LIVER CARCINOGENESIS BY METHYL CARBAMATE IN F344 RATS AND NOT IN B6C3F1 MICE

Short-term and long-term carcinogenicity of methyl carbamate (MCB) was evaluated in F344 rats and B6C3F1 mice. In experiments lasting 6, 12, and 18 months, MCB was given in water by gavage to groups of 10 male and 10 female rats at 0 or 400 mg/kg body weight, 5 days per week, and to similar groups of mice at 0 or 1,000 mg/kg. At 6 months, MCB induc ed atypical mitoses, cytologic alterations, cytomegaly, pigmentation, necrosis, and neoplastic nodules of the liver in rats. At 12 and 18 mo nths, carcinomas of the liver were induced by MCB in 80-90% of male ra ts and in 60-80% of female rats. None was observed in control rats or in mice. In the 2-year studies, MCB was given to groups of 50 male and 50 female rats at 0, 100, or 200 mg/kg and to similar groups of mice at 0, 500, or 1,000 mg/kg, 5 days/week. Chronic focal inflammation, cy tologic alteration, hyperplasia, and neoplastic nodules and carcinomas (200 mg/kg groups only) of the liver were induced by MCB in rats. Liv er tumor incidence data for combined experiments in rats were: males - 5% in controls, 0% in 100 mg/kg group, 14% in 200 mg/kg group, and 77 % in 400 mg/kg group; females - 0% in controls, 0% in 100 mg/kg group, 12% in 200 mg/kg group, and 63% in 400 mg/kg group. MCB was not shown to be carcinogenic in mice.