THE TOXICITY OF BENZYLPENICILLIN IN ANIMALS ON VITAMIN A DEFICIENT TEST DIET, U.S.P. XIV

Abstract

Young, adult albino mice and rats became more susceptible to the acute and chronic toxic effects of benzylpenicillin after they had been fed vitamin A deficient test diet, U.S.P. XIV, for about 1 month. At and after this interval, there occurred a significant increase in the percentage mortality from a single oral or subcutaneous LD₅₀ of benzylpenicillin in mice and the chronic toxicity of a daily oral 0.1 L-LD₅₀ of benzylpenicillin was augmented in rats. Replacement of vitamin A, in the deficient diet or by daily intramuscular injection, did not affect the increased susceptibility to benzylpenicillin toxicity. A dietary supplement containing nine other vitamins was also without effect. Change in diet alone was not a factor since rats did not become appreciably more susceptible to the toxic effects of a daily oral 0.1 L-LD₅₀ of benzylpenicillin when their diet was changed from a standard laboratory chow to a rachitogenic test diet. Some unknown factor or factors in vitamin A deficient test diet, U.S.P. XIV, therefore, made the animals more susceptible to the toxic effects of benzylpenicillin.