Neuropathological Evaluation of Acrylamide- and 3,3'-Iminodipropionitrile-Induced Neurotoxicity in a Rat 28-Day Oral Toxicity Study-Collaborative Project for Standardization of Test Procedures and Evaluation of Neurotoxicity.

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In order to standardize test procedures for evaluation of neurotoxicity of chemical exposure, a collaborative study with a common protocol based on the Organization for Economic Cooperation and Development (OECD) test guideline TG407 was conducted by eleven laboratories, using acrylamide and 3,3’-iminodipropionitrile (IDPN) as positive neurotoxicants. This report summarizes the results of this neuropathological evaluation of neurotoxicity, when acrylamide (3, 10, and 30 mg/kg) and IDPN (20, 50, and 100 mg/kg) were orally administered to rats for 28 days. The study revealed typical alterations, including degeneration of peripheral nerve fibers and Purkinje's cell necrosis with acrylamide, and axonal swelling in the brainstem and spinal cord with IDPN. In addition to the neurotoxicity, IDPN exerted toxic effects on the cerebral arteries, hyalinization of vessel walls being observed. In general, the neuropathological findings well demonstrated the neurotoxicity of both chemicals. These results indicate that neuropathological evaluation can play a crucial role in screening for potential neurotoxicants with risk for human health, the expected neurotoxic effects being detected in this collaborative study consistently in all the laboratories.

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