EFFECTS OBSERVED IN THE WHOLE ANIMAL 727 



the perfused cat limb with 1 mM arsenite could be detected by Hitchcock 

 (1946). Oelkers (1936) in a rather thorough study could not obtain good 

 evidence for a significant vasodilatation by arsenite in a variety of prepara- 

 tions, and argued that arsenite exerts most of its effects directly on the 

 tissues. Hanna and McHugo (1960) recently demonstrated that injections 

 into rabbits of 1 mg/kg sodium arsenite lead to an increase in capillary 

 permeability, as measured by trypan blue staining of the internal organs, 

 and confirmed the sensitivity of the splanchnic capillaries. Poisoning and 

 death from the arsenicals can definitely occur without obvious vascular 

 changes, and Butzengeiger (1940) reported circulatory disturbances in only 

 15 of 180 patients with chronic arsenic poisoning, gangrene of the extremi- 

 ties occurring in six. The results from direct studies of the capillary res- 

 ponses to the arsenicals have thus been at variance and more thorough and 

 critical work must be done before definite statements can be made. 



Magnus (1899) was the first to report the occurrence of edema following 

 injections of arsenite. Dogs given subcutaneous arsenite over 4-9 days 

 developed marked edema in various organs, and Magnus concluded that 

 this originates from the damage to the capillaries. Bornstein and Budelmann 

 (1930) rightly concluded that it is impossible to assign a site for the action 

 in whole animal work and investigated isolated preparations, such as the 

 dog leg, in which they claim edema is produced, although no controls are 

 evident. Edema of the skin, especially in the head and neck region, has 

 been noted several times; this could be due to a direct effect on the capil- 

 laries, a blockade of the sympathetics (although this usually does not cause 

 edema), or release of some substance, such as histamine, for which there is 

 no evidence. Even 5 mM arsenite solutions are not very irritant or inflam- 

 matory when applied to abraded skin, the tongue, or the eye (Heubner, 

 1925). The differentiation between direct and vascular actions was at- 

 tempted by using the cornea, which is avascular, but Ellinger (1931) found 

 irritation and Oelkers (1936) did not, so that these experiments did not 

 settle the issue, which is not surprising considering the quality of the work. 



The responses of the skin to the organic arsenicals are not as easy to 

 interpret as has generally been assumed. Lewisite and related vesicants are 

 irritant to the skin and mucous membranes, but the striking effects are due 

 in part to the greater volatility and penetrability of these compounds rela- 

 tive to other arsenicals. Much of the work with lewisite on the skin has 

 been done with either pure lewisite or fairly highly concentrated solutions 

 or vapors; even in the metabolic work of Thompson (1946) the small 

 amounts of lewisite applied to the skin correspond to concentrations of 

 0.25-0.75 mM, assuming homogeneous distribution. The ability of various 

 phenylarsenoxides to induce local skin reactions upon intracutaneous in- 

 jection varies quite markedly, this depending on the ring groups, only 

 the hydroxy, amino, and unsubstituted phenylarsenoxides being potent 



