Thirteen-week oral toxicity study of methyl carbamate in rats and mice

The purpose of this study was to identify the toxicologic effects produced by methyl carbamate in F344 rats and B6C3F1 mice. Administration of methyl carbamate by gavage five times a week for 13 weeks to male (50, 100, 200, 400, or 800 mg/kg) and female (62.5, 125, 250, 500, or 1000 mg/kg) rats resulted in dose-related lesions in the liver characterized by proliferative changes in hepatocytes consisting of foci of cellular alteration and frequent mitoses with atypical forms. Toxic alterations consisted of focal hepatocellular necrosis, pigmentation of Kupffer's cells, and the presence of basophilic inclusions resembling nucleoli in the cytoplasm of hepatocytes. Other toxic effects observed in rats were weight loss, testicular hypoplasia, bone marrow hyperplasia, and excessive pigmentation of the spleen. The survival of male and female rats was reduced following administration of the highest dose of methyl carbamate. In contrast to these findings, administration of the chemical to male (93.75, 187.5, 375, 750, or 1500 mg/kg) and female (125, 250, 500, 1000, or 2000 mg/kg) mice five times a week for 13 weeks resulted only in weight loss and inflammatory changes of the liver. The proliferative nature of the hepatic lesions observed in rats suggests that the compound is potentially hepatocarcinogenic.