Detecting functional neurotoxicity in the course of safety evaluations with laboratory animals

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