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

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Abstract
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 bens 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.