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.

§ 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.

[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.

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:--

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.