Clinical Uses of 2,3—dimercaptopropanol (Bal). Iii. Studies on the Toxicity of Bal on Percutaneous and Parenteral Administration 1

Abstract

Ointments and vehicles containing BAL may, on occasion, have to be used over extensive skin areas, and also repeatedly, within relatively short periods of time. For this reason it was essential to ascertain the possible systemic toxic effects of BAL on repeated application to extensive skin areas in man. Moreover, before the parenteral administration of BAL could be adopted as a method for treating certain metallic poisonings, it was imperative to ascertain the toxicity of BAL preparations when administered parenterally in human subjects.The following are among the important findings which form the background of the present studies. Early experiments in laboratory animals had demonstrated that the external application of BAL to the skin can produce systemic toxic manifestations and even lethal effects (1 to 4). With 1 early sample of BAL, doses of 600 mgm. per kgm. killed about 1/2 the mice when applied externally. It has been shown, however, that early lots of BAL were considerably more toxic than the standard product of later manufacture.Also, there was evidence that significant quantities of BAL penetrate the grossly normal human. skin quite rapidly when BAL is applied, either undiluted or in various vehicles. This is shown by the almost immediate whealing and erythema produced, and by certain systemic effects which have been observed following external application.The latter include the benefits produced on arsenical dermatitis in skin areas distant from the actual sites of application (5), and the occasional malaise, nausea, etc. seen during the course of experimental application of BAL to the skin.Thus Stocken and Thompson (1) applied 0.5 ml., and later 1 ml., of undiluted British BAL to

Clinical Uses of 2,3—dimercaptopropanol (Bal). Ii. The Effect of Bal on the Excretion of Arsenic in Normal Subjects and After Minimal Exposure to Arsenical Smoke

“…Significant but temporary local pain followed all injections. The incidence of these symptoms was higher than those reported by other investigators (7, 4) …”

“…Significant but temporary local pain followed all injections. The incidence of these symptoms was higher than those reported by other investigators (7,4) Table I. They are graphically shown in Figure 1, in which the excretion in each 2-hour period after the injection of BAL has been plotted relative to the average 2-hourly excretion for that individual prior to the administration of BAL.…”

Clinical Uses of 2,3-Dimercaptopropanol (Bal). Vii. The Treatment of Arsenical Dermatitis With Preparations of Bal

“…of BAL per kgm. of body weight at 6-hour intervals.2 2 While our studies were in progress, the effects of injection of large doses of BAL in peanut oil were tested in human volunteers (4,10,11 continued, but could be controlled by reinstituting treatment, and that the excretion of arsenic in the urine increased during each course of treatment by BAL, but decreased rapidly each time that the administration of BAL was omitted. suggested very strongly that there was a relationship between the 2 sets of conditions.…”

Clinical Uses of 2,3-Dimercaptopropanol (Bal). V. Skin Sensitization to Bal 1

“…The applications were to be stopped as soon as a persistent and definite erythema or other type of eruption appeared. The transitory erythema and whealing (6), which are quite regularly observed 15 minutes to 2 hours after application of BAL, were discounted.…”