Contents

CHAPTER XIII

THE PHYSIOLOGICAL ACTION OF MISCELLANEOUS GASES

In the following pages is given a brief indication of the physiological action of a variety of gases possessed of possibilities as agents in chemical warfare. More detailed account of the physiological effects of the gases enumerated is not possible at this time, since extensive investigation in this direction has not been carried through.

CYANOGEN DERIVATIVES

CYANOGEN ¹ (CN)₂

In its action cyanogen belongs to the group of paralysants, and in general the symptoms produced are similar to those for hydrocyanic acid. The minimum effective concentration in animals is about 1 to 3,000, or 0.75 mgm. per liter of air for an exposure of 30 minutes. The minimum lethal concentration is 1 to 2,000, or 0.928 mgm. per liter. The gas is rather less poisonous than hydrocyanic acid.

SYMPTOMS IN ANIMALS

The symptoms produced after experimental gassing by cyanogen were rapid respiration, followed later by spasm and unconsciousness, during which the respiration became extremely slow and spasmodic in character. There were differences in the symptoms elicited by cyanogen and by hydrocyanic acid. With cyanogen there was an early stage of sneezing, lacrymation, and salivation arising from local irritation. The symptoms set in much later than was true for hydrocyanic acid. Spasms from hydrocyanic acid began within a few minutes after contact with the poison; that is, while the vapor was present in full strength. The cyanogen spasm at low concentrations began only about 20 minutes after the administration, the animal remaining practically normal during the latent period, except for the symptoms of local irritation. The whole train of events suggested that possibly the cyanogen was rather slowly transformed to hydrocyanic acid in the tissues and that the intoxication was due to the cyanide rather than to the cyanogen. Animals quickly recovered (except for some soreness of the eyes) when they were withdrawn from the poisonous atmosphere as soon as spasms began and some warning was given by the extraordinary quick, panting respiration.

HYDROCYANIC ACID ² (HCN)

In animals (mice and dogs) this substance acted by a short preliminary stimulation, followed by paralysis of the nervous system. Death was caused by failure of the respiratory functions due to a paralysis of the respiratory center. It was not a lung irritant or lacrymator, but acted only after absorption into the circulation.

SYMPTOMS

The first symptoms were muscular weakness and often vomiting. This was followed by partial loss of coordination and dyspnea, which increased in violence until convulsions occurred. At this stage the pupils were dilated.

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The limbs were rigid, and the eye reflex was absent. The convulsions occurred after this and were followed each time by a period of calm, in which respiration often ceased for nearly a minute. The respiration become more and more irregular until it finally ceased altogether, following which the heart beat stopped. At high concentration (0.5 mgm. per liter) convulsions set in almost immediately, death following in four or five minutes. At very low concentrations, the symptoms were slower in onset and much less severe. There were no delayed symptoms after exposure to this gas and recovery always occurred if the animal survived for a period of two hours.

The following were the relative concentrations necessary to kill the species enumerated.

CHART

With hydrocyanic acid, species seemed to be a much more corrct guide than size, while both differed from man: yet experience has shown that a man can exist without serious injury to himself in 1-2,000 HCN for a minute and one half. This being lethal to dogs.

CYANOGEN CHLORIDE ³ (CNCL)

A considerable variation in susceptibility to the toxic effects of cyanogen chloride was evident when different species of animals were employed (Table 45). The guinea pig, mouse, rat, dog, and canary were studied. The following conclusions may be drawn. Guinea pigs appeared to be the most resistant and dogs the most sensitive of the animals studied. For each animal there appeared to be a different concentration below which death did not take place, regardless of the length of exposure. This was probably the concentration that may be destroyed or detoxicated by the particular species. Animals died very shortly after exposure to this gas or ultimately completely recovered. There appeared to be no delayed action. In field trials with this gas, guinea pigs should be among the animals employed in offensive experiments and dogs among those for defensive investigation. A few experiments with the monkey indicated that this animal is very little more resistant than the dog. Canaries were much more susceptible than any of the animals studied and may prove useful as test objects for this gas in manufacturing operations.

TABLE 45.- Animals gassed with cyanogen chloride

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TABLE 45.- Animals gassed with cyanogen chloride-Continued

SYMPTOMS

Dogs.-The symptoms during exposure were very similar to those of hydrocyanic acid poisoning, with the addition of irritation symptoms of the eyes, nose, and respiratory tract. The animal immediately exhibited irritation of the eyes and nose, then lacrymation and salivation. Retching and vomiting were observed in most instances, except where the concentrations were very high and convulsions set in very soon. The respiration was generally at first rapid, then slow and labored. Convulsions, prostration, unconsciousness, and death ensued if the concentration was lethal for the period of exposure. Death might occur during the exposure or within 5 or 10 minutes after removal from the atmosphere of the gas. There were no delayed deaths. If an animal lived for from 15 to 20 minutes after removal, he survived. Depression, slightly difficult respiration, discharge from the eyes and nose, and clouded cornea sometimes existed for a few days.

Mice.-The symptoms during exposure were immediate excitement, irritation of eyes and nose, dyspnea, depression and convulsions, prostration, gasping, and death, provided the concentration was lethal for the period of exposure.

Rats.-The symptoms were very similar to those shown by dogs exposed to this gas.

Rabbits.-During exposure the symptoms were in order of their occurrence as follows: Immediate irritation of eyes and nose; excitement for a few minutes; salivation; then depression, the animal keeping its head thrown back and breathing in deep gasps, with long intervals between gasps. If the concentration was lethal for the period of exposure the animals later recovered, being very much excited for a few moments, and then passed into convulsions and lay prostrate and gasping. Death occurred in from a few minutes to half an hour. If the animal survived, it was likely to be apparently quite normal the day following exposure.

Guinea pigs.-Animals exposed to toxic concentrations exhibited the following symptoms: Irritation of eyes and respiratory tract; lacrymation, salivation, excitement, paralysis, prostration, convulsions, and gasping. Animals invariably recovered if they survived exposure to the gas and lived a few hours afterwards. Out of a total of 61 animals exposed, no delayed deaths occurred

CYANOGEN BROMIDE ⁴ (CNBr)

Of the species of animals exposed to the toxic action of the true vapor of this substance the dog and rat were of about equal susceptibility and were the most resistant; the mouse was the most susceptible; the guinea pig and rabbit were of about an equal degree of susceptibility and occupied an intermediate position.

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The pharmacological action of this substance was apparently twofold: (1) There was an action similar to that of hydrocyanic acid or cyanogen chloride on the control nervous system, causing death by paralysis of the respiratory center, and (2) an irritant action in the lungs, causing delayed death, probably by lung edema. An animal which survived the first action might later die from the second. The relative intensity of these two actions seemed to differ in different species.

The results obtained in regard to the species and time variation with this substance are summarized in Table 46.

TABLE 46.- Animals gassed with cyanogen bromide

SYMPTOMS

Inasmuch as the symptoms elicited were more or less similar in the various species of animals studied, only those for the dog need be detailed. During the exposure there was immediate irritation of the eyes and respiratory tract, then lacrymation and salivation. At the higher concentrations the animal might become wildly excited, have convulsions, and become paralyzed within a few minutes. Death could occur during the exposure, minutes afterward, or might be delayed for several hours or days. Retching or vomiting occurred usually even with the lower concentrations. Clouding of the cornea sometimes occurred during the exposure. With concentrations as low as 0.20 mgm. per liter death with convulsions might occur during the exposure provided it was sufficiently prolonged. Even after having had severe convulsions and paralysis during exposure, dogs could recover from the immediate effects and either die later from lung damage or survive. Animals which survived the immediate action usually had severe respiratory symptoms. Marked depression, sore eyes, with swelling of the cornea, and nasal discharge generally occurred. If the animal survived the symptoms might persist for from 3 to 10 days. Delayed deaths from the lung irritant effect of the gas usually occurred within 48 hours, although some animals died 5 days later.

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ARSENIC DERIVATIVES

ARSINE ⁵ (AsH₃)

Arsine produced no striking symptoms in animals exposed to it. It is true that there might be slight shivering and some evidences of depression toward the end of the period of exposure. In one or two instances there was vomiting and slowing of respiration. The animals (dogs) exposed to both high and low concentrations of arsine were usually very depressed for a number of days, voiding bloody urine and black stools. They usually refused food and seemed to have little or no appetite for a time and then ate very sparingly. These animals showed symptoms for a considerable period of time. Some days they seemed apparently normal and then would show depression, alternating this way for weeks. The toxic concentration might be placed at 0.33 mgm. per liter. Arsine was fatal in the ratio of 1 to 2,000 inhaled for 20 minutes. On the other hand, exposure for 20 minutes to an atmosphere of 1 to 5,000 was not fatal, and in concentration of 1 to 20,000 no harm seemed to result during the above-mentioned period of exposure.

Experimental observation on animals, as well as reports of human cases, point to the conclusion that the toxicity of arsine was due in large measure to hemolysis. The striking clinical symptoms of this action were hemoglobinuria, hemoglobinemia, icterus, and rapidly developing anemia. Upon the entrance into the blood of arsine it is taken up by the red corpuscles, forming a compound which imparts a brown color to the blood. In the presence of the oxygen in the corpuscles, the arsenic hemoglobin compound is gradually converted into arsenic oxide, and during this process of oxidation hemolysis takes place. In the kidney, hemoglobin thus liberated is partially converted into methemoglobin, which appears in the urine, together with xyhemoglobin.

ARSENIC TRICHLORIDE⁶ (AsCl₃)

In high concentration mice were very much excited and showed respiratory difficulty. The eyes were inflamed and there was a nasal and lacrymal discharge. Finally, convulsiform movements were followed by what appeared to be a marked depression. In lower concentrations the symptoms were less marked and were those of local irritation-closing the eyes, rubbing the nose, and nasal and lacrymal discharge. The toxic concentration was 2.5 mgm. per liter of air. The effects observed were those of a combination of arsenical and hydrochloric acid poisoning.

ARSENIC TRIBROMIDE⁷ (AsBr₃)

Mice exposed for a period of 10 minutes to vapors of arsenious bromide showed very marked nasal irritation, dyspnea, and later occasional gasping. The toxic concentration of this substance for mice on 10 minutes' exposure may be placed at 2.0 mgm. per liter, 100 percent of the mice dying in 48 hours.

ARSENIC TRIFLUORIDE ⁸ (AsF₃)

The toxic concentration of arsenic trifluoride for mice was reported as 0.7 mgm. per liter of air. The symptoms were as follows: Nasal irritation is shown by vigorous rubbing of the nose. The eyes soon became moist and were then closed tightly. Dyspnea and gasping soon occurred. The extremities were very cyanotic at the end of exposure. The skin was ashen in color at death which usually occurred within 24 hours.

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For dogs the toxic concentration was 0.73 mgm. per liter of air. The symptoms follow:

SYMPTOMS DURING EXPOSURE

At all concentrations from 0.13 to 0.81 mgm. per liter there was severe irritation of the eyes and mucous membrane of the nose and throat; lacrymation, salivation, and nasal secretion were in most instances profuse. Several of the animals sneezed, retched, and vomited.

SUBSEQUENT SYMPTOMS

Dogs exposed to a concentration of 0.53 mgm. per liter or above were very depressed after exposure. Within 24 hours they had developed sore eyes, a wheeze or cough, and were very much depressed. There was also dulling of the cornea after the second day. In the cases of dogs surviving, this condition persisted for 10 or 12 days without very marked improvement. The deaths occurred in from 2 to 4 days. Dogs exposed to lower concentrations showed only slight depression but this condition persisted for a number of days without marked improvement.

USE AS A SKIN IRRITANT

Arsenic trifluoride was one of the important skin irritants. Its effects were felt almost immediately upon application. Dilution with alcohol (1:25 to:100) showed some irritation but, aside from a slight temporary discoloration of the skin, there was no reaction. A dilution of 1 to 500 in alcohol showed no symptoms in seven days.

Immediately upon application of the undiluted substance, the skin was discolored, the rabbit struggled violently, as though in considerable pain, and the respiratory rate was considerably increased. Both animals tested died within 24 hours.

DICHLORMETHYLARSINE⁹ (CH₃AsCl₃)

The toxicity of dichloromethylarsine approached that of phosgene. The symptoms included an initial period of excitement, which was soon followed by an interval of depression. For about 5 minutes of exposure there were alternate periods of activity and depression. Finally the mice became greatly depressed. Intense irritation of the nose and eyes was evident. Hyperemia of the nose and eyelids were marked, and both a nasal and lacrymal discharge occurred. Respiration was deep, slow, and irregular. Death usually occurred within 24 hours.

SKIN IRRITANT PROPERTIES

This poison was less irritating than phenyldichlorarsine, probably because of its higher volatility, and it was more irritating as a gas. The vapors were as irritating as mustard gas; the liquid seemed somewhat more irritating. The vapor caused immediate hyperemia of a light pink color, with very marked swelling. In 24 hours a capillary hemorrhage appeared and the swelling had mostly receded. After four days the local area was as intense as one treated with phenyldichlorarsine, but there was no spreading.

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CACODYL CHLORIDE (CHLORODIMETHYLARSINE) ¹⁰ ((CH₃)₂AsCl)

This poison is less toxic than arsine. A cat exposed to a concentration of I to 1,000 cacodyl chloride for one hour showed progressively increasing dyspnea, became comatose 2 hours after removal, and died about 10 hours later. A cat exposed to a concentration of 1 to 10,000 cacodyl chloride for a period of 1 hour developed marked (lyspnea; food was refused on the following day, and the animal gradually became apathetic and died on the fourth day. A cat exposed to the gas in a concentration of 1 to 50,000 for a period of 1 hour showed no effects except the secretion of thick saliva. It remained well after removal from contact with the poison.

CACODYL CYANIDE¹⁰ ((CH₃)₂AsCN)

This substance had an irritant action both on the eyes and on the respiratory passages. The former action, however, was less powerful than that of various other lacrymators tested. The physiological action and effects of cacodyl cyanide varied somewhat from those of substances previously investigated. The prominent features were the following: There was no appreciable lacrymation at concentrations of less than 1 in 1,000,000. Lacrymation was very pronounced with three out of four subjects (men) who reached a concentration of 1 in 125,000. Nasal irritation was definite, inducing in the higher concentrations an attack of sneezing. The odor and taste had a distinct tendency to produce nausea. In three cases a definite sensation of giddiness and a feeling of compression in the head was experience.

ETHYL ARSINE¹² (C₂H₅AsH₂)

For mice the toxic concentration of this gas was 6.5 mgm. per liter of air. At concentrations of 47 and 69 mgm. per liter there was marked nasal irritation, continued gasping, convulsions, and death in a few minutes. After death there was a marked flexor rigidity. At concentrations of 10 and 6.5 mgm. per liter there was marked nasal and lacrymnal irritation. There was a brief period of increased activity which was soon followed by deep depression. The respiration was deep and irregular at first, but soon became rapid and shallow. Near the end of the period of exposure, the mice became weak, uncertain in movements, trembled convulsively, and finally became prostrate. Death occurred within 30 minutes after exposure and was preceded by a brief convulsion. At a concentration of 1.5 mgmn. per liter both nasal and lacrymal irritation were shown. A brief period of increased activity was succeeded by deep depression. Respiration was slow, shallow, and irregular, with occasional gasping.

DICHLORPHENYLARSINE ¹³ (C₆H₅AsCl₂)

EXPERIMENTS WITH MICE

During the period of exposure there was very marked irritation of the nose and eyes, with lacrymation, and hyperemia of the nose and eyelids occurred almost immediately. Dyspnea, with occasional gasping, was shown in a few minutes, and gasping became convulsive and almost continual near the end of the exposure. One of the two mice exposed to a concentration of 0.18 mgm. per liter died within 48 hours, with no external evidences of irritation. 'Ihe other mouse, on the seventh day, developed a marked swelling of the head.

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On the tenth day its head and back were covered with dry ulcers. The skin seemed to have cracked and curled up leaving a dry ulcer. The hair had fallen off one side of its head, while its ears were dry, shriveled, and stiff. The eyes were closed by a yellow secretion. On the fourteenth day the swelling of the head had decreased and the right ear had dropped off close to the base. On the sixteenth day the swelling had entirely disappeared, the eyes were clearing of the secretion, and the hair had dropped off both sides of the head and in spots on the back. The ulcers on its head and back seemed to be healing. On the seventeenth day the left ear had dropped off, the eyes were partially open, and the discharge from them was watery instead of thick and yellow as before. On the nineteenth day more hair had dropped off the head and back. On the twenty-first day one eye was entirely open, while the other was partially closed. Both seemed weak and the watery discharge still continued. The ulcers had entirely healed.

Of the two mice exposed to a concentration of 0.13 mgm. per liter, one died in 22 hours. The other at the end of 10 days had developed swelling of the hind legs, feet, and head. Its ears were shriveled and hard. It died on the seventeenth day. The skin was cyanotic, ears shriveled, hind feet swollen and ulcerated. The mice exposed to a concentration of 0.08 mgm. per liter at the end of 10 days were both alive. The ears were dry and shriveled, the head and back were ulcerated, and the hair was coming off the head and back.

EXPERIMENTS WITH DOGS

At all concentrations there was severe irritation of the eyes and mucous membrane of the respiratory passages. Dogs exposed to concentrations of 0.06 mgm. per liter and above showed excitement, severe irritation of the eyes, lacrymation, salivation, retching, vomiting, and sneezing. At a concentration of 0.02 mgm. per liter there was still irritation of the eyes and nose, but one dog exposed to 0.01 mgm. per liter showed no symptoms during exposure.

Within 24 hours after exposure all the dogs exposed to concentrations of 0.02 mgm. per liter and above had sore eyes, cough, rattle or wheeze, and were generally very depressed. This condition persisted for 5 or 10 days, or longer in cases where the animals had been subjected to sublethal concentrations. Four deaths occurred in from 18 hours to 3 days. One was delayed after exposure. Two dogs exposed to a concentration of 0.25 mgm. per liter died within 3 days. Of 4 dogs exposed to concentrations of 0.14 and 0.21 mgm. per liter 3 survived. The toxic concentration may be placed at 0.26 mgm. per liter of air.

SKIN IRRITANT PROPERTY

Phenyldichlorarsine produced marked swelling in 15 minutes, which increased throughout a period of from 6 to 8 hours. It was accompanied by a quick hyperemia and in from 3 to 6 hours by very extensive hemorrhages. The exposed area became white and hard, having the appearance of entirely dead skin. The hardening of the skin and the translucent white color gradually replaced the capillary hemorrhage until only a small hyperemic area was left encircling the burn. It appeared from its immediate action that phenyldichlorarsine was a much more severe irritant than mustard gas. A burn up to 4 days old would be judged three to four times as extensive as a mustard-gas burn of the same age and equally severe.

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DIPHENYLCHLORARSINE¹⁴ ((C₆H₅)₂AsCl)

This gas was a lacrymator and a respiratory irritant. Very minute amounts caused sneezing. Large amounts caused painful irritation of the respiratory tract. The gas produced headache, giddiness, and depression, which soon wore off. There were no after effects and no visible influence on the skin. One part in 500,000,000 was intolerable for continuous respiration.

EFFECT ON MAN

One part of the gas in 100,000,000 (0.00012 mgm. per liter) was just detectable. One part in 50,000,000 (0.00024 mgm. per liter) caused nasal irritation after two minutes. One part in 20,000,000 (0.0006 mgm. per liter) induced marked nasal irritation without sneezing. One part in 1,000,000 (0.0012 mgm. per liter) became intolerable with or without the eyes protected. It also produced severe irritation of the respiratory tract.

INFLUENCE ON MICE

The gas in small concentrations was not very toxic, as mice continued to live for nine days in an atmosphere of 1 to 2 parts per million.

ACTION ON DOGS

At a concentration of 0.02 mgm. per liter and above the animals showed immediate excitement, and severe irritation of the eyes and mucous membrane of the nose and throat. Salivation and lacrymation were profuse and there was increased nasal secretion. Dogs exposed to concentrations below 0.2 mgm. per liter showed few or no symptoms. Three dogs exposed to a concentration of 0.06 mgm. per liter or higher were very depressed, had sore eyes, increased nasal secretion and developed a bad cough and rattle in the throat. One animal exposed to a concentration of 0.1 mgm. per liter died in six days. Another dog exposed to a concentration of 0.09 mgm. per liter was in very bad condition at the end of 10 days and did not seem likely to recover. The animal exposed to a concentration of 0.06 mgm. per liter had apparently recovered at the end of eight days. Below this concentration the dogs with a single exception recovered.

SUSCEPTIBILITY OF DIFFERENT SPECIES

Dogs and monkeys are killed by approximately the same doses. Expressed as fatal concentrations relative to that for the dog, the following results were obtained for different species:

CHART

The following gives the comparison with phosgene and chloropicrin at the concentration which was fully tested; i. e., 1 in 200,000 for 30 minutes exposure: Chloropicrin killed goats, monkeys, and guinea pigs; did not kill dogs, cats, rabbits, or rats. Phosgene killed cats, rabbits, rats, monkeys, and guinea pigs; did not kill goats or dogs. Diphenylchlorarsine killed goats, dogs, cats, monkeys, and guinea pigs; did not kill rabbits or rats.

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SKIN IRRITANT PROPERTIES

There was no swelling or hyperemia in 45 minutes. In 90 minutes the skin presented a white, blistered appearance. After 2 hours some hyperemia and swelling appeared, and the former became very distinct in 6 hours, but with no spreading through the unexposed skin. In 24 hours the area of exposure was swollen equally with a mustard-gas control, and was deeply hyperemic, but there was not the lateral swelling presented by the mustard-gas control.

Diphenylchlorarsine was a strong irritant, but doubtfully as strong as mustard gas and certainly far less irritant than phenyldichlorarsine. The vapor yielded negative results.

Using a saturated solution in carbon tetrachloride, application to the flexor surface of the forearm for 10 to 20 minutes gave no abnormal sensation. At the end of the application the skin was reddened and a papular erythema developed. A warm solution applied for 10 minutes gave a more marked erythema, and after 30 hours, a blister formed; after an application lasting 30 minutes the results were similar but more intense.

SUPERPALITE AND INTERMEDIATES

METHYLCHLOROFORMATE ¹⁵ (CIHCOOCH₃)

The toxic concentration of this gas for mice for an exposure of 30 minutes was 1.2 mgm. per liter, or 276 parts per million. In high concentrations (24 mgm.) the mice immediately rubbed the nose and within a few minutes became dyspneic. Dyspnea progressed; they gasped wildly, while their eyes protruded. This was followed by convulsions and death. In concentrations of 4 mgm. the eyes were closed almost at once, but were opened again during the severe dyspnea which followed in the course of 2 to 3 minutes. At this concentration some of the mice died in convulsions in the gas chamber, while others with their feet spread, gasped in deep labored respiration, the expiration being accompanied by a sharp clicking sound, and death ensued in about an hour. In concentrations of 1.5 mgm. mice almost at once began to show signs of depression, during which they lay in the cage with deep respiration, their eyes partially closed. At this time there was a slight salivation, sometimes accompanied with a lacrymal discharge. Soon after gasping began, which continued till death, some hours later. In smaller concentrations the signs were somewhat similar, but the dyspnea was less intense. Although they gasped while exposed to the gas this ceased on removal.

CHLORMETHYLCHLOROFORMATE ¹⁶ (ClCO₂CH₂Cl) (PALITE OR "K-STOFF")

Its physiological effects were very similar to those of phosgene: it was heavier, less easily dissipated, and so was better suited for employment in shells. In fairly high concentrations death occurred soon; low concentrations caused delayed effects exactly similar to phosgene. The delay was often protracted, deaths having occurred after intervals of from 10 to 15 days.

ACTION ON ANIMALS

Rat.-An exposure of 1 to 1,000 (5.76 mgm. per liter) for 1 hour caused death 2 hours later. A concentration of 1 to 2,000 caused death within 12 hours.

Cat.-After an exposure of 1 hour to a concentration of 1 to 1,000 the animal was very ill, with dvspnea and slow, prolonged inspiration. The lungs, upon

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death, were edematous and congested. In a concentration of 1 to 5,000 there was marked lacrymation, but the respiratory effect was noticeable only toward the end of the hour. About 2 hours after release from exposure to the gas severe dyspnea and convulsions were in evidence. The animal died during the night, with lungs congested and edematous. A concentration of 1 to 20,000 produced lacrymation, salivation, and coughing. After 24 hours the animal was apparently well, but after 45 hours some bronchitis was present. In a concentration of 1 to 100,000 the animal showed lacrymation and some respiratory irritation. It was quite well two days later.

Dogs.-The minimum lethal concentration for dogs exposed for one-half hour is 1 to 6,000 (0.96 mgm. per liter), the animals dying in 24 hours. In a concentration of 1 to 3,000 the dogs died in about 12 hours.

EFFECT ON MAN

A concentration of 1 to 100,000 caused slight lacrymation and 1 to 200,000 was extremely irritant but could be respired by a resistant subject. In two observers this strength became irrespirable in 3 and 10 minutes, respectively, owing to cough and irritation. The toxicity was probably of the same order as that of phosgene.

TRICHLORMETFIYLCHLOROFORMATE ¹⁷ (Cl₃CCOCl) (SUPERPALITE OR PHOSGENE)

The toxicity of this gas for different species of animals was as follows:

ACTION ON ANIMALS

Mice.-When exposed for periods of 10 minutes to concentrations of 0.5 to 13.5 mgm. per liter, death was caused in nearly all instances. The toxic concentration was found to be 0.2 mgm. per liter, or 25 parts per million. When exposed to the gas in higher concentrations the mice showed signs of local irritation, a slight lacrymal and nasal secretion developing, a severe dyspnea then followed, and the animal died. In smaller concentration the signs were similar but less pronounced.

Cats.- Cats appeared to be more sensitive to this gas than dogs; for while dogs survived a concentration less than 0.30 mgm. per liter, the cats exposed to 0.2 and 0.11 mgm. per liter all died in 24 hours or less.

Other experiments gave results as follows:

CHART

Rabbits. - With these animals the following results were obtained:

Dogs.-At summary of a series of experiments with dogs is given in Table 47.

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TABLE 47.- Toxicity of diphosgene on dogs

The symptoms during exposure (7.5 minutes) were immediate excitement and irritation of the eyes and nose. Within a minute the animals usually quieted down and became drowsy and depressed. Salivation and lacrymation were profuse. Toward the end of the exposure the dogs were very drowsy, respiration was irregular and almost shallow. Frequently there was paling of the mucous membrane of the mouth. Soon after exposure the dogs had sore eyes, increased nasal secretion, and were generally depressed. Within 24 hours they developed a cough with labored and painful respiration. This condition persisted for from 5 to 25 days or longer. Death occurred anywhere from a few hours to 20 days after exposure.

After an exposure of 4 hours to a concentration from 0.046 to 0.09 mgm. per liter the symptoms observed were at first irritation of the eyes and nose, lacrymation and increased nasal secretion, salivation, frequently retching and vomiting, and occasionally defecation. The animals were usually drowsy and depressed before the end of the exposure. Later symptoms included depression, loss of appetite, sore eyes, cough, and labored respiration. This condition lasted for a period of from 1 to 13 days or longer. The deaths occurred usually in from 1 to 2 days, although one was delayed for 13 days.

Miller¹ studied the effect of repeated exposure to superpalite upon dogs. Twenty-one (logs that had been previously gassed with superpalite and had recovered were then reexposed; seven of them at a concentration of about 0.78 mgm. per liter, and the remaining 14 at concentrations varying from 0.40 to 0.62 mgm. per liter. The result was that 6 of the 7 exposed to the lethal concentration died. Only 6 exposed to the lower concentrations died, which is about what would have happened if fresh dogs had been subjected to the same conditions. After three weeks, the surviving dogs were again gassed, part to the lethal concentration and part to a lower concentration. The results were similar to those obtained in the first gassing. Four out of six exposed to the higher concentration and 2 of the 10 exposed to the lower concentration died. This procedure was continued until only 6 dogs were left.

From these results it seems probable that the susceptibility of dogs to superpalite was neither materially increased nor lessened by repeated exposure to sublethal concentration.

Sherwood and Snyder ² investigated the smallest concentration that can be detected by the nose, mouth, and respiratory tract. The tests summarized in Table 48 were interrupted when the subject began to cough.

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TABLE 48.- Effect on the respiratory tract of different concentrations of diphosgene

A concentration of 1.52 parts per million (0.013 mgm. per liter) caused throat irritation of almost all the subjects, and 2.81 parts per million (0.025 mgm. per liter) caused coughing in 82 per cent of cases.

Experiments were conducted to ascertain what concentration could be breathed without breaking down in about 3 minutes, and 16 subjects were tested with results as follows.

Breathing by the mouth only, eyes protected:
  
  ConcentrationNumber breaking down
1-500,000 (0.0176 mgm. per liter)..........................2
1-333,000 (0.0265 mgm. per liter)..........................8
1-250,000 (0.0354 mgm. per liter)..........................3
1-200,000 (0.0442 mgm. per liter)..........................1
1-166,000 (0.053 mgm. per liter)............................2


Breathing by the nose, eyes unprotected:

Concentration   Number breaking down
1-500,000..............................................................2
1-333,000..............................................................6
1-250,000..............................................................5
1-200,000..............................................................3

ACROLEIN ¹⁸ (CH₂=CHCHO)

Acrolein is a lacrymator and respiratory irritant; the effects on the eyes and throat occur simultaneously. In concentrations of 0.025 mgm. per liter it induces secretion of saliva, lacrymation, nasal secretion, and slight narcosis.

ACTION ON MAN

One part in 200,000 acted as a lacrymator and nasal irritant, while 1 part in 100,000 was intolerable. The minimum effective concentration with or without eye protection was 1 to 100,000 (0.025 mgm. per liter). The toxicity was about the same as phosgene.

ACTION ON ANIMALS

Mice.-At an exposure of 10 minutes the immediate toxic concentration was between 0.55 and 0.38 mgm. per liter. This killed more than 50 percent of the mice within 48 hours. The delayed toxic point (that which killed after 48 hours and in less than 10 days) was between 0.16 and 0.17 mgm. per liter. In concentration of 1 mgm. or more there was increased excitement but lower concentrations produce depression. All concentrations caused irritation as shown by rubbing of the nose and closing of the eyes. Gasping was also a constant symptom, it being only occasional with the low concentrations but continual with the highest concentration, namely, 4 mgm. per liter. The delayed deaths took place in from 48 to 65 hours.

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With concentration of 4.1 mgm. per liter all 4 mice died within 7 minutes. They showed violent excitement from the onset and died with convulsions. Moderate concentrations killed all within 1 to 46 hours.

Rats.- One part in 1,000 killed in 50 minutes.

Cats.- A dose above 0.04 mgm. per liter caused such intense irritation that some days were required for recovery. With 0.2 mgm. per liter the lung-irritation phenomena were not recognizable, but were obviously painful, and the muscles came into activity. A dose of 1.5 mgm. per liter seriously affected the animal, which died after 21 hours' exposure to the gas of lung edema and hemorrhage of the lungs; with a dose of 1.98 mgm. per liter death resulted 2.5 hours later.

Dogs.-The dogs were very much excited during the early part of the exposure. The eves and nose were at once irritated and the animal blinked and licked his nose the instant the gas was turned on. Lacrymation and salivation were both profuse. After a short time the animals kept their eves tightly closed. The cornea was usually dulled. Nasal secretion was very much increased. Respiration was early affected, becoming very slow and labored. Toward the end of the exposure the animal was usually much depressed. Within a few hours after exposure the animal developed a severe tracheal rattle, was very depressed, coughed, and had labored respiration. With toxic concentrations death occurred in four hours to two days. With nontoxic concentrations the aninal was very sick for several days and did not recover completely for a week or more. The toxic concentration might he placed at 0.35 mgm. per liter.

SENSITIVENESS OF INDIVIDUALS

Experiments to determine the smallest concentration of acrolein that could be detected by the eves, nose, throat or lower respiratory tract showed that acrolein was detectable by its odor at a concentration of 0.0028 mgm. per liter or 1.12 parts per million and that some individuals could detect it at even smaller concentrations. When the amount of gas was increased to 0.0077 mgm. per liter (3.06 parts per million) irritation of the eves and nose became a prominent symptom in the majority of tests. Lacrymation did not become pronounced until the concentration reached 0.010 mgm. per liter or 4 parts per million.

REFERENCES ^a

(1) West, C. J.: Chemical Warfare Monograph, Vol. XXIII, Chapter I, May, 1919.
(2) Ibid.: Vol. XXIII, Chapter II.
(3) Ibid.: Vol. XXIV, Part I, Chapter I, April, 1919.
(4) Ibid.: Vol. XXIV, Part II, Chapter III, April, 1919.
(5) Ibid.: Vol. XX, Part I, Chapter I, May, 1919.
(6) Ibid.: Vol. XX, Part II, Chapter III, May, 1919.
(7) Ibid.: Vol. XX, Part II, Chapter IV, May, 1919.
(8) Ibid.: Vol. XX, Part II, Chapter V, May, 1919.
(9) Ibid.: Vol. XXI, Part I, Chapter III, April, 1919.
(10) Ibid.: Vol. XXI, Part I, Chapter IX, April, 1919.
(11) Ibid.: Vol. XXI, Part I, Chapter X, April, 1919.
(12) Ibid.: Vol. XXI, Part I, Chapter XIII, April, 1919.
(13) Ibid.: Vol. XXI, Part II, Chapter V, April, 1919.
(14) Ibid.: Vol. XXI, Part III, p. 182, April, 1919.
(15) Ibid.: Vol. XXV, Chapter II, March, 1919.
(16) Ibid.: Vol. XXV, Chapter III, March, 1919.
(17) Ibid.: Vol. XXV, Chapter V, May, 1919.
(18) Ibid.: Vol. XXIX, Chapter 1, May, 1919.
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^a The monographs cited are based on official documents on file in the office of the Chief, Chemical Warfare Service, Munitions Buildings, Washington, D. C., or in the Medical Research Division, Edgewood Arsenal, Md. All monographs on file, Medical Research Division, Edgewood Arsenal.