Comparison of toxicities of acrylamide and 2,5-hexanedione in hens and rats on 3-week dosing regimens.

Survival rates, changes in body weight, gait/ataxia scores, and neuropathological lesions were compared between adult Long-Evans rats and adult White Leghorn hens given equivalent dosages of the peripheral neurotoxicants acrylamide and 2,5-hexanedione (12, 25, and 50 mg/kg acrylamide 3 times per week; or 75, 105, 150, 225, or 350 mg 2,5-hexanedione/kg/d, with hens receiving the lowest 3 dosages of 2,5-hexanedione and rats receiving the highest 3 dosages of this test compound). All rats survived the 3-wk acrylamide study period, although those given 50 mg/kg did not gain weight and showed alterations in gait. Hens given 50 mg/kg acrylamide were moribund by 2 wk and were sacrificed before the end of the 3-wk study period. By this time they had lost 29 +/- 3% of their body weight, but none showed significant renal or hepatic lesions on necropsy. Hens given all doses of acrylamide showed dose-related ataxia, weakness, and depression. Gait changes were seen in rats given the high dose of acrylamide for the 3-wk test period. Neuropathological studies revealed that both rats and hens given acrylamide had distal myelinated fibers with dose-related neurofilament-rich axonal swelling and Wallerian-like degeneration, better developed in the rodents. In addition, high-dose acrylamide rats had recent necrosis of cerebellar Purkinje cells. Deaths occurred in all groups of hens given 2,5-hexanedione (75, 105, or 150 mg/kg) before sacrifice at 3 wk, but all rats given 2,5-hexanedione (150, 225, 350 mg/kg) survived a 4-wk study period, even though gait changes were evident in the 225 and 350 mg/kg dosage groups by 3 wk. Neither hens nor rats dosed with 2,5-hexanedione for 3 wk had significant neuropathic lesions, although the hens showed dose-related ataxia, weakness, and depression. Early neurofilamentous intraaxonal masses in distal levels of selected myelinated tracts were seen in rats given the high dose of 2,5-hexanedione for an additional week. These studies suggest that hens are sensitive to acrylamide and 2,5-hexanedione toxicities, and that the rat is more likely than the hen to develop neuropathological lesions.