Subchronic (13-week) toxicity studies of N,N-dimethylaniline administered to Fischer 344 rats and B6C3F1 mice.

The subchronic toxicity of N,N-dimethylaniline (DMA) was studied by administration in corn oil by gavage at doses of 31.25, 62.5, 125, 250, 20, or 500 mg/kg body weight to groups of 10 male and 10 female F344 rats and B6C3F1 mice 5 d per week for 13 wk. No compound-related mortality was noted in either rats or mice. Significant decrease in body weight gain was observed in male rats at 250 and 500 mg/kg. The body weight gain of female rats and female mice was not adversely affected by the treatment. Clinical signs of toxicity (cyanosis and decrease in motor activity) occurred in both species and sexes in a dose-dependent fashion. Splenomegaly was observed in all treated groups of rats and mice, with the severity being dose-related. Microscopic examination revealed the presence of hemosiderin in the spleen, liver, testes, and kidney of treated rats and mice. Bone marrow hyperplasia and increased hematopoiesis in the spleen occurred in treated rats, and hematopoiesis was increased in the spleen and liver of treated mice. The severity of these lesions was dose-related. A no-observable-effect for mice was estimated at 31.25 mg/kg; however, a no-effect level was not reached in rats in this study. This suggests that rats are more sensitive than mice to the toxic effect of DMA.