Acrylamide neurotoxicity in rats: A correlated neurobehavioral and pathological study

Male Fisher albino rats of the F-344 strain were dosed with 5, 10, or 20 mg/kg of acrylamide in distilled water vehicle three times weekly for 13 weeks. Control animals were either not dosed or given 1 ml/100 g ml/100g distilled water vehicle. There were 10 animals per group. Neurobehavioral tests were administered during the week prior to dosing (week 0) and after 1, 4, 7, 10 and 13 weeks of dosing. At the end of the dosing period, 10 rats in the 10 mg/kg group, 5 rats in the 20 mg/kg group, and 5 rats in the distilled water group were sacrificed and assessed for histopathological evidence of acrylamide neurotoxicity. The remaining rats in the high dose group (N = 5) and distilled water control group (N = 5) were retested for neurobehavioral effects 1 and 5 weeks after cessation of dosing and then sacrificed for neuropathological examination. Those rats receiving 20 mg/kg of acrylamide had significantly lower body weights at 4-13 weeks of dosing. Significant decreases in hindlimb function were observed in these animals at 7-13 weeks of dosing, while motor activity was decreased at 10-13 weeks. Forelimb grip strength was not affected during the dosing period. In rats receiving 10 mg/kg of acrylamide, there was a significant decrease in body weight only at the 7 week test. Neurobehavioral measures were not affected at any time in animals dosed with 10 mg/kg. No effects of any sort were seen at 5 mg/kg. At the end of the 13 weeks of dosing, signs of early fiber degeneration were observed in the peripheral nerves of all animals receiving 10 mg/kg of acrylamide, while the rats in the high dose group were found to have signs of moderate to severe acrylamide neurotoxicity. One week after cessation of dosing, fore- and hindlimb scores, spontaneous motor activity, and body weights were significantly decreased in the high dose rats. Five weeks after cessation of dosing, the acrylamide-treated rats did not differ from controls on neurobehavioral measures. Neuropathological examination showed signs of regenerating and remyelinating fibers in the animals previously exposed to acrylamide.