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

DIVISION I.--POISONS SECRETED BY LIVING ANIMALS.

I.--Poisonous Amphibia.

§ 623. The glands of the skin of certain amphibia possess a secretion that is poisonous; the animal is unable to empty the poison glands by any voluntary act, but the secretion can readily be obtained by pressure. Zalesky found the juice in the skin glands of the _Salamandra maculosa_, milky, alkaline in reaction, and bitter in taste. He isolated from it an organic base, which he named _Salamandrine_ (C₃₄H₆₀N₂O₅), it is soluble in water and in alcohol, and forms salts. Salamandrine is a strong poison; injected subcutaneously into rabbits it causes shivering, epileptiform convulsions, and salivation; then tetanus, followed by oppressed respiration, dilated pupils, and anæsthesia. Death occurs after a kind of paralytic state. When given to dogs, it causes vomiting. In frogs, tetanus occurs first and then paralysis--the result of all the experiments being that salamandrine acts on the brain and spinal cord, leaving the heart and muscular substance unaffected. A similar secretion obtained from the water salamander (_Triton cristatus_), causes, according to Vulpian, the death of dogs in from three to eighteen hours; the symptoms being progressive weakness, slowing of the respiration, and depression of the heart’s action.

§ 624. The secretion of the skin of the common toad contains methylcarbylaminic acid, carbylamine, and, according to Fornara, an alkaloid which is soluble in alcohol, and to which the name of _phrynine_ has been applied; its action is toxic on all animals experimented upon, save toads. Administered subcutaneously to frogs, it has a digitalis-like action, causing rapid paralysis of the heart, and the breathing soon after ceases; the muscles become early rigid.

II.--The Poison of the Scorpion.

§ 625. There are several species of scorpions. The small European variety (_Scorpio europæus_) is found in Italy, the south of France, and the Tyrol; the African scorpion (_Bothus afer_, L.), which attains the length of 16 cm., is found in Africa and the East Indies; _Androctonus bicolor_ in Egypt; and the _Androctonus occitanus_ in Spain, Italy, Greece, and North Africa.

In the last joint of the tail the scorpion is provided with a poisonous apparatus, consisting of two oval glands, the canal of which leads into a round bladder, and this last is connected with a sting. When the sting is inserted, the bladder contracts, and expels the poison through the hollow sting into the wound. The smaller kinds of scorpion sting with as little general effect as a hornet, but the large scorpion of Africa is capable of producing death. There is first irritation about the wound, and an erysipelatous inflammation, which may lead to gangrene. Vomiting and diarrhœa then set in, with general weakness and a fever, which may last from one to one and a half days; in the more serious cases there are fainting, delirium, coma, convulsions, and death. According to G. Sanarelli[632] the blood corpuscles of birds, fishes, frogs, and salamanders are dissolved by the poison; only the nucleus remaining intact; the blood corpuscles of warm-blooded animals are not affected.

[632] G. Sanarelli, _Bollet. della Soc. della sez. dei cult. delle Scienze med._, v., 1888, 202.

Valentin made some experiments on frogs with the _Androctonus occitanus_. He found that soon after the sting the animal remains quiet, but on irritation it moves, and is thrown into a transitory convulsion; to this follow twitchings of single muscular bundles. The frog is progressively paralysed, and the reflex irritability is gradually extinguished from behind forwards; at first the muscles may be excited by electrical stimuli to the nerves, but later they are only capable of contraction by direct stimuli.

III.--Poisonous Fish.

§ 626. A large number of fish possess poisonous properties; in some cases the poison is local; in others the poison is in all parts of the body.

Many fish are provided with poison glands in connection with the fins or special weapons, and such are used for purposes of defence; for example, _Synanceia brachio_ is provided with a back fin consisting of 13 spines, each of which has two poison reservoirs; the reservoirs are connected with 10 to 12 tubular glands which secrete the poison, a clear feebly acid bluish fluid, exciting in a concentrated condition, local gangrene; in a diluted one, paralysis of the nervous centres.

Another kind of localisation is the localisation in certain of the internal organs. Remy states, that there are twelve varieties of _Tetrodon_ in Japanese waters, all of which are poisonous. M. Minra and K. Takesaki[633] find that the poison of the _Tetrodon_ is confined to the sexual organs of the female, and at the time of activity of these glands, the poisonous properties are most intense; but, even in winter, when the glands are atrophied, Remy found the glands were so poisonous that he could prepare from them a fluid, which, administered subcutaneously, killed dogs within two hours. The symptoms in the dog are restlessness, salivation, vomiting of slimy masses, dilatation of the pupil, paralysis and great dyspnœa. Death occurs by the lung. After death the appearances are similar to those from asphyxia; in addition to which there are small ecchymoses in the stomach and intestines; the salivary glands and pancreas are also injected. The symptoms observed in man are similar, there is headache, dilated pupils, vomiting, sometimes hæmatamesis, convulsions, paralysis, dyspnœa and death.

[633] Virchow’s _Archiv_, 1890, Bd. 122.

Some fishes are poisonous on account of the food they live upon; the _Meletta venenosa_ is only poisonous when it feeds upon a certain green monad; _Clupea thrissa_, _C. venenosa_ and certain species of _Scarus_, neither possess poison glands nor poisonous ovaries; but also derive their poisonous properties from their food. In the West Indies it is well-known that fish caught off certain coral banks are unwholesome, while the same species caught elsewhere may be eaten with safety.

A good many shell-fish, especially mussels, occasionally cause intense poisonous symptoms; those usually noticed are high fever, nettle rash, dilated pupils, and diarrhœa. It may be that in these cases a ptomaine, the product of bacterial action, has been ingested. To the agency of bacteria has been ascribed illness produced in Russia by a good many fish of the sturgeon species. The symptoms are those of cerebro-spinal paralysis. The “Icthyismus gastricus” of Germany may belong to the same type. Prochorow[634] has described illness from ingestion of _Petromyzon fluviatilis_ in Russia. Whether the fish was eaten raw or cooked, the effect was the same, producing a violent diarrhœa, dysenteric in character. Even the broth in which the fish had been boiled produced symptoms. Fresh blood of the eel is stated to be intensely poisonous; this property is apparently due to a toxalbumin; Pennavaria[635] relates the case of a man who took, in 200 c.c. of wine, 0·64 kilo. of fresh eel blood and suffered from diarrhœa with symptoms of collapse.

[634] _Pharmac. Ztg._, 1885.

[635] _Il Farmacista Italiano_, xii., 1888.

In the _Linnean Transactions_ for November, 1860, is recorded a fatal accident, which took place on board the Dutch ship “Postillion” at Simon’s Bay, Cape of Good Hope. The boatswain and purser’s steward partook of the liver of the _toad_ or _ball-bladder_ (_Diodon_); within twenty minutes the steward died; in ten minutes the boatswain was violently ill; the face flushed, the eyes glistening, and the pupils contracted; there was cyanosis of the face, the pulse was weak and intermittent, and swallowing was difficult, the breathing became embarrassed, and the body generally paralysed. Death took place in seventeen minutes. The liver of one fish only is said to have been eaten. This might weigh 4 drachms. If the account given is literally correct, the intensity of the poison equals that of any known substance.

The poisonous nature of the goby has also led to several accidents, and we possess a few experiments made by Dr. Collas,[636] who fed chickens with different parts of the fish, and proved that all parts were alike poisonous. The effects were slow in developing; they commenced in about an hour or an hour and a half, and were well developed in five hours, mainly consisting of progressive muscular weakness and prostration. Death occurred without convulsions.

[636] _Soc. Sci. Rev._, July 19, 1862; _Brit. and For. Med. Chir. Rev._, Oct. 1862, p. 536.

IV.--Poisonous Spiders and Other Insects.

§ 627. It is probable that all spiders are poisonous; the only species, however, of which we have any definite information relative to their poisonous properties, are _Lycosa tarantula_ and the _Latrodectus malmignatus_, to which may be added the New Zealand _katipo_. These spiders possess a poisonous gland connected with their masticatory apparatus, which secretes a clear, oily, bitter acid-reacting fluid; the acidity seems due to formic acid.

Zangrilli has observed several cases of tarantula bite; soon after the occurrence the part bitten is anæsthetic, after a few hours there are convulsive shiverings of the legs, cramps of the muscles, inability to stand, spasm of the pharyngeal muscles, quickening of the pulse, and a three days’ fever, with vomiting of yellow, bilious matter; recovery follows after copious perspiration. In one case there was tetanus, and death on the fourth day. The extraordinary effects attributed to the bite of the tarantula, called _tarantism_ in the Middle Ages, are well detailed by Hecker;[637] this excitement was partly hysterical and partly delirious, and has not been observed in modern times.

[637] “The Epidemics of the Middle Ages,” by J. F. C. Hecker, translated by B. G. Babington, M.D., F.R.S. (_The Dancing Mania_, chap, ii., &c.)

Dax has described the effects of the bite of the _L. malmignatus_; it occasioned headache, muscular weakness, pain in the back, cramps, and dyspnœa; the symptoms disappeared after several days.

§ 628. The _katipo_ is a small poisonous spider confined to New Zealand. Mr. W. H. Wright has recorded the case of a person who, in 1865, was bitten by this spider on the shoulder. The part rapidly became swollen, and looked like a large nettle-rash wheal; in an hour the patient could hardly walk, the respiration and circulation were both affected, and there was great muscular prostration; but he recovered in a few hours. In other cases, if the accounts given are to be relied upon, the bite of the spider has produced a chronic illness, accompanied by wasting of the body, followed by death after periods varying from six weeks to three months.[638]

[638] _Transac. of the New Zealand Inst._, vol. ii., 1869; _Brit. and For. Med. Chir. Review_, July 1871, p. 230.

§ 629. =Ants.=--The various species of ants possess at the tail special glands which secrete _formic acid_. Certain exotic species of ants are provided with a sting, but the common ant of this country has no special piercing apparatus. The insect bites, and then squirts the irritating secretion into the wound, causing local symptoms of swelling and inflammation.

§ 630. =Wasps, &c.=--Wasps, bees, and hornets all possess a poison-bag and sting. The fluid secreted is as clear as water, and of an acid reaction; it certainly contains formic acid, with some other poisonous constituent. An erysipelatous inflammation generally arises round the sting, and in those cases in which persons have been attacked by a swarm of bees, signs of general poisoning, such as vomiting, fainting, delirium, and stupor, have been noticed. Death has occasionally resulted.

§ 631. =Cantharides.=--Commercial cantharides is either the dried entire, or the dried and powdered blister-beetle, or Spanish fly (_Cantharis vesicatoria_). The most common appearance is that of a greyish-brown powder, containing shining green particles, from which cantharidin is readily extracted by exhausting with chloroform, driving off the chloroform by distillation or evaporation, and subsequently treating the extract with bisulphide of carbon, which dissolves the fatty matters only. Finally, the cantharidin may be recrystallised from chloroform, the yield being ·380 to ·570 per cent. Ferrer found in the wings and their cases, ·082 per cent.; in the head and antennæ, ·088; in the legs, ·091; in the thorax and abdomen, ·240; in the whole insect, ·278 per cent. Wolff found in the _Lytta aspera_, ·815 per cent.; Ferrer in _Mylabris cichorei_, ·1 per cent.; in _M. punctum_, ·193; and in _M. pustulata_, ·33 per cent. of _cantharidin_.

§ 632. =Cantharidin= (C₁₀H₁₂O₄) has two crystalline forms--(1) Right-angled four-sided columns with four surfaces, each surface being beset with needles; and (2) flat tables. It is the anhydride of a ketone acid (cantharidic acid), C₈H₁₃O₂-CO-COOH. It is soluble in alkaline liquids, and can be recovered from them by acidifying and shaking up with _ether_, _chloroform_, or _benzene_; it is almost completely insoluble in water. 100 parts of alcohol (99 per cent.) dissolve at 18° 0·125 part; 100 of bisulphide of carbon, at the same temperature, 0·06 part; ether, ·11 part; chloroform, 1·2 part; and benzene, ·2 part. Cantharidin can be completely sublimed, if placed in the subliming cell (described at p. 258), floating on mercury; a scanty sublimate of crystals may be obtained at so low a temperature as 82·5°; at 85°, and above, the sublimation is rapid. If the cantharidin is suddenly heated, it melts; but this is not the case if the temperature is raised gradually. The tube melting-point is as high as 218°. Potassic chromate with sulphuric acid decomposes cantharidin with the production of the green oxide of chromium. An alkaline solution of permanganate, iodic acid, and sodium amalgam, are all without influence on an alcoholic solution of cantharidin. With bases, cantharidin forms crystallisable salts, and, speaking generally, if the base is soluble in water, the “_cantharidate_” is also soluble; the lime and magnesic salts dissolve readily. From the soda or potash salt, mineral acid will precipitate crystals of cantharidin; on heating with pentasulphide of phosphorus, o-xylol is produced.

§ 633. =Pharmaceutical Preparations of Cantharides.=--The P.B. preparations of cantharides are--_Acetum cantharides_, or vinegar of cantharides, containing about ·04 per cent. of cantharidin.

_Tincture of cantharides_, containing about ·005 per cent. of cantharidin.

A solution of cantharides for blistering purposes, _Liquor epispasticus_, a strong solution of the active principle in ether and acetic acid, containing about ·16 per cent. of cantharidin.

There are also--An _ointment_; a blistering paper, _Charta epispastica_; a blistering plaster, _Emplastrum cantharides_; and a warm plaster, _Emplastrum calefaciens_.

§ 634. =Fatal Dose.=--It is difficult to state the fatal dose of cantharidin, the unassayed powder or tincture having mostly been taken. A young woman died from 1·62 grm. (25 grains) of the powder, which is perhaps equivalent to 6·4 mgrms. (1 grain) of cantharidin, whilst the smallest dose of the tincture known to have been fatal is (according to Taylor) an ounce. This would be generally equivalent to 15 mgrms. (·24 grain). Hence the fatal dose of cantharidin may be approximately stated as from 6 mgrms. upwards. But, on the other hand, recovery has taken place from very large doses.

§ 635. =Effects on Animals.=--Certain animals do not appear susceptible to the action of cantharidin. For example, hedgehogs and swallows are said to be able to take it with impunity. Radecki[639] found that cantharidin might even be injected into the blood of fowls without any injury, and frogs also seem to enjoy the same impunity; while dogs, cats, and other animals are sensitive to the poison. Galippe ascertained that after the injection of 5 mgrms. into the veins of a dog, there was exaltation of the sexual desire; the pupils quickly dilated, the dog sought a dark place, and became sleepy. Animals when poisoned die in asphyxia from paralysis of the respiratory centre. Schachowa[640] made some observations on the effect of cantharides on the renal excretion of a dog fed daily with 1 grm. in powder. On the third day, pus corpuscles were noticed; on the fifth, bacteria; on the thirteenth, the urine contained a large quantity of fatty matters, and several casts; and on the seventeenth, red shrivelled blood corpuscles were observed.

[639] _Die Cantharidin Vergift._, Diss., Dorpat, 1806.

[640] _Unters. über die Nieren_, Diss., Bern, 1877; Cornil, _Gaz. Méd._, 1880.

=Effects on Man.=--Heinrich[641] made the following experiments upon himself:--Thirty living blister-beetles were killed, and digested, without drying, in 35 grms. of alcohol for fourteen days, of this tincture ten drops were taken. There ensued immediately a feeling of warmth in the mouth and stomach, salivation, the pulse was more frequent than in health, there was a pleasant feeling of warmth about the body, and some sexual excitement lasting three hours. In half an hour there was abdominal pain, diarrhœa, and tenesmus, and frequent painful micturition. These symptoms subsided in a few hours, but there was a want of appetite, and pain about the kidneys lasting until the following day. In the second experiment, on taking 1 cgrm. of cantharidin, there were very serious symptoms of poisoning. Blisters formed on the tongue, and there was salivation, with great difficulty in swallowing, and a general feeling of illness. Seven hours after taking the poison, there were frequent micturitions of bloody urine, diarrhœa, and vomiting. Twenty hours after the ingestion the face was red, the skin hot, the pulse twenty beats beyond the normal pulsation, the tongue was denuded to two-thirds of its extent of its epithelium, and the lips and mucous membrane were red and swollen; there was great pain in the stomach, intestines, and in the neighbourhood of the kidneys, continuous desire to micturate, burning of the urethra, and swelling of the glands. There was no sexual excitement whatever; the urine was ammoniacal, and contained blood and pus; the symptoms gradually subsided, but recovery was not complete for fourteen days.

[641] Schroff, _Zeitschrift d. Ges. d. Aerzte in Wien_, 13, 56.

§ 636. The foregoing is a fair picture of what may be expected in cantharides poisoning. It is remarkable that the popular idea as to the influence of cantharidin in exciting the sexual passion, holds good only as to the entire cantharides, and not with cantharidin. It is very possible that cantharidin is not the only poisonous principle in the insect. The symptoms in other cases, fatal or not, have been as follows:--Immediate burning in the mouth and throat, extending to the stomach and alimentary canal, and increasing in intensity until there is considerable pain. Then follow salivation, difficulty in swallowing, and vomiting, and generally diarrhœa, pain in the kidneys, irritation of the bladder, priapism, and strangury, are all present. The pulse is accelerated, the breathing disturbed, there are pains in the head, and often mydriasis, giddiness, insensibility, delirium, and convulsions; trismus has been noticed. The desire to micturate frequently is urgent, the urine is generally bloody, and contains pus. Pregnant women have been known to abort. In a few of the cases in which a different course has been run, the nervous symptoms have predominated over those of gastro-intestinal irritation, and the patient has sunk in a kind of collapse. In a case of chronic poisoning by cantharides, extending over three months, and recorded by Tarchioni Bonfanti,[642] after the first dose appeared tetanic convulsions, which subsided in twenty-four hours, there was later cystitis, and from time to time the tetanic convulsions returned; gastro-enteritis followed with frequent vomiting, when, cantharides being found in the matters ejected, the otherwise obscure nature of the illness was shown.

[642] _Gaz. Med. Ital. Lomb._, 1863.

In a case recorded by Sedgwick,[643] following the gastro-enteric symptoms, there were epileptic convulsions; in this instance also was noticed an unpleasant smell, recalling the notion formerly held that cantharides imparted a peculiar odour to the breath and urine. In a case of chronic poisoning related by Tardieu, six students, during several months, used what they thought was pepper with their food, but the substance proved to be really powdered cantharides. The quantity taken each day was probably small, but they suffered from pain about the loins, and also irritation of the bladder. There was no sexual excitement.

[643] _Med. Times_, 1864.

§ 637. =Post-mortem Appearances.=--In a French criminal case, in which a man poisoned his step-brother by giving cantharides in soup, the pathological signs of inflammation of the gastro-intestinal tract were specially evident, the mouth was swollen, the tonsils ulcerated, the gullet, stomach, and intestines were inflamed, and the mucous membrane of the intestines covered with purulent matter. In another case there was an actual perforation 3 inches from the pylorus. The inflammatory appearances, however, are not always so severe, being confined to swelling and inflammation without ulceration. In all cases there has been noted inflammation of the kidneys and urinary passages, and this is seen even when cantharidin is administered to animals by subcutaneous injection. In the urine will be found blood and fatty epithelial casts, as well as pus. The contents of the stomach or the intestines will probably contain some remnants of powdered cantharides, if the powder itself has been taken.

§ 638. =Tests for Cantharidin, and its Detection in the Tissues, &c.=--The tests for cantharidin are--(1.) Its form, (2.) its action in the subliming cell, and (3.) its power of raising a blister.

The most convenient method of testing its vesicating properties, is to allow a chloroformic solution of the substance supposed to be cantharidin to evaporate to dryness, to add to this a drop of olive oil (or almond oil), and to take a drop up on the smallest possible quantity of cotton wool, and apply the wool to the inside of the arm, covering it with good oilskin, and strapping the whole on by the aid of sticking-plaster. In about an hour or more the effect is examined. The thin skin of the lips is far more easily blistered than that of the arm, but the application there is inconvenient.

Dragendorff has ascertained that cantharidin is not present in the contents of a blister raised by a cantharides plaster, although it has been found in the urine of a person treated by one; and Pettenkofer has also discovered cantharidin in the blood of a boy to whose spine a blister had been applied.

The great insolubility of cantharidin in water has led to various hypotheses as to its absorption into the system. It is tolerably easily dissolved by potash, soda, and ammonia solutions, and is also taken up in small proportion by sulphuric, phosphoric, and lactic acids. The resulting compounds quickly diffuse themselves through animal membranes. Even the salts with lime, magnesia, alumina, and the heavy metals, are not quite insoluble. A solution of salt with cantharidin, put in a dialysing apparatus, separates in twenty-four hours enough cantharidin to raise a blister.

Cantharidin has actually been discovered in the heart, brain, muscles, contents of the stomach, intestines, and fæces (as well as in the blood and urine) of animals poisoned by the substance. A urine containing cantharidin is alkaline and albuminous. Cantharidin, although readily decomposed by chemical agents, is so permanent in the body that it has been detected in the corpse of a cat eighty-four days after death.

In any forensic case, the defence will not improbably be set up that some animal (_e.g._, a fowl poisoned by cantharides) has been eaten and caused the toxic symptoms, for cantharides is an interesting example of a substance which, as before stated, for certain animals (such as rabbits, dogs, cats, and ducks), is a strong poison, whilst in others (_e.g._, hedgehogs, fowls, turkeys, and frogs), although absorbed and excreted, it appears inert. Experiment has shown that a cat may be readily poisoned by a fowl saturated with cantharides; and in Algeria the military surgeons meet with cystitis among the soldiers, caused by eating frogs in the months of May and June, the frogs living in these months almost exclusively on a species of cantharides.

Dragendorff recommends the following process:--The finely-pulped substance is boiled in a porcelain dish with potash-lye (1 part of potash and 12 to 18 of water) until the fluid is of a uniform consistence. The fluid, after cooling, is (if necessary) diluted with an equal bulk of water, for it must not be too thick; then shaken with chloroform in order to remove impurities; and after separation of the chloroform, strongly acidified with sulphuric acid, and mixed with about four times its volume of alcohol of 90 to 95 per cent. The mixture is kept for some time at a boiling temperature, filtered hot, and the alcohol distilled from the filtrate. The watery fluid is now again treated with chloroform, as above described. The chloroform extract is washed with water, the residue taken up on some hot almond oil, and its blistering properties investigated. The mass, heated with potash in the above way, can also be submitted to dialysis, the diffusate supersaturated with sulphuric acid, and shaken up with chloroform.

In order to test further for cantharidin, it can be dissolved in the least possible potash or soda-lye. The solution, on evaporation in the water-bath, leaves crystals of a salt not easily soluble in alcohol, and the watery solution of which gives with chloride of calcium and baryta a white precipitate; with sulphate of copper and sulphate of protoxide of nickel, a green; with cobaltous sulphate, a red; with sugar of lead, mercury chloride and argentic nitrate, a white crystalline precipitate. With palladium chloride there occurs a yellow, hair-like, crystalline precipitate; later crystals, which are isomorphous with the nickel and copper salts.

If the tincture of cantharides has been used in considerable quantity, the urine may be examined; in such a case there will collect on the surface drops of a green oil, which may be extracted by petroleum ether; this oil is not blister-raising. Cantharides in powder may, of course, be detected by its appearance.

To the question whether the method proposed would extract any other blister-producing substance, the answer is negative, since ethereal oil of mustard would be decomposed, and the active constituents of the _Euphorbias_ do not withstand the treatment with KHO. Oils of anemone and anemonin are dissolved by KHO, and again separated out of their solutions, but their blistering property is destroyed. They are volatile, and found in anemone and some of the _Ranunculaceæ_. In the _Aqua pulsatilla_ there is an oil of anemone, which may be obtained by shaking with ether; but this oil is not permanent, and if the _Aqua pulsatilla_ stand for a little time, it splits up into anemonic acid and anemonin, and then cannot be reobtained. A blistering substance, obtained from the _Anacardia orientalia_ and the fruit of the _Anacardium occidentale_ and _Semecarpus anacardium_, is not quite destroyed by a short action with potash, but is by one of long duration; this substance, however, cannot be confused with cantharidin, for it is oily, yellow, easily soluble in alcohol and ether, and differs in other respects.

V.--Snake Poison.

§ 639. The poisonous snakes belong chiefly to two classes, the _Proteroglypha_ and the _Solenoglypha_.

Weir Mitchell and Ed. T. Reichert[644] have made some important experiments on snake poison, using the venom of some 200 snakes. Most of the snakes were rattlesnakes, a few were cobras and other species. They came to the conclusion that the active constituents are contained in the fluid part alone, the solid particles suspended in the fluid having no action. The poison they considered to consist of two toxalbumins, one a globulin, acting more particularly on the blood, the other, a peptone (albumose?), acting more particularly on the tissues. Differences in snake venom depend on the relative proportions of these two substances. The peptone, which acts more especially locally on the tissues, determines an inflammatory action, with much swelling and multiple extravasation of blood, which may proceed to a moist gangrene. The globulin has a paralysing influence on the heart, the vasomotor centres, the peripheral ends of the splanchnic nerves, as well as on the respiratory centres of both warm and cold-blooded animals. Feoktisow’s[645] researches show that although the heart continues to beat after the respiration has ceased for a few minutes, it has no force. The blood pressure sinks immediately after the injection. Whether the globulin is injected subcutaneously or direct into the veins, there is commonly considerable extravasation of blood in the chest and abdomen; the intestine is often filled with blood as well as the pericardium; and the urine is bloody. The poison of _Vipera ammodytes_ in watery solution may be boiled for six minutes, and yet is as active as before. According to Lewin, snake poison generally can be heated to 125° and yet preserve its poisonous properties. These last observations are not in accordance with the belief of some that the active principle of snake venom is a ferment, or, indeed, in harmony with the idea that it is a globulin or toxalbumin; for such bodies have not, so far as we know, the stability to withstand so high a degree of heat.

[644] _Smithsonian Contributions to Knowledge_, Washington, 1886.

[645] _Exp. Unters. über Schlangengift. Inaug. Diss._, Dorpat, 1888.

§ 640. =The Poison of the Cobra.=--The poison excreted from the salivary glands of the cobra di capello is the most deadly animal fluid known. When first ejected, it is an amber-coloured, rather syrupy, frothy liquid, of specific gravity 1·046, and of feeble acid reaction; it dries rapidly on exposure to air to a yellow film, which readily breaks up into brilliant yellow granules, closely imitating crystals. The yellow powder is very acrid and pungent to the nostrils, and excites a painful (though transitory) inflammation, if applied to the mucous membrane of the eye; the taste is bitter, and it raises little blisters on the tongue. It is perfectly stable, and preserves its activity for an indefinite time. The dried poison as described is perfectly soluble in water, and if the water is added in proper proportions, the original fluid is without doubt reproduced, the solution usually depositing a sediment of epithelial _débris_, and often containing little white threads.

The poison has been examined by several chemists, but until of late years with a negative result. The writer was the first to isolate, in 1876, a crystalline principle, which appears to be the sole acting ingredient; the yellow granules were dissolved in water, the albumen which the venom so copiously contains coagulated by alcohol, and separated by filtration; the alcohol was then driven off at a gentle heat, the liquid concentrated to a small bulk, and precipitated with basic acetate of lead. The precipitate was separated, washed, and decomposed in the usual way by SH₂, and on removing the lead sulphide, crystals having toxic properties were obtained.

Pedler,[646] precipitating the albumen by alcohol, and then to the alcoholic solution adding platinic chloride, obtained a semi-crystalline precipitate, which from an imperfect combustion he thinks may have something like the composition PtCl₄(C₁₇H₂₅N₄O₇HCl)₂. I have examined the platinum compound, and made several combustions of different fractions, but was unable to obtain the compound in a sufficient state of purity to deduce a formula. My analysis agreed with those of Pedler for nitrogen--viz., 9·93 per cent. (Pedler, 9·69); hydrogen 4·17 (Pedler, 4·28); but were higher for carbon, 41·8 per cent. (Pedler, 33·42 per cent.); one fraction gave 7·3 per cent. of platinum, another double that amount. Material was insufficient to thoroughly investigate the compound, but it was evident that several double salts were formed. The blood of the cobra is also poisonous. A. Calmette[647] has found that 2 c.c. of fresh cobra blood, injected into the peritoneum of a rabbit weighing 1·5 kilo., causes death in six hours; the same dose of the defibrinated blood injected into the veins is fatal in three minutes.

[646] _Proc. Roy. Soc._, vol. xxvii. p. 17.

[647] _Compt. Rend., Soc. de Biol._, 1894.

§ 641. =Fatal Dose.=--From my experiments on cats, rabbits, and birds, it seems probable that the least fatal dose for cats and rabbits, lies between ·7 and ·9 mgrm. per kilo., and for birds somewhere about ·7 mgrm. per kilo. of the dried poison; the venom contains about 60 per cent. of albuminous matter, and about 10 per cent. of poisonous substance; therefore, the lethal power is represented by something like ·07 to ·09 mgrm. per kilo., if the pure toxic principle free from albumen and diluting impurities be considered.

§ 642. =Effects on Animals.=--Almost immediately local pain or signs of uneasiness at the seat of injection are observed. There is then a variable interval, seldom exceeding 20 minutes (and generally much less), but in one of my experiments half an hour elapsed after the injection of a fatal dose before any effect was evident. The symptoms once produced, the course is rapid, and consists, first, of acceleration of the respirations, and then a progressive slowing, soon followed by convulsions. The convulsions are probably produced by the interference with the respiration and the deficient oxidation of the blood, and are therefore, the so-called “carbonic acid convulsions.” There is paresis or paralysis of the limbs. Death seems to occur from asphyxia, and the heart beats for one or more minutes after the respirations have ceased. If the dose is so small as not to produce death, no after-effects have been observed; recovery is complete.

Sir J. Fayrer, and Dr. Lauder Brunton consider that the terminations of the motor nerves suffer; on the other hand, Dr. Wall would explain the phenomena by referring the action entirely to the central nervous system, and concludes that the effects of the cobra poison consist in the extinction of function extending from below upwards of the various nerve centres constituting the cerebro-spinal system. In addition to this, there is a special and rapid action on the respiratory and allied nuclei, and this it is that causes death.

§ 643. =Effects on Man.=--By far the best account hitherto published of the effects of the cobra poison is a paper by Dr. Wall,[648] in which he points out the very close similarity between the symptoms produced and those of glosso-pharyngeal paralysis. This is well shown in the following typical case:--A coolie was bitten on the shoulder about twelve at midnight by a cobra; he immediately felt burning pain at the spot bitten, which increased. In fifteen minutes afterwards he began, he said, to feel intoxicated, but he seemed rational, and answered questions intelligently. The pupils were natural, and the pulse normal; the respirations were also not accelerated. He next began to lose power over his legs, and staggered. In thirty minutes after the bite his lower jaw began to fall, and frothy viscid mucous saliva ran from his mouth; he spoke indistinctly, like a man under the influence of liquor, and the paralysis of the legs increased. Forty minutes after the bite, he began to moan and shake his head from side to side, and the pulse and respirations were somewhat accelerated; but he was still able to answer questions, and seemed conscious. There was no paralysis of the arms. The breathing became slower and slower, and at length ceased one hour and ten minutes after the bite, the heart beating for about one minute after the respiration had stopped.

[648] “On the Difference of the Physiological Effects Produced by the Poison of Indian Venomous Snakes,” by A. T. Wall, M.D., _Proc. Roy. Soc._, 1881, vol. xxxii. p. 333.

There is often very little sign of external injury, merely a scratch or puncture being apparent, but the areolar tissue lying beneath is of a purple colour, and infiltrated with a large quantity of coagulable, purple, blood-like fluid. In addition, the whole of the neighbouring vessels are intensely injected, the injection gradually diminishing as the site of the poisoned part is receded from, so that a bright scarlet ring surrounds a purple area, and this in its turn fades into the normal colour of the neighbouring tissues. At the margin is also a purple blood-like fluid, replaced by a pinkish serum, which may often be traced up in the tissues surrounding the vessels that convey the poison to the system, and may extend a considerable distance. These appearances are to be accounted for in great part by the irritant properties of the cobra venom. The local hyperæmia and the local pain are the first symptoms. In man there follows an interval (which may be so short as a few minutes, or so long as four hours) before any fresh symptoms appear; the average duration of the interval is, according to Dr. Wall, about an hour. When once the symptoms are developed, then the course is rapid, and, as in the case quoted, a feeling like that of intoxication is first produced, and then loss of power over the legs. This is followed by a loss of power over the speech, over swallowing, and the movement of the lips; the tongue becomes motionless, and hangs out of the mouth; the saliva is secreted in large quantities, and runs down the face, the patient being equally unable to swallow it or to eject it, and the glosso-pharyngeal paralysis is complete.

§ 644. =Antidotes and Treatment.=--Professor Halford some years ago proposed ammonia, and M. Lacerda in recent times has declared potassic permanganate an antidote to the cobra poison. The ammonia theory has been long disproved, and before Lacerda had made his experiments I had published the chemical aspect of some researches,[649] which showed that mixing the cobra venom with an alkaline solution of potassic permanganate destroyed its poisonous properties. Other experiments were also made in every conceivable way with potassic permanganate, injecting it separately, yet simultaneously, into different parts of the same animal’s body, but so long as it does not come into actual contact with the poison it has no antidotal power whatever over the living subject. Other observers, previous to the researches mentioned and since, all agree that permanganate is no true antidote.[650] It only acts when it comes directly into contact with the venom, but when the venom is once absorbed into the circulation potassic permanganate, whether acid, alkaline, or neutral, is powerless. That it is of great use when applied to a bite is unquestionable, for it neutralises or changes any of the venom hanging about the wound, and which, if allowed to remain, might yet be absorbed; but here it is obvious that the venom is, so to speak, outside the body. A. Galmette (_Annales de l’Institut Pasteur_, 25th March 1892) has found that gold chloride forms an insoluble compound with the cobra poison, which is not poisonous, and that animal living tissues impregnated with gold chloride will not absorb the poison. He even advances some evidence tending to show that gold chloride may overtake, as it were, the venom in the circulation, and thus act as a true antidote. This is improbable, and, until confirmed, the general treatment most likely to be successful is the immediate sucking of the wound, followed by the application of an alkaline solution of permanganate; and lastly, if the symptoms should nevertheless develop, an attempt should be made to maintain the breathing by galvanism and artificial respiration.[651]

[649] _Analyst_, Feb. 28, 1877.

[650] See Note on the effect of various substances in destroying the activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer, _Proc. Roy. Soc._, vol. xxvii. p. 17.

[651] Some of my experiments on the cobra poison may be briefly detailed, illustrating the general statement in the text:--

1. A quantity equal to 1 mgrm. of the dried venom was injected subcutaneously into a chicken. The symptoms began in two minutes with loss of power over both legs. In eight minutes the legs were perfectly paralysed. There were convulsive movements of the head and wings, slowing of the respiration, and death in ten minutes. The same quantity of poison was treated with a little tannin, and the clear liquid which separated from the precipitate injected into another chicken. The respiration became affected in ten minutes; in eighteen minutes the bird had become very quiet, and lay insensible; in twenty minutes it was dead, the respiration ceasing before the heart.

2. In seven experiments with cobra poison, first rendered feebly alkaline with an alkaline solution of potassic permanganate, no effect followed. Three of the experiments were on chickens, four on rabbits.

3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and in the other simultaneously with a solution of potassic permanganate. Death followed in sixteen minutes. Another chicken was treated in the same way, but with injections of potassic permanganate solution every few minutes. Death resulted in thirty-seven minutes. Four other similar experiments were made--two with feebly alkaline permanganate, two with permanganate made feebly acid with sulphuric acid--but death occurred with the usual symptoms.

4. Cobra poison was mixed with a weak solution of iodine, and a quantity equal to half a mgrm. was injected into a chicken. The symptoms began directly, were fully developed in ten minutes, and death took place in twenty-one minutes.

5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity equivalent to 1 mgrm. of the cobra poison injected. The symptoms were immediate paralysis and insensibility, and the respiration rapidly fell. Death occurred in four minutes without convulsions.

6. The cobra venom was mixed with a feebly alkaline solution of pyrogallic acid, and injected subcutaneously into a chicken. In six minutes the usual symptoms commenced, followed in thirteen minutes by death.

7. One mgrm. was injected into a chicken. The respirations at the commencement were 120; in twenty-two minutes they sank to 96, in twenty-five minutes to 84, in twenty-seven minutes to 18, and then to occasional gasps, with slight movement of the wings and toes. There was death in thirty-two minutes after the injection.

8. A young rabbit was injected with ·5 mg. (equal to 1 mgrm. per kilo.) of cobra poison. In two hours it was apparently moribund, with occasional short gasps. Artificial respiration was now attempted. There was considerable improvement, but it was intermitted during the night, and the animal was found dead in the morning, having certainly lived six hours.

9. A strong healthy kitten was injected with 1 mgrm. of cobra venom (equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well developed, and in an hour the animal was gasping--about twelve short respirations per minute. Artificial respiration was kept up for two hours, and the animal recovered, but there was great muscular weakness lasting for more than twenty-four hours.

10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms. (6 per kilo.) of the cobra poison. The symptoms developed within ten minutes; ammonia was injected, and also given by the nostril. The heart’s action, which, previous to the administration of the ammonia, had been beating feebly, became accelerated, but death followed within the hour, the heart beating two minutes after the respiration had ceased.

11. A brown rabbit, about 2 kilos. in weight, was injected with 1·5 mgrms. of cobra poison (·75 per kilo.). There were no symptoms for nearly an hour, then sudden convulsions, and death.

12. Another rabbit of the same size was treated similarly, but immediately after the injection made to breathe nitrous oxide; death took place in thirty minutes. A rabbit, a little over 2 kilos. in weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10 mgrms. of monobromated camphor were administered. In fifteen minutes there was general paralysis of the limbs, from which in a few minutes the animal seemed to recover; thirty minutes after the injection there were no very evident symptoms, but within forty minutes there was a sudden accession of convulsions, and death. Experiments were also made with chloroform, morphine, and many other substances, but none seemed to exercise any true antidotal effect.

§ 645. =Detection of the Cobra Venom.=--In an experiment on a rabbit, the animal was killed by the subcutaneous injection of 8 mgrms. per kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood were injected into a small rabbit; in fifteen minutes there was slow respiration with pains in the limbs; in thirty minutes this had, in a great measure, passed off, and in a little time the animal was well. In any case in which it is necessary to attempt to separate the cobra venom, the most likely method of succeeding would be to make a cold alcoholic extract, evaporate in a vacuum, take up the residue in a little water, and test its effect on small animals.

§ 646. =Duboia Russellii.=--The _Duboia russellii_ or _Russell’s viper_ is one of the best known and most deadly of the Indian vipers. The effects of the poison of this viper are altogether different from those of the cobra. The action commences by violent general convulsions, which are often at once fatal, or may be followed by rapid paralysis and death; or these symptoms, again, may be recovered from, and death follow at a later period. The convulsions do not depend on asphyxia, and with a small dose may be absent. The paralysis is general, and may precede for some time the extinction of the respiration, the pupils are widely dilated, there are bloody discharges, and the urine is albuminous. Should the victim survive the first effects, then blood-poisoning may follow, and a dangerous illness result, often attended with copious hæmorrhages. A striking example of this course is recorded in the _Indian Med. Gaz._, June 1, 1872.

A Mahommedan, aged 40, was bitten on the finger by Russell’s viper; the bitten part was soon after excised, and stimulants given. The hand and arm became much swollen, and on the same day he passed blood by the rectum, and also bloody urine. The next day he was sick, and still passing blood from all the channels; in this state he remained eight days, losing blood constantly, and died on the ninth day. Nothing definite is known of the chemical composition of the poison; it is probably qualitatively identical with “viperin.”

§ 647. =The Poison of the Common Viper.=--The common viper still abounds in certain parts of Great Britain, as, for example, on Dartmoor. The venom was analysed in a partial manner by Valentin. In 1843 Prince Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and transparent, which he called _echidnin_ or _viperin_; it was a neutral nitrogenous body without taste, it arrested the coagulation of the blood, and, injected into animals, produced all the effects of the bite of the viper. Phisalix and G. Bertrand have studied the symptoms produced in small animals after injection. A guinea-pig, weighing 500 grms., was killed by 0·3 grm. of the dried venom dissolved in 5000 parts of saline water; the symptoms were nausea, quickly passing into stupor. The temperature of the body fell. The autopsy showed the left auricle full of blood, the intestine, lungs, liver, and kidneys injected. The blood of the viper is also poisonous, and produces the same symptoms as the venom.[652] The same observers have shown (_Compt. rend._, cxviii., Jan. 1894) that the blood of the water-snake (_Tropidonotus natrix_) and of the Thuringian adder (_Tropidonotus viperinus_) is poisonous, producing the same symptoms as that of the viper.

[652] _Compt. rend. Soc. de Biol._, t. v. 997.

=The Venom of Naja Haje= (=Cleopatra’s Asp=).--It has been stated that 20,000 persons annually die in Ceylon from the bite of Cleopatra’s asp. Graziani (_Rif. Med._, October 7, 1893) has undertaken a physiological study of the venom, which has already received attention at the hands of Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The venom, when dried, appears as transparent scales, easily soluble in water, very slightly so in alcohol, ether, or chloroform; its aqueous solution has an unpleasant odour, and is neutral to test paper. Chemically it gives all the tests described by Weir Mitchell and others as characteristic of the venom of _Naja tripudians_. The physiological effects of this dried venom were tried on guinea-pigs, rabbits, and frogs, to all of which it proved fatal in extremely minute doses. The guinea-pig, a few seconds after injection, becomes paralysed in its hind limbs, it foams at the mouth, and makes violent attempts at vomiting. The eyes are half closed, but occasionally for short periods there is a partial disappearance of the paralysis, and the animal makes feeble attempts to support itself. Respiratory embarrassment is soon added to the foregoing symptoms, and the animal lies perfectly prone, devoting all its attention to breathing, which is rendered still more difficult by the vomiting and frothy saliva which is secreted in abundance. Finally death ensues from asphyxia. The _post-mortem_ examination reveals the heart still feebly beating, the lungs pallid, and the blood in the organs very dark. The liver and kidneys are hyperæmic, but the brain and cord, with their coverings, are anæmic. In the rabbit the course of the poisoning is practically identical with that described above. Histologically, the following facts are made out in addition to the foregoing. The red blood-corpuscles are in great measure broken down, and there are also effusions into the muscular tissues. The kidneys are very hyperæmic, and there is marked degeneration of the epithelium lining the glomeruli and convoluted tubules. The glomerular capsules are much distended, and numerous leucocytes are discernible throughout the organ. The liver, also, is hyperæmic, and shows numerous broken-down blood-corpuscles, and partial necrosis of many of the liver cells. Examination of the central nervous system reveals no particular changes.

DIVISION II.--PTOMAINES--TOXINES.

§ 648. =Definition of a Ptomaine.=--A ptomaine may be considered as a basic chemical substance derived from the action of bacteria on nitrogenous substances. If this definition is accepted, a ptomaine is not necessarily formed in the dead animal tissue; it may be produced by the living, and, in all cases, it is the product of bacterial life. A ptomaine is not necessarily poisonous; many are known which are, in moderate doses, quite innocuous.

When Selmi’s researches were first published there was some anxiety lest the existence of ptomaines would seriously interfere with the detection of poison generally, because some were said to be like strychnine, others like colchicine, and so forth. Farther research has conclusively shown that at present no ptomaine is known which so closely resembles a vegetable poison as to be likely in skilled hands to cause confusion.

Isolation of Ptomaines.

§ 649. =Gautier’s[653] Process.=--The liquid is acidified with oxalic acid, warmed, filtered, and distilled in a vacuum.

[653] _Ptomaines et Leucomaines_, E. J. A. Gautier, Paris, 1886.

In this way pyrrol, skatol, phenol, indol, and volatile fatty acids are separated and will be found in the distillate. The residue in the retort is treated with lime, filtered from the precipitate that forms, and distilled in a vacuum, the distillate being received in weak sulphuric acid. The bases accompanied with ammonia distil over. The distillate is now neutralised by sulphuric acid[654] and evaporated nearly to dryness, separating the mother liquid from sulphate of ammonia, which crystallises out. The mother liquids are treated with absolute alcohol, which dissolves the sulphates of the ptomaines. The alcohol is got rid of by evaporation, the residue treated with caustic soda, and the bases shaken out by successive treatment with ether, petroleum ether, and chloroform. The residue remaining in the retort with the excess of lime is dried, powdered, and exhausted with ether; the ethereal extract is separated, evaporated to dryness, the dry residue taken up in a little water, slightly acidulated, and the bases precipitated by an alkali.

[654] The first acid apparently is so dilute that the distillate more than neutralises it, hence more sulphuric acid is added to complete neutralisation.

§ 650. =Brieger’s Process.=--Brieger[655] thus describes his process:--

[655] _Untersuchungen über Ptomaine_, Theil iii., Berlin, 1886.

“The matters are finely divided and boiled with water feebly acidulated with hydrochloric acid.

“Care must be taken that on boiling, the weak acid reaction must be retained, and that this manipulation only lasts a few minutes.

“The insoluble portion is filtered off, and the filtrate evaporated, either in the gas-oven or on the water-bath, to syrupy consistency. If the substances are offensive, as alcoholic and watery extracts of flesh usually are, the use of Bocklisch’s simple apparatus (see diagram) is to be recommended. The filtrate to be evaporated is placed in a flask provided with a doubly perforated caoutchouc cork carrying two bent tubes; the tube _b_ terminates near the bottom of the flask, while the tube _a_ terminates a little above the level of the fluid to be evaporated. The tube _a_ is connected with a water pump which sucks away the escaping steam. In order to avoid the running back of the condensed water forming in the cooler part of the tube, the end of the tube _a_ is twisted into a circular form. Through the tube _b_, which has a fine capillary bore, a stream of air is allowed to enter, which keeps the fluid in constant agitation, continually destroying the scum on the surface, and avoiding sediments collecting at the bottom, which may cause fracture of the flask. According to the regulation of the air current, a greater or smaller vacuum can be produced. The fluid, evaporated to the consistency of a syrup, is treated with 96 per cent. alcohol, filtered, and the filtrate precipitated with lead acetate.

“The lead precipitate is filtered off, the filtrate evaporated to a syrup, and the syrup again treated with 96 per cent. alcohol. This is again filtered, the alcohol got rid of by evaporation, water added, the lead thrown down by SH₂, and the fluid, after the addition of a little hydrochloric acid, evaporated to the consistence of a syrup; this syrup is exhausted with 96 per cent. alcohol, and precipitated with an alcoholic solution of mercury chloride. The mercury precipitate is boiled with water, and by the different solubility of the mercury salts of certain ptomaines some separation takes place. If it is suspected that some of the ptomaines may have been separated with the lead precipitate, this lead precipitate can be decomposed by SH₂ and investigated. I have only (says Brieger) in the case of mussels been able to extract from the lead precipitate small quantities of ptomaines.

“The mercury filtrate is freed from mercury and evaporated, the excess of hydrochloric acid being carefully neutralised by means of soda (for it must only be slightly acid); then it is again treated with alcohol, so as to separate as much as possible the inorganic constituents. The alcoholic extract is evaporated, dissolved in a little water, neutralised with soda, acidulated with nitric acid, and precipitated with phospho-molybdic acid. The phospho-molybdic acid precipitate is decomposed with neutral lead acetate, which process may be facilitated by heating on the water-bath. After getting rid of the lead by treatment with SH₂, the fluid is evaporated to a syrup and alcohol added, by which process many ptomaines may be eliminated as hydrochlorates; or they can be converted into double salts (of platinum or gold) for the purpose of separation. In the filtrate from phospho-molybdate, ptomaines may also be found by treating with lead acetate to get rid of the phospho-molybdic acid, and then adding certain reactives. Since it is but seldom that the hydrochlorates are obtained in a state of purity, it is preferable to convert the substance separated into a gold or platinum salt or a picrate, since the greater or less solubility of these compounds facilitates the purification of individual members; but which reagent is best to add, must be learned from experience. The melting-point of these salts must always be taken, so that an idea of their purity may be obtained. It is also to be noted that many gold salts decompose on warming the aqueous solution; this may be avoided by the addition of hydrochloric acid. The hydrochlorates of the ptomaines are obtained by decomposing the mercury, gold, or platinum combinations by the aid of SH₂, while the picrates can be treated with hydrochloric acid and shaken up with ether, which latter solvent dissolves the picric acid.

“Considerable difficulty in the purification of the ptomaines is caused by a nitrogenous, amorphous, non-poisonous, albumin-like substance, which passes into all solutions, and can only be got rid of by careful precipitation with an alcoholic solution of lead acetate, in which it is soluble in excess. This albuminoid forms an amorphous compound with platinum, and acts as a strongly reducing agent (the platinum compound contains 29 per cent. platinum). When this albuminoid is eliminated, then the hydrochlorates or the double salts of the ptomaines crystallise.”

§ 651. =The Benzoyl Chloride Method.=--The fatty diamines in dilute aqueous solutions, shaken with benzoyl chloride and soda, are converted into insoluble dibenzoyl derivatives; these may be separated from benzamide and other nitrogenous products by dissolving the precipitate in alcohol, and pouring the solution into a large quantity of water.[656] Compounds which contain two amido groups combined with one and the same carbon atom, do not yield benzoyl derivatives when shaken with benzoyl chloride and soda. Hence this reaction can be utilised for certain of the ptomaines only. The solution must be dilute, because concentrated solutions of creatine, creatinine, and similar bodies also give precipitates with benzoyl chloride; no separation, however, occurs unless these bodies are in the proportion of five per thousand.

[656] L. V. Udrànsky and Baumann, _Ber._, xxi. 2744.

The process is specially applicable for the separation of ethylenediamine, pentamethylenediamine (cadaverine), and tetramethylenediamine (putrescine) from urine. In a case of cystinuria Udrànsky and E. Baumann[657] have found 0·24 grm. of benzoyltetramethylenediamine, 0·42 grm. of benzoylpentamethylenediamine in a day. Diamines are absent in normal fæces and urine. Stadthagen and Brieger[658] have also found, in a case of cystinuria diamines, chiefly pentamethylenediamine.

[657] L. V. Udrànsky and Baumann, _Zeit. f. physiol. Chem._, xiii. 562.

[658] _Arch. pathol. Anatom._, cxv. p. 3.

The operation is performed by making the liquid alkaline with soda, so that the alkalinity is equal to about 10 per cent., adding benzoyl chloride, shaking until the odour of benzoyl chloride disappears, and then filtering; to the filtrate more benzoyl chloride is added, the liquid shaken, and, if a precipitate appears, this is also filtered off, and the process repeated until all diamines are separated.

The precipitate thus obtained is dissolved in alcohol, and the alcoholic solution poured into a considerable volume of water and allowed to stand over night; the dibenzoyl compound is then usually found to be in a crystalline condition. The compound is crystallised once or twice from alcohol or ether, and its melting-point and properties studied. Mixtures of diamines may be separated by their different solubilities in ether and alcohol.

A solution of 0·00788 grm. of pentamethylenediamine in 100 c.c. of water gave 0·0218 grm. of the dibenzoyl-derivative when shaken with benzoyl chloride (5 c.c.) and 40 c.c. of soda (10 per cent.) and kept for twenty-four hours. In a second experiment with a similar solution only 0·0142 grm. of dibenzoyl-derivative was obtained;[659] hence the process is not a good quantitative process, and, although convenient for isolation, gives, so far as the total amount recovered is concerned, varying results.

[659] _Ber._, xxi. 2744.

§ 652. =The Amines.=--The amines are bases originating from ammonia and built on the same type. Those that are interesting as poisons are monamines, diamines, and the quaternary ammonium bases.

Considered as compound ammonias, the amines are divided into primary or amide bases, secondary or imid bases, and tertiary or nitrile bases, according as to whether one, two, or three atoms of hydrogen have been displaced from the ammonia molecule by an alkyl; for instance, methylamine NH₂CH₃ is a primary or amide base, because only one of the three atoms of H in NH₃ has been replaced by methyl; similarly, dimethylamine is a secondary or imid base, and trimethylamine is a tertiary or nitrile base.

The quaternary bases are derived from the hypothetical ammonium hydroxide NH₄OH, as, for example, tetraethyl ammonium hydroxide (C₂H₅)₄N,OH.

The diamines are derived from two molecules of NH, and therefore contain, instead of one molecule of nitrogen, two molecules of nitrogen; in two molecules of ammonia there are six atoms of hydrogen, two, four, or six of which may be replaced by alkyls; as, for example,

C₂H₄ / \ / \ N--HH--N \ / \ / HH

Ethylenediamine.

C₂H₄ / \ / \ N--C₂H₄--N \ / \ / HH

Diethylenediamine.

C₂H₄ / \ / \ N--C₂H₄--N \ / \ / C₂H₄

Triethylenediamine.

The monamines are similar to ammonia in their reactions; some of them are stronger bases; for instance, ethylamine expels ammonia from its salts. The first members of the series are combustible gases of pungent odour, and easily soluble in water; the higher homologues are fluids; and the still higher members solids.

The hydrochlorides are soluble in absolute alcohol, while chloride of ammonium is insoluble; this property is taken advantage of for separating amines from ammonia. The amines form double salts with platinic chloride; this is also utilised for recognition, for the purpose of separation, and for purification; for instance, ammonium-platinum-chloride on ignition yields 43·99 per cent. of platinum, and methylamine-platinum-chloride yields 47·4 of platinum. It is comparatively easy to ascertain whether an amine is primary, secondary, or tertiary.

The primary and secondary amines react with nitrous acid, but not the tertiary; the primary amines, for instance, are converted into alcohols, and there is an evolution of nitrogen gas; thus methylamine is decomposed into methyl alcohol, nitrogen, and water.

CH₃NH₂ + (OH)NO = CH₃(OH) + N₂ + H₂O.

The secondary amines, treated in the same way, evolve no nitrogen, but are converted into nitrosamines; thus dimethylamine, when treated with nitrous acid, yields nitrosodimethylamine,

(CH₃)₂NH + (OH)NO = (CH₃)₂(NO)N + H₂O;

and the nitrosamines respond to the test known as Lieberman’s nitroso-reaction, which is thus performed:--The substance is dissolved in phenol and a few drops of concentrated sulphuric acid added. The yellow colour at first produced changes into blue by adding to the acid liquid a solution of potash.

The primary amines, and the primary amines alone, treated with chloroform and alcoholic potash, yield the peculiarly offensive smelling carbylamine or isonitrile (Hofmann’s test),

V NH₂(CH₃) + CHCl₃ + 3KOH = C≣N-CH₃ + 3KCl + 3H₂O.

Again the primary bases, when treated with corrosive sublimate and carbon disulphide, evolve sulphuretted hydrogen, and mustard oil is produced, _e.g._,

NH₂(C₂H₅) + CS₂ = CS=N-C₂H₅ + H₂S. Ethylamine. Ethylmustard oil.

Where a sufficient quantity of an amine is obtained, the primary, secondary, or tertiary character of the amine may be deduced with certainty by treating it with methyl or ethyl iodide.

A molecule of the base is digested with a molecule of methyl iodide and distilled with potash; the distillate is in the same manner again treated with methyl iodide and again distilled; and the process is repeated until an ammonium base is obtained, which will take up no more iodide. If three methyl groups were in this way introduced, the original substance was primary, if two, secondary, if one, tertiary.

The quaternary bases, such as tetraethyl ammoniumoxhydrate, decompose, on heating, into triethylamine and ethylene; the corresponding methyl compound in like manner yields trimethylamine and methyl-alcohol.

On the other hand, the primary, secondary, and tertiary bases do not decompose on heating, but volatilise without decomposition.

The chief distinctions between these various amines are conveniently put into a tabular form as follows:--

+--------------------+-----------+-----------+-----------+-----------+ | | Primary, |Secondary, | Tertiary, |Quaternary,| | | NH₂R. | NHR₂. | NR₃. | NR₄(OH). | +--------------------+-----------+-----------+-----------+-----------+ |On treating with | 3 | 2 | 1 | ... | |methyl iodide it | | | | | |takes up the follow-| | | | | |ing number of methyl| | | | | |groups, | | | | | | | | | | | |Reaction with |Decomposes |Formation | | | |nitrous acid, |with evolu-|of nitro- | ... | ... | | |tion of |samine. | | | | |nitrogen | | | | | |gas. | | | | | | | | | | |Mustard oil, &c., on|Mustard oil| | | | |treatment with CS₂ |formed. | ... | ... | ... | |and sublimate, | | | | | | | | | | | |Chloroform and |Formation | ... | ... | ... | |alcoholic potash, |of carbyl- | | | | | |amine. | | | | | | | | | | |Effect of strong |Sublimes. |Sublimes. |Sublimes. |Decomposes.| |heat, | | | | | | | | | | | |On addition of |Combines to|Combines to|Combines to| ... | |acids, |form salts.|form salts.|form salts.| | +--------------------+-----------+-----------+-----------+-----------+

§ 653. =Methylamine,= CH₃NH₂.--This is a gas at ordinary temperatures; it is inflammable, and possesses a strong ammoniacal odour. It has been found in herring brine, and is present in cultures of the comma bacillus; it has also been found in poisonous sausages, but it is not in itself toxic.

It forms crystalline salts, such as, for example, the hydrochloride, the platinochloride (Pt = 41·4 per cent.), and the aurochloride (Au = 53·3 per cent. when anhydrous). The best salt for estimation is the platinochloride, insoluble in absolute alcohol and ether.

§ 654. =Dimethylamine=, (CH₃)₂NH.--Dimethylamine is also a gas; it has been found in various putrefying substances. It forms crystalline salts, such as the hydrochloride, the platinochloride (Pt = 39·1 per cent.), and an aurochloride (Au = 51·35 per cent.). It is not poisonous.

In Brieger’s process it may occur in both the mercuric chloride precipitate and filtrate. From cadaverine it may be separated by platinum chloride; cadaverine platinochloride is with difficulty soluble in cold water and crystallises from hot water, while dimethylamine remains in the mother liquor. From choline it may be separated by recrystallising the mercuric precipitate from hot water. From methylamine it may be separated by converting into chloride and extracting with chloroform; dimethylamine chloride is soluble, methylamine chloride insoluble in chloroform.

§ 655. =Trimethylamine=, (CH₃)₃N.--Trimethylamine in the free state is an alkaline liquid with a fishy odour, boiling at 9·3°; it is not toxic save in large doses.

It occurs in a great variety of plants, and is also found in putrefying substances. It is a product of the decomposition of choline, betaine, and neuridine, when these substances are distilled with potash.

In Brieger’s process, if an aqueous solution of mercuric chloride is used as the precipitant, trimethylamine (if present) will be almost entirely in the filtrate, from which it can be obtained by getting rid of the mercury by SH₂, filtering, evaporating to dryness, extracting with alcohol, and precipitating the alcoholic solution with platinic chloride. It forms crystalline salts with hydrochloric acid, platinum chloride, and gold chloride; the platinum double salt yields 37 per cent. of platinum, the gold salt 49·4 per cent. gold. The gold salt is easily soluble, and this property permits its separation from choline, which forms a compound with gold chloride soluble with difficulty.

§ 656. =Ethylamine=, C₂H₅NH₂.--Ethylamine is in the free state an ammoniacal liquid boiling at 18·7°. It is a strong base, miscible with water in every proportion. It has been found in putrefying yeast, in wheat flour, and in the distillation of beet sugar residues. It is not poisonous; the hydrochloride forms deliquescent plates melting at 76°-80°; the platinochloride contains 39·1 per cent. of platinum, and the gold salt 51·35 per cent. of gold. In other words, the same percentages as the corresponding salts of dimethylamine, with which, however, it cannot be confused.

§ 657. =Diethylamine=, (C₂H₅)₂NH, is an inflammable liquid boiling at 57·5°; it forms salts with hydrochloric acid, platinum and gold, &c.; the gold salt contains 47·71 per cent. of gold, and its melting-point is about 165°.

§ 658. =Triethylamine=, (C₂H₅)₃N, is an oily base but slightly soluble in water, and boiling at 89°-89·5°. It gives no precipitate with mercuric chloride in aqueous solution; it forms a platinochloride containing 31·8 per cent. of platinum. It has been found in putrid fish.

§ 659. =Propylamine.=--There are two propylamines; one, normal propylamine, CH₃CH₂.CH₂.NH₂, boiling at 47°-48°, and iso-propylamine, (CH₃)₂CH.NH₂, boiling at 31·5°; both are ammoniacal fish-like smelling liquids. The hydrochloride of normal propylamine melts at 155°-158°, and iso-propylamine chloride melts at 139·5°.

It has been found in cultures of human fæces on gelatin. None of the above amines are sufficiently active in properties to be poisonous in the small quantities they are likely to be produced in decomposing foods.

§ 660. =Iso-amylamine=, (CH₃)₂CH.CH₂.CH₂.NH₂, is a colourless alkaline liquid, possessing a peculiar odour. It boils at 97°-98°. It forms a deliquescent hydrochloride. The platinochloride crystallises in golden yellow plates.

Iso-amylamine occurs in the putrefaction of yeast, and is a normal constituent of cod-liver oil. It is intensely poisonous, producing convulsions.

Diamines.

§ 661. =Rate of Formation of Diamines.=--Diamines are formed in putrefactive processes, generally where there is abundance of nitrogen. Garcia[660] has attempted to trace the rates at which they are formed by allowing meat extracts to decompose, precipitating by benzoyl chloride (see p. 487) the dibenzoyl compound, and weighing; the following were the results obtained:--

[660] _Zeit. f. physiol. Chemie_, xvii. 6. 571.

Time. Weight of benzoyl compound. 24 hours, 0·56 grm. 2 days, 0·75 „ 3 days, 0·82 „ 4 days, 0·73 „ 5 days, 0·57 „ 6 days, 0·58 „

§ 662. =Ethylidenediamine.=--Brieger found in putrid haddock, in the filtrate from the mercury chloride precipitate:--gadinine, neuridine, a base isomeric with ethylenediamine C₂H₈N₂ (but which Brieger subsequently more or less satisfactorily identified with ethylidenediamine), muscarine, and triethylamine; these bases were separated as follows:--

The filtrate from the mercury chloride solution was freed from mercury by SH₂, evaporated to a syrup, and then extracted with alcohol. From the alcoholic solution platinum chloride precipitated neuridine, this was filtered off, the filtrate freed from alcohol and platinum, and the aqueous solution concentrated to a small volume and precipitated with an aqueous solution of platinum chloride; this precipitated ethylidene platinum chloride. The mother liquor from this precipitate was concentrated on the water-bath, and, on cooling, the platinochloride of muscarine crystallised out. From the mother liquor (freed from the crystals), on standing in a desiccator, the gadinine double salt crystallised out, and from the mother liquor (freed from gadinine after removal of the platinum by SH₂) distillation with KHO recovered trimethylamine.

From the platinochloride of ethylenediamine, the chloride can be obtained by treating with SH₂, filtering, and evaporating; by distilling the chloride with a caustic alkali, the free base can be obtained by distillation.

Ethylidenediamine is isomeric with ethylenediamine, but differs from it in the following properties:--ethylidenediamine is poisonous, ethylenediamine is non-poisonous.

Ethylenediamine forms a platinochloride almost insoluble in hot water, while the ethylidene salt is more easily soluble. The properties of the gold salts are similar, ethylenediamine forming a difficultly soluble gold salt, ethylidene a rather soluble gold salt.

Ethylidenediamine forms a hydrochloride, C₂H₈N₂2HCl, crystallising in long glistening needles, insoluble in absolute alcohol, rather soluble in water. The hydrochloride gives precipitates in aqueous solution with phospho-molybdic acid, phospho-antimonic acid, and potassium bismuth iodide; the latter is in the form of red plates.

The platinochloride, C₂H₈N₂2HCl.PtCl (Pt = 41·5 per cent.), is in the form of yellow plates, not very soluble in cold water.

Ethylidenediamine, when subcutaneously injected into guinea-pigs, produces an abundant secretion from the mucous membranes of the nose, mouth, and eyes. The pupils dilate, and the eyeballs project. There is acute dyspnœa; death takes place after some twenty-four hours, and the heart is stopped in diastole.

Trimethylenediamine is believed to have been isolated by Brieger from cultivations in beef broth of the comma bacillus.

It occurs in small quantity in the mercuric chloride precipitate, and is isolated by decomposing the precipitate with SH₂, evaporating the filtrate from the mercury sulphide to dryness, taking up the residue with absolute alcohol, and precipitating by an alcoholic solution of sodium picrate. The precipitate contains the picrate of trimethylenediamine, mixed with the picrates of cadaverine and creatinine. Cadaverine picrate is insoluble in boiling absolute alcohol, the other picrates soluble; so the mixed picrates are boiled with absolute alcohol, and the insoluble cadaverine filtered off. Next, the picrates of creatinine and trimethylenediamine are freed from alcohol, the solution in water acidified with hydrochloric acid, the picric acid shaken out by treatment with ether, and then the solution precipitated with platinum chloride; the platinochloride of trimethylenediamine is not very soluble, while creatinine easily dissolves; so that separation is by this means fairly easy.

It also gives a difficultly soluble salt with gold chloride.

The picrate consists of felted needles, melting-point 198°. Phospho-molybdic acid gives a precipitate crystallising in plates; potassium bismuth iodide gives dark coloured needles.

It produces in animals violent convulsions and muscular tremors; but the substance has hitherto been obtained in too small a quantity to be certain as to its identification and properties.

§ 663. =Neuridine=, C₅H₁₄N₂.--Neuridine is a diamine, and is apparently the most common basic product of putrefaction; it has been obtained from the putrefaction of gelatin, of horseflesh, of fish, and from the yelk of eggs. It is usually accompanied by choline, from which it can be separated by converting the bases into hydrochlorides, choline hydrochloride being soluble in absolute alcohol, neuridine scarcely so. Brieger isolated neuridine from putrid flesh by precipitating the watery extract with mercuric chloride. He decomposed the mercury precipitate with SH₂, and, after having got rid of the sulphide of mercury by filtration, he concentrated the liquid to a small bulk, when a substance separated in crystals similar in form to urea; this was purified by recrystallisation from absolute alcohol, and converted into the platinum salt.

Another method which may be used for the separation and purification of neuridine is to dissolve it in alcohol and precipitate with an alcoholic solution of picric acid; the picrate may be decomposed by treatment with dilute mineral acid, and the picric acid removed by shaking with ether.

The free base has a strong seminal odour. It is gelatinous, and has not been crystallised. It is insoluble in ether and in absolute alcohol, and not readily soluble in amyl alcohol. It gives white precipitates with mercuric chloride, neutral and basic lead acetates. It does not give Hofmann’s isonitrile reaction. When distilled with a fixed alkali, it yields di- and trimethylamine.

The hydrochloride, C₅H₁₄N₂2HCl, crystallises in long needles, which are insoluble in absolute alcohol, ether, benzol, chloroform, petroleum ether, and amyl alcohol; but the hydrochloride is very soluble in water and in dilute alcohol.

The hydrochloride gives no precipitate with mercuric chloride, potass-mercuric iodide, potass-cadmium iodide, iodine and iodide of potassium, tannic acid, ferricyanide of potassium, ferric chloride, and it does not give any colour with Fröhde’s reagent.

On the other hand, phosphotungstic acid, phospho-molybdic acid, picric acid, potass-bismuth iodide, platinum chloride, and gold chloride all give precipitates.

Neuridine hydrochloride is capable of sublimation, and at the same time it is decomposed, for the sublimed needles show red or blue colours.

Neuridine platinochloride, C₅H₁₄N₂2HCl.PtCl₄, yields 38·14 per cent. of platinum; it crystallises in flat needles, soluble in water, from which it is precipitated on the addition of alcohol.

The aurochloride has the formula C₅H₁₄N₂2HCl2AuCl₃; it is rather insoluble in cold water, and crystallises in bunches of yellow needles. On ignition, it should yield 41·19 per cent. of gold.

The picrate, C₅H₁₄N₂,2C₆H₂(NO₂)₃OH, is almost insoluble in cold water, and crystallises in needles. It is not fusible, but decomposes at about 230°.

Neuridine is not poisonous.

§ 664. =Cadaverine= (Pentamethylenediamine, C₅H₁₄N₂ = NH₂CH₂--CH₂--CH₂--CH₂CH₂NH₂) is formed in putrid animal matters, and in cultures of the genus _Vibrio_. It has been found in the urine and fæces in cases of cystinuria, and Roos[661] has separated it by the benzoyl-chloride method from the fæces of a patient suffering from tertian ague. It may be formed synthetically by dissolving trimethylcyanide in absolute alcohol, and then reducing by sodium (Mendius’ reaction).

[661] _Zeit. f. physiol. Chemie_, xvi., 1892.

Cadaverine is a thick, clear, syrupy liquid, with a peculiar coniine- as well as a semen-like odour. It absorbs eagerly CO₂ from the air, and ultimately is converted into a solid crystalline mass. It volatilises with the steam when boiled with water, and may be distilled in the presence even of the caustic alkalies and the alkaline earths without decomposition. It does not give oil of mustard when treated with CS₂ and mercuric chloride, nor does it give with chloroform and alcoholic potash, carbylamine (isonitrile). If dehydrated by KHO, it boils at from 115°-120° (_Brieger_).[662]

[662] Brieger has also given to the pure base a boiling-point of 175°.

When cadaverine is treated with methyl iodide, two atoms of hydrogen may be replaced with methyl, forming the base C₅H₁₂(CH₃)₂N₂; the platinochloride of this last base crystallises in long red needles.

Cadaverine forms well-defined crystalline salts as well as compounds with metals.

Cadaverine hydrochloride, C₅H₁₄N₂2HCl, crystallises in needles which are deliquescent, or it may be obtained from an alcoholic solution in plates. The crystals are insoluble in absolute alcohol, but readily soluble in 96 per cent. alcohol. Putrescine hydrochloride, on the other hand, is with difficulty soluble in alcohol of that strength; hence the two hydrochlorides can be separated by taking advantage of their difference in solubility in 96 per cent. alcohol; but the better method for separation is the benzoyl-chloride process (p. 487). On dry distillation, cadaverine hydrochloride decomposes into NH₃,HCl and piperidine C₅H₁₁N. The compound with mercury chloride--C₅H₁₄N₂2HCl,4HgCl₂ (Hg = 63·54 per cent.); melting-point, 214°-216°--is insoluble in alcohol and in cold water; this property is also useful to separate it from putrescine, the mercury compound of which is soluble in cold water. The platinochloride, C₅H₁₄N₂2HCl,PtCl₄ (Pt = 38·08 per cent.), crystallises in dirty red needles; but, by repeated crystallisation, it may be obtained in clear chrome yellow, short, octahedral prisms; it is soluble with difficulty in hot water, insoluble in cold water. The salt decomposes at 235°-236°.

The aurochloride--C₅H₁₄N₂2HCl2AuCl (Au = 50·41 per cent.), melting-point 188°--crystallises partly in cubes and partly in needles, and is easily soluble in water.

Other salts are the picrate, C₅H₁₄N₂2C₆H₂(NO₂)₃OH, melting-point 221° with decomposition; with difficulty soluble in cold, but dissolving in hot water, and insoluble in absolute alcohol. There are also a neutral oxalate, C₅H₁₄N₂,H₂C₂O₄ + 2H₂O, melting-point 160°; and an acid oxalate, C₅H₁₄N₂2H₂C₂O₄ + H₂O, melting-point 143° with decomposition; both these oxalates are insoluble in absolute alcohol.

Cadaverine dibenzoyl--C₅H₁₀(NHCOC₆H₅)₂, melting-point 129°-130°--crystallises in needles and plates, soluble in alcohol and slightly soluble in ether, insoluble in water.

It is not acted on by hot dilute acids or alkalis, and when dissolved in concentrated hydrochloric acid and alcohol it is, only after prolonged boiling, decomposed into benzoic acid and the free base. The benzoic acid after getting rid of the alcohol by evaporation, can be removed by shaking up with ether; then the hydrochloride can be decomposed by an alkali and the free base obtained, or the platinum salt of cadaverine may be formed by precipitation with platinum chloride. Should cadaverine and putrescine be in the same liquid, the dibenzoyl compounds may be separated as follows:--the crystalline precipitate is collected on a filter, washed with water until the filtrate runs clear, and then dissolved in warm alcohol; this solution is poured into twenty times its volume of ether and allowed to stand; after a short time crystals form of the putrescine compound, which are far less soluble in alcohol than those of cadaverine dibenzoyl; these crystals are filtered off and repeatedly crystallised from alcohol until the melting-point is about 175°-176°. The filtrate contains the cadaverine compound; this latter is recovered by evaporating off the ether-alcohol.

§ 665. =Putrescine--Tetramethylenediamine=,

C₄H₁₂N₂=NH₂CH₂CH₂CH₂CH₂NH₂.

The free base is a clear liquid, with a semen-like odour, boiling-point 135°. It is a common base in putrefying animal substances, and also occurs in the urine in cases of cystinuria. It can be obtained synthetically by reducing ethylene cyanide by the action of sodium in absolute alcohol.

The best method of separating putrescine is the benzoyl chloride method already given.

Putrescine forms crystalline salts, of which the following are the most important:--

Putrescine hydrochloride, C₄H₁₂N₂2HCl, forms long colourless needles, insoluble in absolute alcohol, easily soluble in water.

The platinochloride, C₄H₁₂N₂2HCl.PtCl₄ (Pt = 39·2 per cent.), is with difficulty soluble in cold water. When pure, the salt is in the form of six-sided plates.

The aurochloride, C₄H₁₂N₂2HCl.2AuCl₃ + 2H₂O (Au = 51·3 per cent.), is insoluble in cold water, in contradistinction to cadaverine aurochloride, which easily dissolves.

The picrate, C₄H₁₂N₂2C₆H₂(NO₂)₃OH, is a salt of difficult solubility. It crystallises in yellow plates. It browns at 230°, and melts with evolution of gas at 250°.

Dibenzoylputrescine, C₄H₈(NHCOC₆H₅)₂, forms silky plates or long needles, melting-point 175°-176°. By boiling it for twelve hours with alcohol and strong hydrochloric acid the compound may be broken up into hydrochloride of putrescine and free benzoic acid. As stated before, it is less soluble in alcohol than the corresponding compound of cadaverine.

Putrescine is not poisonous. On the other hand, by repeated treatment with methyl iodide, it takes up four methyl radicals, and the tetramethyl compound, C₄H₈(CH₃)₄N₂, produces symptoms similar to those of muscarine poisoning.

§ 666. =Metaphenylenediamine=,

NH₂¹ / C₆H₄ , \ NH₂³

is a crystalline substance, melting-point 63°, boiling-point 276°-277°. The crystals are easily soluble in alcohol or ether, with difficulty in water. The least trace of nitrous acid strikes a yellow colour from the formation of triamidobenzol.

§ 667. =Paraphenylenediamine=,

NH₂¹ / C₆H₄ , \ NH₂⁴

is in the form of tabular crystals, melting-point 140°, boiling-point 267°. If this substance is oxidised with ferric chloride or manganese binoxide and sulphuric acid, chinone is produced; if treated with SH₂ and ferric chloride, a violet sulphur-holding colouring matter, allied to methylene blue, is formed; these reactions are tests for the presence of the para-compound.

Both these diamines are poisonous. Metaphenylenediamine produces, in the dog, the symptoms of an aggravated influenza with continual sneezing and hoarse cough, which, if the dose is large enough, ends in coma and death. Paraphenylenediamine produces exophthalmia, the tissues of the eye undergoing complete alteration.[663]

[663] _Comptes Rend._, cvii. 533-535.

Both compounds, in doses of 100 mgrms. per kilo., cause more or less salivation, with diarrhœa. The para-compound is more poisonous than the meta-compound. So far as the author is aware, neither of these diamines have been separated with certainty from the urine of sick persons, nor from products of decomposition.

§ 668. =Hexamethylenediamine=, C₆H₁₆N₂.--Hexamethylenediamine has been found by A. Garcia[664] in a putrefying mixture of horse-flesh and pancreas.

[664] _Zeit. f. physiol. Chemie_, xvii. 543-555.

§ 669. =Diethylenediamine=, C₄H₁₀N₂, is a crystalline substance, melting-point 104°, boiling-point 145°-146°. After melting, it solidifies on cooling, forming a hard crystalline mass. It is extremely soluble in water, and is deposited from alcohol in large transparent crystals. A technical product called “spermin piperazidin” or “piperazine” has been found by A. W. v. Hoffmann[665] to be identical with diethylenediamine. The hydrochloride crystallises in colourless needles, insoluble in alcohol, readily soluble in water. The platinochloride, C₄H₁₀N₂H₂PtCl₆, is in small yellow needles, and is fairly easily soluble in hot water, but dissolves but slightly in hot alcohol. The mercuro-chloride, C₄H₁₀N₂H₂HgCl₄, crystallises in concentrically grouped needles, and is readily soluble in hot water, but is reprecipitated on adding alcohol. The picrate, C₄H₁₀N₂,C₆H₂(NO₂)₃OH, crystallises from water in yellow needles, almost insoluble in alcohol.[666]

[665] _Ber._, xxiii. 3297-3303.

[666] Sieber, J., _Ber._, xxiii. 326-327.

§ 670. =Mydaleine= is a poisonous base discovered by Brieger in putrid animal matters. It is probably a diamine, but has not been obtained in sufficient quantity for accurate chemical study. The platinochloride is extremely soluble in water, and only comes down from an absolute alcohol solution. It has been obtained in a crystalline form, giving on analysis 38·74 per cent. of platinum, C. 10·83 per cent., H. 3·23 per cent.

Mydaleine is very poisonous. Small quantities injected into guinea-pigs cause dilatation of the pupil, an abundant secretion from the nose and eyes, and a rise of temperature. Fifty mgrms. cause death. The _post-mortem_ appearances are not distinctive; the heart is arrested in diastole; the intestines and bladder are contracted. In cats it causes profuse diarrhœa and vomiting.

§ 671. =Guanidine.=--Guanidine may be considered to have a relation to urea; for, if the oxygen of urea is replaced by the imide group NH, guanidine originates thus:--

NH₂ / Urea = O=C \ NH₂

NH₂ / Guanidine = NHC \ NH₂

Hence guanidine from its structural formula is a carbodiamidimide. Guanidine may be formed by the action of oxidising agents, such as potassic chlorate and hydrochloric acid, on guanine; or by heating amide cyanide with ammonium chloride, and so forming guanidine chloride. It is also produced from the oxidation of albumin. When boiled with baryta-water it decomposes into urea and ammonia. It combines with acids to form salts; the gold salt, CH₅N₃HCl,AuCl₃, is in the form of long yellow needles, with difficulty soluble in water. Guanidine nitrate, CH₅N₃HNO₃, is also almost insoluble in cold water and similar to urea nitrate. By dissolving equivalent parts of phenol and guanidine in hot alcohol, triphenylguanidine is formed; on adding picric acid to a solution of triphenylguanidine, phenylguanidine picrate, CH₂Ph₃N₃C₆H₂(NO₂)₃OH, is formed, and falls as a precipitate of slender needles, melting-point 208°; this picrate is very slightly soluble, 1 part dissolving in 12,220 parts of water at 15°. Guanidine is poisonous.[667]

[667] O. Prelinger, _Monatsb._, xiii. 97-100.

A method of separating guanidine from urine has been worked out by Gergers and Baumann.[668] The principle of the method is based upon the fact that guanidine is precipitated by mercurous oxide. The urine is precipitated by hydrate of baryta, the precipitate filtered off, the alkaline filtrate neutralised by hydrochloric acid, and the neutral filtrate evaporated to a syrup on the water-bath; the syrup is exhausted by absolute alcohol, and the alcoholic solution filtered; this filtrate is freed from alcohol by distillation, the alcohol-free residue dissolved in a little water, shaken up with freshly precipitated mercury oxide, and allowed to stand for two days in a warm place; the precipitate formed is collected, acidulated with HCl and treated with SH₂; the mercury sulphide thus obtained is separated by filtration, the filtrate evaporated, and the residue dissolved in absolute alcohol. This solution is precipitated by platinum chloride, filtered, separated from any platinum ammonium salt, and evaporated to a small volume. After long standing the guanidine salt crystallises out. The best method to identify it appears to be, to ascertain the absence of ammonia and of urea, and then to gently warm the supposed guanidine with an alkali, which breaks guanidine up into ammonia and urea, according to the following equation:--

NH=C(NH₂)₂ + H₂O = NH₃ + CO(NH₂)₂.

[668] Pflüger’s _Archiv_, xii. 205.

The physiological effects of guanidine are as follows:--

A centigrm. of guanidine salt injected into the lymph sac in the back of frogs produces, after a few minutes, muscular convulsions: first, there are fibrillar twitchings of the muscles of the back; next, these spread generally so that the whole surface of the frog seems to be in a wave-like motion. Irritation of the limbs produces tetanus. There is, at the same time, increased secretion from the skin. The breathing is irregular. In large doses there is paralysis and death. The heart is found arrested in diastole. The fatal dose for a frog is 50 mgrms.; but 1 mgrm. will produce symptoms of illness. In dogs there is paralysis, convulsions, vomiting, and difficult breathing.

§ 672. =Methylguanidine=,

NH.CH₃ / NH=C . \ NH₂

--Methylguanidine has been isolated by Brieger from putrefying horse-flesh; it has also been found in impure cultures in beef broth of Finkler and Prior’s _Vibrio proteus_. Bocklisch isolated it, working with Brieger’s process, from the mercuric chloride precipitate, after removal of the mercury and concentration of the filtrate, by adding a solution of sodium picrate. The precipitate contained the picrates of cadaverine, creatinine, and methylguanidine; cadaverine picrate, insoluble in boiling absolute alcohol, was separated by filtering from a solution of the picrates of the bases in boiling absolute alcohol; the alcohol was evaporated from the filtrate and the residue taken up with water. From this aqueous solution the picric acid was removed and then the solution precipitated with gold chloride; methylguanidine was precipitated, while creatinine remained in solution.

Methylguanidine aurochloride, C₂H₇N₃HCl.AuCl₃ (Au = 47·7 per cent.), forms rhombic crystals easily soluble in alcohol and ether; melting-point 198°. The hydrochloride, C₂H₇N₃HCl, crystallises in needles insoluble in alcohol. The picrate, C₂H₇N₃C₆H₂(NO₂)₃OH, comes down at first as a resinous mass, but, after boiling in water, is found to be in the form of needles soluble in hot absolute alcohol; melting-point 192°. The symptoms produced by methylguanidine are rapid respiration, dilatation of the pupils, paralysis, and death, preceded by convulsions. The heart is found arrested in diastole.

§ 673. =Saprine=, C₅H₁₄N₂.--Saprine is isomeric with cadaverine and neuridine; it was found by Brieger in human livers and spleens after three weeks’ putrefaction. Saprine occurs, in Brieger’s process, in the mercury precipitate. Its reactions are very similar to those of cadaverine; the main difference being that cadaverine hydrochloride gives a crystalline aurochloride, saprine does not; the platinum salt is also more soluble in water than the cadaverine salt. It is not poisonous.

§ 674. =The Choline Group.=--The choline group consists of choline, neurine, betaine, and muscarine.

All these bodies can be prepared from choline; their relationship to choline can be readily gathered from the following structural formulæ:--

CH₂OH | CH₂ | N(CH₃)₃.OH

Choline.

CH₂ ║ CH | N(CH₃)₃.OH

Neurine.

CO₂H | CH₂ | N(CH₃)₃.OH

Betaine.

CH₂OH | CHOH | N(CH₃)₃.OH

Muscarine.

Choline is a syrup with an alkaline reaction. On boiling with water, it decomposes into glycol and trimethylamine. It gives, when oxidised, muscarine. It forms salts. The hydrochloride is soluble in water and absolute alcohol; neurine hydrochloride and betaine hydrochloride are but little soluble in absolute alcohol, therefore this property can be utilised for their separation from choline. The platinochloride is insoluble in absolute alcohol; it melts at 225° with effervescence, and contains 31·6 per cent. of platinum. The mercurochloride is soluble with difficulty even in hot water. The aurochloride (Au = 44·5 per cent.) is crystalline, and with difficulty soluble in cold water; but is soluble in hot water and in alcohol; melting-point 264° with decomposition.

Choline is only poisonous in large doses.

§ 675. =Neurine= (Trimethyl-vinyl-ammonium hydrate), C₂H₃N(CH₃)₃OH.--Neurine is one of the products of decomposition of choline. It is poisonous, and has been separated by Brieger and others from decomposing animal matters. In Brieger’s process, neurine, if present, will be for the most part in the mercuric chloride precipitate, and some portion will also be in the filtrate. The mercury precipitate is decomposed by SH₂, the mercury sulphide filtered off, and the filtrate, concentrated, treated with absolute alcohol and then precipitated by platinum chloride. It is usually accompanied by choline; the platinochloride of choline is readily soluble in water, neurine platinochloride is soluble with difficulty; this property is taken advantage of, and the platinochloride crystallised from water until pure. Neurine has a strong alkaline reaction.

Neurine chloride, C₅H₁₂N.Cl, crystallises in fine needles. The platinochloride, (C₅H₁₂NCl)₂PtCl₄ (Pt = 33·6 per cent.), crystallises in octahedra. The salt is soluble with difficulty in hot water.

The aurochloride, C₅H₁₂NClAuCl₃ (Au = 46·37 per cent.), forms flat prisms, which, according to Brieger, are soluble with difficulty in hot water.

Neurine is intensely poisonous, the symptoms being similar to those produced by muscarine.

Atropine is an antidote to neurine, relieving in suitable doses the effects, and even rendering animals temporarily immune against the toxic action of neurine.

When a fatal dose of neurine is injected into a frog there is in a short time paralysis of the extremities. The respiration stops first, and afterwards the heart, the latter in diastole.

The symptoms in rabbits are profuse nasal secretion and salivation with paralysis, as in frogs. Applied to the eye, neurine causes contraction of the pupil; to a less degree the same effect is produced by the ingestion of neurine.

=Trimethyloxyammonium= hydrochloride causes similar symptoms to neurine, but the action is less powerful.--V. Cervello, _Arch. Ital. Biol._, vii. 232-233.

§ 676. =Betaine.=--Betaine may be separated from a solution in alcohol as large deliquescent crystals; the reaction of the crystals is neutral. Distilled with potash, trimethylamine and other bases are formed.

Betaine chloride, C₅H₁₂NO₂Cl, forms plates permanent in the air and insoluble in absolute alcohol. A solution of the chloride in water gives, with potassium mercuric iodide, a light yellow or whitish yellow precipitate, soluble in excess; but, on rubbing the sides of the tube with a glass rod, the oily precipitate crystallises as yellow needles; probably this is characteristic.

The aurochloride (Au = 43·1 percent.) forms fine cholesterine plates, soluble in water; melting-point 209°. Betaine is not poisonous.

§ 677. =Peptotoxine.=--Brieger submitted to the action of fresh gastric juice moist fibrin for twenty-four hours at blood heat. The liquid was evaporated to a syrup and boiled with ethylic alcohol, the ethylic alcohol was evaporated, the residue digested with amylic alcohol, and the amyl alcohol in its turn evaporated to dryness; the residue was a brown amorphous mass that was poisonous. It was farther purified by treating the extract with neutral lead acetate and then filtered; the filtrate was freed from lead by SH₂ and treated with ether, the ethereal extract being then separated and evaporated to dryness; this last residue was taken up with amyl alcohol, the alcohol evaporated to dryness, and the residue finally taken up with water and filtered. The filtrate is poisonous. The poisonous substance, to which Brieger gave the provisional name of peptotoxine, is a very stable substance, resisting the action of a boiling temperature, and even the action of strong alkalies. It gives precipitates with alkaloidal group reagents, and strikes a blue colour with ferric chloride and ferricyanide of potassium. The most characteristic test seems to be its action with Millon’s reagent (a solution of mercury nitrate in nitric acid containing nitrous acid); this gives a white precipitate which, on boiling, becomes intensely red.

It is poisonous, killing rabbits in doses of 0·5 grm. per kilogrm., with symptoms of paralysis and coma. The nature of this substance requires further elucidation.

§ 678. =Pyridine Alkaloid from the Cuttle Fish.=--O. de Coninck[669] has obtained, by Gautier’s process, an alkaloid from the cuttle fish, of the formula C₈H₁₁N, in the form of a yellow, mobile, strongly odorous liquid, very soluble in alcohol, ether, and acetone, boiling-point 202°. It quickly absorbs moisture from the air. It forms two mercuric chlorides, one of which has the formula (C₈H₁₁N,HCl)₂HgCl₂; this compound crystallises in small white needles, slightly soluble in water and dilute alcohol, but insoluble in absolute alcohol, and decomposing when exposed to moist air. The other salt is a sesqui-salt, forming long yellowish needles, insoluble in ordinary solvents, and decomposing when exposed to moist air. The alkaloid also forms deliquescent very soluble salts with hydrochloric and hydrobromic acids. A platinum salt is also formed, (C₈H₁₁N)₂H₂PtCl₆; it is of a deep yellow colour, almost insoluble in cold, but soluble in hot water; it is decomposed by boiling water, with the formation of a very insoluble compound in the shape of a brown powder, (C₈H₁₁N)₂PtCl₄. Coninck’s alkaloid, on oxidation with potassic permanganate, yields a gummy acid; this acid, on purifying it by conversion into a potassium salt and then into a cupric salt, was found to be nicotinic acid; so that the alkaloid is undoubtedly a pyridine compound; indeed, the acid, distilled with lime, yields pyridine.

[669] _Comptes Rend._, cvi. 858, 861; cviii. 58-59, 809-810; cvi. 1604-1605.

§ 679. =Poisons connected with Tetanus.=--Brieger, in 1887, isolated a base of unknown composition, to which he gave the name of “spasmotoxine.” It was produced in cultures of the tetanus bacillus in beef broth.

Two more definite substances have also been discovered, viz., tetanine and tetanotoxine.

=Tetanine=, C₁₃H₃₀N₂O₄, is best isolated by the method of Kitasato and Weyl.[670] Their method of treating broth cultures of the tetanus bacillus is as follows:--

[670] _Zeit. f. Hygiene_, viii. 404.

The broth is digested with 0·25 per cent. HCl for some hours at 460°, then rendered feebly alkaline, and distilled in a vacuum. The residue in the retort is then worked up for tetanine by Brieger’s method; the distillate contains tetanotoxine, ammonia, indol, hydrogen sulphide, phenol, and butyric acid. On treating the contents of the retort by Brieger’s mercury chloride method, the filtrate contains most of the poison. The mercury is removed by SH₂, the filtered solution evaporated and exhausted by absolute alcohol, in which the tetanine dissolves. Any ammonium chloride is thus separated, ammonium chloride being insoluble in absolute alcohol. The alcoholic solution, filtered from any insoluble substance, is next treated with an alcoholic solution of platinum chloride, which precipitates creatinine (and any ammonium salts), but does not precipitate tetanine. The platinum salt of tetanine may, however, be precipitated by the addition of ether to the alcoholic solution. The platinum salt, as obtained by precipitation from ether, is very deliquescent; it has, therefore, to be rapidly filtered off and dried in a vacuum. It can then be recrystallised from hot 96 per cent. alcohol, forming clear yellow plates; these plates, if dried in a vacuum, become with difficulty soluble in water.

Tetanine may be obtained as a free base by treating the hydrochloride with freshly precipitated moist silver oxide. It forms a strongly alkaline yellow syrup, and is easily decomposed in acid solution, but is permanent in alkaline solutions.

The platinochloride, as before observed, is precipitable by ether from alcoholic solution; it contains 28·3 per cent. of platinum, and decomposes at 197°.

The base produces tetanus.

§ 680. =Tetanotoxine= may be distilled, and be found in the distillate with other matters. It forms an easily soluble gold salt, melting-point 130°. The platinochloride is soluble with difficulty, and decomposes at 240°. The hydrochloride is soluble in alcohol and in water, melting-point about 205°.

Tetanotoxine produces tremor, then paralysis, and lastly, violent convulsions.

§ 681. =Mydatoxine=, C₆H₁₃NO₂.--A base obtained by Brieger from horse-flesh in a putrefactive condition and other substances. It is found in the mercury chloride precipitate. The free base is an alkaline syrup, isomeric with the base separated by Brieger from tetanus cultures. The hydrochloride is a deliquescent syrup, not forming any compound with gold chloride, but uniting with phospho-molybdic acid in forming a compound crystallising in cubes. It forms a double salt with gold chloride, sparingly soluble in water. The platinochloride (Pt = 29 per cent.) is very soluble in water, but not soluble in alcohol; melting-point 193° with decomposition.

The base in large doses is poisonous, causing lachrymation, diarrhœa, and convulsions.

§ 682. =Mytilotoxine=, C₆H₁₅NO₂.--This is believed to be the poison of mussels. Brieger isolated it as follows:--

The mussels were boiled with water acidified by hydrochloric acid; the liquid was filtered, and the filtrate evaporated to a syrup, and the syrup was repeatedly extracted with alcohol. It was found advisable to exhaust thoroughly with alcohol, otherwise much poison remained behind. The alcoholic solution was treated with an alcoholic solution of lead acetate. The filtrate was evaporated and the residue extracted with alcohol. The lead was removed by SH₂, the alcohol distilled off, water added to the remaining syrup, and the solution decolorised by boiling with animal charcoal. The solution was neutralised by sodium carbonate, acidulated with nitric acid, and precipitated with phosphomolybdic acid. The precipitate was then decomposed by warming with a neutral solution of lead acetate, and the filtrate (after the removal of the lead by the action of SH₂) was acidulated with HCl and evaporated to dryness. The residue was then extracted with absolute alcohol, filtered from any insoluble chloride, _e.g._, betaine chloride, and precipitated by mercury chloride in alcohol.

The free base has a most peculiar odour, which disappears on exposure to air; at the same time, the poisonous properties also diminish. The base is destroyed by boiling with sodium carbonate; on the other hand, the hydrochloride may be evaporated to dryness or be boiled without decomposing.

The hydrochloride crystallises in tetrahedra; the aurochloride crystallises in cubes (Au=41·66 per cent.). Its melting-point is 182°.

§ 683. =Tyrotoxicon= (Diazobenzol, C₆H₅N₂(OH)).--It appears, from the researches of Vaughan and others, that diazobenzol is liable to be formed in milk and milk products, especially in summer time. It is confidently asserted by many that the summer diarrhœa of infants is due to this toxine; however that may be, it is well established that diazobenzol is a violent poison, causing sickness, diarrhœa, and, in large doses, an acute malady scarcely distinguishable from cholera, and which may end fatally. There will always be difficulty in detecting it, because of its instability. The following is the best process of extraction from milk. The milk will probably be acid from decomposition; if so, the whey must be separated by dilution and filtration; without dilution it may be found impracticable to get a clear filtrate. In order to keep the bulk down, 25 c.c. of the milk may be diluted up to 100 c.c., and, having obtained a clear filtrate from this 25 c.c. thus diluted, the filtrate is used to dilute another 25 c.c. of milk and so on. The acid filtrate is neutralised by sodium carbonate, agitated with an equal volume of ether, allowed to stand in a stoppered vessel for twenty-four hours, and the ether then separated and allowed to evaporate spontaneously. The residue is acidified with nitric acid and then treated with a saturated solution of potash, which forms a stable compound with diazobenzol, and the whole concentrated on the water-bath. On cooling, the tyrotoxicon compound forms six-sided plates. Before the whole of this process is undertaken, it is well to make a preliminary test of the milk as follows:--A little of the ether is allowed to evaporate spontaneously. Place on a porcelain slab two or three drops of a mixture of equal parts of sulphuric and carbolic acids, and add a few drops of the aqueous solution; if tyrotoxicon be present, a yellow to orange-red colour is produced. A similar colour is also produced by nitrates or nitrites, which are not likely to be present under the circumstances, milk having mere traces only of nitrates or nitrites; it may also be due to butyric acid, which, in a decomposed milk, may frequently be in solution. Therefore, if a colour occurs, this is not absolutely conclusive; if, however, no colour is produced, then it is certain that no diazobenzol has been separated. That is all that can be said, for the process itself is faulty, and only separates a fractional part of the whole.

§ 684. =Toxines of Hog Cholera.=--Toxines have been isolated by F. G. Novy[671] from a cultivation of Salmon’s bacillus in pork broth. The fluid possessed a strong alkaline reaction. For the isolation, Brieger’s method was used. The mercury chloride precipitate was amorphous and was converted into a chlorine-free platinum compound, to which was assigned the composition of C₈H₁₄N₄PtO₈. After separation of this compound, the mother liquor still contained a platinum salt crystallising in needles, and from this was obtained the chlorhydrate of a new base, to which was given the name of _susotoxine_; it had the composition of C₁₀H₂₆N₂2HCl,PtCl₄. Susotoxine gives general alkaloidal reactions, and is very poisonous.

[671] _Med. News_, September 1890.

§ 685. =Other Ptomaines.=--Besides the ptomaines which have been already described, there are a number of others; the following may be mentioned: isoamylamine,[672] (CH₃)₂CH.CH₂.CH₂NH₂; butylamine, CH₃CH₂CH₂CH₂NH₂; dihydrolutidine,[673] C₇H₁₁N; hydrocollidine,[674] C₈H₁₃N; C₁₀H₁₅N (a base isolated by Guareschi and Mosso[675] from ox-fibrin in a state of putrefaction by Gautier’s method; it forms a crystalline hydrochloride and an insoluble platinochloride; its action is like that of curare but weaker); aselline,[676] C₂₅H₃₂N₄, isolated from cod-liver oil; typhotoxine,[677] C₇H₁₇NO₂, isolated from cultures of Eberth’s bacillus. So far as the published researches go, it would appear that other crystalline substances have been isolated from the urine, from the tissues, and from the secretions of patients suffering from various diseases; the quantity obtained in each case has, however, been, under the most favourable circumstances, less than a gramme; often only a few milligrms. To specifically declare that a few milligrms. of a substance is a new body, requires immense experience and great skill; and, even where those qualifications are present, this is too often impossible. This being so, the long list of named ptomaines, such as erysipeline, varioline, and others, must have their existence more fully confirmed by more than one observer before they can be accepted as separate entities.

[672] Hesse, _Chem. Jahresb._, 1857, 403.

[673] Gautier, A., and Morgues, _Compt. Rend._, 1888.

[674] Gautier et Etard, _Bull. Soc. Chim._, xxxvii., 1882.

[675] Guareschi et Mosso, _Les ptomaines_, 1883.

[676] Gautier, A., et Morgues, _Compt. Rend._, 1888.

[677] Brieger, 1885, _Ptomaines_, iii.

DIVISION III.--FOOD POISONING.

§ 686. A large number of cases of poisoning by food occur yearly; some are detailed in the daily press; the great majority are neither recorded in any journal, scientific or otherwise; nor, on account of their slight and passing character, is medical aid sought. The greatest portion of these cases are probably due to ptomaines existing in the food before being consumed; others may be due to the action of unhealthy fermentation in the intestinal canal itself; in a third class of cases, it is probable that a true zymotic infection is conveyed and develops in the sufferer; the latter class of cases, as, for instance, the Middlesborough epidemic of pleuro-pneumonia, is outside the scope of this treatise.

Confining the attention to cases of food poisoning in which the symptoms have been closely analysed and described, the reader is referred to thirteen cases of food poisoning, investigated by the medical officers of the Local Government Board between the years 1878 and 1891, as follows:--

1878. =A Case of Poisoning at Whitchurch from eating Roast Pork.=--Only the leg of pork was poisonous, other parts eaten without injury. Two persons died after about thirty hours’ illness. The pork itself, on a particular Sunday, was innocuous; it became poisonous between the Sunday and the Monday; the toxicity appeared to gradually increase, for those who ate it for dinner on the Monday were not taken ill for periods of from seven to nineteen hours, while two persons who ate of it in the evening were attacked four hours after eating.

1880. =The Welbeck Epidemic=, due to eating cold boiled ham. Over fifty persons affected. Symptoms commenced in from twelve to forty-eight hours.

1881. =A Series of Poisoning from eating Baked Pork, Nottingham.=--Probably the gravy was the cause and not the pork itself. Many persons seriously ill. One died.

1881. =Tinned American Sausage.=--A man in Chester died from eating tinned American sausage. Poison found to be unequally distributed in the sausage.

1882. =Poisoning at Oldham by Tinned Pigs’ Tongues.=--Two families affected. Symptoms commenced in about four hours. All recovered. After a few days’ keeping it would appear that the poison had been decomposed.

1882. =A Family Poisoned by Roast Beef at Bishop Stortford.=--Only a particular piece of the ribs seemed to be poisonous, the rest of the carcase being innocuous. Symptoms did not commence until several hours after ingestion.

1882. =Ten different Families at Whitchurch Poisoned by eating Brawn.=--First symptoms after about four hours.

1884. =Tinned Salmon at Wolverhampton.=--Five persons, two being children, ate of tinned salmon at Wolverhampton. All suffered more or less. The mother’s symptoms began after twelve hours, and she died in five days; the son died in three days, the symptoms commencing in ten hours. The _post-mortem_ signs were similar to those from phosphorus poisoning, viz., fatty degeneration. Mice fed on the material also suffered, and their organs showed a similar degeneration.

1886. =The Carlisle A Case.=--At a wedding breakfast in Carlisle twenty-four persons were poisoned by food which had been kept in an ill-ventilated cellar. The articles suspected were an American ham, an open game pie, and certain jellies. The bride died. Symptoms commenced in from six to forty-three hours.

1886. =Poisoning by Veal Pie at Iron Bridge.=--Twelve out of fifteen ate of the pie; all were taken ill in from six to twelve hours.

1887. =Poisoning at Retford of Eighty Persons from eating Pork Pie or Brawn.=--Symptoms commenced at various intervals, from eight to thirty-six hours.

1889. =The Carlisle B Case.=--Poisoning by pork pies or boiled salt pork. Number of persons attacked, about twenty-five.

1891. =Poisoning by a Meat Pie at Portsmouth.=--Thirteen persons suffered from serious illness. Portions of the pies were poisonous to mice.

The symptoms in all these cases were not precisely alike; but they were so far identical as to show as great a similarity as in cases when a number of persons are poisoned by the same chemical substance. Arsenic, for instance, produces several types of poisoning; so does phosphorus.

Severe gastro-enteric disturbance, with more or less affection of the nervous system, were the main characteristics. These symptoms commenced, as before stated, at various intervals after ingestion of the food; but they came on with extreme suddenness. Rigors, prostration, giddiness, offensive diarrhœa, followed by muscular twitchings, dilatation of the pupil, drowsiness, deepening in bad cases to coma, were commonly observed. The _post-mortem_ appearances were those of enteritis, with inflammatory changes in the kidney and liver. Convalescence was slow; sometimes there was desquamation of the skin.

In many of these cases Dr. Klein found bacteria which, under certain conditions, were capable of becoming pathogenic; but in no case does there seem to have been at the same time an exhaustive chemical inquiry; so that, although there was evidence of a poison passing through the kidney, the nature of the poison still remains obscure.

The deaths in England and Wales from unwholesome food during ten years were as follows:--

DEATHS IN ENGLAND AND WALES FROM UNWHOLESOME FOOD DURING THE TEN YEARS 1883-1892.

+----------+-----+---+-----+---+-----+---+-----+---+-----+----+----+ | |1883.| |1885.| |1887.| |1889.| |1891.| |To- | | | |1884.| |1886.| |1888.| |1890.| |1892.|tal.| +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+ |Diseased | 1 | ... |...| ... |...| ... |...| ... |...| ... | 1 | |meat, | | | | | | | | | | | | |Poisonous | 2 | 3 | 2 | 1 | 1 | 4 | 3 | 2 | 9 | 6 | 33 | |fish, | | | | | | | | | | | | |Unwholesome|...| 1 |...| ... |...| ... |...| ... |...| ... | 1 | |brawn, | | | | | | | | | | | | |Tinned |...| 2 |...| ... |...| ... |...| ... |...| ... | 2 | |salmon, | | | | | | | | | | | | |Putrid |...| 1 | 1 | 1 |...| ... | 1 | ... |...| ... | 4 | |meat, | | | | | | | | | | | | |Diseased |...| 1 |...| ... |...| ... |...| ... |...| ... | 1 | |food, | | | | | | | | | | | | |Mussels, |...| 1 |...| ... |...| ... | 1 | ... |...| ... | 2 | |Tinned |...| ... |...| ... | 2 | ... |...| ... |...| ... | 2 | |foods, | | | | | | | | | | | | |Whelks, |...| ... |...| ... | 1 | ... |...| ... |...| ... | 1 | |Winkles, |...| ... |...| ... |...| ... |...| 1 |...| ... | 1 | |Ptomaines, |...| ... |...| ... |...| ... |...| ... | 1 | ... | 1 | | +---+-----+---+-----+---+-----+---+-----+---+-----+----+ | | 3 | 9 | 3 | 2 | 4 | 4 | 5 | 3 |10 | 6 | 49 | +-----------+---+-----+---+-----+---+-----+---+-----+---+-----+----+

§ 687. =German Sausage Poisoning.=--A series of cases may be picked out from the accounts of sausage poisoning in Germany, all of which evidently depend upon a poison producing the same symptoms, and the essentially distinctive mark of which is extreme dryness of the skin and mucous membranes, dilatation of the pupil, and paralysis of the upper eyelids (ptosis). In an uncertain time after eating sausages or some form of meat, from one to twenty-four hours, there is a general feeling of uneasiness, a sense of weight about the stomach, nausea, and soon afterwards vomiting, and very often diarrhœa. The diarrhœa is not severe, never assumes a choleraic form, and is unaccompanied by cramps in the muscles. After a considerable interval there is marked dryness of the mucous membrane (a symptom which never fails), the tongue, pharynx, and the mouth generally seem actually destitute of secretion; there is also an absence of perspiration, the nasal mucous membrane participates in this unnatural want of secretion, the very tears are dried up. In a case related by Kraatzer,[678] the patient, losing a son, was much troubled, but wept no tear. This dryness leads to changes in the mucous membrane, it shrivels, and partly desquamates, aphthous swellings may occur, and a diffuse redness and diphtheritic-like patches have been noticed. There is obstinate constipation, probably from a dryness of the mucous lining of the intestines. The breath has an unpleasant odour, there is often a croupy cough, the urinary secretion alone is not decreased but rather augmented. Swallowing may be so difficult as to rise to the grade of aphagia, and the tongue cannot be manipulated properly, so that the speech may be almost unintelligible. At the same time, marked symptoms of the motor nerves of the face are present, the patient’s sight is disturbed, he sees colours or sparks before his eyes; in a few cases there has been transitory blindness, in others diplopia. The pupil in nearly all the cases has been dilated, also in exceptional instances it has been contracted. The _levator palpebrae superioris_ is paralysed, and the resulting ptosis completes the picture. Consciousness remains intact almost to death, there is excessive weakness of the muscles, perhaps from a general paresis. If the patient lives long enough, he gets wretchedly thin, and dies from marasmus. In more rapidly fatal cases, death follows from respiratory paralysis, with or without convulsions.

[678] Quoted by Husemann, _Vergiftung durch Wurstgift_ (Maschka’s _Handbook_).

=The post-mortem appearances= which have been observed are--the mucous membranes of the mouth, gullet, and throat are white, hard, and parchment-like; that of the stomach is more or less injected with numerous hæmorrhages: the kidneys are somewhat congested, with some effusion of blood in the tubuli; the spleen is large and very full of blood, and the lungs are often œdematous, pneumonic, or bronchitic.