Evaluation of the potential developmental toxicity of 3-aminopentanenitrile (3-APN) in the rat

The potential developmental toxicity of 3-aminopentanenitrile (3-APN) was a ssessed in rats. Groups of 25 time-mated female Crl:CD(R)(SD)IGS BR rats we re orally gavaged at daily dose levels of 0, 5, 30, 100 or 300 mg/kg over d ays 6-20 of gestation (days 6-20G); the day of copulation plug detection wa s designated day OG. The dams were euthanized on day 21G and their abdomina l and thoracic viscera were examined grossly. The fetuses were weighed, sex ed, and examined for external, visceral, and skeletal alterations. Evidence of maternal and developmental toxicity was seen at 100 and 300 mg/kg. Rega rding maternal toxicity, there were compound-related, statistically signifi cant reductions in maternal body weight and food consumption at 100 and 300 mg/kg. The incidence of alopecia was significantly increased at these leve ls as well. Regarding developmental toxicity, mean fetal weight was slightl y but significantly reduced at 100 and 300 mg/kg. In addition, at 300 mg/kg , there were significant increases in several skeletal variations (wavy rib s and skull, rib, and vertebral ossification delays) consistent with develo pmental delay. There was no evidence of either maternal or developmental to xicity at 5 or 30 mg/kg. Thus, the maternal and developmental no-observed-e ffect level (NOEL) was 30 mg/kg. Because developmental toxicity was observe d only after administration of doses that also produced signs of maternal t oxicity, 3-APN is not considered to be a selective developmental toxicant i n the rat.