THE EFFICACY OF BAL (2,3-DIMERCAPTOPROPANOL) IN THE TREATMENT OF EXPERIMENTAL LEAD POISONING IN RABBITS

¹ Laboratory of Experimental Therapeutics, U. S. Public Health Service and The Johns Hopkins School of Hygiene and Public Health, Baltimore 5. Maryland

1. Five consecutive daily subcutaneous injections of lead acetate at a dosage of 240 mg. of compound per kg. per injection regularly caused the death of rabbits within 3 to 40 days after the last injection. The intravenous injection of the same salt at a dosage of 12 mg./kg. per injection, repeated every 3 hours for 4 doses, produced an acute poisoning from which the animals died in 1 to 18 days, averaging 3 days.

2. The intramuscular administration of BAL in peanut oil and benzyl benzoate, at individual dosages of 5 to 20 mg./kg., and repeated every 4 hours, failed to protect animals poisoned with lead acetate by either route of administration. In one group of animals with subacute (subcutaneous) lead poisoning, the animals treated with BAL died significantly faster than did the corresponding untreated controls.

3. The administration of BAL caused a marked increase in the urinary excretion of lead. For 2 hours after a single injection of BAL at 20 mg./kg., the urinary excretion of lead increased 11-to 40-fold in animals with a subcutaneous depot, and 3-to 7-fold in animals injected intravenously. This favorable effect on the excretion of lead lasted for approximately four hours after a single injection of BAL. The magnitude of the excretion response diminished with each additional injection of BAL, suggesting that only a small fraction of the lead injected could be dissociated by BAL from its combination with tissues.

4. The failure of BAL to protect these animals may be in part due to the fact that it mobilizes only a small fraction of the total body store of lead, and in part to the fact that the lead-BAL complex proved almost as toxic as the lead salt itself on intravenous injection.

5. The only pathological changes produced by subcutaneous injections of lead acetate were occasional intranuclear inclusions in the renal epithelium and liver parenchyma, seen only in those animals which survived an eventually lethal dose for 3 weeks or more. Treatment with BAL had no demonstrable effect on the development of these inclusions.

6. The implications with respect to the possible use of BAL in the treatment of lead poisoning in man are discussed in the text.