Arsenic

ARSENIC (Arsenum, Arsenium, Arsenicum), a solid metalloid, symbol As; atomic weight 74.96. In the periodic table of elements, it occupies the 33rd place, in the 5th row of Group V. Natural compounds of arsenic with sulfur (realgar and orpiment) were known in antiquity (Aristotle, Pliny). The name Arsenikon was given by Theophrastus. White arsenic (arsenious anhydride) was first apparently obtained by Geber (8th century); in any case, arsenic as such was known in the 13th century (Albertus Magnus). The isolation of the element arsenic was achieved by Schroder (1694); Brandt (1733) obtained it in a pure state and described it in detail. Arsenic is extremely widespread in nature, but never occurs in large quantities. It is mainly found in combination with heavy metals and their sulfides, occasionally in the free state, but more often in compounds with sulfur, forming two minerals: realgar (or sandarach, As₂S₂), arsenic disulfide, a red powder insoluble in water but soluble in alkaline sulfides to form arsenic sulfosalts, and orpiment, arsenic trisulfide (As₂S₃), a yellow powder insoluble in water but soluble in alkaline sulfides, ammonia, and alkaline carbonates; freshly precipitated arsenic trisulfide oxidizes to arsenious acid even at room temperature in aqueous extracts. In the form of salts of arsenic acid, arsenic is less commonly found [in water, in almost all ores, in some clays (ochre), in mineral waters of some springs, etc.]. In small amounts, arsenic is present in plants growing on arsenic-containing soil, in animals (herbivores and carnivores), and in humans. Arsenic is normally present in the thyroid gland (in humans 0.16 mg), in the thymus gland, in the brain, in the skin, in hair, in the intestinal canal (not more than 0.1 mg), in urine (up to 0.5 mg per day), and in rare cases in traces in the liver and spleen. This arsenic enters the body with food and especially with drinking water, wine, NaCl, as well as by inhalation of coal smoke (English coal). At present, most researchers believe that these traces of arsenic in the normal body do not play a physiological role, being only accidental components of it. Arsenic is known in several allotropic modifications, namely: crystalline arsenic (gray β-arsenic and yellow α-arsenic), and amorphous or microcrystalline arsenic (black shiny mass and black-brown powder). The most important of these is crystalline gray arsenic. It has the appearance of a metal, steel-gray in color, brittle and lustrous; specific gravity 5.73. At ordinary temperature it is the stable form; when heated to 450°, without melting, it gives colorless or slightly yellow vapors, which upon cooling deposit crystals of the hexagonal-rhombohedral system. The density of the vapors is 10.2 (with air density equal to 1); it is 150 times greater than that of hydrogen. The arsenic molecule contains 4 atoms (As₄). At +1736° the vapor density decreases by half, consequently the As₄ molecule dissociates into As₂. Water does not decompose arsenic. With nascent hydrogen it combines to form a colorless, extremely poisonous gas with a garlic odor-arsine (see). In dry air or in a hydrogen atmosphere, arsenic does not change, but in moist air under the influence of light or temperature (200°) it oxidizes very easily to white arsenious anhydride As₂O₃. This highly poisonous, colorless and sweetish substance, solid, volatile at 1800°, is known under the name of arsenic or white arsenic (Arsenicum album). It is obtained as a by-product in the roasting of cobalt or other ores containing arsenic. It is known in amorphous and crystalline forms. The amorphous form appears as a colorless, glassy, transparent mass, which upon storage in moist air gradually becomes opaque and turns into a porcelain-like mass of milky-white color consisting of crystalline As₂O₃. The amorphous form is used for technical purposes. Crystalline As₂O₃ is known in 2 forms: crystals of the regular system (octahedra) and of the rhombohedral system (prisms); they are difficultly soluble in water (about 1:65), at atmospheric pressure they do not melt; they are easily reduced by many metals (even copper), and especially when heated with carbon, to metallic arsenic. In water it dissociates into very weak arsenious acid (Acidum arsenicosum) As(OH)₃; its solutions have a weakly acid reaction. The acid forms salts (arsenites); most of them are derived from the hypothetical compound OAsOH (metaarsenites), while others are derived from As(OH)₃ (orthoarsenites). Metaarsenites, to which the alkaline salts belong, undergo further hydrolysis in aqueous solutions; they are easily destroyed by acids (even CO₂). Dissolved arsenites, absorbing oxygen from the air, constantly pass into salts of arsenic acid-arsenates. Of the salts, one can mention: sodium arsenite (Natrium arsenicosum), potassium arsenite (Kalium arsenicosum), quinine arsenite (Chininum arsenicosum) (see below). Salts of copper oxide CuHAsO₃, mixed with an alkaline solution of As₂O₃, give a green precipitate of copper salt called Scheele's green or Swedish green; it probably has the composition CuHAsO₃. When boiling solutions of arsenious acid and copper acetate are mixed, the so-called Schweinfurt green or Vienna green is obtained; like the previous one, it is an insoluble in water green salt of copper oxide. Similar in many respects to the previous one, it has a different shade of green color. When As₂O₃ is oxidized with nitric acid, the highest degree of oxidation of arsenic is obtained-arsenic acid (Acidum arsenicum H₃AsO₄). It has the appearance of a thick syrup and colorless small crystals, easily soluble in water and alcohol; solutions have a strongly acid reaction. It easily gives up oxygen, oxidizing for example SO₂, KI, etc. It forms 3 series of salts (metaarsenates); alkaline salts are soluble in water. By removing water at 180° from arsenic acid, arsenic anhydride As₂O₅ is obtained, which is a white amorphous mass that rapidly attracts moisture from moist air; at high temperature it spontaneously decomposes into As₂O₃ and O₂. Metallic arsenic easily combines with chlorine (AsCl₃), bromine (AsBr₃), and iodine (AsI₃).-Both trivalent (As₂O₃) and pentavalent (As₂O₅) arsenic can be easily introduced into many organic molecules. The organic arsenic compounds used in medicine can be divided into 2 groups: the first group, arsenobenzoles (with trivalent arsenic), contains dihydroxydiaminoarsenobenzole and its derivatives, formed by the introduction of a sulfur-containing chain into its amide group, as seen in the formula: As - As OH OH (see Salvarsan). The second group-substituted arsenic acid (with pentavalent arsenic); its OH is replaced by alkyl or aromatic groups, as seen in the following formulas: arsenic acid O-As OH, OH, cacodylic (dimethylarsenic) acid O. As(CH₃)₂OH, arsanilic (aminophenyl-arsenic) acid O. As(C₆H₄NH₂)(OH)₂ and acetyl arsanilic acid. On the salts of these acids used in medicine-see below. Action on the body. All soluble and absorbable compounds of arsenic have a strong pharmacodynamic action. As an element, metallic arsenic is inactive, passing through the digestive tract unchanged; however, due to its ability to oxidize easily, it can under certain conditions even in small amounts exert an action which with great probability should be attributed to its transformation into arsenious acid. Under normal conditions, as is known, there are no favorable conditions for oxidation in the intestine. When metallic arsenic is introduced under the skin in a thin oil suspension or in the form of colloidal arsenic, as well as when it is rubbed into the skin in the form of an ointment, absorption undoubtedly occurs (arsenic is found in the urine), and general poisoning phenomena may occur. The action of inorganic compounds, with some exceptions, is basically the same, i.e., corresponds to the action of arsenious acid. Gaseous arsine (see) has a special character of action. Among inorganic compounds, arsenious acid and its salts (arsenites) are more active than arsenic acid and its salts (arsenates); according to experiments by Joachimoglu, the toxicity of the former in relation to the latter is 10:6. The pharmacological action of organic arsenic compounds is probably in most cases explained by the fact that in the cells they break down slowly, passing through an intermediate stage of simple organic molecules and gradually splitting off more or less ionized arsenic and at the same time being released in the form of organic compounds. Therefore, their action is slower and milder than that of inorganic compounds.

Thanks to their physicochemical properties, organic compounds probably penetrate certain cells more quickly and are therefore distributed differently in the body than arsenites and arsenates, which is why they can produce different changes than the latter. Experiments on higher animals show much less toxicity of organic compounds than inorganic ones. Thus, the minimum lethal dose for a rabbit upon intravenous administration is 34 mg of Arsenic in the form of salvarsan and 4.56-5.3 mg in the form of potassium arsenite. On the other hand, organic compounds are much more toxic to protozoan parasites than inorganic ones, although in vitro they exhibit very weak parasiticidal action; consequently, they require, like most other antiprotozoal agents, the cooperation of the host to become active. It is possible that this property is due to their conversion into more active breakdown products. Locally, intact skin or mucous membranes are not affected by aqueous solutions of arsenic, unless it is applied repeatedly or left for a long time (e.g., when using cosmetic preparations containing arsenic). Arsenic does not form compounds with proteins similar to albuminates of heavy metals. When applied in substance or as a saturated solution (1:70 arsenious acid), Arsenic has an irritating effect, causing acute pain, inflammation, and death of cells, but this effect occurs very slowly (after 3-4 hours, as is well known from dental practice (nerve destruction) and treatment of epitheliomas). The same is observed with diluted solutions, but when administered under the skin. Repeated application of arsenic solution or ointment to the skin can cause eczema. Arsenious acid in diluted form or as a salt is very quickly absorbed from mucous membranes and wounds. In the blood, it combines with blood corpuscles, but most of it still leaves the blood fairly quickly, being taken up by the tissues. Thanks to the ease of detection of Arsenic even in small quantities in the organs and fluids of the animal organism, it has been possible to show its presence in numerous organs in cases of acute and chronic poisoning, mostly in the liver and kidneys; in the central nervous system and cerebrospinal fluid, its amounts were found to be insignificant (traces). Through the placental circulation, arsenic penetrates into the fetus. According to the assumption of most authors, in the tissues Arsenic takes the place of the phosphorus present there; however, the experimental material presented in support of this assumption is not convincing. Apparently, the liver does not play the role of an organ neutralizing or capturing Arsenic, since the toxicity of Arsenic is the same upon administration into the v. jugularis as into the v. mesenterica. With subcutaneous administration, the toxicity of Arsenic is somewhat less, as it enters into more slowly dissociating compounds with tissue elements. Arsenic is excreted from the body very slowly and incompletely, especially with prolonged administration, after which excretion continues for several (2-7) months. After a single dose, excretion begins after 2-8 hours and lasts 3-10 days. The organs of excretion are the kidneys and intestines, to some extent the skin and mammary glands, Arsenic has also been found in menstrual blood; in the epidermis and hair, Arsenic in the form of insoluble compounds is retained the longest (up to a year). A garlic odor from the mouth is rarely observed with therapeutic use of inorganic arsenic compounds, but it is very strong with the use of cacodylates. Of the theories of Arsenic's action, the following can be mentioned. 1. Liebig expressed the view that arsenious acid, like salts of heavy metals, forms a compound with proteins (albuminates), resulting in its cauterizing action on the mucous membrane of the digestive tract in acute poisoning. However, further research showed that neither aqueous solutions of As2O3 nor arsenites or arsenates alter protein solutions. The same poisoning symptoms occur with subcutaneous administration of Arsenic, although in this case only traces of Arsenic are found in the contents of the stomach and intestines. Thus, the mechanism of cell death from Arsenic is different than from mineral acids and metal salts. 2. Binz (1897) and Schulz (1884) showed that the fresh protoplasm of body cells (liver and small intestines) first converts arsenious acid into arsenic acid, and then the latter back into arsenious acid according to the formula: As2O3 + O2 = As2O5; As2O5 - O2 = As2O3. They assumed that the same thing happens in the body, resulting in a rapid 'stream' of oxygen atoms back and forth within the protein molecule. The different effects of various doses of Arsenic could be explained by the fact that small doses activate only a small amount of oxygen, which as a factor causing irritation, accounts for the phenomena of growth and nutrition, whereas medium and large doses produce correspondingly larger amounts of oxygen, which cause a significant intensification of oxidative processes, accompanied even by fatty degeneration and necrosis of tissues. This theory is disputed in regard to the validity of its factual data; moreover, according to it, ultimately the toxicity of arsenious acid and arsenic acid should be the same, whereas in reality the former is undoubtedly more toxic than the latter in experiments on mammals and especially on lower animals and plants. 3. Schmiedeberg (1906), and even earlier Hermann (1874), expressed the idea that the basis of Arsenic's action is its direct vasodilating effect on the walls of capillaries, especially in the area of the p. splanchnici. In small doses, moderate hyperemia of the intestine promotes enhanced delivery and absorption of nutrients, whereas paralysis of capillaries from toxic doses leads to blood stasis and disruption of nutrition with phenomena of inflammation and necrosis. This theory is not applicable to the paralytic form of acute poisoning, where, as mentioned above, hyperemia of the intestine may not be present; on the other hand, there is also no evidence of the direct paralyzing effect of Arsenic on the central and peripheral nervous system. 4. According to the hypothesis of Loewi (1907), the basis of Arsenic's action is its effect on metabolism: suppression from therapeutic doses and sharp intensification from toxic doses. However, the question of Arsenic's effect on metabolism is still not clear, and moreover, even when accepting this hypothesis, one cannot explain the entire picture of its action, for example, the phenomena of acute poisoning. 5. According to the view of Cushny, Arsenic has a selective and specific action on the epithelium of the digestive tract, which manifests as early fatty infiltration and cloudy swelling of the epithelium of the stomach and intestines with toxic doses of Arsenic; with therapeutic doses, this manifests to a different degree and in a different character, beneficial for the nutrition of organs and tissues. This view requires confirmation. For therapeutic purposes, Arsenic has been used since ancient times. In veterinary practice, it has been prescribed since ancient times against worms, scabies, and as a plasticum (cauterizing agent). It was introduced into medicine later, since in 1707 the prominent clinician Stahl wrote in his 'Teoria medica': 'De cura per arsenicum nihil dicam, quia non decet medicum honestum'. At the end of the 18th century (Fowler; 1776), Arsenic was introduced into therapy as a remedy against malaria. In 1887, Bromwell established its favorable effect in malignant malaria.

76ft» in the blood. Subsequently, inorganic compounds of A. began to be widely used for all types of anemias, and only much later (end of the 19th century) organic compounds appeared on the scene with their parasiticidal effect. A. is used very widely for various diseases. In small doses, it is readily prescribed (usually with bitters) to increase appetite and improve general condition. It is prescribed for various types of anemia, leukemia, initial stage of pulmonary tbc, for chronic (and sometimes acute) forms of malaria, often with great success in trypanosomiasis, for syphilis (in combination with mercury, in the form of Donovan's solution, etc.), in a number of nervous (persistent cases of chorea, nervous asthma, neuralgia, various forms of neurasthenia) and skin diseases (persistent chronic eczema, in large doses - for psoriasis, lichen ruber). Externally, it is used as a caustic for lupus and carious teeth (to destroy the pulp and nerves). In most cases, oral administration of A. begins with small doses, which are gradually increased; it is given during and after meals (if given with bitters, then before meals) for a long time (4-5 weeks). Care is taken not to give it in cases of irritation of the stomach and intestines, as well as during acute febrile conditions (except malaria). Despite the wide and often successful use of A. in medicine, analysis of its therapeutic action encounters great difficulties in many respects. The oldest indication for prescribing A. is various types of anemia. Although a beneficial effect is often noted in this case, systematic examination of the morphological picture of the blood of patients shows that the number of red blood cells often does not increase, but even decreases, the number of leukocytes does not change significantly in any case, and an increase in hemoglobin content does not always occur. The success from the use of A. often manifests itself a long time after its administration has been stopped. Experiments on animals gave extremely contradictory results by different authors. The essence of A.'s action is interpreted in different ways. Bettmann believes that A. increases the breakdown of blood on the periphery, as a result of which regenerative phenomena in the bone marrow arise reactively, which lead to increased formation of new red blood cells. Shustrov (see Anemia) also considers A. a hemolytic poison, but attributes its irritating effect on the bone marrow only to small doses. On the contrary, Gunn believes that A. increases the resistance of red blood cells to hemolytic substances (in his experiments - to water, bile salts, cyclamen). According to Isaak, regeneration of blood from arsenic is carried out through the thyroid gland (increase in the hormonal activity of the latter). Some authors also admit the possibility of parasiticidal action of arsenic on some unknown causative agents of anemia. All these hypotheses are disputed to a greater or lesser degree. With regular long-term administration of small doses of A., an increase in bone growth in length and thickness, deposition of subcutaneous fat, and an increase in body weight are noted. This phenomenon was considered a result of slowing down metabolism, i.e., increasing assimilatory processes due to a decrease in oxidation processes caused by A. The clearest decrease in basal metabolism from A. was observed with its pathological increase (hyperthyreosis), which, as is known, served as the basis for using small doses of A. simultaneously with thyroidin to reduce the excessively stimulating effect of the latter on metabolism. However, many authors deny the specificity of such an action of A. on body cells, since this is contradicted by many experiments on animals and observations on humans. Here one must take into account the property of A. to increase appetite and thirst, enhance the secretion of gastric and intestinal juices, cause hyperemia of the intestines, which can lead to improved digestion and more complete assimilation of abundant food, and hence to improved general condition of the body. Apparently this action manifests itself only in the presence of corresponding (as yet unknown) conditions in the body, since a number of authors did not observe it in their experiments. In connection with this kind of view of the nature of A.'s action, its beneficial effect in external and internal use for various non-parasitic chronic skin diseases, as well as for improving nutrition of the skin and hair, is explained in a similar way. Small doses of A. are attributed to the so-called tonic effect on the cell, which is understood as a more distinct manifestation of its functions. For example, experiments in vitro (Neiman) show a stimulating effect of weak concentrations of A. on the growth of connective tissue. It is possible that this kind of action underlies the improvement under the influence of A. of various functional disorders of the nervous system, neuralgia and chorea. Aqueous solutions of inorganic compounds of A. have long been known for their anti-putrefactive and fermentation-limiting action. The strength of their action is still weaker than that of inorganic compounds of mercury. Attempts to use inorganic compounds of A. for infectious diseases (syphilis, malaria and others) failed, since therapeutic doses proved dangerous for the macroorganism (humans, animals). A huge step forward in this respect was made with the introduction into therapy of organic compounds, in which the difference between therapeutic and toxic doses is much greater. (For more details - see Salvarsan.) These properties of organic compounds of A. have elevated them to the rank of so-called etiotropic agents, of which, as is known, there are very few at the disposal of modern clinics. Habituation to A. With repeated intake of small doses per os, an increase in tolerance to this poison is noted to such an extent that subsequently toxic doses do not have a harmful effect. This fact is well known not only from clinical practice, but also from observations on so-called "arsenic-eaters" (e.g., in Styria and Tyrol), who for the purpose of strengthening the general condition take 1-2 times a week in gradually increasing doses significant amounts (up to 0.05-0.42 g per day) As₂O₃ in substance. Undoubtedly, A. taken in this form is absorbed into the blood, as it has been found in the urine. Such habituation is observed only with respect to solid (powdered) forms of A. administered per os; but in experiments on dogs accustomed to powdered arsenic, it turned out that per os administration of 1/7 of a well-tolerated powdered arsenic causes typical symptoms of fatal poisoning. Similarly, subcutaneous administration of A. in all accustomed animals shows that we do not have habituation of all body cells. It is believed that the cause of habituation is an increase in the resistance of the gastric and intestinal mucosa to the inflammatory and necrotizing effect of A. As a result, the absorption of powdered A. becomes relatively less (Joachimoglu). At the same time, the intestinal mucous membrane produces so little alkaline juice that it is unable to dissolve all the introduced powdered As₂O₃, resulting in limited absorption of the introduced A. Increased absorption will occur only when the solution of As₂O₃, reaching the intestinal canal, due to local irritation will cause abundant secretion and exudation, which will lead to the dissolution and absorption of large amounts of powdered arsenic in the intestine and the appearance of toxic symptoms (Issekutz, Vegh). Thus, with habituation, the absorption of small doses of the poison by the intestine does not decrease (as Cloetta believed), but the poison introduced in large quantities is not completely absorbed due to local changes in the intestine. But this habituation is limited, since large doses can still cause poisoning symptoms. This explains the fact that administration of A. in liquid (i.e., rapidly absorbable form) causes symptoms of acute poisoning. - Sudden cessation of A. administration in accustomed people and animals does not cause any unpleasant symptoms of so-called "withdrawal" (abstinence). Acute poisoning. A toxic dose of A. in the form of As₂O₃ per dose for an unaccustomed person can be considered about 0.01; with idiosyncrasy, toxic effect was observed already from 1 mg. Fatal doses - from 0.06 g to 0.1 g, but recovery can occur after larger doses (after swallowing large pieces with subsequent vomiting). Mortality from acute poisoning is 50-75% (Levin). Dry As₂O₃ or ordinary white A. is so slowly soluble that its toxicity is strongly influenced by the degree of grinding of the powder; e.g. 500 times more coarse powder than solution is required to cause vomiting. Poisonings with A. solutions have a worse prognosis, as they are absorbed faster. In former times (especially in the 17th century) A. was very often used for the purpose of murder, suicide and abortion. For murder, compounds of A. were usually mixed with food, since A. has a pleasant sweetish taste and therefore probably is not detected so easily by victims as other poisons. Since the 19th century, murders with A. have become rare.

This can be explained by the perfection of the chemical methods for its determination, which allow the detection of minimal traces of arsenic. However, accidental poisonings have become less frequent because the arsenic preparations sold (over the counter) must, by the laws of various countries, be covered with either soot or indigo, due to which they lose the appearance of a white powder. This is also important for the diagnosis of poisoning (color of vomit). But still, accidental poisonings or poisonings with suicidal intent are now frequently observed, since arsenic is widely distributed, easily obtainable, and often used as a poison against rats and flies, in painting, etc. The sale of Paris green is unlimited. Many commercial cosmetic preparations contain arsenic. The use of arsenic compounds, such as Schweinfurt green, as paints is absolutely prohibited, but a large number of coal tar dyes, which are now so widely used in practical medicine, are impure and very often contain arsenic: phenolphthalein, phenol sulfonphthalein, phenoltetrachlorophthalein, fluoresceins (uranin, eosin, erythrosin), methylene blue, indigocarmine, flavins (trypaflavin, acriflavin), rosaniline, gentian violet, etc. Fruits after the application of arsenic for spraying to remove insects (Bordeaux mixture, arsenic lead) contain arsenic (or Pb) for a long time, but usually in quantities that have no toxicological significance. Acute poisoning occurs in 2 forms. The gastrointestinal form is most frequently observed; after 1/2 - 1 or more hours after taking arsenic, a metallic taste appears in the mouth, dryness and burning in the pharynx and along the esophagus, difficulty swallowing, severe abdominal pain, repeated persistent vomiting, sometimes with vomit having a garlic odor (probably from the reduction products of As2O3); unbearable thirst, dizziness, headache; after several hours, a cholera-like but painful diarrhea (stools like rice broth, consisting of shreds of exfoliated mucous suspended in a large amount of serous fluid) followed by phenomena of great loss of fluid by the body (sunken face, deeply sunken eyes, hoarse voice or aphonia, dry skin, oliguria or anuria, protein, cylinders, erythrocytes in the urine), cramps in the calf muscles, cyanosis, cooling of the extremities, fall in blood pressure due to paralysis of the capillary walls (mainly in the area of the splanchnic plexus) and their increased permeability, with secondary weakness of the heart muscle. Before death, there are syncope, coma, clonic and tonic convulsions, and general paralysis. Death usually occurs after 1-2 days (sometimes after only 12-18 hours). With a non-lethal dose or when a significant amount of the poison is removed by vomiting, the picture may be limited to the initial symptoms of poisoning and end in recovery or transition to a state of chronic poisoning. In the subacute form of poisoning, the main phenomena are from the mucous membrane of the digestive tract. Inflammation of other mucous membranes (conjunctivitis, runny nose, stomatitis, pharyngitis) is also striking. With prolonged course, skin rashes, symptoms from the nervous system (neuritis) may appear. The patient often lives for 2-4 or more (up to 14) days and then dies from exhaustion as a result of prolonged gastroenteritis. - On autopsy: the gastric mucosa is markedly hyperemic, swollen, covered with viscous mucus in which crystals of arsenic can be found; in places where particles of arsenic have adhered (fundus, posterior wall of the stomach), hemorrhages, inflammation, and defects of the epithelium, but without signs of deep cauterization. The mesenteric vessels are filled with dark, thick blood. The intestinal wall is hyperemic, edematous; the exfoliated mucous membrane is covered with a pseudomembrane consisting of fatty-degenerated epithelium, serous and fibrinous exudate; there are ecchymoses, hemorrhages, and even ulcers in places. In the kidneys, signs of inflammation. In the subacute course of poisoning - fatty degeneration of the intestinal glands, liver, heart muscle, walls of small arteries, and numerous ecchymoses in various organs; disappearance of the subcutaneous fat layer; in the digestive tract - the phenomena described above; under the microscope - gastritis and cellular infiltration. - The paralytic form of acute poisoning is observed much less frequently; it occurs mainly when very large quantities of arsenic are absorbed in a short time; its symptoms are as follows: general weakness, feeling of fear, trembling, painful twitching of various muscle groups, convulsions and finally due to the rapid accumulation of blood in the abdominal cavity and fall in blood pressure - sudden collapse, delirium, loss of consciousness and coma; breathing stops before the heart (asphyxia arsenicalis). Death occurs before the development of enteritis symptoms (after 1-24 hours). On autopsy, there are no characteristic changes. After arsenic poisoning, bodies usually decompose very slowly and can even (rarely) be mummified (compare the frequent use of arsenic in embalming compositions). Treatment of acute poisoning. The best results are given by emetics (apomorphin under the skin), repeated stomach washing (with warm water or a solution of 20.0 calcined magnesia in 1,000 cm3 of water), performed repeatedly (arsenic is poorly soluble and even with vomiting the stomach is still not sufficiently emptied), and laxatives. After washing, give internally, after shaking, 1 teaspoon every 5 minutes until vomiting stops, the arsenic antidote, Antidotum Arsenici (Ph VII) - an official, prepared ex tempore preparation: to 100 parts of a solution of ferrous sulfate (oxide, sp. gr. 1.428 to 1.430), diluted with 300 parts water, add gradually 20 parts of calcined magnesia ground in 300 parts water, shaking vigorously until a uniform brown turbid mixture is obtained. The dose of the obtained preparation is calculated to form a difficultly soluble compound with arsenic and prevent its absorption. This antidote was introduced into practice in 1834 by Bunsen and Berthold on the basis of the fact that As2O3 in vitro forms with iron hydroxide an insoluble compound FeAsO3. It should be borne in mind that this antidote cannot be particularly relied upon, since new experimental data have shown that it delays death by a maximum of several hours and only slightly reduces the mortality rate, and the difference lies within the limits of experimental error. It must be thought that this antidote, like some colloids (milk, protein, mucous drink), interferes with the absorption of arsenic; therefore, their administration makes sense only if it is necessarily accompanied by sufficient removal of the poison (washing, emetic). Calcined magnesia with water (90.0 : 200.0) is also used, a tablespoonful repeatedly every 15 minutes. In collapse - inject caffeine, camphor, digalen under the skin; on the abdomen - hot fomentations; for convulsions of the extremities - rubbing them, warm baths. Chronic poisoning can be the result of taking a single large dose, but more often it is caused by prolonged absorption of small amounts of arsenic entering the body through the respiratory or digestive tracts: in the form of fine dust coming from walls (see Wallpapers) or from other objects (animal specimens, fabrics, etc.) or in liquid form: in wine (e.g., epidemic in Heyres in France), in beer (a large epidemic in northern England in 1900), in milk diluted with arsenic water (mass poisonings in London), in food. In addition, chronic poisoning is often one of the types of so-called professional poisoning (see below). Brouardel and Pouchet, based on the analysis of 400 cases of poisoning with wine containing arsenic, divide the course of chronic poisoning into 4 'phases' or stages: the first phase - phenomena from the digestive tract: loss of appetite, heaviness and unpleasant sensations in the stomach, frequent nausea, tendency to vomit, irregular defecations, fluctuating between diarrhea and constipation, general weakness; diagnosis is facilitated by the detection of arsenic in the urine. The second phase gives more characteristic symptoms from the mucous membranes and skin: conjunctivitis, dryness in the nose and pharynx or, conversely, runny nose with viscous mucous secretion and sneezing, hoarseness (tracheitis), cough (bronchitis). Various skin lesions: arsenic melanosis - limited or diffuse pigmentation from light brown to almost black color. Hyperkeratoses of the palms and soles of the feet (see Keratoses) are considered particularly characteristic, due to which the epidermis peels off in thin brown scales or even in large plates; polymorphic rashes: papules, vesicles (like herpes zoster, but only on the face and extremities, not on the chest and back), erythemas; characteristic pigmentation of the skin, taking on a dark metallic color; in extreme forms, great resemblance to the color caused by rubbing the skin with a lead pencil (melanosis arsenicalis); with prolonged poisoning, hair and nails fall out, liver swelling and jaundice may occur, but they are not always well noticeable. The third phase is characterized by lesions of the central and peripheral nervous system with motor and sensory disorders. As a precursor - persistent headaches or acute pain around the knee or ankle joint.

The palms of the hands and soles of the feet are often red, swollen, and extremely sensitive to touch (erythromelalgia), and pressure on the muscles causes very severe pain; complaints of a sensation of crawling ants and other paresthesias, disorders of pain._; thermal and other types of sensitivity. Later, sensory paralysis (paralysis arsenicalis) occurs, most often in the extremities, especially in the lower ones. In severe poisonings, sensory disorders are accompanied by motor paralysis, usually symmetrical, progressing with rapidly developing muscular atrophy, presence of degeneration reaction (apparently from peripheral neuritis) and contractures. As a general rule, paralysis is limited to the extremities, but in some cases it also affects the trunk. With widespread anesthesia of the lower extremities, gait becomes unsteady and ataxic (tabes arsenicalis). Paralysis of the vocal cords (aphonia arsenicalis) is often observed, changes in sexual sensation—either fading (anaphrodisia arsenicalis) or sharp intensification. Paralysis can occur as early as 3 days after acute poisoning, but may also appear later (after 3-4 weeks). With very prolonged poisoning, an apathic state sets in, reduction of mental abilities to a semi-idiotic state, sometimes seizures similar to epileptic ones. The fourth phase (terminal) is expressed by the following phenomena: after repeated attacks of shortness of breath, death occurs from paralysis of the heart or are preceded by dropsy and marasmus, as a result of fatty degeneration of internal organs (especially the liver, kidneys and heart). The diagnosis of chronic poisoning with M. is often extremely difficult, since the described symptoms are not always bright, the given sequence of phenomena is often disrupted, a number of symptoms give reason to confuse with chronic lead poisoning; for differential diagnosis from the latter, the following differences are important: frequency of paralysis of the calf muscles (with lead, the areas of the forearms); atrophy appears more quickly, there are no blue lines on the gums, in the history there is often acute poisoning (with lead, almost always prolonged absorption). Alcoholic neuritis rarely occurs with skin rashes, runny nose is absent, brain symptoms are more noticeable. In doubtful cases, the urine and hair of the patient should be tested for M. In excretions and in the body (especially in bones and liver), M. is preserved for a very long time.-Treatment of chronic poisoning: removal of the cause, increased excretion of M. by prescribing diuretics, mineral waters, acids, ammonium chloride, soda, potassium iodide. Paralysis is treated by stimulating the muscles with galvanic current, other symptoms—with appropriate general strengthening treatment. Methods for detecting arsenic. Large amounts of M. can be detected by the garlic odor that comes from the blowpipe containing arsenic. Biginelli considers this odor to be the result of the formation of diethylarsine (C₂H₅)₃AsH, while Klason considers it ethylcadmium oxide [As (C₂H₅)₂]₂O or As₂(CH₃)₄O. Such a smell is produced by certain mold fungi (individual species of Aspergillus, Mucor, Penicillium brevicaule) on a nutrient medium containing M., which can be used as a "biological test" for M. (even 0.02 mg M. is detected). This test is especially suitable for determining M. in scales of skin, hair, sweat and urine. For chemical determination of M., several tests have been proposed. 1. Betendorf's test consists in the fact that compounds of M. are reduced in a solution of strong hydrochloric acid by tin chloride, with elementary M. being released as a dark precipitate, and in the case of the presence of a small amount of M., darkening of the solution occurs, depending on the formation of a colloidal solution of M. The test gives reliable results only in the absence of sulfur compounds and salts of sulfurous, sulfuric and nitric acids, as well as compounds of mercury, gold and selenium. The procedure for the test is described in FUP. 2. If sulfuric acid salts are present, then in the absence of antimony for the detection of M., Gutzeit's test is used, based on the fact that arsine with silver nitrate gives yellow arsenic silver AsAg₃, which with further action of moist arsine turns black with the formation of elementary silver. The procedure for the test is described in FVII. Although this test is the most sensitive of all tests for M., it has the significant inconvenience that the presence of minimal traces of hydrogen sulfide makes its results incorrect. 3. For determining small amounts of M. (in poisonings, etc.), the so-called arsenic mirror is used, obtained with the help of Marsh's apparatus. 4. For determining minimal amounts of M. in urine, blood, meat and other organic substances, Lokeman proposed his method of destroying the organic substance by treating it with only a few cm³ of a mixture of 9 parts of fuming HN0₃ and 1 part of concentrated H₂S0₄ (acid treatment) and then fusing with potassium-sodium nitrate (nitrogen fusion). In this way, all organic substances are completely destroyed, and all M. is converted to potassium arsenate, which then precipitates from the aqueous solution with the help of iron hydroxide and is determined quantitatively. 5. Pedersen proposed for determining M. in beer to treat the latter (after removal of CO₂) with concentrated HN0₃ and H₂S0₄ with careful subsequent heating and repeated boiling with ammonium sulfate. The resulting mixture is tested in Marsh's apparatus. This test can determine 0.01 mg M. in 100 cm³ of beer. It turned out that English beer of various varieties contains from 0.005 mg to 0.01 mg M. per 100 cm³, while Danish beer contained none at all. In addition to those mentioned above, there are many other methods for quantitative determination of minimal amounts of M. (for a summary, see Autenrieth). Detection of M. in urine. Heat 10 cm³ of urine with 10 cm³ of concentrated H₂S0₄ and 20 drops of fuming HN0₃ until HN0₃, H₂S0₄ are removed; then allow to cool, after which add 20 cm³ of water and heat again until H₂S0₄ is removed; then dilute with 50 cm³ of water, cool and the resulting solution is tested for M. by Gutzeit, Betendorf or Marsh (see above). Preparations. 1) Acidum arsenicosum anhydricum (FUP), s. acidum arsenicosum, arsenious anhydride As₂0₃; molecular weight 197.92. Heavy, white, porcelain-like or glassy pieces, often of layered structure with a conchoidal fracture (or a heavy powder prepared from such pieces). Very slowly dissolves in 65 parts of cold and 15 parts of boiling water. Solutions give a weakly acidic reaction to litmus. Easily dissolves in hydrochloric acid, as well as in solutions of caustic alkalis and alkali metal carbonates. Internally mostly in pills of 0.0005-0.002 pro dosi. According to FUP, maximum doses: 0.003 per dose and 0.01 per day. Externally—in the form of a paste as a cauterizing agent for cancer, lupus, phagedenic ulcers, together with novocaine and creosote for destroying the dental pulp and nerve (Ac. arsenicosi, Novocaini aa 1.0, Kreosoti q. s. ut f. pasta).- 2) Liquor Kalii arsenicosi (FVII); synonyms: Solutio arsenicalis Fowleri, Liquor arsenicalis Fowleri, solution of arsenic potassium salt or Fowler's arsenic solution. Consists of arsenious anhydride in powder (1 part), pure potassium carbonate (1 part), water (83 parts), lavender alcohol (15 parts). The solution contains 1% arsenious anhydride; in each drop of the solution 0.0005 Ac. arsenicosi. A transparent, colorless liquid, of aromatic odor, alkaline reaction. Internally 2-5 drops or more twice a day (often with bitters). Maximum doses (FUP): 0.2 pro dosi and 0.6 pro die.-3) Chininum arsenicosum, arsenic quinine 3Ca₀H₂₄N₂O₂ + H₃AsO3+4H₂O. Molecular weight 1170. Long needles, difficultly soluble in water, easily soluble in alcohol, ether and chloroform. Occasionally used in malaria.-4) Natrium arsenicicum (FUP), sodium arsenate, Na₂HAs0₄.7H₂O; molecular weight 312. Colorless crystals without odor, efflorescing in warm dry air, soluble in 1.64 parts of cold water, extremely easily soluble in hot water, soluble in 2 parts of glycerin, almost insoluble in alcohol. Solutions have an alkaline reaction. Contains 40.4% water, 36.8% As₂0₅=31.7% As₂0₃. Used internally in doses of 0.001-0.002. Maximum doses (FUP)- 0.003 pro dosi and 0.01 pro die. Under the skin, 0.2-1 cm³ of a 1% solution in a ¹/₄% solution of Ac. carbol. (formula of Prof. Golubov's clinic).-5) Liquor Natrii arsenici, s. Solutio arsenicalis Pearsoni, aqueous solution of sodium arsenate in variable ratios (1:100- 1:500).

Orally, 10-20 drops up to 60 drops pro die. More suitable for subcutaneous and intraparenchymal injections than Fowler's solution, as it does not irritate. - 6) Ammonium arsenicicum, ammonium arsenate (NH₄)₃AsO₄; molecular weight 193. White crystalline powder, easily soluble in water. Rarely used by itself, more often in the form of Liquor arsenicalis Bietti, consisting of Ammonii arsenicici 0.2, Aquae dest. 100.0. 10-45 drops 2-3 times a day. --7) Natrium kakodylicum (FUP), sodium cacodylate (CH₃)₂AsO₂Na·3H₂O; molecular weight 214.1. White crystalline powder that easily deliquesces in air, almost odorless, easily soluble in water and in alcohol. Orally in pills or in aqueous solution (2%, 1 cm³ per day). Maximum doses (FUP): 0.06 pro dosi and 0.2 pro die. -8) Solutio triplex (preparation of the medical supply factory in Leningrad) consists of Strychnini kakodylici 0.0005, Natrii kakodylici 0.05, Calcii glycerophosphorici 0.1. In ampoules of 1 cm³ for daily subcutaneous injections. -9) Ferrum kakodylicum, cacodyliron [(CH₃)₂AsO₂]₂Fe; molecular weight 467. Yellow, yellow-brown powder, soluble in water, almost insoluble in wine alcohol. Orally 0.05-0.3 pro die or under the skin 0.03-0.1 pro die (especially often in chlorosis and its consequences). -10) Atoxyl, s. Natrium arsanilicum, sodium aminophenylarsonate NH₂·C₆H₄·AsO₃HNa [1,4]+4H₂O; molecular weight 311. White crystalline powder, sour taste, soluble in approximately 6 parts water, easily in hot water. In dry air it loses its water of crystallization. In aqueous solution when heated it gradually passes into aniline and sodium arsenite. Contains 24.5% As. Used especially in sleeping sickness, syphilis, malaria, etc. 0.02 pro die under the skin (not given per os) every other day, gradually increasing if necessary to 0.65 pro dosi and to 6.5 for the entire course of treatment. Due to severe poisoning phenomena, it is now almost never used. - 11) Argentum arsanilicum, silver aminophenylarsonate C₆H₄(NH₂)AsO₃HAg; molecular weight 324. White crystalline powder, insoluble in water, soluble in dilute HNO₃. Contains 25% As and 33% Ag. Used in gonorrheal and septic diseases in an oil emulsion 1:10 in the muscle 0.5-0.75 pro die. - 12) Hydrargyrum arsanilicum, mercury oxide arsenilate [NH₂C₆H₄AsO(OH)]₂Hg; molecular weight 632. White powder, insoluble in water, soluble in hydrochloric acid and in NaCl solutions. Gradually turns gray in light. Contains 23.7% As and 31.6% Hg. Used against syphilis, under the skin, starting with 0.005 and increasing to 0.1 triturated (1:9) with Olivarum or other fatty oil. - 13) Arsacetin, s. Natrium acetyl-arsanilicum, sodium acetylaminophenylarsonate CH₃CO·NH·C₆H₄·AsO₃·HNa+4H₂O; mol. wt. 353. White crystalline powder, soluble in 10 parts cold water and in 3 parts boiling water. Due to its stability, it can be sterilized without decomposition; used under the skin (in 10% aqueous solution), starting with 0.02 and rising to 0.1 several times a week, orally 0.05 three to four times a day. -14) Ar-rhenal, s. Natrium monomethyl-arsinicum, sodium methylarsinate, CH₃AsO₃Na₂+5H₂O; molecular weight 274 (or 292). Colorless crystals, easily soluble in water (1:2), poorly in wine alcohol. Orally or under the skin 0.025-0.1, preferably 0.05 pro die for 5 consecutive days, then a week's break to avoid harmful effects. -15) Neo-Arsenodile (factory Leprince, Paris and Block, Basel), sodium monomethylarsinate (synonym of ar-rhenal). Sold in pure form or in pills (0.025 each) and ampoules (0.05 each). -16) Arsamon, ready-to-use 5% solution of sodium monomethylarsinate in ampoules of 1 cm³ (0.05 g). Contains 27% arsenic. Under the skin or in the muscle 0.5 - 1 cm³ every 1 - 2 days for several consecutive weeks. - 17) Solarsone, solution of the monoammonium salt of heptinchloroarsinic acid CH₃(CH₂)₄·CCl₂·CH·AsO(OH)ONH₄ in physiological NaCl solution with 1% heptinchloroarsinic acid. 1 cm³ of solution contains 0.003 As. Used under the skin as a replacement for cacodylate salts. -18) Optarson, a combination of solarsone with strychnine: in 1 cm³ of solarsone - 0.001 Strychnini nitrici. Used under the skin. - On arsenobenzol preparations see Salvarsan. Of mineral waters containing As (also iron), are known: Levico -in the so-called "strong" water 6 mg, and in the "weak" one - 0.9 mg As per 1 l; Roncegno contains in 1 l 10 mg sodium arsenite and 11 mg As₂O₅; Durkheimer Maxquelle (17.4 mg As₂O₃ per 1 l), Mont Dore (5-6 mg As₂O₃ per 1 l), La Bourboule (28 mg As₂O₃ per 1 l), etc. - Some compounds of As, such as diphenylchloroarsine, diphenylaminochloroarsine, diphenylcyanoarsine, etc., have found application as poisonous warfare agents (see Chemical Warfare Agents).

M. Nikolaev. Discovery in legal cases and in protection against professional poisoning. For M., the internal organs of corpses, human secretions (urine, etc.), and the air of work premises are examined. To discover M. in internal organs, the organic matter is destroyed (see Poisons, isolation). The resulting liquid | is saturated with hydrogen sulfide under appropriate conditions. The precipitate of sulfides is treated with excess ammonia, which dissolves arsenic sulfide. The ammonia solution is evaporated on a water bath, the residue is treated with nitric acid, evaporated, and rubbed with dry soda; the mixture is added in small portions to a porcelain crucible containing a small amount of molten sodium nitrate. The addition of the mixture is regulated so that there are no flashes and no carbon accumulates in the crucible (the crucible is weakly heated). After cooling, the alloy is dissolved in water, the solution is filtered, mixed with moderately diluted sulfuric acid, and evaporated in a porcelain dish on a flame with a mesh until all the water (from which nitrogen oxides and nitric acid are removed) has evaporated and heavy sulfuric acid vapors begin to be released. After cooling, a drop of the solution is tested with diphenylamine for nitric acid. If present, the sulfuric acid solution is again mixed with water and evaporated. In the absence of nitric acid, the solution is mixed with ten times its volume of water and tested in a Marsh apparatus (more precisely, the Marsh-Liebig-Berzelius apparatus in modern modifications). The principle of the test consists in obtaining arsenic hydride from M. compounds (by the action of dilute sulfuric acid on zinc) and in its detection. 1) The hydrogen coming out of the apparatus in a mixture with arsenic hydride is ignited (with large amounts of arsenic, the colorless hydrogen flame takes on a bluish tint, and a garlic odor is perceived). When cold porcelain objects (small cups, crucible lids) are introduced into the flame, brown, shiny spots are obtained on the porcelain (arsenic mirror). This test constituted the original Marsh method. 2) The outgoing hydrogen is passed through a solution of silver nitrate (containing a small amount of ammonia): this results in the reduction of metallic silver—darkening of the solution. 3) The most important test in terms of sensitivity and evidentiary value in forensic chemistry is passing the mixture of hydrogen and arsenic hydride through a refractory tube heated at one point. Behind the heated point, in its narrowed portion, a grayish-brown deposit of metallic M. [and solid arsenic hydride (AsH)n] is formed due to decomposition: 2AsH₃-> 2 As+3H₂. The simplest form of the Marsh apparatus is a small Erlenmeyer flask (capacity not more than 100 cm³; increasing the volume reduces the sensitivity of the method) with a cork stopper, through which a dropping funnel and a tube bent at a right angle are inserted, connected to a calcium chloride tube; from the latter, a reduction tube of refractory glass is connected with black rubber. The reduction tube is narrowed in one or more places. 10 g of 'forensic chemical' copper-plated zinc is placed in the flask (copper-plating of zinc consists of immersing it in a ¹/₂₀% solution of copper sulfate for one minute and washing with water) and 'forensic chemical sulfuric acid' (diluted with 8-10 parts water) is added. After displacing the air from the apparatus, the hydrogen is ignited at the outlet of the reduction tube and the reduction tube is heated to red heat before the narrowed portion. The narrowed part of the tube is wrapped in a piece of wet cotton. After a short time, a brownish-gray deposit is observed in the narrowed part of the tube. In the absence of a deposit, the test is begun, gradually adding the test liquid, and first, moving the burner away from the heated part, one observes whether the flame is colored bluish and whether there is a characteristic garlic odor. Then porcelain crucible lids, porcelain cups, etc., are introduced into the flame. With large amounts of M. (several mg), brownish-gray shiny metallic deposits are obtained on the porcelain. Next, the reduction tube is heated to red heat before the narrowed portion. If no deposit forms quickly, the test is continued for an hour. Finally, the reduction tube is turned and its extended end is dipped into a solution of silver nitrate containing ammonia: a browning occurs due to the precipitation (reduction) of metallic silver. The Marsh method (2nd and 3rd tests), being more sensitive, makes it possible to detect thousandths of a milligram, but preliminary precipitation with hydrogen sulfide limits the sensitivity of the method to the detection of tenths of a milligram, which is important for forensic chemical analysis, because due to the widespread presence of M., it would be detected almost everywhere with high sensitivity. The obtained result must be verified: the reduction tube is separated from the apparatus and, held at an angle, carefully heated at the site of the deposit: M. sublimes in an air current, depositing in the cold part as a white layer of arsenious anhydride (As_a0₃). Under the microscope, the crystalline structure of the deposit is visible (octahedra). When dry hydrogen sulfide is passed through the reduction tube, the white deposit turns yellow (arsenic sulfide). Subsequent passage of dry hydrogen chloride does not change the color of the yellow deposit. Deposits on porcelain dissolve in freshly prepared sodium hypochlorite solution (NaOCl) (difference from antimony!). On the other hand, when M. is present in the test object, deposits may not form 1) in the presence of oxidizers, for example nitric acid; 2) in the presence of significant amounts of salts of heavy metals (mercury, copper, iron, etc.); 3) in the presence of selenium in the sulfuric acid; 4) when sulfuric acid is reduced to hydrogen sulfide, which can occur when the liquid is heated in the reaction flask and when using a more concentrated sulfuric acid than 1 part acid to 8-10 parts water. For 'quantitative determination with large amounts of M., it is precipitated with magnesium mixture and weighed as pyroarsenic magnesium, Mg₂As₂0₇', with small amounts, iodometric determination in 33% sulfuric acid (H₃As0₄+2HJ^>H₂0 + J₂ + H₃As0₃). When discovering M. in u r i n e, the latter is evaporated, organic substances are destroyed with sulfuric acid and ammonium nitrate (see Poisons, isolation), and then proceeding as described above. The procedure for discovering M. in urine is similar to that for discovering M. in food and flavor products, hair, etc. When discovering M. in air, the first consideration is finding it in the form of arsenic hydride, formed by the action of more or less diluted acids containing M. on metals: iron, zinc, etc. To discover arsenic hydride, a certain volume of air is passed through washing bottles with bromine water. The bromine water is evaporated, the residue is dissolved and diluted with 'forensic chemical pure sulfuric acid' and tested in the Marsh apparatus, if necessary applying quantitative iodometric determination.'

A. Stepanov. Arsenic as a professional poison. Arsenic and its compounds do not find wide application in industry, but due to the fact that arsenic as an impurity is contained in large quantities of ores (iron, zinc, lead, copper, etc.), in a number of metals, and in unrefined inorganic acids, it presents a danger to the health of workers in a significant number of industries. In industry, arsenious anhydride or white arsenic (As₂O₃) is most frequently used, and arsenic anhydride (As₂O₅) is used much less. Among the industries where these substances are used, shot-blasting, glassmaking (decolorizing glass), etching brass, and others should be mentioned. Among the salts of arsenic, Schweinfurt green, or Paris green, and Scheele's green, used for coloring wallpaper, paper, artificial flowers, etc., have special professional hygienic significance; realgar (As₂S₃) and orpiment (As₂S₃), painting pigments; sodium and calcium salts of arsenious acid, as well as lead arsenate (used as insecticides). As a by-product in metallurgy, arsenic trioxide plays a very important role: it is formed during the smelting of metals and roasting of ores, sometimes in very large quantities; for example, in lead smelters in Utah and Colorado (USA), the dust contains up to 60% arsenic. See Arsenic trihydride for the extremely poisonous AsH₃. Acute poisonings in industrial conditions are almost never encountered. Here, chronic poisonings occur almost exclusively, which manifest either as disturbances in the functions of individual systems, leading to general exhaustion of the entire organism (the gastrointestinal tract and kidneys suffer most strongly), or as specific localized diseases. The following disorders are most often observed: 1) From the gastrointestinal tract - stomatitis, gingivitis, dyspepsia, enterocolitis, etc. 2) From the nervous system - neuritis with various disturbances: sensory, trophic, motor; true paralysis is very rare. 3) The effect of arsenic most often manifests itself in the form of local lesions of the skin and mucous membranes of the upper respiratory tract. In acute cases, skin lesions are expressed in various types of rashes, mainly localized on sweating areas. In chronic poisoning, dermatoses take the form of keratoses, hyperhidrosis, pigmentation, and finally skin cancers. The question of the possibility of developing cancer as a result of the specific effect of arsenic has not yet been fully clarified: a number of authors believe that as a result of prolonged exposure to arsenic (10-20 years or more), epitheliomas develop, and Hopmann even considers arsenic directly the cause of new growths in workers in many other industries (in particular, he attributes bladder cancer in workers at aniline factories to its action). Guillaume considers all skin lesions in arsenicism as a result of photosensitization, with arsenic, obviously being the photosensitizer deposited in the skin. (Regarding new growths in workers in cobalt mines, where arsenic is also mentioned among the causes, see Cobalt.) On the other hand, data from Lehman on the morbidity of Dutch and Belgian workers and experiments by Leitch and Kennaway and others have not confirmed these assumptions. In recent decades, the number of arsenic poisonings has significantly decreased due to its elimination from a number of industries (in particular, it was previously used in the production of fuchsine); nevertheless, due to the production and use of the highly poisonous Schweinfurt green in a number of countries, it is still quite significant. Thus, in England for 1900-1913, 74 cases of arsenic poisoning were registered, of which 46 occurred in workers in the production of Schweinfurt green; Hamilton and others cite many cases of poisoning in the same production for the USA. In the USSR, cases of poisoning in shot-blasting production, where arsenic trioxide is added to lead, in chemical laboratories, and in glass factories have been described; for 1926/27, 11 cases of poisoning were registered, of which 7 were in shot-blasting. Poisonings have also been noted in workers fighting agricultural pests. Prevention. The most radical health measure is the replacement of arsenic in production with other non-toxic substances. This is especially important because it is extremely difficult to achieve complete sealing of the corresponding production processes (especially in paint production); next is the removal of dust by means of local ventilation; finally, personal prevention of workers is of extremely great importance; wearing impermeable special clothing and footwear, gloves or mittens, lubricating the skin with neutral ointments, frequent showers or baths. Special attention should be paid to the rational medical selection of workers and periodic monitoring of their health. In a number of countries, women and adolescents are not allowed to work in industries where they have to work with arsenic (a detailed list is in the article by Balthazard). In the USSR, according to the mandatory resolution of 19/X 1924 on the use of arsenic in production, women and adolescents are not admitted to work with arsenic or to premises where arsenic is used; for workers engaged in the mining and processing of arsenic in the production of arsenious compounds and a number of other professions where contact with arsenic is necessary, a 6-hour working day is established; workers in arsenic production must undergo regular medical examinations [not less than once every 3 months.

N. Rosenbaum, S. Brumstein. Arsenic in experimental pathology. Compounds of arsenic have been quite widely used experimentally in the study of certain questions in pathology. It is known that chronic irritations caused by compounds of As. can lead to the development of tumors. For example, there are observations of workers in the Schneeberg mines in Saxony, whose dust contains a significant amount of As. (15-20% As, 5-6% Co, 2-3% Ni). Among these workers, a mass incidence of cancer is noted; out of 23 autopsies, in 13 cases cancer of the lungs was found as a result of prolonged irritation from inhaled dust, and there is a hypothesis that As. plays an important role in this. In experiment, the so-called "cancerizing" influence of compounds of As. can be detected both in experiments on animals and in tissue cultures in vitro. Carrel, for example, by injecting into the breast muscles of chickens embryonic juice together with a solution of arsenic anhydride (1:125,000), obtained the development of a malignant tumor of the Rous sarcoma type, which kills the bird in 3-4 weeks and gives metastases to the liver, lungs, and spleen. Compounds of As. were also used along with tar in experiments aimed at obtaining skin cancers, and although the carcinogenic properties of As. were sharply inferior to those of tar, nevertheless in a small percentage of cases a positive result was obtained (Leitch, Kennaway). - Extremely interesting are experiments on the transformation under the influence of arsenic compounds of normal cells of tissue cultures into cells of malignant neoplasms. Thus, Carrel, by the action of arsenic on a culture of macrophages, succeeded in obtaining malignant cells that, when transplanted into an animal, produce a typical sarcoma. Fischer (A1. Fischer) repeated these experiments with cultures of fibroblasts by adding to them a solution of As₂O₃ (in a concentration of 10^-8 molar). He also obtained the transformation of cells into malignant ones, and along with an enhancement of enzymatic functions, the cells acquired the typical ability of cells of malignant neoplasms to infiltrate and grow into the normal muscle tissue implanted next to them. This property of compounds of As. is not a specific feature of them, since it is known that it belongs to an even greater degree to coal tar (see more in Tumors). Nothing is currently known about the mechanism of this cancerizing influence of compounds of As. Here it may also be mentioned about the special affinity of sarcoma cells for arsenic compounds, established by Blumenthal. Observations about the beneficial effect of arsenic compounds on the course of anemia have been known for a very long time, based until the end of the 19th century exclusively on clinical data, without precise accounting of the state of the blood and the reaction of the hematopoietic system. Research by Stefanelli, Baumann, and Bergmann, conducted on animals anemic from bloodletting, indicates that the activating effect of compounds of As. on the erythropoietic system is not particularly great, but it becomes significant with the simultaneous use of iron. Under such conditions, regenerative phenomena proceed better than with the administration of only iron compounds. Bergmann also notes a difference in the nature of regeneration. While the administration of iron promotes an increase in the content of Hb more than an increase in the number of red blood cells, arsenic acts in the opposite way: regeneration of red blood cells occurs faster than their hemoglobinization. Some authors note the ability of small doses of arsenic compounds, when administered to normal animals, to cause polycythemia. On leukoblastic tissue, small doses of As. also act as an activator and lead to the development of leukocytosis, while large doses of arsenic compounds cause hemolytic phenomena, destroy red blood cells, and lead to the accumulation of breakdown products of red blood cells in the cells of the reticuloendothelial apparatus. - The reaction of lymphatic tissue to the introduction of inorganic compounds of As. into the body was also studied experimentally (Watjen). It turned out that acute fatal poisoning of dogs and rabbits with As. is accompanied by severe degenerative phenomena and disintegration of cells, mainly of the germinal centers of follicles. These changes fully correspond to those that occur under the action of bacterial toxins. Both are of a non-specific nature and reduce to the necrotizing influence of these agents on the youngest formed elements of lymphoid tissue. Because arsenic hydride causes sharp hemolysis with phenomena of hemoglobinemia, this poison has been repeatedly used for the experimental study of the question of hemolytic (or so-called hematogenous) jaundice. Part of the Hb released during hemolysis from red blood cells is excreted by the kidneys (hemoglobinuria), while another part goes to the formation of bile pigments. Inorganic compounds of As. are also used in pathology as an agent causing degenerative-necrotic changes in parenchymatous organs. It is known that by poisoning animals with As., one can obtain parenchymatous changes in the liver, kidneys, heart, and other organs, starting from phenomena of cloudy swelling and fatty infiltration up to necrosis of cellular elements. The intercellular substance also changes, becoming loose, and the cellular elements are isolated from each other.