Combined repeated dose and reproductive/developmental toxicity screening test of tert-butylhydrazine monohydrochloride in rats.

tert-Butylhydrazine monohydrochloride was daily administered by gavage to groups of Crl:CD (SD)IGS rats at doses of 0 (control), 0.8, 4, or 20 mg/kg/day. Twelve males per group were treated for a total of 42 days from 14 days before mating. Twelve females per group were treated from 14 days before mating to day 4 of lactation throughout the mating and gestation periods. Recovery groups of five males and five non-pregnant females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in any groups of either sex. There were no considerable changes in body weight, food intake, general appearance, functional observations or biochemical analysis. Values of the anemic parameters were decreased in the 20 mg/kg/day males and in all female dose groups. The relative weight of the liver, kidneys and spleen was significantly increased in 20 mg/kg/day females. Histopathological examination showed congestion and hemosiderin deposition in the spleen at 20 mg/kg/day in both sexes, but there were no changes in the liver or kidneys in either sex. Anemic parameters with hemosiderin deposition did not completely recover in the 20 mg/kg/day group in both sexes after the recovery period. As for reproduction, a significant reduction was only observed in the number of corpora lutea at 20 mg/kg/day. It was thus concluded that the LOAEL was 0.8 mg/kg/day based on the decreased values of the anemic parameters of repeated-dose toxicity, and that the NOAEL was 4 mg/kg/day based on the low number of corpora lutea of reproductive/developmental toxicity.