will evolve SH₂ when treated with HCl, and at the same time pass
into solution.[818]

[818] By adding chloride of tin to a solution of chloride of antimony in
sufficient quantity, and passing SO₂ through the liquid, the whole of
the antimony can be thrown down as sulphide, whilst the tin remains in
solution. Thus,--

  9SnCl₂ + 2SbCl₃ + 3SO₂ + 12ClH = Sb₂S₃ + 9SnCl₄ + 6OH₂.

--Federow, _Zeitschrift für Chemie_, 1869, p. 16.

(2) The solution evaporated to get rid of free HCl gives with water a
thick cheesy precipitate of basic chloride of antimony. This may be seen
if only a drop or two of the solution be taken and tested in a
watch-glass.

(3) If tartaric acid be added to the solution, this precipitation does
not occur.

(4) The solution from (3) gives an orange precipitate with SH₂.

Such a substance can only be sulphide of antimony. With regard to (2),
bismuth would act similarly, but under the circumstances could not be
present, for the sulphide of bismuth is insoluble in sodic sulphide.

§ 764. =Quantitative Estimation.=--The quantitative estimation of
antimony is best made by some volumetric process, _e.g._, the sulphide
can be dissolved in HCl, some tartrate of soda added, and then carbonate
of soda to weak alkaline reaction. The strength of the solution of
tartarised antimony thus obtained can now be estimated by a decinormal
solution of iodine, the end reaction being indicated by the previous
addition of a little starch solution, or by a solution of permanganate
of potash, either of which should be standardised by the aid of a
solution of tartar emetic of known strength.


3. CADMIUM.

    § 765. =Cadmium=, Cd = 112; specific gravity, 8·6 to 8·69;
    fusing-point, 227·8° (442° F.); boiling-point, 860° (1580°
    F.).--Cadmium in analysis is seldom separated as a metal, but is
    estimated either as oxide or sulphide.

    § 766. =Cadmium Oxide=, CdO = 128--cadmium, 87·5 per cent.; oxygen,
    12·5 per cent.--is a yellowish or reddish-brown powder, non-volatile
    even at a white heat; insoluble in water, but dissolving in acids.
    Ignited on charcoal, it is reduced to metal, which volatilises, and
    is then deposited again as oxide, giving to the coal a distinct coat
    of an orange-yellow colour in very thin layers; in thicker layers,
    brown.

    § 767. =Cadmium Sulphide=, CdS = 144--Cd, 77·7 per cent.; S, 22·3
    per cent.--known as a mineral termed Greenockite. When prepared in
    the wet way, it is a lemon-yellow powder, which cannot be ignited in
    hydrogen without loss, and is insoluble in water, dilute acids,
    alkalies, alkaline sulphides, sulphate of soda, and cyanide of
    potassium. The solution must not contain too much hydrochloric acid,
    for the sulphide is readily soluble with separation of sulphur in
    concentrated hydrochloric acid. It may be dried in the ordinary way
    at 100° without suffering any decomposition.

    § 768. =Medicinal Preparations.=--_The Iodide of Cadmium_ (CdI₂)
    occurs in white, flat, micaceous crystals, melting at about 215·5°
    (419·9° F.), and at a dull red heat giving off violet vapour. In
    solution, the salt gives the reactions of iodine and cadmium. The
    ointment of iodide of cadmium (_Unguentum cadmii iodidi_) contains
    the iodide in the proportion of 62 grains to the ounce, or 14 per
    cent.

    =Cadmium Sulphate= is officinal in the Belgian, Portuguese, and
    French pharmacopœias.

    § 769. =Cadmium in the Arts, &c.=--Cadmium is used in various
    alloys. The sulphide is found as a colouring ingredient in certain
    toilet soaps, and it is much valued by artists as a pigment. The
    iodide of cadmium is employed in photography, and an amalgam of
    metallic cadmium to some extent in dentistry.

    § 770. =Fatal Dose of Cadmium.=--Although no deaths from the use of
    cadmium appear to have as yet occurred, its use in photography, &c.,
    may lead to accidents. There can be no question about the poisonous
    action of cadmium, for Marmé,[819] in his experiments on it with
    animals, observed giddiness, vomiting, syncope, difficulty in
    respiration, loss of consciousness, and cramps. The amount necessary
    to destroy life can only be gathered from the experiments on
    animals. A strong hound died after the injection of ·03 grm. (·462
    grain) subcutaneously of a salt of cadmium; rabbits are poisoned if
    from 19·4 to 38·8 mgrms. (·3 to ·6 grain) are introduced into the
    stomach. A watery solution of ·5 grm. (7·5 grains) of the bromide
    administered to a pigeon caused instant death, without convulsion;
    the same dose of the chloride killed a second pigeon in six minutes;
    ·25 grm. (3·85 grains) of sulphite of cadmium administered to a
    pigeon excited vomiting, and after two hours diarrhœa; it died in
    eight days. Another pigeon died from a similar dose in fourteen
    days, and cadmium, on analysis, was separated from the liver. From
    the above cases it would seem probable that 4 grms. (61·7 grains)
    would be a _dangerous_ dose of a soluble salt of cadmium for an
    adult, and that in a case of chronic poisoning it would most
    probably be found in the liver.

[819] _Zeitschr. f. rationelle Med._, vol. xxix. p. 1, 1867.

    § 771. =Separation and Detection of Cadmium.=--If cadmium be in
    solution, and the solution is not too acid, on the addition of SH₂
    there is precipitated a yellow sulphide, which is distinguished
    from antimony and arsenical sulphides by its insolubility in ammonia
    and alkaline sulphides. Should all three sulphides be on the filter
    (an occurrence which will seldom, perhaps never, happen), the
    sulphide of arsenic can be dissolved out by ammonia, the antimony by
    sulphide of sodium, leaving the sulphide of cadmium as the
    residue.[820]

[820] It is unnecessary to state that absence of sulphur is presupposed.

    The further tests of the sulphide are:--

    (1) It dissolves in dilute nitric acid to a colourless fluid, with
    separation of sulphur.

    (2) The solution, filtered and freed from excess of nitric acid by
    evaporation, gives with a solution of ammonic carbonate a white
    precipitate of carbonate of cadmium insoluble in excess. This
    distinguishes it from zinc, which gives a similar white precipitate,
    but is soluble in the excess of the precipitant.

    (3) The carbonate thus obtained, heated on platinum foil, is changed
    into the brown-red non-volatile oxide.

    (4) The oxide behaves on charcoal as already detailed.

    (5) A metallic portion can be obtained by melting the oxide with
    cyanide of potassium; it is between zinc and tin in brilliancy, and
    makes a mark on paper like lead, but not so readily. There are many
    other tests, but the above are conclusive.

    If cadmium in any case be specially searched for in the organs or
    tissues, the latter should be boiled with nitric acid. The acid
    solution is filtered, saturated with caustic potash, evaporated to
    dryness, and ignited; the residue is dissolved in dilute
    hydrochloric acid, and treated after filtration with SH₂. Cadmium
    may also be estimated volumetrically by digesting the sulphide in a
    stoppered flask with ferric chloride and hydrochloric acid; the
    resulting ferrous compound is titrated with permanganate, each c.c.
    of a d.n. solution of permanganate = ·0056 grm. of cadmium.


II.--PRECIPITATED BY HYDRIC SULPHIDE IN HYDROCHLORIC ACID
SOLUTION--BLACK.

Lead--Copper--Bismuth--Silver--Mercury.


1. LEAD.

§ 772. =Lead=, Pb = 207.--Lead is a well-known bluish-white, soft metal;
fusing-point, 325°; specific gravity, 11·36.

=Oxides of Lead.=--The two oxides of lead necessary to notice here
briefly are--litharge and minium.

=Litharge, or Oxide of Lead=, PbO = 223; specific gravity, 9·2 to
9·5--Pb 92·82 per cent., O 7·18--is either in crystalline scales, a
fused mass, or a powder, varying in colour (according to its mode of
preparation) from yellow to reddish-yellow or orange. When prepared
below the temperature of fusion it is called “_massicot_.” It may be
fused without alteration in weight; in a state of fusion it dissolves
silicic acid and silicates of the earths. It must not be fused in
platinum vessels.

=Minium, or Red Lead=, 2PbO, PbO₂; specific gravity, 9·08, is a compound
of protoxide of lead with the dioxide. It is of a brilliant red colour,
much used in the arts, and especially in the preparation of flint-glass.

§ 773. =Sulphide of Lead=, PbS = 239; Pb, 86·61 per cent., S, 13·39 per
cent., occurring in the usual way, is a black precipitate insoluble in
water, dilute acids, alkalies, and alkaline sulphides. It dissolves in
strong nitric acid with separation of sulphur, and in strong
hydrochloric acid, with evolution of SH₂. Fuming nitric acid does not
separate sulphur, but converts the sulphide into sulphate.

§ 774. =Sulphate of Lead=, PbSO₄ = 303; specific gravity, 6·3; PbO,
73·61 per cent., SO₃, 26·39 per cent., when produced artificially is a
heavy white powder, of great insolubility in water, 22,800 parts of cold
water dissolving only one of lead sulphate; and if the water contains
sulphuric acid, no less than 36,500 parts of water are required. The
salts of ammonia (especially the acetate and tartrate) dissolve the
sulphate, and it is also soluble in hyposulphite of soda. The sulphate
can be readily changed into the carbonate of lead, by boiling it with
solutions of the alkaline carbonates. The sulphate of lead, fused with
cyanide of potassium, yields metallic lead; it may be also reduced on
charcoal, and alone it may be fused without decomposition, provided
reducing gases are excluded.

§ 775. =Acetate of Lead=, =Sugar of Lead=, Pb(C₂H₃O₂)₂3OH₂ = 379, is
found in commerce in white, spongy masses composed of acicular crystals.
It may, however, be obtained in flat four-sided prisms. It has a sweet
metallic taste, is soluble in water, and responds to the usual tests for
lead. The P.B. directs that 38 grains dissolved in water require, for
complete precipitation, 200 grain measures of the volumetric solution of
oxalic acid, corresponding to 22·3 grains of oxide of lead.

§ 776. =Chloride of Lead=, PbCl₂ = 278; specific gravity, 5·8; Pb, 74·48
per cent., Cl, 25·52 per cent., is in the form of brilliant crystalline
needles. It is very insoluble in cold water containing hydrochloric or
nitric acids. According to Bischof, 1635 parts of water containing
nitric acid dissolve one part only of chloride of lead. It is insoluble
in absolute alcohol, and sparingly in alcohol of 70 to 80 per cent. It
fuses below red heat without losing weight; at higher temperatures it
may be decomposed.

=Carbonate of Lead.=--The commercial carbonate of lead (according to the
exhaustive researches of Wigner and Harland[821]) is composed of a
mixture of neutral carbonate of lead and hydrate of lead, the best
mixture being 25 per cent. of hydrate, corresponding to an actual
percentage of 12·3 per cent. carbonic acid. The nearer the mixture
approximates to this composition the better the paint; whilst samples
containing as much as 16·33 per cent., or as little as 10·39 per cent.,
of CO₂ are practically useless.

[821] “On the Composition of Commercial Samples of White Lead,” by G. W.
Wigner and R. H. Harland.--_Analyst_, 1877, p. 208.

§ 777. =Preparations of Lead used in Medicine, the Arts, &c.=

(1) =Pharmaceutical=:--

=Lead Plaster= (_Emplastrum plumbi_) is simply a lead soap, in which the
lead is combined with oleic and margaric acids, and contains some
mechanically included glycerin.

=Lead Iodide=, PbI₂, is contained in the _Emplastrum plumbi iodidi_ to
the extent of 10 per cent., and in the _Unguentum plumbi iodidi_ to the
extent of about 12·5 per cent.

=Acetate of Lead= is contained in a pill, a suppository, and an
ointment. The pill (_Pilula plumbi cum opio_) contains 75 per cent. of
lead acetate, and 12·5 per cent. of opium, the rest confection of roses.
The suppository (_Suppositoria plumbi composita_) contains 20 per cent.
of acetate of lead, and 6·6 per cent. of opium, mixed with oil of
theobroma. The ointment (_Unguentum plumbi acetatis_) contains 20·6 per
cent. of lead acetate, mixed with benzoated lard.

The solution of subacetate of lead (_Liquor plumbi subacetatis_) is the
subacetate, Pb(C₂H₃O₂)₂PbO, dissolved in water; it contains nearly 27
per cent. of subacetate.

A dilute solution of the stronger, under the name of _Liquor plumbi
subacetatis dilutus_, and commonly called Goulard water, is prepared by
mixing 1 part (by volume) of the solution and 1 part of spirit, and 78
parts of distilled water; the strength is equal to 1·25 per cent.

There is an ointment, called the _Compound Ointment of subacetate of
lead_, which contains the subacetate in about the proportion of 2 per
cent. of the oxide, the other constituents being camphor, white wax, and
almond oil.

=Carbonate of Lead.=--The ointment (_Unguentum plumbi carbonatis_)
should contain about 12·5 per cent. of the carbonate, and the rest
simple ointment.

    (2) =Quack Nostrums, &c.=:--

    The quack medicines composed of lead are not very numerous.

    Liebert’s =Cosmetique Infaillible= is said to have for its basis
    nitrate of lead.

    One of “=Ali Ahmed’s Treasures of the Desert=,” viz., the antiseptic
    malagma, is a plaster made up of lead plaster 37·5 per cent.,
    frankincense 25 per cent., salad oil 25 per cent., beeswax 12·5 per
    cent.

    =Lewis’ Silver Cream= contains white precipitate and a salt of lead.

    =Goulard’s Balsam= is made by triturating acetate of lead with hot
    oil of turpentine.

    There are various ointments in use made up of litharge. Some
    herbalists in the country (from cases that have come under the
    writer’s own knowledge) apply to cancerous ulcers, &c., a liniment
    of linseed and other common oils mixed with litharge and acetate of
    lead.

    Acetate of lead may also be found as a constituent of various
    eye-waters.

    (3) =Preparations of Lead used in the Arts, &c.=:--

    =Ledoyen’s Disinfecting Fluid= has for its basis nitrate of lead.

    In various hair-dyes the following are all used:--Litharge, lime,
    and starch; lime and carbonate of lead; lime and acetate of lead;
    litharge, lime, and potassic bicarbonate. The detection of lead in
    the hair thus treated is extremely easy; it may be dissolved out by
    dilute nitric acid.

    =Lead Pigments.=--The principal pigments of lead are white, yellow,
    and red.

    =White Pigments=:--

    =White Lead=, =Flake White Ceruse=, =Mineral White=, are so many
    different names for the carbonate of lead already described.

    =Newcastle White= is white lead made with molasses vinegar.

    =Nottingham White.=--White lead made with alegar (sour ale), often,
    however, replaced by permanent white, _i.e._, sulphate of baryta.

    =Miniature Painters’ White=, =White Precipitate of Lead=, is simply
    lead sulphate.

    =Pattison’s White= is an oxychloride of lead, PbCl₂PbO.

    =Yellow Pigments=:--

    =Chrome Yellow= may be a fairly pure chromate of lead, or it may be
    mixed with sulphates of lead, barium, and calcium. The pigment known
    as “Cologne yellow” consists of 25 parts of lead chromate, 15 of
    lead sulphate, and 60 of calcic sulphate. The easiest method of
    analysing chrome yellow is to extract with boiling hydrochloric acid
    in the presence of alcohol, which dissolves the chromium as
    chloride, and leaves undissolved chloride of lead, sulphate of lead,
    and other substances insoluble in ClH. Every grain of chromate of
    lead should yield 0·24 grain of oxide of chromium, and 0·4 grain of
    chloride of lead.

    =Turner’s Yellow=, =Cassella Yellow=, =Patent Yellow=, is an
    oxychloride of lead (PbCl₂7PbO) extremely fusible.

    =Dutch Pink= sometimes contains white lead.

    =Red Pigments=:--

    =Chrome Red= is a bichromate of lead.

    =Red Lead= or =Minium= is the red oxide of lead.

    =Orange Red= is an oxide prepared by calcining the carbonate.

    The chief preparations of lead which may be met with in the arts, in
    addition to the oxides and the carbonate, are--

    The =Nitrate of Lead=, much used in calico-printing.

    The =Pyrolignite of Lead=, which is an impure acetate used in
    dyeing; and

    The =Sulphate of Lead= is a by-product in the preparation of acetate
    of aluminium for dyeing.

    The alloys containing lead are extremely numerous; but, according to
    the experiments of Knapp,[822] the small quantity of lead in those
    used for household purposes has no hygienic importance.

[822] _Dingl. Polytech. Journ._, vol. ccxx. pp. 446-453.

§ 778. =Statistics of Lead-Poisoning.=--In the ten years, 1883 to 1892,
no less than 1043 persons died from the effects of lead; of these, 3
only were suicidal, the remaining 1040 were mainly from the manufacture
of white lead or from the use of lead in the arts or from the accidental
contamination of food or drink.

The following table shows in what manner the 1040 were distributed as to
age and sex:--

DEATHS FROM LEAD-POISONING IN ENGLAND AND WALES DURING THE TEN YEARS
1883-1892.

  Ages,          0-1  1-5   5-15  15-25  25-65  65 and  Total
                                                above
  Males,         ...    4    14     44    733     36     831
  Females,         3    5   ...     68    129      4     209
                ---------------------------------------------
    Total,         3    9    14    112    862     40    1040
                ---------------------------------------------

§ 779. =Lead as a Poison.=--All the compounds of lead are said to be
poisonous; but this statement cannot be regarded as entirely correct,
for the sulphocyanide has been proved by experiment not to be so,[823]
and the sulphide is also probably inactive. In the treatment of cases of
lead-poisoning, the flowers of sulphur given internally appear to be
successful.[824]

[823] Eulenberg, _Gewerbe Hygiene_, p. 712.

[824] Mohr’s _Toxicologie_, p. 78.

Lead-poisoning, either in its obscure form (producing uric acid in the
blood, and, as a consequence, indigestion and other evils), or in the
acute form (as lead colic and various nervous affections), is most
frequent among those who are habitually exposed to the influence of the
metal in its different preparations, viz., workers of lead,
house-painters, artists, gilders, workers of arsenic, workers of gold,
calico-printers, colourists, type-founders, type-setters, shot-founders,
potters, faience makers, braziers, and many others.[825] In white-lead
factories so large a number of the employés suffer from poisoning that
it has excited more than once the attention of the Government.[826]

[825] The attention which the use of lead in the arts has always excited
is evident from the fact that one of the oldest works on Trade Hygiene
(by Stockhausen) is entitled, _De lithargyrii fumo noxio, morbifico
ejusque metallico frequentiori morbo vulgo dicto hüttenkatze_, Gaslar,
1556.

[826] A departmental committee, appointed to inquire into the white lead
and allied industries, in a report presented to the Home Secretary
stated:--

“8. (_a_) It is known that if lead (in any form), even in what may be
called infinitesimal quantities, gains entrance into the system for a
lengthened period, by such channels as the stomach, by swallowing lead
dust in the saliva, or through the medium of food and drink; by the
respiratory organs, as by the inhalation of dust; or through the skin;
there is developed a series of symptoms, the most frequent of which is
colic. Nearly all the individuals engaged in factories where lead or its
compounds are manipulated look pale, and it is this bloodlessness and
the presence of a blue line along the margin of the gums, close to the
teeth, that herald the other symptoms of plumbism. (_b_) A form of
paralysis known as wrist-drop or lead-palsy occasionally affects the
hands of the operatives. There is, in addition, a form of acute
lead-poisoning, most frequently met with in young girls from 18 to 24
years of age, which is suddenly developed and is extremely fatal. In it
the first complaint is headache, followed sooner or later by convulsions
and unconsciousness. Death often terminates such a case within three
days. In some cases of recovery from convulsions total blindness
remains.

“9. There has been considerable doubt as to the channels by which the
poison enters the system. The committee have taken much evidence on this
subject, and have arrived at the conclusion (_a_) that carbonate of lead
may be absorbed through the pores of the skin, and that the chance of
this is much increased during perspiration and where there is any
friction between the skin and the clothing; (_b_) that minute portions
of lead are carried by the hands, under and round the nails, &c., on to
the food, and so into the stomach; (_c_) but that the most usual manner
is by the inhalation of lead dust. Some of this becomes dissolved in the
alkaline secretions of the mouth, and is swallowed by the saliva, thus
finding its way to the stomach. Other particles of dust are carried to
the lungs, where they are rendered soluble and absorbed by the
blood.”--_Report of Chief Inspector of Factories for 1893._

Lead, again, has been found by the analyst in most of the ordinary
foods, such as flour, bread, beer, cider, wines, spirits, tea, vinegar,
sugar, confectionery, &c., as well as in numerous drugs, especially
those manufactured by the aid of sulphuric acid (the latter nearly
always containing lead), and those salts or chemical products which
(like citric and tartaric acids) are crystallised in leaden pans. Hence
it follows that in almost everything eaten or drunk the analyst, as a
matter of routine, tests for lead. The channels through which it may
enter into the system are, however, so perfectly familiar to practical
chemists, that a few _unusual_ instances of lead-poisoning only need be
quoted here.

A cabman suffered from lead colic, traced to his taking the first glass
of beer every morning at a certain public-house; the beer standing in
the pipes all night, as proved by analysis, was strongly impregnated
with lead.[827]

[827] _Chem. News._

The employment of red lead for repairing the joints of steam pipes has
before now caused poisonous symptoms from volatilisation of lead.[828]
The use of old painted wood in a baker’s oven, and subsequent adherence
of the oxide of lead to the outside of the loaves, has caused the
illness of sixty-six people.[829]

[828] Eulenberg, _Op. cit._, p. 708.

[829] _Annales d’Hygiène._

Seven persons became affected with lead-poisoning through horse-hair
coloured with lead.[830]

[830] Hitzig, _Studien über Bleivergiftung_.

The manufacture of _American overland cloth_ creates a white-lead dust,
which has caused serious symptoms among the workmen (_Dr. G. Johnson_).
The cleaning of pewter pots,[831] the handling of vulcanised
rubber,[832] the wrapping up of various foods in tinfoil,[833] and the
fingering of lead counters covered with brine by fishmongers, have all
caused accidents in men.

[831] _Med. Gazette_, xlviij. 1047.

[832] _Pharm. Journ._, 1870, p. 426.

[833] Taylor, _Prin. Med. Jurisprud._, i.

The lead in glass, though in the form of an insoluble silicate, is said
to have been dissolved by vinegar and other acid fluids to a dangerous
extent. This, however, is hardly well established.[834]

[834] See _Aerztl. Intelligenzbl. f. Baiern_, Jahrg., 1869; _Buchner’s
Rep. Pharm._, Bd. xix. p. 1; _Med. Centrbl._, Jahrg., 1869, p. 40.

§ 780. =Effects of Lead Compounds on Animals.=--Orfila and the older
school of toxicologists made a number of experiments on the action of
sugar of lead and other compounds, but they are of little value for
elucidating the physiological or toxic action of lead, because they
were, for the most part, made under unnatural conditions, the gullet
being ligatured to avoid expulsion of the salt by vomiting. Harnack, in
order to avoid the local and corrosive effects of sugar of lead, used an
organic compound, viz., plumbic triethyl acetate, which has no local
action. Frogs exhibited symptoms after subcutaneous doses of from 2 to
3 mgrms., rabbits after 40 mgrms.; there was increased peristaltic
action of the intestines, with spasmodic contraction rising to colic,
very often diarrhœa, and death followed through heart paralysis. Dogs
given the ethyl compound exhibited nervous symptoms like chorea.
Gusserno[835] has also made experiments on animals as to the effects of
lead, using lead phosphate, and giving from 1·2 grm. to a rabbit and a
dog daily. Rosenstein[836] and Heubel[837] used small doses of acetate,
the latter giving dogs daily from ·2 to ·5 grm. The results arrived at
by Gusserno were, mainly, that the animals became emaciated, shivered,
and had some paralysis of the hinder extremities; while Rosenstein
observed towards the end epileptiform convulsions, and Heubel alone saw,
in a few of his cases, colic. A considerable number of cattle have been
poisoned from time to time with lead, and one instance of this fell
under my own observation. A pasture had been manured with refuse from a
plumber’s yard, and pieces of paint were in this way strewn about the
field in every direction; a herd of fifteen young cattle were placed in
the field, and in two or three days they all, without exception, began
rapidly to lose condition, and to show peculiar symptoms--diarrhœa, loss
of appetite; in two, blindness, the retina presenting an appearance not
unlike that seen in Bright’s disease; in three, a sort of delirium. Four
died, and showed on _post-mortem_ examination granular conditions of the
kidneys, which was the most striking change observable. In the fatal
cases, paralysis of the hind extremities, coma, and convulsions preceded
death. In another case[838] seven cows and a bull died from eating lead
paint; the symptoms were loss of appetite, obstinate constipation,
suspension of rumination, dry muffle, quick breathing, and coma. In
other cases a marked symptom has been paralysis. Cattle[839] have also
several times been poisoned from eating grass which has been splashed by
the spray from bullets, as in pastures in the vicinity of rifle butts;
here we must allow that the intestinal juices have dissolved the metal,
and transformed it into compounds capable of being taken into the
system.

[835] Virchow’s _Archiv. f. path. Anat._, vol. xxi. p. 443.

[836] _Ib._, vol. xxxix. pp. 1 and 74.

[837] _Pathogenese u. Symptome der chronischen Bleivergiftung_, Berlin,
1871.

[838] See a paper by Professor Tuson, _Veterinarian_, vol. xxxviii.,
1861.

[839] _Ib._; also Taylor, _Op. cit._

§ 781. =Effects of Lead Compounds on Man--Acute Poisoning.=--Acute
poisoning by preparations of lead is not common, and, when it does
occur, is seldom fatal. With regard to the common acetate, it would seem
that a large single dose is less likely to destroy life than smaller
quantities given in divided doses for a considerable period. The
symptoms produced by a considerable dose of sugar of lead usually
commence within a few minutes; there is immediately a metallic taste,
with burning, and a sensation of great dryness in the mouth and throat;
vomiting, which occurs usually within fifteen minutes, is in very rare
cases delayed from one to two hours. The retching and vomiting are very
obstinate, and continue for a long time; the matters thrown up are
sometimes streaked with blood; there is pain in the abdomen of a colicky
character--a pain relieved by pressure. The bowels are, as a rule,
constipated, but occasionally relaxed. The stools at a later date are
black from the presence of lead sulphide. The urine, as a rule, is
diminished. The breath has a foul odour, and the tongue is coated; the
skin is dry, and the pulse small and frequent. The full development of
the toxic action is completed by the appearance of various nervous
phenomena--headache, shooting pains in the limbs, cramps in the legs,
and local numbness. All the symptoms enumerated are not present in each
case; the most constant are the vomiting and the colic. If the sufferer
is to die, death occurs about the second or third day. If the patient
recovers, convalescence may be much retarded, as shown in the case of
two girls,[840] who had each swallowed an ounce of lead acetate by
mistake, and who suffered even after the lapse of a year from pain and
tenderness in the stomach and sickness.

[840] Prov. _Med. Journal_, 1846.

There are “mass-poisonings” by acetate of lead on record, which afford
considerable insight into the varying action of this salt on different
individuals. A case (_e.g._) occurred at Stourbridge in 1840,[841] in
which no less than 500 people were poisoned by thirty pounds of lead
acetate being accidentally mixed with eighty sacks of flour at a
miller’s. The symptoms commenced after a few days; constriction of the
throat, cramping and twisting pains round the umbilicus, rigidity of the
abdominal muscles, dragging pains at the loins, cramps and paralysis of
the lower extremities. There was obstinate constipation; the urine was
scanty and of a deep red colour, and the secretions were generally
arrested; the pulse was slow and feeble; the countenance depressed,
often livid; and the gums showed the usual blue line. The temperature of
the skin was low. In only a few cases was there sickness, and in these
it soon ceased. It is curious that not one of the 500 cases proved
fatal, although some of the victims were extremely ill, and their
condition alarming. It was specially observed that, after apparent
convalescence, the symptoms, without any obvious cause, suddenly
returned, and this even in a more aggravated form. Remittance of this
kind is of medico-legal import; it might, for example, be wrongly
inferred that a fresh dose had been taken. In the 500 cases there were
no inflammatory symptoms; complete recovery took some time. On examining
the bread the poison was found so unequally distributed that no idea
could be formed as to the actual amount taken.

[841] Recorded by Mr. Bancks, _Lancet_, May 5, 1849, p. 478.

There is also recorded[842] an outbreak of lead-poisoning among 150 men
of the 7th Infantry at Tione, in the Southern Tyrol. One case proved
fatal, forty-five required treatment in hospital. The symptoms were
pallor, a blue line in the gums, metallic taste in the mouth, a peculiar
odour of the breath, a loaded tongue with a bluish tint, obstinate
constipation with loss of appetite whilst all complained, in addition,
of dragging of the limbs and of the muscles of the chest, and difficulty
of breathing. In the severer cases there were tetanic spasms, muscular
tremors, and anæsthesia of the fingers and toes. The pulse and
temperature were normal, save in a few cases in which there were fever
and sweats at night. _In none was there colic_, but the constipation was
obstinate. In two of the worst cases there was strangury. Acute cases
occur occasionally from poisoning by _the carbonate of lead_. Dr. Snow
recorded an instance (in 1844) of a child who had eaten a piece as big
as a marble, ground up with oil. For three days the child suffered from
pain in the abdomen and vomiting, and died ninety hours after taking the
poison. In another case, in which a young man took from 19 to 20 grms.
of lead carbonate in mistake for chalk as a remedy for heartburn, the
symptoms of vomiting, pain in the stomach, &c., commenced after a few
hours; but, under treatment with magnesic sulphate, he recovered.

[842] Königschmied, _Centralbl. Allg. für Gesundheitspflege_, 2 Jahrg.,
Heft 1.

=The chromate of lead= is still more poisonous (see Art. “Chromium”).

§ 782. =Chronic Poisoning by Lead.=--Chronic poisoning by lead--often
caused by strange and unsuspected channels, more frequently an incident,
nay, almost a necessity, of certain trades, and occasionally induced by
a cunning criminal for the purpose of simulating natural disease--is of
great toxicological and hygienic importance. In the white-lead trade it
is, as might be expected, most frequently witnessed; but also in all
occupations which involve the daily use of lead in almost any shape. The
chief signs of chronic poisoning are those of general ill-health; the
digestion is disturbed, the appetite lessened, the bowels obstinately
confined, the skin assumes a peculiar yellowish hue, and sometimes the
sufferer is jaundiced. The gums show a black line from two to three
lines in breadth, which microscopical examination and chemical tests
alike show to be composed of sulphide of lead; occasionally the teeth
turn black.[843] The pulse is slow, and all secretions are diminished.
Pregnant women have a tendency to abort. There are also special
symptoms, one of the most prominent of which is often lead colic.

[843] The black line soon develops; Masazza has seen it in a dog,
exposed to the influence of lead, in so short a period as three days
(_Riforma med._, 1889, Nos. 248-257, 1).

In 142 cases of lead-poisoning, treated between 1852 and 1862 at the
Jacob’s Hospital, Leipzig, forty-four patients (or about 31 per cent.)
suffered from colic. Arthralgia--that is, pains in the joints--is also
very common; it seldom occurs alone, but in combination with other
symptoms. Thus, in seventy-five cases of lead-arthralgia treated at
Jacob’s Hospital, in only seven were pain in the joints without other
complications, fifty-six being accompanied by colic, five by paralysis,
and seven by other affections of the nervous system. The total
percentage of cases of lead-poisoning, in which arthralgia occurs,
varies from 32 to 57 per cent.

Paralysis, in some form or other, Tanqueril[844] found in 5 to 8 per
cent. of the cases, and noticed that it occurred as early as the third
day after working in lead. The muscles affected are usually those of the
upper extremity, then the legs, and still more rarely the muscles of the
trunk. It is only exceptionally that the paralysis extends over an
entire limb; it more usually affects a muscular group, or even a single
muscle. Its common seat is the extensors of the hand and fingers; hence
the expression “dropped-wrist,” for the hands droop, and occasionally
the triceps and the deltoid are affected. The paralysis is usually
symmetrical on both sides. Although the extensors are affected most, the
flexors nearly always participate, and a careful investigation will show
that they are weakened. If the paralysis continues, there is a wasting
and degeneration of the muscle, but this is seen in paralysis from any
cause. The muscular affection may cause deformities in the hands,
shoulders, &c. Anæsthesia of portions of the skin is generally present
in a greater or less degree. A complete analgesia affecting the whole
body has been noticed to such an extent that there was absolute
insensibility to burns or punctures; but it is usually confined to the
right half of the body, and is especially intense in the right hand and
wrist.

[844] Tanqueril des Planches, _Traité des Maladies de Plomb_, Paris,
1839. Tanqueril’s monograph is a classical work full of information.

§ 783. The older writers recognised the toxic effect of lead on the
nervous system. Thus Dioscorides speaks of delirium produced by lead,
Aretaeus of epilepsy, and Paul of Ægina refers to it as a factor of
epilepsy and convulsions. But in 1830, Tanqueril first definitely
described the production of a mental disease, which he called “_lead
encephalopathy_.” This he divided into four forms--(1) a delirious form;
(2) a comatose; (3) a convulsive; and (4) a combined form, comprising
the delirious, convulsive, and comatose. Dr. Henry Rayner,[845] and a
few other English alienists, have directed their attention to this
question; and, according to Dr. Rayner’s researches, the number of male
patients admitted into Hanwell Asylum, engaged in trades such as
plumbing, painting, and the like, is larger in proportion to the number
admitted from other trades than it should be, compared with the
proportion of the various trades in the county of Middlesex, as
ascertained from the census. Putting aside coarse lead-poisoning, which
may occasionally produce acute mania, the insanity produced by prolonged
minute lead intoxications possesses some peculiar features. It develops
slowly, and in nearly all cases there are illusions of the senses, of
hearing, taste, or smell, and especially of sight. Thus, in one of Dr.
Rayner’s cases the patient saw round him “wind-bags blown out to look
like men,” apparitions which made remarks to him, and generally worried
him. Besides this form, there is also another which closely resembles
general paralysis, and, in the absence of the history, might be mistaken
for it.

[845] See an important paper, “Insanity from Lead-Poisoning,” by Drs. H.
Rayner, Robertson, Savage, and Atkins, _Journ. of Mental Science_, vol.
xxvi. p. 222; also a paper by Dr. Barton, _Allgemeine Zeitschrift für
Psychiatrie_, Bd. xxxvij. H. 4, p. 9.

§ 784. The degenerative influence on the organ of sight is shown in six
of Dr. Robertson’s patients, whose insanity was ascribed to lead--four
of the six were either totally or partially blind.

The amaurosis has been known to come on suddenly, and after a very brief
exposure to lead, _e.g._, a man, thirty-four years of age, after working
for three days in a white-lead factory, was seized with intense ciliary
neuralgia, had pains in his limbs and symptoms of lead-poisoning, and
the right eye became amaurotic.[846] This form of impairment or loss of
vision is different from the _Retinitis albuminurica_,[847] which may
also be produced as a secondary effect of the poison; the kidneys in
such cases being profoundly affected. The kind of diseased kidney
produced by lead is the granular contracted kidney.

[846] Samelsohn, _Monatsbl. f. Augenheilk._, vol. xi. p. 246, 1873. See
also a case of lead amaurosis, described by Mr. W. Holder, _Pharm.
Journ._, Oct. 14, 1876.

[847] Ran, _Arch. f. Ophthal._, vol. i. (2), p. 205, 1858, and Schmidt’s
_Jahrbuch_, Bd. cxxxiii. p. 116; Bd. cxliii. p. 67.

Eulenberg speaks of the sexual functions being weakened, leading to more
or less impotence.

Lewy,[848] in 1186 patients suffering from lead-poisoning, has found
caries or necrosis in twenty-two cases, or about 1·8 per cent.; fifteen
were carious affections of the upper jaw, four of the fore-arm, two of
the thigh, and one of the rib and sternum. Epilepsy and epileptiform
convulsions occur in a few cases; it is very possible that the epilepsy
may be a result of the uræmic poisoning induced by diseased kidneys.

[848] _Die Berufskrank. d. Bleiarbeiter_, Wien, 1873, S. 61.

Five cases of fatal poisoning occurred between 1884-6 among the employés
of a certain white-lead factory in the east of London. The cases
presented the following common characters. They were all adult women,
aged from 18 to 33, and they had worked at the factory for short
periods, from three to twelve months. They all exhibited mild symptoms
of plumbism, such as a blue line round the gums, and more or less
ill-defined indisposition; paralyses were absent. They were all in their
usual state of health within a few hours or days preceding death. Death
was unexpected, mostly sudden. In four cases it was preceded by
epileptic fits and coma; but in the fifth case no convulsions were
noted, although they may have occurred in the night.

The author[849] had an opportunity of investigating by chemical means
the distribution of lead in the fourth and fifth cases in the liver,
kidney, and brain.

[849] “The Distribution of Lead in the Brains of two Lead Factory
Operatives,” _Journ. of Mental Science_, Jan. 1888.

In the fourth case, from 402 grms. of liver 24·26 mgrms. of lead
sulphate were separated. The right kidney (weighing 81 grms.) yielded
5·42 mgrms. of lead sulphate. The brain was dehydrated with alcohol, and
then treated with ether, hot alcohol, and chloroform until an albuminoid
residue remained; lead was extracted from each of these portions, viz.,
the alcohol used for dehydration, the ethereal and chloroform extracts,
and the albuminoid residue, as follows:--

                                                  Mgrms. of Lead
                                                    Sulphate.
  Soluble in cold alcohol,                            1·11
  Soluble in ether and chloroform and hot alcohol,   25·47
  Albuminoid residue,                                 7·76
                                                     34·34

In the fifth case, the brain was examined more in detail, and the lead
present estimated in the following solutions and substances:--

1. Alcohol used for dehydration. This may be called “the watery
extract,” for, after the brain has remained in strong alcohol for some
weeks, the result is that the alcohol contains much water and substances
extracted with water.

2. White matter--(_a_) from cerebrum; (_b_) from cerebellum.

3. Kephalin--(_a_) from cerebrum; (_b_) from cerebellum.

4. Ether extract, kephalin-free--(_a_) from cerebrum; (_b_) from
cerebellum.

5. Substances soluble in cold alcohol--(_a_) from cerebrum; (_b_) from
cerebellum.

6. The albuminoid residue--(_a_) from cerebrum; (_b_) from cerebellum.

The general results were as follows:--

                                      Cerebrum,        Cerebellum,
                                     460·8 grms.       156·2 grms.
                                  Mgrms. of PbSO₄.   Mgrms. of PbSO₄.

  White matter freed from kephalin
  by ether,                             0·0               5·0
  Kephalin,                             1·5               6·0
  Ether extract, kephalin-free,         0·0               0·0
  Substances soluble in cold alcohol,   0·0               0·0
  Albuminoid residue,                  40·0               6·0
                                       ----              ----
                                       41·5              17·0

The aqueous extract contained 1·5 mgrm. of lead sulphate. In neither of
the cases did the pathologist ascertain the total weight of the brain,
but, presuming that the weight was an average weight, and that the lead
in the remainder of the brain was similarly distributed, the amount of
lead calculated as sulphate would amount to 117 mgrms. From these
results it appears to the author probable that lead forms a substitution
compound with some of the organic brain matters. This view would explain
the absence of changes apparent to the eye found in so many of the fatal
cases of lead encephalopathy.

§ 785. Lead taken for a long time causes the blood to be impregnated
with uric acid. In 136 cases of undoubted gout, 18 per cent. of the
patients were found to follow lead occupations, and presented signs of
lead impregnation.[850]

[850] “On Lead Impregnation in Relation to Gout,” by Dyce Duckworth,
M.D., _St. Barth. Hosp. Reports_, vol. xvii., 1881.

Ellenberger and Hofmeister[851] found that, with chronic poisoning of
sheep with lead, excretion of hippuric acid ceased, and the output of
uric acid was diminished. This may be explained by the formation of
glycocol being arrested.

[851] _Arch. f. wiss. u. pract. Thierheilk._, Bd. x., 1884.

§ 786. There are some facts on record which would seem to countenance
the belief that disease, primarily caused by an inorganic body like
lead, may be transmitted. M. Paul (_e.g._) has related the history of
the offspring (thirty-two in number) of seven men, who were suffering
from lead-poisoning--eleven were prematurely born and one still-born; of
the remaining twenty, eight died in the first year, four in the second,
and five in the third year, so that of the whole thirty-two, only three
survived three years.

The influence of the poison on pregnant women is, indeed, very
deleterious. M. Paul noted that in four women who were habitually
exposed to the influence of lead, and had fifteen pregnancies, ten
terminated by abortion, two by premature confinement, three went the
full term, but one of the three children was born dead, a second only
lived twenty-four hours; so that, out of the whole fifteen, one only
lived fully. In another observation of M. Paul’s, five women had two
natural confinements before being exposed to lead. After exposure, the
history of the thirty-six pregnancies of these women is as
follows:--there were twenty-six abortions (from two to five months), one
premature confinement, two infants born dead, and five born alive, four
of whom died in the first year.

Chronic poisoning may be nearly always accounted for by the inhaling of
lead dust, or by the actual swallowing of some form of lead; but, if we
are to accept the fact narrated by the late Dr. Taylor, viz., that he
himself had an attack of lead colic from sitting in a room for a few
hours daily, in which there was a large canvas covered with white lead
and drying oil, and one or two other similar cases,[852] we must allow
that there is some subtle volatile organic compound of lead evolved. In
the present state of our knowledge, it seems more reasonable to account
for such cases by the suggestion that lead has entered the system by an
unsuspected channel.

[852] The gate-keeper of a graveyard at Bordeaux continually used the
remnants of crosses, covered with lead paint, to replenish his fire; the
chimney smoked; gradually paralysis of the extensors of the right wrist
developed itself, and he suffered from colic and other signs of
lead-poisoning.--Marmisse, _Gaz. des Hôpit._, No. 25, 1866.

In 1882, a very interesting case occurred at Keighley, in which a
mechanic, aged 42, died from the supposed effects of lead-poisoning,
induced from drinking the town water, which was proved by Mr. Allen to
contain about ⅗ of a grain of lead per gallon. For six months he had
been out of health, and a week before his death he suffered from colic,
vomiting, constipation, and a blue line round the gums, and occasional
epileptiform seizures. After death the kidneys were found granular, and
the heart somewhat enlarged. The viscera were submitted to Mr. Allen for
analysis; no lead was found in the heart or brain, a slight,
non-estimable trace in the kidneys, and about a grain was separated from
the liver and spleen. Dr. Tidy, who was called in as an expert, gave a
very guarded opinion, rather against the theory of direct
lead-poisoning; and the verdict returned by the jury was to the effect
that the deceased died from granular kidney, accelerated by
lead-poisoning. Murder by the administration of doses of sugar of lead
is rare, but such a case has occurred.

At the Central Criminal Court, in December 1882, Louisa Jane Taylor was
indicted for poisoning Mary Ann Tregillis at Plumstead, and convicted.
From the evidence it appeared that the prisoner, who was thirty-six
years of age, came to reside with Mr. and Mrs. Tregillis, an aged couple
of eighty-five and eighty-one years respectively. The prisoner was
proved to have purchased at different times an ounce and half an ounce
of sugar of lead, and to have added a white powder to the medicine of
Mrs. Tregillis. The illness of the latter extended from about August 23
to October 23--a period of two months. It is difficult to say when the
first dose could have been given, but it was probably some time between
August 13 and 23, while the administration, without doubt, ceased on or
before October 6, for on that date different nursing arrangements were
made. The symptoms observed were nausea, vomiting, pain in the pit of
the stomach, burning in the throat, very dark teeth, a blue line round
the gums, and slight jaundice. There was great muscular weakness, with
trembling of the hands, and a week before death there was paralysis of
the right side.

Lead was discovered in most of the viscera, which were in great part
normal, but the kidneys were wasted, and the mucous membrane blackened.
The actual quantity of lead recovered by analysis was small, viz., 16·2
mgrms. (¼ grain) from the liver; from 8 ounces of brain, 3·2 mgrms.
(1/20 grain); from half of the stomach, 16·2 mgrms. (¼ grain); and from
the spleen, the kidneys, and the lungs, small quantities. It is,
therefore, probable that, if the whole body had been operated upon, the
yield would have been more than ·15 grm. (a little over 2 grains); but
then, it must be remembered that the deceased lived, at least, seventeen
days after the last dose.

§ 787. =Post-mortem Appearances.=--In acute cases of poisoning by the
acetate, there may sometimes be found a slight inflammatory appearance
of the mucous membrane of the stomach and intestines. Orfila considered
that streaks of white points adherent to the mucous membrane were
pathognomonic; but there have been several cases in which only negative
or doubtful signs of inflammatory or other action have presented
themselves. A general contraction of the intestines has often been
noticed, and is of considerable significance when present; so also is a
grey-black mucous membrane caused by deposited lead sulphide. Loen found
in dogs and guinea-pigs, poisoned by lead, local inflammation areas in
the lungs, liver, and kidneys; but in no case fatty degeneration of the
epithelial cells of the liver, kidneys, or intestines. As a rule, no
unabsorbed poison will be found in the stomach; the case related by
Christison, in which a person died on the third day after taking at a
single dose some large quantity of acetate of lead; and at the autopsy a
fluid was obtained from the stomach, which had a sweet metallic taste,
on evaporation smelt of acetic acid, and from which metallic lead was
obtained--is so very extraordinary in every respect, that its entire
accuracy is to be questioned. In death from chronic lead-poisoning,
there is but little that can be called diagnostic; a granular condition
of the kidneys, and all the pathological changes dependent on such a
condition, are most frequently seen. If the patient has suffered from
colic, a constriction of portions of the intestine has been noticed;
also, in cases in which there has been long-standing paralysis of groups
of muscles, these muscles are wasted, and possibly degenerated. In
instances, again, in which lead has induced gout, the pathological
changes dependent upon gout will be prominent. The blue line around the
gums, and sometimes a coloration by sulphide of lead of portions of the
intestines, may help a proper interpretation of the appearances seen
after death; but all who have given any attention to the subject will
agree that, simply from pathological evidence, it is impossible to
diagnose chronic lead-poisoning.

§ 788. =Physiological Action of Lead.=--The action of lead is still
obscure, but it is considered to have an effect mainly on the nervous
centres. The paralysed muscles respond to the direct current, but not to
the induced, leading to the suspicion that the intramuscular
terminations of the nerves are paralysed, but that the muscular
substance itself is unattacked. On the other hand, the restriction of
the action to groups of muscles supports the theory of central action.

The lead colic is due to a true spasmodic constriction of the bowel, the
exciting cause of which lies in the walls of the bowel itself; the
relief given by pressure is explained by the pressure causing an anæmia
of the intestinal walls, and thus lessening their sensibility. The
slowing of the pulse produced by small doses is explained as due to a
stimulation of the inhibitory nerves; and, lastly, many nervous
phenomena, such as epilepsy, &c., are in part due to imperfect
elimination of the urinary excreta, causing similar conditions to those
observed in uræmia.

§ 789. =Elimination of Lead.=--When a large dose of acetate or carbonate
is taken, part is transformed into more or less insoluble
compounds--some organic, others inorganic; so that a great portion is
not absorbed into the body at all, but passes into the intestines,
where, meeting with hydric sulphide, part is changed into sulphide,
colouring the alvine evacuations black. Some of the lead which is
absorbed is excreted by the kidneys, but the search often yields only
traces. Thudichum[853] states that in fourteen cases of lead-poisoning,
in two only was obtained a weighable quantity from a day’s urine; in the
remaining twelve lead was detected, but only by the brownish colour
produced in an acid solution of the ash by hydric sulphide.

[853] _Pathology of the Urine_, p. 550.

The elimination of lead by the kidneys is favoured by certain medicines,
such, for example, as potassic iodide. Annuschat found in dogs poisoned
by lead from 3·8 to 4·1 mgrms. in 100 c.c. of urine; but, after doses of
potassic iodide, the content of lead rose to 6·9 and even to 14 mgrms.
Lead appears to be eliminated by the skin, being taken up by the
epithelial cells, and minute, insoluble particles coming away with these
cells. If a person who has taken small doses of lead for a time be
placed in a sulphur water-bath, or have his skin moistened with a 5 per
cent. solution of sodium sulphide, the upper layer of the epidermis is
coloured dark; but the perspiration excited by pilocarpin or other
agency contains no lead.

§ 790. =Fatal Dose=--(_a._) =Sugar of Lead.=--It may almost be said that
it is impossible to destroy human life with any single dose likely to be
taken or administered. In three cases an ounce (28·3 grms.) has been
taken without fatal result. Although it must be allowed that repeated
moderate doses, extending over some time, are more dangerous to health
and life than a single large dose, yet there seems to be in some
individuals a great tolerance of lead. Christison has given ·18 grm. in
divided doses daily for a long time without any bad effect, save the
production of a slight colic. Swieten has also given daily 3·9 grms. (60
grains) in ten days without observing toxic effects. That, in other
cases, less than a grain per gallon of some lead compound dissolved in
drinking-water, or in some way introduced into the economy, causes
serious illness, is most inexplicable.

(_b._) =The Basic Acetate= in solution is more poisonous apparently than
the acetate--60 c.c. (1½ drms.) have caused serious symptoms.

(_c._) =The Carbonate of Lead.=--Doses of anything like 28 grms. (an
ounce) would probably be very dangerous to an adult; the only case of
death on record is that of a child who took some unknown quantity,
probably, from the description of the size of the lump, about 10 grms.
(2½ drms.).

§ 791. =Antidotes and Treatment.=--Soluble sulphates (especially
magnesic sulphate) have been given largely in both acute and chronic
cases; in the acute, it stands to reason that it is well to ensure the
presence of plenty of sulphates in the stomach and intestines, in order
to form the sparingly soluble lead sulphate, should any residue remain;
but to expect this double decomposition to go on in the blood and
tissues is not based upon sound observation. The chronic lead-poisoning
is best treated by removal from the source of mischief, the
administration of large quantities of distilled water, and medicinal
doses of potassic iodide.

§ 792. =Localisation of Lead.=--In a dog, which was killed by chronic
lead-poisoning, Heubel found in the bones 0·18 to 0·27 per 1000 of lead;
in the kidneys, 0·17 to 0·20; liver, 0·10 to 0·33; spinal cord, 0·06 to
0·11; brain, 0·04 to 0·05; muscles, 0·02 to 0·04; in the intestines
traces, 0·01 to 0·02; in the spleen, the blood, and the bile, he also
only found traces. Ellenberger and Hofmeister found in the kidneys of
the sheep, 0·44 to 0·47; liver, 0·36 to 0·65; pancreas, 0·54; salivary
glands, 0·42; bile, 0·11 to 0·40; bones, 0·32; fæces, 0·22; spleen,
0·14; central nervous system, 0·07 to 0·18; blood, 0·05 to 0·12; flesh,
0·05 to 0·08; urine, 0·06 to 0·08; and in the unstriped muscles and the
lungs, 0·03 per 1000 of lead.

Without going so far as to say that lead is a natural constituent of the
body, it is certain that it may be frequently met with in persons who
have been apparently perfectly healthy, and quite free from all symptoms
of lead-poisoning. Legrip found in the liver and spleen of a healthy
person, 5·4 mgrms. of lead oxide in every kilogram; Oidtmann, in the
liver of a man fifty-six years of age, 1 mgrm. of lead oxide per
kilogram, and in the spleen 3 mgrms. per kilogram. Hence, the analyst,
in searching for poison, must be very careful in his conclusions. Grave
and serious errors may also arise from complications; suppose, _e.g._,
that a deceased person previous to death had partaken of game, and
inadvertently swallowed a shot--if the analyst had not carefully
searched the contents of the stomach for _solid_ bodies, but merely
treated them at once with acid solvents, he would naturally get very
decided lead reactions, and would possibly conclude, and give evidence
to the effect, that a poisonous soluble salt of lead had been
administered shortly before death.

§ 793. =Detection and Estimation of Lead.=--A great number of fluids
(such as beer, wines, vinegar, water, &c.), if they contain anything
like the amount of one-tenth of a milligramme in 100 c.c., will give a
very marked dark colour with SH₂. It is, however, usually safest in the
first place to concentrate the liquid, to add an acid, and deposit the
lead on platinum, in the way to be shortly described. Nearly all the
lead from oils and fatty matter may be dissolved out by shaking up the
fat with dilute nitric acid; if necessary, the fat should previously be
melted.

If (in the usual course of routine research) a hydrochloric acid
solution is obtained from the treatment or destruction of organic
substances by that agent, and lead sulphide (mixed possibly with other
sulphides) is filtered off, any arsenical sulphide may first be
extracted from the filter by ammonia, and any antimonious sulphide by
sodic sulphide; then the sulphide may be extracted by warm hydrochloric
acid, which will leave undissolved such sulphides as those of copper and
mercury. On diluting the liquid, and filtration at a boiling
temperature, crystals of lead chloride will be deposited on cooling.

If, however, organic matters are _specially_ searched for lead,
hydrochloric acid is not the best solvent, but nitric should always be
preferred; and, if there is reason to think that the lead exists in the
form of sulphate, then the proper solvent is either the acetate or the
tartrate of ammonia; but, in either case, the solution should contain an
excess of ammonia. It must, however, be remembered that organic matters
retain lead with great tenacity, and that in all cases where it can with
any convenience be effected, the substances should be not only
carbonised, but burnt to an ash; for Boucher has shown[854] that carbon
retains lead, and that the lead in carbon resists to a considerable
extent the action of solvents.

[854] _Ann. d’Hygiène_, t. xli.

In the case of sulphate of lead, which may be always produced in an ash
from organic substances by previous treatment with sufficient sulphuric
acid, a very excellent method of identification is to convert it into
sugar of lead. To do this, it is merely necessary to boil it with
carbonate of ammonia, which changes it into carbonate of lead; treatment
with acetic acid will now give the acetate; the solution may (if the
lead is in very small quantity) be concentrated in a watch-glass, a
drop evaporated to dryness on a circle of thin microscopic glass, and
the crystals examined by the microscope; the same film next exposed to
the fumes of SH₂, which will blacken it; and lastly, the solution (which
should be sweet) tasted. A crystalline substance, possessing a sweet
taste, and blackening when exposed to SH₂, can, under the circumstances,
be no other substance than acetate of lead.

If the analyst does not care for this method, there is room for choice.
Lead in solution can be converted into sulphide; in this case it is,
however, absolutely necessary that there should be no great excess of
acid, since as little as 2·5 per cent. of free hydrochloric acid will
prevent all the lead going down. On obtaining the sulphide, the latter,
as already described, can be converted into chloride by hydrochloric
acid, and the crystalline chloride is extremely characteristic.

From the solution of the chloride the metal may be obtained in a solid
state by inserting a piece of zinc in the solution contained in a
crucible; the lead will be deposited gradually, and can be then
collected, washed, and finally fused into a little globule on charcoal.
A lead bead flattens easily when hit with a hammer, and makes a mark on
paper. Solutions of the chloride also give a heavy precipitate of lead
sulphate, when treated with a solution of sodic sulphate.

When lead is in very minute quantity, an electrolytic method is
generally preferable; the lead is precipitated on platinum by using
exactly the same apparatus as in Bloxam’s test, described at p. 566; the
liquid to be tested being placed in the inner cell, the lead film may
now be identified, dissolved in nitric acid, and estimated by a
colorimetric process. For the estimation of the minute fractions of a
grain by a colour method, it is merely necessary to have a very dilute
solution of acetate of lead, to add a known volume of SH₂ water to the
liquid to be tested in a Nessler cylinder, noting the colour, and add to
another a known quantity of the standard lead solution and the same
quantity of SH₂ as was added to the first.

The process has an advantage which is great, viz., that it either
detects copper, or proves its absence at the same time; and there are
few cases in which the analyst does not look for copper as well as for
lead. Lead, if in sufficient quantity, may be most conveniently
estimated as oxide, sulphate, or chloride; the chief properties of these
substances have been already described.

§ 794. =The Detection of Lead in Tartaric Acid, in Lemonade, and Aërated
Waters.=--To detect lead in tartaric acid a convenient method is to burn
it to an ash, digest in a little strong sulphuric acid, and then add
either sodic chloride or a drop of HCl; lead, if present, is
precipitated as chloride, giving a pearly opalescence. Lemonades often
contain minute quantities of iron and copper as well as lead. Neither
copper nor iron are precipitated by ammonium sulphide in presence of
potassic cyanide. On the other hand, the sulphide of lead is not soluble
in the alkaline cyanides. Hence a liquid which, on the addition of
potassium cyanide and then ammonium sulphide, becomes dark coloured, or
from which a precipitate separates, contains lead.[855]

[855] F. L. Teed, _Analyst_, xvii. 142-143.


2. COPPER.

§ 795. =Copper=, Cu = 63·5; specific gravity, from 8·921 to 8·952;
fusing-point, 1091° (1996° F.). Copper in analysis occurs either as a
film or coating on such metals as platinum, iron, &c., or in a state of
fine division; or, finally, as a bead. In thin films, copper has a
yellowish or a yellowish-red colour; it dissolves readily in nitric,
slowly in hydrochloric acid. If air be excluded, hydrochloric acid fails
to dissolve copper, and the same remark applies to ammonia; but, if
there be free access of air, ammonia also acts as a slow solvent.
Metallic copper in a fine state of division can be fused at a white heat
to a bright bluish-green globule, which, on cooling, is covered with
black oxide.

§ 796. =Cupric Oxide= (CuO = 79·5; specific gravity, 6·5, composition in
100 parts, Cu 79·85, O 20·15) is a brownish-black powder, which remains
in the absence of reducing gases unaltered at a red heat. It is nearly
insoluble in water, but soluble in ClH, NO₃H, &c.; it is hygroscopic,
and, as every one who has made a combustion knows, is readily reduced by
ignition with charcoal in the presence of reducing gases.

§ 797. =Cupric Sulphide=, CuS = 95·5, produced in the wet way, is a
brownish powder so insoluble in water that, according to Fresenius,
950,000 parts of water are required to dissolve one part. It is not
quite insoluble in ClH, and dissolves readily in nitric acid with
separation of sulphur. By ignition in a stream of H it may be converted
into the subsulphide of copper. It must always be washed by SH₂ water.

§ 798. =Solubility of Copper in Water and Various Fluids.=--The
solubility of copper in water and saline solutions has been very
carefully studied by Carnelley.[856] Distilled water exerts some solvent
action, the amount varying, as might be expected, according to the time
of exposure, the amount of surface exposed, the quantity of water acting
upon the copper, &c. It would appear that, under favourable
circumstances, 100 c.c. of distilled water may dissolve ·3 mgrm. of
copper (·2 grain per gallon).

[856] _Journ. Chem. Soc._, 1876, vol. ii. p. 4.

With regard to salts, those of ammonium exert a solvent action on
copper more decided than that of any others known. With the others,
however, the nature of the base exerts little influence, the action of
the salt depending chiefly on the nature of its acid radical. Thus,
beginning with the least effective, the following is the order of
dissolving strength:--Nitrates, sulphates, carbonates, and chlorides. It
will then at once be evident that a water, contaminated by sewage, and
therefore containing plenty of ammonia and chlorides, might exert a very
considerable solvent action on copper.

Almost all the oils and fats, as well as syrups, dissolve small
quantities of copper; hence its frequent presence in articles of food
cooked or prepared in copper vessels. In the very elaborate and careful
experiments of Mr. W. Thompson,[857] the only oils which took up no
copper, when digested on copper foil, were English neats’-foot oil,
tallow oil, one sample of olive oil, palm-nut oil, common tallow oil,
and white oil, which was protected from the air by a thick coating of
oxidised oil on its surface.

[857] “Action of Fatty Oils on Metallic Copper,” _Chem. News_, vol.
xxxiv. pp. 176, 200, 313.

The formation of copper compounds with the fatty acids takes place so
readily that Jeannel[858] has proposed the green colouring of fats by
copper as a test for the presence of copper; and Bottger[859] recommends
a copper holding brandy to be shaken up with olive oil to free it from
copper.

[858] _L’Union pharmac._, xvii. 81.

[859] _Arch. de Pharm._, 1853, cxxvi. 67.

Lehmann has made some useful researches on the amount of copper taken up
by fats under different conditions. 100 c.c. of strongly rancid fat
dissolved in fourteen days 8·7 mgrms. of copper; but when heated to 160°
for one hour, and then allowed to stand, a similar amount was found.
Some rancid butter was rubbed into a brass bowl of 90 c.c. capacity, and
then allowed to stand for twenty-four hours; the butter became of a
blue-green colour. Into this dish, thus partially attacked by fatty
acids, 50 c.c. of rancid butter was poured in a melted condition, and
allowed to stand for twenty-four hours. The amount taken up was found to
be equal to 10 mgrms. of copper for every 100 c.c. of fluid butter.

Hilger found a fatty soup, which had stood twelve hours in a clean
copper vessel, to contain 0·163 per cent. copper. According to Tschirch,
the easiest fatty salt to form is the oleate, hydrated copper oxide
dissolving in oleic acid with great ease, and even copper oxide
dissolving to some extent; the palmitate and the stearate are not so
readily produced; hence the amount of copper dissolved is greater in the
case of olive oil and butter (both rich in oleic acids) than in the case
of the firmer animal fats. Acid solutions, such as clarets, acetic acid,
vinegars, and so forth, as might be expected, dissolve more or less
copper. The amount likely to be dissolved in practice has been
investigated by Lehmann. He steeped 600 square metres of copper
sheeting or brass sheeting in vessels holding 2 litres of acid claret;
the sheets were in some of the experiments wholly immersed, in others
partly so. More copper was dissolved by the wine when the copper was
partly immersed than when it was wholly immersed; and more copper was
dissolved from brass sheeting than from pure copper sheeting. With a
sheet of copper, partly immersed, claret may contain as much as 56
mgrms. per litre. Lehmann also investigated the amount of copper, as
acetate, which could be dissolved in wine before the taste betrayed its
presence: with 50 mgrms. per litre no copper taste; with 100 mgrms.
there was a weak after taste; with 150 mgrms. it was scarcely drinkable,
and there was a strong after taste; with 200 mgrms. per litre it was
quite undrinkable, and the colour was changed to bluish-green. Vinegar,
acting under the most favourable circumstances on sheet brass or copper,
dissolved, in seven days, 195 mgrms. of copper per litre from the copper
sheet, 195 from the brass sheet.

Lehmann discusses the amount of copper which may be taken at a meal
under the circumstance that everything eaten or drank has been
artificially coppered, but none “coppered” to the extent by which the
presence of the metal could be betrayed by the taste; and the following
is, he thinks, possible:--

  300 c.c. of soup boiled in a copper vessel,          20 mgrms. Cu.
  1 litre of wine which has been standing in a
  copper vessel,                                       50      „
  50 c.c. vinegar which has been kept in a copper
  vessel,                                              10      „
  50 grms. of fat which has been used for frying in a
  copper vessel,                                        5      „
  200 grms. of strongly coppered peas,                 50      „
  500 grms. of strongly coppered bread,                60      „

The total only amounts to 195 mgrms. of copper, which only slightly
exceeds a high medicinal dose. The metal is tasted more easily in
liquids, such as wine, than in bread; bread may be coppered so that at a
meal a person might eat 200 mgrms. of a copper compound without tasting
it.

It is pretty well accepted that cooking in clean bright copper vessels
will not contaminate any ordinary food sufficiently to be injurious to
health.

§ 799. =Copper in the Vegetable and Animal Kingdom and in
Foods.=--Copper is widely distributed in the vegetable kingdom, and is a
constant constituent of the chief foods we consume; the following
quantities, for example, have been separated from the chief cereals:--

  Wheat,        5·2 to 10·8 mgrms. per kilo.
  Rye,          5   mgrms.              „
  Oats,         8·5  „                  „
  Barley,      11·8  „                  „
  Rice,         1·6  „                  „
  Bread,        1·5 to 4·4 mgrms.       „

It has also been found in vermicelli (2-10 mgrms. per kilo.), groats
(1·6-3 mgrms. per kilo.), potatoes (1·8 mgrm. per kilo.), beans (2-11
mgrms. per kilo.). In similar small quantities it has also been found in
carrots, chicory, spinach, hazel-nuts, blackberries, peaches, pears,
figs, plums, tamarinds, black pepper, and many other fruits and spices.
The most common food which has a high copper content is cocoa, which
contains from 12 mgrms. to 29 mgrms. per kilo., the highest amount of
copper being in the outer husk; copper has also been found in many
supplies of drinking water, in aërated waters, in brandies, wines, and
many drugs.

It has been calculated that the ordinary daily food of an average man
contains the following:--

  Copper.
  900 grms. bread,                   0·45 mgrm.
  260 grms. meat,                    0·25  „
  200 grms. fruit and vegetables,    0·25  „
                                     ----
                                     0·95 mgrm.

That is to say, that, neglecting altogether foods artificially
contaminated with copper, each of us eats daily about 1 mgrm. of copper
(0·015 grain).

In the animal kingdom it is a constant and natural constituent of the
blood of the cephalopods, crustacea, and gasteropods, and is nearly
always present in the liver and kidneys of domestic animals, as well as
in men. Dr. Dupré[860] found ·035 to ·029 grain (1·8 to 2 mgrms.) in
human livers, or about 1 part in 500,000. Bergeron and L. L’Hôte’s
researches on fourteen bodies, specially examined for copper, fully
substantiate those of Dr. Dupré; in twelve the copper was found in
quantities of from ·7 to 1·5 mgrm.; in the remaining two the amount of
copper was very minute, and was not estimated.[861] Copper is also found
normally in the kidneys, and Dupré [862] detected in human kidneys about
1 in 100,000 parts; it is also found in the bile, and in minute traces
in the blood.[863]

[860] _Analyst_, No. 13, 1877.

[861] _Compt. Rendus_, vol. lxxx. p. 268.

[862] _Op. cit._

[863] Hoppe-Seyler, _Handbuch der physiologisch. Analyse_, p. 415.

In the kidneys and livers of the ruminants copper may always be found, a
sheep’s liver containing about 1 part in 20,000.[864] Church found
copper in the feathers of the wings of the turaco; melopsitt in the
feathers of a parroquet (_Melopsittacus undulatus_).[865] In these cases
the copper enters into the composition of the colouring matter to which
the name of “turacin” has been given. Turacin contains 7 per cent. of
copper, and gives to analysis numbers which agree with the formula of
C₈₂H₈₁Cu₂N₉O₃₂.

[864] Dupré, _op. cit._

[865] _Chem. News_, xxviij. 212.

Copper has been discovered in aërated waters, its presence being due to
the use of copper cylinders, the tin lining of which had been rendered
defective by corrosion.[866]

[866] “On the Presence of Lead and Copper in Aërated Waters,” by Dr.
James Milne, _Chem. News_, xxxi. p. 77.

Accidents may also occur from the use of copper boilers. Mr. W. Thompson
found in one case[867] no less than 3·575 grains in a gallon (51 mgrms.
per litre) in water drawn from a kitchen boiler.

[867] _Chem. News_, xxxi. No. 801.

At Roubaix, in France, sulphide of copper had been deposited on the
roof, as a consequence of the use of copper flues; the sulphide was
changed into sulphate by the action of the air, and washed by the rain
into the water-tank.[868]

[868] Author’s _Dictionary of Hygiène_, p. 167.

That preserved vegetables are made of a bright and attractive green
colour by impregnation with copper, from the deliberate use of copper
vessels for this purpose, is a fact long known. Green peas especially
have been coloured in this way, and a number of convictions for this
offence have taken place in England.

§ 800. =The “Coppering” of Vegetables.=--The fact that green vegetables,
such as peas, beans, cucumbers, and so forth, preserve their green
colour, if boiled in copper vessels, has long been known. In this
“coppering” the French have been more active than the English traders;
the French operate in two different ways. One method is, to dip from 60
to 70 litres of the green vegetables in 100 litres of 0·3 to 0·7 per
cent. of copper sulphate, to leave them there for from five to fifteen
minutes, then to remove them, wash and sterilise in an autoclave. A
second method is to put the vegetables into a copper vessel, the wall of
which is connected with the negative pole of an electric current, the
positive pole dips in a solution of salt in the same vessel, the current
is allowed to pass for three minutes, and the vegetables are afterwards
sterilised. Fruits are simply allowed to stand with water in copper
vessels, the natural acidity of the juice dissolving sufficient copper.

The amount of copper taken up in this way is appreciable, but yet not so
much as might be expected; the prosecutions for selling “coppered” peas
in England have been based upon quantities varying from 1 to 3 grains
per lb.; the highest published amount of copper found in peas
artificially coloured is 0·27 per kilo., or 18·9 grains per lb.

The reason why vegetables preserve their green colour longer when
treated with a copper salt has been proved by Tschirch[869] to be owing
to the formation of a phyllocyanate of copper.

[869] _Das Kupfer_, Stuttgart, 1893.

Phyllocyanic acid is a derivative of chlorophyll, and allied to it in
composition; the formula of C₂₄H₂₈N₂O₄ has been ascribed to it. Under
the action of acids generally, mineral or organic, chlorophyll splits up
into this acid and other compounds. Copper phyllocyanate,
(C₂₄H₂₇N₂O₄)₂Cu, contains 8·55 per cent. of copper; it forms black
lamellæ, dissolving easily in strong alcohol and chloroform, but
insoluble in water; it is a little soluble in ether, insoluble in
petroleum ether, and dissolved neither by dilute acetic acid, nor by
dilute nor concentrated hydrochloric acid. The compound dissolves in
caustic alkali on warming. In alcohol it forms a beautiful
non-fluorescent solution. A solution of 1 : 100,000 is still coloured
strongly green.

This solution, in a stratum of 25 mm. thick, gives four absorption bands
when submitted to spectroscopic observation, and Tschirch has worked out
a process of estimation of the amount of copper phyllocyanate based upon
the disappearance of these bands on dilution.

Green substances, so carefully treated that they only contain
phyllocyanate of copper, would yield but small quantities of copper, and
probably they would not be injurious to health; but the coppering is
usually more extensive, and copper leguminate and other compounds are
formed; for the vegetables, when exhausted by alcohol, give a residue
which, successively exhausted by water, by soda-lye, and lastly by
hydrochloric acid, parts with copper into the three solvents mentioned.

It might be argued that, from the insoluble character of the
phyllocyanate of copper, and especially seeing that it does not dissolve
in strong hydrochloric acid, that it would be perfectly innocuous; but
Tschirch has proved that, whether the tartrate of copper (dissolving
easily in water), or copper oxide (not dissolving at all in water, but
soluble in hydrochloric acid), or phyllocyanate of copper (insoluble
both in water and in hydrochloric acid) be used, the physiological
effect is the same.

Copper may be found in spirits, owing to the use of copper condensers, a
remark which applies also to the essential oils, such as _oleum
cajepute_, _menthæ_, &c.[870] In France, it has been added fraudulently
to absinthe, to improve its colour.[871] Green sweetmeats, green toys,
green papers, have all been found to contain definite compounds of
copper to a dangerous extent.

[870] According to Eulenberg (_Gewerbe Hygiene_, p. 716), _Oleum
cajepute_, _Menth. pip._, _Melissæ_, _Tanaceti_, &c., are almost always
contaminated with copper.

[871] Tardieu, _Étude Méd. Lég. sur l’Empoisonnement_.

§ 801. =Preparations of Copper used in Medicine and the Arts.=

(1) =Medicinal Preparations=:--

=Sulphate of Copper=, =Cupri Sulphas=, CuSO₄5H₂O.--This well-known salt
is soluble in water at ordinary temperature, 3 parts of water dissolving
1 of the sulphate; but boiling water dissolves double its weight; 1 part
of copper sulphate dissolves in 2½ of glycerin; it reddens litmus, and
is slightly efflorescent; its solution responds to all the usual tests
for copper and sulphuric acid. A watery solution of the salt to which
twice its volume of a solution of chlorine has been added, gives, when
treated with ammonia in excess, a clear sapphire-blue solution, leaving
nothing undissolved, and thus showing the absence of iron. Besides
iron, sulphate of copper has been found to contain zincic sulphate.

=Nitrate of Copper=, Cu(NO₃)₂3H₂O, is officinal; it is very soluble.

=Cuprum Aluminatum.=--A preparation, called cuprum aluminatum (_Pierre
divine_), is in use in France and Germany, chiefly as an external wash.
It is composed of 16 parts cupric sulphate, 16 potassic nitrate, 16
alum, fused in a crucible, a little camphor being afterwards added.

Regular and irregular medical practitioners, veterinary surgeons,
farriers, and grooms, all use sulphate of copper (bluestone) as an
application to wounds. Copper as an _internal_ remedy is not in favour
either with quacks or vendors of patent medicines. The writer has not
yet found any patent pill or liquid containing it.

(2) =Copper in the Arts.=--Copper is used very extensively in the arts;
it enters into the composition of a number of alloys, is one of the
chief constituents of the common bronzing powders, is contained in many
of the lilac and purple fires of the pyrotechnist, and in a great
variety of pigments. The last-mentioned, being of special importance,
will be briefly described:--

=Pigments=:--

=Schweinfurt and Scheele’s Green=[872] are respectively the
aceto-arsenite and the arsenite of copper (see article “Arsenic”).

[872] The synonyms for Schweinfurt green are extremely numerous:--Mitic
green, Viennic green, imperial green, emerald green, are the principal
terms in actual use.

=Brighton Green= is a mixture of impure acetate of copper and chalk.

=Brunswick Green=, originally a crude chloride of copper, is now
generally a mixture of carbonate of copper and chalk or alumina.

=Mountain Green=, or =Mineral Green=, is the native green carbonate of
copper, either with or without a little orpiment.

=Neuwieder Green= is either the same as mountain green, or Schweinfurt
green mixed with gypsum or sulphate of baryta.

=Green Verditer= is a mixture of oxide and carbonate of copper with
chalk.

=Verdigris= is an acetate of copper, or a mixture of acetates. Its
formula is usually represented as (C₂H₃O₂)CuO. It is much used in the
arts, and to some extent as an external application in medicine. Its
most frequent impurities or adulterations are chalk and sulphate of
copper.

§ 802. =Dose--Medicinal Dose of Copper.=--Since sulphate of copper is
practically the only salt administered internally, the dose is generally
expressed as so many grains of sulphate. This salt is given in
quantities of from ·016 to ·129 grm. (¼ to 2 grains) as an astringent or
tonic; as an emetic, from ·324 to ·648 grm. (5 to 10 grains).

The sulphate of copper is given to horses and cattle in such large
doses as from 30 up to 120 grains (1·9 to 7·7 grms.); to sheep, from
1·3 to 2·6 grms. (20 to 40 grains); rabbits, ·0648 to ·1296 grm. (1 to 2
grains).

§ 803. =Effects of Soluble Copper Salts on Animals.=--Harnack has made
some experiments on animals with an alkaline tartrate of copper, which
has no local action, nor does it precipitate albumin. ½ to ¾ mgrm. of
copper oxide in this form, administered subcutaneously, was fatal to
frogs, ·05 grm. to rabbits, ·4 grm. to dogs. The direct excitability of
the voluntary muscles was gradually extinguished, and death took place
from heart paralysis. Vomiting was only noticed when the poison was
administered by the stomach.[873] The temperature of animals poisoned by
copper, sinks, according to the researches of F. A. Falck, many degrees.
These observations are in agreement with the effects of copper salts on
man, and with the experiments of Orfila, Blake, C. Ph. Falck, and
others.

[873] On the other hand, Brunton and West have observed vomiting
produced in animals after injection of copper peptone into the jugular
vein.--_Barth. Hosp. Rep._, 1877, xii.

Roger[874] experimented on the effect of copper leguminate which was
administered subcutaneously; he found gradual increasing paralysis of
the motor spinal tracts, which finally destroyed life by paralysis of
the breathing centre. The heart beat after the breathing had stopped.
The irritability and contractility of the muscles of frogs were lost,
while sensibility remained. He also found that, if the copper was
injected into the intestinal vessels, the dose had to be doubled in
order to destroy life; this is, doubtless, because the liver, as it
were, strained the copper off and excreted it through the bile. Roger
was unable to destroy life by large doses of copper given by the mouth,
for then vomiting supervened and the poison in great part was removed.

[874] _Revue de Médecine_, 1877, xii.

Bernatzic[875] considers that the poisonous properties of copper are
similar to those of zinc and silver. He says: “Silver, copper, and zinc
are, in their medicinal application, so much allied that, with regard to
their action, they graduate one into the other and show only minor
differences; copper, which is a little the more poisonous of the three
so far as its remote action is concerned, stands between the other two.
If taken, in not too small a quantity, for a long time, the functional
activity of the muscular and nervous systems is influenced injuriously,
the development of the animal cells is inhibited, the number of the red
blood corpuscles decreased, and therefore the oxidising process and
metabolism are likewise diminished, leading ultimately to a condition of
marked cachexia. . . . From a toxic point of view, the three metals
named also stand near each other, and their compounds differ from other
metals injurious to the organism in this, that they do not produce
notable changes of the tissues or coarse functional disturbances leading
to death as other poisonous metals, and therefore are not to be
considered poisons in the same sense as lead, mercury, arsenic,
antimony, phosphorus are considered poisons; for, on stopping the entry
of the poison, any injurious effect is completely recovered from and the
functions again become normal.”

[875] _Encycloped. d. ges. Heilkunde_, xi. S. 429.

Lehmann[876] has also experimented on the effects of copper; his
experiments were made on both animals and men. He found that small
quantities were more thoroughly absorbed than medium or large doses; the
method of separation appeared to be different in different
animals--thus, the chief copper-excreting organ in dogs is the liver; in
rabbits, the intestine; and in man, the kidneys. Of 3 mgrms. of copper
taken by a man in three days, 1 mgrm., or a third, was recovered from
the urine. Lehmann experimented on 6 rabbits, 4 cats, and 1 dog. During
the first few days the animals were given 10 to 30 mgrms. of copper, in
the form of a salt, in their food; then the dose was raised to 50 mgrms.
or even to 100 mgrms., and the experiment continued for from two to four
months; in one case, six months. The sulphate, acetate, chloride,
oleate, butyrate, and lactate were all tried, but no essential
difference in action discovered. Apart from slight vomiting, and in a
few cases, as shown by _post-mortem_, a slight catarrh of the stomach,
the animals remained well. A few increased in weight. Nervous symptoms,
cramps, convulsions, diarrhœa, or the reverse, were not observed. The
analysis of the organs showed considerable copper absorption; the liver
of the cats gave a mean amount of 12 mgrms. of copper, and in the other
organs there was more copper than is found in cases of acute poisoning.

[876] _Münch. med. Wochenschrift_, 1891, Nr. 35 u. 36.

Lehmann has also made experiments upon himself and his pupils on the
effect of the sulphate and the acetate when taken for a long time:--

  One of the experimenters took     for 50 days 10 mgrms. daily Cu as
                                                               sulphate.
   „           „             „ then for 30  „   20   „            „
  Another took      for  3 days                   5 mgrms. as acetate.
      „        then for 10 days                  10  „           „
      „          „       1 day                   15  „           „
      „          „      19 days                  20  „           „
      „          „      18 days                  30  „           „

None of these daily doses had the least effect.

Five farther experiments showed that 75 to 127 mgrms. of copper in peas
and beans, divided in two meals, could be taken daily without effect;
but if 127 mgrms. were taken at one meal in 200 grms. of peas, then,
after a few hours, there might be vomiting; and Lehmann concludes that
doses of copper in food of about 100 mgrms. may produce some transient
derangement in health, such as sickness, a nasty taste in the mouth, and
a general feeling of discomfort, but nothing more; some slight colicky
pains and one or two loose motions are also possible, but were not
observed in Lehmann’s experiments.

§ 804. =Toxic Dose of Copper Salts.=--This is a difficult question,
because copper salts generally act as an emetic, and therefore very
large doses have been taken without any great injury. In fact, it may be
laid down that a medium dose taken daily for a considerable time is far
more likely to injure health, or to destroy life, than a big dose taken
at once. In Tschirch’s[877] careful experiments on animals, he found 10
mgrm. doses of CuO given daily to rabbits, the weight of which varied
from 1200 to 1650 grms., caused injury to health, that is, about 3·5
mgrms. per kilo. If man is susceptible in the same proportion, then
daily doses of 227·5 mgrms. (or about 3½ grains) would cause serious
poisonous symptoms; although double or treble that quantity might in a
single dose be swallowed and, if thrown up speedily, no great harm
result. 120 grms. of sulphate of copper have been swallowed, and yet the
patient recovered after an illness of two weeks.[878] Lewin[879]
mentions the case of an adult who recovered after ten days’ illness,
although the dose was 15 grms.; there is also on record the case of a
child, four and a half years old, who recovered after a dose of 16·5
grms. (a little over half an ounce). On the other hand, 7·7 grms. have
been with difficulty recovered from.[880] A woman died in seventy-two
hours after taking 27 grms. (7 drms.) of copper sulphate mixed with 11·6
grms. (3 drms.) of iron sulphide; 56·6 grms. (2 ozs.) of copper acetate
have caused death in three days; 14·2 grms. (0·5 oz.) in sixty
hours.[881]

[877] _Das Kupfer_, Stuttgart, 1893.

[878] Referred to by Bernatzic, on the authority of Ketli, in _Encycl.
d. ges. Heilkunde_, xi. S. 433.

[879] _Toxicologie_, S. 133.

[880] D Taylor, _op. cit._

[881] Sonnenschein, _op. cit._

§ 805. =Cases of Acute Poisoning.=--Acute poisoning by salts of copper
is rare; in the ten years ending 1892, there were registered in England
8 deaths from this cause--3 suicidal (2 males, 1 female) and 5
accidental (4 males, 1 female). The symptoms produced by the sulphate of
copper are those of a powerful irritant poison: there is immediate and
violent vomiting; the vomited matters are of a greenish colour--a green
distinguished from bile by the colour changing to blue on the addition
of ammonia. There is pain in the stomach, and in a little time
affections of the nervous system, as shown by spasms, cramps, paralysis,
and even tetanus. Jaundice is a frequent symptom, if life is prolonged
sufficiently to admit of its occurrence.

One of the best examples of acute poisoning by copper sulphate is
recorded by Maschka.[882] A youth, sixteen years old, took an unknown
large dose of powdered copper sulphate, mixed with water. Half an hour
afterwards there was violent vomiting, and he was taken to the hospital.
There was thirst, retching, constriction in the throat, a coppery taste
in the mouth, and pain in the epigastrium, which was painful on
pressure. The vomit was of a blue colour, and small undissolved crystals
of copper sulphate were obtained from it. The patient was pale, the
edges of the lips and the angles of the mouth were coloured blue, the
surface of the tongue had also a blue tint, the temperature was
depressed, the extremities cold, nails cyanotic, and the pulse small and
quick. Several loose greenish-yellow evacuations were passed; there was
no blood. The urine was scanty, but contained neither blood nor albumen.
During the night the patient was very restless; the next morning he had
violent headache, pain in the epigastrium, burning in the mouth and
gullet, but no vomiting. The urine was scanty, contained blood, albumen,
and colouring matter from the bile. On the fourth day there was marked
jaundice. The mucous membrane was very pale, the temperature low, pulse
frequent, and great weakness, cardiac oppression, and restlessness were
experienced. There were diarrhœa and tenesmus, the motions being
streaked with blood; the urine also contained much blood. The liver was
enlarged. The patient died in a state of collapse on the seventh day.

[882] _Wiener med. Wochenschr._, 1871, Nro. 26, p. 628.

In 1836 a girl, sixteen months old, was given bluestone to play with,
and ate an unknown quantity; a quarter of an hour afterwards the child
was violently sick, vomiting a bluish-green liquid containing some
pieces of sulphate of copper. Death took place in four hours, without
convulsions, and without diarrhœa.

§ 806. =Subacetate of Copper, Subchloride, and Carbonate=, all act very
similarly to the sulphate when given in large doses.

§ 807. =Post-mortem Appearances.=--In Maschka’s case, the chief changes
noted were in the liver, kidneys, and stomach. The substance of the
liver was friable and fatty; in the gall-bladder there were but a few
drops of dark tenacious bile. The kidneys were swollen, the cortical
substance coloured yellow, the pyramids compressed and pale brown. In
the mucous membrane of the stomach there was an excoriation the size of
a shilling, in which the epithelium was changed into a dirty brown mass,
easily detached, laying bare the muscular substance beneath, but
otherwise normal.

In a case of poisoning by verdigris (subacetate of copper) recorded by
Orfila,[883] the stomach was so much inflamed and thickened that
towards the pyloric end the opening into the intestine was almost
obliterated. The small intestines throughout were inflamed, and
perforation had taken place, so that part of the green liquid had
escaped into the abdomen. The large intestines were distended in some
parts, contracted in others, and there was ulceration of the rectum. In
other cases a striking discoloration of the mucous membrane, being
changed by the contact of the salt to a dirty bluish-green, has been
noticed, and, when present, will afford valuable indications.

[883] _Toxicologie_, vol. i. p. 787 (5th ed.).

§ 808. =Chronic Poisoning by Copper.=--Symptoms have arisen among
workers in copper or its salts, and also from the use of food
accidentally contaminated by copper, which lend support to the existence
of chronic poisoning. In the symptoms there is a very great resemblance
to those produced by lead. There is a green line on the margin of the
gums. Dr. Clapton[884] found the line very distinct in a sailor and two
working coppersmiths, and the two men were also seen by Dr. Taylor.
Cases of chronic poisoning among coppersmiths have also been treated by
Dr. Cameron,[885] but this symptom was not noticed. Corrigan speaks of
the line round the gums, but describes it as purple-red. Among workers
in copper, Lancereaux[886] has seen a black coloration of the mucous
membrane of the digestive canal; its chemical characters appear to agree
with those of carbon.

[884] _Med. Times and Gazette_, June 1868, p. 658.

[885] _Med. Times and Gazette_, 1870, vol. i. p. 581.

[886] _Atlas of Pathological Anatomy._

Metallic copper itself is not poisonous. A Mr. Charles Reed has
published a letter in the _Chemical News_ of Jan. 12, 1894, stating that
he was, when a boy, wounded in the shin by a copper percussion-cap, and
the cap remained in the tissues; it was removed from the shin after a
sojourn thereof some twelve years; about the year 1873 he noticed that
whenever a piece of clean iron or steel came in contact with his
perspiration it was at once covered with a bright coating of copper, and
this continued until the percussion-cap was removed. Presuming the truth
of this, it shows conclusively that metallic copper deposited in the
tissues is in itself not poisonous, and farther, that one method of
elimination is by the skin. The experiments already cited throw doubt as
to whether repeated small doses of copper taken for a long time produce
in a scientific sense chronic poisoning; those which apparently support
the view that there is such a thing as chronic poisoning by copper, have
been produced by copper mixed with other metals; and there is the
possibility that these cases are really due to lead or arsenic, and not
to copper. The great use of late years of solutions of copper sulphate
as a dressing to plants, for the purpose of preventing the ravages of
various parasites, has provided, so far as animals are concerned, much
material for the judgment of this question. Sheep have been fed with
vines which have been treated with copper sulphate, oxen and pigs have
consumed for a long time grass treated with a 3 per cent. of copper
sulphate, without the least health disturbance. Mach[887] has fed cows
with green food coppered up to 200 mgrms. of copper sulphate, without
observing the slightest bad effect, for long periods of time; and
Tschirch[888] summarises the evidence as to chronic poisoning as
follows:--“So it appears the contention that there is no chronic
poisoning in men or animals is at present uncontradicted; it is farther
to be considered proved that the small amounts of copper naturally in
food, or carefully introduced into food, are not injurious to the health
of those that take such food, because the liver, kidneys, and other
organs excrete the copper through the urine and bile, and prevent a
pernicious accumulation.” At the same time, Tschirch does not consider
the question is definitely settled; the experiments should, he thinks,
have been continued not for months, but for years, to obtain a
trustworthy judgment.

[887] Mach, _Bericht über die Ergebnisse der im Jahre 1886 ausgeführten
Versuche zur Bekämpfung der Peronospora_, St. Michele, Tyrol.

[888] _Op. cit._

It may also be remarked that, if we are to rely upon the separation of
copper by the kidneys and the liver, those organs are presumed to be in
a healthy state, which is not the case with a percentage of the
population; to persons whose liver or kidneys are unsound, even the
small amounts of copper found in “coppered” peas may act as a poison,
and the experiments previously detailed throw no light upon the action
of copper under such circumstances.

§ 809. =Detection and Estimation of Copper.=--Copper may occur either in
the routine process of precipitating by SH₂, or it may, as is generally
the case, be searched for specially. If copper is looked for in a
precipitate produced by SH₂, it is taken for granted that the
precipitate has first been treated successively by carbonate of ammonia,
sulphide of sodium, and hydrochloric acid; in other words, arsenic,
antimony, and lead have been removed. The moist precipitate is now
treated with warm nitric acid, which dissolves out copper sulphide with
separation of sulphur; if there is sufficient copper, the fluid shows a
blue colour, which of itself is an indication of copper being present.
The further tests are--(1) Ammonia gives a deeper blue; (2) ferrocyanide
of potash a brown-red colour or precipitate; (3) a few drops mixed with
a solution of tartrate of soda, alkalised with sodic hydrate, and boiled
with a crystal or two of grape-sugar, gives quickly a red precipitate of
oxide of copper; (4) a needle or a clean iron wire, or any simple
galvanic combination, immersed in, or acting on, the liquid, soon
becomes coated with the very characteristic reddish metallic film.
Various other tests might be mentioned, but the above are ample.


Special Examinations for Copper.

(1) =In Water and Liquids generally.=--The liquid may be concentrated,
and the copper separated by electrolysis. A simple method is to place
the liquid in a large platinum dish, and insert a piece of zinc, adding
a sufficient quantity of ClH to dissolve the zinc entirely; the copper
is found as an adherent film on the inner surface of the dish. It is
neater, however, and more accurate, to connect the platinum dish with
the negative plate of a battery, suspending in the liquid the positive
electrode. The modifications of this method are numerous; some chemists
use (especially for small quantities of copper) two small platinum
electrodes, either of foil or of wire, and on obtaining the film, weigh
the electrode, then dissolve the copper off by nitric acid, and
re-weigh. Such solid substances as peas are conveniently mashed up into
a paste with water and ClH; an aliquot part is carefully weighed and put
in a platinum dish, connected, as before described, with a battery; at
the end of from twelve to twenty-four hours all the copper is deposited,
and the dish with its film dried and weighed. The weight of the clean
dish, _minus_ the coppered dish, of course equals the copper. Fat and
oils are best thoroughly washed with hot acid water, which will, if
properly performed, extract all the copper. By the use of separating
funnels and wet filters, the fat or oil can be separated from the watery
liquid.

A galvanic test has been proposed, which is certainly very delicate,
1/100 of a mgrm. in solution being recognised with facility. A zinc
platinum couple is made with two wires; on leaving this in an acid
liquid containing a mere trace of copper, after several hours the
platinum will be found discoloured. If the discoloration is from copper,
on exposing the wire to hydrobromic acid fumes (easily produced from the
action of potassic bromide and sulphuric acid) and bromine, the wire
will become of a violet colour. This colour is easily recognised by
rubbing the wire on a piece of porcelain.[889]

[889] _Chem. News_, Nov. 30, 1877.

(2) =Animal Matters=, such as the liver, brain, spinal cord, &c., are
best entirely burnt to an ash, and the copper looked for in the
latter.[890] The same remark applies to bread and substances consisting
almost entirely of starchy matters. Any injurious quantity of copper
can, however, be extracted with hydrochloric acid and water; and,
although this method of extraction is not quite so accurate, it is
quicker.

[890] In exhumation of long buried bodies, it may be necessary to know
the composition of the soil. Sonnenschein mentions a skull, now in the
museum at Madrid, which was dug out of an old Roman mine, and is quite
green from copper compounds.--Sonnenschein’s _Handbuch_, p. 83.

§ 810. =Volumetric Processes for the Estimation of Copper.=--A number of
volumetric processes have been devised for the estimation of copper, but
for the purposes of this work it is unnecessary to detail them. When
copper is in too small a quantity to be weighed, it may then be
estimated by a colorimetric process.

One of the best of these is based upon the brown colour which
ferrocyanide of potash produces in very dilute solutions of copper. A
standard copper solution is obtained by dissolving sulphate of copper in
a litre of water, so that each c.c. contains 0·1 mgrm. Cu, and a
solution of ferrocyanide of potash in water is prepared, strength 4 per
cent. It is also convenient to have a solution of nitrate of ammonia,
which is found to render the reaction much more delicate.

The further details are on the well-known lines of colorimetric
estimations.


3. BISMUTH.

§ 811. =Bismuth=, Bi = 210; sp. gr., 9·799; fusing-point, 264° (507·2°
F.).--Bismuth, as obtained in the course of analysis, is either a black
metallic powder or an extremely brittle bead of a reddish-white colour.
The compounds which it will be necessary to briefly notice are the
peroxide and tersulphide.

§ 812. =The peroxide of bismuth=, Bi₂O₃ = 468; sp. gr., 8·211; Bi, 89·64
per cent., O, 10·36 per cent., as prepared by igniting the carbonate or
nitrate, is a pale lemon coloured powder, which can be fused without
loss of weight, but is reduced on charcoal, or in a stream of carbon
dioxide, to the metallic state. It is also reduced by fusion with
potassic cyanide or by ignition with ammonium chloride.

§ 813. =The Sulphide of Bismuth=, Bi₂S₃ = 516; Bi, 81·25 per cent., S,
18·75 per cent., occurs, in the course of analysis, as a brownish-black
or quite black precipitate, insoluble in water, dilute acids, alkalies,
alkaline sulphides, sulphate of soda, and cyanide of potassium, but
dissolving in moderately concentrated nitric acid with separation of
sulphur. It continually increases in weight when dried in the ordinary
way, and is completely reduced when fused with cyanide of potassium.

§ 814. =Preparations of Bismuth used in Medicine and the Arts.=

(1) =Pharmaceutical Preparations=:--

=Bismuthi Subnitras=, BiONO₃.H₂O.--A heavy white powder, insoluble in
water, and responding to the usual tests for bismuth and nitric acid.
The formula should yield 77 per cent. of bismuth oxide. Commercial
preparations, however, vary from 79 to 82 per cent.

=Bismuth Lozenges= (=Trochisci bismuthi=) are composed of subnitrate of
bismuth, magnesia carbonate, precipitated lime carbonate, sugar, and
gum, mixed with rose water. Each lozenge should contain 0·13 grm. (2
grains) of subnitrate of bismuth.

=Solution of Citrate of Bismuth and Ammonia= (=Liquor Bismuthi et
Ammoniæ citratis=), a colourless neutral or slightly alkaline fluid, sp.
gr. 1·07, responding to the tests for bismuth and ammonia. As an
impurity lead may be present, citric acid being so frequently
contaminated with lead. Carbonate of bismuth (_Bismuthi carbonas_),
(Bi₂O₂CO₃)₂H₂O is a fine white powder answering to the tests for carbon
dioxide and bismuth; it should yield 89·1 per cent. of bismuth oxide.

=A Nitrate of Bismuth=, Bi(NO₃)₃, an oleate of bismuth, an oxide of
bismuth, a subgallate of bismuth (_dermatol_), and a subiodide of
bismuth are also used in medicine.

(2) =Bismuth in the Arts.=[891]

[891] Bismuth is contained in all copper coinage--from the Bactrian
coins to our own; in all cupreous ores, except the carbonates, and in
nearly all specimens of commercial copper.--Field, _Chem. News_, xxxvi.
261.

The chief use of bismuth is in alloys and solders. The Chromate is
employed in calico-printing, and the subnitrate as a paint under the
name of pearl-white.

The salts of bismuth also occur in washes for the hair, and pearl-white
is used as a cosmetic, but only to a small extent.

§ 815. =Medicinal Doses of Bismuth.=--The subnitrate and carbonate are
prescribed in doses from ·0648 to 1·296 grm. (1 to 20 grains); the
valerianate, from ·1296 to ·648 grm. (2 to 10 grains); and the solution,
from 1·7 c.c. to 5·2 c.c. (½ drachm to 1½ drachm).

§ 816. =Toxic Effects of Bismuth.=--From the researches of Meyer and
Steinfeld[892] on animals, it appears that if birds or mammals are
poisoned with bismuth salts introduced subcutaneously, or by direct
injection, into the veins, death follows in from twenty-four to
forty-eight hours, the fatal issue being preceded by convulsions; after
death, the colon is intensely blackened, and it may be ulcerated, while
the small intestines and the stomach are healthy. If, however, sulphur
preparations are given by the mouth, there is then blackening of the
stomach, and there may also be ulcers. Meyer is of the opinion that SH₂
precipitates bismuth in the parenchyma, and the particles occluding the
capillaries thus cause small local necroses; that which escapes
precipitation is mainly excreted by the kidneys. Poisonous symptoms in
man have been known to occur from the treatment of wounds with bismuth
preparations;[893] the symptoms have been somewhat similar to mercurial
poisoning; there have been noticed stomatitis with salivation, loosening
of the teeth, a black colour of the mucous membrane of the mouth and
ulceration, also catarrh of the intestines, and the inflammatory
condition of the kidneys usual when that organ has to excrete metallic
substances not natural to the body, the “metallniere,” or metal kidney,
of the German writers. One case is recorded of death in nine days of an
adult after taking 7·7 grms. (2 drms.) of bismuth subnitrate. The
recorded symptoms were a metallic taste in the mouth, pain in the
throat, vomiting, purging, coldness of the surface, and spasms of the
arms and legs. A _post-mortem_ examination showed inflammatory changes
in the gullet, windpipe, and throughout the intestinal canal. Recovery
has, however, taken place from a single dose three times the amount
mentioned. It is possible that the fatal case was due to impure bismuth.

[892] L. Feder-Meyer, _Rossbach’s pharmak. Unters._, iii., 1882, No. 23;
Steinfeld, _Wirkung des Wismut. Inaug. Diss._, Dorpat, 1884; _Arch. exp.
P._, Bd. xx. 1886.

[893] _B. Med. Journal_, 1887, i. 749.

§ 817. =Extraction and Detection of Bismuth in Animal Matters.=--Bismuth
appears to be excreted principally by the bowels as sulphide of bismuth;
but it has also been detected in the urine, spleen, and liver; and
Lubinsky has found it in the saliva and in the epithelium of the mouth
of persons taking one of its preparations. Without denying the
possibility of its existing in a soluble state in the saliva, its
presence in the mouth may, under such circumstances, be ascribed to the
lodgment of particles of subnitrate or subcarbonate of bismuth in the
interstices of the teeth, &c. It will then be evident that, if a person
is supposed to have been poisoned by a large dose of bismuth, and the
analyst fail to find it in the stomach, the contents of the bowels
should be next examined.

The extraction of bismuth must be undertaken by nitric acid, and boiling
for at least two hours may be necessary to dissolve it out from the
tissues. Such organs as the liver and spleen are boiled in a finely
divided state with a litre of dilute nitric acid (strength, 5 per
cent.), for the time mentioned, filtered, and the filtrate evaporated to
dryness; the remainder is then carbonised by strong nitric acid; and,
finally, the charcoal is boiled with equal parts of nitric acid and
water, and the whole evaporated to dryness. By this method every trace
of bismuth is extracted. The dry residue may now be brought into
solution, and tested for bismuth. The best solvent for the nitrate of
bismuth is dilute nitric acid 50 per cent.; the dry residue is therefore
dissolved in 100 or 200 c.c. of the acid, and fractional parts taken for
examination:--

(1) The solution, poured into a large volume of warm distilled water,
gives a crystalline precipitate of subnitrate of bismuth. The only metal
giving a similar reaction is antimony, and this is excluded by the
method employed.

(2) The filtered fluid gives on addition of sodic chloride a precipitate
of oxychloride. This, again, is distinguished from oxychloride of
antimony by its insolubility in tartaric acid.

(3) Any bismuth precipitate, fused with soda on charcoal, gives a
brittle bead of bismuth; the coal is coated whilst warm a dark
orange-yellow, on cooling citron-yellow.

(4) The bead may be identified by powdering it, placing it in a short
subliming tube, and passing over it dry chlorine. The powder first turns
black, then melts to an amber-yellow fluid, and finally, by prolonged
heating, sublimes as terchloride of bismuth.

(5) A very delicate test proposed by Abel and Field, in 1862,[894]
specially for the detection of bismuth in copper (but by no means
confined to mineral analysis), utilises the fact that, if iodide of lead
be precipitated from a fluid containing the least trace of bismuth,
instead of the yellow iodide the scales assume a dark orange to a
crimson tint. A solution of nitrate of lead is used; to the nitric acid
solution ammonia and carbonate of ammonia added; the precipitate washed,
and dissolved in acetic acid; and, finally, excess of iodide of
potassium added. It is said that thus so small a quantity as ·00025 grm.
may be detected in copper with the greatest ease, the iodide of lead
becoming dark orange; ·001 grain imparts a reddish-brown tinge, and ·01
grain a crimson.

[894] _Journ. Chem. Soc._, 1862, vol. xiv. p. 290; _Chem. News_, vol.
xxxvi. p. 261.

(6) A solution of a bismuth salt, which must contain no free HCl, when
treated with 10 parts of water, 2 of potassium iodide, and 1 part of
cinchonine, gives a red orange precipitate of cinchonine
iod.-bismuth.[895]

[895] E. Légar, _Bull. de la Soc. Chim._, vol. iv., 1888, 91.

(7) Van Kobell’s test, as modified by Hutchings,[896] and proposed more
especially for the detection of bismuth in minerals, is capable of being
applied to any solid compound suspected of containing the metal:--A
mixture of precipitated and purified cuprous iodide, with an equal
volume of flowers of sulphur, is prepared, and 2 parts of this mixture
are made into a paste with 1 part of the substance, and heated on a slip
of charcoal on an aluminium support by the blowpipe flame. If bismuth be
present, the red bismuth iodide will sublime, and on clean aluminium is
easily distinguishable.

[896] _Chem. News_, vol. xxxvi. p. 249.

There are many other tests, but the above are sufficient.

§ 818. =Estimation of Bismuth.=--The estimation of bismuth, when in any
quantity easily weighed, is, perhaps, best accomplished by fusing the
sulphide, oxide, or other compound of bismuth, in a porcelain crucible
with cyanide of potassium; the bismuth is reduced to the metallic state,
the cyanide can be dissolved out, and the metallic powder washed (first
with water, lastly with spirit), dried, and weighed.

Mr. Pattison Muir has shown[897] that bismuth may be separated from
iron, aluminium, chromium, and manganese, by adding ammonia to the acid
solutions of these metals.

[897] Pattison Muir on “Certain Bismuth Compounds,” _Journ. Chem. Soc._,
p. 7, 1876.

This observation admits of many applications, and may be usefully taken
advantage of in the separation of bismuth from the nitric acid solution
of such animal matters as liver, &c. The acid liquid is partially
neutralised by ammonia, and, on diluting with warm water containing a
little sodium or ammonium chloride, the whole of the bismuth is
precipitated as oxychloride, which may be collected, and fused with
cyanide of potassium, as above.

If the bismuth precipitate is in small quantity, or if a number of
estimations of bismuth are to be made, it is most convenient to use a
volumetric process. In the case first mentioned, the oxychloride could
be dissolved in nitric acid, sodium acetate added in excess, and
sufficient acetic acid to dissolve any precipitate which has been
produced, and then titrated by the following method, which we also owe
to Mr. Pattison Muir:--

=Estimation of Bismuth by Potassium Dichromate.=[898]--A solution of
recrystallised potassium dichromate (strength, 1 per cent.) is prepared.
A known weight of pure bismuthous oxide (Bi₂O₃) is dissolved in excess
of nitric acid, and a solution of sodium acetate is added to this liquid
until a copious white precipitate is thrown down; acetic acid is then
added in quantity sufficient to dissolve the precipitate completely, and
to insure that, when the liquid is made up with water to a fixed volume,
no precipitate shall be formed. A certain volume of this liquid is
withdrawn by means of a pipette, placed in a beaker, and heated to
boiling; the potassium dichromate is then gradually run in from a
burette, the liquid being boiled between each addition of the solution,
until a drop of the supernatant liquid gives a faint reddish-brown
coloration when spotted with silver nitrate on a white slab.

[898] Pattison Muir on “Certain Bismuth Compounds,” _Journ. Chem. Soc._,
vol. i. p. 659, 1879.

Another very generally applicable volumetric method for bismuth has been
proposed by Mr. Muir.[899] This depends on the fact (observed by Sonchay
and Leussen),[900] that normal bismuth oxalate splits up on boiling into
a basic oxalate of the composition Bi₂O₃2C₂O₃ + OH₂, but slightly
soluble in nitric acid. The process is performed by precipitating the
bismuth by excess of oxalic acid, dissolving the precipitate (first
purified from free oxalic acid) in dilute hydrochloric acid, and lastly,
titrating by permanganate. The absence of free hydrochloric acid before
precipitating must be insured.

[899] _Ibid._, 1877.

[900] _Ann. Chem. Pharm._, vol. cv. p. 245.


4. SILVER.

§ 819. =Silver= = 108; specific gravity, 10·5; fusing-point, 1023°
(1873° F.).--Silver, as separated in analysis, is either a very white,
glittering, metallic bead, or a dull grey powder. It does not lose
weight on ignition, and is soluble in dilute nitric acid.

§ 820. =Chloride of Silver=, AgCl = 143·5; specific gravity, 5·552; Ag,
75·27 per cent., Cl, 24·73 per cent., is a dense, white, curdy
precipitate, when produced in the wet way. It is very insoluble in
water, dilute nitric acid, and dilute sulphuric acid; in many warm
solutions (especially aqueous solutions of the chlorides generally), the
alkaline and alkaline-earthy nitrates, and tartaric acid solutions, the
silver is dissolved to an appreciable extent, but deposited again on
diluting and cooling. The complete solvents of chloride of silver
are--ammonia, cyanide of potassium, and hyposulphite of soda. Chloride
of silver cannot be fused at a high heat without some slight loss by
volatilisation; on coal in the R.F., it fuses very easily to a globule.
It can with soda be reduced to metal, and can also readily be reduced by
ignition in a current of hydrogen, carbon oxide, or carburetted hydrogen
gas.

§ 821. =Sulphide of Silver=, Ag₂S = 248; specific gravity, 7·2; Ag, 87·1
per cent., S, 12·9 per cent., when prepared in the wet way, is a black
precipitate, insoluble in water, dilute acids, and alkaline sulphides.
If ignited in hydrogen it may be reduced to the metallic state; it is
soluble in nitric acid, with separation of sulphur.

§ 822. =Preparations of Silver used in Medicine and the Arts.=

(1) =Medicinal Preparations=:--

=Nitrate of Silver=, AgNO₃; Ag, 63·51 per cent., N₂O₅, 36·49 per cent.
This salt is either sold crystallised in colourless rhombic prisms, or
in the form of small white pencils or sticks. It gives the reactions for
silver and nitric acid, and stains the skin black. 100 parts, dissolved
in distilled water, should give, with hydrochloric acid, a precipitate
which, when washed and dried, weighs 83·4 parts. The silver is, however,
far more quickly estimated by the blowpipe than in the wet way. One grm.
fused in a cavity on charcoal should give a little globule of metallic
silver, weighing about ·6351 grm. The chief adulterations of this
substance are copper, lead, and nitrate of potash. If all the silver is
precipitated by hydrochloric acid, carefully filtered off, and the
filtrate evaporated to dryness, any residue will denote adulteration or
impurity.

=Argenti Oxidum=, =Oxide of Silver=, Ag₂O = 232; Ag, 93·19 per cent.--A
dark olive-brown powder, soluble in ammonia and nitric acid. By ignition
it readily yields metallic silver. The P.B. directs that 29 grains of
the oxide should yield 27 of metallic silver.

=Nitrate of Silver and Potash= (=Argentum nitricum cum kali nitrico=),
AgNO₃ + KNO₃.--This preparation is in most of the pharmacopœias,
Austrian, German, Danish, Swedish, Russian, Swiss, and the British; it
is directed by the B.P. to be composed of 1 part of silver nitrate and
1 part of potassic nitrate fused together. A “toughened silver nitrate”
is made by fusing together potassic nitrate 5, silver nitrate 95. Mild
caustic points are used by oculists by fusing 1 of silver nitrate with
2, 3, 3½, and 4 parts of potassic nitrate.

(2) =Silver in the Arts.=--The uses of the metal in coinage, articles
for domestic purposes, for ornament, &c., are too well known to require
enumeration. The only forms in which silver is likely to give rise to
accident are the salts used in medicine, photography, in the dyeing of
hair, and in the manufacture of marking inks.

=Hair-dyes.=--About one-half of the hair-dyes in use are made with
nitrate of silver. The following are only a few of the recipes:--

=Aqua Orientalis.=--Grain silver 2 drms., nitric acid 1 oz., steel
filings 4 drms., distilled water 1½ oz.--the whole finally made up to 3½
fluid ozs., and filtered.

=Argentan Tincture.=--Nitrate of silver 1 drachm, rose water 1 fluid
oz., sufficient nitrate of copper to impart a greenish tint.

=Eau d’Afrique.=--Two solutions--one of nitrate of silver, the other of
potash, containing ammonium sulphide.

The photographer uses various salts of silver, the chief of which
are--the nitrate, iodide, bromide, cyanide, and chloride of silver.

=Marking Inks.=--Some of the more important recipes for marking ink are
as follows:--

Nitrate of silver 1·0 part, hot distilled water 3·6 parts, mucilage,
previously rubbed with sap-green, 1·0 part. With this is sold a
“pounce,” or preparation consisting of a coloured solution of sodic
carbonate. Another preparation is very similar, but with the addition of
ammonia and some colouring matter, such as indigo, syrup of buckthorn,
or sap-green. A third is made with tartaric acid and nitrate of silver,
dissolved in ammonia solution, and coloured.

=Redwood’s Ink= consists of equal parts of nitrate of silver and
potassic bitartrate, dissolved in ammonia, with the addition of archil
green and sugar; according to the formula, 100 parts should equal 16·6
of silver nitrate.

=Soubeiran’s Ink= is composed of cupric nitrate 3, argentic nitrate 8,
sodic carbonate 4, and the whole made up to 100 parts, in solution of
ammonia. In one of Mr. Reade’s inks, besides silver, an ammoniacal
solution of a salt of gold is used.

§ 823. =Medicinal Dose of Silver Compounds.=--The nitrate and the oxide
of silver are given in doses from ·0162 to ·1296 grm. (¼ grain to 2
grains). Anything like ·1944 to ·2592 grm. (3 or 4 grains) would be
considered a large, if not a dangerous dose; but nothing definite is
known as to what would be a _poisonous_ dose.

§ 824. =Effects of Nitrate of Silver on Animals.=--Nitrate of silver is
changed into chloride by the animal fluids, and also forms a compound
with albumen. Silver chloride and silver albumenate are both somewhat
soluble in solutions containing chlorides of the alkalies, which
explains how a metallic salt, so very insoluble in water, can be
absorbed by the blood.

The action of soluble salts of silver on animals has been several times
investigated. There appears to be some difference between its effects on
warm and cold-blooded animals. In frogs there is quickly an exaltation
of the functions of the spinal cord, tetanic convulsions appear, similar
to those induced by strychnine; later, there is disturbance of the
respiration and cessation of voluntary motion.

The first symptoms with dogs and cats are vomiting and diarrhœa;
muscular weakness, paralysis, disturbance of the respiration, and weak
clonic convulsions follow. Rouget, as well as Curci, considers that the
action of silver is directed to the central nervous system; there is
first excitement, and then follows paralysis of the centres of
respiration and movement. Death occurs through central asphyxia.
According to the researches of F. A. Falck, subcutaneous injections of
silver nitrate into rabbits cause a fall of temperature of 6·7° to
17·6°, the last being the greatest fall which, in his numerous
researches on the effect of poisons on temperature, he has seen.

Chronic poisoning, according to the experiments of Bogoslowsky on
animals, produces emaciation, fatty degeneration of the liver, kidneys,
and also of the muscles--a statement confirmed by others.

§ 825. =Toxic Effects of Silver Nitrate in Man=--(1) =Acute
Poisoning.=--This is very rare. Orfila relates an attempt at suicide;
but most of the cases have been accidental, and of these, in recent
times, about five are recorded, mostly children. The accident is usually
due to the application of the solid nitrate to the throat, as an
escharotic, the stick breaking or becoming detached, and being
immediately swallowed; such an accident is related by Scattergood.[901]
A piece of silver nitrate ¾ inch long, slipped down the throat of a
child, aged fifteen months--vomiting immediately occurred, followed by
convulsions and diarrhœa; chloride of sodium was administered, but the
child died in six hours. In other cases paralysis and an unconscious
state has been observed.

[901] _Brit. Med. Journal_, May 1871.

(2) =Chronic Poisoning.=--Salts of silver taken for a long period cause
a peculiar and indelible colour of the skin, the body becomes of a
greyish-blue to black colour, it begins first around the nails and
fingers, then patches of a similar hue appear in different parts of the
body, and gradually coalesce, being most marked in those parts exposed
to the light. The colour is not confined to the outer skin, but is also
seen in the mucous membranes. There is also a slight inflammation of the
gums, and a violet line around their edge. Ginpon observed this line
after two months’ treatment of a patient by silver nitrate; the whole
quantity taken being 3·9 grms. (about 60 grains). The peculiar colour of
the skin is only seen after large dose; after 8 grms. taken in divided
doses Chaillon could not observe any change, but after 15 grms. had been
taken it was evident. So also Riemer has recorded a case, in which,
after a year’s use of silver nitrate (total quantity 17·4 grms.) a
greyish-black colour of the face was produced, and, when nearly double
the quantity had been taken, the colour had invaded the whole body.

§ 826. =Post-mortem Appearances.=--In the acute case recorded by
Scattergood, the mucous membranes of the gullet, of the great curvature
of the stomach, and parts of the duodenum and jejunum were eroded, and
particles of curd-like silver chloride adhered to the mucous membrane.

In the case recorded by Riemer of the long-continued use of silver
nitrate, the serous and mucous membranes were coloured dark; the choroid
plexus was of a blue-black; the endocardium, the valves of the heart,
and the aorta pale to dark grey, as well as the rest of the vessels; the
colouring was confined to the intima. The liver and kidney also showed
similar pigmentation. The pigment (probably metallic silver) was in the
form of very fine grains, and, as regards the skin, was situate under
the _rete Malpighia_ in the upper layer of the corium, and also in the
deeper connective tissue and in the sweat glands. Liouville has also
found the kidneys of a woman similarly pigmented, who took silver
nitrate daily for 270 days, in all about 7 grms., five years before her
death.

§ 827. =Detection and Estimation of Silver.=--The examination of the
solid salts of silver usually met with (viz., the nitrate, bromide,
iodide, cyanide, and chloride) is most speedy by the dry method on
charcoal; in this way in less than 120 seconds any practical chemist
could identify each compound. The nitrate, bromide, iodide, and
cyanide, all, if ignited on charcoal, yield buttons of metallic
silver--deflagration, bromine vapours, iodine vapours, and cyanogen
vapours being the respective phenomena observed. Chloride of silver
fuses to a pearl-grey, brown, or black globule on charcoal, according to
its purity; but is only in the R.F. gradually reduced to metal. With
soda, or fused in hydrogen or coal gas, the reduction is rapid enough.

=Nitrate of Silver in solution= might be identified by a very large
number of tests, since it forms so many insoluble salts. In practice one
is, however, satisfied with three tests, viz.: (1) A curdy precipitate
of chloride, on the addition of hydrochloric acid or alkaline chlorides,
soluble only in ammonia, cyanide of potassium, or hyposulphite of soda;
(2) a yellow precipitate, but little soluble in ammonia, on the addition
of iodide of potassium; and (3) a blood-red precipitate on the addition
of chromate of potash.

The separation of silver from the contents of the stomach is best
ensured by treating it with cyanide of potassium; for, unless a very
large quantity of silver nitrate has been taken, it is tolerably certain
that the whole of it has passed into chloride, and will, therefore, not
be attacked easily by acids. The contents of the stomach, then, or the
tissues themselves, are placed in a flask and warmed for some time with
cyanide of potassium, first, if necessary, adding ammonia. The fluid is
separated from the solid matters by subsidence (for an alkaline fluid of
this kind will scarcely filter), and then decomposed by hydrochloric
acid in excess. The flask containing this fluid is put on one side in a
warm place, and the clear fluid decanted from the insoluble chloride.
The latter is now collected on a filter, well washed with hot water, and
then dried and reduced on charcoal; or it may be put in a little
porcelain crucible with a rod of zinc and a few drops of hydrochloric
acid. The silver is soon deposited, and must be washed with water, then
with sulphuric acid. By the aid of a wash-bottle the particles of silver
are now collected on a small filter, again washed, and on the moist mass
a crystal of nitrate of potash and a little carbonate of soda laid. The
whole is then dried, and all the filter cut away, save the small portion
containing the silver. This small portion is now heated on charcoal
until a little button of pure silver is obtained, which may first be
weighed, then dissolved in nitric acid, and tested by the methods
detailed.

In a similar way hair, suspected of being dyed with silver, can be
treated with chlorine gas, and the chloride dissolved in potassic
cyanide.

Spots on linen, and, generally, very small quantities of silver, may be
detected by a simple galvanic process:--The substance is treated with
solution of cyanide of potassium, and submitted to a weak galvanic
current, using for the negative plate a slip of copper, for the
positive, platinum; the silver is deposited on the former.


5. MERCURY.

§ 828. =Mercury=, Hg = 200; specific gravity, 13·596; boiling-point,
350° (662° F.); it becomes solid at -39·4 (-39 F.). This well known and
familiar fluid metal evaporates and sublimes to a minute extent at all
temperatures above 5°.

When precipitated or deposited in a finely divided state, the metal can
be united into a single globule only if it is fairly pure; very slight
_fatty_ impurities especially will prevent the union. It is insoluble in
hydrochloric acid, soluble to a slight extent in dilute cold sulphuric
acid, and completely soluble in concentrated sulphuric and in nitric
acids. It combines directly with chlorine, bromine, and iodine, which,
in presence of free alkali, readily dissolve it. It is unalterable at
100°, and, when exposed to a high temperature, sublimes unchanged.

=Mercurous Chloride= (Calomel, HgCl = 235·5; specific gravity, 7·178;
subliming temperature, 111·6°; Hg, 84·94 per cent., Cl, 15·06 per
cent.), when prepared in the wet way is a heavy white powder, absolutely
insoluble in cold, but decomposed by boiling water. It may be converted
into the mercuric chloride by chlorine water and aqua regia. Chloride of
ammonium, potassium, and sodium, all decompose calomel into metallic
mercury and mercuric chloride. It is easily reduced to metal in a tube
with soda, potash, or burnt magnesia.

§ 829. =Sulphide of Mercury= (HgS, Hg, 86·21 per cent., S, 13·79 per
cent.) is a black powder, dissolving in nitromuriatic acid, but very
insoluble in other acids or in water. It is also insoluble in alkaline
sulphides, with the exception of potassic sulphide.

§ 830. =Medicinal Preparations of Mercury.=--Mercury in the liquid state
has been occasionally administered in constipation; its internal use is
now (or ought to be) obsolete. Gmelin has found samples contaminated
with metallic bismuth--a metal which only slightly diminishes the
fluidity of mercury; the impurity may be detected by shaking the mercury
in air, and thus oxidising the bismuth. Mercury may also contain various
mechanical impurities, which are detected by forcing the metal by means
of a vacuum pump through any dense filtering substance. Tin and zinc may
be dissolved out by hydrochloric acid, and all fixed impurities (such as
lead and bismuth) are at once discovered on subliming the metal.

=Mercury and Chalk= (=Hydrargyrum cum creta=).--Mercury, 33·33 per
cent.; chalk, 66·67.

=Blue Pill= (=Pilula hydrargyri=).--Mercury in a finely divided state,
mixed with confection of roses and liquorice root; the mercury should be
in the proportion of 33·33 per cent.[902]

[902] The chemical composition of blue pill varies according to its age.
Harold Senier has made a careful series of analyses, with the following
result (_Pharm. Journ._, Feb. 5, 1876):--

  +----+------------+---------+---------+-----------+--------+---------+
  |    |    Age.    |Metallic |Mercuric | Mercurous |  Ash.  | Organic |
  |    |            |Mercury. | Oxide.  |   Oxide.  |        | Matter. |
  +----+------------+---------+---------+-----------+--------+---------+
  | 1  | 18 hours,  |  32·49  |  none.  | a trace.  |  1·20  |  66·31  |
  | 2  |  3 weeks,  |  32·26  |   ·09   |      ·25  |  1·20  |  66·20  |
  | 3  |  3 months, |  32·60  |   ·24   |      ·62  |  1·18  |  66·36  |
  | 4  |  3   „     |  31·15  |   ·44   |     1·60  |  1·12  |  65·69  |
  | 5  |  6   „     |  32·44  |   ·50   |      ·80  |  1·70  |  64·56  |
  | 6  | 14   „     |  29·86  |   ·98   |     2·60  |  1·20  |  65·36  |
  | 7  | 19   „     |  31·59  |   ·50   |     2·50  |  1·00  |  64·41  |
  | 8  |  2 years,  |  28·40  |  1·80   |     4·22  |  2·10  |  63·48  |
  | 9  | (?)        |  30·23  |  1·06   |     3·24  |  1·05  |  64·44  |
  +----+------------+---------+---------+-----------+--------+---------+


=Mercury Plaster= (=Emplastrum hydrargyri=).--Made with mercury, olive
oil, sulphur, and lead plaster; it should contain Hg, 33 per cent.;
sulphur, 18 per cent.

=Ammoniac and Mercury Plaster= (=Emplastrum ammoniaci cum
hydrargyro=).--Gum, ammonia, mercury, olive oil, and sulphur; it should
contain 20 per cent. of Hg, and ·1 per cent. of sulphur.

=Mercurial Ointment= (=Unguentum hydrargyri=).--Mercury mixed with lard
and suet, the strength should be nearly 50 per cent. mercury; commercial
samples often contain as little as 38 per cent.

=Compound Mercury Ointment= (=Unguentum hydrargyri compositum=).--Made
with ointment of mercury, yellow wax, olive oil, and camphor; it should
contain 22·2 per cent. Hg.

=Liniment of Mercury= (=Linimentum hydrargyri=) is made of mercurial
ointment, solution of ammonia, and liniment of camphor; it contains
about 16½ per cent. of mercury.

=Mercurial Suppositories= (=Suppositoria hydrargyri=).--Composed of
ointment of mercury and oil of theobroma. Each suppository should weigh
15 grains and contain ⅓ of its weight of mercurial ointment.

=Acetate of Mercury= (=Mercurous acetate=) is not contained in the B.P.,
but is officinal on the Continent. It is a salt occurring in white
micaceous scales, soluble in 133 parts of cold water, giving the
reactions of acetic acid and mercury, and very readily decomposed.

=Mercuric Ethyl Chloride= (=Hydrargyrum æthylo-chloratum=) is used as a
medicine on the Continent. It occurs in white, glittering, crystalline
scales, which take on pressure a metallic appearance, and possess a
peculiar ethereal odour; it is but little soluble in water and ether,
with difficulty in cold alcohol, but copiously soluble on boiling, and
depositing crystals on cooling. It sublimes at about 40° without
residue; on quick heating it burns with a weak flame, developing a
vapour of metallic taste and unpleasant odour. It gives no precipitate
with silver nitrate, nor with albumen.

=Corrosive Sublimate= (=Mercuric chloride=), HgCl₂ = 271; Hg, 73·8 per
cent., Cl, 26·1 per cent.--In commerce this salt occurs in transparent,
heavy, colourless masses, which have a crystalline fracture; if placed
in the subliming cell described at p. 258, it sublimes at about 82·2°
(180° F.), and melts at higher temperatures. The sublimate is generally
in groups of plates drawn to a point at both ends, in crystalline
needles, or in octahedra with a rectangular base. It dissolves in 16
parts of cold water and about 3 of boiling, and is very soluble in
solutions of the alkaline chlorides; it dissolves also in ether, and can
be, to a great extent, withdrawn from aqueous solutions by this agent.
Alcohol dissolves nearly one-third its weight of the salt, and its own
weight when boiling. It combines with albumen; gives, when in solution,
a precipitate of mercuric oxide when tested with solution of potash; a
white precipitate with ammonia; a scarlet with iodide of potassium; and
a black precipitate of finely divided mercury with protochloride of tin.
If a crystal (when placed in the subliming cell) gives a crystalline
sublimate at about the temperature mentioned, and this sublimate becomes
of a red colour when treated with a droplet of iodide of potassium, it
can be no other substance than corrosive sublimate.

=Solution of Perchloride of Mercury= (=Liquor hydrargyri perchloridi=)
is simply 10 grains of perchloride of mercury and chloride of ammonium
in a pint of water; 100 c.c. therefore should contain 114 mgrms.
corrosive sublimate.

=Yellow Mercurial Lotion= (=Lotio hydrargyri flava=).--Perchloride of
mercury, 18 grains, mixed with 10 ounces of solution of lime.

=Calomel=[903] (=Hydrargyri subchloridum=).--The properties of calomel
have been already described. It sometimes contains as an impurity
corrosive sublimate, which may be dissolved out by ether. Carbonate of
lead, sulphate, and carbonate of baryta, gum, and starch, are the usual
adulterants mentioned. If on the application of heat calomel entirely
sublimes, it must be free from the substances enumerated.

[903] It would appear that in America a cosmetic is in use, consisting
of calomel mixed into a paste with water.--_Vide_ “A Dangerous
Cosmetic,” by C. H. Piesse, _Analyst_ (25), 1878, p. 241.

=Oleate of Mercury= (=Hydrargyri oleatum=) is composed of 1 part of
yellow oxide and 9 parts of oleic acid.

=Black Mercurial Lotion= (=Lotio hydrargyri nigra=).--Calomel, 30
grains, mixed with 10 fluid ounces of lime-water.

=Compound Pill of Subchloride of Mercury.=--Calomel and sulphurated
antimony, each 1 ounce, guiac resin 2 ounces, castor-oil 1 fluid ounce.
One grain (·0648 grm.) of calomel, and the same quantity of antimony
sulphide, are contained in every 5 grains (324 mgrms.) of the pill mass,
_i.e._, calomel 20 per cent.

=Ointment of Subchloride of Mercury= (=Unguentum hydrargyri
subchloridi=).--Calomel mixed with benzoated lard; strength about 1 :
6½.

=White Precipitate= (=Hydrargyrum ammoniatum=, NH₂HgCl).--A white, heavy
powder, subliming by heat without residue, and insoluble in water,
alcohol, and ether. With soda, it yields a metallic sublimate. When
boiled with potash, ammonia is evolved, the yellow oxide of mercury
formed, and chloride of potassium passes into solution. It should
contain 79·5 per cent. of mercury.

The fusible white precipitate of the pharmacopœia of the Netherlands
does not appear to be of constant composition, varying between 69·4 to
65·6 per cent. of mercury.[904] It melts on heating, and leaves as a
residue chloride of sodium.

[904] Hirsch, _Die Prüfung der Arzeneimittel_.

Commercial white precipitate is frequently adulterated; Barnes has found
carbonates of lead and lime, the latter to the extent of nearly 2 per
cent.[905] Calomel, according to Nickles,[906] has been substituted for
white precipitate, but this was several years ago. The methods for
detection are obvious.

[905] _Proceed. Brit. Pharm. Conf._, 1867, p. 10.

[906] _Journ. Pharm. et Chim._, le Série, 1858, vol. viij. p. 399.

=Ointment of Ammoniated Mercury= (=Unguentum hydrargyri ammoniati=).--1
part of ammoniated mercury mixed with 9 parts of simple ointment.

=Red Iodide of Mercury= (=Hydrargyrum iodidum rubrum=, HgI₂).--A
crystalline powder of a scarlet colour, becoming yellow on gentle
heating. It is very insoluble in water, one part requiring from 6000 to
7000 parts; soluble in 130 parts of cold, 150 of hot alcohol; and
dissolving freely in ether, or in aqueous solution of iodide of
potassium.

=Ointment of Red Iodide of Mercury= (=Unguentum hydrargyri iodidi
rubri=).--16 grains of the substance mixed with an ounce of simple
ointment.

=Green Iodide of Mercury= (=Hydrargyri iodidum viride=, HgI).--A dingy,
greenish-yellow powder, darkening on exposure to light, and easily
decomposed into the red iodide.

=Red Oxide of Mercury= (=Hydrargyri oxidum rubrum=), HgO = 216; Hg,
92·12 per cent.; specific gravity, 11 to 11·3; small, red, shining,
crystalline scales, very insoluble in water, requiring about 20,000
parts; entirely soluble in hydrochloric acid. By a heat below redness it
may be volatilised, and at the same time decomposed into mercury and
oxygen. Its principal impurity is nitric acid, readily detected by the
usual tests, or by heating in a test-tube, when, if nitric acid is
present, orange vapours will be evolved. Fixed red powders (such as
brick-dust and minium) are detected by being left as a residue, after
the application of heat sufficient to volatilise the mercury. An
ointment (strength 1 : 8) is officinal.

=Sulphate of Mercury.=--A white crystalline powder, decomposed by water
into the very insoluble basic salt of mercury, known as _Turbith
mineral_, HgSO₄2HgO.

=Turbith, or Turpeth, Mineral= is contained in the French pharmacopœia,
HgSO₄2HgO; Hg, 82·4 per cent.; specific gravity, 8·319. It requires for
solution 2000 parts of cold, and 600 of boiling water; but dissolves
with tolerable ease in hydrochloric acid.

=The Sulphide of Mercury=, known in commerce under the name of _Ethiops
mineral_, is officinal in France, the Netherlands, and Germany. Its
properties have been already described. The German and Dutch
pharmacopœias require in it 50, the French only 33⅓ per cent. of
metallic mercury.

=Hahnemann’s Soluble Mercury= (=Hydrargyrum solubile Hahnemanni=) is
officinal in the Dutch pharmacopœia. As found in commerce it contains
metallic mercury, nitric acid, and ammonia. The mercury should be in the
proportion of 86·33 per cent., the ammonia 2·44 per cent.

=Crystallised Nitrate of Mercury= (=Hydrargyrum nitricum oxidulatum=) is
officinal in the pharmacopœias of Germany, Switzerland, and France. The
salt is in white crystals, giving the reactions of nitric acid and
mercury, decomposed by the addition of water, but fully soluble in
water, if first moistened with nitric acid. The formula of the neutral
salt is Hg2NO₃HgO2H₂O, which requires 69·4 per cent. of mercury. An acid
solution of mercuric nitrate is officinal.

=An Ointment of Nitrate of Mercury= (=Unguentum hydrargyri nitratis=)
(often called citrine ointment) is contained in the B.P.; it is made
with 4 parts of mercury, nitric acid 12, lard 15, olive oil, 32; the
strength is about 1 in 15½.

=A Chloride of Mercury and Quinine= exists in commerce, prepared by
mixing 1 part of corrosive sublimate in solution with 3 parts of quinine
chloride, evaporating, and crystallising.

=Cyanide of Mercury=, HgCy, is contained in the French pharmacopœia. It
occurs in small, colourless, prismatic crystals, easily soluble in
water. If to the solution chloride of tin be added, a black precipitate
of reduced metal and stannous oxide is thrown down, and the odour of
prussic acid is developed.

=Mercuric Sulphide= (=Sulphide of Mercury=, =Cinnabar=, =Vermilion=) is
officinal in Germany, the Netherlands, and France; HgS = 232; specific
gravity, solid, 8·2; Hg, 86·21 per cent., O, 13·79 per cent. For
medicinal purposes it is made artificially. It is a beautiful red
powder, insoluble in all alkaline and all acid liquids, with the
exception of aqua regia. The solution gives the reactions of a sulphide
and mercury. On heating, it must burn away entirely without residue;
adulterations or impurities are--minium, lead, copper, and other metals.
The detection of minium is conveniently executed in the dry way. Pure
cinnabar, when heated in a matrass, gives a black sublimate, which
becomes red on friction. If minium is present, sulphide of lead remains
as a residue, and may be recognised on coal; the same remark applies to
sulphide of antimony. If it be desired to take the percentage of mercury
in cinnabar, equal parts of oxalate and cyanide of potassium should be
well mixed with the cinnabar, and heated in the bent tube described at
p. 654; by this means the whole of the metallic mercury is readily
obtained.[907]

[907] Dr. Sutro has published a case (quoted by Taylor), in which the
vapour of vermilion, applied externally, produced poisonous symptoms;
yet, according to Polak, the Persians inhale it medicinally, smoking it
with tobacco, catechu, mucilage, &c., the only bad effect being an
occasional stomatitis.--Eulenberg, _Gewerbe Hygiene_, p. 741.

§ 831. =Mercury in the Arts.=--The use of mercury in the arts is so
extensive, that any one in analytical practice is almost certain
occasionally to meet with cases of accidental poisoning, either from the
vapour[908] or some of its combinations.

[908] A singular case is cited by Tardieu (_Étude méd.-légal sur
l’Empoisonnement_), in which a man, supposing he had some minerals
containing gold, attempted the extraction by amalgamation with mercury.
He used a portable furnace (for the purpose of volatilising the mercury)
in a small room, and his wife, who assisted him, suffered from a very
well-marked stomatitis and mercurial eruption.

Quicksilver is used in the extraction of gold, the silvering of mirrors,
the construction of barometers, and various scientific instruments and
appliances; also for the preservation of insects, and occasionally for
their destruction.[909] An alloy with zinc and cadmium is employed by
dentists for stopping teeth; but there is no evidence that it has been
at all injurious, the mercury, probably, being in too powerful a state
of combination to be attacked by the fluids in the mouth.[910] Cinnabar
has also been employed to give a red colour to confections, and it may
be found in tapers, cigarette papers, and other coloured articles. The
nitrate of mercury in solution finds application in the colouring of
horn, in the etching of metals, in the colouring of the finer sorts of
wool, and in the hat manufacture.

[909] Forty-three persons were salivated from fumigating rooms with
mercury for the purpose of destroying bugs (Sonnenschein’s _Handbuch_,
p. 96).

[910] More danger is to be apprehended from the vulcanised rubber for
artificial teeth; and, according to Dr. Taylor, accidents have occurred
from the use of such supports or plates.

The sulphocyanide of mercury gives, when burnt, a most abundant ash, a
fact utilised in the toy known as Pharaoh’s serpent; the products of
combustion are mercurial vapours and sulphurous anhydride. That the
substance itself is poisonous, is evident from the following
experiment:--·5 grm. was given to a pigeon without immediate result; but
ten hours afterwards it was indisposed, refused its food, and in forty
hours died without convulsions.[911]

[911] Eulenberg, _Op. cit._, p. 472.

§ 832. The more Common Patent and Quack Medicines containing Mercury.

    =Mordant’s Norton’s Drops.=--This patent medicine is a mixture of
    the tincture of gentian and ginger, holding in solution a little
    bichloride of mercury, and coloured with cochineal.

    =Solomon’s Anti-impetigines= is a solution of bichloride of mercury,
    flavoured and coloured.

    =Poor Man’s Friend.=--An ointment of nitrate of mercury.

    =Brown’s Lozenges.=--Each lozenge contains ½ grain of calomel, and
    3½ grains of resinous extract of jalap; the rest is white sugar and
    tragacanth.

    =Ching’s Worm Lozenges.=--Each lozenge contains 1 grain of calomel;
    the rest white sugar and tragacanth, with saffron as a colouring
    matter.

    =Storey’s Worm Cakes.=--Each cake 2 grains of calomel, 2 grains of
    cinnabar, 6 grains of jalap, 5 grains of ginger, and the remainder
    sugar and water.

    =Wright’s Pearl Ointment= is said to be made up of 8 ozs. of white
    precipitate rubbed to a cream in 1 pint of Goulard’s extract, and to
    the mixture is added 7 lbs. of white wax and 10 lbs. of olive oil.

    =Keyser’s Pills.=--The receipt for these pills is--red oxide of
    mercury 1½ oz., distilled vinegar (dilute acetic acid) 1 pint;
    dissolve, add to the resulting solution manna 2 lbs., and triturate
    for a long time before the fire, until a proper consistence is
    attained; lastly, divide the mass into pills of 1½ grain each.

    =Mitchell’s Pills.=--Each pill contains aloes ·8 grain, rhubarb 1·6
    grain, calomel ·16 grain, tartar emetic ·05 grain.

    Many =Antibilious Pills= will be found to contain calomel, a few
    mercury in a finely divided state.

§ 833. =Mercury in Veterinary Medicine.=--Farmers and farriers use the
ointment (_blue ointment_) to a dangerous extent, as a dressing for the
fly, and wholesale poisoning of sheep has been in several instances the
consequence.[912] Ethiops mineral and Turpeth mineral are given to dogs
when affected by the distemper, worms, or the mange. Mercury, however,
is not very frequently given to cattle by veterinary surgeons, ruminants
generally appearing rather susceptible to its poisonous effects.

[912] Twenty-five tons of blue ointment are said to have been sold to
farmers by a druggist in Boston, Lincolnshire, in the course of a single
year.--Taylor’s _Medical Jurisprudence_, vol. i. p. 279.

§ 834. =Medicinal and Fatal Dose--Horses.=--Cinnabar 14·2 grms, (½ oz.),
calomel 14·2 grms. (½ oz.) or more, corrosive sublimate ·13 to ·38 grm.
(2 to 6 grains), and as much as 1·3 grm. (20 grains) have been given in
farcy.

=Cattle.=--Mercury with chalk 3·8 to 11·6 grms. (1 to 3 drms.), calomel
3·8 to 7·7 grms. (1 to 2 drms.) for worms; ·65 to 1·3 grm. (10 to 20
grains) as an alterative; Ethiops mineral, 7·7 to 15·5 grms. (2 to 4
drms.).

=Dogs.=--Ethiops or Turpeth mineral ·13 to 1·3 grm. (2 to 20 grains),
according to the size.

=Fowls.=--Mercury and chalk are given in fractions of a grain.

=Hogs= are also treated with mercury and chalk; the dose usually given
does not exceed ·32 grm. (5 grains).

It may be remarked that many of the doses quoted appear very large; the
writer cannot but consider that 20 grains of corrosive sublimate
administered to a horse would be more likely to kill the animal than to
cure the disease.

=Man.=--Corrosive sublimate has been fatal in a dose so small as ·19
grm. (3 grains); white precipitate has caused dangerous symptoms in
doses of from 1·9 to 2·6 grm. (30 to 40 grains); the cyanide of mercury
has killed a person in a dose of ·64 grm. (10 grains)--_Christison_; and
Turpeth mineral has proved fatal in doses of 2·6 grms. (40 grains).

Other preparations of mercury have also been fatal, but a doubt has
existed as to the precise quantity. Sometimes, also, there is probably a
chemical change in the substance, so that it is impossible to state the
fatal dose. For example, it is well known that calomel, under the
influence of alkaline chlorides, can be converted into the bichloride--a
fact which probably explains the extensive corrosive lesions that have
been found after death from large doses of calomel.

§ 835. =Poisoning by Mercury--Statistics.=--In the Registrar-General’s
death returns for the ten years ending 1892, it appears that in England
the deaths from mercurial poisoning[913] were 40 males, 19 females; of
these, 16 males and 18 females were cases of suicide, the remainder were
referred to accident.

[913] The deaths are registered under the term “_Mercury_,” but the
majority are poisonings by “_Corrosive Sublimate_.”

The effects of the different compounds of mercury may be divided into
two groups, viz., (1) Those caused by the finely divided metal and the
non-corrosive compounds; (2) the effects caused by the corrosive
compounds.

§ 836. (1) Effects of Mercurial Vapour, and of the Non-Corrosive
Compounds of Mercury.

(_a_) =Vegetable Life.=--Priestly and Boussingault have shown that
plants under a glass shade in which mercury is exposed in a saucer,
first exhibit black spots on the leaves; ultimately, the latter blacken
entirely, and the plants die.

(_b_) =Animal Life.=--Mercury in the form of vapour is fatal to animal
life, but it is only so by repeated and intense application.
Eulenberg[914] placed a rabbit under a large glass shade, and for four
days exposed it daily for two hours to the volatilisation of 2 grms. of
mercury on warm sand; on the sixth and seventh day 1·5 grm. was
volatilised. On the fifteenth day there was no apparent change in the
aspect of the animal; 5 grms. of mercury were then heated in a retort,
and the vapour blown in at intervals of ten minutes. Fourteen days
afterwards the gums were reddened and swollen, and the appetite lost;
the conjunctivæ were also somewhat inflamed. The following day these
symptoms disappeared, and the animal remained well.

[914] _Op. cit._, p. 728.

In another experiment 20 grms. of mercury were volatilised, and a rabbit
exposed to the vapour under a small glass shade. The following day the
conjunctivæ were moist and reddened; two days afterwards 10 grms. of
mercury were volatilised in the same way; and in two days’ interval
other 10 grms. were volatilised in three-quarters of an hour. There was
no striking change noticeable in the condition of the animal, but
within forty-eight hours it was found dead. The cause of death proved to
be an extravasation of blood at the base of the brain. The bronchia were
reddened throughout, and the lungs congested. Mercury, as with man, is
also readily absorbed by the broken or unbroken skin; hence thousands of
sheep have been poisoned by the excessive and ignorant external
application of mercurial ointment as a remedy against the attacks of
parasites. The sheep become emaciated, refuse food, and seem to be in
pain, breathing with short quick gasps.

In experiments on rabbits, dogs, and warm-blooded animals generally,
salivation and stomatitis are found to occur as regularly as in man; so
also in animals and man, paralytic and other nervous affections have
been recorded.

§ 837. (_c_) =Effects on Man.=--In 1810[915] an extraordinary accident
produced, perhaps, the largest wholesale poisoning by mercurial vapour
on record. The account of this is as follows:--H.M.S. “Triumph,” of
seventy-four guns, arrived in the harbour of Cadiz in the month of
February 1810; and in the following March, a Spanish vessel, laden with
mercury for the South American mines, having been driven on shore in a
gale, was wrecked. The “Triumph” saved by her boats 130 tons of the
mercury, and this was stowed on board. The mercury was first confined in
bladders, the bladders again were enclosed in small barrels, and the
barrels in boxes. The heat of the weather, however, was at this time
considerable; and the bladders, having been wetted in the removal from
the wreck, soon rotted, and mercury, to the amount of several tons, was
speedily diffused as vapour through the ship, mixing more or less with
the bread and the other provisions. In three weeks 200 men were affected
with ptyalism, ulceration of the mouth, partial paralysis, and, in many
instances, with diarrhœa. The “Triumph” was now ordered to Gibraltar,
the provisions were removed, and efforts were made to cleanse the
vessel. On restowing the hold, every man so employed was salivated. The
effects noted were not confined to the officers and ship’s company, for
almost all the stock died from the fumes--mice, cats, a dog, and even a
canary bird shared the same fate, though the food of the latter was kept
in a bottle closely corked up. The vapour was very deleterious to those
having any tendency to pulmonic affections. Three men, who had never
complained before they were saturated with mercury, died of phthisis;
one, who had not had any pulmonic complaint, was left behind at
Gibraltar, where his illness developed into a confirmed phthisis. Two
died from gangrene of the cheeks and tongue. A woman, confined to bed
with a fractured limb, lost two of her teeth; and many exfoliations of
the jaw took place.

[915] “An Account of the Effect of Mercurial Vapours on the Crew of His
Majesty’s Ship ‘Triumph,’ in the year 1810.”--_Phil. Trans._, 113,
1823.

Accidents from the vapour of mercury, quite independently of its
applications in the arts, have also occurred, some of them under curious
circumstances; such, for example, is the case mentioned in the footnote
to p. 639. Witness, again, a case mentioned by Seidel,[916] in which a
female, on the advice of an old woman, inhaled for some affection or
other 2·5 grms. of mercury poured on red-hot coals, and died in ten days
with all the symptoms of mercurial poisoning.

[916] Maschka’s _Handbuch_, Bd. ii. 295.

The metal taken in bulk into the stomach has been considered
non-poisonous, and, probably, when perfectly pure, it is so; we have,
however, the case of a girl who swallowed 4½ ozs. by weight of the
liquid metal, for the purpose of procuring abortion--this it did not
effect; but, in a few days, she suffered from a trembling and shaking of
the body and loss of muscular power. These symptoms continued for two
months, but there was no salivation and no blue marks on the gums. This
case is a rare one, and a pound or more has been taken without injury.

§ 838. =Absorption of Mercury by the Skin.=--Mercury in a finely divided
form, rubbed into the skin, is absorbed, and all the effects of
mercurialism result. This method of administering mercury for medicinal
purposes has long been in use, but, when the inunction is excessive,
death may occur. Thus, Leiblinger records a case in which three persons
were found dead in bed; the day before they had rubbed into the body,
for the purpose of curing the itch, a salve containing 270 grms. of
mercury finely divided.

It is difficult to say in what proportion workers in mercury, such as
water-gilders, &c., suffer. According to Hirt, not only do 1·5 to 2·1
per cent. of the workmen employed in smelting mercury ores suffer
acutely, but as high a proportion as 8·7 per cent. are slightly
affected.

§ 839. =Symptoms of Poisoning by Mercury Vapour.=--The symptoms of
poisoning by mercury vapour, or by the finely divided metal, are the
same as those which arise from the corrosive salts, with the exception
of the local action. In mild cases there is pallor, languor, and sore
mouth (from slightly inflamed gums), fœtid breath, and disorder of the
digestive organs. If the action is more intense, there is an
inflammation of the gums and, indeed, of the whole mouth, and
salivation, which is sometimes so profuse that as much as two gallons of
saliva have been secreted daily. The saliva is alkaline, has a bad
odour, and its specific gravity in the early stages is increased, but
ultimately becomes normal; the gums are raised into slight swellings,
which gradually enlarge and coalesce. The teeth that are already
carious, decay more rapidly; they become loose, and some may be shed;
the inflammatory action may extend to the jaw, and necrosis of portions
of the bone is no unusual occurrence. On recovery, the cheeks sometimes
form adhesions with the gums, and cicatrices always mark the loss of
substance which such an affection entails. With the stomatitis there are
disturbances of the gastro-intestinal tract--nausea and vomiting, pain
in the stomach, and diarrhœa alternating with constipation.
Conjunctivitis is very common, both in man and animals, from exposure to
mercury vapours. The further action of the metal is shown in its
profound effects on the nervous system. The patient is changed in his
disposition, he is excitable, nervous, or torpid; there are
sleeplessness and bad dreams, at the same time headache, noises in the
ears, giddiness, faintings, &c.

§ 840. =Mercurial Tremor.=--Mercurial tremor[917] may follow, or
accompany the above state, or it may be the chief and most prominent
effect. It specially affects the arms, partly withdrawing the muscles
from the control of the will, so that a person affected with mercurial
tremor is incapacitated for following any occupation, especially those
requiring a delicate and steady touch. In cases seriously affected, the
tremor spreads gradually to the feet and legs, and finally the whole
body may be invaded. The patient is no longer master of his muscles--the
muscular system is in anarchy, each muscle aimlessly contracting and
relaxing independently of the rest--the movement of the legs becomes
uncertain, the speech stuttering, the facial expressions are even
distorted into grimaces, and the sufferer sinks into a piteous state of
helplessness. The convulsive movements generally cease during sleep. The
tremors are accompanied by interference with the functions of other
organs: the respiration is weakened and difficult; dyspnœa, or an
asthmatic condition, results; the pulse is small and slow; paresis,
deepening into paralysis of the extremities, or of a group of muscles,
follows; and, lastly, if the condition is not alleviated, the patient
becomes much emaciated and sinks from exhaustion. Pregnant women are
liable to abortion, and the living infants of women suffering from
tremor have also exhibited tremor of the limbs.

[917] A case of mercurial tremor (in _Bericht. des K. K. Allgem.
Krankenhauses zu Wien im Jahre 1872_, Wien, 1873) is interesting, as
showing the influence of pregnancy. A woman, twenty years of age,
employed in making barometers, had, in 1869, mercurial tremor and
salivation. During a three months’ pregnancy the tremor ceased, but
again appeared after she had aborted. She again became pregnant, and the
tremor ceased until after her confinement in November 1871. The tremor
was so violent that the patient could not walk; she also had stomatitis;
but ultimately, by treatment with galvanism and other remedies, she
recovered.

In the case of the “mass poisoning” on board the “Triumph,” it has been
mentioned that several of the sailors became consumptive, and the same
effect has been noticed among all workers in the metal; it is now,
indeed, an accepted fact that the cachexia induced by mercurialismus
produces a weak habit of body specially liable to the tuberculous
infection.

The course of the poisoning is generally more rapid when it has
resulted from the taking of mercury internally as a medicine than when
inhaled by workers in the metal, _e.g._, a patient suffering from
mercurial tremor shown to the Medical Society by Mr. Spencer Watson in
1872, had resisted for seven years the influence of the fumes of
mercury; and then succumbed, exhibiting the usual symptoms. Idiosyncrasy
plays a considerable _rôle_; some persons (and especially those whose
kidneys are diseased) bear small doses of mercury ill, and are readily
salivated or affected; this is evidently due to imperfect elimination.

§ 841. =Mercuric Methide=, Hg(CH₃)₂.--This compound is obtained by the
action of methyl iodide on sodium amalgam in the presence of acetic
ether. It is a dense, stable liquid, of highly poisonous properties. In
1865, mercuric methide, in course of preparation in a London laboratory,
caused two cases of very serious slow poisoning.[918] One was that of a
German, aged 30, who was engaged in preparing this compound for three
months, and during this time his sight and hearing became impaired; he
was very weak, his gums were sore, and he was ultimately admitted into
St. Bartholomew’s Hospital, February 3rd, 1865. His urine was found to
be albuminous, and his mental faculties very torpid. On the 9th he
became noisy, and had to be put under mechanical restraint. On the 10th
he was semi-comatose, but there was no paralysis; his breath was very
offensive, his pupils dilated; at intervals he raised himself and
uttered incoherent howls. There was neither sensation nor motion in the
left leg, which was extended rigidly; the knee and the foot were turned
slightly inward. On the 14th he died insensible.

[918] _St. Barth. Hosp. Reports_, vol. i., 1866, p. 141.

The only appearance of note seen at the autopsy was a congestion of the
grey matter in the brain; the kidneys and liver were also congested, and
there were ecchymoses in the kidneys.

The second case--a young man, aged 23, working in the same
laboratory--was admitted into the hospital, March 28th, 1865. In the
previous January he had been exposed to the vapour of mercuric methide
for about a fortnight; during the illness of the other assistant he felt
ill and weak, and complained of soreness of the gums and looseness of
the teeth. He had also dimness of vision, pain and redness of the eyes,
giddiness, nausea and vomiting, the ejected matters being greenish and
watery. At the beginning of March his sight and taste became
imperfect--all things tasted alike; his tongue was numb and his gums
sore, he was also salivated slightly. A week before admission he lost
his hearing, and first his hands and then his feet became numb; on
admission his breath was very offensive, his pupils dilated; the sight
impaired; he was very deaf, and his powers of speech, taste, and smell
were deficient. There was anæsthesia of the body, and the movement of
the limbs was sluggish and difficult. He continued in the hospital for
nearly a month, with but little change. On April 24th, it was noticed
that he was getting thinner and slightly jaundiced; he moved his arms
aimlessly in an idiotic manner, and passed his urine involuntarily. On
April 27th he was more restless, and even violent, shrieking out and
making a loud, incoherent noise, or laughing foolishly; he passed his
motions and urine beneath him. On July 7th he was in a similar
state--perfectly idiotic. He died on April 7th, 1866, about a year and
three months from his first exposure to the vapour; the immediate cause
of death was pneumonia. The _post-mortem_ appearances of the brain and
membranes differed little from the normal state; the grey matter was
pink, but otherwise healthy; there was a considerable amount of
cerebro-spinal fluid; the arachnoid along the longitudinal fissure was
thickened; the total weight of the brain with medulla was 41 ozs. The
stomach was of enormous size; the pyramids of the kidneys were
congested, as was also the small intestine; the lungs showed the usual
signs of pneumonia.[919]

[919] _St. Barth. Hosp. Reports_, vol. ii. p. 211.

§ 842. =Effects of the Corrosive Salts of Mercury.=--The type of the
corrosive salts is mercuric chloride, or corrosive sublimate--a compound
which acts violently when administered, either externally or internally,
in large doses.[920] If the poison has been swallowed, the symptoms come
on almost immediately, and always within the first half hour; the whole
duration also is rapid. In 36 cases collected by F. A. Falck, 11 died on
the first or second day, and 11 on the fifth day; so that 61 per cent.
died in five days--the remainder lived from six to twenty-six days. The
shortest fatal case on record is one communicated to Dr. Taylor by Mr.
Welch; in this instance the man died from an unknown quantity within
half an hour.

[920] The effects on animals are similar to those on man. Richard Mead
gave a dog with bread 3·8 grms. (60 grains) of corrosive
sublimate:--“Within a quarter of an hour he fell into terrible
convulsions, casting up frequently a viscid frothy mucus, every time
more and more bloody, till, tired and spent with this hard service, he
lay down quietly, as it were, to sleep, but died the next morning.”

In the very act of swallowing, a strong metallic taste and a painful
sensation of constriction in the throat are experienced. There is a
burning heat in the throat extending downwards to the stomach. All the
mucous membranes with which the solution comes in contact are attacked,
shrivelled, and whitened; so that, on looking into the mouth, the
appearance has been described as similar to that produced by the recent
application of silver nitrate. The local changes may be so intense as to
cause œdema of the glottis, and death through asphyxia. In a few minutes
violent pain is felt in the stomach; so much so, that the sufferer is
drawn together, and is in a fainting condition; but there are rare cases
in which pain has been absent. There are nausea and vomiting, the
ejected matters being often streaked with blood; after the vomiting
there is purging; here also the motions are frequently bloody.[921] The
temperature of the body sinks, the respiration is difficult, and the
pulse small, frequent, and irregular. The urine is generally scanty, and
sometimes completely suppressed.[922] Sometimes there is profuse
hæmorrhage from the bowel, stomach, or other mucous membrane, and such
cases are accompanied by a considerable diminution of temperature. In a
case recorded by Lœwy,[923] after a loss of blood by vomiting and
diarrhœa, the temperature sank to 33·4°. The patient dies in a state of
collapse, or insensibility, and death is often preceded by convulsions.

[921] The mixture of blood with the evacuations is more constantly
observed in poisoning by corrosive sublimate than in poisoning by
arsenic, copper, or lead.

[922] In a case recorded by Dr. Wegeler (Casper’s _Wochenschrift_,
January 10, 1846, p. 30), a youth, aged 17, swallowed 11·6 grms. (3
drachms) of the poison. No pain was experienced on pressure of the
abdomen; he died on the sixth day, and during the last three days of
life no urine was secreted.

[923] _Vierteljahrsschr. für ger. Med._, 1864, vol. i. p. 187.

§ 843. Two remarkable cases of death from the external use of corrosive
sublimate are recorded by Anderseck. An ointment, containing corrosive
sublimate, was rubbed into the skin of two girls, servants, in order to
cure the itch. The one, during the inunction, complained of a burning of
the skin; the other also, a little while after, suffered in the same
way. During the night the skin of each swelled, reddened, and became
acutely painful. There were thirst and vomiting, but no diarrhœa, On the
following day there was an eruption of blebs or little blisters. On the
third day they had diarrhœa, tenesmus, fever, and diminution of the
renal secretion; on the fourth day, fœtid breath, stomatitis,
hyperæsthesia of the body, and a feeling of “pins and needles” in the
hands and feet were noted. The first girl died in the middle of the
fifth day, fully conscious; the other died on the sixth. So also
Taylor[924] gives the case of a girl, aged 9, who died from the effects
of an alcoholic solution of corrosive sublimate (strength, 80 grains to
the oz.) applied to the scalp as a remedy for ringworm. The same
author[925] further quotes the case of two brothers who died--the one on
the fifth, the other on the eleventh day--from the effects of absorbing
corrosive sublimate through the unbroken skin.

[924] _Op. cit._

[925] _Poisons_, 1848, p. 394.

§ 844. =The Nitrates of Mercury= are poisons, but little (if at all)
inferior in corrosive action to mercuric chloride. Death has resulted
from both the external and internal use. Application of the nitrate as
an escharotic to the _os uteri_, in one case,[926] produced all the
symptoms of mercurial poisoning, but the woman recovered; in another
case,[927] its use as a liniment caused death.

[926] _Med. Gazette_, vol. 45, p. 1025.

[927] _Edin. Monthly Journal_, 1864, p. 167.

§ 845. When taken internally, the symptoms are scarcely different from
those produced by corrosive sublimate. It seems an unlikely vehicle for
criminal poisoning, yet, in the case of _Reg._ v. _E. Smith_ (Leicester
Summer Assizes, 1857), a girl was proved to have put a solution of
nitrate of mercury in some chamomile tea, which had been prescribed for
the prosecutrix. The nauseous taste prevented a fatal dose being taken;
but the symptoms were serious.

§ 846. =Mercuric Cyanide= acts in a manner very similar to that of
corrosive sublimate, 1·3 grm. (about 20 grains) in one case,[928] and in
another[929] half the quantity, having destroyed life.

[928] Orfila, i. p. 735.

[929] Christison, p. 427.

§ 847. =White Precipitate= (ammoniated mercury), as a poison, is weak.
Out of fourteen cases collected by Taylor, two only proved fatal; one of
these formed the subject of a trial for murder, _Reg._ v. _Moore_ (Lewes
Lent Assizes, 1860). The effects produced are vomiting, purging, &c., as
in corrosive sublimate.[930] Other preparations of mercury, such as the
red iodide, the persulphide, and even calomel,[931] have all a more or
less intense poisonous action, and have caused serious symptoms and
death.

[930] See Dr. Th. Stevenson, “Poisoning by White Precipitate,” _Guy’s
Hospital Reports_, vol. xix. p. 415.

[931] Seidel quotes a case from Hasselt, in which a father, for the
purpose of obtaining insurance money, killed his child by calomel.

§ 848. =Treatment of Acute and Chronic Poisoning.=--In acute poisoning,
vomiting usually throws off some of the poison, if it has been
swallowed; and the best treatment seems to be, to give copious
albuminous drinks, such, for example, as the whites of eggs in water,
milk, and the like. The vomiting may be encouraged by subcutaneous
injections of apomorphine. The after-treatment should be directed to
eliminating the poison, which is most safely effected by very copious
drinks of distilled water (see “Appendix”).

The treatment of slow poisoning is mainly symptomatic; medicinal doses
of zinc phosphide seem to have done good in mercurial tremors. Potassic
iodide is also supposed to assist the elimination of mercury.

§ 849. =Post-mortem Appearances.=--The pathological effects seen after
chronic poisoning are too various to be distinctive. In the museum of
the Royal College of Surgeons there is (No. 2559) the portion of a colon
derived from a lady aged 74.[932] This lady had been accustomed for
forty-three years to take a grain of calomel every night; for many years
she did not suffer in health, but ultimately she became emaciated and
cachectic, with anasarca and albuminuria. The kidneys were found to be
granular, and the mucous membrane of a great part of the intestine of a
remarkable black colour, mottled with patches of a lighter hue,
presenting somewhat the appearance of a toad’s back. From the portion of
colon preserved mercury was readily obtained by means of Reinsch’s
test. The black deposit is in the submucosa, and it is, without doubt,
mercurial, and probably mercury sulphide. In acute poisoning (especially
by the corrosive salts) the changes are great and striking. After rapid
death from corrosive sublimate, the escharotic whitening of the mouth,
throat, and gullet, already described, will be seen. The mucous membrane
right throughout, from mouth to anus, is more or less affected and
destroyed, according to the dose and concentration of the poison. The
usual appearances in the stomach are those of intense congestion, with
ecchymoses, and portions of it may be destroyed. Sometimes the coats are
very much blackened; this is probably due to a coating of sulphide of
mercury.

[932] _Path. Soc. Trans._, xviii. 111.

    In St. George’s Hospital Museum (Ser. ix. 43, y. 337) there is a
    stomach, rather large, with thickened mucous coats, and having on
    the mucous surface a series of parallel black, or black-brown lines
    of deposit; it was derived from a patient who died from taking
    corrosive sublimate. With the severe changes mentioned, perforation
    is rare.[933] In the intestines there are found hyperæmia,
    extravasations, loosening of the mucous membrane, and other changes.
    The action is particularly intense about the cæcum and sigmoid
    flexure; in one case,[934] indeed, there was little inflammatory
    redness of the stomach or of the greater portion of the intestine,
    but the whole surface of the cæcum was of a deep black-red colour,
    and there were patches of sloughing in the coats. The kidneys are
    often swollen, congested, or inflamed; changes in the respiratory
    organs are not constantly seen, but in a majority of the cases there
    have been redness and swelling of the larynx, trachea, and bronchi,
    and sometimes hepatisation of smaller or larger portions of the
    lung.

[933] There is only one case of perforation on record.

[934] _Lancet_, 1845, p. 700.

    In St. George’s Hospital Museum, there are (from a patient dying in
    the hospital) preparations which well illustrate what pathological
    changes may be expected in any case surviving for a few days. The
    patient was Francis L----, aged 45, admitted to the hospital,
    February 27, 1842. He took a quantity of corrosive sublimate spread
    on bread and butter, was immediately sick, and was unable to take as
    much as he had intended. The stomach-pump and other remedies were
    used. On the following day his mouth was sore, and on March 1st his
    vision was dim; his mouth was drawn over to the right side, and he
    lost power over the left eyelid, but he had no pain; he passed some
    blood from the bowel. On the 2nd he passed much blood, and was
    salivated; still no pain. On March 4, on the evening of the sixth
    day, he expired; he was drowsy during the last day, and passed
    watery evacuations.

    Prep. 14a, Ser. ix., shows the pharynx, œsophagus, and tongue; there
    is ulceration of the tonsils, and fibrinous exudation on the gullet.
    The stomach (43b, 199) shows a large dark slough, three inches from
    the cardiac extremity; the margin surrounding the slough is
    thickened, ulcerated, and irregular in shape, the submucous tissue,
    to some extent, being also thickened; there is fibrine in the ileum,
    pharynx, and part of the larynx. The action extended to the whole
    intestine, the rectum in prep. 145a, 36, is seen to be thickened,
    and has numerous patches of effused fibrine.

It is a curious fact that the external application of corrosive
sublimate causes inflammatory changes in the alimentary canal of nearly
the same intensity as if the poison had been swallowed. Thus, in the
case of the two girls mentioned _ante_ (p. 647), there was found an
intense inflammation of the stomach and intestines, the mucous tissues
being scarlet-red, swollen, and with numerous extravasations.

§ 850. The effects of the nitrate of mercury are similar to the
preceding; in the few cases which have been recorded, there has been
intense redness, and inflammation of the stomach and intestines, with
patches of ecchymosis. White precipitate, cyanide of mercury, mercuric
iodide, and mercurous sulphide (turpeth-mineral) have all caused
inflammation, more or less intense, of the intestinal tract.

§ 851. =Elimination of Mercury.=--The question of the channels by which
mercury is eliminated is of the first importance. It would appear
certain that it can exist in the body for some time in an inactive
state, and then, from some change, be carried into the circulation and
show its effects.[935] Voit considers that mercury combines with the
albuminous bodies, separating upon their oxidation, and then becoming
free and active.[936]

[935] Tuson gave a mare, first, 4 grains, and afterwards 5 grains of
corrosive sublimate twice a day; at the end of fourteen days, in a pint
of urine no mercury was detected, but at the end of three weeks it was
found.

[936] _Voit, Physiol. chem. Unters._, Augsburg, 1857.

Ullmann[937] found most mercury in the following order:--Kidneys, liver,
spleen, a small quantity in the stomach, no mercury in the small
intestine, but some in the large intestine; small weighable quantities
in the heart and skeletal muscles, also in the lungs; but no mercury,
when the dose was small, in brain, the salivary glands, abdominal
glands, thyroid glands, the bile, or the bones.

[937] _Chem. Centr._, 1892, ii. 941.

The main channel by which absorbed mercury passes out of the body is the
kidneys, whilst mercurial compounds of small solubility are in great
part excreted by the bowel. A. Bynssen,[938] after experimenting with
mercuric chloride (giving ·015 to ·15 grm., with a little morphine
hydrochlorate), came to the conclusion that it could be detected in the
urine about two hours, and in the saliva about four hours, after its
administration; he considered that the elimination was finished in
twenty-four hours.

[938] _Journal de l’Anat. et de Physiol._, 1872, No. 5, p. 500. On the
separation of mercury by the urine, see also Salkowsky in Virchow’s
_Archiv_, 1866.

From the body of a hound that, in the course of thirty-one days, took
2·789 grms. of calomel (2·368 Hg) in eighty-seven doses, about 94 per
cent. of the substance was recovered on analysis:--

                                                 Mercurous
                                                 Sulphide.
                                                   Grms.
  In the fæces,                                   2·1175
    „    urine,                                   0·0550
    „    brain, heart, lungs, spleen, pancreas,
         kidneys, scrotum, and penis,             0·0090
    „    liver,                                   0·0140
    „    muscles,                                 0·0114
                                                  ------
                                                  2·2069

This equals 1·9 of metallic mercury.[939] Thus, of the whole 2·2 grms.
of mercuric sulphide separated, over 95 per cent. was obtained from the
fæces.

[939] Riederer, in Buchner’s _Neues Repert. f. Pharm._, Bd. xvii. 3,
257, 1868.

This case is of considerable interest, for there are recorded in
toxicological treatises a few cases of undoubted mercurial poisoning in
which no poison had been detected, although there was ample evidence
that it had been administered by the mouth. In such cases, it is
probable that the whole length of the intestinal canal had not been
examined, and the analysis failed from this cause. When (as not
unfrequently happens) the mercurial poison has entered by the skin, it
is evident that the most likely localities are the urine, the liver, and
the kidneys.[940]

[940] A woman died from the effects of a corrosive sublimate lotion
applied by a quack to a wound in her leg. The writer found no poison in
the stomach, but separated a milligramme of metallic mercury from the
liver; the urine and intestines were not sent.

In a case related by Vidal,[941] the _Liquor Bellostii_ (or solution of
mercuric nitrate) was ordered by mistake instead of a liniment. Although
externally applied, it caused salivation, profuse diarrhœa, and death in
nine days. The whole of the intestinal tract was found inflamed with
extravasations, and mercury detected in the liver.

[941] _Gaz. des Hôp._, Juillet 1864.

In any case of external application, if death ensues directly from the
poison, evidence of its presence will probably be found; but too much
stress must not be laid upon the detection of mercury, for, as Dr.
Taylor says, “Nothing is more common than to discover traces of mercury
in the stomach, bowels, liver, kidneys, or other organs of a dead
body.”[942]

[942] Taylor, _Medical Jurisprudence_, i. p. 288.

§ 852. =Tests for Mercury.=--Mercury, in combination and in the solid
form, is most readily detected by mixing the substance intimately with
dry anhydrous sodic carbonate, transferring the mixture to a glass tube,
sealed at one end, and applying heat. If mercury be present, a ring of
minute globules condenses in the cool part of the tube. If the quantity
of mercury is likely to be very minute, it is best to modify the process
by using a subliming cell (p. 258), and thus obtain the sublimate on a
circle of thin glass in a convenient form for microscopical examination.
If there is any doubt whether the globules are those of mercury or not,
this may be resolved by putting a fragment of iodine on the lower disc
of the subliming cell, and then completing it by the disc which contains
the sublimate (of course, the supposed mercurial surface must be
undermost); on placing the cell in a warm, light place, after a time the
scarlet iodide is formed, and the identification is complete. Similarly,
a glass tube containing an ill-defined metallic ring of mercury can be
sealed or corked up with a crystal of iodine, and, after a few hours,
the yellow iodide, changing to scarlet, will become apparent. There are
few (if any) tests of greater delicacy than this.

Mercury in solution can be withdrawn by acidulating the liquid, and then
inserting either simply a piece of gold foil, gold wire, or bright
copper foil; or else, by a galvanic arrangement, such as iron wire wound
round a gold coin, or gold foil attached to a rod of zinc; or, lastly,
by the aid of gold or copper electrodes in connection with a battery. By
any of these methods, mercury is obtained in the metallic state, and the
metal with its film can be placed in a subliming cell, and globules
deposited and identified, as before described.

The =Precipitating Reagents= for mercury are numerous: a solution of
stannous chloride, heated with a solution of mercury, or any
combination, whether soluble or insoluble, reduces it to the metallic
state.

=Mercurous Salts= in solution yield, with potash, soda, or lime, a black
precipitate of mercurous oxide. =Mercuric Salts=, a bright yellow
precipitate of mercuric oxide.

=Mercurous Salts= yield black precipitates, with sulphides of ammonium
and hydrogen. =Mercuric Salts= give a similar reaction, but, with
sulphuretted hydrogen, first a whitish precipitate, passing slowly
through red to black.

=Mercurous Salts=, with solutions of the chlorides, give a white
precipitate of calomel; the =Mercuric Salts= yield no precipitate under
similar circumstances. =Mercurous Salts=, treated with iodide of
potassium, give a green mercurous iodide; =Mercuric=, a scarlet.

§ 853. =The Detection of Mercury in Organic Substances and
Fluids.=--Ludwig’s process, previously described, is found in practice
the best. Fluids, such as urine, must be evaporated to dryness, and then
treated with hydrochloric acid. Such organs as the liver are cut up and
boiled in 20 per cent. HCl. Distinct evidence of mercury in the liver
has been obtained on a piece of copper gauze, in a case where a child
had been given 2 grains of calomel before death. “Four ounces of the
liver were treated with hydrochloric acid and water, and a small piece
of pure copper placed in the acid liquid while warm, and kept there for
about forty-eight hours. It acquired a slight silvery lustre, and
globules of mercury were obtained from it by sublimation.”

To detect the cyanide of mercury may require special treatment, and
Vitali[943] recommends the following process:--The fluid is acidified
with tartaric acid and neutralised by freshly precipitated CaCO₃; a
slight excess of hydric sulphide is added, and the flask allowed to rest
for twenty-four hours in the cold. Then a further quantity of SH₂ is
added, and a current of hydrogen passed through the liquid; the effluent
gas is first made to bubble through a solution of bismuth nitrate in
dilute nitric acid (for the purpose of absorbing SH₂), and then through
aqueous potash (to absorb HCl); in the first flask the analyst will
separate and identify mercury sulphide, while in the last flask there
will be potassic cyanide, which will respond to the usual tests.

[943] _L’Orosi_, xii. 181-196.

In those cases where no special search is made for mercury, but an acid
(hydrochloric) solution is treated with sulphuretted hydrogen, mercury
is indicated by the presence of a black precipitate, which does not
dissolve in warm nitric acid.

The further treatment of the black sulphide may be undertaken in two
ways:--

(1) It is collected on a porcelain dish, with the addition of a little
nitric acid, and evaporated to dryness in order to destroy organic
matter. Hydrochloric and a few drops of nitric acid are next added; the
action is aided by a gentle heat, the solution finally evaporated to
dryness on the water-bath, and the residue taken up by warm distilled
water. The solution is that of a persalt of mercury, and the mercury can
be separated by electrolysis, or indicated by the tests already
detailed.

(2) The other method, and the most satisfactory, is to mix the sulphide
while moist with dry carbonate of soda, make it into a pellet which will
easily enter a reducing or subliming tube, dry it carefully, and obtain
a sublimate of metallic mercury.

A neat method of recognising mercury when deposited as a film on copper
has been proposed by E. Brugnatelli:[944] the copper, after being
washed, is transferred to a glass vessel, and a porcelain lid, on which
a drop of gold chloride solution has been placed, adjusted over the
dish. The whole is heated by a water-bath. The mercury vapour reduces
the gold chloride, and gold is deposited as a bluish-violet stain; 1/10
mgrm. mercury may by this test be identified.

[944] _Gazzetta_, xix. 418-422.

Of special methods for the separation and detection of mercury,
Ludwig’s[945] is, without a doubt, the best when organic matters have to
be dealt with; the finely divided solid substances are boiled for some
hours with hydrochloric acid, strength 20 per cent.; then the liquid is
cooled to 60°, and potassic chlorate added in half gramme quantities
until the dark liquid becomes clear; the liquid is cooled and filtered,
and the substances on the filter washed with water. To the filtrate 5
grms. of zinc dust are added, and the liquid is violently shaken from
time to time; a second portion is afterwards added, and also vigorously
shaken. After some hours the clear liquid is separated from the zinc and
the zinc washed, first with water, then with a little soda solution, and
finally, again with water. The zinc is now collected on a glass-wool
filter, treated with absolute alcohol to remove water, and dried by
suction in a stream of air. The zinc is put into a combustion-tube, the
tube being drawn out into a thin capillary extremity, and a combustion
made, the mercury collecting at the capillary part. It is a necessary
refinement, should the zinc be contaminated with a trace of organic
matter, to pack the combustion-tube as follows:--First, the zinc dust on
which any mercury present has been deposited, then a plug of asbestos;
next, some cupric oxide; and lastly, some pure zinc dust.
Bondzynski[946] prefers to use copper rather than zinc; for he says that
zinc so frequently contains cadmium, which latter metal also gives a
mirror, so that, unless the mercury is afterwards identified by turning
it into an iodide, error may be caused.

[945] _Zeit. f. physiolog. Chemie_, 1882, i. 495; _Chem. Centrblt._,
1892, ii. 941.

[946] _Zeit. f. anal. Chem._, xxxii. 302-305.

[Illustration]

§ 854. =Estimation of Mercury.=--All pharmaceutical substances
containing mercury, as well as the sulphide prepared in the wet way, and
minerals, are best dealt with by obtaining and weighing the metal in the
solid state. The assay is very simple and easy when carried out on the
method that was first, perhaps, proposed by Domeyko. A glass tube (which
should not be too thin), closed at one end, is bent, as shown in the
figure, the diameter should be about three lines, the length from 7 to 8
inches, the shorter arm not exceeding 2 inches. The powdered substance
is mixed with two or three times its weight of litharge, and introduced
into the tube at _a_. The portion of the tube containing the mercury is
at first heated gently, but finally brought to a temperature sufficient
to fuse the substance and soften the glass. The mercury collects in an
annular film at _b_ in the cooler limb, and may now, with a little
management of the lamp, be concentrated in a well-defined ring; the
portion of the tube containing this ring is cut off, weighed, then
cleansed from mercury, and reweighed. Many of the pharmaceutical
preparations do not require litharge, which is specially adapted for
ores, and heating with sodic carbonate (in great excess) will suffice.
Mercury mixed with organic matter must be first separated as described,
by copper or gold, the silvered foil rolled up, dried, introduced into
the bent tube, and simply heated without admixture with any substance;
the weight may be obtained either by weighing the foil before and after
the operation, or as above.

§ 855. =Volumetric Processes for the Estimation of Mercury.=--When a
great number of mercurial preparations are to be examined, a volumetric
process is extremely convenient. There are several of these processes,
some adapted more particularly for mercuric, and others for mercurous
compounds. For mercuric, the method of Personne[947] is the best. The
conversion of the various forms of mercury into corrosive sublimate may
be effected by evaporation with aqua regia, care being taken that the
bath shall not be at a boiling temperature, or there will be a slight
loss.

[947] _Comptes Rendus_, lvi. 68; Sutton’s _Vol. Anal._, 177.

Personne prefers to heat with caustic soda or potash, and then pass
chlorine gas into the mixture; the excess of chlorine is expelled by
boiling, mercuric chloride in presence of an alkaline chloride not being
volatilised at 100°. The standard solutions required for this process
are:--

(1) 33·2 grms. of potassic iodide in 1 litre of water, 1 c.c. = 0·01
grm. Hg, or 0·01355 grm. HgCl₂.

(2) A solution of mercuric chloride containing 13·55 grms. to the litre,
1 c.c. = 0·1 grm. Hg.

The process is founded on the fact that, if a solution of mercuric
chloride be added to one of potassic iodide, in the proportion of one of
the former to four of the latter, mercuric iodide is formed, and
immediately dissolved, until the balance is overstepped, when the red
colour is developed; the final reaction is very sharp, and with
solutions properly made is very accurate. The mercuric solution must
always be added to the alkaline iodide; a reversal of the process does
not answer. It therefore follows that the solution to be tested must be
made up to a definite bulk, and added to a known quantity of the
potassic iodide until the red colour appears.

=Mercurous Salts= may be titrated with great accuracy by a decinormal
solution of sodic chloride. This is added to the cold solution in very
slight excess, the calomel filtered off, the filtrate neutralised by
pure carbonate of soda, and the amount of sodic chloride still unused
found by titration with nitrate of silver, the end reaction being
indicated by chromate of potash. Several other volumetric processes are
fully described in works treating upon this branch of analysis.


III.--PRECIPITATED BY HYDRIC SULPHIDE FROM A NEUTRAL SOLUTION.

Zinc--Nickel--Cobalt.


1. ZINC.

§ 856. =Zinc=--At. wt., 65; specific gravity, 6·8 to 7·1; fusing-point,
412° (773° F.)--is a hard, bluish-white, brittle metal, with a
crystalline fracture. Between 100° and 150° it becomes ductile, and may
be easily wrought, but at a little higher temperature it again becomes
brittle, and at a bright red heat it fuses, and then volatilises, the
fumes taking fire when exposed to the air. In analysis, zinc occurs
either as a metallic deposit on a platinum foil or dish, or as a brittle
bead, obtained by reducing a zinc compound with soda on charcoal.

The salts of zinc to be briefly described here are the carbonate, the
oxide, and the sulphide,--all of which are likely to occur in the
separation and estimation of zinc, and the sulphate and chloride,--salts
more especially found in commerce, and causing accidents from time to
time.

§ 857. =Carbonate of Zinc=, in the native form of calamine, contains, as
is well known, 64·8 per cent. of oxide of zinc; but the carbonate
obtained in the course of an analysis by precipitating the neutral hot
solution of a soluble salt of zinc by carbonate of potash or soda, is
carbonate of zinc _plus_ a variable quantity of hydrated oxide of zinc.
Unless the precipitation takes place at a boiling temperature, the
carbonic anhydride retains a portion of the oxide of zinc in solution.
By ignition of the carbonate, oxide of zinc results.

§ 858. =Oxide of Zinc= (ZnO = 81; specific gravity, 5·612; Zn, 80·24, O,
19·76) is a white powder when cool, yellow when hot. If mixed with
sufficient powdered sulphur, and ignited in a stream of hydrogen, the
sulphide is produced; if ignited in the pure state in a rapid stream of
hydrogen gas, metallic zinc is obtained; but, if it is only a feeble
current, the oxide of zinc becomes crystalline, a portion only being
reduced.

§ 859. =Sulphide of Zinc= (ZnS = 97; specific gravity, 4·1; Zn, 67·01,
S, 32·99).--The sulphide obtained by treating a neutral solution of a
soluble salt of zinc by hydric sulphide is hydrated sulphide, insoluble
in water, caustic alkalies, and alkaline sulphides, but dissolving
completely in nitric or in hydrochloric acid. When dry, it is a white
powder, and if ignited contains some oxide of zinc. The anhydrous
sulphide is produced by mixing the precipitated sulphide with sulphur,
and igniting in a crucible in a stream of hydrogen gas.

=Pharmaceutical Preparations.=--The officinal compounds of zinc used in
medicine are the _acetate_, _carbonate_, _chloride_, _oxide_,
_sulphate_, _sulphocarbolate_, and _valerianate_.

=Sulphate of Zinc= (ZnSO₄7H₂O 161 + 126; specific gravity, crystals,
1·931).--This salt is officinal in all the pharmacopœias, is used in
calico-printing, and is commonly known as _white vitriol_. By varying
the temperature at which the crystals are allowed to be formed, it may
be obtained with 6, 5, 2, or 1 atoms of water. The commercial sulphate
is in crystals exactly similar to those of Epsom salts; it is slightly
efflorescent, and gives the reactions of zinc and sulphuric acid.

§ 860. =Chloride of Zinc= is obtained by dissolving zinc in hydrochloric
acid, or by direct union of zinc and chlorine. Chloride of zinc is the
only constituent in the well-known “Burnett’s disinfectant fluid.” A
solution of chloride of zinc may be heated until it becomes water-free;
when this takes place it still remains fluid, and makes a convenient
bath, for warmth may be applied to it above 370° without its emitting
fumes to inconvenience; at a red heat it distils. A concentrated
solution of zinco-ammonic chloride (2H₄NClZnCl₂) is used for the purpose
of removing the film of oxide from various metals preparatory to
soldering.

§ 861. =Zinc in the Arts.=--The use of zinc as a metal in sheeting
cisterns, articles for domestic use, alloys, &c., is well known; oxide
of zinc enters largely into the composition of india-rubber. Sulphide of
zinc has been employed as a substitute for white lead, and may possibly
supersede it. Zinc white is further employed as a pigment, and, mixed
with albumen, is an agent in calico-printing; it is also used in the
decoloration of glass, in the polishing of optical glasses, and in the
manufacture of artificial meerschaum pipes.[948]

[948] Artificial meerschaum pipes are composed of zinc white, magnesia
usta, and caseine ammonium.

=Chromate of Zinc= (ZnCrO₄) is used in calico-printing, and there is
also in commerce a basic chromate known as _zinc yellow_. Zinc green, or
Rinman’s green, is a beautiful innocuous colour, formed by igniting a
mixture of dry zincic and cobaltous carbonates.

The use of zinc vessels in the preparation of foods may occasionally
bring the metal under the notice of the analyst. When exposed to a moist
atmosphere, zinc becomes covered with a thin film of oxide, perfectly
insoluble in ordinary water; but, if the water should be charged with
common salt, a considerable quantity may be dissolved. It may generally
be laid down as a rule that the solvent power of water on zinc has a
direct relation to the chlorides present, whilst carbonate of lime
greatly diminishes this solubility.[949]

[949] Ziurek, indeed, found in a litre of water contained in a zinc
cistern no less than 1·0104 grm. of zinc, and the same water showed only
0·074 grm. of common salt to the litre.--_Vierteljahrsschr. für gericht.
Medicin_, 1867, Bd. 6, p. 356.

Milk may become contaminated by zinc; for, it is a matter of common
knowledge, that milk contained in zinc vessels does not readily turn
sour. This may be explained by the zinc oxide combining with the lactic
acid, and forming the sparingly soluble lactate of zinc 2(C₃H₅O₃)Zn +
3H₂O, thus withdrawing the lactic acid as fast as it is formed,
preventing the coagulation of the casein. With regard to this important
practical subject, MM. Payne and Chevallier made several experiments on
the action of brandy, wine, vinegar, olive oil, soup, milk, &c., and
proved that zinc is acted on by all these, and especially by alcoholic,
acetic, and saline liquids. M. Schaufféle has repeated these
experiments, and determined the amount of zinc dissolved in fifteen
days by different liquids from a galvanised iron as well as a zinc
vessel.

The amount found was as follows:--

                                         The liquid from
                     The liquid from     the galvanised
                     the zinc vessel,     iron vessel,
                     grms. per litre.    grms. per litre.
  Brandy,                 0·95                0·70
  Wine,                   3·95                4·10
  Orange-flower water,    0·50                0·75
  Vinegar,               31·75               60·75
  Fatty soup,             0·46                1·00
  Weak soup,              0·86                1·76
  Milk,                   5·13                7·00
  Salt water,             1·75                0·40
  Seltzer water,          0·35                0·30
  Distilled water,       traces.             traces.
  Ordinary water,        traces.             traces.
  Olive oil,             none.               none.

§ 862. =Effects of Zinc, as shown by Experiments on Animals.=--Harnack,
in experiments with sodium-zinc oxide pyrophosphate, has shown that the
essential action of zinc salts is to paralyse the muscles of the body
and the heart, and, by thus affecting the circulation and respiration,
to cause death; these main results have been fully confirmed by Blake,
Letheby, and C. Ph. Falck. For rabbits the lethal dose is ·08 to ·09
grm. of zinc oxide, or about ·04 per kilogrm. The temperature during
acute poisoning sinks notably--according to F. A. Falck’s researches on
rabbits, from about 7·3° to 13·0°. Zinc is eliminated mainly by the
urine, and has been recognised in that fluid four to five days after the
last dose. It has also been separated in small quantity from the milk
and the bile.

§ 863. =Effects of Zinc Compounds on Man=--(=a=) =Zinc Oxide=.--The
poisonous action of zinc oxide is so weak that it is almost doubtful
whether it should be considered a poison. Dr. Marcett has given a pound
(453·6 grms.) during a month in divided doses without injury to a
patient afflicted with epilepsy; and the workmen in zinc manufactories
cover themselves from head to foot with the dust without very apparent
bad effects. It is not, however, always innocuous, for Popoff has
recorded it as the cause of headache, pain in the head, cramps in the
calves of the legs, nausea, vomiting, and diarrhœa; and he also obtained
zinc from the urine of those suffering in this manner.[950] Again, a
pharmacy student[951] filled a laboratory with oxide of zinc vapour, and
suffered from well-marked and even serious poisonous symptoms,
consisting of pain in the head, vomiting, and a short fever. It must be
remembered that, as the ordinary zinc of commerce is seldom free from
arsenic, and some samples contain gallium, the presence of these metals
may possibly have a part in the production of the symptoms described.

[950] The so-called “zinc fever” has only been noticed in the founding
of brass; it is always preceded by well-marked shivering, the other
symptoms being similar to those described.

[951] Rust’s _Magazin_, Bd. xxi. § 563.

§ 864. (=b=) =Sulphate of Zinc.=--Sulphate of zinc has been very
frequently taken by accident or design, but death from it is rare. The
infrequency of fatal result is due, not to any inactivity of the salt,
but rather to its being almost always expelled by vomiting, which is so
constant and regular an effect, that in doses of 1·3 grm. (20 grains),
sulphate of zinc is often relied upon in poisoning from other substances
to quickly expel the contents of the stomach. In a case reported by Dr.
Gibb, an adult female swallowed 4·33 grms. (67 grains), but no vomiting
occurred, and it had to be induced by other emetics; this case is
unique. It is difficult to say what would be a fatal dose of zinc
sulphate, but the serious symptoms caused by 28 grms. (1 oz.) in the
case of a groom in the service of Dr. Mackenzie, leads to the view that,
although not fatal in that particular instance, it might be in others.
The man took it in mistake for Epsom salts: a few minutes after he was
violently sick and purged, and was excessively prostrated, so that he
had to be carried to his home; the following day he had cramps in the
legs, and felt weak, but was otherwise well.

In a criminal case related by Tardieu and Roussin, a large dose of zinc
sulphate, put into soup, caused the death of an adult woman of sixty
years of age in about thirty hours.[952] The symptoms were violent
purging and vomiting, leading to collapse. From half of the soup a
quantity of zinc oxide, equal to 1·6 grm. of zinc sulphate, was
separated. Zinc was also found in the stomach, liver, intestines, and
spleen--(see also a case of criminal poisoning recorded by
Chevallier).[953]

[952] Taylor notices this case, but adds that she died in three days.
This is a mistake, as the soup was taken on the 12th of June, probably
at mid-day, and the woman died on the 13th, at 8 P.M.

[953] “Observations toxicologiques sur le zinc,” _Annales d’Hygiène
Publique_, July 1878, p. 153.

§ 865. (=c=) =Zinc Chloride.=--Chloride of zinc is a powerful poison,
which may kill by its primary or secondary effects; its local action as
a caustic is mainly to be ascribed to its intense affinity for water,
dehydrating any tissue with which it comes in contact. The common use of
disinfecting fluids containing zinc chloride, such as Burnett’s fluid,
leads to more accidents in England than in any other European country.
Of twenty-six cases of poisoning by this agent, twenty-four occurred in
England, and only two on the Continent. Death may follow the external
use of zinc chloride. Some years ago, a quack at Barnstaple, Devon,
applied zinc chloride to a cancerous breast; the woman died with all
the general symptoms of poisoning by zinc, and that metal was found in
the liver and other organs.

The symptoms observed in fatal cases of chloride of zinc poisoning
are--immediate pain in the throat, and burning of the lips, tongue, &c.
There is difficulty in swallowing, an increase in the secretion of
saliva, vomiting of bloody matters, diarrhœa, collapse, coma, and death.
In some cases life has been prolonged for days; but, on the other hand,
death has been known to occur in a few hours. In those cases in which
either recovery has taken place, or in which death is delayed, nervous
symptoms rarely fail to make their appearance. In a case recorded by Dr.
R. Hassall, 3 ounces of Burnett’s fluid were swallowed. The usual
symptoms of intense gastro-intestinal irritation ensued, but there was
no purging until the third day; after the lapse of a fortnight, a train
of nervous symptoms set in, indicated by a complete perversion of taste
and smell. In other cases, aphonia, tetanic affections of groups of
muscles, with great muscular weakness and impairment of sight, have been
noticed. Very large doses of zinc chloride have been recovered from,
_e.g._, a man had taken a solution equivalent to about 13 grms. (200
grains) of the solid chloride. Vomiting came on immediately, and there
was collapse, but he recovered in sixteen days. On the other hand, ·38
grm. (6 grains) has destroyed life after several weeks’ illness.

§ 866. =Post-mortem Appearances.=--In poisoning by sulphate of zinc, the
appearances usually seen are inflammation, more or less intense, of the
mucous membrane of the stomach and bowels. In the museums of the London
hospitals, I could only find (1882) a single specimen preserved
illustrating the effects of this poison. This preparation is in St.
George’s Hospital Museum, and shows (ser. ix. 43 and 198) the stomach of
a man who died from zinc sulphate, and whose case is reported in the
_Lancet_, 1859. The mucous membrane is wrinkled all over like a piece of
tripe; when recent it was vascular and indurated, but uniformly of a
dirty grey colour; the lining membrane of the small intestine is very
vascular, and in the duodenum and upper part of the jejunum the colour
is similar to that of the stomach, but in a less marked degree; the
stomach and intestines are contracted.

The pathological appearances after chloride of zinc vary according to
the period at which death takes place. When it has occurred within a few
hours, the lining membrane of the mouth and gullet shows a marked change
in texture, being white and opaque, the stomach hard and leathery, or
much corrugated or ulcerated. In cases in which life has been prolonged,
contractions of the gullet and stomach may occur very similar to those
caused by the mineral acids, and with a similar train of symptoms. In a
case which occurred under Dr. Markham’s[954] observation, a person died
ten weeks after taking the fatal dose, the first symptoms subsiding in a
few days, and the secondary set of symptoms not commencing for three
weeks. They then consisted mainly of vomiting, until the patient sank
from exhaustion. The stomach was constricted at the pyloric end, so that
it would scarcely admit a quill.

[954] _Med. Times and Gazette_, June 11, 1859, p. 595.

In Guy’s Hospital there is a good preparation, 1799³⁵, from the case of
S. R., aged 22; she took a tablespoonful of Burnett’s fluid, and died in
about fourteen weeks. There were at first violent vomiting and purging,
but she suffered little pain, and in a day or two recovered sufficiently
to move about the house; but the vomiting after food continued,
everything being ejected about five minutes after swallowing. Before
death she suffered from pneumonia. The stomach is seen to be much
contracted--5 inches in length; it is ulcerated both near the pylorus
and near the gullet; at the latter part there is a pouch-like portion of
the mucous membrane of the stomach adherent to the spleen, which
communicates by a perforation with an abscess formed and bounded by the
stomach, diaphragm, and spleen; it contained 3 ozs. of dirty-looking
pus. At the pylorus, in the centre, there is a second perforation, but
extravasation of the contents is prevented by the adherent omentum and
transverse colon. The muscular coats are thickened.

§ 867. =Detection of Zinc in Organic Liquids or Solids.=--In cases where
the poison has been expelled from the stomach by vomiting, the muscles
and bones would appear to be the best tissues to examine chemically; for
Matzkewitsch investigated very carefully a dog poisoned by 100 parts of
zinc, subcutaneously injected in the form of acetate, and found it
distributed over the several organs of the body in the following
ratios:--Muscles 60·5, bones 24·41, stomach and intestines 4·63, skin
3·70, place of injection 2·19, liver 1·75, lungs and heart 1·68,
kidneys, bladder, and urine 1·14.

The only certain method of detection is to produce the sulphide of zinc,
best effected by saturating a neutral or feebly acid liquid with hydric
sulphide. If an organic liquid, which can be easily filtered, is
operated upon, it may be strongly acidulated with acetic acid, and at
once treated with hydric sulphide. If, however, zinc is sought for as a
part of a systematic examination (as will most likely be the case), the
solution will have been treated with hydrochloric acid, and already
tested for arsenic, antimony, lead, &c., and filtered from any
precipitate. In such a case the hydrochloric acid must first be replaced
by acetic, which is effected by adding a slight excess of sodic acetate;
the right quantity of the latter is easily known, if the hydrochloric
acid originally added was carefully measured, and its specific gravity
ascertained; 3·72 of crystallised sodic acetate saturating one of HCl.
Lastly, should the distillation process, given at p. 49, have been
adopted, the contents of the retort will only require to be treated
with water, filtered, and saturated with sulphuretted hydrogen. In any
of the above cases, should a white, dirty white or lightish-coloured
precipitate (which is not sulphur) be thrown down, zinc may be
suspected; it will, however, be absolutely necessary to identify the
sulphide, for there are many sources of error. The most satisfactory of
all identifications is the production of Rinman’s green. The supposed
sulphide is dissolved off the filter with hot nitric acid, a drop or
more (according to the quantity of the original precipitate) of solution
of cobalt nitrate added, the solution precipitated with carbonate of
soda and boiled, to expel all carbonic anhydride; the precipitate is
then collected on a filter, washed, dried, and ignited in a platinum
dish. If zinc be present in so small a proportion as 1·100,000 part, the
mass will be permanently green.

§ 868. Other methods of procedure are as follows:--The supposed zinc
sulphide (after being well washed) is collected in a porcelain dish, and
dissolved in a few drops of sulphuric acid, filtered, nitric acid added,
evaporated to dryness, and heated to destroy all organic matter. When
cool, the mass is treated with water acidulated by sulphuric acid, and
again filtered. The solution may contain iron as well as zinc, and if
the former (on testing a drop with ferrocyanide of potash) appears in
any quantity, it must be separated by the addition of ammonia in excess
to the ammoniacal filtrate; sodic carbonate is added in excess, the
liquid well boiled, and the precipitate collected on a filter and
washed. The carbonate of zinc thus obtained is converted into zinc oxide
by ignition, and weighed. If oxide of zinc, it will be yellow when hot,
white when cold: it will dissolve in acetic acid; give a white
precipitate with sulphuretted hydrogen; and, finally, if heated on
charcoal in the oxidising flame, and moistened with cobalt nitrate
solution, a green colour will result. Zinc may also be separated from
liquids by electrolysis. The simplest way is to place the fluid under
examination in a platinum dish of sufficient size, acidify, and insert a
piece of magnesium tape. The metallic film so obtained may be dissolved
by hydrochloric acid, and the usual tests applied.


2. NICKEL--COBALT.

§ 869. The salts of nickel and cobalt have at present no toxicological
importance, although, from the experiments of Anderson Stuart,[955] both
may be classed as poisonous. The experiments of Gmelin had, prior to
Stuart’s researches, shown that nickel sulphate introduced into the
stomach acted as an irritant poison, and, if introduced into the blood,
caused death by cardiac paralysis. Anderson Stuart, desiring to avoid
all local irritant action, dissolved nickel carbonate in acid citrate of
soda by the aid of a gentle heat; he then evaporated the solution, and
obtained a glass which, if too alkaline, was neutralised by citric acid,
until its reaction approximated to the feeble alkalinity of the blood;
the cobalt salt was produced in the same way. The animals experimented
on were frogs, fish, pigeons, rats, guinea-pigs, rabbits, cats, and
dogs--in all 200. The lethal dose of nickelous oxide, when
subcutaneously injected in the soluble compound described, was found to
be as follows:--frogs, ·08 grm. per kilogram; pigeons, ·06; guinea-pigs,
·030; rats, ·025; cats, ·01; rabbits, ·009; and dogs, ·007. The
cobaltous oxide was found to be much less active, requiring the above
doses to be increased about two-thirds. In other respects, its
physiological action seems to be very similar to that of nickelous
oxide.

[955] “Nickel and Cobalt; their Physiological Action on the Animal
Organism,” by T. P. Anderson Stuart, M.D., _Journ. of Anat. and
Physiol._, vol. xvii., Oct. 1882.

§ 870. =Symptoms--Frogs.=--A large dose injected into the dorsal lymph
sac of the frog causes the following symptoms:--The colour of the skin
all over the body becomes darker and more uniform, and not infrequently
a white froth is abundantly poured over the integument. In an interval
of about twenty minutes the frog sits quietly, the eyes retracted and
shut; if molested, it moves clumsily. When quiet, the fore limbs are
weak, and the hind legs drawn up very peculiarly, the thighs being
jammed up so against the body, that they come to lie on the dorsal
aspect of the sides of the frog, and the legs are so much flexed that
the feet lie on the animal’s back, quite internal to the plane of the
thighs. Soon fibrillary twitchings are observed in the muscles of the
abdominal wall, then feeble twitchings of the fingers, and muscles of
the fore limbs generally; lastly, the toes are seen to twitch, and then
the muscles of the hind limbs--this order is nearly always observed; now
spasmodic gaping and incoördinate movements are seen, and the general
aspect is not unlike the symptoms caused by picrotoxin. After this,
tetanus sets in, and the symptoms then resemble those of strychnine; the
next stage is stupefaction and voluntary motor paresis; the respiratory
movements become feeble, and the paresis passes into paralysis. The
heart beats more and more slowly and feebly, and death gradually and
imperceptibly supervenes. The _post-mortem_ appearances are well marked,
_i.e._, rigor mortis, slight congestion of the alimentary tract, the
heart with the auricle much dilated and filled with dark blood, the
ventricle mostly small, pale, and semi-contracted. For some time after
death, the nerve trunks and muscles react to the induction current.

=Pigeons.=--In experiments on pigeons the symptoms were those of dulness
and stupor, jerkings of different sets of muscles, and then death
quietly.

=Guinea-pigs.=--In guinea-pigs there were dulness and stupefaction, with
some weakness of the hind limbs.

=Rats.=--The symptoms in rats were almost entirely nervous; they became
drowsy and apathetic, and there was paralysis of the hind legs.

=Rabbits.=--In rabbits, also, the symptoms were mainly those caused by
an affection of the nervous system. There was paralysis, which affected
either the hind legs only, or all four limbs. The cervical muscles
became so weak that the animal was unable to hold its head up. Diarrhœa
occurred and persisted until death. If the dose is not large enough to
kill rapidly, the reflex irritability is decidedly increased, so that
the slightest excitation may cause the animal to cower and tremble all
over. Now appear twitchings and contractions of single groups of
muscles, and this excitement becomes general. The respirations also
become slower and more difficult, and sometimes there is well-marked
dilatation of the vessels of the ears and _fundi oculi_. Convulsions
close the scene.

§ 871. =Circulation.=--The effect of the salt on the frog’s heart was
also studied in detail. It seems that, under the influence of a soluble
salt of nickel, the heart beats more and more slowly, it becomes smaller
and paler, and does not contract evenly throughout the whole extent of
the ventricle; but the rhythm of the ventricular and auricular
contractions is never lost.

It is probable that there is a vaso-motor paralysis of the abdominal
vessels; the blood-pressure falls, and the heart is not stimulated by
the blood itself as in its normal state. In support of this view, it is
found that, by either pressing on the abdomen or simply inverting the
frog, the heart swells up, fills with blood, and for a time beats well.

=Nervous System.=--The toxic action is referable to the central nervous
system, and not to that of peripheral motor nerve-endings or motor
nerve-fibres. It is probable that both nickel and cobalt paralyse to
some extent the cerebrum. The action on the nerve-centres is similar to
that of platinum or barium, and quite different from that of iron.

§ 872. =Action on Striped Muscle.=--Neither nickel nor cobalt has any
effect on striped muscle. In this they both differ from arsenic,
antimony, mercury, lead, and iron--all of which, in large doses,
diminish the work which healthy muscle is capable of performing.

§ 873. =Separation of Nickel or Cobalt from the Organic Matters or
Tissues.=--It is very necessary, if any case of poisoning should occur
by either or both of these metals, to destroy completely the organic
matters by the process already detailed on p. 51. Both nickel and cobalt
are thrown down, if in the form of acetate, from a neutral solution by
sulphuretted hydrogen; but the precipitation does not take place in the
presence of free mineral acid; hence, in the routine process of
analysis, sulphuretted hydrogen is passed into the acid liquid, and any
precipitate filtered off. The liquid is now made almost neutral by
potassic carbonate, and then potassic acetate added, and a current of
sulphuretted hydrogen passed through it. The sulphides of cobalt and
nickel, if both are present, will be thrown down; under the same
circumstances zinc, if present, would also be precipitated. Cobalt is
separated from zinc by dissolving the mixed sulphides in nitric acid,
precipitating the carbonates of zinc and cobalt by potassic carbonate,
collecting the carbonates, and, after washing, igniting them gently in a
bulb tube, in a current of dry hydrochloric acid; volatile zinc chloride
is formed and distils over, leaving cobalt chloride.

§ 874. To estimate cobalt, sulphide of cobalt may be dissolved in nitric
acid, and then precipitated by pure potash; the precipitate washed,
dried, ignited, and weighed; 100 parts of cobaltous oxide (Co₃O₄) equals
73·44 of metallic cobalt. Cobalt is separated from nickel by a method
essentially founded on one proposed by Liebig. The nitric acid solution
of nickel and cobalt (which must be free from all other metals, save
potassium or sodium) is nearly neutralised by potassic carbonate, and
mixed with an excess of hydrocyanic acid, and then with pure caustic
potash. The mixture is left exposed to the air in a shallow dish for
some hours, a tripotassic cobalticyanide (K₃CoCy₆) and a
nickelo-potassic cyanide (2KCy, NiCy₄) are in this way produced. If this
solution is now boiled with a slight excess of mercuric nitrate,
hydrated nickelous oxide is precipitated, but potassic cobalticyanide
remains in solution, and may be filtered off. On carefully neutralising
the alkaline filtrate with nitric acid, and adding a solution of
mercurous nitrate, the cobalt may then be precipitated as a mercurous
cobalticyanide, which may be collected, washed, dried, decomposed by
ignition, and weighed as cobaltous oxide. After obtaining both nickel
and cobalt oxides, or either of them, they may be easily identified by
the blowpipe. The oxide of nickel gives, in the oxidising flame with
borax, a yellowish-red glass, becoming paler as it cools; the addition
of a potassium salt colours the bead blue. In the reducing flame the
metal is reduced, and can be seen as little greyish particles
disseminated through the bead. Cobalt gives an intense blue colour to a
bead of borax in the oxidising flame.


IV.--PRECIPITATED BY AMMONIUM SULPHIDE.

Iron--Chromium--Thallium--Aluminium--Uranium.


1. IRON.

§ 875. It was Orfila’s opinion that all the salts of iron were
poisonous, if given in sufficient doses; but such salts as the
carbonate, the phosphate, and a few others, possessing no local action,
may be given in such very large doses, without causing disturbance to
the health, that the statement must only be taken as applying to the
more soluble iron compounds. The two preparations of iron which have any
forensic importance are the perchloride and the sulphate.

§ 876. =Ferric Chloride= (Fe₂Cl₆ = 325).--Anhydrous ferric chloride will
only be met with in the laboratory. As a product of passing dry chlorine
over red-hot iron, it sublimes in brown scales, is very deliquescent,
and hisses when thrown into water. There are two very definite
hydrates--one with 6 atoms of water, forming large, red, deliquescent
crystals; and another with 12 of water, less deliquescent, and
crystallising in orange stellate groups.

The pharmaceutical preparations in common use are:--

=Stronger Solution of Perchloride of Iron= (=Liquor Ferri Perchloridi
Fortior=).--An orange-brown liquid of specific gravity 1·42, and
containing about 58 per cent. of ferric chloride.

=Tincture of Perchloride of Iron= (=Tinctura Ferri Perchloridi=), made
by diluting 1 part of the strong solution with 1 volume of rectified
spirit, and adding distilled water to measure 4.

=Solution of Perchloride of Iron= (=Liquor Ferri Perchloridi=).--Simply
5 volumes of the strong solution made up to 20 by the addition of water;
hence, of the same strength as the tincture.

§ 877. =Effects of Ferric Chloride on Animals.=--A very elaborate series
of researches on rabbits, dogs, and cats was undertaken a few years ago
by MM. Bérenger-Féraud and Porte[956] to elucidate the general symptoms
and effects produced by ferric chloride under varying conditions. First,
a series of experiments showed that, when ferric chloride solution was
enclosed in gelatine capsules and given with the food of the animal, it
produced either no symptoms or but trifling inconvenience, even when the
dose exceeded 1 grm. per kilogrm.; anhydrous ferric chloride and the
ferric chloride solution were directly injected into the stomach, yet,
when food was present, death did not occur, and the effects soon
subsided. In animals which were fasting, quantities of the solution
equal to ·5 grm. per kilogrm. and above caused death in from one hour to
sixteen hours, the action being much accelerated by the addition of
alcohol--as, for example, in the case of the tincture: the symptoms were
mainly vomiting and diarrhœa, sometimes the vomiting was absent. In a
few cases the posterior extremities were paralysed, and the pupils
dilated: the urine was scanty or quite suppressed; death was preceded by
convulsions.

[956] “Étude sur l’empoisonnement par le perchlorure de fer,” par MM.
Bérenger-Féraud et Porte, _Annales d’Hygiène Publique_, 1879.

§ 878. =Effects on Man.=--Perchloride of iron in the form of tincture
has been popularly used in England, from its supposed abortive property,
and is sold under the name of “steel drops.” It has been frequently
taken by mistake for other dark liquids; and there is at least one case
on record in which it was proved to have been used for the purpose of
murder. The latter case[957] is peculiarly interesting from its great
rarity; it occurred in Martinique in 1874-1876, no less than four
persons being poisoned at different dates. All four were presumed to
have had immoral relations with a certain widow X----, and to have been
poisoned by her son. In three of the four cases, viz., Char----,
Duf----, and Lab----, the cause of death seems pretty clear; but the
fourth, Ab----, a case of strong suspicion, was not sufficiently
investigated. All three took the fatal dose in the evening, between
eight and nine o’clock--Lab---- the 27th of December 1874, Duf---- the
22nd of February 1876, and Char---- on the 14th of May 1876. They had
all passed the day in tippling, and they all had eaten nothing from
mid-day, so that the stomach would, in none of the three, contain any
solid matters. The chloride was given to them in a glass of “punch,” and
there was strong evidence to show that the son of the widow X----
administered it. Char---- died after about thirteen hours’ illness,
Duf---- and Lab---- after sixty-five hours’ illness; Ab---- lived from
three to four days. With Char---- the symptoms were very pronounced in
an hour, and consisted essentially of violent colicky pain in the
abdomen and diarrhœa, but there was no vomiting; Duf---- had also great
pain in the abdomen and suppression of the urine. Lab---- had most
violent abdominal pains; he was constipated, and the urinary secretion
was arrested; there was besides painful tenesmus. According to the
experiments of Bérenger-Féraud and Porte,[958] the perchloride in the
above cases was taken under conditions peculiarly favourable for the
development of its toxic action, viz., on an empty stomach and mixed
with alcohol.

[957] Fully reported in Bérenger-Féraud’s paper, _loc. cit._

[958] _Dub. Med. Press_, February 21, 1849.

There have been several cases of recovery from large doses of the
tincture, _e.g._, that of an old man, aged 72, who had swallowed 85 c.c.
(3 ozs.) of the tincture; the tongue swelled, there were croupy
respiration and feeble pulse, but he made a good recovery. In other
cases,[959] 28·3 c.c. (an ounce) and more have caused vomiting and
irritation of the urinary organs. The perchloride is not unfrequently
used to arrest hæmorrhage as a topical application to the uterine
cavity--a practice not free from danger, for it has before now induced
violent inflammation and death from peritonitis.

[959] _Provincial Journal_, April 7 and 21, 1847, p. 180; see also
Taylor’s _Principles and Practice of Medical Jurisprudence_, vol. i. p.
320, 2nd Edition.

§ 879. =Elimination of Iron Chloride.=--Most of the iron is excreted in
the form of sulphide by the fæces, and colours them of a black hue; a
smaller portion is excreted by the urine.

§ 880. =Post-mortem Appearances.=--In the experiments on animals already
referred to, the general changes noted were dryness, pallor, and
parchment-like appearance of the cavity of the mouth, the mucous
membrane being blackened by the contact of the liquid. The gullet was
pale and dry, not unfrequently covered with a blackish layer. The mucous
membrane of the stomach was generally healthy throughout; but, if the
dose was large and very concentrated, there might be one or more
hyperæmic spots; otherwise, this did not occur. The internal surface of
the intestines, similarly, showed no inflammation, but was covered with
brownish coating which darkened on exposure to the air. The liver, in
all the experiments, was large and gorged with black and fluid blood;
there were ecchymoses in the lungs and venous congestion. The kidneys
were usually hyperæmic, and contained little hæmorrhages. There was also
general encephalic engorgement, and in one experiment intense congestion
of the meninges was observed. Few opportunities have presented
themselves for pathological observations relative to the effects
produced by ferric chloride on man. In a case related by Christison, in
which a man swallowed 42·4 c.c. (1½ oz.) of the tincture, and died in
five weeks, there was found thickening and inflammation of the pyloric
end of the stomach.

The case of Char----, already alluded to, is that in which the most
complete details of the autopsy are recorded, and they coincide very
fairly with those observed in animals; the tongue was covered with a
greenish fur, bordered at the edges with a black substance, described as
being like “mud”; the lining membrane of the gullet was pale, but also
covered with this dark “mud.” The stomach contained a greenish-black
liquid; the liver was large and congested; the kidneys were swollen,
congested, and ecchymosed; the cerebral membranes were gorged with
blood, and the whole brain hyperæmic.

§ 881. =Ferrous Sulphate, Copperas, or Green Vitriol=, FeSO₄7H₂O = 152 +
126; specific gravity, anhydrous, 3·138; crystals, 1·857; composition in
100 parts, FeO, 25·92; SO₃, 28·77; H₂O, 45·32.--This salt is in
beautiful, transparent, bluish-green, rhomboidal prisms. The crystals
have an astringent, styptic taste, are insoluble in alcohol, but
dissolve in about 1·5 times their weight of water; the commercial
article nearly always responds to the tests, both for ferrous and ferric
salts, containing a little persalt. The medicinal dose of this salt is
usually given as from ·0648 to ·324 grm. (1 to 5 grains), but it has
been prescribed in cases requiring it in gramme (15·4 grains) doses
without injury. Sulphate of iron has many technical applications; is
employed by all shoemakers, and is in common use as a disinfectant. The
salt has been employed for criminal purposes in France, and in this
country it is a popular abortive. In recorded cases, the symptoms, as
well as the pathological appearances, have a striking resemblance to
those produced by the chloride. There are usually colic, vomiting, and
purging; but in one case (reported by Chevallier), in which a man gave a
large dose of sulphate of iron to his wife, there was neither vomiting
nor colic; the woman lost her appetite, but slowly recovered. Probably
the action of ferrous sulphate, like that of the chloride, is profoundly
modified by the presence or absence of food in the stomach. Anything
like 28·3 grms. (an ounce) of sulphate of iron must be considered a
dangerous dose, for, though recovery has taken place from this quantity,
the symptoms have been of a violent kind.

§ 882. =Search for Iron Salts in the Contents of the Stomach,
&c.=--Iron, being a natural component of the body, care must be taken
not to confound the iron of the blood or tissues with the “iron” of a
soluble salt. Orfila attempted to distinguish between the two kinds of
iron by treating the contents of the stomach, the intestines, and even
the tissues, with cold acetic acid, and allowing them to digest in it
for many hours before filtering and testing for iron in the filtrate,
and this is generally the process which has been adopted. The acid
filtrate is first treated with sulphuretted hydrogen, which gives no
precipitate with iron, and then with sulphide of ammonium, which
precipitates iron black. The iron sulphide may be dissolved by a little
hydrochloric acid and a drop of nitric acid, and farther identified by
its forming Prussian blue when tested by ferrocyanide of potash, or by
the bulky precipitate of oxide, when the acid liquid is alkalised by
ammonia. In the case of Duf----, the experts attempted to prove the
existence of foreign iron in the liver by taking 100 grms. of Duf----’s
liver and 100 grms. of the liver of a non-poisoned person, and
destroying each by nitro-muriatic acid, and estimating in each acid
solution the ferric oxide. Duf----’s liver yielded in 100 parts ·08
mgrm. of ferric oxide, the normal liver ·022--nearly three times less
than Duf----’s.

To obtain iron from the urine, the fluid must be evaporated down to a
syrup in a platinum dish, a little nitric acid added, heated, and
finally completely carbonised. The residue is dissolved in hydrochloric
acid. Normal urine always contains an unweighable trace of iron; and,
therefore, any quantity, such as a mgrm. of ferric oxide, obtained by
careful precipitation of the hydrochloric acid solution out of 200 to
300 c.c. of urine, would be good evidence that a soluble salt of iron
had been taken. The hydrochloric acid solution is first precipitated by
ammonia and ammonic sulphide. The precipitate thus obtained will not be
pure iron sulphide, but mixed with the earth phosphates. It should be
redissolved in HCl, precipitated by sodic carbonate, then acidified by
acetic acid and sodic acetate added, and the solution well boiled; the
iron will then be precipitated for the most part as oxide mixed with a
little phosphate of iron.

Since, as before mentioned, a great portion of the iron swallowed as a
soluble salt is converted into insoluble compounds and excreted by the
fæces, it is, in any case where poisoning by iron is suspected, of more
importance to examine chemically the fæces and the whole length of the
alimentary canal, than even the contents of the stomach. In particular,
any black material lying on the mucous membrane may be sulphide of iron
mixed with mucus, &c., and should be detached, dissolved in a little
hydrochloric acid, and the usual tests applied.

In the criminal cases alluded to, there were iron stains on certain
linen garments which acquired an importance, for, on dissolving by the
aid of nitric acid, they gave the reactions of chlorine and iron. Any
stains found should be cut out, steeped in water, and boiled. If no iron
is dissolved the stain should then be treated with dilute nitric acid,
and the liquid tested with ferrocyanide of potash, &c. It need scarcely
be observed that iron-mould is so common on shirts and any fabric
capable of being washed, that great care must be exercised in drawing
conclusions from insoluble deposits of the oxide.


2. CHROMIUM.

§ 883. The only salts of chromium of toxicological importance are the
neutral chromate of potash, the bichromate of potash, and the chromate
of lead.

=Neutral Chromate of Potash=, CrO₃K₂O = 194·7, containing 56·7 per cent.
of its weight of chromic anhydride, CrO₃.--This salt is in the form of
citron-yellow rhombic crystals, easily soluble in water, but insoluble
in alcohol. Its aqueous solution is precipitated yellow by lead acetate
or basic acetate; the precipitate being insoluble in acetic acid. If
chromate of potash in solution is tested with silver nitrate, the red
chromate of silver is thrown down; the precipitate is with difficulty
soluble in dilute nitric acid.

§ 884. =Potassic Bichromate=, CrO₃K₂O = 295·2, containing 68·07 per
cent. of its weight of chromic anhydride, CrO₃.--This salt is in
beautiful large, red, transparent, four-sided tables; it is anhydrous
and fuses below redness. At a high temperature it is decomposed into
green oxide of chromium and yellow chromate of potash. It is insoluble
in alcohol, but readily soluble in water. The solution gives the same
precipitates with silver, lead, and barium as the neutral chromate. On
digesting a solution of the bichromate with sulphuric acid and alcohol,
the solution becomes green from the formation of chromic oxide.

§ 885. =Neutral Lead Chromate=, PbCrO₄ = 323·5, composition in 100
parts, PbO, 68·94, CrO₃, 31·06.--This is technically known as “_Chrome
Yellow_,” and is obtained as a yellow precipitate whenever a solution of
plumbic acetate is added, either to the solutions of potassic chromate
or bichromate; by adding chrome yellow to fused potassic nitrate,
“chrome red” is formed; it has the composition CrO₃2PbO. Neutral lead
chromate is insoluble in acids, but may be dissolved by potassic or
sodic hydrates.

§ 886. =Use in the Arts.=--Potassic bichromate is extensively used in
the arts--in dyeing, calico-printing, the manufacture of porcelain, and
in photography; the neutral chromate has been employed to a small extent
as a medicine, and is a common laboratory reagent; lead chromate is a
valuable pigment.

§ 887. =Effects of some of the Chromium Compounds on Animal Life.=--In
the chromates of potash there is a combination of two poisonous metals,
so that it is not surprising that Gmelin found the chloride of chromium,
CrCl₃, less active than the neutral chromate of potash; 1·9 grm. of the
last, administered to a rabbit by the stomach, caused death within two
hours, while 3 grms. of chromous chloride had no action. Subcutaneous
doses of ·2 to ·4 grm. of neutral chromate (according to the experiments
of E. Gergens[960] and Carl Posner[961]) act with great intensity on
rabbits. Immediately after the injection the animals are restless, and
show marked dyspnœa; death often takes place within a few hours.

[960] _Arch. f. experiment. Pathol. u. Pharmakol._, Bd. 6, Hft. 1 and 2,
§ 148, 1875.

[961] Virchow’s _Archiv f. path. Anat._, Bd. 79, Hft. 2, § 333, 1880.

Diarrhœa does not seem, as a rule, to follow when the salt is
administered by subcutaneous injection to animals; but Gmelin’s rabbits
had considerable diarrhœa when 1·9 grm. was introduced into the stomach.
The same quantity, injected beneath the skin of a dog, caused loss of
appetite, and, after six days, there was a dry exanthem on the back, and
the hair fell off in patches; there was, however, neither diarrhœa nor
vomiting. Bichromate of potash causes (according to the researches of
Pelikan)[962] symptoms similar to those produced by arsenic or corrosive
sublimate; it acts as a powerful irritant of the stomach and intestinal
canal, and may even cause inflammation; on its absorption a series of
symptoms are produced, of which the most prominent are albuminuria,
bloody urine, and emaciation. From ·06 to ·36 grm. (1-5½ grains) is
fatal to rabbits and dogs.

[962] _Beiträge zur gerichtl. Medicin, Toxikol. u. Pharmakodynamik_,
Würzburg, 1858.

§ 888. =Effects of some of the Chromium Salts on Man--Bichromate
Disease.=--In manufacturing potassic bichromate, the workmen exposed to
the dust have suffered from a very peculiar train of symptoms, known
under the name of “bichromate disease.” It was first described in
England by Sir B. W. Richardson.[963] It appears that if the workmen
inspire the particles chiefly through the mouth, a bitter and
disagreeable taste is experienced, with an increase of saliva. This
increase of the buccal secretion gets rid of most of the poison, and in
that case but little ill effect is experienced; but those who keep the
mouth closed and inspire by the nose, suffer from an inflammation of the
septum, which gradually gets thin, and ultimately ulcerated; finally the
whole of the septum is in this way destroyed. It is stated that when a
workman has lost his nasal septum, he no longer suffers from nasal
irritation, and has a remarkable immunity from catarrh. The Chemical
Works Committee of Inquiry report (1893) that the manufacture of
bichromate of potash or soda is practically in the hands of three firms
at Glasgow, Rutherglen, and Falkirk, and that they visited all of them,
and found “that almost all the men working where dust was prevalent,
more especially between the furnaces and the dissolving tanks, had
either perforation of the septum of the nose, or had lost the
septum altogether.” The bichromate also causes painful skin
affections--eruptions akin to eczema or psoriasis; also very deep and
intractable ulcerations. These the workers call “chrome holes.” These
cutaneous maladies start from an excoriation; so long as the skin is not
broken, there seems to be little local effect, if any. The effects of
the bichromate are also seen in horses employed at the factories; the
salt getting into a wound or crack in the leg, produces ulceration:
horses may even lose their hoofs.

[963] _Brit. and For. Med. Chirurg. Review_, Oct. 1863. See also a paper
by the same writer, read before the Medical Society, reported in the
_Lancet_, March 11, 1882.

§ 889. Acute poisoning by the chromates is rare. In the ten years ending
1892, in England and Wales, 4 accidental deaths are ascribed to potassic
bichromate and 1 to chromic acid. Falck has, however, been able to find
in medical literature 17 cases, 6 of which were suicidal, 10 accidental,
and in 1 the bichromate was used as an abortive. In a case of poisoning
by the chromate of potash (related by Maschka),[964] in which a woman,
aged 25, took for a suicidal purpose a piece of potassic chromate, which
she described as the size of a hazel-nut (it would probably be at least
6 grms. in weight), the chief symptoms were vomiting, diarrhœa, pain in
the stomach, and rapid collapse; death took place fourteen hours after
swallowing the poison.

[964] _Prager Vierteljahrsschr. f. d. prakt. Heilk._, Bd. 131, § 37,
1877; Schmidt’s _Jahrb._ 1878, Bd. 178, § 237. See also Schuchardt in
Maschka’s _Handbuch_, Bd. ii. p. 3.

In poisoning by potassic bichromate, there may be much variety in the
symptoms, the more usual being those common to all irritant poisons,
_i.e._, vomiting, diarrhœa, and collapse, with cramps in the limbs and
excessive thirst; and the rarer affecting more especially the nervous
system, such as narcosis, paralysis of the lower limbs, and dilatation
of the pupils; occasionally there is slight jaundice.

In a case recorded by Dr. Macniven,[965] a man took a lump of bichromate
of potash, estimated to be over 2 drachms (7·7 grms.). The symptoms
commenced in fifteen minutes, and consisted of lightness in the head,
and a sensation of great heat in the body, which was followed by a cold
sweat; in twenty minutes he vomited; he then suffered from great pain in
the stomach, giddiness, specks before the eyes, a devouring thirst, and
there was loss of power over the legs. These symptoms, again, were
followed by severe rigors and great coldness of the extremities. On the
patient’s admission to hospital, two hours after taking the poison, it
was noted that the pupils were dilated, the face pale and cold, and the
pulse feeble. He complained of intense epigastric pain, and a feeling of
depression; there was some stupor; the stomach was emptied by emetics
and by the stomach-pump, and the patient treated with tepid emollient
drinks, whilst subcutaneous doses of sulphuric ether were administered.
He made a good recovery.

[965] “On a Case of Poisoning with Bichromate of Potash,” by Ed. O.
Macniven, M.B., _Lancet_, Sept. 22, 1883.

In a case recorded by Mr. Wilson,[966] a man, aged 64, was found dead in
his bed twelve hours after he had gone to rest. During the night he was
heard to snore loudly; there were no signs of vomiting or purging, and
bichromate of potash was found in the stomach.[967]

[966] _Med. Gazette_, vol. 33, 734.

[967] See also cases recorded by Dr. M’Lachlan, _Glasgow Med. Journ._,
July 1881; Dr. M’Crorie, _ibid._, May 1881; Dr. R. A. Warwick, _Lancet_,
Jan. 31, 1880; and Dr. Dunbar Walker, _ibid._, Sept. 27, 1879--a summary
of all of which may be found in Dr. Macniven’s paper, _loc. cit._

§ 890. Chromate of lead has also caused death. In one case[968] the
breathing of chromate of lead dust seems to have been fatal; and there
is also a double poisoning recorded by Dr. Linstow,[969] of two
children, aged three and a half and one and three-quarter years
respectively, who ate some yellow ornaments,[970] which were used to
adorn a cake, and which contained chrome yellow (chromate of lead). The
younger died in two and the elder in five days. The symptoms were
redness of the face, dulness, and an inclination to sleep; neither
complained of pain; the younger one had a little diarrhœa, but the elder
neither sickness nor purging.

[968] _Ueber tödtliche Vergiftung durch Einathmen des Staubes von mit
Chromsäuren Blei-Oxyde gefärbten Garne.--Vierteljahrsschr. f. ger.
Med._, 1877, Bd. xxvii. Hft. i. p. 29.

[969] _Ibid._, Bd. xx. s. 60, 1874.

[970] The ornaments were imitations of bees; each contained ·27 grm. gum
tragacanth, ·0042 grm. neutral lead chromate.

§ 891. =Post-mortem Appearances.=--We possess some very exact
researches[971] upon the pathological changes induced by subcutaneous
injections of solutions of potassic bichromate on animals, and
especially on the changes which the kidneys undergo. If the animal is
killed, or dies a few hours after the injection, there are apparently no
striking appearances, but a closer microscopical examination shows
considerable changes. The epithelium of the tubuli contorti exhibits a
yellow cloudiness, and the outline of the cells is irregular and jagged.
The glomeruli are moderately injected, and their capsules contain an
albuminous exudation; the canaliculi are filled with round cells
imbedded in a fluid which, on heating, coagulates, and is therefore
albuminous or fibrinous; probably this is the first stage of the
formation of fibrinous casts.

[971] C. Posner, _op. cit._

In the case quoted of the woman who poisoned herself with potassic
chromate, very striking changes were found in the stomach and
intestines. The stomach contained above a litre of dark chocolate fluid
of alkaline reaction; the mucous membrane, in the neighbourhood of the
cardiac and pyloric extremities, was swollen and red in sharply defined
patches; portions of the epithelial layer were detached, the rest of the
mucous membrane was of a yellow-brown colour, and the whole intestine,
from the duodenum to the sigmoid flexure, was filled with a partly
bloody, partly treacly-looking fluid; the mucous membrane, throughout
its entire extent, was swollen, with numerous extravasations, and in
places there were losses of substance. Similar appearances to these have
been found in other instances; the anomalous case recorded by Mr. Wilson
(_ante_) is an exception. In this instance a pint of inky, turbid
liquid, which yielded to analysis potassic bichromate, was found in the
stomach; but there were no marked changes anywhere, save a slight
redness of the cardiac end of the gullet. In Linstow’s two cases of
poisoning by lead chromate, there were found in both fatty degeneration
of the liver cells, and red points or patches of redness in the stomach
and intestines. In the elder boy the changes in the duodenum were very
intense, the mucous membrane was swollen and easily detached, in the
upper part strongly injected with blood; in one place there was a
perforation, and in several places the membrane was extremely thin. In
the younger boy the kidneys seem to have been normal, in the elder
congested and containing pus. Although it was clear that the two
children died from lead chromate, a chemical analysis gave no result.

§ 892. =Detection of the Chromates and Separation of the Salts of
Chromium from the Contents of the Stomach, &c.=--If in the methodical
examination of an acid liquid, which has been already filtered from any
precipitate that may have been obtained by sulphuretted hydrogen, this
liquid is made alkaline (the alkali only being added in slight excess),
and hydrated chromic oxide is thrown down mixed, it may be with other
metals of the second class, the precipitate may then be fused with nitre
and potassic carbonate, and will yield potassic chromate, soluble in
water, and recognised by the red precipitate which it gives with silver
nitrate, the yellow with lead acetate, and the green colour produced by
boiling with dilute sulphuric acid and a little alcohol or sugar. If by
treating a complex liquid with ammonium hydrosulphide, sulphides of
zinc, manganese, and iron are thrown down mixed with chromic oxide, the
same principles apply. If a chromate is present in the contents of the
stomach, and the organic fluid is treated with hydrochloric acid and
potassic chlorate, chromic chloride is formed, and dissolving imparts a
green colour to the liquid--this in itself will be strong evidence of
the presence of a chromate, but it should be supplemented by throwing
down the oxide, and transforming it in the way detailed into potassic
chromate.

A general method of detecting and estimating both chromium and barium in
organic matters has been worked out by L. de Koningh.[972] The
substances are burnt to an ash in a platinum dish. The ash is weighed;
to the ash is added four times its weight of potassium sodium carbonate
and the same amount of potassium nitrate; and the whole is fused for
fifteen minutes. The fused mass is boiled with water and filtered; if
chromium is present, the filtrate is of a more or less pronounced yellow
colour, but manganese may produce a green colour and mask the yellow;
this colour is removed by boiling with a little alcohol. The liquid is
concentrated down to 20 c.c., filtered into a test-tube, and a
colorimetric estimation made of the chromium present by imitating the
colour by a solution of potassium chromate of known strength. To prove
that the colour is really due to chromium, acetic acid and lead acetate
are added, when the yellow chromate of lead is at once thrown down. (If
lead was in the ash, a yellow precipitate may appear on the addition of
acetic acid.) To the portion of ash insoluble in water strong
hydrochloric acid is added, and to the acid solution a large excess of
calcium sulphate is added; this precipitates barium as sulphate free
from lead sulphate, for, if the latter should be present, it does not,
under the circumstances, come down, being soluble in strong hydrochloric
acid.

[972] _Arch. Pharm._ (3), xxvii. 944.


3. THALLIUM.

    § 893. Thallium was discovered by Crookes in 1861. Its atomic weight
    is 204; specific gravity, 11·81 to 11·91; melting-point, 290°. It is
    a heavy diamagnetic metal, very similar to lead in its physical
    properties. The nitrate and sulphate of thallium are both soluble in
    water, the carbonate less so, requiring about 25 parts of water for
    solution, while the chloride is sparingly soluble, especially in
    hydrochloric acid.

    § 894. =Effects.=--All the salts of thallium are poisonous. One of
    the earlier experimenters on the physiological action, Paulet, found
    1 grm. (15·4 grains) of thallium carbonate sufficient to kill a
    rabbit in a few hours; there were loss of muscular power, trembling
    of the limbs, and death apparently from asphyxia. Lamy[973] used
    thallium sulphate, and found that dogs were salivated, and suffered
    from trembling of the limbs, followed by paralysis. The most
    definite results were obtained by Marmé,[974] who found that ·04 to
    ·06 grm. of a soluble thallium salt, injected subcutaneously or
    directly into the veins, and ·5 grm. administered through the
    stomach of rabbits, caused death. The action is cumulative, and
    something like that of mercury: there are redness and swelling of
    the mucous membrane of the stomach, with mucous bloody discharges;
    hæmorrhage may also occur from the lungs. Thallium is eliminated
    through the urine, and is also found in the fæces; it passes into
    the urine from three to five minutes after injection: the
    elimination is slow, often taking as long as three weeks. It has
    been found in the milk, in the tears, in the mucous membrane of the
    mouth, of the trachea, in the secretion of the gastric mucous
    membrane, and in the pericardial fluid; and in these places, whether
    the poison has been introduced by subcutaneous injection, or by any
    other channel. It seems probable that the reason of its being
    detected so readily in all the secretions is the minute quantity
    which can be discovered by spectroscopic analysis.

[973] _Chem. News_, 1863.

[974] _Göttinger Gelehrt. Nachrichten_, Aug. 14, No. 20.

    § 895. =Separation of Thallium from Organic Fluids or Tissues.=--The
    salts of thallium, if absorbed, would only be extracted in traces
    from the tissues by hydrochloric acid, so that, in any special
    search, the tissues are best destroyed by either sulphuric or nitric
    acid, or both. In the ordinary method of analysis, when an acid
    liquid is first treated with sulphuretted hydrogen, and then made
    alkaline by ammonia and ammonic sulphide, thallium would be thrown
    down with the manganese and iron of the blood. From the mixed
    sulphides, thallium may be separated by oxidising and dissolving the
    sulphides with nitric acid, evaporating off the excess of acid,
    dissolving in a very little hot water, and precipitating thallous
    chloride by solution of common salt. The ease, however, with which
    thallium may be separated from solutions of its salts by galvanism
    is so great as to render all other processes unnecessary: the best
    way, therefore, is to obtain a deposit of the metal on platinum by a
    current from one or more cells, and then to examine the deposit
    spectroscopically. Thallium gives, when heated in a Bunsen flame, a
    magnificent green line, the centre of which corresponds with wave
    length 534·9; a second green line, the centre of which coincides
    with W.L. 568, may also be distinguished.


4. ALUMINIUM.

§ 896. =Aluminium and its Salts.=--A strong solution of acetate of
alumina has irritant properties, and has given rise to accidents. The
term alum, in a chemical sense, is given to a class of bodies of the
type of AlKSO₄. Common alum is at the present time ammonia alum,
NH₄Al(SO₄)₂ + 12H₂O; when made anhydrous by heat it is known by the name
of burnt alum, and possesses caustic properties.

§ 897. =Action of Alum Salts.=--Death or illness has hitherto only taken
place from the ingestion of large doses of alum or the acetate, and the
symptoms in these cases have been those of an irritant poison; we are,
however, indebted to Paul Siem[975] for a research on the absorbed
substance, in which the local effects as far as possible have been
reduced.

[975] _Ueber die Wirkungen des Aluminiums u. Berylliums, Inaug. Diss._,
Dorpat, 1886; Schmidt’s _Jahrbuch_, vol. ccxi. 128.

Siem’s research was made on frogs, cats, and dogs. For frogs he employed
a double salt, consisting of sodic and aluminic lactate, to which he
ascribed the formula Al₂(C₃H₅O₃)₃(C₃H₄NaO₃)₃, equal to 15·2 per cent. of
Al₂O₃. Twenty to thirty mgrms., administered by subcutaneous injection
to frogs, caused death in from ten to twenty-four hours. After the
injection there was restlessness, and, ultimately, general paralysis of
the central nervous system. The circulation was not affected; the heart
was the last to die.

For warm-blooded animals he used the double tartrate of sodium and
aluminium. Beginning with a small dose subcutaneously administered, he
gradually increased it, and found, under these circumstances, that the
lethal dose for rabbits was 0·3 grm. per kilo. of body weight; for dogs
0·25 grm., and for cats 0·25 to 0·28 grm.; if, however, a single dose
was administered, then cats could be killed by 0·15 grm. per kilo. The
symptoms commenced ten to twelve hours after the injection of a large
dose, but with a medium dose the symptoms might be delayed for from
three to four days, then there was loss of appetite, constipation,
emaciation, languor, and a disinclination to move. Vomiting and loss of
sensation to pain followed, the power of swallowing even saliva was
lost, and a condition supervened similar to bulbar paralysis. However
true this picture may be when large doses are given subcutaneously, it
does not follow that hydrate of alumina in small doses, given by the
mouth, mixed with food, produces any symptoms whatever.

Alum baking-powders, containing from 30 to 40 per cent. of alum mixed
with carbonate of soda, are in commerce, and have been for a long time,
many tons being sold yearly. When water is added to such powders
decomposition takes place, the result being sodic sulphate and aluminic
hydrate, carbonic acid being given off. Were the hydrate, in small
doses, capable of producing indigestion or disease of the central
nervous system, it seems astonishing that, considering the enormous
number of persons who use alum baking-powders, there should not be some
definite evidence of its effect. The author and his family for months
together have used alum baking-powders without any apparent injury, and
there is little doubt that alumina hydrate passes out of the system
mainly by the bowel, without being absorbed to any great extent. In a
trial with regard to an alum baking-powder at Pontypridd (1893), the
prosecution advanced the theory, and supported it by eminent scientific
opinion, that aluminium hydrate was dissolved by the hydrochloric acid
of the gastric juice, forming chloride of aluminium, some of which might
be absorbed and enter the circulation; that which was not absorbed in
the stomach passed on, and, meeting the alkaline fluids of the
intestines, was again separated as aluminium hydrate, and as such
absorbed.

If this does occur, still there is no direct evidence of its toxic
influence in the small quantities used in baking-powder. It may be
pointed out, also, that with regard to the possible lethal effect of a
non-corrosive salt of alum, presuming that the lethal dose for man is
the same as that for a cat, the amount of alumina to kill a
68-kilogramme man would have to be equal to 17 grms., or about 3 ozs. of
ammonia alum. This important question can only be settled by careful
feeding of animals carried on for a long period of time.

§ 898. =Post-mortem Appearances.=--In the few cases in which persons
have been killed by large doses of alum or its salts there have been
found corrosion of the mouth, throat, and stomach, and hyperæmia of the
kidneys and intestine. In the animals experimented upon by Paul Siem,
hyperæmia of the intestine, fatty degeneration of the liver and hyaline
degeneration of the kidneys were the chief changes noted.

§ 899. =Detection of Alumina.=--In all operations for the detection of
alumina, glass and porcelain vessels are to be avoided. The substances
should be burned to an ash in a platinum dish, the ash treated with
hydrochloric acid, the acid driven off by heat, and a few drops of
nitric acid added, and dissolved in hydrochloric acid, and the solution
boiled and filtered. If organs of the body are operated upon, iron and
phosphoric acid will be present in the ash; this will, indeed, be the
case with most organic substances. The filtered solution is boiled, and,
while boiling, poured into a strong solution of sodic hydrate contained
in a silver or platinum dish; the iron will now separate as oxide, and
can be filtered off. To the filtrate is added a little sodic phosphate;
it is then feebly acidified with hydrochloric acid, and ammonia added
just sufficient to render it alkaline; a light whitish cloud of alumina
phosphate, should alumina be present, is thrown down, and can be
collected, thoroughly washed, dried, ignited, and weighed as alumina
phosphate.[976] The alumina phosphate is then fused with sodic sulphate
in a platinum dish or crucible, and the fused mass treated with hot
water; the sodic phosphate dissolves, and the alumina oxide may be
filtered off and dissolved in a little hydrochloric acid or sulphuric
acid.

[976] One part of al. phosphate is equal to 0·42 Al₂O₃, 3·733 ammonia
alum, and 4·481 potash alum.

A solution thus prepared has the following properties:--

Ammonium sulphide; white precipitate of hydroxide.

Potash or soda; white precipitate, soluble in excess.

Ammonia; white precipitate, only slightly soluble in excess.

There is also a blowpipe-test: if a little of the hydroxide be
collected, moistened with cobalt nitrate, and heated on charcoal by the
oxidising flame, alumina, under these circumstances, becomes of a blue
colour.


5. URANIUM.

    § 900. =Uranium.=--The salts of uranium are intensely poisonous. The
    nitrate of uranium is used in photography and the arts, and is a
    common reagent in chemical laboratories.

    According to Kowalewsky,[977] the acetate of uranium possesses an
    unusual power of uniting with albumin; the other soluble uranium
    salts act also in a similar way. Hence concentrated solutions of
    uranium salts corrode the mucous membranes, transforming, for
    example, the walls of the stomach into a dead uranic albuminate. If
    a non-corrosive salt of uranium is injected subcutaneously,
    glycosuria is produced, with fatty degeneration of the walls of the
    blood-vessels, and fatty changes in the kidneys, liver, &c. The
    animal wastes and ultimately dies; 0·5 to 2·0 mgrms. of UO₃ per
    kilogrm. will kill a cat, dog, or rabbit, if injected
    subcutaneously. The nitrate or acetate, when given by the mouth,
    produces gastro-enteritis and nephritis, with hæmorrhages in the
    substance of the kidney. Uranium is not used in medicine.

[977] _Ztschr. f. Anal. Chemie_, xxiv., 1885, p. 551.

    § 901. =Detection and Estimation of Uranium.=--Uranium forms uranous
    and uranic salts. Both classes of salts are not precipitated by SH₂,
    but are precipitable by ammonium sulphide, and, therefore, in
    toxicological analyses are likely to be met with in conjunction with
    iron.

    The sulphides of iron and uranium may be dissolved in strong
    hydrochloric acid, boiled to expel SH₂, and the solution then
    oxidised with a little nitric acid; the solution is now alkalised
    with ammonium carbonate, which precipitates the iron as oxide and
    leaves the uranium in solution. On now acidifying with nitric acid
    in slight excess, a solution of sodic phosphate will precipitate
    uranium phosphate as a white precipitate, alkalies will give a
    yellow precipitate, alkaline carbonates a yellow precipitate soluble
    in excess. Barium carbonate also gives a precipitate, and is useful
    in separations. Uranium oxide gives a green glass in the oxidising
    flame with borax or with sodic metaphosphate.


V.--ALKALINE EARTHS.

Barium.

§ 902. The soluble salts of barium are undoubtedly poisonous, and are of
frequent occurrence in the arts. The chloride of barium is used in the
staining of wool, the nitrate and the chlorate in the green fires of the
pyrotechnist, the oxide and the carbonate in the manufacture of glass.
The chromate is used by artists under the name of “yellow ultramarine,”
while the sulphate, technically known as “permanent white,” is, on
account of its weight and cheapness, occasionally used as an adulterant
of white powders and other substances. Barium sulphide, under various
names, such as Bottcher’s depilatory, Thompson’s hair destroyer, _Poudre
épilatoire_, and other names, is in commerce, and has caused poisonous
symptoms.[978]

[978] Barium carbonate and sulphate are usually enumerated as occasional
adulterants of bread, but there is no modern authentic instance of this.

§ 903. =Chloride of Barium=, BaCl₂2H₂O 208 + 36; anhydrous, Ba, 65·86
per cent., Cl, 34·14; specific gravity, 3·75, is in commerce in the form
of white, four-sided, tabular crystals; water dissolves about half its
weight at ordinary temperatures, three-fourths at 100°. Its solution
gives a white precipitate with sulphuric acid, quite insoluble in water
and nitric acid.

The salt imparts a green hue to an otherwise colourless flame; viewed by
the spectroscope, green bands will be visible. We may note that chloride
of barium gives two different spectra--the one at the moment of the
introduction of the salt, the other when the substance has been exposed
for some time to a high temperature. This is caused by a rapid loss of
chlorine, so that the first spectrum is due to BaCl₂, with a variable
mixture of BaCl, the second to BaCl alone.

§ 904. =Baric Carbonate=, BaCO₃ = 197; specific gravity, 4·3; BaO, 77·69
per cent., CO₂, 22·31, in its native form termed _Witherite_, is a
dense, heavy powder, insoluble in pure water, but dissolving in acetic,
nitric, and hydrochloric acids, the solution giving the reactions of
barium.

A rat-poison may be met with composed of baric carbonate, sugar, and
oatmeal, flavoured with a little oil of aniseed and caraway.

§ 905. =Sulphate of Barium=, BaSO₄; specific gravity, 4·59; BaO, 65·66
per cent., SO₃, 34·34 per cent., is a pure white powder when recently
precipitated, absolutely insoluble in water, and practically insoluble
in cold dilute acids. It is quite unalterable in the air at a red heat;
on ignition with charcoal, it may be converted almost entirely into
sulphide of barium; and by ignition with CaCl₂ into chloride.

§ 906. =Effects of the Soluble Salts of Barium on Animals.=--One of the
early notices of the poisonous characters of barium compounds was by
James Watt,[979] who found that _witherite_, given to dogs, produced
vomiting, diarrhœa, and death in a few hours. Sir Benj. Brodie[980]
administered barium chloride, and noticed its paralysing effect on the
heart. Orfila[981] made several experiments, and observed that 4 grms.
of the carbonate produced death in dogs in periods varying from one to
five hours; but in these experiments the gullet was tied. The later
investigators have been Gmelin, Onsum, Cyon, and Böhm.[982] Gmelin
found barium carbonate and barium chloride act in a very similar manner;
and, indeed, it is improbable that barium carbonate, _as_ carbonate, has
any action, but, when swallowed, the hydrochloric and other acids of the
stomach form with it soluble compounds. J. Onsum made eight experiments
with both barium carbonate and chloride on animals. The respiration was
quickened and, at the same time, made weak and shallow; the heart’s
action was accelerated; the animals became restless: and there was great
muscular prostration, with paralytic symptoms; convulsions did not occur
in any one of the eight animals. He found, on _post-mortem_ examination,
the right side of the heart full of blood from backward engorgement; he
describes a plugging of the small arteries with little fibrinous
coagula, having an inorganic nucleus, with constant hæmorrhagic
extravasations. Onsum seems to have held the theory that the baryta
salts circulated in the blood, and then formed insoluble compounds,
which were arrested in the lungs, causing minute emboli, just in the
same way as if a finely-divided solid were introduced directly into the
circulation by the jugular vein.

[979] _Memoirs of the Literary and Philosophical Society of Manchester_,
1790, vol. iii. p. 609.

[980] _Phil. Trans._, 1812.

[981] _Traité des Poisons_, 3rd ed., t. i., Paris, 1826.

[982] Gmelin, C. G., _Versuche über die Wirkungen des Baryts,
Strontians, Chroms, Molybdäns, Wolframs, Tellurs, u. s. w. auf den
thierischen Organismus_, Tübingen, 1824; Onsum, J., Virchow’s _Archiv_,
Bd. 2, 1863; Cyon, M., _Archiv f. Anatomie, Physiologie, &c._, 1866;
Böhm, _Archiv f. experiment. Pathol._, Bd. 3, 1874.

Onsum stands alone in this view. Cyon found no emboli in the lungs, and
refers the toxic effect to a paralysing influence on the heart and
voluntary muscles, and also on the spinal cord. Cyon, to settle the
embolic theory, injected into the one jugular vein of a rabbit barium
chloride, and into the other sodic sulphate, but the small arteries and
capillaries of the lungs remained clear. Böhm, operating on frogs, found
a great similarity between the action of small doses of barium salts and
that of certain organic poisons; as, for example, cicutoxin, ·012 to ·02
grm. subcutaneously injected into frogs, acted as a heart-poison. So
also Blake[983] found the heart slowed, and concluded that barium
chloride had a direct action on the cardiac muscle, and also a toxic
influence on the nervous system. F. A. Falck, in experiments on rabbits,
found a great reduction of temperature after poisoning with barium
chloride (3° to 12·6°).

[983] _Journ. of Anat. and Physiol._ 2nd series, 1874.

§ 907. =Effects of the Salts of Barium on Man.=--There were about
fifteen cases of poisoning by barium salts on record by the end of
1883--three of which were suicidal, but most of them were due to
accident or mistake. In three cases, barium chloride was taken instead
of Glauber’s salts; in one, instead of Carlsbad salts; in another, a
mixture of barium nitrate and sulphur, instead of pure sulphur; in a
sixth case, a mixture of barium acetate and raspberry syrup, instead of
sodic ethylsulphate; in a seventh, a chemist put a larger dose than was
ordered by the prescription; and in four cases barium carbonate had been
mixed with flour, and this flour used in the making of pastry. Of the
fifteen cases, nine, or 60 per cent., proved fatal; the fifteen cases
have now (1894) been increased to twenty-six.

=Fatal Dose.=--The recorded cases of poisoning have not satisfactorily
settled the question as to the least fatal dose of the barium salts. 6·5
grms. (about 100 grains) of the chloride have destroyed the life of an
adult woman in fifteen hours; 14 grms. (½ oz.) of the nitrate of baryta
have killed a man in six and a half hours; and the carbonate of baryta
has destroyed a person in the relatively small dose of 3·8 grms. (60
grains). On the other hand, certain Continental physicians have
prescribed barium chloride in large medicinal doses; for example,
Pirondi[984] and Lisfranc[985] have gradually raised the dose of barium
chloride from 4 decigrams up to 3 grms. (48 grains) daily, given, of
course, in divided doses. Pirondi himself took in a day 7·7 grms. (119
grains) without bad effect.

[984] _De la Tumeur Blanche de Genou_, éd. 2, Paris, 1836.

[985] _Gaz. Med. de Paris_, 1835, No. 14.

§ 908. =Symptoms.=--The local action of barium salts must be sharply
distinguished from the action of the absorbed salts. Kobert divides the
symptoms into seven groups:--

(1) Local, consisting in _malaise_, nausea, salivation, vomiting, and
pain in the stomach. This group merges so much into the next as hardly
to admit of precise separation.

(2) Excitation of the alimentary canal, both of the nervous and muscular
apparatus. Hence vomiting, painful colic, and acute diarrhœa. All these
phenomena may be produced in animals by subcutaneous injection, and,
therefore, do not depend alone upon local action.

(3) Excitation of the brain motor centres, which leads to convulsions,
or may result in paralysis. About half the recorded cases of barium
poisoning in the human subject have been convulsed; the other half
paralysed. In one case mania resulted.

(4) Weakness or destruction of the power of muscular contraction; this
produces in frogs, when the muscular test movements are recorded
graphically, a veratrin-like convulsion curve. In the human subject the
effect is that of great muscular weakness.

(5) Digitalin-like influence on the heart and blood-vessels, showing
itself in great slowing of the pulse, præcordial anxiety, and strong
beating of the heart (not only sensible to the patient, but which can be
heard and felt by the bystanders). The arteries are incompressible and
rigid, the blood-pressure strikingly raised. The blood-vessels of old
people do not stand the pressure, hence hæmorrhages in the lungs,
stomach, and other organs. Frogs die with the heart in systole.

(6) Catarrhal affection of the conjunctiva, the mucous membrane of the
respiratory tract, and the nose.

(7) Formation of insoluble baryta salts in the blood-vessels, according
to Onsum. This has not been observed in man, and the fact is disputed
(see _ante_).

In Dr. Tidy’s case,[986] in which a man, suffering from rheumatism, but
otherwise healthy, took a mixture of barium nitrate, flowers of sulphur,
and potassic chlorate, instead of sulphur, the symptoms were blisters on
the tongue, a burning pain in the gullet and stomach, with vomiting,
diarrhœa, convulsions, aphonia, and coldness of the extremities. A case,
copiously detailed by Seidel,[987] in which a pregnant woman,
twenty-eight years old, took carbonate of baryta for the purpose of
self-destruction, is interesting. She probably took the poison some
little time before six in the evening; she vomited and had great pain in
the stomach, but slept during the night without further sickness. The
next morning, after drinking some coffee, the sickness was renewed;
nevertheless, at 7 A.M., she repaired to her employment, which was
distant an hour’s walk; she probably suffered much on the way, for she
did not arrive until 9 A.M. The vomiting, accompanied by diarrhœa,
continuing, she was sent to bed at 2 P.M. She was very cold, and
complained of great weakness; the vomiting now ceased. At 8 P.M. she
shivered violently, could scarcely swallow, and the respiration was
oppressed. At 11 she seemed a little improved; but at 3 A.M. she was
found much worse, breathing rapidly, but fully conscious; at 4 A.M. she
was again seen, but found dead; she thus lived about thirty-four hours
after taking the fatal dose.

[986] _Pharm. Journ._, June 1868.

[987] Eulenberg’s _Vierteljahrsschrift f. ger. Med._, Bd. 27, § 213.

§ 909. =Distribution of Barium in the Body.=--Neumann has shown that,
after repeated injection of insoluble barium sulphate into the veins of
rabbits, barium is to be found in the liver, kidneys, spleen, and spinal
cord, but not in the muscles, thymus, or brain. G. Linossier[988] has
made a similar series of experiments, but with the more soluble
carbonate, and this salt was injected into animals for a period of
thirty days. All the organs contained some barium; lungs, muscles, and
the heart only contained traces, the liver rather more, the kidneys,
brain, and spinal cord still more, and, lastly, the bones a considerable
quantity, as much as 0·056 per cent.

[988] _Compt. rend. Soc. Biol._ (8), iv. 122-123.

§ 910. =Post-mortem Appearances.=--The _post-mortem_ appearances are
usually changes in the stomach and intestinal tract, but there are only
rarely traces of great inflammation. It is true, that in a case recorded
by Wach,[989] perforation of the stomach was found; but, since there was
old-standing disease of both liver and stomach, it is not clear that
this is to be attributed entirely to poison. In the case of suicide just
detailed, the mucous membrane of the stomach was much ecchymosed; over
the whole were strewn little white grains, sticking to the mucous
membrane, and there were also ecchymoses in the duodenum.

[989] Henke’s _Zeitschrift f. Staatsarzneik._, 1835, Bd. 30, Hft. 1, §
1.

§ 911. =The Separation of Barium Salts from Organic Solids or Fluids,
and their Identification.=--In the usual course of examination of an
unknown substance, the matter will already have been extracted by
hydrochloric acid, and the solution successively treated with hydric and
ammonic sulphides. The filtrate from any precipitate, after being
boiled, would in such a case give a precipitate if treated with
sulphuric acid, should a salt of barium soluble in hydrochloric acid be
present.

If there, however, should be _special_ grounds to search for baryta in
particular, it is best to extract the substances with pure boiling
water, to concentrate the solution, and then add sulphuric acid,
collecting any precipitate which may form. If the latter is found to be
sulphate of baryta, it must be derived from some soluble salt, such as
the nitrate or the chloride. The substances which have been exhausted
with water are now treated with hydrochloric acid, and to the acid
filtrate sulphuric acid is added. If sulphate of baryta is thrown down,
the baryta present must have been a salt, insoluble in water, soluble in
acids--probably the carbonate. Lastly, the organic substances may be
burnt to an ash, the ash fused with carbonate of soda, the mass, when
cool, dissolved in HCl, and the solution precipitated with sulphuric
acid. Any baryta now obtained was present, probably in the form of
sulphate; nevertheless, if obtained from the tissues, it would prove
that a soluble salt had been administered, for (so far as is known)
sulphate of barium is not taken up by the animal fluids, and is
innocuous.

The sulphate of barium is identified as follows:--

(1) A part of the well-washed precipitate is boiled with distilled
water, filtered, and to the filtrate a solution of chloride of barium
added. If there is no precipitate, the sulphate can be none other than
baric sulphate, for all the rest, without exception, are soluble enough
to give a slight cloud with baric chloride.

(2) The sulphate may be changed into sulphide by ignition on charcoal,
the sulphide treated with HCl, the solution evaporated to dryness, and
the resulting chloride examined spectroscopically; or, the sulphide may
be mixed with chloride of calcium, taken up on a loop of platinum wire,
heated strongly in the flame of a Bunsen burner, and the flame examined
by the spectroscope.

(3) A solution of the chloride of barium obtained from (2) gives a
yellow precipitate with neutral chromate of potash, insoluble in water,
but soluble in nitric acid.




APPENDIX.


Treatment by Antidotes or otherwise of Cases of Poisoning.

§ 912. All medical men in practice are liable to be summoned hastily to
cases of poisoning. In such emergencies not a moment is to be lost, for
valuable lives have ere this been sacrificed simply from the delay
caused by searching for medicines and instruments, and visiting the
patient unprovided with suitable remedies. Hence it is far the safest
plan for every medical man to provide himself with an “_antidote bag_,”
which, to be complete, should be furnished with the following
requisites:--


I. INSTRUMENTS:--

(1.) A =stomach-pump= or =tube=,[990] with proper mouth gags.

[990] The stomach-tube is simply a tube of india-rubber, from 6 to 8
feet in length, one end of which should be a little stiff, and
have a solid rounded extremity pierced with two lateral oval
holes--catheter-like; but, on an emergency, any india-rubber tube of a
suitable length will do. It is used by passing the proper end gently
down the throat into the stomach; if the patient is insensible, or, as
in some determined suicides, obstinate, the jaws must be forcibly opened
by the handle of a spoon, and some solid substance placed between the
teeth so as to give sufficient room for the entry of the tube. If the
tube is now passed in the median line well into the grasp of the
pharynx, it is actually drawn down into the stomach by the pharyngeal
muscles, so that the operator has, as it were, only to “pay out” a
sufficient quantity of the tubing. Holding the tube in a perpendicular
position, it may then be filled with water by means of a small funnel.
When full, the end must be pinched and brought down to the ground to
deliver in a basin; it will then act as a syphon and the contents of the
stomach will be syphoned off. The tube is elevated again above the body,
and the stomach filled with water; this syphoned off, and the process
repeated. Coffee, also, or antidotes may be conveniently introduced. If
the recumbent position is necessary, the patient must, of course, be
placed on a bed or table, in order that there should be sufficient fall
for the syphon.

(2.) A =hypodermic syringe=.

(3.) An ordinary bleeding =lancet=.

(4.) A =glass-syringe= with suitable canula, which may, in case of
necessity, be used for transfusion.

(5.) =Bistoury=, =forceps= and =tubes= suitable for performing
=tracheotomy=.

A small =battery= (interrupted current).


II. EMETICS:--

(1.) _Sulphate of zinc._

(2.) _Apomorphine._

(3.) _Mustard._

(4.) _Ipecacuanha._

The _sulphate of zinc_ may either be carried in 30-grain powders or in
the ordinary solid crystalline state, together with a little measure
made out of a small pill-box which, when exactly full, is found to
contain from 25 to 30 grains.

A still more convenient form is that of the compressed tablets, sold as
a speciality by one or more firms. The same remarks apply to
_ipecacuanha._

The _apomorphine hydrochlorate_ should be in solution, a suitable
strength is 2 per cent.; a few drops of this substance, injected
hypodermically, will cause vomiting in a few minutes.

Besides the above list, the bag should be furnished with a selection of
the so-called antidotes.


III. ANTIDOTES:--

(_a._) _Chemicals neutralising the poison._

=Acetic acid= and =calcined magnesia=.

(_b._) _Precipitants of alkaloids._

=Tannin=--A solution of =iodine in potassic iodide=.

(_c._) _Narcotics, or anæsthetics,_ for the treatment of the tetanic
class.

=Chloral=--chloroform.

(_d._) _Substances which act physiologically._

=French oil of turpentine.=--A solution of =atropine sulphate= for
hypodermic use (strength ·8 per cent.); hypodermic dose from 5 to 6
drops.

Solution of =nitrate of pilocarpine= (strength 5 per cent.); dose, 10
drops or more.

=Muscarine=--a solution in water (strength 5 per cent.); dose, 10 drops.

=Morphine meconate= in solution (strength 10 per cent.); dose, from 5
drops.

A solution of =nitrate of strychnine= (strength 2 per cent.); hypodermic
dose, from 2 to 3 drops.

=Potassium Permanganate= in crystals.

To these may be added a bottle of =Wyeth’s dialysed iron= for use in
arsenic poisoning, a flask of =brandy=, some =chloric ether=, =aromatic
spirits of ammonia=, and some really good =extract of coffee=.


TREATMENT.

§ 913. ACID CARBOLIC.

Use the =stomach-tube= or =pump=, unless there is great destruction of
the mucous membrane. In the latter case, excite vomiting by injecting
subcutaneously from 5 to 6 drops of the =apomorphine= solution; or give
an emetic of =zinc sulphate=, =ipecacuanha=, or =mustard=.

The stomach may, by the aid of the tube, be washed out with a weak
alkaline solution of =soda=; =albumen= may also be given, and such
stimulants as =brandy= and =water=, =chloric ether=, and =aromatic
spirits of ammonia=.

It is important to apply warmth to the extremities.

Inject subcutaneously from 2 to 3 drops of the =atropine hypodermic=
solution.

=Nitrite of amyl= by inhalation is said to have been useful.

In desperate cases =bleeding=, followed by =transfusion=, is to be
considered.


ACIDS--MINERAL, including SULPHURIC, NITRIC, HYDROCHLORIC, GLACIAL
ACETIC ACIDS.

=Stomach-tube= or =pump=, inadmissible.

Neutralise by calcined =magnesia=, =lime=, =chalk=, or =soda,= but not
with potash, if there is choice.

If no neutralising agent can be immediately procured, then dilute with
plenty of water.

Other remedies are--=oil=, =milk=, =white of eggs=, =gruel=.

It is often recommended in such cases to administer hypodermically a
little =morphine=.


ACONITE--ACONITINE.

Use at once the =stomach-tube= or =pump=, or give emetics of =sulphate
of zinc=, or hypodermic solution of =apomorphine=.

Keep the patient in the recumbent posture.

After the stomach has been emptied, give =atropine=, either by
hypodermic injection or by the mouth, say 4 drops of the P.B. solution;
failing atropine, 20 drops of the tincture of =belladonna=. The dose may
be repeated more or less frequently according to the condition of the
patient.

If there is great tendency to heart-syncope, tincture of =digitalis= in
½-drachm doses by the mouth, or in hypodermic doses of from 10 drops
upwards.

Apply a mustard poultice to the pericardium; aid vomiting and
elimination of the poison by plenty of water, to which may be added
brandy or any form of alcohol.

Inhalations of =nitrite of amyl= are said to have been useful. If the
breathing stops, try =artificial respiration=.


ALCOHOL.

Empty the stomach by the =tube= or =pump=, and then wash it out with
warm coffee; if the stomach-tube is not at hand, then empty the stomach
by hypodermic injection of 5 drops of =apomorphine=, or by a =mustard=
emetic, or =sulphate of zinc=. Keep the body very warm, but the cold
=douche= may be applied to the head.

Endeavours should be made to rouse the patient, if insensible, by
shaking, shouting at him, &c.

Inhalations of =amyl nitrite= are said to be useful.


ALKALIES--AMMONIA--POTASH--SODA.--=Stomach-pump= or =tube= not to be
used.

Vomiting nearly always present, or may be produced by administering
plenty of lukewarm water; after which give =dilute vinegar=, or the
juice of =lemons= or =oranges=; =olive oil=, the =white of eggs=,
=barley water=, =arrowroot=,= and always plenty of =water= may be
administered.

There may be œdema of the glottis, especially if ammonia has been taken.
In such a case, and death threatening from suffocation, perform
=tracheotomy=. In poisoning by ammonia, with croupous respiration, keep
the room warm, and fill it with steam by means of a bronchitis kettle.

Relieve pain by small doses of =morphine= injected subcutaneously.


AMMONIA.--See ALKALIES.


ANTIARIN.--See DIGITALIS.


ANTIMONY--TARTAR-EMETIC--ANTIMONIAL WINE, &C.

The stomach will generally have been emptied by vomiting. In those rare
cases in which this does not take place, use the =stomach-pump= or
=tube=, or give hypodermic injection of =apomorphine=.

Follow this with doses of =strong tea=, or give half-a-drachm of
=tannin= or =gallic acid= in warm water.

Give also demulcent drinks, and stimulants in small doses, frequently
repeated.

Keep the patient very warm by hot blankets and wraps.

The interrupted galvanic current to the heart may be useful.


APOCYNIN.--See DIGITALIS.


ARSENIC.

Use the =stomach-pump= or =tube=, or empty stomach by emetics, such as
hypodermic solution of =apomorphine=, or give =mustard= or =sulphate of
zinc=. The stomach should then be washed out by large quantities of
water, most conveniently administered by the pump or tube.

If the tube or pump is not at hand, then administer at once either
=dialysed iron=, or the freshly-precipitated =hydrated oxide of iron=,
obtained by precipitating the ordinary perchloride by means of carbonate
of soda or ammonia, avoiding excess of the latter. If the operator has
sufficient chemical knowledge to precipitate the iron with fair
exactness, so that there is no great excess of ammonia, or of sodic
carbonate, then filtration is unnecessary. In other cases, filter
through a handkerchief.

=Oil=, =mucilaginous drinks=, the =white of eggs=, and, if faintness
exists, small doses of =stimulants= may all be given.

If the skin is cold, warmth must be applied to the body by means of hot
blankets, &c.

Pain may be relieved by =morphine=.


ATROPINE--BELLADONNA--TINCTURE OF BELLADONNA.

Empty the stomach by means of the =stomach-pump= or =tube=.

Give an enema of =coffee=.

Administer half a grain of =pilocarpine nitrate=; or, if that is not at
hand, =morphine= or =opium= in suitable doses will act to a certain
extent antagonistic to the poison.

A subcutaneous dose of =muscarine= may be administered instead of
pilocarpine, but is not quite so good.

Hot water to the feet, alternate =douches= of cold and hot water are
found useful.

If the respiration seems likely to stop, =artificial respiration= must
be practised.


BELLADONNA.--See ATROPINE.


BENZENE.

If swallowed, then empty the stomach by =pump= or =tube=, or by the
hypodermic injection of =apomorphine=; or give emetics, such as =zinc
sulphate=, =mustard=, or =ipecacuanha=.

If the vapour has been _inhaled_, this is unnecessary.

Plenty of =fresh air=.

A subcutaneous dose of =atropine=, say 1-60th of a grain, or from 30 to
40 drops of =belladonna= tincture.

Alternate =douches= of hot and cold water to the chest, =artificial
respiration=, if necessary. The heart to be maintained by mild
interrupted shocks of the =battery= over the region of the heart.


BICHROMATE OF POTASH.--See CHROMIUM.


BRUCINE.--See STRYCHNINE.


CALABAR BEAN--PHYSOSTIGMINE.

Use =stomach-pump= or =tube=, or emetics, such as =sulphate of zinc=,
=mustard=, or =ipecacuanha=; or, better still, hypodermic solution of
=apomorphine=.

Give hypodermic doses of 1-60th grain =atropine= until the pupils
dilate. This treatment seeming to fail, =chloral= in 10-grain doses,
every quarter of an hour, has been recommended.

In certain cases =strychnine= has been used in hypodermic doses of
1-12th of a grain.

=Stimulants= and =artificial respiration= will probably be necessary in
some cases.


CAMPHOR.

Use =stomach-pump= or =tube=, or empty the stomach by emetics.

Hypodermic injections of =brandy=, inhalations of =ether=, the alternate
hot and cold =douche=, warmth to the extremities by hot blankets, &c.,
seem to be the best methods of treatment.


CANTHARIDES--CANTHARIDINE.

Use =stomach-pump= or =tube=, if the mucous membrane of the throat is
not inflamed; or, administer hypodermic dose of =apomorphine=, or give
emetics--=sulphate of zinc, mustard,= or =ipecacuanha=.

Allay pain with =morphine=. Give plenty of water and =demulcent drinks=.


CHLORAL.

Use =stomach-pump= or =tube=, and, when the stomach is emptied,
introduce by the same means =warm coffee=, or give a hypodermic
injection of =apomorphine=, or administer emetics of =sulphate of zinc=,
or =mustard=, or =ipecacuanha.=

An =enema of coffee= will be useful.

Keep the limbs warm.

Administer hypodermically 2 or 3 drops of the solution of =strychnine=
at intervals of from fifteen to twenty minutes.

Rouse the patient by various means, such as shouting, shaking, flapping
the skin with a wet towel, &c.

Inhalations of =amyl nitrite= are recommended.

=Artificial respiration= may be necessary.


CHLORATE OF POTASH.

Use the same treatment as for =nitrate of potash= (_which see_, p.
696).


CHLORIDE OF ZINC.--See ZINC.


CHLOROFORM--(_Inhaled_).

Give plenty of =fresh air=, pull the tongue forward, and commence at
once =artificial respiration=. If the heart has stopped, strike the
chest two or three times very hard, over the region of the heart; this
has been found occasionally to restore its beat. Apply the =battery=,
but with a weak current only; one pole may be placed on the larynx, the
other at the pit of the stomach.

Inhalations of =nitrite of amyl= are useful. The hot and cold =douche=
may also be used.


CHLOROFORM--(_Swallowed_).

Empty the stomach by =pump= or =tube=, or by emetics, such as 5 drops of
the hypodermic solution of =apomorphine=, or =sulphate of zinc=, or
=mustard=.

Give an enema of =hot coffee=.

Administer large draughts of =water=, which may advantageously contain a
little =sodic carbonate= in solution.

Attempt to rouse the patient. =Nitrite of amyl= inhalations, and, if
necessary, =artificial respiration= may be used.


CHROMATE OF POTASH.--See CHROMIUM.


CHROMIC ACID.--See CHROMIUM.


CHROMIUM--BICHROMATE OF POTASH--CHROMATE OF POTASH--CHROMIC ACID.

Empty the stomach by =pump= or =tube=; administer a subcutaneous
injection of =apomorphine=, or give =sulphate of zinc=, =mustard=, or
=ipecacuanha= as emetics. Follow up by administering, suspended in
water, calcined magnesia, or carbonate of magnesia, or chalk.

=Demulcent drinks=, such as =barley-water=, &c.


COCCULUS INDICUS.--See PICROTOXIN.


COLCHICUM--MEADOW SAFFRON--COLCHICUM WINE, TINCTURE, &C.

Use =stomach-pump= or =tube=, or empty the stomach by emetics, such as
=sulphate of zinc=, or =mustard=, or =ipecacuanha=; or, better than all,
give a hypodermic injection of 4 or 5 drops of the solution of
=apomorphine=.

Give =tannin= or =gallic acid= in ½-drachm doses, or strong tea or
coffee.

Allay the pain in the bowels and purging by small doses of =opium= or
=morphine=.

Keep the extremities warm, apply hot fomentations to the abdomen;
=stimulants= may be used, give plenty of =water= and =demulcent
drinks=.


COLOCYNTH.

Treatment on the same lines as that for COLCHICUM.


CONIUM--HEMLOCK.

Empty the =stomach= by the =pump= or =tube=, or give a hypodermic
injection of 4 or 5 drops of the solution of =apomorphine=, or emetics
of =sulphate of zinc=, or =mustard=.

Keep up the temperature of the body by hot wraps.

Administer, as a drink, strong =tea=, =tannin=, =gallic acids=, or any
harmless vegetable decoction containing tannin.

=Stimulants= may be administered.

If necessary, use =artificial respiration=.


COPPER--SALTS OF.

Empty stomach by =pump= or =tube=, and either inject by the same means
or administer =white of egg= in solution in water; if no white of eggs
can be had, substitute milk; give plenty of =water= and =emollient
drinks=.

Pain may be allayed by =opium= or =morphine=.


CORROSIVE SUBLIMATE--PERCHLORIDE OF MERCURY--NITRATE OF MERCURY.

Empty the stomach by the =tube= or =pump=, and wash the organ out with
plenty of white of egg, dissolved in water or milk. If the stomach-pump
is not at hand, then give emetics, such as the solution of
=apomorphine=, hypodermically, in from 4 to 5-drop doses, or a =zinc
sulphate= emetic, or =mustard=, or =ipecacuanha=. Probably violent
vomiting is already present, then stomach-tube or emetics are
unnecessary: but, in any case, give plenty of albuminous fluids, such as
=white of egg= in water or =milk=. If neither of these is at hand, chop
any =fresh meat= up as finely as can be done in a short space of time,
diffuse in water, and administer. Follow up with =demulcent drinks=,
such as =barley-water=, =flour= and =water=, &c.

Pain may be allayed with a little =opium= or =morphine=.

=Stimulants= are admissible, if necessary.


CROTON OIL.

Empty stomach by means of =tube= or =pump=, or give emetics of =mustard=
or =sulphate of zinc=, or administer hypodermic injection of
apomorphine.

Give 10 drops of =laudanum= every twenty minutes or half hour, until the
pain and purging are somewhat abated, or else inject subcutaneously
small doses of =morphine= at intervals.

Give plenty of =demulcent drinks=.

Two or three drops of =essence of camphor= in milk are useful.

Stimulants, such as =brandy=, =ammonia=, or =chloric ether=, are
admissible.


CYTISINE.--See LABURNUM.


CURARINE--WOORARI--URARI.

The poison is of course introduced by a wound; if any is likely to be
still in the wound apply a =ligature=, =suck the wound=, and then wash
it with a slightly alkaline solution of =potassic permanganate=.

Keep up the =respiration artificially=, give plenty of =water= and a
dose of spirits of nitre, apply warmth to the loins. By these means the
poison will be rapidly separated by the urine; and, if the patient can
only be kept alive by artificial respiration for a little time, he may
recover, for elimination is very rapid.


CYANIDE OF POTASSIUM.--See PRUSSIC ACID.


DIGITALIS GROUP OF HEART POISONS, _including_, besides the DIGITALINS,
ANTIARIN, APOCYNIN, NERIIN, OLEANDRIN, EVONYMIN, THEVETIN, SCILLAIN,
STROPHANTIN, and ERYTHROPHLEIN.

Empty the stomach by the =tube= or =pump=, or administer a subcutaneous
dose (4 drops) of =apomorphine=, or give a tablespoonful of =mustard= in
water, or =sulphate of zinc=.

Follow up with strong =tea=, or half a drachm of =tannin=, or =gallic
acid= in aqueous solution.

A very small dose of =aconitine nitrate= in solution (say 1-200th of a
grain) may be injected subcutaneously and the effect watched; if in a
little time it seems to do good, repeat the dose. On no account let the
patient rise from the recumbent posture, or he may faint to death.

=Stimulants= in small doses may be given frequently by the mouth, or, if
there is vomiting, by the bowel.


ERGOT.

Use =stomach-pump= or =tube=, or empty the stomach by a =mustard= or
=sulphate of zinc emetic=, or give a subcutaneous injection of
=apomorphine=.

Give a purgative, such as a drop of =croton oil=, and assist its action
by plenty of warm drinks.

=Tannin= and =gallic acid= have also been recommended, but are probably
of but little use.

After the bowels have well acted, and the stomach has been emptied, give
small doses of =opium= at intervals.

Dr. Murrell recommends 1-50th of a grain of =nitro-glycerin= every
fifteen minutes.

The recumbent position is necessary, and the circulation should be
maintained by warmth, and, if necessary, by friction.


ERYTHROPHLEIN.--See DIGITALIS.


ETHER.--The same treatment as with CHLOROFORM.


EVONYMIN.--See DIGITALIS.


FUNGI.--See MUSHROOMS.


GELSEMININE.

If seen soon after taking the dose, use the =stomach-pump= or =tube=, or
give a tablespoonful of =mustard=.

Administer a small dose of =atropine= subcutaneously, or give by the
mouth tincture of belladonna in 20-drop doses.

=Stimulants= are admissible.

If necessary, use =artificial respiration=.

Rouse the patient by hot and cold =douches=.


HEMLOCK.--See CONIINE--CONIUM.


HENBANE--HYOSCYAMINE.--The same treatment as for ATROPINE.


HYDROCHLORIC ACID.--See ACIDS, MINERAL.


HYDROCYANIC ACID.--See PRUSSIC ACID.


HYOSCYAMINE.--The same treatment as for ATROPINE.


IODINE.

Empty the stomach by =pump= or =tube=, or administer emetics, such as
the hypodermic solution of =apomorphine=, or give by the mouth =mustard=
or =sulphate of zinc=.

Give plenty of =starch= diffused in warm water, or in the form of a
dilute paste; or give any =farinaceous substance= whatever, such as
=arrowroot=, =boiled rice=, or =flour=, or thin =gruel=.

Inhalations of =amyl nitrite= have been recommended.

Pain may be relieved by =morphine= or =opium=.


JABORANDI.--Treatment the same as PILOCARPINE.


LABURNUM SEEDS--CYTISINE.

Empty stomach by =tube= or =pump=, and wash it out with =tea= or
=coffee=, or give (as an emetic) a hypodermic dose of =apomorphine=, or
(by the mouth) =mustard= or =zinc sulphate=; follow up this treatment by
an enema, or a brisk =purgative=.

=Stimulants= may be administered, the patient may be roused by the hot
or cold =douche=.


LAUDANUM.--See MORPHINE.


LAUREL WATER.--See PRUSSIC ACID.


LEAD--SALTS OF.

Empty stomach by =pump= or =tube=, or administer subcutaneously a dose
of =apomorphine=, 4 to 5 drops; or give by the mouth a =sulphate of
zinc= or =mustard= emetic. Follow up with half a drachm of =dilute
sulphuric acid=, or half an ounce of =magnesic= or =sodic sulphate=.

=Milk= and =albuminous fluids= may be given.

Allay pain with =opium= or =morphine=. Treat colic with hot
fomentations.


MEADOW SAFFRON.--See COLCHICUM.


MERCURY, SALTS OF.--See CORROSIVE SUBLIMATE.


MONKSHOOD.--See ACONITE.


MORPHINE--OPIUM--_Laudanum and preparations in which the OPIUM ALKALOIDS
predominate._

If taken by the mouth, give at once a solution of potassium permanganate
and then empty the stomach, but, if taken by hypodermic injection, both
these would be useless. The stomach in opium-poisoning is best relieved
by the =pump= or =tube,= and should then be well washed out with hot
=coffee=, leaving in the organ a pint or more. If the stomach-pump or
tube is not at hand, a large subcutaneous dose of =apomorphine= (say 10
minims) may be given, or =mustard= or =zinc sulphate=, but there may be
difficulty in obtaining vomiting from any emetic.

Attempt to rouse the patient by the =battery=, if at hand; by flips with
a towel, and by shaking. In all books will be found the usual direction
that you are to keep walking the patient about; but this treatment is
questionable, and likely to favour the toxic action of morphine on the
heart.

=Ammonia= may be applied to the nostrils.

Hot =coffee= may also be introduced into the bowels by an =enema=
apparatus, or by a simple tube.

The alternate =cold and hot douche= to the head is good, but the body
should be kept warm with hot wraps.

Small subcutaneous doses of =atropine= (say 1-20th of a grain) may be
administered, repeating the close every twenty minutes, and watching the
effect.

If necessary, apply =artificial respiration=.

Inhalations of =nitrite of amyl= have been used.


MUSCARINE.--See MUSHROOMS.


MUSHROOMS--MUSCARINE--POISONOUS FUNGI GENERALLY.

Empty stomach by =stomach-pump= or =tube=, or give a subcutaneous dose
of =apomorphine=, or administer by the mouth either =mustard= or =zinc
sulphate=.

Inject as soon as possible a subcutaneous dose of 2 to 4 drops of the
solution of atropine; or, after the stomach has been emptied, give
=tincture of belladonna= every half hour, in from 20 to 30-min. doses.

It is equally important to remove the remains of the fungi from the
intestines, and for this purpose it is well to give a dose of =castor
oil=, and to use an enema.

=Stimulants= may be given. The body should be kept warm.


NERIIN.--See DIGITALIS.


NICOTINE--TOBACCO.

Unless the stomach has been already emptied by vomiting, use
=stomach-pump= or =tube=, or give an emetic of =mustard= and plenty of
water.

Inject subcutaneously a small dose of =strychnine= (say 1-25th of a
grain of the nitrate), or give half a drachm of tincture of =nux
vomica=.

=Stimulants=, such as =brandy=, =chloric ether=, &c., may be given.

Keep the body warm, but the =cold douche= may be applied to the head.

=Tannin= and vegetable infusions containing =tannin= may also be given,
but it is questionable if they are of much use, unless any remnants
remain in the stomach.

Keep the patient lying down for fear of fatal syncope.


NITRE--NITRATE OF POTASH.

Empty the stomach immediately by the =pump= or =tube=, or give a
subcutaneous dose of =apomorphine= (from 2 to 3 drops), or administer by
the mouth a tablespoonful of =mustard=, or a scruple of =sulphate of
zinc=.

Dilute the poison, and attempt to wash it out of the system by giving
plenty of =water= or =mucilaginous drinks=.

Apply hot fomentations to the loins, and keep the patient as warm as
possible.

Stimulants that are likely to increase the kidney congestion are to be
avoided.

Inhalations of =nitrite of amyl= have been recommended.


NITRIC ACID.--See ACIDS, MINERAL.


NITRO-BENZENE.

Empty the stomach at once by the= stomach-pump= or =tube=, and wash the
organ out with plenty of warm water, to which advantageously a little
spirit may be added; or give emetics, such as =zinc sulphate= or
=mustard=.

Administer stimulants, either by the stomach-tube, as an enema, or by
subcutaneous injection.

Keep up the respiration artificially, if necessary, and maintain the
heart’s action by application of weak, interrupted shocks to the
chest-wall, by means of the =battery=.

Rouse the patient by the =douche=.

=Atropine= subcutaneously has been recommended.


NITROUS OXIDE GAS.

The treatment is the same essentially as for chloroform (_which see_).

Inhalations of =oxygen= may do good, but oxygen is very rarely at hand.


NUX VOMICA.--See STRYCHNINE.


OLEANDRIN.--See DIGITALIS.


OPIUM.--See MORPHINE.


OXALIC ACID--BINOXALATE OF POTASH--SODIC OXALATE.

Unless the patient has already vomited freely, empty the stomach at once
by emetics of =zinc sulphate= or =mustard=; or the =stomach-pump= or
=tube= may, in most cases, be used. If the acid has been taken,
neutralise by =chalk=, =lime water=, or, better, by =saccharated lime
water=; but on =no= account neutralise by carbonate of soda or any
alkali, for the alkaline oxalates are extremely poisonous.

Assist elimination by the kidneys by giving plenty of water; apply hot
fomentations to the loins.

An enema may be given, if necessary, to empty the bowels well.


PHOSPHORUS.

Empty the stomach by =tube= or =pump=, and, at the same time, wash the
organ out with water to which has been added a drachm of =French
turpentine=, or give emetics. The best emetic for phosphorus is said to
be =sulphate of copper=, 4 or 5 grains dissolved in water, and given
every ten minutes until vomiting is produced.

In default of sulphate of copper, then =sulphate of zinc= or =mustard=.

Give ½-drachm doses of =turpentine=, floating on water or on mucilage,
every half hour. Inhalations of turpentine vapour, much diluted, are
also of service. The American and German turpentines are said to be of
no avail. Probably the turpentine will freely purge the patient; but, if
not, the bowels should be opened by a suitable purgative, such, for
instance, as =magnesic sulphate=.


PHYSOSTIGMINE.--See CALABAR BEAN.


PICROTOXIN--COCCULUS INDICUS.

Use =stomach-pump= or =tube=, or empty stomach by usual emetics, _e.g._,
=mustard=, =zinc sulphate=, or =apomorphine=, subcutaneously.

=Chloral=, in doses of from 10 to 20 grains, may be given every half
hour to allay or prevent tetanus, the effects being, of course, watched.
For the same purpose =bromide of potassium= has been recommended. In
severe cases, it may be combined with choral, 1 drachm of the bromide
with 20 grains of chloral.


PILOCARPINE.

The best treatment is a subcutaneous dose of =atropine= (say 1-60th of a
grain) or tincture of =belladonna= by the mouth in 20-minim doses, to be
repeated every twenty minutes until the pupils dilate.


POTASH.--See ALKALIES


PRUSSIC ACID.[991]

[991] J. Kossa, considering that potassium permanganate ought,
theoretically, to act as a chemical antidote to potassium cyanide, by
checking the paralysis of the respiratory centres, has performed some
experiments. Rabbits were shown to be fatally affected in a few minutes
by 0·01 grm. of the poison, but if, at the time of administration, 0·5
grm. of permanganate dissolved in 50 c.c. of water was also introduced
into the stomach, doses of cyanide up to 0·1 grm. failed to cause death.
Larger quantities (0·2 grm.) proved fatal under similar conditions, but
the action of the poison was much delayed. Successful experiments were
also performed with aqueous solutions of hydrocyanic acid containing 0·1
per cent. It is suggested, therefore, that, in cases of cyanide
poisoning, ½ to ⅓ litre of a 3 to 5 per cent. solution of permanganate
should be administered immediately (_Vratch_, through _Nouv. rem._, ix.
567).

Use =stomach-pump= or =tube=, or, if not at hand, an emetic of =mustard=
or =sulphate of zinc=.

If the breathing has stopped, try =artificial respiration= and weak
shocks to the heart.

1-60th of a grain of =atropine= subcutaneously is recommended to assist
the heart’s action.

A =brandy enema= may be given, or brandy injected under the skin.

The body must be kept warm, but the cold =douche= may be advantageously
applied to the head.


SALTS OF SORREL.--See OXALIC ACID.


SAVIN.

If the patient has not already emptied the stomach by repeated vomiting,
and the throat is not inflamed, use the =stomach-pump= or =tube=, and
wash the organ out with water, or give any one of the usual
emetics--such as =mustard=, =sulphate of zinc=, or =ipecacuanha=.

If the bowels have not acted well, give a dose of =castor oil=; allay
pain with small doses of morphine.


SCILLAIN.--See DIGITALIS.


SNAKES, BITE OF.

Suck the wound, and apply an alkaline solution of =permanganate of
potash=.

In severe cases of cobra poisoning and other extremely venomous snakes,
death threatening, the only likely means of saving life would be
bleeding at one arm and =transfusing= blood by the other.

=Ammonia= may be given by the mouth, and also smelt.

In cobra poisoning and venoms which kill mainly through the respiration,
the breathing must be kept up artificially; and, should there be signs
of the heart failing, weak, interrupted =galvanic= shocks may be applied
to the walls of the chest.

Lacerda’s plan of injecting permanganate of potash under the skin is not
alone useless but mischievous, for it takes up time which might be more
valuably employed.


SODA CAUSTIC.--See ALKALIES.


SOLANINE--SOLANUM DULCAMARA--BITTER SWEET--WOODY NIGHTSHADE.--The same
treatment as for ATROPINE (_which see_).


STRAMONIUM.--The same treatment as for ATROPINE.


STROPHANTIN.--See DIGITALIS.


STRYCHNINE--BRUCINE--NUX VOMICA.

Empty the stomach as quickly as possible by an emetic of =mustard=, or
=zinc sulphate=, or by a hypodermic solution of =apomorphine= (4 drops).

The =stomach-pump= or =tube= inadmissible; for, if tetanus is present,
it cannot be applied; or, if absent, it is likely to excite a spasm.

Place patient at once under =chloroform= or =ether=, and keep up a
gentle narcosis for several hours, if necessary.

Darken the room, stifle all noise; if in a town, and opportunity permit,
have straw or peat placed at once before the house to deaden noise.

If the spasms threaten the respiration, =artificial respiration= is
absolutely necessary; and, to facilitate this, it would be justifiable,
in a dangerous case, to perform =tracheotomy=, of course under
chloroform.

=Chloral= may be given in place of chloroform, but the latter is best;
the dose of =chloral= should be, at least, half a drachm, and if no
effect is produced in half an hour, then doses of 20 grains should be
given at intervals of a quarter of an hour.

If neither chloroform nor chloral is at hand, the juice from a
recently-smoked pipe may be diffused in a little water and a few drops
injected subcutaneously, and the effect watched. If there is a marked
improvement the treatment may be persevered in.

=Bromide of potassium= in combination with chloral has been recommended.

=Nitrite of amyl= inhalations are said to be of use.

=Curarine= in a subcutaneous dose of one-third of a grain is
antagonistic so far that it paralyses the voluntary muscles.


SULPHURIC ACID.--See ACIDS, MINERAL.


TARTAR EMETIC.--See ANTIMONY.


TARTARIC ACID.--The same treatment as for OXALIC ACID (_which see_).


THEVETIN.--See DIGITALIS.


TOBACCO.--See NICOTINE.


TURPENTINE.

Empty stomach by =tube= or =pump=, or administer the usual emetics, such
as =mustard=, or =sulphate of zinc=, or =ipecacuanha=, or give
hypodermically 3 or 4 drops of the solution of apomorphine.

If purging is not already present, empty the bowel by enema; give plenty
of water and demulcent drinks to aid elimination by kidneys.

Apply hot fomentations to the loins.

Allay pain with =opium= or =morphine.=


VERATRINE.

Empty the stomach by the =tube= or =pump=, or give any one of the usual
emetics--such as =mustard=, or =zinc sulphate=, or =ipecacuanha=.

Keep the patient lying down.

=Stimulants= may be administered.

An enema of =hot coffee= has been recommended.

Keep the body warm with wraps, hot blankets, &c.


WHITE PRECIPITATE.--The same treatment as for CORROSIVE SUBLIMATE.


WASPS, BEES, HORNETS--STING OF.

An =onion= immediately applied to the part stung is a favourite popular
remedy; but =ammonia= is better.

=Extract the sting=, if it remains in the wound.

Give =stimulants=, if necessary.


ZINC.

The only salt likely to cause poisonous symptoms is the chloride, which
is used in the arts, and is the active principle of Burnett’s
disinfecting fluid.

=Stomach-pump= or =tube= inadmissible. Give plenty of =water=, in which
=carbonate of soda= is dissolved; or, if that is not at hand, =carbonate
of potash=.

=Eggs= and =milk= should also be given.

Solutions of =tannin=, strong =tea=, and the like, also, to some extent,
neutralise the poison.

The pain in the abdomen is to be allayed in the usual way--by hot
fomentations and small frequent doses of =morphine= or =opium=.


DOMESTIC READY REMEDIES FOR POISONING.

§ 914. Large households, more especially those in which no one possesses
any special medical knowledge, would do well to furnish an ANTIDOTE
CUPBOARD, for use in cases of emergency. This cupboard may contain:--

(1.) _The Multiple Antidote_, which consists of saturated solution of
sulphate of iron 100 parts, water 800, magnesia 88, animal charcoal 44
parts. It is best to have the animal charcoal and magnesia mixed
together in the dry state and kept in a well-corked bottle; when
required for use, the saturated solution of sulphate of iron is mixed
with eight times its bulk of water, and the mixture of charcoal and
magnesia added with constant stirring. The multiple antidote may be
given in wine-glassful doses, frequently repeated, in poisoning by
arsenic, zinc, opium, digitalis, mercury, or strychnine; it is of no use
in phosphorus poisoning, or in poisoning by the caustic alkalies or
antimony.

(2.) _Calcined Magnesia_, for use in poisoning by acids.

(3.) _French Turpentine_, for poisoning by phosphorus.

(4.) Powdered ipecacuanha in a well-corked bottle; the bottle containing
a small pill-box which is cut down, so that when full it contains 30
grains--the proper dose as an emetic. A similar small supply of sulphate
of zinc may also be provided.

(5.) A tin of mustard.

(6.) A bottle of vinegar.

If, then, provided with such a supply, any member is known to have taken
poison, and yet the precise poison is not known, give a =sulphate of
zinc= or =ipecacuanha emetic=, and follow it up by the =multiple
antidote=, which is in itself not poisonous.

If PHOSPHORUS has been taken, then give the =French turpentine= as
directed under Phosphorus (p. 697).

If ACIDS, neutralise by the =calcined magnesia= (see Acids, mineral, p.
687).

If ALKALIES, neutralise with =vinegar= (see Alkalies, p. 688).




INDEX.


  Abel and Field’s test for bismuth, 627.
  Abrin, 462.
  Abrus, 462.
  Absynthin, 244.
  Acetaldehyde, 154.
  Acetanilide, 40.
  Aceta-trimethyl-colchicin-amide, 409.
  Acetic acid, 110.
    „    Deaths from, 29.
  Acetum digitalis, 422.
  Acetyl phenyl hydrazine, 40.
  Acid, carbolic. See _Carbolic acid_.
  Acid hæmatin, Spectrum of, 58.
  Acids, mineral. See _Hydrochloric_, _Nitric_, _Sulphuric acid_, &c.
  Acolyctin, 252.
  Aconine, 351, 354.
  Aconite alkaloids, 351.
  Aconite, Bibliography of papers relating to physiological action of,
           360, 361.
     „     Deaths from, 30.
     „     extract, 351.
     „     liniment, 351.
     „     ointment, 351.
     „     treatment of poisoning by (App.), 687.
     „     Old knowledge of, 3.
     „     Pharmaceutical preparations of, 351.
     „     poisoning, Statistics of, 361.
     „     _Post-mortem_ appearances after poisoning by, 366.
     „     root, Poisoning by, 361.
     „     seeds, 350.
     „     tincture, 351.
  Aconitine, 243, 252, 253, 351.
      „      acetate, 245 (footnote).
      „      action on fish, 359.
      „         „      frogs, 359.
      „         „      insects, 358.
      „         „      mammals, 359, 360.
      „      Carbon and nitrogen percentage in, 262.
      „      Colour reactions of, 240.
      „      Commercial, 355.
      „      gold salt, 264, 352.
      „      Phospho-molybdate of, 238.
      „      Physiological action of, 366.
      „      Poisoning by, 362.
      „      Properties of, 351, 352.
      „      Separation of, from tissues, &c., 367.
      „      Sublimation of, 259.
      „      Tests for, 352, 353.
      „      Value of Mayer’s precipitate of, 263.
  Acquetta di Perugia, 11.
  Acqua Toffana, 10, 11.
  Adder, Thuringian, 484.
  Adonidin, 434.
  Aërated waters, Detection of lead in, 609.
  Æsculin, 345 (footnote).
  Æthusa cynapium, 457.
  Agaricus pantherinus, 418.
      „    phalloides, Poisoning by, 417.
      „    ruber, 418.
  Agrostemma sapotoxin, 436.
  Ague drops, 532.
  Alchid Becher, 5.
  Alcohol, Deaths from, 29.
     „     Detection of, in chloroform, 144.
     „     Excretion of, 139.
     „     Fatal dose of, 137.
     „     _Post-mortem_ appearances after poisoning by, 138.
     „     Separation of, 51.
     „     Statistics of poisoning by, 136.
     „     Symptoms of poisoning by, 137.
     „     Toxicological detection of, 140.
     „     Treatment of poisoning by (App.), 688.
  Alcoholic poisoning, criminal or accidental, 137.
  Aldehyde, 154.
     „      groups, 39.
     „      in chloroform, 145.
  Alexander VI., Death of, by poisoning, 7.
  Ali Ahmed’s treasures of the desert, 593.
  Alkalies, Fixed caustic, 116-122.
     „      Chronic poisoning by, 120.
     „      Effects on animal and vegetable life, 118.
     „      Estimation of, 121.
     „      Local effects of, 119.
     „      _Post-mortem_ appearances of poisoning by, 119.
     „      Statistics of poisoning by, 118.
     „      Symptoms of poisoning by, 119.
      „     Toxicological detection of, 127.
      „     Treatment of poisoning by (App.), 688.
  Alkaloids, Discovery of, 15.
      „      General properties of, 236.
      „      of the veratrums, 390.
      „      Quantitative estimation of, 262.
  Alkyls replacing hydrogen, 36.
  Allantoin, 39.
  Alloxantin, 39.
  Almonds, bitter, Case of poisoning by, 209.
  Aloetin, 244.
  Alum, 676, 677.
    „   Action of, 676, 677.
    „   _Post-mortem_ appearances after poisoning by, 678.
  Aluminium, 676-679.
  Aluminic and sodic lactate, 677.
      „        „     tartrate, 677.
  Alumina, Detection of, 678, 679.
     „     Test for, 678, 679.
  Amanita muscaria, 413.
  Amanitine, Carbon and nitrogen percentage in, 262.
      „      gold salt, 264.
  Amarin, 40.
  Amines, 488-490.
  Ammonia, 111-116.
     „     action on animal life, 113.
     „     action on plants, 113.
     „     -alum, 676.
  Ammoniac and mercury plaster, 635.
  Ammonia, Deaths from, 29.
     „     Effects of, 113.
     „     Estimation of, 116.
     „     liniment, 111.
     „     and hypochlorite test for carbolic acid, 177.
     „     _Post-mortem_ appearances after poisoning by, 115.
     „     Properties of, 111.
     „     salts, Detection of, 128.
     „     Separation of, 115.
     „     Statistics of poisoning by, 112.
     „     Solution of, 111.
     „     Symptoms of poisoning by, 112.
     „     Tests for, 116.
     „     Uses of, 111.
     „     vapours, Poisoning by, 112.
  Ammoniated mercury, Effects of, 648.
      „      ointment, 637.
  Ammonic cyanide, 210.
  Amygdalin, 194.
  Amyl nitrite poisoning, 141.
  Amylic alcohol, 141.
  Anderseck’s case of corrosive sublimate poisoning, 647.
  Androctonus bicolor, 468.
       „      occitanus, 468.
  Angelic acid, 392.
  Aniline, 250.
     „     Characters of phospho-molybdate precipitate, 237.
     „     Detection of, 281.
     „     Fatal dose of, 281.
     „     Production of, from nitro-benzene, 133, 188.
     „     Properties of, 280.
     „     Separation of, 51.
     „     Spectrum of colour reaction, 55.
     „     Symptoms of poisoning by, 280.
  Animal bases, 3.
  Antiarin, 432.
  Antidote bag, 685.
  Antimonial compounds used in pyrotechny, 581.
      „      powder, 579.
  Antimonious sulphide, 577.
  Antimony, black, 580.
     „      chloride, 580.
     „      Deaths from, 29.
     „      Detection of, 587.
     „      Effects of, 582.
     „      Elimination of, 586.
     „      Flowers of, 581.
     „      Glass of, 581.
     „      in alloys, 582.
     „      metal, 577.
     „      Mirror of, 537.
     „      oxide, 579.
     „         „      vapour, 585.
     „      pentasulphide, 578.
     „      Pharmaceutical preparations of, 79, 80.
     „      pills, 580.
     „      _Post-mortem_ appearances from poisoning by, 585, 586.
     „      poisoning (chronic), 585.
     „      Quantitative estimation of, 589.
     „      salts, Doses of, 582.
     „      Separation of, 50.
     „      sulphide, Separation of, 52.
     „      sulphurated, 580.
     „      tartarated, Antidotes for, 586.
     „         „      Effects of, 583.
     „         „      Estimation of, 578.
     „      treatment of poisoning by (App.), 688.
  Antimony wine, 579.
      „    yellow, 582.
  Antipater, Trial of, 2.
  Antipyrine, Deaths from, 30.
  Antiseptic action of hydric cyanide, 203 (footnote).
  Ants, Poisonous properties of, 471.
  Aplysia, 3.
  Apocynin, 434.
  Apollodorus, 3.
  Apomorphine, 317.
       „       Separation of, 51.
  Aqua Orientalis, 630.
  Aromatic spirits of ammonia, 112.
  Aromatic sulphuric acid, 76.
  Arsen-dimethyl chloride, 38.
  Arseniate of iron, 530.
      „     of soda, 530.
  Arsenic chloride, 529, 575, 576.
  Arsenic, Deaths from, 29.
     „     Detection of, 555.
     „          „    in antimony sulphide, 578.
     „     Doses of, 535.
     „     eaters, 538.
     „     Effects of, on animals, 536, 537.
     „        „    man, 538.
     „        „    plants, 535.
     „     Elimination of, 553.
     „     Estimation of, 566-568.
     „           „        as trisulphide, 571.
     „     Imbibition of, after death, 563.
     „     in the arts, 529.
     „     in glycerin, 560.
     „     in organic matters, 560.
     „     Introduction of, 539.
     „     Hydrochloric acid solution of, 530.
     „     (arsenious anhydride), Properties of, 524, 525.
     „     Law relating to, 535.
     „     Localisation of, in the body, 561, 562.
     „     Metallic properties of, 524.
     „     Mirrors of, 557.
     „     Pharmaceutical preparations of, 530.
     „     Physiological action of, 552.
     „     poisoning, Absence of symptoms in, 545.
     „         „      Antidotes for, 553, 554.
     „         „      Microscopical appearances of liver in, 552.
     „         „      Museum preparations illustrative of, 550, 551.
     „         „      _Post-mortem_ appearances of, 548-552.
     „     Separation of, 49, 50.
     „         „      by Chittenden’s method, 568, 569.
     „     Slow poisoning by, 546.
     „     Solubility of, 525.
     „     Statistics of poisoning by, 534.
     „     sulphide, 52, 528, 529, 573, 575.
     „     treatment of poisoning by (App.), 689.
  Arsenious acid. See _Arsenic_.
  Arsenites and Arseniates, Tests for, 555.
  Arsen-methyl-chloride, 38.
  Arseniuretted hydrogen. See _Arsine_.
  Arsine, Development of, in Fleitmann’s process, 571.
     „    effects on man, 527.
     „    uses in the arts, 527.
     „    Properties of, 525, 526.
  Arum maculatum, 465.
    „  seeds, Death from, 30.
  Aselline, 506.
  Asiatic knowledge of poisons, 4.
  Asparagin, Percentage of carbon and nitrogen in, 262.
  Aspidospermine, 344.
  Atkinson’s infant preserver, 288.
  Atropine, 251, 368, 369.
     „      Action of, on animals, 377.
     „          „         infusoria, 42.
     „          „         man, 377, 378.
     „      and strychnine, Tests for, 374.
     „      antagonistic to muscarine, 416.
     „      Accidental and criminal poisoning by, 375, 376.
     „      Carbon and nitrogen content of, 262.
     „      Chronic poisoning by, 379.
     „      Colour reactions of, 240.
     „      Deaths from, 30.
     „      effects on the iris, 374.
     „      effects on the heart in digitalis poisoning, 429.
     „      Fatal dose of, 376, 377.
     „      Gold salt of, 264.
     „      Melting point of, 259.
     „      Pharmaceutical preparations of, 371.
     „      Physiological action of, 380.
     „      Phospho-molybdate of, 238.
     „      poisoning, Diagnosis of, 380.
     „          „      _Post-mortem_ signs after poisoning by, 380.
     „          „      Statistics of, 375.
     „          „      Treatment of, 380.
     „      Properties of, 371, 372.
     „      Separation of, from organic matters, 381.
     „      Separation of, from the urine, 381.
     „      Tests for, 372, 373.
     „      Treatment of poisoning by (App.), 689.
     „      Value of Mayer’s precipitate, 263.
  Attalus Phylometer, 2.
  Autenrieth’s general process of analysis for poisons, 50-54.

  Bain de Tessier, 533.
  Baking-powder, 677.
  Bamberger’s views as to hydrogenised bases, 36.
  Barium, 679.
     „    carbonate, 680.
     „    Characters of, 680.
     „    chloride, Deaths from, 29.
     „    Koningh’s method of detection, 675.
  Barium salts, Effect of, on man, 681, 682.
     „     „    Fatal dose of, 682.
     „     „    Localisation of, 683.
     „     „    Separation and detection of, 684.
     „     „    Symptoms of poisoning by, 682.
     „   sulphate, 680.
     „       „     Identification of, 684.
     „   sulphide, 680.
  Barley, Content of copper in, 612.
  Battle’s vermin-killer, 328.
  Bécoeur’s soap, 533.
  Belladonna, Alkaloids of, 369.
      „       Deaths from, 30.
      „       Pharmaceutical preparations of, 370, 371.
  Benzene, 131-133.
     „     Purification of, 132.
     „     Treatment of poisoning by (App.), 689.
  Benzoic acid, Tests for, 354.
  Benzoline, 129.
  Benzoyl-aconine, 351-353.
  Benzoyl chloride method of isolating diamines, 487.
  Berberine, 245.
      „      Carbon and nitrogen content of, 262.
      „      Gold salt of, 264.
      „      Phospho-molybdate of, 238.
  Bergeron and L’Hôte’s researches on copper, 613.
  Bernatzic’s views on copper poisoning, 617.
  Bernhardt’s case of poisoning by carbon disulphide, 164.
  Berzelius’ test for arsenic, 554.
  Besnou on specific gravity of alcohol and chloroform, 145.
  Betaine, 501, 502.
     „     Carbon and nitrogen percentage of, 262.
  Bibliography of chief works on toxicology, 16.
  Bicarbonate of soda lozenges, 118.
  Bichromate of potash. See _Chromium_.
  Bichromate disease, 671, 672.
  Binoxalate of potash, 572.
  Binz’s theory of the action of arsenic, 553.
  Bishop Stortford cases of food poisoning, 507.
  Bismuth citrate solution, 625.
     „    Extraction and detection of, 626.
     „    Estimation of, 627, 628.
     „    in the arts, 625.
     „    lozenges, 624.
     „    Medicinal doses of, 625.
     „    nitrate, 625.
     „    oxide, 625.
     „    oleate, 625.
     „    peroxide, 624.
     „    potassium iodide, 237.
     „    Properties of, 624.
     „    Separation of, 50.
     „    subgallate, 625.
     „    subiodide, 625.
     „    sulphide, 624.
     „    Tests for, 626, 627.
     „    Toxic effects of, 625.
  Bitter aloes, Deaths from poisoning by, 30.
  Black drop, 287.
    „   bryony, 465.
  Blair’s gout pills, 412.
  Bleaching-powder, 71.
  Blondlot’s apparatus for production of phosphine, 231.
      „      modification of Marsh’s test, 56.
  Blood, Action of ammonia on, 114.
    „    Characters of, in arsine poisoning, 527.
    „         „         carbon oxide poisoning, 59, 66.
    „         „         dinitrobenzol poisoning, 191.
    „         „         hydric sulphide poisoning, 58.
    „         „         nitrobenzol poisoning, 187, 191.
    „         „         phosphine poisoning, 224.
    „         „         phosphorus poisoning, 222.
    „         „         sulphuric acid poisoning, 90.
    „    Examination of, 56-63.
    „    Guaiacum test for, 61.
    „    corpuscles of man and animals, 62.
    „    Spectroscopic examination of, 57.
    „    spots, Treatment of, 60, 61.
  Blowfly, Action of digitalins on, 429.
     „     Action of poisons on, 43.
  Blue pill, 634.
  Bluestone, 616.
  Bocarmé, Count, 274.
  Bocklisch’s flask, 486.
  Böhm’s experiments on barium, 681.
  Boletus satanas, 418.
  Bottcher’s depilatory, 680.
  Bottger’s observations on copper, 611.
  Boyle, Hon. Robert, 13.
  Braun’s method of estimating HCl, 101.
  Bread, Content of copper in, 612.
  Brieger’s process for ptomaines, 485.
  Brighton Green, 616.
  Brinvilliers, Mad. de, 11.
  Britannia metal, 582.
  Britannicus, Death of, by poison, 6.
  Bromine as a test for carbolic acid, 178.
  Bromo-picrotoxin, 452.
  Brown’s lozenges, 639.
  Brucine, 248, 251, 340.
     „     Colour reactions of, 240.
     „     Melting-point of, 260.
     „     picrate, 340.
     „     Phospho-molybdate of, 238.
     „     Physiological action of, 341.
     „     Platinum salt of, 264.
     „     Separation of, from organic matters, 343.
     „     Separation of, from strychnine 323.
     „     Spectrum of colour reactions, 55.
     „     sulphate, 341.
     „     Tests for, 342, 343.
     „     Value of Mayer’s reagent, 263.
  Brugnatelli’s method of detecting mercury, 653.
  Brunswick green, 616.
  Buchner on solubility of arsenic, 525.
  Burnett’s fluid, 657.
     „      Symptoms of poisoning by, 660.
  Busscher’s case of aconitine poisoning, 363.
  Butter of antimony, 587.
  Butylamine, 506.
  Bynssen’s observations on the elimination of mercury, 650.

  Cadaverine, 494, 495.
  Cadmium, 590.
     „     Fatal dose of, 590.
     „     in the arts, 590, 591.
     „     oxide, 590.
     „     Separation and detection of, 50, 52, 590.
     „     sulphide, 590.
  Caffein, 40.
     „     Spectrum of murexide test for, 55.
  Calabar bean. See _Physostigmine_.
  Calomel, 634, 636.
  Calvert’s Carbolic acid powder, 167.
  Camphor, 135, 243.
     „     Compound liniment of, 111.
     „         „    tincture of, 285.
     „     Deaths from, 30.
     „     Effects of, 135.
     „     _Post-mortem_ appearances after poisoning by, 136.
     „     Separation of, 136.
     „     Spirits of, 135.
     „     Treatment of poisoning by (App.), 690.
     „     water, 135.
  Camphorated oil, 30.
  Camphoric acid, 135.
  Cantharides, 471.
       „       Deaths from poisoning by, 30.
       „       Effects of, on animals, 472.
       „          „           man, 473.
       „       Fatal dose of, 472.
       „       Pharmaceutical preparations of, 472.
       „       _Post-mortem_ appearances after poisoning by, 474.
       „       Tincture of, 472.
       „       Treatment of poisoning by (App.), 690.
  Cantharidin, 244, 260, 471, 472.
       „       Tests for, 475.
  Capsicin, 243.
  Capsicum alkaloids, 248.
      „    seeds, as distinguished from Datura, 248.
  Carbolic acid, 242.
        „        Changes in urine after taking, 174.
        „        Colorimetric method of estimating, 183.
        „        Deaths from, 29.
        „        Effects of, on animals, 169, 170.
        „        effects on man, 173.
        „        Examination of urine for, 181.
        „        Fatal dose of, 169.
        „        in organic fluids, 180.
        „        Museum preparations illustrative of poisoning by, 176.
        „        _Post-mortem_ appearances in cases of poisoning by,
                 166.
        „        powder, 167, 183.
        „           „    Assay of, 181, 183.
        „        Properties of, 166,
        „        Separation of, 51, 176, 180.
        „        soap, 167, 183.
        „        Statistics relating to poisoning by, 167.
        „        Symptoms produced by, 170.
        „        Tests for, 177, 178.
        „        Uses of, 167.
  Carbon bisulphide, 163-165.
     „        „      Deaths from, 29.
     „        „      Chronic poisoning by, 164.
     „        „      Poisoning by, 163.
     „        „      Properties of, 165.
  Carbon monoxide, 64-71.
     „      „      blood, Characters of, 58, 59.
     „      „      Detection of, 70.
     „      „      Mass poisoning by, 67.
     „      „      Properties of, 64.
     „      „      Symptoms of poisoning by, 64.
     „      „      _Post-mortem_ appearances after poisoning by, 67.
  Carbylamine, 490.
  Carnelley’s observations on the solubility of copper, 610, 611.
  Carlisle, A case of food poisoning, 508.
  Cascarillin, 245.
  Cassava root, Prussic acid in, 195.
  Cassella, Yellow, 582.
  Castor seeds, 462.
     „   Deaths from, 30.
  Cattle poisoning by meadow saffron, 411.
  Cayenne pepper, 30.
  Cedrenes, 133.
  Cephalopods, Action of poisons on, 43.
  Cerbera odallam, 434.
  Cevadine, 392.
  “Chandoo,”  305.
  Charles IX. as a poisoner, 8.
  Chelidonine, Carbon and nitrogen content of, 262.
       „       Spectrum of colour reaction of, 55.
  Chenot’s death by carbon monoxide, 65.
  Ching’s Worm lozenges, 639.
  Chittenden’s method of estimating arsenic, 568.
       „       on the local distribution of arsenic, 562.
  Chloral, 154.
     „     Chronic poisoning by, 160.
     „     Deaths from, 30.
     „     Detection of poisoning by, 155.
     „     Effects of, on animals, 156.
     „        „           man, 157.
     „     Excretion of, 161.
     „     Fatal dose of, 158.
     „     Statistics of poisoning by, 155.
     „     Treatment of poisoning by, 160, (App.) 690.
     „     Properties of, 154.
     „     Separation of, 51, 162.
     „     Symptoms of poisoning by, 159.
  Chlorcodeine, 299.
  Chlorine, 72.
      „     Detection of, 72.
      „     Effects of, 72.
      „     _Post-mortem_ appearances in cases of poisoning by, 72.
  Chlorodyne, 288.
       „      Deaths from, 30.
  Chloroform, 143.
       „      Chronic poisoning by, 151.
       „      Detection and estimation of, 152, 153.
       „      Effects of liquid, 148.
       „         „       vapours of, 148-152.
       „      Fatal dose of liquid, 147.
       „      Impurities in, 144.
       „      Local action of, 146.
       „      Manufacture of, 145, 146.
       „      Physiological effects of, 150.
       „      Properties of, 144.
       „      _Post-mortem_ appearances after poisoning by, 148, 152.
       „      Separation of, 51.
       „      Statistics of poisoning by, 146, 148.
       „      Suicidal and criminal poisoning by, 149.
       „      Treatment of poisoning by (App.), 691.
  Chloroxalmethyline, 522.
  Chodomisky on the solubility of arsenic, 525.
  Choline, 41, 415, 500.
  Chromate of lead, Poisoning by, 673.
      „       potash, 670.
  Chrome red, 594, 671.
     „   yellow, 594, 671.
  Chromic acid, Deaths from, 29.
  Chromium, 670-675.
     „      compounds, Effects of, 671.
     „      Detection of, 674, 675.
     „      Separation of, 53.
     „      Statistics of poisoning by, 672.
     „      Treatment of poisoning by (App.), 691.
  Chrysammic acid, 244.
  Chrysophyllum glycyphleum, 437.
  Cicutoxin, 456, 457.
      „      Effects of, on animals, 456.
      „         „           man, 456, 457.
      „      Separation of, 457.
  Cinchonidine colour reaction with potash, 240.
        „      Platinum salt of, 264.
  Cinchonine, 246, 252, 253.
       „      colour reaction with potash, 240.
       „      Phospho-molybdate of, 238.
       „      Platinum salt of, 264.
       „      Value of Mayer’s precipitate of, 263.
  Cinnabar, 638.
  Cleator Moor case of mass poisoning by hydric sulphide, 74.
  Clemen’s solution of arsenic, 530.
  Cleopatra’s asp, 484.
  Cloth, Action of hydrochloric acid on, 95.
  Clupea thrissa, 469.
  Coal gas, Content of carbon monoxide in, 64.
    „  creasote, 165.
    „  tar naphtha, 130-133.
  Cobalt nitrate as an antidote to prussic acid, 203 (footnote).
  Cobalt. See _Nickel and Cobalt_.
  Cobra poison, 478-480.
    „      „    Antidotes to, 480.
    „      „    Detection of, 482.
    „      „    Effects of, on animals and man, 479.
    „      „    Fatal dose, 479.
    „      „    Treatment of poisoning by (App.), 698, 699.
  Cocaine, Action of, on pilocarpine, 403.
     „      Carbon and nitrogen percentage of, 262.
     „     Chronic poisoning by, 349.
     „     Deaths from, 30.
     „     Effects of, 349.
     „     Fatal dose of, 350.
     „     hydrochlorate, 348.
     „     Pharmaceutical preparations of, 348.
     „     _Post-mortem_ appearances in cases of poisoning by, 349.
     „     Properties of, 347, 348.
     „     Separation of, and Tests for, 348, 349.
     „     Sublimation of, 259.
  Cocculus Indicus, Deaths from, 30. See _Picrotoxin_.
  Cochineal, Spectrum of, 59.
  Codamine, Reactions of, 317.
  Codeine, 252.
     „     Carbon and nitrogen of, 262.
     „     Colour reactions of, 240.
     „     Effects of, 311.
     „     nitrate, 342.
     „     phospho-molybdate, 238.
     „     platinum salt, 264.
     „     Properties of, 310.
     „     Spectrum of colour reaction of, 55.
  Colchiceine, 409.
       „       Carbon and nitrogen content of, 262.
  Colchicine, 244, 408-413.
       „      Carbon and nitrogen content of, 262.
       „      Colour reactions of, 240.
       „      Effects of, on animals and man, 411.
       „      Pharmaceutical preparations of, 410.
       „      Phospho-molybdate of, 238.
       „      _Post-mortem_ appearances in cases of poisoning by, 412.
       „      Quack and patent medicines containing, 410.
       „      Separation of, 413.
       „      Tests for, 409.
  Colchicum, Ancient knowledge of, 4.
      „      Deaths from, 30.
      „      Treatment of poisoning by (App.), 691.
      „      seeds, Amount of colchicine in, 408.
  Collidine, 39.
  Colocynth, Deaths from, 30.
      „      Treatment of poisoning by (App.), 692.
  Colocynthin, 244.
  Colophene hydrocarbons, 133.
  Come’s cancer paste, 532.
  Conhydrine, 262.
  Coniine, 39, 248, 249.
     „     Carbon and nitrogen content of, 262.
     „     Colour reactions of, 240.
     „     Effects of, on animals, 267.
     „        „           blowflies, 267.
     „        „           cats, 267.
     „        „           frogs, 267.
     „        „           man, 268.
     „     Fatal dose of, 268.
     „     Pharmaceutical preparations of, 266, 267.
     „     Phospho-molybdate of, 238.
     „     Physiological action of, 268.
     „     Platinum salt of, 264.
     „     _Post-mortem_ appearances in cases of poisoning by, 264.
     „     Properties of, 264.
     „     Separation of, from organic matters, 269.
     „     Statistics of poisoning by, 267.
     „     Tests for, 265.
     „     Value of Mayer’s precipitate of, 263.
  Conium, Botanical characters of, 264.
     „    Treatment of poisoning by, 266.
  Convallamarin, 246, 254.
  Copper, Chronic poisoning by, 621.
     „    carbonate, 620.
     „    Deaths from, 29.
     „    Detection of, 625.
     „    Estimation of, 622.
     „    leguminate, 617.
     „    Medicinal dose of, 616.
     „    nitrate, 616.
     „    oxide, 610.
     „    poisoning, Statistics of, 619.
     „    _Post-mortem_ appearances in cases of poisoning by, 620.
     „    Properties of metallic, 610.
     „    salts, Toxic dose of, 619.
     „    Separation of, 52.
     „    Solubility of, in various fluids, 610-612.
     „    subacetate, 620.
     „    subchloride, 620.
     „    sulphate, 615, 616.
     „    sulphide, 610.
     „    tartrate, 617.
     „    Treatment of poisoning by, 692.
     „    Volumetric processes for estimation of, 624.
  Copperas, 668.
  Coppering of vegetables, 614.
  Cornutin, 445, 450.
  Corrosive sublimate, Dose of, 640.
      „         „      Effects of, 646.
      „         „      Treatment of poisoning by (App.), 692.
  Corydaline, 350.
  Cotton seeds, 464.
  Cream, Neill, Murders by, 325.
  Creasote, 179.
      „     Deaths from, 30.
  Cresol, 166, 178, 179.
    „     Examination of urine for, 181.
  Cresylic acid. See _Cresol_.
  Cresyl-sulphate of potash, 181.
  Criminal poisoning, 33.
  Croton oil, Deaths from, 30.
     „   Treatment of poisoning by (App.), 692.
  Crowfoot, Deaths from, 30.
  Crum’s method of estimating nitrates, 110.
  Cryptopine, Properties of, 315, 316.
  Cubebin, 244.
  Cuckoo-pint, 465.
  Curarine, 254, 405-408.
      „     Action of, on cephalopods, 43.
      „     Carbon and nitrogen content of, 262.
      „     Colour reactions of, 240.
      „     Physiological effects of, 407.
      „     Platinum salt of, 264.
      „     Separation of, 407.
      „     Treatment of poisoning by (App.), 693.
  Cushman’s method of separating strychnine, 334, 335.
  Cuttle fish, 502.
  Cyanmethæmoglobin, 203.
  Cyanogen chloride, 211.
  Cyanuric acid, 211.
  Cyclamen, 436.
  Cymene, 135.
  Cymogene, 129.
  Cyon’s experiments on barium, 681.
  Cystinuria, Amides in, 494.
  Cytisine, 387-390.
      „     Carbon and nitrogen content of, 262.
      „     Effects of, on animals and man, 389.
      „     Properties of, 388.
      „     Reactions of, 388.
      „     Treatment of poisoning by (App.), 694.

  Dalby’s carminative, 287.
  Darlaston case of poisoning by carbon monoxide, 68.
  Da Silva’s test for eserine, 399.
  Datura plant, 370.
    „    seeds, 370.
    „    poisoning in India, 376.
  Davidson’s cancer remedy, 532.
  Davie, Margaret, Execution of, 9.
  Davy’s method of generating arsine, 571.
  Delirium from Datura poisoning, 379.
  Delphinine, 252.
       „      Carbon and nitrogen content, 262.
       „      Colour reactions of, 240.
       „      Gold salt of, 264.
       „      Melting-point, 260.
       „      Phospho-molybdate of, 238.
  Delphinoidine, Gold and platinum salts of, 264.
  De Pauw’s case of poisoning by digitalis, 430.
  Dermatol, 625.
  Desquamation after chloral poisoning, 161.
  Diamines, Rate of formation of, 492.
     „      Separation of, 487.
  Dichlorethyl sulphide, 35.
  Diethylamine, 491.
  Diethylenediamine, 497.
  Digitalacrin, 421.
  Digitalein, 419, 420.
  Digitaleretin, 419, 421.
  Digitaletin, 419, 420.
  Digitalin, 245, 246, 419, 420, 422.
      „      Action of, on intestinal tract, 429.
      „      Case of poisoning by, 426.
      „      Fatal dose of, 423.
      „      Local action of, 427.
      „      Physiological action of, 427.
      „      Reactions of, 422.
      „      Spectrum of colour reactions of, 55.
  Digitalis, Doses of, 424.
      „      Effects of, on man, 424-427.
      „      group of poisons, 419, 431.
      „      leaf, 422.
      „      Pharmaceutical preparations of, 422.
      „      _Post-mortem_ appearances after poisoning by, 430.
      „      Separation of, from the tissues, &c., 430, 431.
      „      Statistics of poisoning by, 424.
      „      Treatment of poisoning by (App.), 693.
  Digitonin, 419.
  Digitoxin, 419, 420, 426.
  Dihydrolutidine, 506.
  Dimethylamine, 491.
  Dimethyl resorcin, 38.
  Dinitrobenzene, 189-192.
         „        Detection of, 192.
         „        Effects of, 189.
  Dinitrobrucine, 341.
  Diodon, Poisonous properties of, 470.
  Dioscorides, 3.
  Disinfectants, Assay of, 188.
  Disinfecting fluids, 166.
  Dixon’s pills, 581.
  Dolbeau’s experiments on anæsthetising sleeping persons with
  chloroform, 149.
  Domeyko’s method of mercury assay, 654.
  Donovan’s solution of arsenic, 530.
  Dott’s, Dr., process for assay of opium, 283, 284.
    „     tests for purity of chloroform, 145.
  Dover’s powder, 286.
  Dragendorff’s method for detecting cantharidine, 476.
       „        method for detecting curarine, 407.
       „        process for separating alkaloids, 241-254.
       „        shorter process, 254, 255.
       „        reagent, 239.
  Duboia Russellii, 483.
  Duc de Praslin, Suicide of, 544.
  Duflos’ hydric cyanide, 193.
  Dulcamara, 437.
  Dunstan’s researches on aconite, 351.
  Dutch pink, 594.
  Dupré’s observations on copper, 613.
  Dworzak and Heinrich’s auto-experiments on nicotine, 277.

  Ecboline, 443, 444.
  Ecgonin methyl ester, 347.
  Eczema due to chromium salts, 672.
  Eel, Poisonous properties of the blood of, 469.
  Egyptian knowledge of poisons, 2.
  Elaterin, 243.
  Electrolytic method of separating lead, 609.
  Emetics as antidotes (App.), 586.
  Emetine, 249, 253.
     „     Platinum salt of, 264.
     „     Phospho-molybdate of, 238.
  Emplastrum calefaciens, 472.
      „      cantharides, 472.
      „      plumbi, 593.
  Ergot, 442-450.
    „    Chemical characters of, 443.
    „    Dose of, 446.
    „    Liquid extract of, 445.
    „    oil, 443.
    „    Pharmaceutical preparations of, 446.
    „    Physiological action of, 448, 449.
    „    Separation of active principles of, 450.
    „    Symptoms of poisoning by, 448.
  Ergotin, 446.
  Ergotinine, 443.
  Ergotism, 446-448.
  Erythrophlein, 436.
  Eserine. See _Physostigmine_.
  Essential oils, 133.
  Ether, 141.
    „    as an anæsthetic, 142.
    „    as a poison, 142.
    „    Deaths from, 29.
    „    Fatal dose of, 142.
    „    recovery apparatus, 48.
    „    Separation of, from organic matters, 143.
  Ethylamine, 41, 491.
  Ethyl chloride in chloroform, 145.
  Ethylidene-diamine, 492.
  Ethiops mineral, 637.
     „    of antimony, 581.
  Ethyl-mustard oil, 490.
    „   sulphide as a poison, 35.
  Euchlorine test for carbolic acid, 178.
  Eulenberg’s experiments on effects of benzene vapour, 132.
      „       experiments on effects of creasote vapour, 180.
      „       experiments on effects of hydrochloric acid gas, 95.
      „       experiments on effects of mercury vapour, 641.
      „       experiments on effects of oxalic acid vapour, 514.
      „       experiments on effects of petroleum vapour, 130.
  Euonymin, 433.
  Eyesight, Affection of, from dinitrobenzene, 190.

  Falck’s observations on brucine poisoning, 341, 342.
    „          „       on phosphorus poisoning, 216.
    „          „       on silver nitrate poisoning, 631.
    „          „       on strychnine poisoning, 325.
  Ferric chloride, 666.
    „       „      Effects of, on animals and man, 666, 667.
    „       „      test for carbolic acid, 177.
  Ferrous sulphide, 668.
  Ferrocyanide, Poisonous action of, 210.
  Filehne’s observations on nitrobenzene poisoning, 187.
  Filicic acid, 466.
  Fish, Effects of carbolic acid on, 170.
   „    Effects of picrotoxin on, 452.
   „    Poisonous, 468-470.
  Fitzwalter, Maud, Poisoning of, 8.
  Fleitmann’s method of detecting arsenic, 571.
  Fleming’s tincture of aconite, 351.
     „         „          „      Poisoning by, 357.
  Fleury’s method of opium assay, 284, 285 (footnote).
  Flour, Detection of ergot in, 445.
  Flowers of antimony, 581.
  Flückiger’s test for brucine, 343.
      „         „      carbolic acid in creasote, 180.
      „         „      coniine, 266.
      „         „      strychnine, 338.
  Fly poison, 531.
   „  water, 532.
  Food poisoning, 506-508.
  Fool’s parsley, 457.
  Fougnies, Case of, 274.
  Foxglove. See _Digitalis_.
  Fraenkel’s observations on the effect of sulphuric acid on the kidney,
  85.
  Fraser’s observations on the effect of strophantin, 434.
  French law as to poison, 22.
  Fresenius and Hintz’s method of detecting arsenic in wall paper, 566.
  Friedländer’s aconitine nitrate, Fatal dose of, 356.
  Frog’s heart, Action of digitalis on, 429-431.
  Fröhde’s reagent, 239.
  Fuchsine as a test for alcohol in chloroform, 145.
  Fungi, Poisonous, 413-418.
    „        „      Deaths from, 30.

  Galmette’s experiments on cobra poison, 481.
  Gasoline, 129.
  Gastric juice, Hydrochloric acid in, 93.
  Gautier’s method of isolating ptomaines, 485.
  Gehlen’s death from breathing arsine, 527.
  Gelsemic acid, 345.
  Gelsemine, Carbon and nitrogen content of, 262.
      „      Effects of, on animals and man, 345, 346.
      „      Fatal dose of, 345.
      „      Separation of, 347.
      „      Treatment of poisoning by, 694.
  Gelsemium sempervirens, Botanical characters of, 345.
  Gergen and Posner’s observations on chromium, 671.
  Gerger and Baumann’s method of separating guanidine, 499.
  German law as to poison, 21.
  Gipsies, Knowledge of poisons possessed by, 5.
  Goby, Poisonous properties of, 470.
  Godfrey’s cordial, 237.
  Gold chloride as an antidote to cobra poisoning, 481.
       „        as a test for alkaloids, 287.
  Goulard balsam, 593.
     „    water, 593.
  Grandeau’s test for digitalin, 422.
  Grandval and Lajoux’s method of separating alkaloids, 255.
  Grasset and Amblard’s observations on the action of morphine, 297.
  Gratiolin, 244.
  Green vitriol, 668.
  Greek knowledge of poisons, 2.
  Gréhant’s observations on carbon monoxide poisoning, 66.
  Gréhant and Martin’s experiments on opium smoke, 305.
  Grinrod’s remedy for spasms, 287.
  Group reagents, 236.
  Grypsophila-sapotoxin, 436.
  Guaiacol, 179.
  Guaiacum test for blood, 61.
  Guanidine, 498.
  Gunn’s method of detecting oxalic acid, 520.
  Günzburg’s test for hydrochloric acid, 99.
  Gusserno’s experiments on lead, 597.

  Hæmatin crystals, 58, 59.
     „    Spectrum of, 60.
  Hahnemann’s soluble mercury, 638.
  Hair-dyes, 630.
  Halogens, Influence of, in compounds, 35.
  Ham (American), poisoning by, 507.
  Harley’s experiments on aconitine, 356.
  Harnack’s experiments on copper, 617.
      „     lead, 596.
  Heart, Action of digitalis on, 428.
    „      „    poisons on, 44.
  Hebrew knowledge of poisons, 5.
  Heinrich’s auto-experiments on cantharides, 473.
  Hellebore, 242, 246, 432, 433.
  Helleborein, 433.
  Helleboretin, 433.
  Hellebore infusion, Death from, 433.
      „     Poisoning by, 396.
      „     root, Poisoning by, 433.
  Helleborin, 247, 432, 433.
  Helleborus fœtidus, Odorous principle in, 433.
  Hemlock. See _Coniine_, _Conium_.
  Hempel’s method of detecting carbon monoxide, 71.
  Henbane. See _Hyoscyamus_, _Hyoscyamine_.
  Henry VIII.’s apprehensions as to poison, 12 (footnote).
  Herniari-saponin, 436.
  Hexamethylene diamine, 497.
  Hilger’s experiments on the solubility of copper, 611.
    „      test for sulphuric acid, 88.
  Hind’s sweating ball, 581.
  Hofmann’s tests for amines, 490.
     „         „      carbon disulphide, 165.
  Hog cholera, Toxines of, 505.
  Homolle’s digitalin, 421.
  Horse chestnut, Deaths from, 30.
  Hottot’s aconitine, Case of poisoning by, 365 (footnote).
  Hubers observations on dinitrobenzol poisoning, 189-191.
  Hunter’s solution of chloral, 160.
  Hydric sulphide, 72-74.
         „         Chronic poisoning by, 74.
         „         Detection of, 74.
         „         Effects of, 73.
         „         _Post-mortem_ appearances in cases of poisoning by,
                   74.
  Hydric sulphocyanide, 211.
  Hydrobenzamide, 40.
  Hydrochloric acid, 29, 91-102.
       „       Detection of, 98.
       „       Effects of, 96.
       „       Estimation of, 100.
  Hydrochloric acid, Fatal dose of, 93.
       „       Influence of, on vegetation, 94.
       „       in gastric juice, 93.
       „       Museum preparations of effects of poisoning by, 97, 98.
       „       _Post-mortem_ appearances in cases of poisoning by, 97.
       „       Properties of, 91.
       „       Statistics of poisoning by, 92.
       „       Treatment of poisoning by, (App.), 687.
  Hydrocollidine, 506.
  Hydrocotarnine nitrate, 342.
        „           „     Reactions of, 317.
  Hydrocyanic acid (Prussic acid), 192.
        „          Accidental and criminal poisoning by, 197.
        „          Action of, on living organisms, 198.
        „          Chronic poisoning by, 203.
        „          Deaths from, 30.
        „          Distribution of, in vegetable kingdom, 194.
        „          Estimation of, 209.
        „          Fatal dose of, 198.
        „          Length of time after death detectable, 208.
        „          Medicinal preparations of, 192.
        „          Poisoning by, 193.
        „          _Post-mortem_ appearances in cases of poisoning by,
                   203.
        „          Properties of, 192.
        „          Separation of, from organic matter, 51, 206.
        „          Statistics of poisoning by, 196.
        „          Symptoms observed in animals poisoned by, 199.
        „          Symptoms observed in man poisoned by, 201.
        „          Tests for, 204.
        „          Treatment of poisoning by, 698.
        „          Use of, in the arts, 193.
  Hydrofluoric acid, Deaths from, 29.
  Hydropotassic Oxalate. See _Oxalic acid_.
        „       tartrate, 122.
  Hyoscine, 385.
  Hyoscyamine, 251.
  Hyoscyamine, Association of, with atropine, 369.
       „       Carbon and nitrogen content of, 262.
       „       distinguished from atropine, 373.
       „       gold salt, 264.
       „       Melting-point of, 259.
       „       Phospho-molybdate of, 238.
       „       Properties of, 383.
       „       Separation of, from organic matters, 385.
       „       Tests for, 384.
       „       Treatment of cases of poisoning by, 694.
  Hyoscyamus, Alkaloids of, 382.
       „      Extract of, 384.
       „      Juice of, 384.
       „      Oil of, 384.
       „      Ointment of, 384.
       „      Pharmaceutical preparations of, 383, 384.
       „      Tincture of, 384.
  Hypaphorine, 339.
  Hypochlorite and Ammonia as a test for carbolic acid, 177.

  Ibsen’s experiments on strychnine, 337.
  Icthyismus gastricus, 469.
  Ictrogen, 463.
  Igasurine, 344.
  Illicium religiosum, 484.
  Imide groups, 39.
  Indian knowledge of poisons, 4.
  Indican, Carbon and nitrogen content of, 262.
  Infusoria, Action of poisons on, 42.
      „      Effects of carbolic acid on, 169.
  Insects, Action of poisons on, 43.
  Iodic acid test for morphine, 294.
  Iodine, Deaths from, 29.
     „    with hydriodic acid as a test for alkaloids, 236.
     „    with potassic iodide as a test for alkaloids, 237.
     „    Treatment of poisoning by (App.), 694.
  Iodoform test for alcohol in chloroform, 145.
  Ipecacuanha and morphine lozenges, 286.
       „      Compound powder of, 286.
  Iris, Action of poisons on, 45.
  Iron chloride, Elimination of, 667.
   „       „     Deaths from, 29.
   „       „     Cases of murder by, 667.
   „       „     Poisonous properties of, 665-670.
   „   salts, Separation of, from contents of stomach, 669.
   „   stains, 676.
  Isatropic acid, 372.
  Iso-amyl-amine, 492-506.
      „           nitrite, 141.
  Iso-cicutine, 266.
  Iso-nitrite, 490.
  Iso-santonin, 442.

  Jaborandi, 402.
      „      Treatment of poisoning by (App.), 694.
  Jaksch’s test for hydrochloric acid, 99.
  Javelle water, 118.
  Jequirity, 462.
  Jervine, 246, 393.
     „     Carbon and nitrogen content of, 262.
     „     Phospho-molybdate of, 238.
     „     Spectrum of furfurol reaction of, 55.
  John of Ragubo, 9.
  Johnson’s pills, 580.

  Kamschatkan custom of taking Amanita muscaria, 414.
  Katipo, 470, 471.
  Keighley, Cases of lead poisoning in, 604.
  Keyser’s pills, 640.
  Kidneys, Appearance of, in oxalic acid poisoning, 517.
     „     Appearance of, in phosphorus poisoning, 517.
  King’s yellow, 532.
  Kino, Compound powder of, 285.
  Kobert and Küssner’s experiments on sodic oxalate, 513.
  Kobert’s classification of poisons, 24, 25.
     „     observations on barium as a poison, 682.
     „           „      „  sphacelic acid and cornutin, 450.
     „     on the influence of carbon monoxide on the nervous system,
           66.
     „     test for prussic acid, 206.
  Koller’s prussic acid, 193.
  Koningh’s, L. de, process for detecting chromium, 675.
  Koppeschaar’s method of assaying carbolic acid, 182.
  Kreozote. See _Creasote_.
  Kŭsa-ūsū (Japanese Aconite root), 368 (footnote).
  Küster’s observations on carbonic acid, 173.

  Laburnum seeds, Deaths from, 30.
  Laburnum. See _Cytisine_.
  Langaard’s observations on Illicium religiosum, 454.
  Langley’s observations on pilocarpine, 403.
  Lanthopine, Reactions of, 317.
  Lassar’s researches on nitric acid vapour, 104.
  Lathyrus sativus, 464.
  Latrodectus malmignatus, 470.
  Laudanum. See _Opium_.
  Laudamine nitrate, Lethal dose of, 342.
      „     Reactions of, 317
  Laudamosine, 317.
  Lauro-cerasin, 195.
    „   Carbon and nitrogen content of, 262.
  Lead, 591-607.
   „    acetate, 592, 593.
   „    Acute poisoning by, 597.
   „    as a poison, 595.
   „    basic acetate, 607.
   „    carbonate, 592, 593.
   „        „      Dose of, 607.
   „    chromate, 599, 670, 671.
   „        „     Case of poisoning by, 173.
   „    Chronic poisoning by, 603, 604.
   „    Deaths from, 29.
   „    Detection and estimation of, 608.
   „    Effects of, on animals, 596.
   „       „        man, 597.
   „       „        nervous system, 600.
   „    Elimination of, 606.
   „    Encephalopathy, 600.
   „    Fatal dose of, 606, 607.
   „    in American overland cloth, 596.
   „    in foods, 596.
   „    in glass, 596.
   „    iodide, 593.
   „    Localisation of, 607.
   „         „       „   in the brain, 602, 603.
   „    nitrate, 594.
   „    oxides, 591, 592.
   „    Physiological action of, 605.
   „    pigments, 594.
   „    plaster, 593.
   „    poisoning among white lead employés, 601-603.
   „        „     from water, 604.
   „        „     Influence of, on pregnancy, 603.
   „        „     _Post-mortem_ appearances in, 605.
   „        „     Statistics relative to, 594.
   „        „     Treatment of, 607, 694.
   „    pyrolignite, 594.
   „    Separation of, 50, 52.
   „    sulphate, 592, 594.
   „    sulphide, 592, 609.
  Ledoyen’s disinfecting fluid, 593.
  Lehmann’s experiments on amount of copper soluble in fats, 611.
     „      experiments on the effect of copper, 618.
     „      observations on sulphuric acid, 89.
  Lemaurier’s odontalgic essence, 287.
  L’Emery, Nicholas, 14.
  Lemonade, Detection of lead in, 609, 610.
  Lemy’s experiments on thallium, 676.
  Lettuce, Content of hyoscyamine in, 381.
  Lewis’ silver cream, 593.
  Lieberman’s nitroso reaction, 489.
  Liebert’s _Cosmetique Infaillible_, 593.
  Life tests, 42-46.
  Lime, Deaths from, 29.
   „    Oxalate identification, 520, 521.
  Linstow’s case of poisoning by lead chromate, 673.
  Lipowitz’s sulphur test for phosphorus, 232.
  Liquor Ammoniæ Arsenitis, 530.
    „    Arsenicalis, 530.
    „    Arsenii et Hyd. Iod., 530.
    „    Bellostii, 651.
    „    Epispasticus, 472.
    „    potassæ, 117.
    „    sodæ, 118.
    „     „    effervescens, 118.
  Litharge, 591.
  Liver, Fatty degeneration of, in poisoning by phosphorus, 225.
    „    Microscopy of, in phosphorus poisoning, 227.
    „    of antimony, 581.
    „    Yellow atrophy of, 228.
  Lobelia, Deaths from, 30.
  Lobeliin, 249.
  Locusta, 6.
  Locust tree, 465.
  Loew’s theory as to poisons, 39.
  Lowe’s method of assaying disinfectants, 181.
  Ludwig’s experiments on the localisation of arsenic, 561, 562.
     „     method for the detection of mercury, 650.
  Lungs, Changes of, in phosphorus poisoning, 228.
  Lupinine, 463.
  Lupins, 463.
  Lutidine as an antidote for strychnine, 334 (footnote).
     „     in tobacco smoke, 276.
  Lycosa tarantula, 470.

  Macdonnell’s disinfecting powder, 167.
  Macphail’s case of poisoning by carbolic acid, 171.
  MacMunn’s observations on the blood in nitrobenzol poisoning, 191.
  Macniven’s case of poisoning by potassic bichromate, 673.
  Madagascar ordeal bean, 436.
  Male fern, 465, 466.
  Malpurgo’s test for nitrobenzene, 188.
  Mandelin’s reagent, 239.
  Mann’s reagent, 239.
  Marking inks, 620.
  Marsh’s test for arsenic, 14, 556.
  Maschka’s case of acute poisoning by copper sulphate, 620.
  Maschka’s case of acute poisoning by oleandrin, 435.
  Mason’s case of arsenical poisoning, 564, 565.
  Matches and Vienna paste, 213.
  Maybrick case, 546-548.
  Mayer’s reagent, 263.
  Meadow crowfoot, Deaths from, 30.
  Meconic acid, 318, 319.
  Meconin, Chemical composition of, 90.
     „     Properties of, 317, 318.
  Melanthin, 437.
  Meletta venenosa, 469.
  Melting-point, 261.
  Menispermine, 451.
  Merck’s aconitine, Fatal dose of, 356.
    „     veratrine, 392.
  Mercurial lotion, 636.
      „     ointment, 635.
      „     tremor, 644.
  Mercuric cyanide, 210, 648.
     „     ethyl chloride, 635.
     „     methide, 645.
     „     potass-iodide, 237.
     „     salts, Tests for, 652.
     „       „    Volumetric estimation of, 655.
     „     sulphide, 638.
  Mercurous acetate, 635.
     „      salts, 634.
     „        „    Tests for, 652.
     „        „    Volumetric estimation of, 655.
  Mercury, 633.
     „     Absorption of, by the skin, 643.
     „     and chalk, 634.
     „     and quinine, 638.
     „     cyanide, 638.
     „        „     Tests for, 652.
     „     Deaths from, 29.
     „     Detection of, in organic substances, 652.
     „     Elimination of, 650.
     „     Estimation of, 654.
     „     Green iodide of, 637.
     „     in the arts, 639.
     „     in veterinary medicine, 640.
     „     liniment, 635.
     „     Localisation of, 650.
     „     Medicinal preparations of, 634-639.
     „     Museum preparations of, illustrative of cases of poisoning
           by, 649.
     „     nitrate, Pathological changes in cases of poisoning by, 650.
     „        „     poisonous action of, 647, 648.
     „     oleate, 636.
     „     perchloride of, 636.
     „     plaster, 635.
     „     poisoning, statistics of, 641.
     „     _Post-mortem_ appearances in cases of poisoning by, 648, 649.
     „     Red iodide of, 637.
     „      „  oxide of, 637.
     „     Separation of, 50, 52.
     „     subchloride, Ointment of, 636.
     „          „       Pill of, 636.
     „     sulphide, 637.
     „         „     Identification of, 653.
     „     sulpho-cyanide, 639.
     „     Tests for, 651.
     „     Treatment of poisoning by, 648, 692.
     „     vapour, Effects of, 641-643.
  Metacresol, 179.
  Meta-dinitrobenzol, 189.
  Metaldehyde, 154.
  Metantimonic acid, 579.
  Metaphenylenediamine, 497.
  Methæmoglobin, Spectrum of, 58.
  Methene dichloride, 154.
  Metho-codeine, 299.
  Methylamine, 491.
       „       Carbon and nitrogen content of, 262.
  Methylated chloroform, 144.
       „     spirits, Deaths from, 29.
  Methyl brucine, 339 (footnote).
    „       „     iodide, 342.
    „    coniine, 248.
    „    cresol, 179.
    „    cyanide, 211.
    „    guanidine, 499, 500.
    „    salicylic acid, 38.
    „    strychnine, 37, 339 (footnote).
  Mezereic acid, 442.
  Mezereon, 442.
  Michet’s experiments on the relative toxicity of metals, 41.
  Micro-spectroscope, 54.
  Milk, Contamination of, by zinc, 657.
  Mineral acids, Treatment of poisoning by, 83.
     „    blue, 532.
     „    green, 616.
  Mitchell and Reichert’s experiments on snake poison, 477.
  Mitchell’s pills, 580, 640.
  Mithradetes Eupator, 2.
  Mitscherlich’s process for the detection of phosphorus, 229.
  Monkshood. See _Aconite_.
  Monobromated camphor, 135.
  Monochlor-ethyl sulphide, 35.
  Mordant’s Norton’s drops, 639.
  Morgagni’s case of poisoning by hellebore, 433.
  Morphine, 253.
     „      acetate, 292, 293.
     „      and strychnine, Detection of, 338.
     „      bimeconate, 287.
     „      Carbon and nitrogen content of, 262.
     „      Chemical constitution of, 293.
     „      Deaths from, 30.
     „      derivatives, 299.
     „      Effects of, 298.
     „      Extraction of, 308, 309.
     „      hydrate, 293.
     „      hydrochlorate, 292.
     „      lozenges, 287.
     „      meconate, 292.
     „      phospho-molybdate, 237.
     „      Physiological action of, 298.
     „      Platinum salt of, 264.
     „      Properties of, 291, 292.
     „      Separation of, 51, 307.
     „      Solutions of, 286, 287.
     „      Spectra of colour reactions of, 55.
     „      sulphate, 293.
     „      Suppository of, 286.
     „      tartrate, 292.
     „      Tests for, 294.
     „      Treatment of poisoning by (App.), 695.
     „      Value of Mayer’s precipitate of, 263.
  Morelle, Poisonous properties of, 418.
  Morson’s English creasote, 179.
  Moulds, Effects of, on arsenical wallpapers, 542.
  Mountain green, 616.
  Mucor phymocetes, 5.
  Multiple antidote (App.), 701.
  Muscarine, 413-417.
      „      Action of, on heart in poisoning by digitalin, 429,
      „      Carbon and nitrogen content of, 262.
      „      Detection of, 416, 417.
      „      Gold salt of, 264.
      „      Poisoning by, 414-417.
      „      Solution of (App.), 686.
      „      Treatment of poisoning by (App.), 695.
  Mussels, Poisoning by, 504.
  Mydaleine, 498.
  Mydatoxine, 504.
  Mytilotoxine, 504.

  Nagelvoort’s test for physostigmine, 399.
  Naja Haje, Poison of, 484.
  Naples yellow, 582.
  Naphtha, Deaths from, 29.
  Naphthal-amine (acyclic and aromatic), 36.
  Narceine, 247, 253, 254.
     „      Carbon and nitrogen content of, 262.
     „      Colour reactions of, 240.
     „      Effects of, 313.
     „      Melting point of, 259.
     „      Platinum salts of, 264.
     „      Properties of, 312.
  Narcotine, 252.
      „      Carbon and nitrogen content of, 262.
      „      Colour reactions of, 240.
      „      Effects of, 310.
      „      Gold and platinum salts of, 264.
      „      Melting-point of, 259.
      „      Spectrum of colour reactions, 55.
      „      Tests for, 309, 310.
      „      Value of Mayer’s precipitate of, 263.
  Neill, Thomas, Murders by, 325.
  Nepaline, 252, 253.
     „      Carbon and nitrogen content of, 287.
  Neriin, 435.
  Neuridine, 493, 494.
  Neurine, 501.
  Neuwieder green, 616.
  Nevin’s experiments on chronic antimony poisoning, 583, 586.
  Newcastle white, 594.
  Nicander of Colophon, 3.
  Nickel and cobalt, 662-665.
    „    Effects of, on animals, 663, 664.
    „    Identification of, 665.
    „    Separation of, 664.
  Nickelo-potassic cyanide, 665.
  Nicotine, 249.
     „      and coniine, Distinguishing marks between, 272, 273.
     „      Carbon and nitrogen in, 262.
     „      Colour reactions of, 240.
     „      Effects of, on animals and man, 273, 274.
     „      Estimation of, in tobacco, 270.
     „      Fatal dose of, 278.
     „      in various species of tobacco, 270.
     „      Phospho-molybdate of, 238.
     „      Physiological action of, 277.
     „      Platinum salt of, 264.
     „      _Post-mortem_ appearances in cases of poisoning, 278.
     „      Properties of, 271, 272.
     „      Separation of, from organic matters, 278.
     „      Treatment of poisoning by (App.), 696.
  Nikitin’s researches on sclerotic acid, 449.
  Nitrate of mercury, 638.
  Nitre, 123.
  Nitric acid, 102-110.
    „     „    Action of, on vegetation, 104.
    „     „    Deaths from, 29.
    „     „    Detection and estimation of, 109.
    „     „    Effects of liquid, 105.
    „     „    Fatal dose of, 104.
    „     „    Local action of, 106.
    „     „    Museum preparations of, 107.
    „     „    _Post-mortem_ appearances in cases of poisoning by, 107.
    „     „    Properties of, 102.
    „     „    Symptoms of poisoning by, 103.
    „     „    Uses in the arts of, 103.
    „     „    vapours, 104.
  Nitrobenzene, 132, 183-188.
       „        Action of, 187.
       „        Detection and separation of, 188.
       „        Effects of liquid, 185, 186.
       „        Effects of, on the blood, 191.
       „        Fatal dose, 186.
       „        Pathological appearances after poisoning by, 187.
       „        Poisoning by liquid, 185.
       „             „       vapour, 184.
       „        Separation of, 51.
       „        Symptoms of poisoning by, 184.
       „        Treatment of poisoning by (App.), 696.
  Nitro-glycerin, Deaths from, 30.
  Nitro-picrotoxin, 452.
  Nottingham, Cases of food poisoning in, 507.
      „       white, 594.
  Nurse’s drops, 287.
  Nux Vomica, 319.
   „    „     Aqueous extract of, 322.
   „    „     Deaths from, 30.
   „    „     Pharmaceutical preparations of, 322-324.
   „    „     powder, Analysis of, 323.
   „    „     Spirituous extract of, 322.
   „    „     Tincture of, 323.

  Oats, Content of copper in, 612.
  Obolouski’s process for separating colchicine, 413.
  Œnanthe crocata, Poisoning by, 458, 459.
  Ogston’s test for chloral, 162.
  Oil of almonds, Deaths from, 30.
     „   bitter almonds, 188, 193, 209.
     „   juniper, Deaths from, 29.
  Oils, power of dissolving copper, 611.
  Ointment of subacetate of lead, 593.
  Oldham, Cases of food poisoning in, 507.
  Oleandrin, 435.
  Onsum’s experiments on barium, 681.
  Opianine, 316.
  Opium, Action of solvents on, 282.
    „    Analysis of, 282.
    „    Assay of, 283, 284.
    „    Composition of, 281-284.
    „    Compound powder of, 285.
    „       „     tincture of, 285.
    „    Confection of, 286.
    „    Deaths from, 30.
    „    Detection of, 290.
    „    Diagnosis of poisoning by, 303.
    „    eating, 304, 305.
    „    Extract of, 286.
    „    Fatal dose of, 290.
    „    Liniment of, 286.
    „    Pharmaceutical preparations of, 285-287.
    „    Poisoning of children by, 289.
    „    _Post-Mortem_ appearances in cases of poisoning by, 306, 307.
    „    smoking, 305.
    „    Statistics of, 288.
    „    Tincture of, 285.
    „    Treatment of poisoning by (App.), 695.
    „    wine, 286.
    „    and chalk, Compound powder of, 286.
    „    and galls, Ointment of, 286.
    „    and lead pills, 285.
    „    and morphine, Absorption by the skin of, 303.
    „         „        Action of, on dogs, 297.
    „         „        Action of, on frogs, 296.
    „         „        Action of, on man, 299-302.
    „         „        Dose of, 289, 290.
    „         „        Poisoning by, 296.
    „         „        Treatment of poisoning by, 306, 695 (App.).
  Orfila as a toxicologist, 15.
  Organic analysis, Identification by, 261.
  Organic matter, Destruction of, by hydrochloric acid, 49.
  Orpiment, 529.
  Ortho-cresol, 179.
  Ortho-dinitrobenzene, 189.
  Ortho, para, and meta derivatives as poisons, 36, 37.
  Oxalate of lime, 511, 512.
  Oxalic acid, Deaths from, 29.
    „     „    Effects of, on animals, 513.
    „     „        „          leeches, 514.
    „     „        „          man, 515.
    „     „    Estimation of, 521, 522.
    „     „    Fatal dose of, 513.
    „     „    in the form of vapour, 514.
    „     „    Pathological changes produced by, 516, 518.
    „     „    Physiological action of, 516.
    „     „    Properties of, 510, 511.
    „     „    Separation of, 512.
    „     „    Statistics of poisoning by, 512.
    „     „    Treatment of poisoning by (App.), 697.
    „     „    Uses in the arts of, 512.
  Oxal-methyline, 522.
  Oxal-propyline, 522.
  Oxyacanthine, Carbon and nitrogen content of, 262.
  Oxycresol, 179.
  Oxymandelic acid, 229.

  Pagenstecher and Schönbein’s test for prussic acid, 205.
  Papaverine, 246, 253.
      „       Carbon and nitrogen content of, 262.
      „       Colour reactions of, 240.
      „       Effects of, 314.
      „       Melting-point of, 259.
      „       Platinum salt of, 264.
      „       Spectrum of colour reactions of, 55.
  Papier moure, 531.
  Paraceto-amido-phenol, 37.
  Para-coniine, 266.
  Para-cresol, 179.
  Para-digitaletin, 419, 421.
  Para-dinitrobenzol, 189.
  Paraffin, Deaths from, 29.
      „     oil, 130.
  Paraldehyde, 154.
  Paralysis from lead, 600.
  Paramenispermine, 451.
  Para-phenylene-diamine, 497.
  Paregoric. See _Opium_.
  Parillin, 437.
  Pattison’s white, 594.
  Payne and Chevallier’s experiments on zinc, 657.
  Peach, Prussic acid in, 195.
  Pedler’s experiments on cobra poison, 478.
  Pelikan’s observations on the poisonous properties of potassic
  dichromate, 671.
  Pellagra’s test for morphine, 295.
  Pennyroyal, Deaths from, 30.
  Pental, 154.
  Pentamethylene-diamine, 494-496.
  Pentane, 154.
  Peptotoxine, 502.
  Perchloride of iron solution, 666.
  Pereirine, 344, 345.
  Personnes’ method of volumetrically estimating mercury, 655.
  Petroleum, 129-131.
      „      Effects of, 130.
      „      naphtha, 130.
  Petit’s aconitine nitrate, 355.
  Petromyzon fluviatilis, 469.
  Pfaff’s prussic acid, 193.
  Pharaoh’s serpent, 639.
  Phenic acid. See _Carbolic acid_.
  Phenol. See _Carbolic acid_.
  Phenylene-diamine, 40.
  Phenylsulphate of potassium, 181.
  Phloro-glucin, 37, 466.
  Phlorol, 179.
  Pierre divine, 616.
  Phosphine, 213.
      „      Production of, as a test for phosphorus, 230.
      „      Spectrum of, 232.
  Phospho-molybdic acid as a test, 237.
  Phosphorated oil, 213.
  Phospho-tungstic acid, 238.
  Phosphorus, 5, 212-235.
      „       Antidotes to poisoning by, 223; (App.), 697.
      „       Criminal poisoning by, 221.
      „       Deaths from, 29.
      „       Detection of, 229.
      „       Effects of, 217.
      „       Fatal dose of, 216.
      „       paste, 214.
      „       Period of death by, 220.
      „       period after which it may be detected, 234.
      „       period of commencement of symptoms, 220.
      „       Poisoning effects of, 291.
      „       _Post-mortem_ appearances in cases of poisoning by, 224.
      „       Properties of, 212.
      „       Quantitative estimation of, 234.
      „       Separation of, 51.
      „       Statistics of poisoning by, 215.
      „       Treatment of poisoning (App.), 697.
      „       vapour, Effects of, 220, 221.
  Phosphuretted hydrogen. See _Phosphine_.
  Physostigmine, 251, 397-401.
        „        Carbon and nitrogen content of, 262.
        „        Effects of, on animals and man, 400.
        „        Extract of, 398.
        „        Fatal dose of, 402.
        „        Pharmaceutical preparations of, 399.
        „        Physiological action of, 401.
        „        _Post-mortem_ appearances in cases of poisoning by,
                 401.
        „        Separation of, 401, 402.
        „        Spectra of colour reactions, 55.
        „        Tests for, 399.
        „        Treatment of poisoning by (App.), 690.
  Picoline in tobacco smoke, 276.
  Picraminic acid, 455.
  Picric acid, 243, 244.
       „       and picrates, 454, 455.
       „             „       Effects of, 455.
       „             „       Tests for, 455.
  Picrotoxin, 247, 451.
       „      Effects of, on man and animals, 452, 453.
       „      Fatal dose of, 452.
       „      Physiological action of, 453.
       „      Separation from organic matters of, 453, 454.
       „      Sublimate of, 260.
       „      Treatment of poisoning by (App.), 697.
  Pilocarpine, 402-404.
       „       Chemical characters of, 402, 403.
       „       Effects of, 403.
       „       Gold and platinum salts of, 264.
       „       nitrate, Solution of (App.), 686.
       „       Sublimate of, 260.
       „       Tests for, 403.
       „       Treatment of poisoning by (App.), 698.
  Pimento, 244.
     „     Volatile alkaloid of, 250.
  Pinewood test for carbolic acid, 177.
  Piperidine, 39.
  Piperine, 242, 244.
      „     Carbon and nitrogen content of, 262.
      „     Phospho-molybdate of, 238.
      „     Platinum salt of, 264.
  Piturie, 279.
  Platinum chloride as a test for alkaloids, 237.
  Plugge’s researches on fatality of aconite, 355.
  Pocula emetica, 582.
  Poisons, Author’s classification of, 25.
     „     Classification of, 23.
     „     General method of search for, 46-54.
     „     Husemann’s definition of, 22.
     „     Kobert’s classification of, 24.
     „        „     definition of, 23.
     „     Legal definition of, 20.
     „     Lore of, 1-13.
     „     Scientific definition of, 22, 23.
     „     Statistics relative to, 28-34.
  Polygalic acid, 436.
  Pommerais, Case of, 430, 431.
  Poor man’s friend, 639.
  Poppy syrup, 287.
    „   tea, 289.
  Populin, 243.
  Pork, poisoning by, 507, 508.
  Porta, J. Baptista, 10.
  Portsmouth-case of food poisoning, 508.
  Potash binoxalate, Deaths from, 29.
    „        „       Fatal dose of, 513.
    „        „       Pathological changes produced by, 518.
    „    carbonates, 117.
    „    caustic, Deaths from, 29.
    „    Colour reactions with the alkaloids, 240 (footnote).
    „    Pharmaceutical preparations of, 117.
    „    Properties of, 116, 117.
    „    Statistics of poisoning by, 118.
    „    Treatment of poisoning by (App.), 688.
  Potassic and sodic nitrate, Action of, 123.
  Potassic bichromate, 470.
      „        „       Deaths from, 29.
      „        „       Use in the arts of, 671
      „    bromide, Deaths from, 29.
      „    chlorate, 124.
      „       „      Deaths from, 29.
      „       „      Detection and estimation of, 126.
      „       „      Effects of, 125, 126.
      „       „      Elimination of, 126.
      „       „      Experiments on animals with, 124.
      „       „      Poisonous properties of, 124.
      „       „      Uses of, 124.
      „    cyanide, Deaths from, 30.
      „       „     Effects on animals and men of, 198.
      „       „     Length of time detectable, 208.
      „       „     _Post-mortem_ appearance in cases of poisoning by,
                    204.
      „       „     Separation of, 206.
      „       „     Tests for, 204.
      „       „     Treatment of cases of poisoning by (App.), 698.
      „    nitrate, 123.
      „       „     Statistics of poisoning by, 123.
      „       „     Treatment of poisoning by (App.), 696.
      „    phenyl-sulphate, 181.
      „    sulphate, 122.
      „    sulpho-cyanide, 211.
      „    xanthate, 165.
      „    xantho-genate, 165.
      „    xanthylamate, 165.
      „    zinc-iodide, 239.
  Potassium salts, Elimination of, 123.
         „         Tests for, 121.
  Poudre épilatoire, 680.
  Powell’s balsam of aniseed, 287.
  Preyer’s separation of curarine, 406.
  Prince of Wales, precaution against poison, 12.
  Pritchard, Mrs., Poisoning of, 585.
  Propylamine, 491.
  Protapine, Reactions of, 317.
  Protoveratridine, 393.
  Protoveratrine, 391.
  Prussic acid. See _Hydrocyanic acid_.
  Pseudo-jervine, 293.
    „   -morphine, 316.
  Ptomaine analogous to coniine, 269.
      „        „        nicotine, 278.
      „        „        veratrine, 397.
      „    Definition of, 485.
  Putrescine, 496, 497.
  Pyraconine, 351, 354.
  Pyraconitine, 351, 354.
  Pyridine, 39, 276.
     „      alkaloid in the cuttle fish, 502.
  Pyro-catechin, 175.
  Pyro-gallol, 37.

  Quebrachine, 344.
       „       Spectra of colour reactions of, 55.
  Quillaja-sapotoxin, 436.
  Quillajic acid, 436.
  Quinidine colour reaction with potash, 240 (footnote).
      „     Value of Mayer’s precipitate of, 263.
  Quinine, 248, 252.
     „     Carbon and nitrogen content of, 262.
     „     Colour reactions of, 240.
     „     Gold and platinum salts of, 264.
     „     Phospho-molybdate of, 238.
     „     Spectrum of colour reaction, 55.
     „     Value of Mayer’s precipitate of, 263.

  Rat poison, 531, 680.
  Rayner, Dr. Henry, on connection between insanity and lead poisoning,
  600, 601.
  Realgar, 528.
  Red lead, 594.
  Redwood’s ink, 630.
  _R._ v. _Lamson_, 364, 365.
  _R._ v. _M’Conkey_, 361.
  _R._ v. _Moore_, 648.
  _R._ v. _Smith_, 648.
  _R._ v. _Taylor_, 604.
  _R._ v. _Wilson_, 411.
  _R._ v. _Wren_, 324.
  Reid, Dr., on Darlaston case of poisoning by carbon monoxide, 68.
  Reinsch’s test for arsenic, 558, 559.
  Resorcin, 38.
  Retford case of food poisoning, 508.
  Rettgers’s observations on arsenical mirror, 558.
  Reynold’s gout specific, 410.
  Rhigolene, 129.
  Rhœadine, Carbon and nitrogen content of, 262.
     „      Properties of, 316.
  Rhubarb syrup, Death from, 30.
  Rice, Content of copper in, 612.
  Richardson’s liquor bismuthi, 330 (footnote).
  Richet’s observations on strychnine poisoning, 329, 332.
  Rinman’s green, 657.
    „        „    Production of, 662.
  Ringer and Murrell’s observations on gelseminine, 346.
  River’s prussic acid, 193.
  Robinia pseudo-acacia, 465.
  Robiquet’s prussic acid, 193.
  Roburite in connection with dinitrobenzol poisoning, 190.
  Rogers’ experiments on copper, 617.
  Roman knowledge of poisons, 2.
  Rowalewsky’s experiments on uranium, 679.
  Rubi-jervine, 394.
  Russell’s viper, 483.
  Rye, Content of copper in, 612.

  Sabadilline, 249, 252.
       „       Carbon and nitrogen content of, 262.
       „       Spectra of colour reactions of, 55.
  Sabatrin, 252.
  Sabina communis, 459.
  Saikowsky on antimony poisoning, 586.
  St. Croix as a poisoner, 11.
  St. Ignatius’ bean, Extract of, 323.
  Salamandrine, 467.
  Salicin, 254.
     „     Melting-point of, 260.
  Salicylic acid, 38, 179.
  Salmon, Poisoning by tinned, 507.
  Sanarelli’s observations on the poison of the scorpion, 468.
  Sanger’s method of estimating arsenic, 570.
  Sanguinarine, carbon and nitrogen content of, 262.
        „       Spectra of colour reactions of, 55.
  Santonin, 244, 439-442.
      „     Effects of, on animals and man, 440.
      „     Fatal dose of, 440.
      „     Poisoning by, 440.
      „     _Post-mortem_ appearances in cases of poisoning by, 441.
      „     Separation of, 441, 442.
  Sapindus sapotoxin, 436.
  Sapogenin, 437.
  Saponin, 246, 254, 436-439.
     „     Detection of, 439.
     „     Effects of, 437, 438.
     „     Melting-point of, 260.
     „     Properties of, 437.
     „     Separation of, 438.
  Saprine, 500.
  Sarracinin, 249.
  Sarsaparilla saponin, 436.
  Sarsa-saponin, 436.
  Sausage, Poisoning from, 507, 509, 510.
  Savin oil, 459, 460.
  Savin, Treatment of poisoning by (App.), 698.
  Schacht’s method of assaying opium, 284 (footnote).
  Schaufféle’s observations on the solubility of zinc, 657, 658.
  Scheele, 14.
  Scheele’s green, 616.
      „     prussic acid, 193.
  Scheibler’s process for alkaloids, 238, 255.
  Schleppe’s salt, 578.
  Schmiedeberg’s process for estimating chloroform, 153.
  Schneider and Fyfe’s method of developing arsenic chloride, 576.
  Schönbein’s test for prussic acid, 206.
  Schraeder’s prussic acid, 193.
  Schroff’s case of poisoning by colchicum corms, 411.
  Schulze’s reagent, 239.
  Schweinfurt green, 532, 616.
  Scillain, 434.
  Scillitin, 434.
  Sclererythrin, 444, 445.
  Sclerocrystallin, 445.
  Scleroidin, 445.
  Scleromucin, 444.
  Sclerotic acid, 444.
  Scolosuboff’s experiments on the localisation of arsenic, 561.
  Scorpion poison, 468.
  “Sea Hare” as a poison, 3.
  Seidel’s case of barium poisoning, 683.
     „     mercury poisoning, 643.
  Senegin, 246, 254, 436.
  Senier’s analysis of blue pill, 634.
  Shale naphtha, 150.
  Sheep dipping arsenical compounds, 553.
  Siebold’s test for morphine, 295.
  Siem’s researches on alumina, 677.
  Silico-tungstic acid, 238.
  Silver, 628.
    „     Chronic poisoning by salts of, 631.
    „     chloride, 629.
    „     cyanide, 205, 211.
    „     Detection of, 632.
    „     Doses of salts of, 630.
    „     Use of, in the arts, 630.
    „     nitrate, 629.
    „        „     Deaths from, 29.
    „        „     Effects of, on man and animals, 630, 631.
    „        „     Tests for, 632.
    „     oxide, 629.
    „     _Post-mortem_ appearances in case of poisoning by the salts
          of, 652.
    „     Separation of, 50, 52.
    „     sulphide, 629.
  Sjokvist’s method of estimating free hydrochloric acid, 100.
  Smelling salts, 112.
  Snell’s case of dinitrobenzol poisoning, 190.
  Soap pill (compound), 286.
  Soda bicarbonate, 118.
   „   Deaths from caustic, 29.
   „   oxalate, 513.
   „   Properties of, 117.
   „   Statistics of poisoning by, 118.
  Sodic chloride, 122.
    „   cyanide, 210.
    „   nitrate, 124.
  Sodium salts, 122-128.
    „    Tests for, 121.
  Sokoloff’s method of separating prussic acid, 207.
  Solanidine, 386.
  Solanine, 385.
     „      Carbon and nitrogen content of, 262.
     „      Colour reactions of, 240.
     „      Spectra of colour reactions, 55.
     „      Phospho-molybdate of, 238.
     „      Poisoning by, 387.
     „      Properties of, 386.
     „      Separation of, 387.
     „      Treatment of poisoning by (App.), 699.
  Solomon’s anti-impetigines, 639.
  Soothing syrup, Deaths from, 30.
  Soubeiran’s ink, 630.
  Spanish fly, 471.
  Sparteine, 249, 279, 280.
  Spectroscope as an aid to identification of poisons, 54-56.
  Spectrum of aniline, 281.
     „        blood in nitrobenzol poisoning, 191.
     „          „   phosphine poisoning, 232.
  Sphacelic acid, 445, 450.
  Spiders, Poisonous, 470, 471.
  Spiritus Etheris Nitrosi, Deaths from, 29.
  Staphisagrine, Carbon and nitrogen content of, 262.
  Stas, Process of, for alkaloids, 239.
  Statira, Poisoning of, 6.
  Statistics of poisoning, 32, 33.
  Steel drops, 667.
  Stibine, 588.
  Stillbazoline, 266.
  Stockman and Dott’s observations on morphine poisoning, 299.
  Stomach, Redness of, 551.
  Storey’s worm cakes, 640.
  Stourbridge case of lead poisoning, 598.
  Stramonium extract, 371.
       „     tincture, 371.
  Strophantin, 434.
  Struve’s experiments on the detection of potassic cyanide, 209.
  Strychnic acid, 344.
  Strychnine, 248.
      „       and atropine, Tests for, 373.
      „       Action of, on cephalopods, 43, 328.
      „            „        frogs, 328.
      „            „        infusoria, 42.
      „            „        man, 329.
      „       Carbon and nitrogen content of, 262.
      „       chromate, 321.
      „       Colour reactions of, 240.
      „       Deaths from, 30.
      „       Double salts of, 322.
      „       Estimation of, 339.
      „       ethyl and methyl, 251.
      „       Fatal dose of, 325-328.
      „       Gold and platinum salts of, 264.
      „       Identification of, 337, 338.
      „       Iodide of, 322.
      „       nitrate, 321.
      „          „     Fatal dose of, 342.
      „       phospho-molybdate, 238.
      „       Physiological action of, 332.
      „             „       test for, 338, 339.
      „       picrate, 325, 340.
      „       Poisoning by, 331.
      „       _Post-mortem_ appearances in cases of poisoning by, 333.
      „       Properties of, 319-321.
      „       Separation of, from brucine, 323.
      „       Separation of, from organic matters, 334.
      „       Spectra of colour tests, 55.
      „       Statistics of poisoning by, 324.
      „       Sublimate of, 260.
      „       sulphate, 321.
      „       Sulpho-cyanide of, 322.
      „       Treatment of poisoning by (App.), 333, 699.
      „       trichloride, 322.
      „       Value of Mayer’s precipitate of, 263.
  Sublimation of the alkaloids, 256-261.
  Sugar of lead, 593.
        „        Fatal dose of, 606, 607.
  Suicide by poison, 2.
  Suicidal poisoning, 32.
  Sulphuretted hydrogen. See _Hydric sulphide_.
  Sulphuric acid, 75.
      „       „   Accidental, criminal, and suicidal poisoning by, 77,
                  78.
      „       „   Character of blood in cases of poisoning by, 90.
      „       „   Chronic poisoning by, 86.
      „       „   Deaths from, 29.
      „       „   Detection and estimation of, 87.
      „       „   External effects of, 81.
      „       „   Fatal dose of, 78.
      „       „   Internal effects of, 82.
      „       „   Local action of, 79.
      „       „   _Post-mortem_ appearances in cases of poisoning by,
                  83, 85.
      „       „   Properties of, 75.
      „       „   spots on clothing, &c., 81.
      „       „   Statistics as to poisoning by, 76, 77.
      „       „   Symptoms produced by, 81.
      „       „   Urine in cases of poisoning by, 88.
      „     anhydride, 76.
  Sulphur in bile, 90.
  Suppositoria plumbi composita, 593.
  Susotoxine, 505.
  Syringin, 247, 437.

  Tamus Communis, 465.
  Tanqueril’s observations on lead poisoning, 600.
  Tarantula, 470.
  Tar oil, Deaths from, 30.
  Tartar emetic. See _Antimony_.
  Tartaric acid, Deaths from, 29.
         „       Detection of lead in, 609, 610.
  Tartas’ case of poisoning by nitric acid, 107.
  Taxine, 404, 405.
  Terebenthene hydrochloride, 134.
  Terpenes, 133.
  Teschemacher and Smith’s method for assaying opium, 283.
  Tetanine, 503.
  Tetanotoxine, 503, 504.
  Tetramethylenediamine, 496, 497.
  Tetrodon, 469.
  Thallium, 675, 676.
  Thebaine, 253.
     „      Carbon and nitrogen content of, 262.
     „      Colour reactions of, 240.
     „      Effects of, 315.
     „      Gold and platinum salts of, 264.
     „      nitrate, Lethal dose of, 342.
     „      Properties of, 314, 315.
     „      Sublimate of, 259.
  Theine, 243.
     „    Carbon and nitrogen content of, 262.
     „    Gold and platinum salts of, 264.
     „    Phospho-molybdate of, 238.
     „    Sublimate of, 257-260.
  Theobromine, 40, 246.
      „        Carbon and nitrogen content of, 262.
      „        Phospho-molybdate of, 238.
      „        Platinum, salt of, 264.
      „        Sublimate of, 260.
  Theveresin, 434.
  Thevetin, 434.
  Thompson’s hair destroyer, 680.
      „      W., observation on solubility of copper in oils, 611.
  Thorn Apple, Deaths from (see _Datura_), 30.
  Thudichum’s method of separating potass-phenyl sulphate from urine,
  181.
  Tiglic acid, 392.
  Tin, separation of, 50-52.
  Tincture of digitalis, 422.
      „       iron, 666.
  Tione,  Mass  poisoning by lead in, 599.
  Tobacco, Deaths from, 30.
     „     Effects of, 274.
     „     juice, Effects of, 273, 275.
     „     smoke, Chemical composition of, 275, 276 (footnote).
     „     Species of, 269, 270.
  Toffana, 10.
  Toluylenediamine, 40.
  Tongue, Poisoning by tinned, 507.
  Toxalbumins of Castor and Abrus, 462, 463.
  Toxic action and chemical composition, 35-42.
    „   mydriasis and myosis, 46.
  Toxines of Hog cholera, 505.
  Toxiresin, 421.
  Traube’s observations on the action of digitalis, 428.
  Tri-bromo-phenol, 178.
  Tri-chlor-morphine, 299.
  Tri-ethyl-amine, 491.
  Tri-ethyl-phosphine, 165.
  Trimethylamine, 250, 443, 491.
        „         Carbon and nitrogen content of, 262.
  Trimethylenediamine, 493.
  Trimethyl-hydroxy-amine, 501.
  Trimethyl-vinyl-ammonium hydrate, 501.
  Triton cristatus, 467.
  Tritopine, Properties of, 317.
  Triumph (H.M.S.), Mass poisoning by mercury on, 642.
  Tropic acid, 371.
  Tropidonotus natrix, 483.
        „      viperinus, 484.
  Tropine, 371.
  Tschirch’s observations and experiments on copper poisoning, 611, 619,
  622.
  Turacin, 613.
  Turbith mineral, 637.
  Turner’s yellow, 594.
  Turpentine, 133, 134.
      „       Deaths from, 29.
      „       Treatment of poisoning by (App.), 700.
  Type metal, 582.
  Typho-toxine, 506.
  Tyrotoxicon, 504, 505.

  Udrànsky and Baumann’s process for isolating diamines, 488.
  Ullmann on the localisation of mercury, 650.
  Upas tree of Singapore, 436.
  Uppmann’s experiments on oxalic acid, 514.
  Uranium, 679.
  Uric acid in cases of lead poisoning, 603.
  Urine, examination of, for poison, 233.
    „         „          in poisoning by carbolic acid, 181.
    „         „          in poisoning by chloral, 161.
    „         „          in poisoning by phosphorus, 222.
    „         „          in poisoning by sulphuric acid, 88.
  Urobutylchloral acid, 161.
  Urochloral acid, 161.

  Valanguis’ solutio solventes mineralis, 531.
  Valentine’s experiments on scorpion poison, 468.
  Van Kobell’s test for bismuth, 627.
  Vauquelin’s prussic acid, 193.
  Vas’ observations on tobacco juice, 273.
  Veal, poisoning by, 507.
  Vegetation, Action of hydrochloric acid on, 94.
    „           „    nitric acid, 104.
  Venetian poisoners, 9.
  Venturoli’s process for the separation of prussic acid, 208.
  Veratralbine, 394.
  Veratric acid, 392.
  Veratrine, 248, 252, 390-392.
     „       Action of, on infusoria, 42.
     „       Carbon and nitrogen content of, 262.
     „       Colour reactions of, 240.
     „       Commercial, 394, 395.
     „       Effects of, on animals and man, 395, 396.
     „       Fatal dose, 395.
     „       Gold salt of, 264.
     „       Phospho-molybdate of, 238.
     „       Separation of, from organic matters, 397.
     „       Spectra of colour reactions, 55.
     „       Treatment of poisoning by (App.), 700.
     „       Value of Mayer’s precipitate of, 263.
  Veratroidine, 394.
  Veratroidine, Carbon and nitrogen content of, 262.
  Veratrum, Old knowledge of, 4.
  Verdigris, 616.
  Vermicelli, Content of copper in, 612.
  Vermilion, 638.
  Vermin killers, Composition of, 324.
       „          Deaths from, 30.
  Vetchlings, 464.
  Veterinary arsenical medicines, 531.
  Vidali’s method of estimating chloroform, 153 (footnote).
    „         „      testing for atropine, 373.
    „         „      testing for mercury cyanide, 652.
    „         „      testing for morphine, 295.
  Villiers and Favolle’s test for hydrochloric acid, 99.
  Vinylamine, 41.
  Viper, 477.
  Vis’ constitutional formula for atropine, 294.
  Vohl and Eulenberg’s observations on tobacco smoke, 276 (footnote).
  Voisin and Liouville’s experiments on curare, 407.

  Wagner’s method of obtaining sulphates of the alkaloids, 263.
  Wall on the effects of cobra poison, 479.
  Waller’s, E., method of assaying carbolic acid powders, 182.
  Waltisham cases of ergot poisoning, 447, 448.
  Walz’s method of preparing digitalin, 421.
  Ward’s red pill, 581.
  Wasps, Poison of, 471.
  Water gas, Leeds case of poisoning by, 67.
    „   hemlock, Deaths from. See _Œnanthe crocata_, 30.
    „   salamander, 467.
    „   snake, blood of, 485.
  Welbeck cases of food poisoning, 507.
  Wheat, Content of copper in, 612.
  Whin flower, Death from, 30.
  Whitchurch case of food poisoning, 507.
  White lead, 594, 595.
  Whitelock’s case of carbolic acid poisoning, 171.
  White precipitate, 636, 648.
  Williams’ apparatus, 44.
  Witherite, 680.
  Wittstock’s process for colchicine, 413.
  Wolverhampton case of poisoning by tinned salmon, 507.
  Wormwood, 244.
  Woudreton, Confession of, 8.
  Wright’s pearl ointment, 640.
  Wunderlich’s case of poisoning by nitric acid, 106.
  Wyeth’s dialysed iron (App.), 686.
  Wyss (Oscar) case of poisoning by sulphuric acid, 84.

  Xanthin, 39, 40.
  Xanthogenic acid, 165.

  Yellow atrophy of the liver, distinguished from phosphorus poisoning,
  226.
  Yew, Poisoning by, 404.

  Zinc ammonia chloride, 657.
   „   carbonate, 656.
   „   chloride, 656.
   „      „      Deaths from poisoning by, 29.
   „      „      Poisonous effects of, 659, 660.
   „      „      _Post-mortem_ appearances after poisoning by, 660, 661.
   „   Detection of, 661.
   „   Effects of, 658.
   „   green, 657.
   „   in the arts, 657.
   „   oxide, 656.
   „     „    Effects of, on man, 658.
   „   Separation of, 53.
   „   sulphate, 656.
   „      „      Poisonous effects of, 659.
   „      „      _Post-mortem_ appearances after poisoning by 660.
   „   sulphide, 656, 657.
   „      „      Properties of, 661.
   „   Tests for, 662.
   „       „      poisoning by soluble salts of (App.), 700.
   „   white, 657.
   „   yellow, 657.

    NEILL AND COMPANY, PRINTERS, EDINBURGH.




  A CATALOGUE OF
  MEDICAL WORKS
  PUBLISHED BY
  CHARLES GRIFFIN & COMPANY, LIMITED.


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INDEX TO AUTHORS.

                                                                PAGE
  AITCHISON (R.), Medical Handbook,                              23
  AITKEN (Sir W., M.D.), Science and Practice of Medicine,       26
  ANDERSON (Prof. M’Call), Skin Diseases,                        13
  BLYTH (A. W.), Foods and Poisons,                              31
  BURNET (R., M.D.), Foods and Dietaries,                        33
  BURY (Judson, M.D.) Clinical Medicine,                          7
  CAIRD & CATHCART, Surgical Handbook,                           23
  CLARK (Sir Andrew), Fibroid Phthisis,                           6
  CRIMP (W. S.), Sewage Disposal Works,                          21
  ---- and COOPER, Sanitary Rules,                               24
  DAVIES (Surg. Major), Hygiene,                                 24
  DAVIS (Prof. J. R. A.), Biology,                               30
  ---- The Flowering Plant,                                      30
  ---- Zoological Pocket-book,                                   30
  DONALD (Arch., M.D.), Midwifery,                               25
  DONKIN (H. Bryan), Diseases of Childhood,                       9
  DUCKWORTH (Sir D., M.D.), Gout,                                10
  DUPRE and HAKE, Manual of Chemistry,                           32
  ELBORNE (W.), Pharmacy,                                        32
  GARROD (A. E., M.D.), Rheumatism,                              11
  HADDON (Prof.), Embryology,                                    22
  HELLIER (Dr.), Infancy and Infant-Rearing,                     35
  HEWITT (F. W., M.D.), Anæsthetics,                             26
  HILL (Dr.), Physiologist’s Note-Book,                          27
  HORSLEY (V.), Brain and Spinal Cord,                           15
  ---- Brain Surgery,                                            15
  HUMPHRY (Laur.), Manual of Nursing,                            33
  HUNTER (Wm. M.D.), Diseases of the Blood,                       9
  JAKSCH (v.) and CAGNEY, Clinical Diagnosis,                     8
  LANDIS (Dr.), Management of Labour,                            25
  LANDOIS and STIRLING’S Physiology,                              5
  LEWIS (Bevan), Mental Diseases,                                16
  MACALISTER (Prof.), Human Anatomy,                              4
  MACREADY (J., F.R.C.S.), Ruptures,                             19
  MANN (Prof. Dixon, M.D.), Forensic Medicine and Toxicology,    19
  MERCIER (Ch., M.D.), Asylum Management,                        17
  MEYER and FERGUS, Ophthalmology,                               14
  OBERSTEINER and HILL, Central Nervous Organs,                  18
  PAGE (H. W., F.R.C.S.), Railway Injuries,                      20
  PHILLIPS (Dr. J.), Diseases of Women,                          25
  POLLARD (B., F.R.C.S.), Diseases of Childhood (Surgical),       9
  PORTER and GODWIN, Surgeon’s Pocket-book,                      24
  REID (Geo., D.P.H.), Practical Sanitation,                     34
  RIDEAL (Samuel, D.Sc.), Disinfectants,                         33
  RIDDELL (J. Scott, M.D.), Manual of Ambulance,                 35
  ROSS and BURY, Peripheral Neuritis,                            15
  SANSOM (A. E., M.D.), Diseases of the Heart,                   12
  SEXTON (Prof.), Quantitative Analysis,                         32
  ---- Qualitative Analysis,                                     32
  SMITH (Johnson, F.R.C.S.), Sea-Captain’s Medical Guide,        35
  SQUIRE, (Ed. J, M.D.), Consumption, Hygienic Prevention of,    34
  STIRLING (Prof.), Practical Physiology,                        28
  ---- Practical Histology,                                      29
  THORBURN (W.), Surgery of Spine,                               20
  THORNTON (J.), Surgery of Kidneys,                             20
  WESTLAND (A., M.D.), The Wife and Mother,                      35
  SCIENTIFIC SOCIETIES (Year-book of),                           36


INDEX TO SUBJECTS.

                                                                PAGE
  AMBULANCE,                                                     35
  ANÆSTHETICS,                                                   26
  ANATOMY, Human,                                                 4
  _Anatomy and Physiology_ (_Journal of_),                       22
  ASYLUM MANAGEMENT,                                             17
  BIOLOGY,                                                       30
  BLOOD, Diseases of,                                             9
  BOTANY,                                                        30
  BRAIN, The,                                    15, 16, 17, 18, 19
  CHEMISTRY, Inorganic,                                          32
  ---- Analysis, Qualitative and Quantitative,                   32
  CHILDHOOD, Diseases of,                                         9
  CLINICAL Diagnosis,                                             8
  CLINICAL Medicine,                                           6, 7
  CONSUMPTION,                                                6, 34
  DIETARIES for the Sick,                                        33
  DISINFECTION and DISINFECTANTS,                                33
  EMBRYOLOGY,                                                    22
  EYE, Diseases of the,                                          14
  FOODS, Analysis of,                                            31
  FOODS and Dietaries,                                           33
  FORENSIC MEDICINE,                                             19
  GOUT,                                                          10
  HEART, Diseases of the,                                        12
  HISTOLOGY,                                                     29
  HYGIENE and Public Health,                         24, 31, 33, 34
  INFANTS, Rearing of,                                           35
  INSANITY, Medico-legal Evidence of,                            19
  KIDNEYS, Surgery of the,                                       20
  LABORATORY Hand-books--
    Chemistry,                                                   32
    Histology,                                                   29
    Pharmacy,                                                    32
    Physiology,                                                  28
  MEDICAL SOCIETIES, Papers read annually before,                36
  MEDICINE, Science and Practice of,                             26
  MENTAL DISEASES,                                           16, 17
  NERVOUS ORGANS, Central,                                       18
  NURSING, Medical and Surgical,                                 33
  OBSTETRICS,                                                    25
  PHARMACY,                                                      32
  PHTHISIS, Fibroid,                                              6
  PHYSIOLOGIST’S Note-book,                                      27
  PHYSIOLOGY,                                                 5, 28
  POCKET-BOOK of Hygiene,                                        24
  ----  Medical,                                                 23
  ----  of Sanitary Rules,                                       24
  ----  Surgical,                                            23, 24
  ----  Zoological,                                              30
  POISONS, Detection of,                                         31
  RAILWAY INJURIES,                                              20
  RHEUMATISM,                                                    11
  RUPTURES,                                                      19
  SANITATION,                                                    34
  SEA-CAPTAINS, Medical Guide for,                               35
  SEWAGE Disposal Works,                                         21
  SKIN, Diseases of the,                                         13
  SPINAL Cord,                                                   20
  SURGERY of Brain,                                              15
  ---- Civil,                                                    23
  ---- of Kidneys,                                               20
  ---- Military,                                                 24
  ---- of Spinal Cord,                                           20
  WOMEN, Diseases of,                                        25, 35
  ZOOLOGY,                                                       30


Charles Griffin & Co.’s Medical Series.

_Standard Works of Reference for Practitioners and Students._

Issued in LIBRARY STYLE, large 8vo, Handsome Cloth, very fully
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1. ANATOMY AND PHYSIOLOGY.

                                                                    PAGE
  =Human Anatomy=,                      PROF. MACALISTER, M.D.,       4
  =Human Physiology=,                   PROFS. LANDOIS AND STIRLING,  5
  =Embryology=,                         PROF. HADDON,                22


2. THE BRAIN, NERVOUS SYSTEM, AND LEGAL MEDICINE.

  =The Brain and Spinal Cord=,          VICTOR HORSLEY, F.R.C.S.,    15
  =Central Nervous Organs=,             DRS. OBERSTEINER AND HILL,   18
  =Peripheral Neuritis=,                DRS. ROSS AND BURY,          15
  =Mental Diseases=,                    BEVAN LEWIS, M.R.C.S.,       16
  =Asylum Management=,                  CHAS. MERCIER, M.D.,         17
  =Forensic Medicine and Toxicology=,   PROF. DIXON MANN,            19


3. DIAGNOSIS AND TREATMENT OF DISEASE.

  =Clinical Diagnosis=,                 DRS. V. JAKSCH AND CAGNEY,    8
  =Clinical Medicine=,                  JUDSON BURY, M.D.,          6-7
  =Fibroid Phthisis=,                   SIR AND. CLARK, M.D.,         6
  =Gout=,                               SIR DYCE DUCKWORTH, M.D.,    10
  =Rheumatism=,                         ARCH. GARROD, M.D.,          11
  =Diseases of the Blood=,              WM. HUNTER, M.D.,             9
  =   „        Childhood=,              BRYAN DONKIN, M.D.,           9
  =   „        the Eye=,                DRS. MEYER AND FERGUS,       14
  =   „        the Heart=,              A. E. SANSOM, M.D.,          12
  =   „        the Skin=,               PROF. M’CALL ANDERSON,       13


4. SURGERY.

  =Brain Surgery=,                      VICTOR HORSLEY, F.R.C.S.,    15
  =Surgery of the Kidneys=,             KNOWSLEY THORNTON, F.R.C.S., 20
  =      „        Spinal Cord=,         WM. THORBURN, F.R.C.S.,      20
  =Surg. Diseases of Childhood=,        BILTON POLLARD, F.R.C.S.,     9
  =Railway Injuries=,                   H. W. PAGE, F.R.C.S.,        20
  =Ruptures=,                           J. F. C. MACREADY, F.R.C.S., 19


⁂ Other Volumes in active Preparation.


~By Prof. MACALISTER, M.P., F.R.S.~

  HUMAN ANATOMY
  (SYSTEMATIC AND TOPOGRAPHICAL),
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  INCLUDING THE EMBRYOLOGY, HISTOLOGY, AND MORPHOLOGY OF
  MAN, WITH SPECIAL REFERENCE TO THE REQUIREMENTS
  OF PRACTICAL SURGERY AND MEDICINE.

BY

ALEXANDER MACALISTER, M.A., M.D., F.R.S., F.S.A.,

    Professor of Anatomy in the University of Cambridge, and Fellow of
    St. John’s College; Examiner in Human Anatomy, University of London.

_In Large 8vo. With 816 Illustrations. Handsome Cloth, 36s._


OPINIONS OF THE PRESS.

    “By far THE MOST IMPORTANT WORK ON THIS SUBJECT that has appeared in
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    brain and spinal cord, the ear, and the eye, contain _all that is
    really valuable in the most recent researches_.”--_Glasgow Medical
    Journal._

    “The book bears an unmistakable stamp of erudition and labour, and
    will be VALUED both by teachers and pupils AS A WORK OF
    REFERENCE.”--_British Medical Journal._

    “Dr. Macalister’s extensive knowledge of comparative anatomy enables
    him to speak with authority on many interesting but difficult
    morphological problems. . . . A VERY ABLE and SCIENTIFIC
    treatise.”--_Edinburgh Medical Journal._


~Professors LANDOIS and STIRLING.~

  HUMAN PHYSIOLOGY
  (A TEXT-BOOK OF).
  WITH SPECIAL REFERENCE TO PRACTICAL MEDICINE.

By DR. L. LANDOIS,

    PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF GREIFSWALD.

_Translated from the Seventh German Edition, with Annotations and
Additions_,

By WM. STIRLING, M.D., Sc.D.,

    BRACKENBURY PROFESSOR OF PHYSIOLOGY IN OWENS COLLEGE, AND VICTORIA
    UNIVERSITY, MANCHESTER; EXAMINER IN THE UNIVERSITIES of OXFORD,
    EDINBURGH, AND LONDON: AND FOR THE FELLOWSHIP OF THE ROYAL COLLEGE
    OF SURGEONS, ENGLAND.

In Two Large 8vo Volumes, Handsome Cloth, 42s.

With 845 Illustrations (some in Colours).

FOURTH ENGLISH EDITION.


GENERAL CONTENTS.

    Part I.--Physiology of the Blood, Circulation, Respiration,
    Digestion, Absorption, Animal Heat, Metabolic Phenomena of the Body;
    Secretion of Urine; Structure of the Skin.

    Part II.--Physiology of the Motor Apparatus; the Voice and Speech;
    General Physiology of the Nerves: Electro-Physiology; the Brain;
    Organs of Sight, Hearing, Smell, Taste, Touch; Physiology of
    Development.

⁂ Since its first appearance in 1880, Prof. LANDOIS’ TEXT-BOOK OF
PHYSIOLOGY has been translated into three Foreign languages, and passed
through SEVEN LARGE EDITIONS.

The Fourth English Edition has again been thoroughly revised, and a new
feature introduced--that of printing some of the Illustrations in
Colours. The number of figures has also been largely increased, from 494
in the First, to 845 in the present Edition. In order to do full justice
to the coloured illustrations, and to admit of more of the text being
printed in large type, it has been found necessary to put the work once
again in two volumes.


Opinions of the Press.

    “So great are the advantages offered by Prof. LANDOIS’ TEXT-BOOK,
    from the EXHAUSTIVE and EMINENTLY PRACTICAL manner in which the
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IN HANDSOME CLOTH. PRICE ONE GUINEA NET.

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  FIBROID DISEASES OF THE LUNG, INCLUDING
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BY

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    _Late Consulting Physician and Lecturer on Clinical Medicine to the
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AND

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From Dr. JUDSON BURY’S NEW WORK on “CLINICAL MEDICINE”

(_See opposite page._)

[Illustration: FIG. 221.--Showing wasting of Pectorales, and the drawing
up of the Upper Angles of the Scapulæ. From the Section on Examination
of the Nervous System (Disorders of Muscular Action).]


_In Large 8vo, Handsome Cloth, With numerous Illustrations and Coloured
Plate. 21s._

  CLINICAL MEDICINE.
  A PRACTICAL HANDBOOK FOR PRACTITIONERS
  AND STUDENTS.

BY JUDSON BURY, M.D., F.R.C.P.,

    Senior Assist. Phys., Manchester Royal Infirmary.


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    “This Manual is sure AT ONCE to take a FOREMOST PLACE as a guide in
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    . . . Belongs to the same series of Manuals which has given us the
    issue of LANDOIS’ ‘Physiology,’ wherein Prof. STIRLING sought to
    bring the most advanced Physiology into relationship with clinical
    work; and the very valuable treatise of V. JAKSCH on ‘Clinical
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GENERAL CONTENTS.

=Introductory.=--Symptoms and Physical Signs--Importance of
Inspection--Method of Examining a Patient--Case-taking. =Symptoms for
the most part Subjective in Character.=--Symptoms indicating Disturbance
of the Functions of the Nervous System--Indicating Disturbance of the
Functions of the Respiratory and Circulatory Organs--Indicating
Disturbance of the Functions of the Digestive Organs--Indicating
Disturbance of the Urinary Organs. =Examination of the Surface
of the Body.=--Changes in Size and Shape--Expression of
Face--Attitude--Walking. =Temperature.=--Temperature in Health--in
Disease. =Examination of the Skin and its Appendages.=--Changes in the
Colour of the Skin--The Moisture of the Skin--Cutaneous Eruptions:--I.
General Diseases with Cutaneous Lesions; II. Diseases of the Skin
due to Parasites; III. Local Diseases of the Skin not due to
Cutaneous Parasites--Abnormal Conditions of the Nails. =Examination
of the Respiratory System.=--Artificial Divisions of the
Chest--Inspection--Palpation--Percussion--Auscultation--The Sputum--The
Examination of the Larynx. =Examination of the Circulatory
System.=--Anatomical Relations of the Heart--Inspection and
Palpation--Percussion-Auscultation--The Pulse. =Examination of the
Blood.= =Examination of the Digestive System and of the Abdominal
Organs.=--The Tongue--The Teeth--The Gums--The Mucous Membrane of the
Mouth--Saliva--The Soft Palate, Fauces and Pharynx--The Œsophagus--The
Abdomen---The Stomach--Examination of Vomited Matters--Investigation of
the Contents of the Stomach and of its Activity during Digestion--The
Intestines--Examination of the Fæces---The Liver and Gall
Bladder--The Spleen--The Pancreas--The Omentum--The Mesentery and
Retroperitoneal Glands--The Kidneys. =Examination of the
Urine.=--Variations in the Quantity of the Urine--In the
Colour--Odour--Consistence--Translucency--Specific Gravity and Reaction
of the Urine--Chemical Examination of the Urine--Sediments and
Microscopical Examination of the Urine:--(_a_) Unorganised
Sediments; (_b_) Organic Deposits. =Examination of Puncture
Fluids.=--Exudations--Transudations--Contents of Cysts.
=Examination of the Nervous System.=--Anatomical and Physiological
Introduction--Investigation of the Symptoms Produced by Diseases of the
Nervous System:--Disorders of Muscular Action; of Sensation; of Reflex
Action; of Language; of Vision; of Hearing; of Taste; of Smell.


~By Prof. von JAKSCH.~

[Illustration: Fig. 86.--_a_, _b._ Cylindroids from the urine in
congested kidney.]

  CLINICAL DIAGNOSIS:
  THE
  Bacteriological, Chemical, and Microscopical
  Evidence of Disease.

BY PROF. R. V. JAKSCH,

    Of the University of Prague.

TRANSLATED FROM THE THIRD GERMAN EDITION AND ENLARGED

BY JAMES CAGNEY, M.A., M.D.,

    Phys. to the Hosp. for Epilepsy and Paralysis, Regent’s Park.

With ADDITIONAL ILLUSTRATIONS, many Coloured.

_In large 8vo. Handsome Cloth. 25s._

SECOND ENGLISH EDITION.


GENERAL CONTENTS.

The Blood--The Buccal Secretion--The Nasal Secretion--The
Sputum--The Gastric Juice and Vomit--The Fæces--Examination of the
Urine--Investigation of Exudations, Transudations, and Cystic
Fluids--The Secretions of the Genital Organs--Methods of Bacteriological
Research--Bibliography.


OPINIONS OF THE PRESS.

    “A striking example of the application of the Methods of Science to
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    admirable manner. . . . A _standard work_ . . . as TRUSTWORTHY as it
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    “A new and valuable work . . . worthy of a FIRST PLACE AS A
    TEXT-BOOK. . . . Of great value both to medical practitioners and
    medical students.”--_Journal of American Med. Association, Chicago._


_In Large 8vo, Handsome Cloth._ 16_s._

  THE DISEASES OF CHILDHOOD
  (MEDICAL).

BY

H. BRYAN DONKIN, M.A., M.D., F.R.C.P.,

    PHYSICIAN TO THE WESTMINSTER HOSPITAL AND THE EAST LONDON HOSPITAL
    FOR CHILDREN: JOINT LECTURER ON MEDICINE AND CLINICAL MEDICINE AT
    THE WESTMINSTER HOSPITAL MEDICAL SCHOOL.


OPINIONS OF THE PRESS.

    _The Lancet._--“DR. DONKIN’s book is in every sense of the word a
    piece of ORIGINAL WORK, REMARKABLY WELL WRITTEN, and founded on his
    own LARGE EXPERIENCE.”

    _British Medical Journal._--“DR. DONKIN’s work possesses characters
    which will earn for it a DISTINCT PLACE in the estimation of the
    profession. . . . May be confidently recommended to the study of
    every practitioner who takes an interest in the subjects with which
    it deals.”

    _Practitioner._--“Unquestionably a VERY VALUABLE contribution to the
    list of works on the diseases of childhood.”

    _Edinburgh Medical Journal._--“A thoughtful, accurate, and
    compendious treatise, written in a charming style, and with much
    vigour.”

    _Medical Magazine._--“A TRULY PRACTICAL work, the record of the
    personal experience and observation of an independent mind.”


  THE DISEASES OF CHILDHOOD
  (SURGICAL).

BY

BILTON POLLARD, M.B., B.S., F.R.C.S,

    Surgeon, N.E. Hospital for Children; Assist.-Surgeon, University
    College Hospital; Assist. Prof. of Clinical Surgery and Teacher of
    Practical Surgery, University College.

_EACH VOLUME PUBLISHED SEPARATELY._


  DISEASES OF THE BLOOD.

BY

WILLIAM HUNTER, M.D., F.R.S.E.

    _Assist.-Phys. London Fever Hospital; Arris and Gale Lect. R.C.S.
    Eng., &c., &c._


~By SIR DYCE DUCKWORTH, M.D., F.R.C.P.~

[Illustration: Fig. 1.--Human Articular Cartilage from head of a
metatarsal bone (Normal).]

  GOUT
  (A TREATISE ON).

BY

SIR DYCE DUCKWORTH,

    M.D. Edin., LL.D., Hon. Physician to H.R.H. the Prince of Wales,
    Physician to, and Lecturer on Clinical Medicine in, St.
    Bartholomew’s Hospital.

_In Large 8vo. With Chromo-Lithograph, Folding Plate, and Illustrations
in the Text. Handsome Cloth, 25s._

⁂ This work is the result of the special opportunities which London
Practice affords as, probably, the largest field of observation for the
study of Gout. It is based on the experience derived from both Hospital
and Private Practice, each of which furnishes distinctive phases of the
disease.


OPINIONS OF THE PRESS.

    “Thoroughly practical and highly philosophical. The practitioner
    will find in its pages an ENORMOUS AMOUNT OF INFORMATION. . . . A
    monument of clinical observation, of extensive reading, and of close
    and careful reasoning.”--_Practitioner._

    “All the known facts of Gout are carefully passed in review. . . .
    We have chapters upon the clinical varieties of Gout, and the
    affections of special organs and textures. . . . A very VALUABLE
    STOREHOUSE of material on the nature, varieties, and treatment of
    Gout.”--_Lancet._

    “A very well written, clear, and THOROUGHLY SATISFACTORY EPITOMÉ of
    our present knowledge upon the subject of Gout.”--_Philadelphia
    Therapeutic Gazette._

    “Impartial in its discussion of theories, full and accurate in its
    description of clinical facts, and a TRUSTWORTHY GUIDE TO
    TREATMENT.”--_British Medical Journal._


[Illustration: Fig. 1.--Gangliform Swelling on the Dorsum of the Hand of
a Child aged Eight.]

~By A. E. GARROD, M.D., F.R.C.P.~

  Rheumatism
  AND
  Rheumatoid Arthritis
  (A TREATISE ON).

BY

ARCHIBALD E. GARROD,

    M.A., M.D. Oxon., F.R.C.P., Assistant-Physician to the West London
    Hospital, &c.

_In Large 8vo, with Charts and Illustrations. Handsome Cloth, 21s._


⁂ The author’s aim is to give a consistent picture of Rheumatism as a
systemic disease presenting one definite set of phenomena, the result,
it is believed, of one single and specific morbid process.


OPINIONS OF THE PRESS.

    “The wide subject of the etiology of rheumatism is _carefully
    treated_. . . . The discussion of etiology is completed by a _full
    analysis_ of the conditions which determine individual attacks.
    . . . Dr. Garrod is to be congratulated on having put before the
    profession SO CLEAR AND COHERENT an account of the rheumatic
    diseases. The style of his work is eminently readable.”--_Lancet._

    “Well written and reliable. . . . We have little doubt that this
    monograph _will take rank with the best treatises_ on special
    medical subjects in the English language.”--_Dublin Medical
    Journal._

    “An EXCELLENT ACCOUNT of the clinical features of the diseases in
    question. The chapters on treatment are THOROUGHLY
    PRACTICAL.”--_Manchester Medical Chronicle._


_In Large 8vo, with Illustrations in the Text and 13 Folding-Plates,
28s._

  DISEASES OF THE HEART
  AND THORACIC AORTA
  (THE DIAGNOSIS OF).

by

A. ERNEST SANSOM, M.D, F.R.C.P.,

    Physician to the London Hospital; Consulting Physician,
    North-Eastern Hospital for Children; Examiner in Medicine, Royal
    College of Physicians (Conjoint Board for England), and University
    of Durham; Lecturer on Medical Jurisprudence and Public Health,
    London Hospital Medical College, &c.

(From Chap. ix.--“The Observed Signs of Neuro-Cardiac Disease.”)

[Illustration: FIG. 6.--Case of Grave’s disease with well-marked
retraction of upper eyelid (Stellway’s sign). There was very little
projection of the eyeball, though prominence appeared to be extreme.
Patient aged twenty-four. (_From a photograph._)]


    “Dr. Sansom has opened to us a TREASURE-HOUSE OF KNOWLEDGE. . . .
    The originality of the work is shown on every page, an originality
    so complete as to mark it out from every other on the subject with
    which we are acquainted.”--_Practitioner._

    “A book which does credit to British Scientific Medicine. We warmly
    commend it to all engaged in clinical work.”--_The Lancet._


~By PROFESSOR T. M’CALL ANDERSON, M.D.~

_SECOND EDITION. Now Ready, with Four Chromo-Lithographs, Steel Plate,
and numerous Woodcuts. 25s._

  DISEASES OF THE SKIN
  (A TREATISE ON),

  With Special Reference to Diagnosis and Treatment, Including
  an Analysis of 12,000 Consecutive Cases.

By T. M’CALL ANDERSON, M.D.,

    _Professor of Clinical Medicine, University if Glasgow._

PROFESSOR M’CALL ANDERSON’s Treatise, affording, as it does, a complete
_résumé_ of the best modern practice, is written--not from the
standpoint of the University Professor--but from that of one who, during
upwards of a quarter of a century, has been actively engaged both in
private and in hospital practice, with unusual opportunities for
studying this class of disease, hence the PRACTICAL and CLINICAL
directions given are of great value.

Speaking of the practical aspects of Dr. ANDERSON’s work, the _British
Medical Journal_ says:--“Skin diseases are, as is well known, obstinate
and troublesome, and the knowledge that there are ADDITIONAL RESOURCES
besides those in ordinary use will give confidence to many a puzzled
medical man, and enable him to encourage a doubting patient. ALMOST ANY
PAGE MIGHT BE USED TO ILLUSTRATE THE FULNESS OF THE WORK IN THIS
RESPECT. . . . The chapter on Eczema, that universal and most
troublesome ailment, describes in a comprehensive spirit, and with the
greatest accuracy of detail, the various methods of treatment. Dr.
Anderson writes with the authority of a man who has tried the remedies
which he discusses, and the information and advice which he gives cannot
fail to prove extremely valuable.”


OPINIONS OF THE PRESS.

    “Professor M’Call Anderson has produced a work likely to prove VERY
    ACCEPTABLE to the busy practitioner. The sections on treatment are
    very full. For example, ECZEMA has 110 pages given to it, and 73 of
    these pages are devoted to treatment.”--_Lancet._

    “Beyond doubt, the MOST IMPORTANT WORK on Skin Diseases that has
    appeared in England for many years. . . . Conspicuous for the AMOUNT
    AND EXCELLENCE of the CLINICAL AND PRACTICAL information which it
    contains.”--_British Medical Journal._

    “The work may be regarded as a storehouse of FACTS gathered and
    sifted by one whose opinion is entitled to the highest respect, and
    we have no hesitation in stating our belief that it has NO EQUAL in
    this country.”--_Edinburgh Medical Journal._

    “ESSENTIALLY a useful book, clear and graphic in description,
    dogmatic and hopeful on questions of treatment.”--_Birmingham
    Medical Review._


~By Drs. MEYER and FERGUS.~

_Now Ready, with Three Coloured Plates and numerous Illustrations. Royal
8vo, Handsome Cloth, 25s._

  DISEASES OF THE EYE
  (A PRACTICAL TREATISE ON),

BY EDOUARD MEYER,

  _Prof. à l’École Pratique de la Faculté de Médecine de Paris,
  Chev. of the Leg. of Honour, &c._

Translated from the Third French Edition, with Additions as contained in
the Fourth German Edition,

By F. FERGUS, M.B., Ophthalmic Surgeon, Glasgow Infirmary.


The particular features that will most commend Dr. Meyer’s work to
English readers are--its CONCISENESS, its HELPFULNESS in explanation,
and the PRACTICALITY of its directions. The best proof of its worth may,
perhaps, be seen in the fact that it has now gone through _three_ French
and _four_ German editions, and has been translated into most European
languages--Italian, Spanish, Russian, and Polish--and even into
Japanese.


Opinions of the Press.

    “A GOOD TRANSLATION OF A GOOD BOOK. . . . A SOUND GUIDE in the
    diagnosis and treatment of the various diseases of the eye that are
    likely to fall under the notice of the general Practitioner. The
    Paper, Type, and Chromo-Lithographs are all that could be desired.
    . . . We know of no work in which the DISEASES and DEFORMITIES of
    the LIDS are more fully treated. Numerous figures illustrate almost
    every defect remediable by operation.”--_Practitioner._

    “A VERY TRUSTWORTHY GUIDE in all respects. . . . THOROUGHLY
    PRACTICAL. Excellently translated, and very well got up. Type,
    Woodcuts, and Chromo-Lithographs are alike excellent.”--_Lancet._

    “Any Student will find this work of GREAT VALUE. . . . The chapter
    on Cataract is excellent. . . . The Illustrations describing the
    various plastic operations are specially helpful.”--_Brit. Med.
    Journal._

    “An EXCELLENT TRANSLATION of a standard French Text-Book. . . . We
    can cordially recommend Dr. Meyer’s work. It is essentially a
    PRACTICAL WORK. The Publishers have done their part in the TASTEFUL
    and SUBSTANTIAL MANNER CHARACTERISTIC OF THEIR MEDICAL PUBLICATIONS.
    The Type and the Illustrations are in marked contrast to most
    medical works.”--_Ophthalmic Review._ #/


    _In Large 8vo, with Numerous Illustrations, Handsome Cloth, 10s.
    6d._

  THE BRAIN AND SPINAL CORD

  (The Structure and Functions of).

    BY

    VICTOR HORSLEY, B.S., F.R.C.S., F.R.S.,

    Professor of Pathology, University College; Assistant-Surgeon,
    University College Hospital, &c.


    “The portion treating of the development of the Nervous System from
    the simplest animals up to man, everywhere replete with interest.
    . . . In the last four Lectures we have most clearly stated the
    results of modern work. . . . WELL WORTH the study of all who wish
    to apply the lessons of recent physiological research.”--_Edinburgh
    Medical Journal._

    “We HEARTILY COMMEND the book to all readers and to ALL CLASSES OF
    STUDENTS ALIKE, as being almost the only lucid account extant,
    embodying the LATEST RESEARCHES and their conclusions.”--_British
    Medical Journal._


_IN PREPARATION--BY THE SAME AUTHOR._

  SURGERY OF THE BRAIN.

BY VICTOR HORSLEY, F.R.S, &c.,

    Assistant Surgeon, University College Hospital; Professor of
    Pathology, University College, &c., &c.


_In Large 8vo. With Illustrations. 21s._

ON PERIPHERAL NEURITIS.

BY JAS. ROSS, M.D., LL.D.,

    Late Physician to the Manchester Royal Infirmary, and Joint
    Professor of Medicine at the Owens College;

AND JUDSON BURY, M.D., M.R.C.P.,

    Senior Assistant Physician to the Manchester Royal Infirmary.

    “It will for many years remain the AUTHORITATIVE TEXT-BOOK on
    peripheral neuritis.”--_British Medical Journal._

    “A monument of industry--should be carefully read by
    all.”--_Edinburgh Medical Journal._

    “A MOST COMPLETE and masterly treatise.”--_Sheffield Med. Journal._


~By W. BEVAN LEWIS.~

  MENTAL DISEASES
  (A TEXT-BOOK OF):

  Having Special Reference to the Pathological
  Aspects of Insanity.

BY

W. BEVAN LEWIS, L.R.C.P. Lond., M.R.C.S. Eng.,

    Medical Director of the West Riding Asylum, Wakefield.

_In Large 8vo, with Eighteen Lithographic Plates and Illustrations in
the Text. Handsome Cloth, 28s._


OPINIONS OF THE PRESS.

    “Will take the HIGHEST RANK as a Text-Book of Mental
    Diseases.”--_British Medical Journal._

    “Without doubt the BEST BOOK in English of its kind. . . . The
    chapter on Epileptic Insanity and that on the Pathology of Insanity
    are perfect, and show a power of work and originality of thought
    which are admirable.”--_Journal of Mental Science._

    “The work, all through, is the outcome of original observation and
    research.”--_Mind._

    “A SPLENDID ADDITION to the literature of mental diseases. . . . The
    anatomical and histological section is ADMIRABLY DONE. . . . The
    clinical section is concise and tersely written. It is, however, to
    the pathological section that the work owes its chief merit. As a
    STANDARD WORK on the pathology of mental diseases this work should
    occupy a prominent place in the library of every alienist
    physician.”--_Dublin Medical Journal._

    “Affords a fulness of information which it would be difficult to
    find in any other treatise in the English language.”--_Edin. Medical
    Journal._

    “We record our conviction that the book is the best and most
    complete treatise upon the pathological aspect of the subject with
    which we are familiar. . . . An ABSOLUTELY INDISPENSABLE addition to
    every alienist’s and neurologist’s library.”--_The Alienist and
    Neurologist._

    “It would be quite impossible to say too much in praise of the
    ILLUSTRATIONS.”--_American Journal of Insanity._

    “The Section on Pathological Anatomy is UNRIVALLED in English
    literature.”--_Bulletin de la Soc. Méd. Mentale de Belgique._


_Large 8vo, Handsome Cloth, 16s._

  LUNATIC ASYLUMS:
  THEIR ORGANISATION AND MANAGEMENT.

BY CHARLES MERCIER, M.B.,

    _Late Senior Assistant-Medical Officer at Leavesden Asylum, and at
    the City of London Asylum._


    =PART I. HOUSING.=--=General Principles=: Sanitary
    Conditions--Supervision--Treatment and Grouping--Precautions--Size;
    Cost; Equipment; Accessibility. =General Arrangements=: General
    Construction; Walls; Floors; Windows; Blinds; Locks--Heating; Open
    Fires; Hot Coils in the Wards; Hot Coils outside the Ward; The
    Fire-places; Fire-guards--Lighting; Gas Meters--Water; The Softening
    of Water; Water Meters. =Wards and Ward Offices=: (_a_) The Day
    Rooms--Furniture; Floor Covering; Curtains; Tables; Seats; Screens;
    Bookcase; Newspaper Stand; Letter-Box; Piano; Decorations; Flowers
    and Plants; Medicine and other Cupboards--(_b_) Dormitories--Beds;
    Woven Wire Mattresses; Bed Feet; Special Forms of Bedstead;
    Mattresses; Pillows; Blankets; Quilts; Chamber Utensils; Mirrors;
    Brushes and Combs; Lockers; Screens--Supervision Dormitories--Single
    Rooms; Shutters; Ventilation and Lighting--Padded Rooms--Bath Rooms
    and Baths--Urinals--Water-Closets; Position; Floor and Walls; Forms;
    Water Waste Preventers--Lavatories; Basins; Towels--Sculleries--Slop
    and Brush Closets--Boot Rooms--Soiled Linen Closets--Coal
    Stores--Ward Stores. =The Dining and Recreation Halls, Chapel, &c.=:
    Recreation Hall; Heating; Ventilation--The Chapel--Receiving
    Room--Visiting Room. =Communication=: Passages; Staircases.
    =Administrative Portion=: The Kitchen--Scullery--Laundry--Wash
    House; Drying Room; Ironing Room; Foul Laundry; Boiler
    House--Stores--Workshops--Offices; Superintendent’s; Assistant
    Medical Officer’s; Other Officers’; Library; Dispensary; Mortuary;
    Photographic Studio. =Accommodation for the Staff=: For the Medical
    Superintendent--For Attendants--For Assistant Medical Officers.
    =Airing Courts=: Plants--Flower Beds--Paths--Seats--Birds and Games.

    =PART II. FOOD AND CLOTHING.=--=Food=: Character of
    Food--Beverages--Dietaries. =Testing=: Meat; Salt Meat; Flour;
    Bread; Butter; Milk; Cheese; Sugar; Tea; Coffee; Cocoa; Vinegar;
    Pepper; Mustard; Salt; Beer; Tinned Provisions; Rice; Peas and
    Beans; Potatoes. =Storing and Keeping=: Meat; Tea; Coffee; Cocoa;
    Mustard; Pepper; and Spices; Tinned Goods; Milk; Butter; Cheese;
    Potatoes. =Serving=: Mode of--Table Furniture--Extra Diets.
    =Clothing=: Women’s Clothing; Dresses; Petticoats; Stays; Undermost
    Garment; Stockings; Boots; Hats and Bonnets; Shawls; Men’s Clothing;
    Trousers; Coats; Waistcoats; Shirts and Undershirts; Drawers;
    Neckties; Boots; Overcoats; Hats and Caps.

    =PART III. OCCUPATION AND AMUSEMENT.=--=Occupation=: Inducement to
    Work--Difficulty from want of Intelligence--Dangers--From Use of
    Tools; From Relaxation of Supervision; To Security; To Health; From
    Mingling of the Sexes. =Amusements=: in the Wards--in the Airing
    Courts; Quoits; Bowls; Lawn-Tennis; Skittles; Badminton; Rackets;
    Fives; Croquet; Golf; Cricket; Football; Grounds; Other Open-Air
    Amusements; Races, &c.--Recreations in the Recreation Hall; Dances;
    Theatricals; Concerts.

    =PART IV. DETENTION AND CARE.=--=Detention=: Meaning of Term;
    Limitation of Restraint. =Care=: Suicide; Suicidal Tendency in the
    First Degree--Suicides in the Second Degree--Suicides in the Third
    Degree--Treatment of the First Degree--Treatment of the Third
    Degree--Supervision--Precautions; Razors; Knives and Scissors;
    Broken Glass and Crockery; Home-Made Knives; Points of Suspension;
    Means of Suspension; Fire; Water. =Violence=: Provocations and
    Inducements--Aggressive Restraint--Closeness of Aggregation--Insane
    Peculiarities--Treatment of Violent Patients--Dispersion--Removal of
    Causes--Change of Surroundings--Forewarnings of Violence--Mode of
    Assault--Assaults with Weapons--Precautions as to
    Weapons--Management of Patients when Violent--Pretended Violence.
    =Accident=: Causes of Accidents--Falls--Epileptic Fits--Warnings of
    Fits--Amplitude of Warning--Direction of Fall--Labour of
    Epileptics--Various Precautions for Epileptics--Falls from Defective
    Footgear--from Feebleness--from Jostling--from Obstacles--from
    Defects in Flooring--Suffocation; Impaction of Food in the
    Throat--Precautions--Inhalation of Food into the
    Windpipe--Epileptics at Night--Scalding--Fire--Precautions in
    Construction--Precautions in Management--Provisions for the Safety
    of Patients--Locks of Single Rooms--Removal of Patients should be
    Practised--Fire-Extinguishing Apparatus. =Cleanliness=:
    Bathing--Dirty Habits--Causes; Treatment; Neatness of Apparel.

    =PART V. THE STAFF.=--Responsibility--Treatment according to
    Deserts; Awards to Merit; Awards to Faulty Conduct; Amount of
    Punishment; Punishment should be Prompt; Punishment should fit the
    Crime; Who should Punish; Reward and Punishment both
    necessary--Supervision; Inspection; Surprise Visits--Reports. =The
    Chaplain=: The Library--Repairing Books--Torn Pages: Loose Pages;
    Back half off; Back wholly gone; Covers Torn; Re-sewing--Other
    Duties. =The Superintendent=: Supremacy--Character--Duties--Medical
    Duties. =Statutory Duties=: Duties attending the Reception of
    Patients--Original Reception--Private Patient--Reception on Judicial
    Order on Petition; The Order; The Certificates.


~By Drs. OBERSTEINER and HILL.~

  THE
  CENTRAL NERVOUS ORGANS:
  _A GUIDE TO THE STUDY OF THEIR STRUCTURE IN
  HEALTH AND DISEASE._

BY

PROFESSOR H. OBERSTEINER,

    University of Vienna.

_TRANSLATED, WITH ANNOTATIONS AND ADDITIONS_,

BY

ALEX HILL, M.A., M.D.,

    Master of Downing College, Cambridge.

_With all the Original Illustrations. Large 8vo, Handsome Cloth, 25s._


⁂ The Publishers have the pleasure to announce that to the English
version of this important Treatise, numerous original ADDITIONS and a
GLOSSARY of the subject have been contributed by the EDITOR, whose
admirable work in this department of research is so well known. These
Additions greatly increase the value of the book to students.

Special attention is also directed to the ILLUSTRATIONS. Many of these
are on a plan peculiarly helpful to the student--the one-half being in
outline, the other filled in.


OPINIONS OF THE PRESS.

    “Dr. Hill has enriched the work with many notes of his own. . . .
    Dr. Hill’s translation is most accurate, the English is excellent,
    and the book is very readable. . . . Dr. Obersteiner’s work is
    admirable. He has a marvellous power of marshalling together a large
    number of facts, all bearing on an extremely intricate subject, into
    a harmonious, clear, consecutive whole. . . . INVALUABLE as a
    text-book.”--_British Medical Journal._

    “A MOST VALUABLE CONTRIBUTION to the Study of the Anatomy and
    Pathology of the Nervous System. We cannot speak too highly of the
    ability and skill which Prof. Obersteiner has brought to bear on
    this most difficult subject, and of the way in which the whole work
    is illustrated.”--_Brain._

    “The FULLEST and MOST ACCURATE EXPOSITION now attainable of the
    results of anatomical inquiry. The Translation is done by one who is
    himself a Master of Anatomy, able not only to follow his author, but
    also to supplement him with the results of independent research. Dr.
    Hill’s additions add materially to the value of the original. The
    work is specially commended to all students of mental science. . . .
    The illustrative figures are of particular excellence and admirably
    instructive.”--_Mind._


_In Large 8vo, Handsome Cloth. 21s._

  FORENSIC MEDICINE
  AND
  TOXICOLOGY.

  for the Use of Practitioners and Students.

BY

J. DIXON MANN, M.D., F.R.C.P.,

    Professor of Medical Jurisprudence and Toxicology in Owens College,
    Manchester; Examiner in Forensic Medicine in the University of
    London, and in the Victoria University; Physician to the Salford
    Royal Hospital.


PART I.--Forensic Medicine. PART II.--Insanity in its Medico-legal
Bearings. PART III.--Toxicology.

    _Dublin Medical Journal._--“By far the MOST RELIABLE, MOST
    SCIENTIFIC, and MOST MODERN book on Medical Jurisprudence with which
    we are acquainted.”

    _The Law Journal._--“This new work will be of value to all those who
    as medical men or lawyers are engaged in cases where the testimony
    of medical experts forms a part of the evidence. . . . A MOST USEFUL
    work of reference.”

    _Medical Press._--“This EXCELLENT TEXT-BOOK cannot fail to be a
    success; it gives all a student requires for examination, and all
    that is necessary for the practitioner.”


_In Large 8vo, Handsome Cloth. 25s._

  A TREATISE ON RUPTURES.

BY

JONATHAN F. C. H. MACREADY, F.R.C.S.,

    Surgeon to the Great Northern Central Hospital; to the City of
    London Hospital for Diseases of the Chest, Victoria Park; to the
    Cheyne Hospital for Sick and Incurable Children; and to the City of
    London Truss Society.

_With Twenty-four Lithographed Plates and Illustrations in the Text._


    _Lancet._--“A MINE OF WEALTH to those who will study it--a great
    storehouse of FACTS.”

    _Edinburgh Medical Journal._--“Certainly by far the MOST COMPLETE
    and AUTHORITATIVE WORK on the subject with which we are acquainted.
    The text is clear and concise, the numerous illustrations are
    REPRODUCTIONS FROM PHOTOGRAPHS from nature; the author’s statements
    are founded on an UNIQUE EXPERIENCE, watch is freely drawn upon.”

    _Dublin Journal of Medical Science._--“This really is a COMPLETE
    MONOGRAPH on the subject.”


~By W. THORBURN, F.R.C.S. Eng.~

  THE SURGERY OF THE SPINAL CORD

  (A Contribution to the Study of):

By WILLIAM THORBURN, B.S., B.Sc., M.D. Lond., F.R.C.S. Eng.,

    Assistant Surgeon to the Manchester Royal Infirmary.

_In Large 8vo, with Illustrations and Tables. Handsome Cloth, 12s. 6d._


    “We congratulate Dr. Thorburn on his MASTERLY MONOGRAPH.”--_Saturday
    Review._

    “A MOST VALUABLE CONTRIBUTION to the literature of a field of
    surgery which, although but recently brought under cultivation, is
    already yielding such brilliant results.”--_Birmingham Medical
    Review._

    “Really the FULLEST RECORD we have of Spinal Surgery. . . . The work
    marks an important advance in modern Surgery.”

    “A most THOROUGH and EXHAUSTIVE work on Spinal Surgery.”--_Bristol
    Medical Journal._

    “A MOST VALUABLE contribution both to Physiology and
    Surgery.”--_Ophthalmic Review._

    “A VERY VALUABLE contribution to practical neurology. . . . This
    book is an excellent, clear, concise monograph.”--_Philadelphia
    Therapeutic Gazette._


~By H. W. PAGE, F.R.C.S.~

  RAILWAY INJURIES:

  _With Special Reference to those of the Back and Nervous System, in
  their Medico-Legal and Clinical Aspects._

By HERBERT W. PAGE, M.A., M.C. (Cantab), F.R.C.S. (Eng.),

    Surgeon to St. Mary’s Hospital, Dean, St. Mary’s Hospital Medical
    School, &c.

_In Large 8vo. Handsome Cloth, 6s._


    “A work INVALUABLE to those who have many railway cases under their
    care pending litigation. . . . A book which every lawyer as well as
    doctor should have on his shelves.”--_British Medical Journal._

    “Deserves the most careful study. . . . A book which every medical
    man would do well to read before he presents himself for examination
    and cross-examination in the witness-box on a railway
    case.”--_Dublin Med. Journal._

    “This book will undoubtedly be of great use to Lawyers.”--_Law
    Times._


~By J. KNOWSLEY THORNTON, M.B., M.C.~

  THE SURGERY OF THE KIDNEYS,

  Being the Harveian Lectures, 1889.

By J. KNOWSLEY THORNTON, M.B., M.C.,

    Surgeon to the Samaritan Free Hospital, &c.

_In Demy 8vo, with Illustrations. Handsome Cloth, 5s._


    “The name and experience of the author confer on the Lectures the
    stamp of authority.”--_British Medical Journal._

    “These Lectures are an exposition by the hand of an EXPERT of what
    is known and has been done, up to the present, in the Surgery of the
    Kidneys.”--_Edinburgh Medical Journal._

    “The book will necessarily be widely read, and will have an
    important influence on the progress of this domain of
    Surgery.”--_University Medical Magazine._


SECOND REVISED AND ENLARGED EDITION. _With Illustrations in the Text,
and Thirty-Seven Plates. Large 8vo. Handsome Cloth, 30s._

  SEWAGE DISPOSAL WORKS:

  A GUIDE TO THE

  _Construction of Works for the Prevention of the Pollution by Sewage
  of Rivers and Estuaries._

BY

W. SANTO CRIMP, MEM. INST. C.E., F.G.S.,

    Late Assistant-Engineer to the London County Council.

SECOND EDITION. REVISED AND ENLARGED.


PART I.--INTRODUCTORY.

  Introduction.
  Details of River Pollutions and Recommendations of Various
  Commissions.
  Hourly and Daily Flow of Sewage.
  The Pail System as Affecting Sewage.
  The Separation of Rain-water from the Sewage Proper.
  Settling Tanks.
  Chemical Processes.
  The Disposal of Sewage-sludge.
  The Preparation of Land for Sewage Disposal.
  Table of Sewage Farm Management.


PART II.--SEWAGE DISPOSAL WORKS IN OPERATION--THEIR CONSTRUCTION,
MAINTENANCE, AND COST.

_Illustrated by Plates showing the General Plan and Arrangement adopted
in each District._

  LONDON.
  Doncaster Irrigation Farm.
  Beddington Irrigation Farm, Borough of Croydon.
  Bedford Sewage Farm Irrigation.
  Dewsbury and Hitchin Intermittent Filtration.
  Merton, Croydon Rural Sanitary Authority.
  Rochester, Kent, and Swanwick, Derbyshire.
  The Ealing Sewage Works.
  Chiswick.
  Kingston-on-Thames, A.B.C. Process.
  Salford Sewage Works.
  Bradford, Precipitation.
  New Malden, Chemical Treatment and Small Filters.
  Friern Barnet.
  Acton, Ferozone and Polarite Process.
  Ilford, Chadwell, and Dagenham Sewage Disposal Works.
  Coventry.
  Wimbledon.
  Birmingham.
  Margate.
  Portsmouth.
  BERLIN.
  Sewage Precipitation Works, Dortmund (Germany).
  Treatment of Sewage by Electrolysis.

    “All persons interested in Sanitary Science owe a debt of gratitude
    to Mr. Crimp. . . . His work will be especially useful to SANITARY
    AUTHORITIES and their advisers . . . EMINENTLY PRACTICAL AND USEFUL
    . . . gives plans and descriptions of MANY OF THE MOST IMPORTANT
    SEWAGE WORKS of England . . . with very valuable information as to
    the cost of construction and working of each. . . . The
    carefully-prepared drawings permit of an easy comparison between the
    different systems.”--_Lancet._

    “Probably the BEST AND MOST COMPLETE TREATISE on the subject which
    has appeared in our language. . . . Will prove of the greatest use
    to all who have the problem of Sewage Disposal to face. . . . The
    general construction, drawings, and type are all
    excellent.”--_Edinburgh Medical Journal._


~By Prof. A. C. HADDON.~

  EMBRYOLOGY

  (AN INTRODUCTION TO THE STUDY OF).

BY

ALFRED C. HADDON, M.A., M.R.I.A.,

    Professor of Zoology, Royal College of Science, Dublin.

_In Large 8vo, with 190 Illustrations. Handsome Cloth, 18s._


OPINIONS OF THE PRESS.

    “WELL and CLEARLY WRITTEN. . . . Many important discoveries or
    theories are described, which are necessarily absent from Balfour’s
    work.”--_Nature._

    “Dr. Haddon has written the BEST of the three modern English works
    on the subject.”--_Dublin Medical Journal._

    “The later chapters of Prof. Haddon’s work ably demonstrate the
    development of organs from the mesoblast and epiblast.”--_Brit. Med.
    Journal._

    “The zoological student, to whom as a text-book it is invaluable,
    will find it THOROUGH, TRUSTWORTHY, AND SOUND in all its teachings,
    and well up to date. . . . We specially commend the book to our
    readers.”--_Nat. Monthly._


  THE JOURNAL
  OF
  ANATOMY & PHYSIOLOGY:
  NORMAL AND PATHOLOGICAL.

Conducted by

SIR GEORGE MURRAY HUMPHRY, M.D., LL.D., F.R.S.,

    Professor of Surgery, Late Professor of Anatomy in the University of
    Cambridge;

SIR WILLIAM TURNER, M.B., LL.D., D.C.L., F.R.S.,

    Prof. of Anatomy in the University of Edinburgh;

AND

J. G. M’KENDRICK, M.D., F.R.S.,

    Prof. of the Institutes of Medicine in the University of Glasgow.

_Published Quarterly, Price 6s. Annual Subscription, 20s.; Post Free,
21s. Subscriptions payable in advance._


~By R. S. AITCHISON.~

_SECOND EDITION. Pocket-Size, Elegantly bound in Leather, Rounded edges,
8s. 6d._

  A MEDICAL HANDBOOK
  For the use of Practitioners and Students.

BY

R. S. AITCHISON, M.B. (EDIN.), F.R.C.P.E.,

    Physician, New Town Dispensary, Edinburgh; Visiting Physician, St.
    Cuthbert’s Hospital, Edinburgh, &c., &c.

_WITH NUMEROUS ILLUSTRATIONS._


=General Contents.=--Introduction--Diagnosis, Case-Taking, &c.--Diseases
of the Circulatory System--Diseases of the Respiratory System--The
Urine--Diseases of the Urinary System--Diseases of the Digestive
System--Diseases of the Nervous System--Diseases of the Hæmopoietic
System--Constitutional and General Diseases--Fevers and
Miasmatic Diseases--General Data, Rules, and Tables useful
for Reference--_Post-mortem_ Examination--Rules for
Prescribing--Prescriptions.

    “Such a work as this is really NECESSARY for the busy practitioner.
    The field of medicine is so wide that even the best informed may at
    the moment miss the salient points in diagnosis . . . he needs to
    refresh and revise his knowledge, and to focus his mind on those
    things which are ESSENTIAL. We can speak HIGHLY of Dr. Aitchison’s
    Handbook. . . . HONESTLY EXECUTED. No mere compilation, the
    scientific spirit and standard maintained throughout put it on a
    higher plane. . . . EXCELLENTLY got up, handy and portable, and well
    adapted for READY REFERENCE.”--_The Lancet._

    “As a means of ready reference, MOST COMPLETE. The busy practitioner
    will often turn to its pages.”--_Journ. of the American Med.
    Association._


~By MM. CAIRD and CATHCART.~

_FIFTH EDITION, Revised. Pocket-Size, Elegantly bound in Leather,
Rounded edges, 8s. 6d. With very Numerous Illustrations._

  A SURGICAL HANDBOOK,

  For Practitioners, Students, House-Surgeons, and Dressers.

BY

F. M. CAIRD, M.B., F.R.C.S., & C. W. CATHCART, M.B., F.R.C.S.,

    Assistant-Surgeons, Royal Infirmary, Edinburgh.


=General Contents.=--Case-Taking--Treatment of Patients before
and after Operation--Anæsthetics: General and Local--Antiseptics
and Wound-Treatment--Arrest of Hæmorrhage--Shock and
Wound-Fever--Emergency Cases--Tracheotomy: Minor Surgical
Operations--Bandaging--Fractures--Dislocations, Sprains,
and Bruises--Extemporary Appliances and Civil Ambulance
Work--Massage--Surgical Applications of Electricity--Joint-Fixation and
Fixed Apparatus--The Urine--The Syphon and its Uses--Trusses and
Artificial Limbs--Plaster-Casting--Post-Mortem Examination--Appendix:
Various Useful Hints, Suggestions, and Recipes.

    “THOROUGHLY PRACTICAL AND TRUSTWORTHY, well up to date, CLEAR,
    ACCURATE, AND SUCCINCT. The book is handy, and very well got
    up.”--_Lancet._

    “ADMIRABLY ARRANGED. The best practical little work we have seen.
    The matter is as good as the manner.”--_Edinburgh Medical Journal._

    “Will prove of real service to the Practitioner who wants a useful
    _vade mecum_.”--_British Medical Journal._

    “Fulfils admirably the objects with which it has been
    written.”--_Glasgow Medical Journal._

    “THIS EXCELLENT LITTLE WORK. Clear, concise, and very readable.
    Gives attention to important details often omitted, but ABSOLUTELY
    NECESSARY TO SUCCESS.”--_Athenæum._

    “A dainty volume.”--_Manchester Medical Chronicle._


Griffin’s Pocket-Book Series.

~By Drs. PORTER and GODWIN.~

_FOURTH EDITION. Revised and Enlarged. Leather, Rounded Edges, with 128
Illustrations and Folding-plate. 8s. 6d._

  THE SURGEON’S POCKET-BOOK.
  Specially adapted to the Public Medical Services.

BY SURGEON-MAJOR J. H. PORTER.

_REVISED AND IN GREAT PART REWRITTEN_

BY BRIGADE-SURGEON C. H. Y. GODWIN,

    Late Professor of Military Surgery in the Army Medical School.


    “Every Medical Officer is recommended to have the ’Surgeon’s
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    engaged, in Field Medical Service.”--_Lancet._

    “A complete _vade mecum_ to guide the military surgeon in the
    field.”--_British Medical Journal._


_Pocket Size. Leather. With Illustrations. At Press._

  PRACTICAL HYGIENE:
  INCLUDING
  Air and Ventilation; Water, Supply and Purity; Food and the
  Detection of Adulterations; Sewage Removal, Disposal,
  and Treatment; Epidemics, &c., &c.

BY

SURGEON-MAJOR A. M. DAVIES, D.P.H.Camb.,

    _Late Assistant-Professor of Hygiene, Army Medical School._


_POCKET SIZE. LEATHER. SHORTLY._

  SANITARY RULES AND TABLES:
  A Pocket-Book of Data and General Information

Useful to Medical Men, Medical Officers of Health, Sanitary Authorities,
Municipal Engineers, Surveyors, and Sanitary Inspectors.

BY

W. SANTO CRIMP, M.INST.C.E., F.G.S,

AND

CHARLES HAMLET COOPER, A.M.I.C.E.


_With Numerous Illustrations and Plate in Colours. 5s._

  MIDWIFERY
  (_AN INTRODUCTION TO THE STUDY OF._)
  For the Use of Young Practitioners, Students, and Midwives.

BY ARCHIBALD DONALD, M.A., M.D., C.M.EDIN.,

    Surgeon to St. Mary’s Hospital for Women and Children, Manchester;
    and the Manchester and Salford Lying-in Institution.


    _British Gynæcological Journal._--“HIGHLY CREDITABLE to the author,
    and should prove of GREAT VALUE to Midwifery Students and Junior
    Practitioners.”

    _Sheffield, Medical Journal._--“As an introduction to the study of
    Midwifery, NO BETTER BOOK could be placed in the hands of the
    Student.”


_In Crown 8vo, with Illustrations. 7s. 6d._

  THE DISEASES OF WOMEN
  (OUTLINES OF).
  A CONCISE HANDBOOK FOR STUDENTS.

BY JOHN PHILLIPS, M.A., M.D., F.R.C.P.,

    Physician, British Lying-in Hospital; Assist. Obst. Physician,
    King’s College Hospital; Fell. and Mem. Bd. for Exam. of Midwives,
    Obstet. Society; Examiner in Midwifery, University of Glasgow, &c.,
    &c.


⁂ Dr. Phillips’ work is ESSENTIALLY PRACTICAL in its nature, and will be
found invaluable to the student and young practitioner.


    “Contains a GREAT DEAL OF INFORMATION in a VERY CONDENSED form.
    . . . The value of the work is increased by the number of sketch
    diagrams, some of which are HIGHLY INGENIOUS.”--_Edin. Med.
    Journal._

    “Dr. PHILLIPS’ MANUAL is written in a SUCCINCT style. He rightly
    lays stress on Anatomy. The passages on CASE-TAKING are EXCELLENT.
    Dr. Phillips is very trustworthy throughout in his views on
    THERAPEUTICS. He supplies an excellent series of SIMPLE but VALUABLE
    PRESCRIPTIONS, an INDISPENSABLE REQUIREMENT for students.”--_Brit.
    Med. Journal._

    “This EXCELLENT TEXT-BOOK . . . gives just what the student
    requires. . . . The prescriptions cannot but be helpful.”--_Medical
    Press._


_In 8vo, with Illustrations. Cloth, 7s. 6d._

  The Management of Labour and of the Lying-in Period.

BY PROF. H. G. LANDIS, M.D.,

    Starling Medical College.


    “Fully accomplishes the object kept in view by its author. . . .
    Will be found of GREAT VALUE by the young practitioner.”--_Glasgow
    Medical Journal._


BY SIR WILLIAM AITKEN, M.D. Edin., F.R.S,

    Late Professor of Pathology in the Army Medical School; Examiner in
    Medicine for the Military Medical Services of the Queen; Fellow of
    the Sanitary Institute of Great Britain; Corresponding Member of the
    Royal Imperial Society of Physicians of Vienna, and of the Society
    of Medicine and Natural History of Dresden.


SEVENTH EDITION.

  THE SCIENCE AND PRACTICE OF MEDICINE.

_In Two Volumes, Royal 8vo, Cloth, 42s._

    “The STANDARD TEXT-BOOK in the English Language. . . . There is,
    perhaps, no work more indispensable for the Practitioner and
    Student.”--_Edin. Medical Journal._


  OUTLINES OF THE SCIENCE AND PRACTICE OF MEDICINE.
  A TEXT-BOOK FOR STUDENTS.

Second Edition. Crown 8vo, 12s. 6d.

    “Students preparing for examinations will hail it as a perfect
    godsend for its conciseness.”--_Athenæum._


_In Large Crown 8vo. With numerous Illustrations. 10s. 6d._

  ANÆSTHETICS AND THEIR ADMINISTRATION:
  A PRACTICAL HAND-BOOK FOR MEDICAL AND DENTAL
  PRACTITIONERS AND STUDENTS.

BY FREDERIC HEWITT, M.A., M.D.,

    _Anæsthetist and Instructor in Anæsthetics, London Hospital;
    Chloroformist and Lecturer on Anæsthetics, Charing Cross Hospital;
    Anæsthetist, Dental Hospital, London; and National Orthopædic
    Hospital, &c., &c._

    “The MOST TRUSTWORTHY book for reference on the subject with which
    we are acquainted.”--_Edinburgh Med. Journal._

    “Should be on EVERY medical bookshelf.”--_Practitioner._

    “May truly be described as a valuable addition to medical
    literature. . . . ABSOLUTELY ESSENTIAL to junior
    practitioners.”--_Practitioner._

    “The BEST TREATISE on the subject we have yet read.”--_Dublin Journ.
    Med. Science._


_In Large 8vo. Cloth, 12s. 6d._

  THE
  PHYSIOLOGIST’S NOTE-BOOK:
  A SUMMARY OF THE
  Present State of Physiological Science for Students.

BY

ALEX HILL, M.A., M.D.,

    Master of Downing College, Cambridge.

_With Numerous Illustrations and Blank Pages for MS. Notes._

General Contents.--The Blood--The Vascular System--The
Nerves--Muscle--Digestion--The Skin--The Kidneys--Respiration--The
Senses--Voice and Speech--Central Nervous
System--Reproduction--Chemistry of the Body.


CHIEF FEATURES OF DR. HILL’S NOTE-BOOK.

  1. It helps the Student to CODIFY HIS KNOWLEDGE.
  2. Gives a grasp of BOTH SIDES of an argument.
  3. Is INDISPENSABLE for RAPID RECAPITULATION.

    _The Lancet_ says of it:--“The work which the Master of Downing
    College modestly compares to a Note-book is an ADMIRABLE COMPENDIUM
    of our present information . . . will be a REAL ACQUISITION to
    Students . . . gives all ESSENTIAL POINTS. . . . The TYPOGRAPHICAL
    ARRANGEMENT is a chief feature of the book. . . . Secures at a
    glance the EVIDENCE on both sides of a theory.”

    _The Hospital_ says:--“The Physiologist’s Note-book bears the
    hall-mark of the Cambridge School, and is the work of one of the
    most successful of her teachers. . . . Will be INVALUABLE to
    students.”

    _The British Medical Journal_ commends in the volume--“Its admirable
    diagrams, its running bibliography, its clear Tables, and its
    concise statement of the anatomical aspects of the subject.”

    “If a Student could rely on remembering every word which he had ever
    heard or read, such a book as this would be unnecessary; but
    experience teaches that he constantly needs to recall the form of an
    argument and to make sure of the proper =classification of his
    facts=, although he does not need a second time to follow the author
    up all the short steps by which the ascent was first made. With a
    view to rendering the book useful for rapid recapitulation, I have
    endeavoured to strike out every word which was not essential to
    clearness, and thus, without I hope falling into ‘telegram’ English,
    to give the text the form which it may be supposed to take in a
    well-kept Note-book; at the same time, space has been left for the
    =introduction in MS.= of such additional facts and arguments as seem
    to the reader to bear upon the subject-matter. For the same reason
    the drawings are reduced to =diagrams=. All details which are not
    necessary to the comprehension of the principles of construction of
    the apparatus or organ, as the case may be, are omitted, and it is
    hoped that the drawings will, therefore, be easy to grasp, remember,
    and reproduce.

    “As it is intended that the ‘Note-book’ should be essentially a
    Student’s book, no references are given to foreign literature or to
    recondite papers in English; but, on the other hand, references are
    given to a number of =classical English memoirs=, as well as to
    descriptions in text-books which appear to me to be particularly
    lucid, and the Student is strongly recommended to study the passages
    and Papers referred to.”--_Extract from Author’s Preface._


By WILLIAM STIRLING, M.D., Sc.D.,

    Professor in the Victoria University, Brackenbury Professor of
    Physiology and Histology in the Owens College, Manchester; and
    Examiner in the Universities of Oxford, Edinburgh, and London; and
    for the Fellowship of the Royal College of Surgeons, England.


_SECOND EDITION. In Extra Crown 8vo, with 234 Illustrations. Cloth, 9s._

  PRACTICAL PHYSIOLOGY (Outlines of):
  A Manual for the Physiological Laboratory,

  INCLUDING

  CHEMICAL AND EXPERIMENTAL PHYSIOLOGY, WITH REFERENCE TO PRACTICAL
  MEDICINE.

  Part I.--Chemical Physiology.
  Part II.--Experimental Physiology.

⁂ _In the Second Edition, revised and enlarged, the number of
Illustrations has been increased from 142 to 234._

[Illustration: Fig. 118.--Horizontal Myograph of Frédéricq. _M_, Glass
plate, moving on the guides _f_, _f_; _l_, Lever; _m_, Muscle; _p_, _e_,
_e_, Electrodes; _T_, Cork plate; _a_, Counterpoise to lever; _R_, Key
in primary circuit.]


OPINIONS OF THE PRESS.

    “This valuable little manual. . . . The GENERAL CONCEPTION of the
    book is EXCELLENT; the arrangement of the exercises is all that can
    be desired; the descriptions of experiments are CLEAR, CONCISE, and
    to the point.”--_British Medical Journal._

    “The Second Edition has been thoroughly worked up to date, and a
    large number of well-executed woodcuts added. It may be recommended
    to the student as one of the BEST MANUALS he can possess as a guide
    and companion in his Physiological Work, and as one that will
    usefully supplement the course given by a Physiological
    Teacher.”--_Lancet._

    “The student is enabled to perform for himself most of the
    experiments usually shown in a systematic course of lectures on
    physiology, and the practice thus obtained must prove INVALUABLE.
    . . . May be confidently recommended as a guide to the student of
    physiology, and, we doubt not, will also find its way into the hands
    of many of our scientific and medical practitioners.”--_Glasgow
    Medical Journal._

    “An exceedingly convenient Handbook of Experimental
    Physiology.”--_Birmingham Medical Review._


~Companion Volume by Prof. Stirling.~

_SECOND EDITION. In Extra Crown 8vo, with 368 Illustrations. Cloth, 12s.
6d._

  PRACTICAL HISTOLOGY (Outlines of):
  A MANUAL FOR STUDENTS.

⁂ Dr. Stirling’s “Outlines of Practical Histology” is a compact Handbook
for students, providing a COMPLETE LABORATORY COURSE, in which almost
every exercise is accompanied by a drawing. Very many of the
Illustrations have been prepared expressly for the work.

[Illustration: Fig. 200.--L.S., Cervical Ganglion of Dog. _c_, Capsule;
_s_, Lymph sinus; _F_, Follicle; _a_, Medullary cord; _b_, Lymph paths
of the medulla; _V_, Section of a blood-vessel; _HF_, Fibrous part of
the hilum. × 10.]


OPINIONS OF THE PRESS.

    “The general plan of the work is ADMIRABLE. . . . It is very evident
    that the suggestions given are the outcome of a PROLONGED EXPERIENCE
    in teaching Practical Histology, combined with a REMARKABLE JUDGMENT
    in the selection of METHODS. . . . Merits the highest praise for the
    ILLUSTRATIONS, which are at once clear and faithful.”--_British
    Medical Journal._

    “We can confidently recommend this small but CONCISELY-WRITTEN and
    ADMIRABLY ILLUSTRATED work to students. They will find it to be a
    VERY USEFUL and RELIABLE GUIDE in the laboratory, or in their own
    room. All the principal METHODS of preparing tissues for section are
    given, with such precise directions that little or no difficulty can
    be felt in following them in their most minute details. . . . The
    volume proceeds from a MASTER in his craft.”--_Lancet._

    “We have no doubt the OUTLINES will meet with most favourable
    acceptance among workers in Histology.”--_Glasgow Medical Journal._


WORKS

By J. R. AINSWORTH DAVIS, B. A.,

    PROFESSOR OF BIOLOGY, UNIVERSITY COLLEGE, ABERYSTWYTH.

  BIOLOGY
  (AN ELEMENTARY TEXT-BOOK OF).

SECOND EDITION. In Two Parts.

    PART I. VEGETABLE MORPHOLOGY AND PHYSIOLOGY. With Complete
    Index-Glossary and 128 Illustrations. Price 8s. 6d.

    PART II. ANIMAL MORPHOLOGY AND PHYSIOLOGY. With Complete
    Index-Glossary and 108 Illustrations. Price 10s. 6d.

_EACH PART SOLD SEPARATELY._

    ⁂ NOTE.--The SECOND EDITION has been thoroughly Revised and
    Enlarged, and includes all the leading selected TYPES in the various
    Organic Groups.

    Of the SECOND EDITION, the _British Medical Journal_
    says:--“Certainly THE BEST ‘BIOLOGY’ with which we are acquainted,
    and it owes its pre-eminence to the fact that it is an EXCELLENT
    attempt to present Biology to the Student as a CORRELATED and
    COMPLETE SCIENCE. The glossarial Index is a MOST USEFUL addition.”

    “Furnishes a CLEAR and COMPREHENSIVE exposition of the subject in a
    SYSTEMATIC form.”--_Saturday Review._

    “Literally PACKED with information.”--_Glasgow Medical Journal._


  THE FLOWERING PLANT,
  AS ILLUSTRATING THE FIRST PRINCIPLES OF BOTANY.

    Specially adapted for London Matriculation, S. Kensington, and
    University Local Examinations in Botany. SECOND EDITION. With
    numerous Illustrations. 3s. 6d.

    “It would be hard to find a Text-book which would better guide the
    student to an accurate knowledge of modern discoveries in Botany.
    . . . The SCIENTIFIC ACCURACY of statement, and the concise
    exposition of FIRST PRINCIPLES make it valuable for educational
    purposes. In the chapter on the Physiology of Flowers, an _admirable
    résumé_ is given, drawn from Darwin, Hermann Müller, Kerner, and
    Lubbock, of what is known of the Fertilization of
    Flowers.”--_Journal of the Linnean Society._

    ⁂ Recommended by the National Home-Reading Union; and also for use
    in the University Correspondence Classes.


  A ZOOLOGICAL POCKET-BOOK:
  or, Synopsis of Animal Classification.

_Comprising Definitions of the Phyla, Classes, and Orders, with
explanatory Remarks and Tables._

By Dr. EMIL SELENKA,

    Professor in the University of Erlangen.

Authorised English translation from the Third German Edition.

In Small Post 8vo, Interleaved for the use of Students. Limp Covers, 4s.


    “Dr. Selenka’s Manual will be found useful by all Students of
    Zoology. It is a COMPREHENSIVE and SUCCESSFUL attempt to present us
    with a scheme of the natural arrangement of the animal
    world.”--_Edin. Med. Journal._

    “Will prove very serviceable to those who are attending Biology
    Lectures. . . . The translation is accurate and clear.”--_Lancet._


WORKS by A. WYNTER BLYTH, M.R.C.S., F.C.S.,

    Public Analyst for the County of Devon, and Medical Officer of
    Health for St. Marylebone.

_NEW EDITION. Revised and partly Rewritten._


  FOODS: THEIR COMPOSITION AND ANALYSIS.

_In Crown 8vo, Cloth, with Elaborate Tables, Folding Litho-Plate, and
Photographic Frontispiece._

_THIRD EDITION. Price 16s._


GENERAL CONTENTS.

  History of Adulteration--Legislation, Past and Present--Apparatus
  useful to the Food-Analyst--“Ash”--Sugar--Confectionery--Honey--
  Treacle--Jams and Preserved Fruits--Starches--Wheaten-Flour--Bread--
  Oats--Barley--Rye--Rice--Maize--Millet--Potato--Peas--Chinese Peas--
  Lentils--Beans--MILK--Cream--Butter--Cheese--Tea--Coffee--Cocoa and
  Chocolate--Alcohol--Brandy--Rum--Whisky--Gin--Arrack--Liqueurs--Beer--
  Wine--Vinegar--Lemon and Lime Juice--Mustard--Pepper--Sweet and Bitter
  Almond--Annatto--Olive Oil--Water. _Appendix_: Text of English and
  American Adulteration Acts.

    “Thoroughly practical. . . . Should be in the hands of every medical
    practitioner.”--_Lancet._

    “An admirable digest of the most recent state of knowledge. . . .
    Interesting even to lay readers.”--_Chemical News._

    “STANDS UNRIVALLED for completeness of information.”--_Sanitary
    Record._

    ⁂ =The THIRD Edition contains many Notable Additions, especially on
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  THE
  SEA-CAPTAIN’S MEDICAL GUIDE.

BY

WM. JOHNSON SMITH, F.R.C.S., L.S.A.,

    Of the Seamen’s Hospital, Greenwich; Surgeon, Seamen’s Hospital,
    Royal Albert Docks; Surgeon, Seamen’s Hospital Society, &c., &c.




    Transcriber’s Notes

    This text follows the original work. Inconsistencies in spelling,
    hyphenation, capitalisation, etc. have been retained, except as
    mentioned below. This applies to chemical compound names as well.

    Textual remarks:
    Page 13, Footnote [18], Jerome Cardan: also known as Jérôme Cardan,
    Girolamo Cardano, Hieronymus Cardanus.
    Page 18, Praag van, Leonides: should be Leonides van Praag,
    Isidorus. This is the (enlarged) Dutch translation of Werber’s book.
    Page 52: reference to the separate article on (the detection of)
    Tin: there is no such article in the book.
    Page 62, footnote [55]: micro-millimetre should be micro-metre.
    Page 175, structural formulas: the original work gives two identical
    structural formulas; both are correct, but they do not show the
    difference between the two compounds.
    Page 192, that of Borussica: possibly a typographical error for
    Borussia (Borussica is the adjective).
    Page 399, 18·1 mgrms. (·18 grain): at least one of the numbers is
    wrong (possibly the second number should be ·28).
    Page 507: 6·4 mgmrs. (1 grain): this should probably be either 64
    mgrms. or ·1 grain. In the context, the latter seems more probable.
    Buchner/Büchner are different persons, both are spelled correctly.
    Hofman/Hoffman/Hofmann/Hoffmann, Köhler/Koehler, Liné/Linné,
    Pellagra/Pellagri, Schuchardt/Schuchart: possibly these are spelling
    variants or typographical errors referring to the same persons.
    Kapferschlaeger: should possibly be Kupferschlaeger.
    Schaufféle: should possibly be Schauffele or Schäuffele.
    The index has been left as in the original work, even though it is
    not always alphabetic.
    Advertisements: there are some references to pages 35 and 36 of the
    advertisements. These pages were not present in the original.

    Changes made to the text
    Some minor obvious punctuation and typographical errors have been
    corrected silently. French accents and German umlauts have been
    added or corrected where needed.
    Multi-page tables have been combined into single tables; many tables
    have been re-arranged.
    Structural formulas have been moved to separate lines.
    Some sections starting with § were printed as section headers in the
    original work; they have been treated as regular numbered sections
    here.
    Footnotes have been moved to under the paragraph, table, etc. they
    refer to.

    Various pages:
    Chever/Chever’s changed to Chevers/Chevers’s
    Ein natürliches System der Gift-wirkungen/Giftwirkungen standardised
    to Gift-Wirkungen as in Loew’s original
    Aertzt (also in compound words) changed to Aerzt
    Bérenger-Férraud changed to Bérenger-Féraud
    L. L. Hote and similar spellings changed to L. L’Hôte
    Gréhaut changed to Gréhant

    Page xxv: Duboia Ruselli changed to Duboia Rusellii
    Page xxix: Aerated changed to Aërated as in text
    Page xxx: (3) Silver in the Arts changed to (2) Silver in the Arts
    Page xxxii: 90-392 changed to 390-392
    Page 14: Médicine changed to Médecine
    Page 16: Vénéneuse changed to Vénéneuses
    Page 17: Dagendorff changed to Dragendorff
    Page 18: Webber changed to Werber; In Zwee Theilen changed to In
    Zwei Theilen
    Page 25: list under A. numbered (as following lists)
    Page 27: Mezerein changed to Mezereon
    Page 31: Section number § 21. added
    Page 39: alloxanthin changed to alloxantin as elsewhere
    Page 44: V´ changed to V¹ as in illustration
    Page 51: chloralhydrate changed to chloral hydrate as elsewhere
    Page 60, table: June changed to Jan. (as described in text below
    table)
    Page 64: Ni(CO)⁴ changed to Ni(CO)₄
    Page 82: Salkowski changed to Salkowsky as elsewhere
    Page 94, footnote [92]: Schwefelsäure changed to Schwefelsäure-
    Page 96: bood changed to blood
    Page 124: of the legs; changed to of the legs);
    Page 129: PART IV changed to PART V
    Page 134: tape-worn changed to tape-worm
    Page 141: IV. Ether. changed to IV.--Ether. for consistency with
    other headings
    Page 143: Soubeyran changed to Soubeiran
    Page 164, footnote [194]: 1865 changed to 1856
    Page 214: to contains changed to to contain; Afol. changed to Afl.
    Page 222: that normal changed to than normal
    Page 232: Boisbeaudran changed to Boisbaudran
    Page 232: see Index changed to See § 314
    Page 246: Jervin changed to Jervine
    Page 249: γ inserted in table
    Page 257: Mikroscop changed to Mikroskop
    Page 270: table and paragraph “It is therefore obvious ...” moved to
    before description of analysis
    Page 277: β. lutidine changed to β-lutidine
    Page 280, § 340, platinum compound: C₆H₅ etc. changed to (C₆H₅ etc.
    Page 299, § 359: of the French; changed to of the French);
    Page 302: menbrane changed to membrane
    Page 313: α[r] changed to [α]r as elsewhere
    Page 318, § 384: (C₅H₄O₃-- changed to (C₅H₄O₃)--
    Page 320: Pettenkoffer changed to Pettenkofer
    Page 328: cephalapoda changed to cephalopoda
    Page 329: under goes changed to undergoes
    Page 371, footnotes [487a] and [487b]: the original work has one
    footnote with two footnote anchors; the footnote has been copied for
    clarity
    Page 373: homotatropine changed to homatropine
    Page 398: Harnach changed to Harnack
    Page 409: skaken changed to shaken
    Page 423: ·15 to ·13 grain changed to ·15 to ·18 grain
    Page 448: They eat changed to They ate
    Page 449: Wenzeln’s changed to Wenzel’s
    Page 451: [α]D changed to [α]_{D} as elsewhere
    Page 458: oenanthe changed to œnanthe as elsewhere
    Page 465: toxalumin changed to toxalbumin
    Page 469: Petromyzon fluviatalis changed to Petromyzon fluviatilis
    Page 491: bot hare changed to both are
    Page 492: Heading DIAMINES. changed to Diamines. for consistency
    Page 514: Uppmain changed to Uppmann
    Page 533: bain de tersier changed to bain de Tessier
    Page 534, table: 25-35 changed to 25-65
    Page 588: pp. 558 and 555 changed to pp. 558 and 559
    Page 591, Heading II. PRECIPITATE changed to PRECIPITATED as
    elsewehere
    Page 614: lamellae changed to lamellæ as elsewhere
    Page 617: (20 to 40 grains; changed to (20 to 40 grains);
    Page 637, Ointment of Red Iodide of Mercury: closing ) added after
    rubri
    Page 638: Hahneman’s changed to Hahnemann’s
    Page 656: from to time changed to from time to time
    Page 662: deat changed to death
    Page 679: mgrs. changed to mgrms. as elsewhere
    Page 686: ANTIDOTES:-- changed to III. ANTIDOTES:--
    Page 698: zine changed to zinc
    Page 702: Acolycoctin changed to Acolyctin
    Page 704: Fleetman’s changed to Fleitmann’s
    Page 705: Bécœur changed to Bécoeur;
    Page 706: Bynsen’s changed to Bynssen’s
    Page 710: Duboia Ruselii changed to Duboia Rusellii
    Page 711: Günzburgh changed to Günzburg
    Page 713: Jecquirity changed to Jequirity; Kreosote changed to
    Kreozote; Lanthropine changed to Lanthopine
    Page 715: Mithridates changed to Mithradetes
    Page 717: Pharoah’s serpent changed to Pharaoh’s serpent
    Page 719: Rettger’s changed to Rettgers’s
    Page 720: Sanarelle’s changed to Sanarelli’s; Scheppe’s changed to
    Schleppe’s; Schræder changed to Schraeder
    Page 721: antimpetigines changed to anti-impetigines
    Page 722: Teschmacher changed to Teschemacher
    Page 723: Vidale’s changed to Vidali’s
    Page 739: Bain de Tersier changed to Bain de Tessier