The Effect of Bal on the Excretion of Arsen‐oxides

Abstract

SHORTLY after their discovery of BAL (British Anti-Lewisite, 2:3-dimercaptopropanol), Stocken and Thompson [1946] showed that application of this substance to the skin hastened the excretion of lewisite in rats. Some time later it was found by Eagle [quoted by Walters and Stock, 1945] that injection of BAL led to a more rapid elimination of arsenic in animals poisoned with arsenicals of therapeutic interest.In a previous communication [Chance, Crawford and Levvy, 1945], the fate of arsenic in the body after injection of rabbits with phenylarsenoxide, mapharsen (m-anmino-p-hydroxyphenylarsenoxide) and the corresponding arsenic acids was described. At the same time as these experiments, others were done in which the effect of BAL on the clearance of the two arsenoxides fronm the body was studied, but it has not hitherto been possible to publish the results of the latter. A brief account of the work with BAL is given below. It should be noted that it had to be terminated while still incomplete. EXPERIMENTAL AND RESULTS.The experimental procedure was described in detail in the previous paper [Chance et al., 1945]. BAL was injected subcutaneously as a 5 per cent. (w/v) solution in peanut oil, the dosage being 30 mg./kg. in all cases. Doses of the arsenicals, which were injected intravenously, are given in Table I in terms of elemental arsenic. The table shows the amounts of arsenic in the urine and fieces, expressed as ,ug.As excreted for each mg. As injected. When the animals were sacrificed at the end of the seventh day, the lung, liver, kidneys and gall-bladder were analysed for arsenic. Since, at the most, only traces of arsenic were present, the results are not given in detail. Fig. 1 shows the cumulative daily excretion of arsenic in the urine in experiments 25 to 28. For comparison, figures from the previous paper for the excretion of arsenic in the urine after the injection of a similar dose of each arsenoxide, but in absence of BAL, are also plotted.

The Effect of Dithiols on Survival Time in Rats and Mice Poisoned With Organic Arsenicals

“…In practice, no instance has been observed where the increment in survival time produced by dimercaprol was larger than could be Lewy (1945) showed that in rabbits poisoned with phenylarsenoxide or oxophenarsine, phenylarsenoxide was excreted much more slowly than oxophenarsine. Chance and Levvy (1947) showed that dimercaprol given to phenylarsenoxide poisoned rabbits increased the excretion of arsenic tenfold, and in oxophenarsine poisoned rabbits increased the excretion of arsenic only 2.5 times. Peters and Stocken (1947) showed that the compound formed in vitro between oxophenarsine and dimercaprol (4-hydroxymethyl-2-(3'-amino-4'-hydroxyphenvl)-1: 3-dithia-2-arsacyclopentane) was much more toxic than oxophenarsine, and that treatment with dimercaprol prevented toxic effects of the oxophenarsinedimercaprol compound.…”