792 6. ARSENICALS 



ever, is apparently not the hemolytic substance, or at least does not readily 

 produce hemolysis. The acute toxicity of arsine cannot be explained on the 

 basis of the arsenite formed, inasmuch as arsine is much more toxic; the 

 amount of arsenite formed from a lethal dose would be quite small even 

 with complete conversion. There is always the possibility that arsine pene- 

 trates where arsenite does not and releases arsenite in regions where even 

 small amounts are toxic, but there is no evidence for this. The changes 

 occurring in hemoglobin are disputed: some have claimed that methemo- 

 globin is formed (Wolff, 1936; Jung, 1939) and some that it is not (Heub- 

 ner, 1935). Certainly arsine does not produce methemoglobin directly and, 

 in fact, can reduce methemoglobin. There is some evidence that hemoglo- 

 bin may eventually be degraded to hematin (Wolff, 1936). Various inter- 

 mediary products of the oxidation of arsine have been believed responsible 

 for the hemolysis: elementary colloidal arsenic (Labes, 1928; Heubner, 

 1935), diarsine or HgAs-AsHa (Heubner and Wolff, 1936), hydroxyarsine 

 or AsHgOH (Wolff, 1936), and hydrogen peroxide (Jung, 1939). Another 

 suggestion, for which there is little evidence, is that catalase is inhibited 

 in the erythrocytes by some intermediate of arsine metabolism, or that 

 glutathione is reacted (glutathione is antihemolytic) (Jung, 1939). Thus, 

 although arsine is the most powerful hemolytic agent found in industry, 

 we still do not know the mechanism by which it acts. 



There is, unfortunately, very little reported concerning the effects of 

 arsine on other tissues. Direct actions on the central nervous system and 

 damage to the liver and kidneys seem likely, but these are complicated by 

 the hypoxemia. It has been shown to act on the isolated frog heart, anaer- 

 obically stopping it in diastole and aerobically stopping it in systole, which 

 led to the idea that hydrogen peroxide might be a factor in its action (Rich- 

 ter, 1941). The respiration of liver and kidney slices is depressed by rather 

 high concentrations of arsine (see accompanying tabulation) (Hughes and 



Tissue Arsine (mJf) % Inhibition 



Liver 



Kidney 



Levvy, 1947). The respiration of liver is thus about 5 times more sensitive 

 than that of kidney. Arsenite is somewhat more inhibitory than arsine in 

 the kidney, and less inhibitory in the liver. It had been generally thought 



