Developmental toxicity of N-methylformamide administered by gavage to CD rats and New Zealand white rabbits.

N-Methylformamide (NMF) is a metabolite of dimethylformamide (DMF), a solvent with wide applications in the chemical industry. The potential developmental toxicity of NMF was evaluated in CD rats and New Zealand white rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation Days 6-15 and 6-18, respectively. Doses for rats were 0, 1, 5, 10, or 75 mg/kg; doses for rabbits were 0, 5, 10, or 50 mg/kg. Cesarean sections were performed on rats and rabbits on Gestation Days 20 and 29, respectively. No treatment-related maternal deaths or clinical signs occurred in either species. Body weight gain and food consumption were depressed in rats given 75 mg/kg and rabbits given 50 mg/kg. Fetal viability was reduced at 75 mg/kg in rats and at 50 mg/kg in rabbits. In rats, a significant increase in the incidence of malformations including cephalocele and sternoschisis was observed in fetuses from the 75 mg/kg group. In addition, a developmental delay was indicated by reduction of fetal weight and by a significant increase in the occurrence of incomplete ossification of various skeletal structures. In the rabbit, fetal body weight was reduced at 50 mg/kg. Malformations observed at 50 mg/kg included gastroschisis, cephalocele, domed head, flexed paw, and skull and sternum anomalies. The lowest-observed-adverse-effect levels for maternal and developmental toxicity in the rat and rabbit were 75 and 50 mg/kg, respectively. The no-observed-adverse-effect level for maternal and developmental toxicity in the rat and rabbit was 10 mg/kg.

Developmental toxicity of amesergide administered by gavage to CD rats and New Zealand white rabbits.

Amesergide is a selective serotonin 5-HTIC/2 receptor antagonist being developed for the treatment of depression. The potential developmental toxicity of amesergide was evaluated in CD rats and New Zealand white rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation Days 6-17 and 6-18, respectively. Doses for rats were 0, 3, 10, and 30 mg/kg; doses for rabbits and 0, 0.2, 2, and 15 mg/kg. Cesarean sections were performed on rats and rabbits on Gestation Days 20 and 28, respectively. In rats, maternal effects expressed as depression of body weight gain and food consumption were observed at the 30 mg/kg dose level. Fetal viability and morphology were not affected at any dose level. Fetal weight was depressed at the 30 mg/kg dose level. The no-observed-effect level (NOEL) in the rat was 10 mg/kg. In rabbits, maternal effects expressed as a decrease in food consumption occurred at the 2 and 15 mg/kg dose levels; weight gain was depressed at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. The NOELs for maternal and developmental effects in the rabbit were 0.2 and 15 mg/kg, respectively.