DIVISION IV.—VARIOUS VEGETABLE POISONOUS PRINCIPLES—NOT ADMITTING OF CLASSIFICATION UNDER THE PREVIOUS THREE DIVISIONS.
I.—Ergot of Rye.
§ 577. Ergot is a peculiar fungus attacking the rye and other graminaceous plants;[599] it has received various names, Claviceps purpurea (Tulasne), Spermœdia clavus (Fries), Sclerotium clavus (D.C.), &c. The peculiar train of symptoms arising from the eating of ergotised grain (culminating occasionally in gangrene of the lower limbs), its powerful action on the pregnant uterus, and its styptic effects, are well known.
[599] Some of the Cyperaceæ are also attacked.
The very general use of the drug by accoucheurs has, so to speak, popularised a knowledge of its action among all classes of society, and its criminal employment as an abortive appears to be on the increase.[600]
[600] The Russian peasantry use the drug for the same purpose. Vide Mackenzie Wallace’s “Russia,” i. p. 117.
The healthy grain of rye, if examined microscopically in thin sections, is seen to be composed of the seed-coating, made up of two layers, beneath which are the gluten-cells, whilst the great bulk of the seed is composed of cells containing starch. In the ergotised grain, dark (almost black) cells replace the seed-coat and the gluten-cells, whilst the large starch-containing cells are filled with the small cells of the fungus and numerous drops of oil.
§ 578. The chemical constituents of ergot are a fixed oil, trimethylamine, certain active principles, and colouring-matters.
The fixed oil is of a brownish-yellow colour, of aromatic flavour and acrid taste; its specific gravity is 0·924, and it consists chiefly of palmitin and olein; it has no physiological action.
Trimethylamine is always present ready formed in ergot; it can also be produced by the action of potash on ergot.
With regard to the active principles of ergot considerable confusion still exists, and no one has hitherto isolated any single substance in such a state of purity as to inspire confidence as to its formula or other chemical characters. They may, however, be briefly described.
C. Tamet[601] has separated an alkaloid, which appears identical with Wenzel’s ergotinine. To obtain this the ergot is extracted by alcohol of 86°, the spirit removed by distillation, and the residue cooled; a resin (which is deposited) and a fatty layer (which floats on the surface) are separated from the extractive liquor and washed with ether; the ethereal solution is filtered and shaken with dilute sulphuric acid, which takes up the alkaloid; the aqueous solution of the substance is then filtered, rendered alkaline by KHO, and agitated with chloroform. The ergotinine is now obtained by evaporating the chloroform solution, care being taken to protect it from contact with the air. It gives precipitates with chloride of gold, potassium iodohydrargyrate, phosphomolybdic acid, tannin, bromine water, and the chlorides of gold and platinum. With moderately concentrated SO4H2, it gives a yellowish-red coloration, changing to an intense violet, a reaction which does not occur if the alkaloid has been exposed to the air. The composition of the base is represented by the formula C70H40N4O12, and a crystalline sulphate and lactate have been obtained.[602]
[601] Compt. Rendus, vol. xxxi. p. 896.
[602] Compt. Rendus, April 1878.
Wenzel’s Ecboline is prepared by precipitating the cold watery extract of ergot with sugar of lead, throwing out the lead in the usual way by hydric sulphide, concentrating the liquid, and adding mercuric chloride, which only precipitates the ecboline. The mercury salt is now decomposed with hydric sulphide, and after the mercury precipitate has been filtered off, the filtrate is treated with freshly precipitated phosphate of silver, and refiltered; lastly, the liquid is shaken up with milk of lime, again filtered, and the lime thrown out by CO2. The last filtrate contains ecboline only, and is obtained by evaporation at a gentle heat. It is an amorphous, feebly bitter substance, with an alkaline reaction, forming only amorphous salts.
The most recent research by Dragendorff on ergot tends to show that Wenzel’s alkaloids, ergotinine and ecboline, are inactive. Dragendorff describes also (a.) Scleromucin, a slimy substance which goes into solution upon extraction of the ergot with water, and which is again precipitated by 40 to 45 per cent. alcohol. It is colloidal and soluble with difficulty in water. It contains nitrogen, but gives no albuminoid reaction, nor any reaction of an alkaloidal or glucosidal body; it yields to analysis—
| 8 | ·26 | per cent. | Water. |
| 26 | ·8 | „ | Ash. |
| 39 | ·0 | „ | Carbon. |
| 6 | ·44 | „ | Hydrogen. |
| 6 | ·41 | „ | Nitrogen. |
(b.) Sclerotic Acid.—A feebly-acid substance, easily soluble in water and dilute and moderately concentrated alcohol. It passes, in association with other constituents of the ergot extract, into the diffusate, when the extract is submitted to dialysis; but after its separation in a pure state it is, like scleromucin, colloidal. It is precipitated by 85 to 90 per cent. alcohol, together with lime, potash, soda, silica, and manganese; but after maceration with hydrochloric acid, the greater part of the ash constituents can be separated by a fresh precipitation with absolute alcohol. The sample gave 40·0 per cent. of carbon, 5·2 per cent. hydrogen, 4·2 per cent. nitrogen, 50.6 per cent. oxygen, with 3·4 per cent. of ash. Sclerotic acid forms with lime a compound that is not decomposed by carbonic acid, and which upon combustion leaves from 19 to 20 per cent. of calcium carbonate. Both these substances are active, although evidently impure. Sclerotic acid is sold in commerce, and has been employed subcutaneously in midwifery practice in Russia and Germany for some time.
The inert principles of ergot are—(1.) A red colouring matter, Sclererythrin, insoluble in water, but soluble in dilute and strong alcohol, ether, chloroform, dilute solutions of potash, ammonia, &c. It can be obtained by dissolving in an alkali, neutralising with an acid, and shaking up with ether. Alcoholic solution of sclererythrin gives with aluminium sulphate, and with zinc chloride, a splendid red mixture; with salts of calcium, barium, and many of the heavy metals, it gives a blue precipitate; the yield is only ·1 to ·05 in a thousand parts.
(2.) Another colouring-matter, dissolving in concentrated sulphuric acid with the production of a fine blue violet colour, the discoverer has named Scleroidin. This is not soluble in alcohol, ether, chloroform, or water, but dissolves in alkaline solutions, potash producing a splendid violet colour; yield about 1 per 1000.
(3, 4.) Two crystalline substances, which may be obtained from ergot powder, first treated with an aqueous solution of tartaric acid, and the colouring-matters extracted by ether. One Dragendorff names Sclerocrystallin (C10H10O4); it is in colourless needles, insoluble in alcohol and water, with difficulty soluble in ether, but dissolving in ammonia and potash solutions. The other crystalline substance is thought to be merely a hydrated compound of sclerocrystallin. Both are without physiological action.
Kobert recognises two active substances in ergot, and two alone; the one he calls sphacelic acid, the other cornutin.
§ 579. Detection of Ergot in Flour (see “Foods”).—The best process is to exhaust the flour with boiling alcohol. The alcoholic solution is acidified with dilute sulphuric acid, and the coloured liquid examined by the spectroscope in thicker or thinner layers, according to the depth of colour. A similar alcoholic solution of ergot should be made, and the spectrum compared. If the flour is ergotised, the solution will be more or less red, and show two absorption bands, one in the green, and a broader and stronger one in the blue. On mixing the original solution with twice its volume of water, and shaking successive portions of this liquid with ether, amyl alcohol, benzene, and chloroform, the red colour, if derived from ergot, will impart its colour to each and all of these solvents.
§ 580. Pharmaceutical Preparations.—Ergot itself is officinal in all the pharmacopœias, and occurs in grains from 1⁄3 to 1 inch in length, and about the same breadth, triangular, curved, obtuse at the ends, of a purple colour, covered with a bloom, and brittle, exhibiting a pinkish interior, and the microscopical appearances already detailed. Ergot may also occur as a brown powder, possessing the unmistakable odour of the drug. A liquid extract of the B.P. is prepared by digesting 16 parts of ergot in 80 parts of water for twelve hours, the infusion is decanted or filtered off, and the digestion repeated with 40 parts of water; this is also filtered off, and the residue pressed, and the whole filtrate united and evaporated down to 11 parts; when cold, 6 parts of rectified spirit are added, and, after standing, the liquid is filtered and made up to measure 16. A tincture and an infusion are also officinal; the latter is very frequently used, but seldom sold, for it is preferable to prepare it on the spot. The tincture experience has shown to be far inferior in power to the extract, and it is not much used. Ergotin is a purified extract of uncertain strength; it is used for hypodermic injection; it should be about five times more active than the liquid extract.
§ 581. Dose.—The main difficulties in the statement of the medicinal dose, and of the minimum quantity which will destroy life, are the extreme variability of different samples of ergot, and its readiness to decompose. A full medicinal dose of ergot itself, as given to a woman in labour, is 4 grms. (61·7 grains), repeated every half hour. In this way enormous doses may be given in some cases without much effect. On the other hand, single doses of from 1 to 4 grms. have caused serious poisonous symptoms. The extract and the tincture are seldom given in larger doses than that of a drachm as a first dose, to excite uterine contraction. In fact, the medical practitioner has in many cases to experiment on his patient with the drug, in order to discover, not only the individual susceptibility, but the activity of the particular preparation used. From the experiments of Nikitin, it is probable that the least fatal dose of sclerotic acid for an adult man is 20 mgrms. per kilogrm.
§ 582. Ergotism.—Ergotised cereals have played a great part in various epidemics, probably from very early times, but the only accurate records respecting them date from the sixteenth century. According to Dr. Tissot,[603] the first recorded epidemic was in 1596, when a strange, spasmodic, convulsive disease broke out in Hessia and the neighbouring regions. It was probably due to spurred rye. In Voigtländer, the same disease appeared in 1648, 1649, and 1675; in 1702 the whole of Freiberg was attacked. In Germany and in France successive epidemics are described throughout the eighteenth century. In France, in 1710, Ch. Noel, physician at the Hôtel Dieu, had no less than fifty cases under treatment at the same time.
[603] Dr. Tissot in Phil. Trans., vol. lv. p. 106, 1765. This is a Latin letter by Dr. Baker, and gives a good history of the various epidemics of ergotism.
It is generally said that in 1630, Thuillier, in describing an ergot epidemic which broke out in Cologne, first referred the cause of the disease to spurred rye.
It is interesting to inquire into the mortality from this disease. In 1770, in an epidemic described by Taube, in which 600 were affected, 16 per cent. died. In a nineteenth-century epidemic (1855), in which, according to Husemann, 30 were ill, 23·3 per cent. died. In other epidemics, according to Heusinger, out of 102, 12 per cent. died; according to Griepenkerl, out of 155, 25 or 16 per cent. died; and, according to Meyer, of 283 cases, 6 per cent. died.
There are two forms of chronic poisoning by ergot—one a spasmodic form, the other the gangrenous form.
§ 583. The convulsive form of ergotism mostly begins with some cerebral disturbance. There are sparks before the eyes, giddiness, noises in the ears, and a creeping feeling about the body. There is also very commonly anæsthesia of the fingers and toes, and later of the extremities, of the back, and even of the tongue. Diarrhœa, vomiting, colic, and other signs of intestinal irritation seldom fail to be present; there are also tetanic spasms of the muscles, rising in some cases to well-marked tetanus; epilepsy, faintings, aberrations of vision, amaurosis, and amblyopia are frequent; the skin becomes of a yellow or earthy colour, and is covered with a cold sweat; boils and other eruptions may break out; blebs, like those caused by burns or scalds, have in a few cases been noticed. Death may occur in from four to twelve weeks after the eating of the spurred grain from exhaustion. In those individuals who recover, there remain for some time weakness, contractions of groups of muscles, anæmia, or affections of vision.
§ 584. The Gangrenous Form of Ergotism.—In this form there is generally acute pain in the limb or limbs which are to mortify; and there may be prodromata, similar to those already described. The limb swells, is covered with an erysipelatous blush, but at the same time feels icy cold; the gangrene is generally dry, occasionally moist; the mummified parts separate from the healthy by a moist, ulcerative process; and in this way the toes, fingers, legs, and even the nose, may be lost. During the process of separation there is some fever, and pyæmia may occur with a fatal result.
Fontenelle described a case in which a rustic lost all the toes of one foot, then those of the other; after that, the remnant of the first foot, and lastly the leg. But probably the most extraordinary case of gangrene caused by the use of ergot is that which occurred at Wattisham, Suffolk, in the family of a labouring man named John Downing. He had a wife and six children of various ages, from fifteen years to four months. On Monday, January 10, 1762, the eldest girl complained of a pain in the calf of her left leg; in the evening, her sister, aged 10, also experienced the same symptoms. On the following Monday, the mother and another child, and on Tuesday, all the rest of the family except the father became affected. The pain was very violent. The baby at the breast lived a few weeks, and died of mortification of the extremities. The limbs of the family now began to slough off, and the following are the notes on their condition made by an observer, Dr. C. Wollaston, F.R.S., on April 13:—
“The mother, aged 40. Right foot off at the ankle, the left leg mortified; a mere bone left, but not off.
“Elizabeth, aged 13. Both legs off below the knees.
“Sarah, aged 10. One foot off at the ankle.
“Robert, aged 8. Both legs off below the knees.
“Richard, aged 4. Both feet off at the ankle.
“Infant, four months old, dead.”
The father was also attacked a fortnight after the rest of the family, and in a slighter degree—the pain being confined to the fingers of his right hand, which turned a blackish colour, and were withered for some time, but ultimately got better.
As a remarkable fact, it is specially noted that the family were in other respects well. They ate heartily, and slept soundly when the pain began to abate. The mother looked emaciated. “The poor boy in particular looked as healthy and florid as possible, and was sitting on the bed, quite jolly, drumming with his stumps.” They lived as the country people at the time usually lived, on dried peas, pickled pork, bread and cheese, milk, and small beer. Dr. Wollaston strictly examined the corn with which they made the bread, and he found it “very bad; it was wheat that had been cut in a rainy season, and had lain in the ground till many of the grains were black and totally decayed.”[604]
[604] In the Phil. Trans. for 1762 there are two strictly concordant accounts of this case; and in the parish church of Wattisham, there is said to be a memorial tablet, which runs as follows:—“This inscription serves to authenticate the truth of a singular calamity which suddenly happened to a poor family in this parish, of which six persons lost their feet by a mortification not to be accounted for. A full narrative of their case is recorded in the Parish Register and Philosophical Transactions for 1762.”
§ 585. Symptoms of Acute Poisoning by Ergot.—In a fatal case of poisoning by ergot of rye, recorded by Dr. Davidson,[605] in which a hospital nurse, aged 28, took ergot, the symptoms were mainly vomiting of blood, the passing of bloody urine, intense jaundice, and stupor. But in other cases, jaundice and vomiting of blood have not been recorded, and the general course of acute poisoning shows, on the one hand, symptoms of intense gastro-intestinal irritation, as vomiting, colicky pains, and diarrhœa; and, on the other, of a secondary affection of the nervous system, weakness of the limbs, aberrations of vision, delirium, retention of urine, coma, and death.
[605] Lancet, Sept. 30, 1882.
§ 586. Physiological Action as shown by Experiments on Animals.—In spite of numerous experiments on animals and man, the action of the ergot principles remains obscure. It has been found in medicine to exert a specific action on the uterus,[606] causing powerful contractions of that organ, especially in labour. It is also a hæmostatic, and is used to check bleeding from the lungs and other internal organs of the body. This hæmostatic action, as well as the extraordinary property possessed by ergot, of producing an arrest or disturbance of the circulation inducing gangrene has naturally led to the belief that ergot causes a narrowing in the calibre of the small arteries, but this has not received the necessary experimental sanction. Holmes,[607] Eberty, Köhler,[608] and Wernick,[609] all observed a contraction in the part to which the ergot was applied, both in frogs and in warm-blooded animals; but L. Hermann,[610] although he made many experiments, and used the most different preparations, never succeeded in observing a contraction. It would also seem reasonable to expect that with a narrowing of the vessels, which means a peripheral obstruction, the blood-pressure would rise, but on the contrary the pressure sinks, a fact on which there is no division of opinion.
[606] In a case in which the author was engaged, a dabbler in drugs, having seduced a young woman, administered to her a dose of ergot which produced a miscarriage, and for this offence he was convicted. The defence raised was that ergot is a common medicine used by physicians in the treatment of amenorrhœa, and other uterine affections. Although in itself this statement was perfectly true, as a defence it was invalidated by the large dose given, the fact of the seduction, and the other circumstances of the case.
[607] Archiv d. Physiol. Norm. u. Pathol., iii. p. 384.
[608] Ueber die Wirkungen des Secale Cornutum, Dissert. Halle, 1873.
[609] Arch. f. pathol. Anat., lvi. p 505.
[610] Lehrbuch der exper. Toxicologie, Berlin, 1874, p. 386.
Nikitin has made some researches with pure sclerotic acid, which certainly possesses the most prominent therapeutic effects of ergot; but since it is not the only toxic substance, it may not represent the collective action of the drug, just in the same way that morphine is not equivalent in action to opium. Cold-blooded animals are very sensitive to sclerotic acid; of the warm-blooded the carnivoræ are more sensitive than the herbivoræ. The toxic action is specially directed to the central nervous system—with frogs, the reflex excitability is diminished to full paralysis; with warm-blooded animals reflex excitability is only diminished, and continues to exist even to death.
The temperature falls, the breathing is slowed, and the respiration stops before the heart ceases to beat; the peristaltic action of the intestines is quickened, and the uterus (even of non-pregnant animals) is thrown into contraction. The terminations of the sensory nerves are paralysed by the direct action of sclerotic acid, but they remain intact with general poisoning. The heart of frogs is slowed by sclerotic acid. Eberty observed that this slowing of the heart (he used ergotin) was produced even after destruction of the spinal cord; he therefore considered it as acting on the inhibitory nerve apparatus of the heart itself. Rossbach, using Wenzel’s ecbolin, has also studied its action on the heart of the frog, and observed that the slowing affected the ventricles rather than the auricles, so that for one ventricle-systole there were two contractions of the auricles; besides which, the contractions themselves were peculiar and abnormal in character. The cause of death from sclerotic acid seems to be paralysis of the respiration. It is said not to affect animal fœtal life. With regard to the effects produced by feeding animals with ergotised grain, experiments made during the last century have proved that it produces a gangrenous disease, e.g., C. Salerné mixed one part of spurred rye with two of good barley, and fed pigs with the mixture; a few days afterwards the pigs perished with dilated, hard, and black bellies, and offensively ulcerated legs; another pig fed entirely on the rye, lost its four feet and both ears.
Kobert[611] has investigated the effects produced on animals by “sphacelic acid,” and by “cornutin.” Sphacelic acid appears to cause gangrene, like ergot, and Kobert believes that in “sphacelic acid” is to be found the gangrene-producing substance. In cases of death putrefaction is rapid, the mucous membrane of the intestine is swollen, and the spleen enlarged. If the mucous membrane of the intestine is examined microscopically, a large quantity of micro-organisms are found in the vessels, in the villi, between the muscular bundles and in the deeper layers of the intestinal walls; this is evidence that the protective epithelial cells have been destroyed. The mesentery of cats, pigs, and fowls, contains numerous small extravasations of blood. The organs generally, and especially the subcutaneous cellular tissue, are tinged with the colouring matters of the bile; this Kobert considers as evidence of weakened vitality of the red blood corpuscles. The walls of the blood-vessels show hyaline degeneration, and give with iodine a quasi-amyloid reaction. The vessels are often partly filled with a hyaline mass, in which, at a later date, a fine black pigment appears. These pigmented hyaline masses probably occlude the vessels, and hence cause gangrene.
[611] Lehrbuch der Intoxicationen, by Dr. Rudolph Kobert, Stuttgart, 1893.
Cornutin, according to Kobert, first excites the vagus; consequently there is slow pulse and heightened blood pressure; then it paralyses the vaso-motor centre, and the pulse is accelerated. Severe convulsions, preceded by formication, follow. Paralysis of the extensor muscles, with permanent deformity, may result. Cornutin stimulates the uterus to contraction, but it does not act so well in this respect alone as when given with sphacelic acid. In animals poisoned with cornutin, no special pathological changes of a distinctive nature have been described.
§ 587. Separation of the Active Principles of Ergot from Animal Tissues.—There has been no experience in the separation of the constituents of ergot from the organs of the body; an attempt might be made on the principles detailed in [page 425], but success is doubtful.
II.—Picrotoxin, the Active Principle of the Cocculus indicus (Indian Berry, Levant Nut).
§ 588. The berries of the Menispermum cocculus comprise at least three definite crystalline principles: menispermine,[612] paramenispermine (nitrogen containing bases), and picrotoxin, which possesses some of the characters of an acid.
[612] Menispermine (C18H24N2O2?), discovered in 1834 by Pelletier and Courbe, is associated with a second named paramenispermine. The powdered berries are extracted by alcohol of 36°; the picrotoxin removed by hot water from the alcoholic extract; the menispermine and paramenispermine dissolved out together by acidulated water, and from this solution precipitated by ammonia. The brown precipitate is dissolved by acetic acid, filtered, and again precipitated by ammonia. This precipitate is dried, treated with cold alcohol, to separate a yellow resinous substance, and lastly with ether, which dissolves out the menispermine, but leaves the paramenispermine.
Menispermine forms white semi-transparent, four-sided, truncated prisms, melting at 120°, decomposed at a higher temperature, insoluble in water, but dissolving in warm alcohol and ether. Combined with 8 atoms of water it crystallises in needles and prisms. The crystals are without any taste; in combination with acids, salts may be formed.
Paramenispermine forms four-sided prisms, or radiating crystalline masses, melting at 250°, and subliming undecomposed. The crystals are soluble in absolute ether, insoluble in water, and scarcely soluble in ether.
Paramenispermine dissolves in acids, but apparently without forming definite salts.
§ 589. Picrotoxin (C30H34O13) was discovered in 1820 by Boullay. It is usually prepared by extracting the berries with boiling alcohol, distilling the alcohol off, boiling the alcoholic residue with a large quantity of water, purifying the watery extract with sugar of lead, concentrating the colourless filtrate by evaporation, and crystallising the picrotoxin out of water.
Picrotoxin crystallises out of water, and also out of alcohol, in colourless, flexible, four-sided prisms, often arborescent, and possessing a silky lustre. They are unalterable in the air, soluble in 150 parts of cold, and 25 parts of boiling water, dissolving easily in acidified water, in spirit, in ether, in amyl alcohol, and chloroform. They are without smell, but have an extremely bitter taste. Caustic ammonia is also a solvent.
The crystals are neutral in reaction. They melt at 192°-200° C. to a yellow mass; at higher temperatures giving off an acid vapour, with a caramel-like odour, and lastly carbonising. Picrotoxin in cold concentrated sulphuric acid dissolves with the production of a beautiful gold-yellow to saffron-yellow colour, which becomes on the addition of a trace of potassic bichromate, violet passing into brown. An alcoholic solution turns a ray of polarised light to the left [α]D = -28·1°.
Picrotoxin behaves towards strong bases like a weak acid. Its compounds with the alkalies and alkaline earths are gummy and not easily obtained pure. Compounds with quinine, cinchonine, morphine, strychnine, and brucine can be obtained in the crystalline condition. Dilute sulphuric acid transforms it, with assimilation of water, into a weak gummy-like acid, which corresponds to the formula C12H16O6. Nitric acid oxidises it to oxalic acid. Nitropicrotoxin and bromopicrotoxin, C30H33(NO2)O13, and C30H32Br2O13, can by appropriate treatment be obtained.
Concentrated aqueous solutions of alkalies and ammonia decompose picrotoxin fully on warming. It reduces alkaline copper solution, and colours bichromate of potash a beautiful green. The best test for its presence is, however, as follows:—The supposed picrotoxin is carefully dried, and mixed with thrice its bulk of saltpetre, the mixture moistened with sulphuric acid, and then decomposed with soda-lye in excess, when there is produced a transitory brick-red colour. For the reaction to succeed, the picrotoxin should be tolerably pure.
Solutions of picrotoxin are not precipitated by the chlorides of platinum, mercury, and gold, iodide of potassium, ferro- and ferri-cyanides of potassium, nor by picric nor tannic acids.
§ 590. Fatal Dose.—Vossler killed a cat in two hours with a dose of ·12 grm. (1·8 grain); and another cat, with the same dose, died in 45 minutes. Falck destroyed a young hound with ·06 grm. (·92 grain) in 24 to 26 minutes. Given by subcutaneous or intravenous injection, it is, as might be expected, still more lethal and rapid in its effects. In an experiment of Falck’s, ·03 grm. (·46 grain), injected into a vein, destroyed a strong hound within 20 minutes; ·016 grm. (·24 grain) injected under the skin, killed a guinea-pig in 22 minutes; and ·012 grm. (·18 grain) a hare in 40 minutes. Hence it may be inferred that from 2 to 3 grains (12·9 to 19·4 centigrms.) would in all probability, be a dangerous dose for an adult person.
§ 591. Effects on Animals.—The toxic action of picrotoxin on fish and frogs has been proposed as a test. The symptoms observed in fish are mainly as follows:—The fish, according to the dose, show uncertain motions of the body, lose their balance, and finally float to the surface, lying on one side, with frequent opening of the mouth and gill-covers. These symptoms are, however, in no way distinguishable from those induced by any poisonous substance in the water, or by many diseases to which fish are liable. Nevertheless, it may be conceded that in certain cases the test may be valuable—if, e.g., beer be the matter of research, none of the methods used for the extraction of picrotoxin will be likely to extract any other substance having the poisonous action described on fish, so that, as a confirmatory test, this may be of use.
Frogs, under the influence of picrotoxin, become first uneasy and restless, and then somewhat somnolent; but after a short time tetanic convulsions set in, which might lead the inexperienced to imagine that the animal was poisoned by strychnine. There is, however, one marked distinction between the two—viz., that in picrotoxin poisoning an extraordinary swelling of the abdomen has been observed, a symptom which, so far as known, is due to picrotoxin alone. The frog is, therefore, in this instance, the most suitable object for physiological tests.
Beer extract containing picrotoxin is fatal to flies; but no definite conclusion can be drawn from this, since many bitter principles (notably quassia) are in a similar manner fatal to insect life.
§ 592. Effects on Man.—Only two fatal cases of poisoning by picrotoxin are on record. In 1829 several men suffered from drinking rum which had been impregnated with Cocculus indicus; one died, the rest recovered. In the second case, a boy, aged 12, swallowed some of a composition which was used for poisoning fish, the active principle of which was Cocculus indicus; in a few minutes the boy experienced a burning taste, he had pains in the gullet and stomach, with frequent vomiting, and diarrhœa. A violent attack of gastro-enteritis supervened, with fever and delirium; he died on the nineteenth day. The post-mortem signs were those usual in peritonitis: the stomach was discoloured, and its coats thinner and softer than was natural; there were also other changes, but it is obvious that, as the death took place so long after the event, any pathological signs found are scarcely a guide for future cases.
§ 593. Physiological Action.—The convulsions are considered to arise from an excitation of the medulla oblongata; the vagus centre is stimulated, and causes spasm of the glottis and slowing of the heart’s action during the attack. Röhrig also saw strong contraction of the uterus produced by picrotoxin. According to the researches of Crichton Browne, chloral hydrate acts in antagonism to picrotoxin, and prevents the convulsions in animals if the dose of picrotoxin is not too large.
§ 594. Separation from Organic Matters.—Picrotoxin is extracted from aqueous acid solutions by either chloroform, amyl alcohol, or ether; the first is the most convenient. Benzene does not extract it, if employed in the same manner. On evaporation of the solvent the crude picrotoxin can be crystallised out of water, and its properties examined.
R. Palm[613] has taken advantage of the fact that picrotoxin forms a stable compound with freshly precipitated lead hydroxide, by applying this property as follows:—the solution supposed to contain picrotoxin is evaporated to dryness, and the extract then taken up in a very little water, acidified and shaken out with ether. The ether is evaporated, the ethereal extract dissolved in a little water, the aqueous solution filtered through animal charcoal, and precipitated by means of lead acetate, avoiding excess. The solution is filtered and shaken with freshly prepared lead hydroxide. The lead hydroxide is dried and tested direct for picrotoxin; if it does contain picrotoxin then on adding to it concentrated H2SO4 a beautiful saffron yellow is produced as bright as if the substance was pure picrotoxin.
[613] J. Pharm., (5), xvii. 19-20.
III.—The Poison of Illicium Religiosum—A Japanese Plant.
§ 595. A new poison belonging to the picrotoxin class has been described by Dr. A. Langaard. In 1880, 5 children in Japan were poisoned by the seeds of the Illicium religiosum; 3 of the children died. Dr. Langaard then made various experiments on animals with an active extract prepared by exhaustion with spirit, and ultimate solution of the extract in water. Eykmann has also imperfectly examined the chemistry of the plant, and has succeeded in isolating a crystalline body which is not a glucoside; it is soluble in hot water, in chloroform, ether, alcohol, and acetic acid, but it is insoluble in petroleum ether; it melts at 175°, and above that temperature gives an oily sublimate. Langaard’s conclusions are that all parts of the plant are poisonous. The poison produces excitation of the central apparatus of the medulla oblongata and clonic convulsions analogous to those produced by picrotoxin, toxiresin, and cicutoxin. Before the occurrence of convulsions, the reflex excitability of frogs is diminished, the respiratory centre is stimulated, hence frequency of the respiration. Small doses cause slowing of the pulse through stimulation of the vagus and of the peripheral terminations of the vagus; in the heart the functional activity is later diminished. Small doses kill by paralysing the respiratory centre, large by heart paralysis. The proper treatment seems to be by chloral hydrate, for when animals are poisoned by small lethal doses it appears to save life, although when the dose is large it has no effect.—Ueber die Giftwirkung von Japanischem Sternanis (Illicium religiosum, Sieb.), Virch. Archiv, Bd. lxxxvi., 1881, S. 222.
IV.—Picric Acid and Picrates.
§ 596. Picric Acid, C6H3N3O7, or
is trinitrophenol; it forms a number of salts, all of which are more or less poisonous. Picric acid is much used in the arts, especially as a dye. The pure substance is in the form of pale yellow crystals, not very soluble in cold water, but readily soluble in hot water, and readily soluble in benzene, ether, and petroleum ether. The solution is yellow, tastes bitter, and dyes animal fibres, such as wool; but it can be washed out of plant fibres such as cotton.
§ 597. Effects of Picric Acid.—Picric acid and its salts have a tendency to decompose the elements of the blood, and to produce methæmoglobin; picric acid is also an excitor of the nervous system, producing convulsions. To these two effects must be added a third; in acid solution it has a strong affinity for albumin, so that if it meets with an acid tissue it combines with the tissue, and in this way local necroses are set up. The action on albumin is somewhat weakened by the reduction in the body of part of the picric acid to picraminic acid C6H2(NO2)2NH2OH, a substance that does not so readily form compounds with albuminous matters. Doses of 0·5 to 0·9 grm. (about 8 to 14 grains) may be taken several days in succession without marked symptoms. Ultimately, however, what is known as “picric jaundice” appears, the conjunctiva and the whole skin being stained more or less yellow. The urine, at first of a dark yellow, is later of a red brown colour. Dyspepsia, with flatulence and an inclination to diarrhœa have been noticed. A single dose of a gramme (15·4 grains) caused in a case described by Adler[614] pain in the stomach, headache, weakness, diarrhœa, vomiting of yellow matters, quickening and afterwards slowing of the pulse; the skin was of a brown yellow colour, and there were nervous symptoms. The urine was ruby red. In both fæces and urine picric acid could be recognised. The excretion of picric acid continued for six days. A microscopical examination of the blood showed a diminution of the red blood corpuscles, an increase in the white. Chéron[615] has described a case in which the application of 0·45 grm. (6·9 grains) to the vagina produced yellowness of the skin in an hour, and the urine was also coloured red. Erythema, somnolence, burning and smarting in the stomach and in the kidneys were also noticed.
[614] Wiener. med. Woch., 1880, 819.
[615] J. Chéron, Journ. de Thêr., 1880, 121.
§ 598. Tests.—Picric acid is easily separated from either tissues or other organic matters. These are acidified with sulphuric acid and then treated with 95 per cent. alcohol; the alcohol is filtered off, distilled, and the residue treated with ether; this last ethereal extract will contain any picric acid that may be present.
If the ether extract contains much impurity, it may be necessary to drive off the ether, and to take up the residue with a little warm water, then to cool, filter through a moistened filter paper, and test the aqueous solution. Picric acid, warmed with KCN and KHO gives a blood-red colour, from the production of iso-purpurate of potash. Ammoniacal copper sulphate forms with picric acid yellow-green crystals which strongly refract the light. If a solution of picric acid be reduced by the addition of a hydrochloric acid solution of stannous chloride, the subsequent addition of ferric chloride produces a blue colour, due to the formation of amidoimidophenol hydrochloride C6H2OH(NH2)(NH)2HCl.
V.—Cicutoxin.
§ 599. The Cicuta virosa, a not very common umbelliferous plant growing in moist places, is extremely poisonous. It is from 3 to 4 feet in height, with white flowers; the umbels are large, the leaves are tripartite, the leaflets linear lanceolate acute, serrate decurrent; the calyx has five leaf-like teeth, the petals are obcordate with an inflex point; the carpels have five equal broad flattened ridges with solitary stripes. Böhm[616] succeeded, in 1876, in separating an active principle from this plant. The root was dried, powdered, and exhausted with ether; on evaporation of the ether the extract was taken up with alcohol, and after several days standing the filtrate was treated with petroleum ether; after removing the petroleum, the solution was evaporated to dryness in a vacuum; it was found to be a resinous mass, to which was given the name cicutoxin. It was fully soluble in alcohol, ether, or chloroform, and was very poisonous, but what its exact chemical nature may be is still unknown.
[616] Arch. f. exp. Path., Bd. v., 1876.
§ 600. Effects on Animals.—Subcutaneously injected into frogs, cicutoxin acts something like picrotoxin, and something like the barium compounds. Ten to fifteen minutes after the injection the animal assumes a peculiar posture, holding the legs so that the thigh is stretched out far from the trunk, and the leg at right angles with the thigh; voluntary motion is only induced by the strongest stimuli, and when the frog springs, he falls down plump with stiffly stretched-out limbs. The frequency of breathing is increased, the muscles of the abdomen are thrown into contraction, and the lungs being full of air, on mechanical irritation there is a peculiar loud cry, depending upon the air being forced under the conditions detailed through the narrow glottis. Tetanic convulsions follow, gradually paresis of the extremities appears, and, lastly, full paralysis and death; these symptoms are seen after doses of from 1 to 2 mgrms. The lethal dose for cats is about 1 centigrm. per kilo. Diarrhœa, salivation, and frequent breathing are first seen, and are followed by tonic and clonic convulsions, then there is an interval, during which there is heightened excitability of reflex action, so that noises will excite convulsions. Small doses by exciting the vagus slow the pulse; larger doses quicken the pulse, and raise the arterial pressure. Cicutoxin is supposed to act specially on the medulla oblongata, while the spinal cord and the brain are only secondarily affected.
§ 601. Effects on Man.—F. A. Falck was able to collect thirty-one cases of poisoning by cicuta; of these 14 or 45·2 per cent. died. The symptoms are not dissimilar to those described in animals. There are pain and burning in the stomach, nausea, vomiting, headache, and then tetanic convulsions. These, in some cases, are very severe, and resemble those induced by strychnine; but in a few cases there is early coma without convulsions. There is also difficulty or absolute impossibility of swallowing. In fatal cases the respiration becomes stertorous, the pulse small, the pupils dilated, and the face cyanotic, and death occurs within some four hours, and in a few cases later. The fatal dose is unknown.
§ 602. Separation of Cicutoxin from the Body.—An attempt might be made to extract cicutoxin from the tissues on the same principles as those by which it has been separated from the plant, and identified by physiological experiments. In all recorded cases, identification has been neither by chemical nor physiological aids, but by the recognition of portions of the plant.
VI.—Æthusa Cynapium (Fool’s Parsley).
§ 603. This plant has long been considered poisonous, and a number of cases are on record in which it is alleged that death or illness resulted from its use. Dr. John Harley,[617] however, in an elaborate paper, has satisfactorily proved the innocence of this plant, and has analysed the cases on record. He has experimented on himself, on animals, and on men, with the expressed juice and with the tincture. The results were entirely negative: some of the published cases he refers to conium, and others to aconite.
[617] St. Thomas’ Hospital Reports, N.S., 1875.
VII.—Œnanthe Crocata.
§ 604. The Water Hemlock.[618]—This, a poisonous umbelliferous plant, indigenous to England, and growing in moist places such as ditches, &c., is in flower in the month of August. It resembles somewhat celery, and the root is something like the parsnip, for which it has been eaten. All parts of the plant are said to be poisonous, but the leaves and stalks only slightly so, while the root is very deadly. We unfortunately know nothing whatever about the active principles of the plant, its chemistry has yet to be worked out. M. Toulmouche (Gaz. Méd., 1846) has recorded, as the expert employed in the case, an attempt to murder by using the œnanthe as a poison; a woman scraped the root into her husband’s soup with evil intent, but the taste was unpleasant, and led to the detection of the crime. The root has been mistaken several times for parsnip and other edible roots, and has thus led to poisonings. The case of 36 soldiers poisoned in this way, in 1758, has been recorded by Orfila; there was one death. In 1803 three soldiers were poisoned at Brest—1 died. In Woolwich Bossey witnessed the poisoning of 21 convicts who ate the roots and leaves of the plant—6 died. In 1858 there were several sailors poisoned in a similar way—2 died; while there have been numerous cases in which the plant has been partaken of by children.
[618] The earliest treatise on poisoning by the water-hemlock is by Wepfer. Cicutæ Aquat. Historia et Noxæ, 1679; for cases see Trojanowsky, Dorp. med. Ztg., 1875; Meyer, Med. Zeitg. f. Preussen, 1842; Schlesier in Casper’s Wochenschrift, 1843; Maly, Œster. med Wochenschr., 1844; Badgeley, Montreal med. Gaz., 1844; Lender, Viertelj. f. ger. Med., 1865; Gampf, Cöln. Pharm. Zeitg., 1875; and the treatises of Taylor and others.
§ 605. The effects of the poison may be gathered from a case of poisoning[619] which occurred in 1882 at Plymouth; a Greek sailor, aged thirty, found on the coast what he considered “wild celery,” and ate part of the root and some of the stem. Two hours after this he ate a good meal and felt perfectly well, but fifteen minutes later he suddenly and violently vomited; the whole contents of the stomach were completely evacuated. In five minutes he was completely unconscious, and had muscular twitchings about the limbs and face. There was a copious flow of a thick tenacious mucus from the mouth which hung about the lips and clothing in viscid strings. Twenty-four hours after the poisoning he was admitted into the South Devon Hospital apparently semi-comatose; his legs dragged, and he had only feeble control of them; the extremities were cold, but there was general free sweating. He could be roused only with difficulty. There were no spasms, the pupils were dilated and sluggish, the respiration only 14 per minute. Twelve hours after admission he became warmer, and perspired freely; he slept continuously, but could easily be roused. On the following day he was quite conscious, and made a good recovery. Two companions who had also eaten a smaller quantity of the hemlock dropwort, escaped with some numbing sensations, and imperfect control over the extremities. In the Woolwich cases the symptoms seem to have been something similar; in about twenty minutes, one man, without any apparent warning, fell down in strong convulsions, which soon ceased, although he looked wild; a little while afterwards his face became bloated and livid, his breathing stertorous and convulsive, and he died in five minutes after the first symptoms had set in. A second died with similar symptoms in a quarter of an hour; a third died in about an hour, a fourth in a little more than an hour; two other cases also proved fatal, one in nine days, the other in eleven. In the two last cases there were signs of intestinal irritation. The majority of the others fell down in a state of insensibility with convulsions, the after-symptoms being more or less irritation of the intestinal canal.
[619] Lancet, Dec. 18, 1882.
§ 606. Post-mortem Appearances.—It was noticed in the Woolwich cases that those who died quickly had congestion of the cerebral vessels, and, in one instance, there was even extravasation of blood, but the man who died first of all had no congestion of the cerebral vessels. The lining membrane of the wind-pipe and air tubes was intensely injected with blood, and the lungs were gorged with fluid blood; the blood in the heart was black and fluid. The stomach and intestines were externally of a pink colour. The mucous membrane of the stomach was much corrugated, and the follicles particularly enlarged. In the two protracted cases the stomach was not reddened internally, but the vessels of the brain were congested.
VIII.—Oil of Savin.
§ 607. The leaves of the Sabina communis (Juniperus Sabina), or common savin, an evergreen shrub to be found in many gardens, contains a volatile oil, which has highly irritant properties. Savin leaves are occasionally used in medicine, maximum dose 1 grm. (15·4 grains). There is also a tincture—maximum dose 3 c.c. (about 45 mins.)—and an ointment made by mixing eight parts of savin tops with three of yellow wax and sixteen parts of lard, melting and digesting for twenty minutes, and then straining through calico. The oil, a tincture, and an ointment, are officinal pharmaceutical preparations.
The oil of savin is contained to the extent of about 2 per cent. in the leaves and 10 per cent. in the fruit. It has a peculiar odour, its specific gravity is ·89 to ·94, and it boils at 155° to 160°. An infusion of savin leaves (the leaves being drunk with the liquid) is a popular and very dangerous abortive.
It is stated by Taylor that oil of savin has no abortive effect, save that which is to be attributed to its general effect upon the system, but this is erroneous. Röhrig found that, when administered to rabbits, it had a very evident effect upon the pregnant uterus, throwing it into a tetanic contraction. The action was evident after destruction of the spinal cord. The plant causes great irritation and inflammation, whether applied to the skin or taken internally. The symptoms are excruciating pain, vomiting, and diarrhœa, and the person dies in a kind of collapse.
In a case in which the author was engaged some years ago, a woman, pregnant by a married man, took an unknown quantity of infusion of savin tops. She was violently sick, suffered great pain, with diarrhœa, and died in about 26 hours. The pharynx was much reddened, and the gullet even congested; the stomach was inflamed, and contained some greenish matter, in which the author was able to detect savin tops, as well as to separate by distillation a few drops of a strong savin-like smelling oil. The time which would elapse between the swallowing of the poison and the commencement of the pain was an important factor in this case, for the man was accused of having supplied her with the infusion. From the redness of the pharynx, and, generally, the rapid irritation caused by ethereal oils, the author was of opinion that but a few minutes must have passed between the taking of the liquid and the sensation of considerable burning pain, although it is laid down in some works, as for example Falck’s Toxicologie, that commonly the symptoms do not commence for several hours. Symptoms which have been noticed in many cases are—some considerable irritation of the urinary organs, such as strangury, bloody urine, &c.; in a few cases vomiting of blood, in others anæsthesia, convulsions, and coma. Death may occur within 12 hours, or may be postponed for two or three days.
§ 608. Post-mortem Appearances.—More or less inflammation of the bowels, stomach, and intestinal tract, with considerable congestion of the kidneys, are the signs usually found.
§ 609. Separation of the Poison and Identification.—Hitherto reliance has been placed entirely on the finding of the savin tops, or on the odour of the oil. There is no reliable chemical test.
IX.—Croton Oil.
§ 610. Croton oil is an oil expressed from the seeds of Croton tiglium, a plant belonging to the natural order Euphorbiaceæ, growing in the West Indies. The seeds are oval in shape, not unlike castor-oil seeds, and about three-eighths of an inch in length. Both the seeds and the oil are very poisonous. The chemical composition of croton oil can scarcely be considered adequately settled. The most recent view, however, seems to be that it contains a fixed oil (C9H14O2) with certain glycerides.[620] On saponifying and decomposing the soap a series of volatile fatty acids can be distilled over, the principal of which are methyl crotonic acid, with small quantities of formic, acetic, iso-butyric, valeric, and perhaps propionic, and other acids.[621] The peculiar properties of croton are due rather to the fixed oil than to the volatile principles. The only officinal preparation in the British pharmacopœia is a “croton oil liniment,” containing one part of croton oil to seven of equal parts of oil of cajuput and rectified spirit.
[620] G. Schmidt, Arch. Pharm. [3] 13, 213-229. Schlippe, Liebig’s Annalen, 105, 1. Geuther and Fröhlich, Zeitschrift f. Chem., 1870, 26 and 549; Journ. Chem. Society, March 1879, p. 221.
[621] Benedikt has found 0·55 per cent. of unsaponifiable matter in croton oil. Lewkowitsch gives the iodine value 101·7 to 104·7, and solidifying point as 18·6°-19·0°. (Cheml. Analysis of the Oils, Fats, and Waxes, by R. Benedikt, translated and enlarged by J. Lewkowitsch, London, 1895.)
§ 611. Dose.—The oil is given medicinally as a powerful purgative in doses up to 65 mgrms. (about a grain). It is used externally as an irritant or vesicant to the skin. A very dangerous dose would be from fifteen to twenty times the medicinal dose.
Effects.—Numerous cases of poisoning from large doses of croton oil are recorded in medical literature, but the sufferers have mostly recovered. The symptoms are pain, and excessive purging and vomiting.
In the case of a chemist,[622] who took half an ounce of impure croton oil instead of cod-liver oil, the purging was very violent, and he had more than a hundred stools in a few hours; there was a burning pain in the gullet and stomach, the skin was cyanosed, the pupils dilated, and great faintness and weakness were felt, yet the man recovered. A child, aged four, recovered from a teaspoonful of the oil given by mistake directly after a full meal of bread and milk. In five minutes there were vomiting and violent purging, but the child was well in two days. A death occurred in Paris, in 1839, in four hours after taking two and a half drachms of the oil. The symptoms of the sufferer, a man, were those just detailed, namely, burning pain in the stomach, vomiting, and purging. Singularly enough, no marked change was noticed in the mucous membrane of the stomach when examined after death. An aged woman died in 3 days from a teaspoonful of croton-oil embrocation; in this case there were convulsions.
[622] Revue de Thérapeut., May 1881.
In the case of Reg. v. Massey and Ferraud,[623] the prisoners were charged with causing the death of a man, by poisoning his food with jalap and six drops of croton oil. The victim, with others who had partaken of the food, suffered from vomiting and purging; he became better, but was subsequently affected with inflammation and ulceration of the bowels, of which he died. In this case it was not clear whether the inflammation had anything to do with the jalap and croton oil or not, and the prisoners were acquitted. In a criminal case in the United States, a man, addicted to drink, was given, when intoxicated, 2 drachms of croton oil in a glass of whisky. He vomited, but was not purged, and in about twelve hours was found dead. The mucous membrane of the stomach and small intestines proved to be much inflamed, and in some parts eroded, and croton oil was separated from the stomach.
[623] Orfila, t. i. p. 108.
§ 612. Post-mortem Appearances.—Inflammation of the stomach and intestines are the signs usually found in man and animals.
§ 613. Chemical Analysis.—The oil may be separated from the contents of the stomach by ether. After evaporation of the ether, the blistering or irritant properties of the oil should be essayed by placing a droplet on the inside of the arm.
X.—The Toxalbumins of Castor-Oil Seeds and of Abrus.
§ 614. The Toxalbumin of Castor-Oil Seeds.—In castor-oil seeds, besides the well-known purgative oil, there exists an albuminous body intensely poisonous, which has been carefully investigated by Stillmark,[624] under the direction of Kobert.[625] Injected into the circulation it is more poisonous than strychnine, prussic acid, or arsenic; and since the pressed seeds are without taste or smell, this poison has peculiar dangers of its own.
[624] H. Stillmark, Dorp. Arb., Bd. iii., 1889.
[625] Kobert’s Lehrbuch, 453-456.
It is essentially a blood poison, coagulating the blood.
The blood, if carefully freed from all fibrin, is yet again brought to coagulation by a small amount of this body.
If castor-oil seeds are eaten, a portion of the poison is destroyed by the digestive processes; a part is not thus destroyed, but is absorbed, and produces in the blood-vessels its coagulating property. Where this takes place, ulcers naturally form, because isolated small areas are deprived of their blood supply. These areas thus becoming dead, may be digested by the gastric or intestinal fluids, and thus, weeks after, death may be produced. The symptoms noted are nausea, vomiting, colic, diarrhœa, tenesmus, thirst, hot skin, frequent pulse, sweats, headache, jaundice, and death in convulsions or from exhaustion. Animals may be made immune by feeding them carefully with small doses, gradually increased.
The post-mortem appearances are ulceration in the stomach and intestines. In animals the appearances of hæmorrhagic gastro-enteritis, with diffuse nephritis, hæmorrhages in the mesentery and so forth have been found.
§ 615. Toxalbumin of Abrus.—A toxalbumin is found in the Abrus precatorius (Jequirity) which causes quite similar effects and symptoms. That it is not identical is proved by the fact that, though animals may become immune by repeated doses of Jequirity against “Abrin,” the similar substance from castor-oil seeds only confers immunity against the toxalbumin of those seeds, and not against abrin; and similarly abrin confers no immunity against the castor albumin. Either of these substances applied to the conjunctiva produces coagulation in the vessels and a secondary inflammation, to which in the case of jequirity has been given the name of “jequirity-ophthalmia.”[626]
[626] Heinr. Hellin, Der giftige Eiweisskorper-Abrin u. seine Wirkung auf das Blut. Inaug.-Diss., Dorpat., 1891.
The general effect of these substances, and, above all, the curious fact that a person may acquire by use a certain immunity from otherwise fatal doses is so similar to poisonous products evolved in the system of persons suffering from infectious fevers, that they have excited of late years much interest, and a study of their methods of action will throw light upon many diseased processes.
At present there are no chemical means of detecting the presence of the toxalbumins mentioned. Should they be ever used for criminal purposes, other evidence will have to be obtained.
XI.—Ictrogen.
§ 616. Ictrogen.—Various lupins, e.g., Lupinus luteus, L. angustifolius, L. thermis, L. linifolius, L. hirsutus, contain a substance of which nothing chemically is known, save that it may be extracted by weakly alkaline water, and which has been named “ictrogen”; this must not be confused with the alkaloid of lupins named “lupinine,” a bitter tasting substance. In large doses a nerve poison. Ictrogen has the unusual property of acting much like phosphorus. It causes yellow atrophy of the liver, and produces the following symptoms:—Intense jaundice; at first enlargement of the liver, afterwards contraction; somnolence, fever, paralysis. The urine contains albumen and the constituents of the bile. After death there is found to be parenchymatous degeneration of the heart, kidneys, muscles, and liver. If the animal has suffered for some time the liver may be cirrhotic.
Hitherto the cases of poisoning have been confined to animals. Many thousands of sheep and a few horses and deer have, according to Kobert, died in Germany from eating lupin seeds. Further information upon the active principles of lupins may be obtained by referring to the following treatises:—G. Schneidemuhl, Die lupinen Krankheit der Schafe; Vorträge f. Thierärzte. Ser. 6, Heft. 4, Leipzig, 1883. C. Arnold and G. Schneidemuhl, Vierter Beitrag zur Klarstellung der Ursache u. des Wesens der Lupinose, Luneburg, 1883; Julius Löwenthal, Ueber die physiol. u. toxicol. Wirkungen der Lupinenalkaloide, Inaug.-Diss., Königsberg, 1888.
XII.—Cotton Seeds.
§ 617. Cotton seeds, used as an adulterant to linseed cake, &c., have caused the death of sheep and calves. Cotton seeds contain a poison of which nothing is chemically known, save that it is poisonous. It produces anæmia and cachexia in animals when given in small repeated doses.
After death the changes are, under these circumstances, confined to the kidney; these organs showing all the signs of nephritis. If, however, the animal has eaten a large quantity of cotton seeds, then there is gastro-enteritis, as well as inflammation of the kidneys.
XIII.—Lathyrus Sativus.
§ 618. Various species of vetchlings, such as L. sativus, L. cicera, L. clymenum, are poisonous, and have caused an epidemic malady in parts of Spain, Africa, France, and Italy, among people who have eaten the seeds. The symptoms are mainly referable to the nervous system, causing a transverse myelitis and paraplegia. In this country it is chiefly known as a poisonous food for horses; the last instance of horse-poisoning by lathyrus was that of horses belonging to the Bristol Tramways and Carriage Company.[627] The company bought some Indian peas; these peas were found afterwards to consist mainly of the seeds of Lathyrus sativus, for out of 335 peas no fewer than 325 were the seeds of Lathyrus. The new peas were substituted for the beans the horses had been having previously on the 2nd November, and the horses ate them up to the 2nd December. Soon after the new food had been given, the horses began to stumble and fall about, not only when at work, but also in their stalls; to these symptoms succeeded a paralysis of the larynx; this paralysis was in some cases accompanied by a curious weird screaming, which once having been heard could never be forgotten; there was also gasping for breath and symptoms of impending suffocation. A few of the horses were saved by tracheotomy. Some died of suffocation; one horse beat its brains out in its struggles for breath; 127 horses were affected; 12 died.
[627] Bristol Tramways and Carriage Company v. Weston & Co., Times, July 17, 1894.
The above train of symptoms has also been recorded in similar cases; added to which paralysis of the lower extremities is frequent. After death atrophy of the laryngeal muscles, wasting of the nervus recurrens, and atrophy of the ganglion cells of the vagus nucleus as also of the multipolar ganglion cells in the anterior horns of the spinal cord have been found.
The active principle of the seeds has not been satisfactorily isolated. The symptoms suggest the action of a toxalbumin. Teilleux found a resin acid; Louis Astier a volatile alkaloid, and he explains the fact that the seeds, after being heated, are no longer poisonous by the dissipation of this alkaloid.
XIV.—Arum—Bryony—Locust Tree—Male Fern.
§ 619. Arum maculatum, the common cuckoo-pint, flowering in April and May, and frequent in the hedges of this country, is extremely poisonous. Bright red succulent attractive berries are seen on a single stalk, the rest of the plant having rotted away, and these berries are frequently gathered by children and eaten. The poison belongs to the class of acrid irritants, but its real nature remains for investigation.
Some of the species of the same natural order growing in the tropics are far more intensely poisonous.
§ 620. The Black Bryony.—Tamus communis, the black bryony, a common plant by the wayside, flowering in May and June, possesses poisonous berries, which have been known to produce death, with symptoms of gastro-enteritis. In smaller doses the berries are stated to produce paralysis of the lower extremities.[628]
[628] Contagne, Lyon med., xlvi., 1884, 239.
§ 621. The Locust Tree.—The Robinia pseudo-acacia, a papilionaceous tree, contains a poison in the leaves and in the bark. R. Coltmann [629] has recorded a case in China of a woman, twenty-four years of age, who, at a time of famine, driven by hunger, ate the leaves of this tree. She became ill within forty-eight hours, with high fever; the tongue swelled and there was much erysipelatous-like infiltration of the tissues of the mouth; later the whole body became swollen. There was constipation and so much œdema of the eyelids that the eyeballs were no longer visible. Recovery took place without special treatment. Power and Cambier[630] have separated from the bark an albumose, which is intensely poisonous, and is probably the cause of the symptoms detailed.
[629] Medical and Surgical Reporter, lxi., 1889.
[630] Pharm. Journ., 1890, 711.
§ 622. Male Fern.—An ethereal extract of Aspidium Filix mas is used as a remedy against tape worm.
Poullson[631] has collected up to the year 1891 sixteen cases of poisoning by male fern; from which it would appear that 7 to 10 grms. (103 to 154 grains) of the extract may be fatal to a child, and 45 grms. (rather more than 11⁄2 oz.) to an adult. The active principle seems to be filicic acid and the ethereal oil. Filicic acid, under the influence of saponifying agencies, breaks up into butyric acid and phloroglucin.
[631] Arch. exp. P., Bd. 29.
The symptoms produced are pain, heaviness of the limbs, faintness, somnolence, dilatation of the pupil, albuminuria, convulsions, lock-jaw, and collapse. In animals there have also been noticed salivation, amaurosis, unsteady gait, dragging of the hind legs, dyspnœa, and paralysis of the breathing centres. The post-mortem appearances which have been found are as follows:—Redness and swelling with hæmorrhagic spots of the mucous membranes of the stomach and intestines; acute œdema of the brain and spinal cord with petechia in the meninges; the kidneys inflamed, the liver and spleen congested, and the lungs œdematous.
There is no characteristic reaction for male fern; the research most likely to be successful is to attempt to separate from an ethereal extract filicic acid, and to decompose it into butyric acid and phloroglucin; the latter tinges red a pine splinter moistened with hydrochloric acid.