Subchronic toxicity of acrylamide administered to rats in the drinking water followed by up to 144 days of recovery.

Abstract

Groups of male and female Fischer 344 rats were administered acrylamide in their drinking water at 0, 0.05, 0.2, 1, 5, or 20 mg/kg/day for up to 93 days. Following the administration of acrylamide in the drinking water, male rats from each dose level were held for up to 144 days of recovery. The 20 mg/kg/day groups had definite treatment-related effects after 92 (males) and 93 (females) days. They were dragging the rear limbs, body weights were decreased, serum cholinesterase activity was decreased in top dose females, and packed cell volume, red blood cell, and hemoglobin values were slightly decreased in males and females. In the 20 mg/kg/day groups, the primary target tissue was the peripheral nerve with lesions consisting of severe degeneration characterized by demyelinization and axonal loss. Slight spinal cord degeneration was observed. Other effects included atrophy of skeletal muscle, testicular atrophy, and distended urinary bladders; these were probably secondary to the nerve degeneration. After 144 days of recovery, the lesions had partially or completely reversed. Parameters affected at the 5 mg/kg/day dose level after 92 (males) and 93 (females) days consisted of peripheral nerve degeneration which were of a lesser degree of severity than those seen in the 20 mg/kg/day groups and appeared to have completely reversed after 111 days of recovery. In rats given 1 mg/kg/day, a minimal treatment-related effect was observed in males after 92 days, and this was limited to very slight nerve degeneration using electron microscopy (females were not examined by electron microscopy). This observed effect appeared to have reversed after 25 days of recovery. No treatment-related effects were seen in any of the parameters monitored in the rats given 0.05 or 0.2 mg/kg/day of acrylamide.