Chapter XXVIII: Part VI: Alkaloids and Poisonous Vegetable Principles Separated for the (2)

§ 315. =Melting-point.=--The method of sublimation just given also determines the melting-point; such a determination will, however, seldom compare with the melting-points of the various alkaloids as given in text-books, because the latter melting-points are not determined in the same way. The usual method of determining melting-points is to place a very small quantity in a glass tube closed at one end; the tube should be almost capillary. The tube is fastened to a thermometer by means of platinum wire, and then the bulb of the thermometer, with its attached tube, is immersed in strong sulphuric acid or paraffin, contained in a flask. The thermometer should be suspended midway in the liquid and heat carefully applied, so as to raise the temperature gradually and equably. It will be found that rapidly raising the heat gives a different melting-point to that which is obtained by slowly raising the heat. During the process careful watching is necessary: most substances change in hue before they actually melt. A constant melting-point, however often a substance is purified by recrystallisation, is a sign of purity.

§ 316. =Identification by Organic Analysis.=--In a few cases (and in a few only) the analyst may have sufficient material at hand to make an organic analysis, either as a means of identification or to confirm other tests. By the vacuum process described in “Foods,” in which carbon and nitrogen are determined by measuring the gases evolved by burning the organic substance in as complete a vacuum as can be obtained, very minute quantities of a substance can be dealt with, and the carbon and nitrogen determined with fair accuracy. It is found in practice that the carbon determinations appear more reliable than those of the nitrogen, and there are obvious reasons why this should be so.

Theoretically, with the improved gas-measuring appliances, it is possible to measure a c.c. of gas; but few chemists would care to create a formula on less than 10 c.c. of CO₂. Now, since 10 c.c. of CO₂ is equal to 6·33 mgrms. of carbon, and alkaloids average at least half their weight of carbon, it follows that 12 mgrms. of alkaloid represent about the smallest quantity with which a reliable single combustion can be made.

The following table gives a considerable number of the alkaloids and alkaloidal bodies, arranged according to their content in carbon:--

TABLE SHOWING THE CONTENT OF CARBON AND NITROGEN IN VARIOUS ALKALOIDAL BODIES.

Carbon. Nitrogen.

Asparagin, 36·36 21·21
Methylamine, 38·71 45·17
Betaine, 44·44 10·37
Theobromine, 46·67 31·11
Theine, 49·48 28·86
Indican, 49·60 2·22
Muscarine, 50·42 11·77
Lauro-cerasin, 52·47 1·53
Amanitine, 57·69 13·46
Narceine, 59·63 3·02
Colchicine, 60·53 4·15
Oxyacanthine, 60·57 4·42
Solanine, 60·66 1·68
Trimethylamine, 61·02 23·73
Jervine, 61·03 5·14
Sabadilline, 61·29 3·46
Aconitine, 61·21 2·16
Nepaline, 63·09 2·12
Colchicein, 63·44 4·38
Veratroidine, 63·8 3·1
Narcotine, 63·92 3·39
Veratrine, 64·42 2·91
Delphinine, 64·55 3·42
Physostigmine, 65·49 15·27
Rhœadine, 65·79 3·65
Cocaine, 66·44 4·84
Gelsemine, 67·00 7·10
Conhydrine, 67·12 9·79
Staphisagrine, 67·5 3·6
Chelidonine, 68·06 12·34
Atropine, Hyoscyamine, 70·58 4·84
Sanguinarine, 70·59 4·33
Papaverine, 70·79 4·13
Delphinoidine, 70·9 3·9
Morphine and Piperine, 71·58 4·91
Berberine, 71·64 4·18
Codeine, 72·24 4·68
Thebaine, 73·31 4·50
Cytisine, 73·85 12·92
Nicotine, 74·08 17·28
Quinine, 75·02 8·64
Coniine, 76·81 11·20
Strychnine, 77·24 8·92
Curarine, 81·51 5·28

§ 317. =Quantitative Estimation of the Alkaloids.=--For medico-legal purposes the alkaloid obtained is usually weighed directly, but for technical purposes other processes are used. One of the most convenient of these is titration with normal or decinormal sulphuric acid, a method applicable to a few alkaloids of marked basic powers--_e.g._, quinine is readily and with accuracy estimated in this way, the alkaloid being dissolved in a known volume of the acid, and then titrated back with soda. If a large number of observations are to be made, an acid may be prepared so that each c.c. equals 1 mgrm. of quinine. A reagent of general application is found in the so-called _Mayer’s reagent_, which consists of 13·546 grms. of mercuric chloride, and 49·8 grms. of iodide of potassium in a litre of water. Each c.c. of such solution precipitates--

Of Strychnine, ·0167 grm.
„ Brucine, ·0233 „
„ Quinine, ·0108 „
„ Cinchonine, ·0102 „
„ Quinidine, ·0120 „
„ Atropine, ·0145 „
„ Aconitine, ·0268 „
„ Veratrine, ·0269 „
„ Morphine, ·0200 „
„ Narcotine, ·0213 „
„ Nicotine, ·00405 „
„ Coniine, ·00416 „

The final reaction is found by filtering, from time to time, a drop on to a glass plate, resting on a blackened surface, and adding the test until no precipitate appears. The results are only accurate when the strength of the solution of the alkaloid is about 1 : 200; so that it is absolutely necessary first to ascertain approximatively the amount present, and then to dilute or concentrate, as the case may be, until the proportion mentioned is obtained.

A convenient method of obtaining the sulphate of an alkaloid for quantitative purposes, and especially from organic fluids, is that recommended by Wagner. The fluid is acidulated with sulphuric acid, and the alkaloid precipitated by a solution of iodine in iodide of potassium. The precipitate is collected and dissolved in an aqueous solution of hyposulphite of soda. The filtered solution is again precipitated with the iodine reagent, and the precipitate dissolved in sulphurous acid, which, on evaporation, leaves behind the pure sulphate of the base.

It is also very useful for quantitative purposes to combine an alkaloid with gold or platinum, by treating the solution with the chlorides of either of those metals--the rule as to selection being to give that metal the preference which yields the most insoluble and the most crystallisable compound.

The following table gives the percentage of gold or platinum left on ignition of the double salt:--

Gold. Platinum.

Atropine, 31·57 ...
Aconitine 20·0 ...
Amanitine, 44·23 ...
Berberine, 29·16 18·11
Brucine, ... 16·52
Cinchonine, ... 27·36
Cinchonidine, ... 27·87
Codeine, ... 19·11
Coniine, ... 29·38
Curarine, ... 32·65
Delphinine, 26·7 ...
Delphinoidine, 29·0 15·8
Emetine, ... 29·7
Hyoscyamine, 34·6 ...
Morphine, ... 19·52
Muscarine, 43·01 ...
Narcotine, 15·7 15·9
Narceine, ... 14·52
Nicotine, ... 34·25
Papaverine, ... 17·82
Pilocarpine, 35·5 23·6 to 25·2.
Piperine, ... 12·7
Quinine, 40·0 26·26
Strychnine, 29·15 18·16
Thebaine, ... 18·71
Theine, 37·02 24·58
Theobromine, ... 25·55
Veratrine, 21·01 ...

II.--Liquid Volatile Alkaloids.

THE ALKALOIDS OF HEMLOCK--NICOTINE--PITURIE--SPARTEINE.

1. THE ALKALOIDS OF HEMLOCK (CONIUM).

§ 318. The _Conium maculatum_, or spotted hemlock, is a rather common umbelliferous plant, growing in waste places, and flowering from about the beginning of June to August. The stem is from three to five feet high, smooth, branched, and spotted with purple; the leaflets of the partial involucres are unilateral, ovate, lanceolate, with an attenuate point shorter than the umbels; the seeds are destitute of vittæ, and have five prominent crenate wavy ridges. The whole plant is fœtid and poisonous. Conium owes its active properties to a volatile liquid alkaloid, _Coniine_, united with a crystalline alkaloid, _Conhydrine_.

§ 319. =Coniine= (=conia=, =conicine=), (C₈H₁₇N)--specific gravity 0·862 at 0°; melting-point, -2·5°; boiling-point, 166·6°. Pure coniine has been prepared synthetically by Ladenburg, and found to be propyl-piperidine C₅H₁₀NC₃H₇, but the synthetically-prepared piperidine has no action on polarised light. By uniting it with dextro-tartaric acid, and evaporating, it is possible to separate the substance into dextro-propyl-piperidine and lævo-propyl-piperidine. The former is in every respect identical with coniine from hemlock; it is a clear, oily fluid, possessing a peculiarly unpleasant, mousey odour. One part is soluble in 150 parts of water,[341] in 6 parts of ether, and in almost all proportions of amyl alcohol, chloroform, and benzene. It readily volatilises, and, provided air is excluded, may be distilled unchanged. It ignites easily, and burns with a smoky flame. It acts as a strong base, precipitating the oxides of metals and alkaline earths from their solutions, and it coagulates albumen. Coniine forms salts with hydrochloric acid (C₈H₁₅N.HCl), phosphoric acid, iodic acid, and oxalic acid, which are in well-marked crystals. The sulphate, nitrate, acetate, and tartrate are, on the other hand, non-crystalline.

[341] The saturated watery solution of coniine at 15°, becomes cloudy if gently warmed, and clears again on cooling.

If coniine is oxidised with nitric acid, or bichromate of potash, and diluted sulphuric acid, butyric acid is formed; and since the latter has an unmistakable odour, and other characteristic properties, it has been proposed as a test for coniine. This may be conveniently performed thus:--A crystal of potassic bichromate is put at the bottom of a test-tube, and some diluted sulphuric acid with a drop of the supposed coniine added. On heating, the butyric acid reveals itself by its odour, and can be distilled into baryta water, the butyrate of baryta being subsequently separated in the usual way, and decomposed by sulphuric acid, &c.

Another test for coniine is the following:--If dropped into a solution of alloxan, the latter is coloured after a few minutes an intense purple-red, and white needle-shaped crystals are separated, which dissolve in cold potash-lye into a beautiful purple-blue, and emit an odour of the base.[342] Dry hydrochloric acid gives a purple-red, then an indigo-blue colour, with coniine; but if the acid is not dry, there is formed a bluish-green crystalline mass. This test, however, is of little value to the toxicologist, the pure substance alone responding with any definite result.

[342] Schwarzenbach, _Vierteljahrsschr. f. prakt. Pharm._, viij. 170.

The ordinary precipitating agents, according to Dragendorff, act as follows:--

Potass bismuth iodide.
1 : 2000, a strong orange precipitate.
1 : 3000. The drop of the reagent is surrounded with a muddy border.
1 : 4000. The drop of the reagent is surrounded with a muddy border.
1 : 5000, still perceptible.
1 : 6000. The last limit of the reaction.

Phosphomolybdic acid gives a strong yellow precipitate; limit, 1 : 5000.

Potass. mercuric iodide gives a cheesy precipitate; limit, 1 : 1000 in neutral, 1 : 800 in acid, solutions.

Potass. cadmic iodide gives an amorphous precipitate, 1 : 300. The precipitate is soluble in excess of the precipitant. (Nicotine, under similar circumstances, gives a crystalline precipitate.)

Flückiger recommends the following reaction:[343]--“Add to 10 drops of ether in a shallow glass crystallising dish 2 drops of coniine, and cover with filter paper. Set upon the paper a common-sized watch-glass containing bromine water, and invert a beaker over the whole arrangement. Needle-shaped crystals of coniine hydro-bromine soon form in the dish as well as in the watch-glass.” Hydrochloric acid, used in the same way, instead of bromine water, forms with coniine microscopic needles of coniine hydrochlorate; both the hydro-bromide and the hydrochlorate doubly refract light. Nicotine does not respond to this reaction.

[343] _Reactions_, by F. A. Flückiger, Detroit, 1893.

Coniine forms with carbon disulphide a thiosulphate and a sulphite. If carbon disulphide, therefore, be shaken with an aqueous solution of coniine, the watery solution gives a brown precipitate with copper sulphate, colours ferric chloride solution dark brown red, and gives a milky opalescence with dilute acids. If coniine itself is added to carbon disulphide, there is evolution of heat, separation of sulphur, and formation of thiosulphate. Nicotine does not respond to this reaction.

§ 320. =Other Coniine Bases.=--Methyl- and ethyl-coniine have been prepared synthetically, and are both similar in action to coniine, but somewhat more like curarine. By the reduction of coniine with zinc dust conyrine (C₈H₁₁N) is formed; between coniine and conyrine stands coniceine (C₈H₁₅NO). De Coninck has made synthetically by the addition of 6 atoms of hydrogen to β collidine, a new fluid alkaloid (C₈H₁₁N + 6H = C₈H₁₇N), which he has called _isocicutine_: it has the same formula as coniine. Paraconiine Schiff prepared synthetically from ammonia and normal butyl aldehyde; it has the formula C₈H₁₅N, and therefore differs from coniine in containing two atoms less of hydrogen. All the above have a similar physiological action to coniine. α-stillbazoline (C₁₁H₁₉N), prepared by Baurath from benzaldehyde and picoline, is analogous to coniine, and according to Falck has similar action, but is more powerful.

§ 321. =Pharmaceutical Preparations.=--The percentage of coniine in the plant itself, and in pharmaceutical preparations, can be approximately determined by distilling the coniine over, in a partial vacuum,[344] and titrating the distillate with Mayer’s reagent, each c.c. = about ·00416 grm. of coniine. It appears to be necessary to add powdered potassic chloride and a small quantity of diluted sulphuric acid before titrating, or the precipitate does not separate. In any case, the end of the reaction is difficult to observe.[345]

[344] This is easily effected by uniting a flask containing the alkaloidal fluid, air-tight, with a Liebig’s condenser and a receiver, the latter being connected with Bunsen’s water-pump, or one of the numerous exhausting apparatuses now in use in every laboratory.

[345] Dragendorff, _Die Chemische Werthbestimmung einiger starkwirkender Droguen_, St. Petersb., 1874.

The fresh plant is said to contain from about ·04 to ·09 per cent., and the fruit about 0·7 per cent. of coniine.

The officinal preparations are--the leaves, the fruit, a tincture of the fruit, an extract of the leaves, the juice of the leaves (_Succus conii_), a compound hemlock pill (composed of extract of hemlock, ipecacuanha, and treacle), an inhalation of coniine (_Vapor conii_), and a poultice (_Cataplasma conii_) made with the leaves.

§ 322. =Statistics of Coniine Poisoning.=--F. A. Falck[346] has been able to collect 17 cases of death recorded in medical literature, up to the year 1880, from either coniine or hemlock. Two of these cases were criminal (murders), 1 suicidal, 2 cases in which coniine had been used medicinally (in one instance the extract had been applied to a cancerous breast; in the other, death was produced from the injection of an infusion of hemlock leaves). The remaining 12 were cases in which the root, leaves, or other portions of the plant had been ignorantly or accidentally eaten.

[346] _Prakt. Toxicologie_, p. 273.

§ 323. =Effects on Animals.=--It destroys all forms of animal life. The author made some years ago an investigation as to its action on the common blow-fly. Droplets of coniine were applied to various parts of blow-flies, which were then placed under glass shades. The symptoms began within a minute by signs of external irritation, there were rapid motions of the wings, and quick and aimless movements of the legs. Torpor set in speedily, the buzz soon ceased, and the insects lay on their sides, motionless, but for occasional twitching of the legs. The wings, as a rule, became completely paralysed before the legs, and death occurred at a rather variable time, from ten minutes to two hours. If placed in a current of air in the sun, a fly completely under the influence of coniine may recover. Coniine causes in frogs, similar to curarine, peripheral paralysis of the motor nerves, combined with a transitory stimulation, and afterwards a paralysis of the motor centres; in frogs the paralysis is not preceded by convulsions. Dragendorff experimented on the action of coniine when given to five cats, the quantities used being ·05 to ·5 grm. The symptoms came on almost immediately, but with the smaller dose given to a large cat, no effect was witnessed until twenty-five minutes afterwards; this was the longest interval. One of the earliest phenomena was dilatation of the pupil, followed by weakness of the limbs passing into paralysis, the hinder legs being affected prior to the fore. The respiration became troubled, and the frequency of the breathing diminished; the heart in each case acted irregularly, and the sensation generally was blunted; death was preceded by convulsions. In the cases in which the larger dose of ·4 to ·5 grm. was administered, death took place within the hour, one animal dying in eight minutes, a second in eighteen minutes, a third in twenty minutes, and a fourth in fifty-eight minutes. With the smaller dose of ·051 grm. given to a large cat, death did not take place until eight hours and forty-seven minutes after administration.

§ 324. =Effects on Man.=--In a case recorded by Bennet,[347] and quoted in most works on forensic medicine, the symptoms were those of general muscular weakness deepening into paralysis. The patient had eaten hemlock in mistake for parsley; in about twenty minutes he experienced weakness in the lower extremities, and staggered in walking like a drunken man; within two hours there was perfect paralysis of both upper and lower extremities, and he died in three and a quarter hours. In another case, related by Taylor, the symptoms were also mainly those of paralysis, and in other instances stupor, coma, and slight convulsions have been noted.

[347] _Edin. Med. and Surg. Journ._, July 1845, p. 169.

§ 325. =Physiological Action.=--It is generally agreed that coniine paralyses, first the ends of the motor nerves, afterwards their trunks, and lastly, the motor centre itself. At a later period the sensory nerves participate. In the earlier stage the respiration is quickened, the pupils contracted, and the blood-pressure increased; but on the development of paralysis the breathing becomes slowed, the capillaries relaxed, and the blood-pressure sinks. Death takes place from cessation of the respiration, and not primarily from the heart, the heart beating after the breathing has stopped. Coniine is eliminated by the urine, and is also in part separated by the lungs, while a portion is, perhaps, decomposed in the body.

§ 326. =Post-mortem Appearances.=--There is nothing characteristic in the appearances after death.

=Fatal Dose.=--The fatal dose of coniine is not accurately known; it is about 150 mgrms. (2·3 grains). In the case of Louise Berger, 10 to 15 drops appear to have caused death in a few minutes. The auto-experiments of Dworzak, Heinrich, and Dillaberger would indicate that one drop may cause unpleasant symptoms. Albers, in the treatment of a woman suffering from cancer of the breast, witnessed convulsions and loss of consciousness from a third dose of 4 mgrms. (·06 grain); and Eulenberg, its full narcotic effects on a child after subcutaneous injection of 1 mgrm. (·015 grain).

§ 327. =Separation of Coniine from Organic Matters or Tissues.=--The substances are digested with water, acidulated with H₂SO₄, at a temperature not exceeding 40°, and then filtered. If the filtrate should be excessive, it must be concentrated; alcohol is then added, the liquid refiltered, and from the filtrate the alcohol separated by distillation.

On cooling, the acid fluid is agitated with benzene, and the latter separated in the usual way. The fluid is now alkalised with ammonia, and shaken up once or twice with its own volume of petroleum ether; the latter is separated and washed with distilled water, and the alkaloid is obtained almost pure. If the petroleum ether leaves no residue, it is certain that the alkaloid was not present in the contents of the stomach or intestine.

The affinity of coniine with ether or chloroform is such, that its solution in either of these fluids, passed through a _dry_ filter, scarcely retains a drop of water. In this way it may be conveniently purified, the impurities dissolved by water remaining behind.

In searching for coniine, the stomach, intestines, blood, urine, liver, and lungs are the parts which should be examined. According to Dragendorff, it has been discovered in the body of a cat six weeks after death.

Great care must be exercised in identifying any volatile alkaloid as coniine, for the sources of error seem to be numerous. In one case[348] a volatile coniine-like ptomaine, was separated from a corpse, and thought to be coniine; but Otto found that in its behaviour to platinic chloride, it differed from coniine; it was very poisonous--·07 was fatal to a frog, ·44 to a pigeon, in a few minutes. In the seeds of _Lupinus luteus_ there is a series of coniine-like substances,[349] but they do not give the characteristic crystals with hydrochloric acid.

[348] Otto, _Anleitung z. Ausmittlung d. Gifte_, 1875.

[349] Sievert, _Zeitschrift für Naturwissenschaften_.

2. TOBACCO--NICOTINE.

§ 328. The different forms of tobacco are furnished by three species of the tobacco plant, viz., _Nicotianum tabacum_, _N. rustica_, and _N. persica_.

Havanna, French, Dutch, and the American tobaccos are in the main derived from _N. tabacum_; Turkish, Syrian, and the Latakia tobaccos are the produce of _N. rustica_. There seems at present to be little of _N. persica_ in commerce.

All the species of tobacco contain a liquid, volatile, poisonous alkaloid (_Nicotine_), probably united in the plant with citric and malic acids. There is also present in tobacco an unimportant camphor (_nicotianin_). The general composition of the plant may be gathered from the following table:--

TABLE SHOWING THE COMPOSITION OF FRESH LEAVES OF TOBACCO (POSSELT AND RIENMANN).

Nicotine, 0·060
Concrete volatile oil, 0·010
Bitter extractive, 2·870
Gum with malate of lime, 1·740
Chlorophyl, 0·267
Albumen and gluten, 1·308
Malic acid, 0·510
Lignine and a trace of starch, 4·969
Salts (sulphate, nitrate, and malate of potash, }
chloride of potassium, phosphate and malate } 0·734
of lime, and malate of ammonia,) }
Silica, 0·088
Water, 88·280
-------
100·836

§ 329. =Quantitative Estimation of Nicotine in Tobacco.=--The best process (although not a perfectly accurate one) is the following:--25 grms. of the tobacco are mixed with milk of lime, and allowed to stand until there is no odour of ammonia; the mixture is then exhausted by petroleum ether, the ether shaken up with a slight excess of normal sulphuric acid, and titrated back by baryta water; the sulphate of baryta may be collected and weighed, so as to control the results. With regard to the percentage of nicotine in commercial tobacco, Kosutany found from 1·686 to 3·738 per cent. in dry tobacco; Letheby, in six samples, from 1·5 to 3·2 per cent.; whilst Schlössing gives for Havanna 2 per cent., Maryland 2·29 per cent., Kentucky 6·09 per cent., Virginian 6·87 per cent., and for French tobacco, quantities varying from 3·22 to 7·96 per cent. Again, Lenoble found in Paraguay tobacco from 1·8 to 6 per cent.; and Wittstein, in six sorts of tobacco in Germany, 1·54 to 2·72 per cent.

Mr. Cox[350] has recently determined the amount of nicotine in a number of tobaccos. The results are tabulated in the following table as follows:--

[350] _Pharm. Journ._, Jan. 20, 1894.

TABLE OF RESULTS, ARRANGED ACCORDING TO PER CENT. OF NICOTINE.

Variety examined. Nicotine
per cent.

1. Syrian leaves (_a_), ·612
2. American chewing, ·935
3. Syrian leaves (_b_), 1·093
4. Chinese leaves, 1·902
5. Turkish (coarse cut), 2·500
6. Golden Virginia (whole strips), 2·501
7. Gold Flake (Virginia), 2·501
8. “Navy-cut” (light coloured), 2·530
9. Light returns (Kentucky), 2·733
10. “Navy-cut” (dark “all tobacco”), 3·640
11. Best “Birds-eye,” 3·931
12. Cut Cavendish (_a_), 4·212
13. “Best Shag” (_a_), 4·907
14. “Cut Cavendish” (_b_), 4·970
15. “Best Shag” (_b_), 5·000
16. French tobacco, 8·711
17. Algerian tobacco (_a_), 8·813
18. Algerian tobacco (_b_), 8·900

It is therefore obvious that the strength of tobacco in nicotine varies between wide limits.

Twenty-five grammes (or more or less, according to the amount of the sample at disposal) of the dried and powdered tobacco were intimately mixed with slaked lime, and distilled in a current of steam until the condensed steam was no longer alkaline; the distillate was slightly acidulated with dilute H₂SO₄, and evaporated to a conveniently small bulk. This was made alkaline with soda, and agitated repeatedly with successive portions of ether. The separated batches of ethereal solution of nicotine were then mixed and exposed to the air in a cool place. This exposure to the air carries away ammonia, if any be present, as well as ether.

Water was added to the ethereal residue, and the amount of nicotine present determined by decinormal H₂SO₄, using methyl-orange as an indicator. One c.c. of decinormal H₂SO₄ represents 0·0162 gramme of nicotine (C₁₀H₁₄N₂).

§ 330. =Nicotine= (C₁₀H₁₄N₂).--Hexahydro dipyridyl (C₅H₄N)₂H₆, when pure, is an oily, colourless fluid, of 1·0111, specific gravity at 15°.[351] It evaporates under 100° in white clouds, and boils at about 240°, at which temperature it partly distils over unchanged, and is partly decomposed--a brown resinous product remaining. It volatilises with aqueous and amyl alcohol vapour notably, and is not even fixed at -10°. It has a strong alkaline reaction, and rotates a ray of polarised light to the right. Its odour, especially on warming, is strong and unpleasantly like tobacco, and it has a sharp caustic taste. It absorbs water exposed to the air, and dissolves in water in all proportions, partly separating from such solution on the addition of a caustic alkali. The aqueous solution acts in many respects like ammonia, saturating acids fully, and may therefore be in certain cases estimated with accuracy by titration, 49 parts of H₂SO₄ corresponding to 162 of nicotine. It gives on oxidation nicotinic acid = m(β) pyridincarbo acid C₅H₄N(COOH), and by oxidation with elimination of water dipyridyl (C₅H₄N)₂, and through reduction dipiperydil (C₅H₁₀N)₂.

[351] J. Skalweit, _Ber. der. deutsch. Chem. Gesell._, 14, 1809.

Alcohol and ether dissolve nicotine in every proportion; if such solutions are distilled, nicotine goes over first. The salts which it forms with hydrochloric, nitric, and phosphoric acids crystallise with difficulty; tartaric and oxalic acid form white crystalline salts, and the latter, oxalate of nicotine, is soluble in alcohol, a property which distinguishes it from the oxalate of ammonia. The best salts are the oxalate and the acid tartrate of nicotine, from which to regenerate nicotine in a pure state.

Hydrochloride of nicotine is more easily volatilised than the pure base. Nicotine is precipitated by alkalies, &c., also by many oxyhydrates, lead, copper, &c. By the action of light, it is soon coloured yellow and brown, and becomes thick, in which state it leaves, on evaporation, a brown resinous substance, only partly soluble in petroleum ether.

A very excellent test for nicotine, as confirmatory of others, is the beautiful, long, needle-like crystals obtained by adding to an ethereal solution of nicotine a solution of iodine in ether. The crystals require a few hours to form.

Chlorine gas colours nicotine blood-red or brown; the product is soluble in alcohol, and separates on evaporation in crystals.

Cyanogen also colours nicotine brown; the product out of alcohol is not crystalline. Platin chloride throws down a reddish crystalline precipitate, soluble on warming; and gallic acid gives a flocculent precipitate. A drop of nicotine poured on dry chromic acid blazes up, and gives out an odour of tobacco camphor; if the ignition does not occur in the cold, it is produced by a gentle heat. It is scarcely possible to confound nicotine with ammonia, by reason of its odour; and, moreover, ammonia may always be excluded by converting the base into the oxalate, and dissolving in absolute alcohol.

On the other hand, a confusion between coniine and nicotine is apt to occur when small quantities only are dealt with. It may, however, be guarded against by the following tests:--

(1.) If coniine be converted into oxalate, the oxalate dissolved in alcohol, and coniine regenerated by distillation (best in _vacuo_) with caustic lye, and then hydrochloric acid added, a crystalline hydrochlorate of coniine is formed, which doubly refracts light, and is in needle-shaped or columnar crystals, or dendritic, moss-like forms. The columns afterwards become torn, and little rows of cubical, octahedral, and tetrahedral crystals (often cross or dagger-shaped) grow out of yellow amorphous masses. Crystalline forms of this kind are rare, save in the case of dilute solutions of chloride of ammonium (the presence of the latter is, of course, rendered by the treatment impossible); and nicotine does not give anything similar to this reaction.

(2.) Coniine coagulates albumen; nicotine does not.

(3.) Nicotine yields a characteristic crystalline precipitate with an aqueous solution of mercuric chloride; the similar precipitate of coniine is amorphous.

(4.) Nicotine does not react with CS₂ to form thiosulphate (see p. 266).

§ 331. =Effects on Animals.=--Nicotine is rapidly fatal to all animal life--from the lowest to the highest forms. That tobacco-smoke is inimical to insect-life is known to everybody; very minute quantities in water kill infusoria. Fish of 30 grms. weight die in a few minutes from a milligram of nicotine; the symptoms observed are rapid movements, then shivering and speedy paralysis, with decreased motion of the gills, and death. With frogs, if doses not too large are employed, there is first great restlessness, then strong tetanic convulsions, and a very peculiar position of the limbs; the respiration after fatal doses soon ceases, but the heart beats even after death. Birds also show tetanic convulsions followed by paralysis and speedy death. The symptoms witnessed in mammals poisoned by nicotine are not essentially dissimilar. With large doses the effect is similar to that of prussic acid--viz., a cry, one or two shuddering convulsions, and death. If the dose is not too large, there is trembling of the limbs, excretion of fæces and urine, a peculiar condition of stupor, a staggering gait, and then the animal falls on its side. The respiration, at first quickened, is afterwards slowed, and becomes deeper than natural; the pulse, also, with moderate doses, is first slowed, then rises in frequency, and finally, again falls. Tetanic convulsions soon develop, during the tetanus the pupils have been noticed to be contracted, but afterwards dilated, the tongue and mouth are livid, and the vessels of the ear dilated. Very characteristic of nicotine poisoning as witnessed in the cat, the rabbit, and the dog, is its peculiarly violent action, for after the administration of from one to two drops, the whole course from the commencement of symptoms to the death may take place in five minutes. F. Vas has drawn the smoke of tobacco from an immense pipe, and condensed the products; he finds the well-washed tarry products without physiological action, but the soluble liquid affected the health of rabbits,--they lost weight, the number of the blood corpuscles was decreased, and the hæmoglobin of the blood diminished.[352]

[352] _Archiv. f. Exper. Pathol. u. Pharm._, Bd. 33.

The larger animals, such as the horse, are affected similarly to the smaller domestic animals. A veterinary surgeon, Mr. John Howard, of Woolwich,[353] has recorded a case in which a horse suffered from the most violent symptoms of nicotine-poisoning, after an application to his skin of a strong decoction of tobacco. The symptoms were trembling, particularly at the posterior part of the shoulders, as well as at the flanks, and both fore and hind extremities; the superficial muscles were generally relaxed and felt flabby; and the pupils were widely dilated. There was also violent dyspnœa, the respirations being quick and short, pulse 32 per minute, and extremely feeble, fluttering, and indistinct. When made to walk, the animal appeared to have partly lost the use of his hind limbs, the posterior quarter rolling from side to side in an unsteady manner, the legs crossing each other, knuckling over, and appearing to be seriously threatened with paralysis. The anus was very prominent, the bowels extremely irritable, and tenesmus was present. He passed much flatus, and at intervals of three or four minutes, small quantities of fæces in balls, partly in the liquid state, and coated with slimy mucus. There was a staring, giddy, intoxicated appearance about the head and eyes, the visible mucous membrane being of a dark-red colour. A great tendency to collapse was evident, but by treatment with cold douches and exposure to the open air, the horse recovered.

[353] _Veter. Journal_, vol. iii.

In a case occurring in 1863, in which six horses ate oats which had been kept in a granary with tobacco, the symptoms were mainly those of narcosis, and the animals died.[354]

[354] _Annales Vétérinaires_, Bruxelles, 1868.

§ 332. =Effects on Man.=--Poisoning by the pure alkaloid nicotine is so rare that, up to the present, only three cases are on record. The first of these is ever memorable in the history of toxicology, being the first instance in which a pure alkaloid had been criminally used. The detection of the poison exercised the attention of the celebrated chemist Stas. I allude, of course, to the poisoning of M. Fougnies by Count Bocarmé and his wife. For the unabridged narrative of this interesting case the reader may consult Tardieu’s _Étude Médico-Légale sur L’Empoisonnement_.

Bocarmé actually studied chemistry in order to prepare the alkaloid himself, and, after having succeeded in enticing his victim to the chateau of Bitremont, administered the poison forcibly. It acted immediately, and death took place in five minutes. Bocarmé now attempted to hide all traces of the nicotine by pouring strong acetic acid into the mouth and over the body of the deceased. The wickedness and cruelty of the crime were only equalled by the clumsy and unskilful manner of its perpetration. The quantity of nicotine actually used in this case must have been enormous, for Stas separated no less than ·4 grm. from the stomach of the victim.

The second known case of nicotine-poisoning was that of a man who took it for the purpose of suicide. The case is related by Taylor. It occurred in June 1863. The gentleman drank an unknown quantity from a bottle; he stared wildly, fell to the floor, heaving a deep sigh, and died quietly without convulsion. The third case happened at Cherbourg,[355] where an officer committed suicide by taking nicotine, but how much had been swallowed, and what were the symptoms, are equally unknown, for no one saw him during life.

[355] _Ann. d’Hygiène_, 1861, x. p. 404.

Poisoning by nicotine, pure and simple, then is rare. Tobacco-poisoning is very common, and has probably been experienced in a mild degree by every smoker in first acquiring the habit. Nearly all the fatal cases are to be ascribed to accident; but criminal cases are not unknown. Christison relates an instance in which tobacco in the form of snuff was put into whisky for the purpose of robbery. In 1854, a man was accused of attempting to poison his wife by putting snuff into her ale, but acquitted. In another case, the father of a child, ten weeks old, killed the infant by putting tobacco into its mouth. He defended himself by saying that it was applied to make the child sleep.

In October 1855,[356] a drunken sailor swallowed (perhaps for the purpose of suicide) his quid of tobacco, containing from about half an ounce to an ounce. He had it some time in his mouth, and in half an hour suffered from frightful tetanic convulsions. There was also diarrhœa; the pupils were dilated widely; the heart’s action became irregular; and towards the end the pupils again contracted. He died in a sort of syncope, seven hours after swallowing the tobacco.

[356] _Edin. Med. Journ._, 1855.

§ 333. In 1829 a curious instance of poisoning occurred in the case of two girls, eighteen years of age, who suffered from severe symptoms of tobacco-poisoning after drinking some coffee. They recovered; and it was found that tobacco had been mixed with the coffee-berries, and both ground up together.[357]

[357] Barkhausen, _Pr. Ver. Ztg._, v. 17, p. 83, 1838.

Accidents have occurred from children playing with old pipes. In 1877[358] a child, aged three, used for an hour an old tobacco-pipe, and blew soap bubbles with it. Symptoms of poisoning soon showed themselves, and the child died in three days.

[358] _Pharm. Journ._ [3], 377, 1877.

Tobacco-juice, as expressed or distilled by the heat developed in the usual method of smoking, is very poisonous. Sonnenschein relates the case of a drunken student, who was given a dram to drink, into which his fellows had poured the juice from their pipes. The result was fatal. Death from smoking is not unknown.[359] Helwig saw death follow in the case of two brothers, who smoked seventeen and eighteen German pipefuls of tobacco. Marshall Hall[360] records the case of a young man, nineteen years of age, who, after learning to smoke for two days, attempted two consecutive pipes. He suffered from very serious symptoms, and did not completely recover for several days. Gordon has also recorded severe poisoning from the consecutive smoking of nine cigars. The external application of the leaf may, as already shown in the case of the horse, produce all the effects of the internal administration of nicotine. The old instance, related by Hildebrand, of the illness of a whole squadron of hussars who attempted to smuggle tobacco by concealing the leaf next to their skin, is well known, and is supported by several recent and similar cases. The common practice of the peasantry, in many parts of England, of applying tobacco to stop the bleeding of wounds, and also as a sort of poultice to local swellings, has certainly its dangers. The symptoms--whether nicotine has been taken by absorption through the broken or unbroken skin, by the bowel, by absorption through smoking, or by the expressed juice, or the consumption of the leaf itself--show no very great difference, save in the question of time. Pure nicotine acts with as great a rapidity as prussic acid; while if, so to speak, it is entangled in tobacco, it takes more time to be separated and absorbed; besides which, nicotine, taken in the concentrated condition, is a strong enough base to have slight caustic effects, and thus leaves some local evidences of its presence. In order to investigate the effects of pure nicotine, Dworzak and Heinrich made auto-experiments, beginning with 1 mgrm. This small dose produced unpleasant sensations in the mouth and throat, salivation, and a peculiar feeling spreading from the region of the stomach to the fingers and toes. With 2 mgrms. there was headache, giddiness, numbness, disturbances of vision, torpor, dulness of hearing, and quickened respirations. With 3 to 4 mgrms., in about forty minutes there was a great feeling of faintness, intense depression, weakness, with pallid face and cold extremities, sickness, and purging. One experimenter had shivering of the extremities and cramps of the muscles of the back, with difficult breathing. The second suffered from muscular weakness, fainting, fits of shivering, and creeping sensations about the arms. In two or three hours the severer effects passed away, but recovery was not complete for two or three days. It is therefore evident, from these experiments and from other cases, that excessive muscular prostration, difficult breathing, tetanic cramps, diarrhœa, and vomiting, with irregular pulse, represent both tobacco and nicotine poisoning. The rapidly-fatal result of pure nicotine has been already mentioned; but with tobacco-poisoning the case may terminate lethally in eighteen minutes. This rapid termination is unusual, with children it is commonly about an hour and a half, although in the case previously mentioned, death did not take place for two days.

[359] The question as to whether there is much nicotine in tobacco-smoke cannot be considered settled; but it is probable that most of the poisonous symptoms produced are referable to the pyridene bases of the general formula (C_{n}H_{2n-5}N). Vohl and Eulenberg (_Arch. Pharmac._, 2, cxlvi. p. 130) made some very careful experiments on the smoke of strong tobacco, burnt both in pipes and also in cigars. The method adopted was to draw the smoke first through potash, and then through dilute sulphuric acid. The potash absorbed prussic acid, hydric sulphide, formic, acetic, propionic, butyric, valeric, and carbolic acids; while in the acid the bases were fixed, and these were found to consist of the whole series of pyridene bases, from pyridene (C₅H₅N), boil. point 117°, picoline (C₆H₇N), boil. point 133°, lutidine (C₇H₉N), boil. point 154°, upwards. When smoked in pipes, the chief yield was pyridene; when in cigars, collidine (C₈H₁₁N); and in general, pipe-smoking was found to produce a greater number of volatile bases. The action of these bases has been investigated by several observers. They all have a special action on the organism, and all show an increase in physiological activity as the series is ascended. The lowest produce merely excitement from irritation of the encephalic nervous centres, and the highest, paralysis of those centres. Death proceeds from gradual failure of the respiratory movements, leading to asphyxia--(Kendrick and Dewar, _Proc. Roy. Soc._, xxii. 442; xxiii. 290). The most recent experimental work is that of A. Gautier; he found that tobacco smoked in a pipe produced basic compounds, a large quantity of nicotine, and a higher homologue of nicotine, C₁₁H₁₆N₂, which pre-exists in tobacco leaves, and a base C₆H₉NO, which seems to be a hydrate of picoline--(_Compt. Rend._, t. cxv. p. 992, 993). The derivatives of the pyridene series are also active. The methiodides strongly excite the brain and paralyse the extremities. A similar but more energetic action is exerted by the ethyl and allyl derivatives; the iodyallyl derivatives are strong poisons. Methylic pyridene carboxylate is almost inactive, but the corresponding ammonium salt gives rise to symptoms resembling epilepsy--(Ramsay, _Phil. Mag._, v. 4, 241). One member of the pyridene series β-lutidine has been elaborately investigated by C. Greville Williams and W. H. Waters--(_Proc. Roy. Soc._, vol. xxxii. p. 162, 1881). They conclude that it affects the heart profoundly, causing an increase in its tonicity, but the action is almost confined to the ventricles. The auricles are but little affected, and continue to beat after the ventricles have stopped. The rate of the heart’s beat is slowed, and the inhibitory power of the vagus arrested. By its action on the nervous cells of the spinal cord, it in the first place lengthens the time of reflex action, and then arrests that function. Finally, they point out that it is antagonistic to strychnine, and may be successfully employed to arrest the action of strychnine on the spinal cord.

[360] _Edin. Med. and Surg. Jour._, xii., 1816.

§ 334. =Physiological Action.=--Nicotine is absorbed into the blood and excreted unchanged, in part by the kidneys and in part by the saliva (_Dragendorff_). According to the researches of Rosenthal and Krocker,[361] nicotine acts energetically on the brain, at first exciting it, and then lessening its activity; the spinal marrow is similarly affected. The convulsions appear to have a cerebral origin; paralysis of the peripheral nerves follows later than that of the nerve centres, whilst muscular irritability is unaffected. The convulsions are not influenced by artificial respiration, and are therefore to be considered as due to the direct influence of the alkaloid on the nervous system. Nicotine has a striking influence on the respiration, first quickening, then slowing, and lastly arresting the respiratory movements: section of the vagus is without influence on this action. The cause of death is evidently due to the rapid benumbing and paralysis of the respiratory centre. Death never follows from heart-paralysis, although nicotine powerfully influences the heart’s action, small doses exciting the terminations of the vagus in the heart, and causing a slowing of the beats. Large doses paralyse both the controlling and exciting nerve-centres of the heart; the heart then beats fast, irregularly, and weakly. The blood-vessels are first narrowed, then dilated, and, as a consequence, the blood-pressure first rises, then falls. Nicotine has a special action on the intestines. As O. Nasse[362] has shown, there is a strong contraction of the whole tract, especially of the small intestine, the lumen of which may be, through a continuous tetanus, rendered very small. This is ascribed to the peripheral excitation of the intestinal nerves and the ganglia. The uterus is also excited to strong contraction by nicotine; the secretions of the bile and saliva are increased.

[361] _Ueber die Wirkung des Nicotines auf den thierischen Organismus_, Berlin, 1868.

[362] _Beiträge zur Physiologie der Darmbewegung, Leipsic_, 1866.

§ 335. =Fatal Dose.=--The fatal dose for dogs is from ½ to 2 drops; for rabbits, a quarter of a drop; for an adult not accustomed to tobacco the lethal dose is probably 6 mgrms.

§ 336. =Post-mortem Appearances.=--There seem to be no appearances so distinctive as to be justly ascribed to nicotine or tobacco-poisoning and no other.

A more or less fluid condition of the blood, and, generally, the signs of death by the lungs, are those most frequently found. In tobacco-poisoning, when the leaves themselves have been swallowed, there may be some inflammatory redness of the stomach and intestine.

§ 337. =Separation of Nicotine from Organic Matters, &c.=--The process for the isolation of nicotine is precisely that used for coniine (see p. 269). It appears that it is unaltered by putrefaction, and may be separated and recognised by appropriate means a long time after death. Orfila detected it in an animal two or three months after death; Melsens discovered the alkaloid unmistakably in the tongues of two dogs, which had been buried in a vessel filled with earth for seven years; and it has been found, by several experiments, in animals buried for shorter periods. Nicotine should always be looked for in the tongue and mucous membrane of the mouth, as well as in the usual viscera. The case may be much complicated if the person supposed to be poisoned should have been a smoker; for the defence would naturally be that there had been either excessive smoking or chewing, or even swallowing accidentally a quid of tobacco.[363] A ptomaine has been discovered similar to nicotine. Wolckenhaar separated also an alkaloid not unlike nicotine from the corpse of a woman addicted to intemperate habits; but this base was not poisonous, nor did it give any crystals when an ethereal solution was added to an ether solution of iodine. It will be well always to support the chemical evidence by tests on animal life, since the intensely poisonous action of nicotine seems not to be shared by the nicotine-like ptomaines.

[363] In an experiment of Dragendorff’s, nicotine is said to have been detected in 35 grms. of the saliva of a person who had half an hour previously smoked a cigar.

3. PITURIE.[364]

[364] See “The Alkaloid from Piturie,” by Prof. Leversidge, _Chem. News_, March 18 and 25, 1881.

§ 338. Piturie (C₆H₈N) is a liquid, nicotine-like alkaloid, obtained
from the _Duboisia hopwoodii_, a small shrub or tree belonging to
the natural order _Solanaceæ_, indigenous in Australia. The natives
mix piturie leaves with ashes from some other plant, and chew them.
Piturie is obtained by extracting the plant with boiling water
acidified with sulphuric acid, concentrating the liquid by
evaporation, and then alkalising and distilling with caustic soda,
and receiving the distillate in hydrochloric acid. The solution of
the hydrochlorate is afterwards alkalised and shaken up with ether,
which readily dissolves out the piturie. The ether solution of
piturie is evaporated to dryness in a current of hydrogen, and the
crude piturie purified by distillation in hydrogen, or by changing
it into its salts, and again recovering, &c. It is clear and
colourless when pure and fresh, but becomes yellow or brown when
exposed to air and light. It boils and distils at 243° to 244°. It
is soluble in all proportions in alcohol, water, and ether; its
taste is acrid and pungent; it is volatile at ordinary temperatures,
causing white fumes with hydrochloric acid; it is very irritating to
the mucous membranes, having a smell like nicotine at first, and
then, when it becomes browner, like pyridine. It forms salts with
acids, but the acetate, sulphate, and hydrochlorate are varnish-like
films having no trace of crystallisation; the oxalate is a
crystalline salt. Piturie gives precipitates with mercuric chloride,
cupric sulphate, gold chloride, mercur-potassic iodide, tannin, and
an alcoholic solution of iodine. If an ethereal solution of iodine
is added to an ethereal solution of piturie, a precipitate of
yellowish-red needles, readily soluble in alcohol, is deposited. The
iodine compound melts at 110°, while the iodine compound of nicotine
melts at 100°. Piturie is distinguished from coniine by its aqueous
solution not becoming turbid either on heating or on the addition of
chlorine water; it differs from picoline in specific gravity,
picoline being ·9613 specific gravity at 0°, and piturie sinking in
water; it differs from aniline by not being coloured by chlorinated
lime. From nicotine it has several distinguishing marks, one of the
best being that it does not change colour on warming with
hydrochloric acid and the addition to the mixture afterwards of a
little nitric acid. The physiological action seems to be but little
different from that of nicotine. It is, of course, poisonous, but as
yet has no forensic importance.

4. SPARTEINE.

§ 339. In 1851 Stenhouse[365] separated a poisonous volatile
alkaloid from _Spartium scoparium_, the common broom, to which he
gave the name of sparteine. At the same time a crystalline
non-poisonous substance, _scoparin_, was discovered.

[365] _Phil. Trans._, 1851.

Sparteine is separated from the plant by extraction with sulphuric
acid holding water, and then alkalising the acid solution and
distilling: it has the formula (C₁₅H₂₆N₂), and belongs to the class
of tertiary diamines. It is a clear, thick, oily substance, scarcely
soluble in water, to which it imparts a strong, alkaline reaction;
it is soluble in alcohol, in ether, and chloroform; insoluble in
benzene and in petroleum; it boils at 288°. Sparteine neutralises
acids fully, but the oxalate is the only one which can be readily
obtained in crystals. It forms crystalline salts with platinic
chloride, with gold chloride, with mercuric chloride, and with zinc
chloride. The picrate is an especially beautiful salt, crystallising
in long needles, which, when dried and heated, explode. On sealing
sparteine up in a tube with ethyl iodide and alcohol, and heating to
100° for an hour, ethyl sparteine iodide separates in long,
needle-like crystals, which are somewhat insoluble in cold alcohol.

=Effect on Animals.=--A single drop kills a rabbit; the symptoms are
similar to those produced by nicotine, but the pupils are
dilated.[366]

[366] To the nicotine group, gelsemine (C₂₄H₂₈N₂O₄) and oxalathylin (C₆H₁₀N₂) also belong, in a physiological sense, but gelsemine, like sparteine, dilates the pupil.

5. ANILINE.

§ 340. =Properties.=--Aniline or amido-benzol (C₆H₅NH₂) is made by
the reduction of nitro-benzol. It is an oily fluid, colourless when
quite pure, but gradually assuming a yellow tinge on exposure to the
air. It has a peculiar and distinctive smell. It boils at 182·5°,
and can be congealed by a cold of 8°. It is slightly soluble in
water, 100 parts of water at 16° retaining about 3 of aniline, and
easily soluble in alcohol, ether, and chloroform. It does not blue
red-litmus paper, but nevertheless acts as a weak alkali, for it
precipitates iron from its salts. It forms a large number of
crystalline salts. The hydrochloride crystallises in white plates,
and has a melting-point of 192°. The platinum compound has the
formula of (C₆H₅NH₂HCl)₂PtCl₄, and crystallises in yellow needles.

§ 341. =Symptoms and Effects.=--Aniline, like picric acid,
coagulates albumin. Aniline is a blood poison; it produces, even
during life, in some obscure way, methæmoglobin, and it
disintegrates the red blood corpuscles; both these effects lessen
the power of the blood corpuscles to convey oxygen to the tissues,
hence the cyanosis observed so frequently in aniline poisoning is
explained. Engelhardt[367] has found that aniline black is produced;
in every drop of blood there are fine black granules, the total
effect of which produce a pale blue or grey-blue colour of the skin.
Aniline has also an action on the central nervous system, at first
stimulating, and then paralysing. Schmiedeberg finds that
para-amido-phenol-ether-sulphuric acid is produced, and appears in
the urine as an alkali salt; a small quantity of fuchsine is also
produced, and has been found in the urine. Some aniline may be
excreted unchanged.

[367] _Beiträge zur Tox. des Anilins. Inaug.-Diss._, Dorpat, 1888.

The symptoms are giddiness, weakness, cyanosis, blueness of the
skin, sinking of the temperature, and dilatation of the pupil. The
pulse is small and frequent, the skin moist and cold. The patient
smells of aniline. Towards the end coma and convulsions set in. The
urine may be brown to brown-black, and may contain hyaline
cylinders. The blood shows the spectrum of methæmoglobin, and has
the peculiarities already mentioned. Should the patient recover,
jaundice often follows. The outward application of aniline produces
eczema.

Chronic poisoning by aniline is occasionally seen among workers in
the manufacture of aniline. Headache, loss of muscular power,
diminished sensibility of the skin, vomiting, loss of appetite,
pallor, eruptions on the skin, and general malaise are the chief
symptoms. The perspiration has been noticed to have a reddish
colour.

Cases of aniline poisoning are not common; Dr. Fred. J. Smith has
recorded one in the _Lancet_ of January 13, 1894.[368] The patient,
a woman, 42 years of age, of alcoholic tendencies, swallowed, 13th
December 1893, at 1.40 P.M., about 3 ounces of marking ink, the
greatest part of which consisted of aniline; in a very little while
she became unconscious, and remained so until death. At 3 P.M. her
lips were of a dark purple, the general surface of the skin was
deadly white, with a slight bluish tinge; the pupils were small and
sluggish, the breathing stertorous, and the pulse full and slow--60
per minute. The stomach was washed out, ether injected, and oxygen
administered, but the patient died comatose almost exactly twelve
hours after the poison had been taken.

[368] See also a case reported by K. Dehio, in which a person drank 10 grms. and recovered, _Ber. klinis. Wochen._, 1888, Nr. 1.

The _post-mortem_ examination showed slight congestion of the lungs;
the heart was relaxed in all its chambers, and empty of blood; it
had a peculiar green-blue appearance. All the organs were healthy.
The blood was not spectroscopically examined.

§ 342. =Fatal Dose.=--This is not known, but an adult would probably
be killed by a single dose of anything over 6 grms. Recovery under
treatment has been known after 10 grms.; the fatal dose for rabbits
is 1-1·5 grms., for dogs 3-5 grms.