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In the course of routinely performed subchronic toxicity studies with laboratory rodents, functional neurotoxicity, i.e., behavioral changes, usually are noted first during the daily cageside observations of all animals, Observation and neurologic examination of a few key animals provide a tentative diagnosis. Subsequent automated testing procedures for further characterization and quantifying behavioral changes might include motor activity, startle response, hurdle stepping, and maze behavior. Automated testing serves to assess the no observable effect under conditions of blind testing and provides further refinement of the diagnosis. Behavioral changes should be assessed as early as possible after onset of testing, i.e., during acute tests for mortality and the subsequent subchronic range-finding studies. Subsequent subchronic organ toxicity studies are then carried out by following a validated experimental protocol, including automated testing procedures and appropriate neuropathologic evaluation.

Practical Procedure of Testing for Neurotoxicity