Thirteen-Week Oral Toxicity Study of Methyl Carbamate in Rats and Mice

Thirteen-Week Oral Toxicity Study of Methyl Carbamate in Ratsand Mice. Quest, J. A., CHAN, P. C, CRAWFORD, D., KANAGALINGAM,K. K., and HALL, W. C. (1987). Fund. Appl. Toxicol. 8, 389–399.The purpose of this study was to identify the toxicologic effectsproduced by methyl carbamate in F344 rats and B6C3F₁ mice. Administrationof methyl carbamate by gavage five times a week for 13 weeksto 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 theliver characterized by proliferative changes in hepatocytesconsisting of foci of cellular alteration and frequent mitoseswith atypical forms. Toxic alterations consisted of focal hepatocellularnecrosis, pigmentation of Kupffer's cells, and the presenceof basophilic inclusions resembling nucleoli in the cytoplasmof hepatocytes. Other toxic effects observed in rats were weightloss, testicular hypoplasia, bone marrow hyperplasia, and excessivepigmentation of the spleen. The survival of male and femalerats was reduced following administration of the highest doseof methyl carbamate. In contrast to these findings, administrationof 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 timesa week for 13 weeks resulted only in weight loss and inflammatorychanges of the liver. The proliferative nature of the hepaticlesions observed in rats suggests that the compound is potentiallyhepatocarcinogenic.