Effect of dithiocarb on metabolism and covalent binding of carbon tetrachloride

Rat liver microsomes catalyze covalent binding of ¹⁴CCl₄ metabolites to the microsomal protein; this binding was inhibited by dithiocarb at an I50 of 2.3 × 10^-5 m. With mouse liver microsomes, the I50 was 6 × 10^-5 m. The inhibiting potency of dithiocarb on the metabolic activation of carbon tetrachloride was comparable to that of 1-naphthyl-4(5)-imidazole, and was much greater than that of benzothiadiazoles or of SKF 525-A. In vivo, the effect of dithiocarb on the metabolic transformation of carbon tetrachloride was studied in rats and mice exposed to CCl₄ vapor in a closed system. Dithiocarb effectively inhibited metabolic elimination of carbon tetrachloride at a dose of 100 mg/kg. The data suggest that the proven antagonism of dithiocarb with the hepatotoxic effects of carbon tetrachloride should be related to inhibition of metabolic activation of the latter.