A STUDY OF ARSINE POISONING

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. AsH 3 /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. AsH 3 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.