MEPANIPYRIM INDUCES FATTY LIVER IN RATS BUT NOT IN MICE AND DOGS

Abstract

Mepanipyrim, a new fungicide, was administered orally to rats, mice and dogs for 13 weeks to clarify its toxic profiles. Hepatotoxicities were observed characteristically in these species with high concentrations of mepanipyrim; more than 200 ppm in rats, more than 1, 000 ppm in mice, and more than 50 mg/kg/day in dogs. In rats, obvious fatty vacuolation in the perilobular hepatocytes and changes in the serum-lipid concentrations such as total cholesterol(TC), triglyceride(TG), phospholipid(PL)and non-esterified fatty acid(NEFA)were observed. This fatty liver appeared to be based on the alteration of lipid metabolism. In contrast, no remarkable changes were observed in mice and dogs except for an enhancement of anisonucleosis in mice or a lipofuscin deposition in Kuppffer cells and hepatocytes in dogs. It appeared that there species differences in the hepatotoxicities of mepanipyrim.