Acrylamide, a widely used industrial chemical with neurotoxic properties, was evaluated for developmental toxicity in CD-1 mice. ACRL (0, 3, 15 or 45 mg/kg) in distilled water was administered once daily by gavage on gestational days 6 through 17. Timed-mated females (25-29 confirmed-pregnancies/ group) were weighed and observed daily during treatment for clinical signs. At scheduled necropsy (gd 17). the maternal body, liver and intact uterus were weighed. The number and status of uterine implantation sites were recorded. Each live fetus was weighed, sexed, and examined for external, visceral and skeletal malformations.
Maternal body weight on gd 17, as well as weight gain during treatment (gd 6-17) and gestation (gd 0-17) were reduced at the high dose. Hindlimb weakness was observed at the high dose during the final three days of the treatment period with the highest incidence on gd 17 (0%, 0%, 0% and 48% of females in the control through high-dose groups, respectively). Embryo/fetal toxicity was expressed as a significant reduction in average fetal body weight per litter at the high dose, accompanied by significantly reduced gravid uterine weight. At the mid-dose level, significantly reduced gravid uterine weight appeared to be secondary to a spurious increase in prenatal mortality. The incidence of major malformations (external, skeletal or visceral) was not increased at any dose. The incidence of extra lumbar rib(s), classified as an anatomical variation, showed an increasing dose-response trend, but no statistically significant pairwise comparisons occurred between individual acrylamide-treated groups and the control group.
In conclusion, the low- and mid-dose levels (3 and 15 mg ACRL/kg/day) were NOAEL's for all maternal and embryo/fetal endpoints. Well-defined maternal and embryo/fetal toxicity was observed at the high dose (45 mg ACRL/kg/day).