The effects of acrylamide given acutely or in repeated doses on fore- and hindlimb function of rats

Abstract

Male, albino rats of the Fischer strain were given 50 to 250 mg/kg acrylamide orally. The LD50 (and 95% confidence intervals) was estimated to be 251 mg/kg (203–300) at 24 hr postdosing and 175 mg/kg (159–191) at 168 hr postdosing. Rats given 50, 100, and 200 mg/kg acrylamide orally were tested for muscular dysfunction at 12 and 168 hr post-dosing. At 12 hr after dosing, acrylamide produced marked deficits in hindlimb motor functioning, as measured by the hindlimb extensor test and performance on the inclined screen. Recovery of hindlimb function was complete at 168 hr after dosing. Forelimb grip strength was not affected at either test period. In a 4-week repeated dosing experiment, rats given 10 or 20 mg/kg/day, 5 days per week, showed hindlimb dysfunction at a cumulative dose of 50 to 100 mg/kg while rats receiving up to 400 mg/kg over a period of 4 weeks showed no signs of diminished forelimb grip strength. Recovery of hindlimb motor function was evident, but not complete, 2 weeks after cessation of dosing. The tests of motor function used in this study were sensitive to and capable of detecting specific motor deficits in rats treated with relatively low doses of acrylamide. The rapidity and ease with which the tests can be used in experiments involving repeated measures suggest their use in assessing other chemicals for potential neurotoxicity.