CLINICAL USES OF 2,3—DIMERCAPTOPROPANOL (BAL). III. STUDIES ON THE TOXICITY OF BAL ON PERCUTANEOUS AND PARENTERAL ADMINISTRATION 1

Abstract

Approximately 0.3 g. of BAL applied to the skin in the form of BAL 10% in K-Y jelly, or BAL 10% in petrolatum, produced no signs or symptoms in 5 healthy, white, d* sub-jects except for transitory local erythema, whealing, and itching at the site of application. Approx. 1.7 gs. of BAL applied to large areas of the skin in the form of a 5% concn. of K-Y jelly produced no convulsive phenomena, blood changes, kidney or other damage, and no other forms of systemic poisoning in any of 5 healthy young cf subjects. However, one subject with a previous history of fainting spells became faint within 20 mins. after the application. There were various degrees of local whealing, ranging from scarcely visible isolated evanescent wheals in some subjects, to severe generalized and rather persistent whealing of all the areas receiving the inunction in one subject. These effects were never incapacitating. A soln. containing 10% BAL and 20% benzyl benzoate in peanut oil was injected intramusc. according to various dosage schedules in a total of 34 human volunteers. There was considerable variation in the individual response, but, in general, toxic manifestations appeared at a dose of approximately 3.6-5.5 mg./kg. These manifestations included nausea, vomiting, headache, burning sensation of lips, mouth and throat, feeling of constriction and sometimes pain in throat and chest, burning and tingling of extremities, conjunctivitis, tearing, rhinorrhea, salivation, sweating of forehead and hands, abdominal pain, and general agitation. Local pain at the site of injn. and muscle spasm of the leg were also quite common. Perhaps the most significant finding was elevation of systolic and diastolic blood pressure within about 1/2 hr. after the injn. Except for 1 subject in whom some of the ill effects persisted for over 24 hrs., the subjects had returned to normal within 45 mins. to 2 hrs. after the injns. No regular cumulative effects were noted when 4 doses of approx. 5 mg./kg. were given in 4 successive injns. 4 hrs. apart. However, when the first 2 doses were given with an interval of only 2 hrs., distinct cumulative toxicity was observed. Reinjns. of a total avg. dose of 6.2 mg. BAL/kg. administered 15-27 days after the last previous injn. elicited no signs of systemic sensitization. Attention is called to the fact that these studies were carried out in volunteers who were not suffering from arsenical or other metallic poisoning. The presence or absence of such poisoning may or may not be a factor in determining the tolerance of BAL. It is concluded that topical application of BAL prepns., at least within the dosage range of the studies, and as would be administered in applying 5% ointments to as much as 50% of the skins'' surface, is a safe procedure.