Rat two-generation reproduction and dominant lethal study of acrylamide in drinking water

Abstract

Fischer 344 (F344) F 0 weanling rats, 30/sex/group, were exposed to acrylamide in drinking water at 0.0, 0.5, 2.0, or 5.0 mg/kg/day for 10 weeks and then mated. Exposure of F 0 females continued through gestation and lactation of F 1 litters. F 0 males, after F 0 mating, were removed from exposure and mated (one male: two untreated females) for the dominant lethal (DL) assay. Thirty F l weanlings/sex/group were exposed for 11 weeks to the same dose levels as their parents, and then mated to produce F 2 offspring. F 0 and F l parents and F 1 and F 2 weanlings were necropsied. Prebreeding exposure of F 0 and F l animals resulted in systemic toxicity at 2.0 to 5.0 mg/kg/day, with head tilt and/or foot splay increased at 0.5 to 5.0 mg/kg/day. F 0 and F l reproductive indices and gestational length were unaffected. Implantations and live pups/litter at birth were reduced at 5.0 mg/kg/day. Survival of F l and F 2 pups was reduced at 5.0 mg/kg/day for PND 0 through 4 only. In the DL assay, total and live implants were reduced, pre- and postimplantation loss was increased, and the frequency of DL factors (F L%) was increased at 5.0 mg/kg/day. At 5.0 mg/kg/day, adult F l male peripheral nerves exhibited axonal fragmentation and/or swelling; F l female spinal cord sections were unremarkable. The NOEL for prenatal DL was 2.0 mg/kg/day; the NOEL for adult systemic toxicity, including neurotoxicity, was ≤ 0.5 mg/kg/day. Therefore, neurotoxicity and DL were differentially affected.