A Study of Arsine Poisoning

Abstract

1. In experiments in which the arsenic in the carcases of miceexposed to arsine was determined, the percentage of the gas inhaled which was absorbed appeared to be approximately the same (64 percent.) over a hundredfold range in gas concentration. 2. The median lethal dose of arsine for mice, in terms of the gas absorbed, increased with decreasing concentration inhaled, suggesting that arsine is rapidly detoxicated in the body. At the highest concentration studied, the median lethal dose was 0–67 mg. AsH3/kg. 3. The ventilation rate in mice appeared to be different in exposures to arsine of different durations. From this, peculiarities in the median lethal exposure curve may be explained. 4. The arsenic in tissues from rabbits killed immediately after short exposures to arsine was determined. Although the tissues were freed from blood before hæmolysis commenced, some organs, in particular the liver, contained considerable amounts of arsenic. It is suggested that this arsenic reached the tissues as arsine, unchanged by reaction with the erythrocytes. 5. Intraperitoneal injection of 17 mg./kg. of ethane‐1:2‐dithiol doubled the duration of the exposure to 0·50 mg. AsH3 per litre required for 50 per cent. mortality in mice. The median lethal dose of the dithiol alone was about 55 mg./kg. It was effective several hours after exposure to arsine. 6. Factors in gas chamber design of importance in carrying out toxicity determinations were studied, and a new type of chamber which permitted accurately controlled exposures of short duration was constructed. 7. It is concluded that the high toxicity of arsine in the higher concentration range may in part be due to the action on vital organs of unchanged gas, reaching them in physical solution in the blood plasma. The author wishes to express his thanks to the late Professor A. J. Clark and to Professor G. F. Marrian for encouragement in carrying out this work, to Professor J. H. Gaddum for suggestions regarding the interpretation of certain of the results, to the late George Abbot and to Charles Bell for technical assistance, and to N. E. Condon for the construction of gas chambers. Permission from the Director General of Scientific Research (Defence), Ministry of Supply, to publish these results is gratefully acknowledged.

The Toxicity of Arsine Administered by Intraperitoneal Injection

“…Mixtures of arsine and hydrogen, prepared and assayed as previously described (Levvy, 1946), were injected from a hypodermic syringe or gas burette. The arsine concentration in the mixture was usually about 10 mg. /100 ml.…”

“…Arsine administered in this way, however, is far from exhibiting its maximum toxicity. The toxicity for mice exposed to the gas (Levvy, 1946) was found to increase as the concentration inhaled increased, and with a concentration of 2.5 mg. AsH3/litre in the atmosphere, the LD50 was only 0.67 mg. AsH3/kg. It did not approximate to the figure obtained when the gas was given intraperitoneally (2.5 mg./kg.)…”

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In a previous paper (Levvy, 1946) accurate figures were given for the median lethal dose of arsine for mice. These figures were obtained by determining the arsenic in the entire carcases after subjecting the animals to exposures to arsine which were known to produce 50 per cent mortality.

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Allometry displayed in the case of response to single exposure to arsine and its use in the extraction of the 0% lethal level

“…As one of the response differences, one should remember the dead rate of lung, and the rate of absorbed arsine per body weight in each organ [1].…”

“…Several approaches have been tested for the determination of the LC0% from the experimental data mentioned by Levvy [1,2]. In order to conduct a coherent methodology in our investigations, it has been necessary to use a preliminary to filter and process the data, since these data were truncated.…”