EVALUATION OF THE NEUROTOXIC POTENTIAL OF CHEMICALS IN ANIMALS

This review provides a scientific view on how to evaluate effectively the neurotoxic potential of chemicals in order to provide adequate saf eguards for human health. Detection of compounds that may cause direct , persistent, adverse effects on the nervous system should be given th e most critical attention. Evaluation of the neurotoxic potential of a chemical should include descriptions of functional and morphological effects as well as the determination of the dose response, no-observed -effect level, time course and reversibility of effects. Evaluation of the nervous system in the context of standard toxicity studies that u se a variety of species and study durations are appropriate screening tests (Tier 1) for the detection of potential neurotoxicity. Studies s pecifically designed to assess neurotoxicity (Tier 2) should be perfor med with chemicals for which there is an indication of neurotoxic pote ntial and where the available data are inadequate for risk assessment. Tier 2 studies should evaluate the function and structure of the nerv ous system by comprehensive clinical examinations and neuropathologica l assessment. These studies may be conducted in conjunction with stand ard toxicity studies so that any potential neurotoxicity can be interp reted in the context of other systemic toxicity. More specific neuroto xicity tests (Tier 3) may be necessary for advanced characterization o f discovered neurotoxicants.