CLINICAL USES OF 2,3—DIMERCAPTOPROPANOL (BAL). I. THE SYSTEMIC TREATMENT OF EXPERIMENTAL ARSENIC POISONING (MAPHARSEN, LEWISITE, PHENYL ARSENOXIDE) WITH BAL 1

Open Access
Publisher Website
Google Scholar
Abstract
BAL injected subcut., intramusc, or intraven. in aqueous or propylene glycol soln., proved effective in the treatment of acute and subacute mapharsen poisoning in rabbits. The antidotal action of BAL was referable to its ability to remove the arsenical from its combination with cells, with the excretion of the stable and relatively non-toxic thio-arsenite so formed. Trypanosomes rapidly immobilized and apparently killed by arsenicals were resuscitated on the addition of BAL, due to the removal of the bound As from the cell. Similarly, in rabbits injected with mapharsen, Lewisite, or phenyl arsenoxide, the admn. of BAL caused a striking increase in the rate of urinary As excretion, in some cases exceeding a 100-fold. Although BAL was unstable in aqueous or propylene glycol soln., solns. in peanut oil could be sterilized by heat with only slight loss in activity. With the addition of 2 gs. of benzyl benzoate for each g. of BAL, the latter was miscible with peanut oil in all proportions. The toxicity of such solns. in peanut oil and benzyl benzoate was detd. in relation to the frequency and number of injns., the route of admn., and the concn. of the soln. BAL dissolved in peanut oil and benzyl benzoate injected intramusc. proved effective in the treatment of mapharsen, Lewisite, and phenyl arsenoxide poisoning in rabbits. The widest margin of safety between the effective and toxic levels of BAL so administered was provided by a schedule involving 4 injns. at 2-4 hr. intervals, followed in some cases by daily injns. for 6 days. On this schedule, individual BAL doses of 1-10 mg./kg. saved approx. half the animals injected with lethal doses of mapharsen, Lewisite, or pheuyl arsenoxide. Since the maximum tolerated dose of BAL so injected was 35 mg./kg., the margin of safety provided was sufficiently large to indicate the feasibility of its human use.