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Although chemical agents were not employed as offensive weapons during the past war, nevertheless it was imperative to pursue vigorously investigations on the treatment of chemical warfare casualties. Inasmuch as a number of chemical warfare agents contain arsenic, attention was focused on the synthesis of compounds capable of antagonizing the local and systemic effects of ar-senical vesicants. These investigations, initiated by the British, led to the synthesis of 2,3-dimer-captopropanol, which is now more familiarly known as BAL (British Anti-Lewisite). In addition to BAL, numerous other SH-containing compounds, including monothiols and dithiols of polyhydric alcohols, were synthesized by the American and British investigators. Among these were thiosorbitol, prepared at the du Pont de Nemours and Company laboratories, and the glu-coside of BAL, first synthesized by Danielli and co-workers (1). The historical background which led to the synthesis of BAL and its derivatives, and the basic contributions which have resulted-from studies on the effect of mercaptans on the toxic action of arsenic and other heavy metals, have been summarized by Peters (2) and Waters and Stock (3). Pertinent to the background of the present study were the observations supporting the general hypothesis that heavy metals are toxic to biological systems because of their reaction with SH groups of the protein moiety of cellular enzymes to form mercaptides. That mercury shares in this action has been demonstrated by Barron and co-workers (3). Moreover, BAL is capable of reactivating enzyme systems poisoned by mercury, a fact which both affords support to the theory of the mechanism of inactivation, and gives promise for the therapeutic efficacy of mercaptans in the treatment of mercury poisoning. The present report is concerned with the efficacy of BAL, BAL glucoside and thiosorbitol in the treatment of experimental , acute, systemic mercury poisoning in rabbits and dogs. The reactions between mercaptans and Hg++ in uitro The reactions between mercaptans and cationic mercury which occur in vitro are presumably indicative of the expected interaction of the two agents in vivo. A brief study of the chemical reactions between the various mercaptans and mercury was, therefore, undertaken. Reactions zvith BAL. When solutions of HgCl, (0.1 M) were added to non-buffered, aqueous solutions of BAL (0.05 M) a copious, flocculent white precipitate formed. Titration with phenolphthalein as an indicator revealed the formation of 2 equivalents of H+ for each mol of HgCl, added. The white precipitate was insoluble in alkali, but could be …

the journal of clinical investigation/the journal of clinical investigation

CLINICAL USES OF 2,3-DIMERCAPTOPROPANOL (BAL). X. THE TREATMENT OF ACUTE SYSTEMIC MERCURY POISONING IN EXPERIMENTAL ANIMALS WITH BAL, THIOSORBITOL AND BAL GLUCOSIDE