714 6. ARSENICALS 



Toxicology of the Organic Arsenoxides 



Most of our knowledge comes from the extensive reports on the toxic 

 reactions to the clinically used arsenicals, and since complete descriptions 

 of these reactions are given in pharmacology texts, only a brief summary 

 will be given here. It may be noted that generally the effects of the arsen- 

 oxides are similar, if not identical, to those of arsenite, so that essentially 

 all the reactions given in the previous section may be observed. None of 

 these, of course, occurs frequently at the therapeutic dosage levels; indeed, 

 some of the reactions occur so infrequently that they may well be sensitivity 

 responses of an allergic type. The differences between the effects of the 

 arsenoxides and arsenite are more interesting. It appears, for example, 

 that the arsenoxides exert relatively less action on the circulation and the 

 gastrointestinal tract; animals may die from oxophenarsine poisoning with- 

 out obvious vasodilatation or signs of intestinal damage. It is a matter 

 of degree only, however, since patients often exhibit diarrhea after intra- 

 venous oxophenarsine, and lewisite given systemically is capable of causing 

 severe mucosal hemorrhage with gastric and intestinal erosions (Cameron 

 et al., 1946). Some species are particularly sensitive to the central effects 

 while others more often die of renal lesions (Gruhzit, 1935). In dogs and 

 man the cerebral blood vessels seem to be more affected than the vessels 

 elsewhere by oxophenarsine, and considerable edema and hemorrhage may 

 be present in the brain with little evidence of vascular derangement else- 

 where (Sexton and Gowdey, 1947). Lewisite is definitely more toxic than ar- 

 senite to the liver and kidney, is more apt to cause pulmonary lesions (e. g., 

 edema and alveolitis), and has relatively less effect on the heart or central 

 nervous system (Cameron et al., 1946). Some of the differences between 

 arsenite and the arsenoxides may be due to different distributions in the 

 tissues, but at the present time one cannot be certain that they produce 

 identical metabolic lesions. It should not be thought that all the phenyl- 

 arsenoxides produce the same toxic effects. Hurst (1959) has shown that 

 Melarsen oxide in single injections to monkeys causes a hemorrhagic ne- 

 crosis at specific sites in the central nervous system, particularly the external 

 geniculate bodies and the ventral pons, while phenylarsenoxide does not 

 produce such lesions, perhaps because it kills through hepatic and renal 

 damage. Nor does arsenite cause these lesions. Possibly the effects of Melar- 

 sen oxide are of vascular origin. 



A few brief remarks relative to the effects of the arsenicals on the liver 

 will not be out of place here because, although the mechanisms are not 

 understood, a metabolic basis is likely which might repay further investiga- 

 tion. Vogel (1928) reported that arsenic is often found in abnormal amounts 

 in patients with jaundice, stated that it might be an etiological factor in 

 cirrhosis and hepatic atrophy, perhaps being responsible for the sporadic 

 outbreaks of liver disease, and felt that the Kver bore the brunt of arsenic 



