[Twenty-eight day repeated dose toxicity test of m-nitroaniline in F344 rats]

A twenty-eight day repeated oral dose toxicity test of m-nitroaniline (m-NA) was carried out in male and female F344 rats at dose levels of 0, 15, 50 or 170 mg/kg/day. Animals of both sexes were divided into 6 groups, each consisting of 30 animals, 4 groups being used for the 28 days dosing study and the remainder for investigation of subsequent recovery. Inhibition of body weight gain, and induction of cyanosis and methemoglobinemia were observed in the highest dose groups of both sexes, but there were no animal mortalities. Testicular atrophy was evident but there was no effect on the ovaries in the same group. In addition to these findings, hemolytic anemia and increases of liver, spleen and kidney weights were also observed in both sexes in a dose-related fashion. Histologically, the highest dose group showed reduction of spermatogenesis with multinucleated giant cell formation, lipofuscin deposition mainly in the proximal renal tubules, and increases in hemosiderin deposition and extramedullary hematopoiesis in the liver. Dose-related increases in the incidence of hemosiderin deposition in the spleen, erythroid hyperplasia in the bone marrow and swelling of hepatocytes were observed in treated groups. After a 14 day recovery period, these findings were attenuated or had disappeared. Based on these results obtained under the present experimental conditions, it was concluded that m-NA induces hemolytic anemia and exerts testicular toxicity in rats and that the non-observed-effect level of m-NA is less than 15 mg/kg/day.