EVALUATION OF THE POTENTIAL DEVELOPMENTAL TOXICITY OF 3-AMINOPENTANENITRILE (3-APN) IN THE RAT

Abstract

The potential developmental toxicity of 3-aminopentanenitrile (3-APN) was assessed in rats. Groups of 25 time-mated female Crl:CD®(SD)IGS BR rats were orally gavaged at daily dose levels of 0, 5, 30, 100 or 300 mg/kg over days 6–20 of gestation (days 6–20G); the day of copulation plug detection was designated day 0G. The dams were euthanized on day 21G and their abdominal and thoracic viscera were examined grossly. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal alterations. Evidence of maternal and developmental toxicity was seen at 100 and 300 mg/kg. Regarding maternal toxicity, there were compound-related, statistically significant reductions in maternal body weight and food consumption at 100 and 300 mg/kg. The incidence of alopecia was significantly increased at these levels as well. Regarding developmental toxicity, mean fetal weight was slightly but significantly reduced at 100 and 300 mg/kg. In addition, at 300 mg/kg, there were significant increases in several skeletal variations (wavy ribs and skull, rib, and vertebral ossification delays) consistent with developmental delay. There was no evidence of either maternal or developmental toxicity at 5 or 30 mg/kg. Thus, the maternal and developmental no-observed-effect level (NOEL) was 30 mg/kg. Because developmental toxicity was observed only after administration of doses that also produced signs of maternal toxicity, 3-APN is not considered to be a selective developmental toxicant in the rat.