Neurological Approach to Neurotoxicological Evaluation in Laboratory Animals

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Abstract
The neurotoxicological potential of a compound is best evaluated with information from a wide variety of tests. Our philosophy is that tests should be applicable across species and emphasize complementarity to neuropathology. Electrophysiologic tests comparable to those in human clinical neurology fulfill these requirements. Animals are not anesthetized but are physically restrained during the tests. Routine tests include flash evoked potentials, auditory brainstem responses to clicks and tone pips, somatosensory evoked responses, and caudal nerve action potentials. Tests can be added (e.g., H-reflex, EMG, or EEG) or deleted as circumstances warrant. A careful clinical examination of all animals (functional observational battery) and, for rats, a test of grip strength are utilized as well. Neuropathology typically includes perfusion fixation and special stains of histological sections from the central and peripheral nervous systems. Approximately half the animals are retained as a recovery group for subsequent tests if warranted by the results of the neurotoxicological evaluation. The neurological approach, in conjunction with standard toxicological studies, provides data with the necessary breadth and depth for a comprehensive evaluation of neurotoxicity.