Nervous System

Clinical diseases characterized by significant neurological deficits are among the most devastating outcomes produced by exposure to toxicants. The exquisite sensitivity of the nervous system results from its limited capacity, especially centrally, to reverse or compensate for destruction as well as its neural cell–specific mechanisms and manifestations of toxicity. Present regulatory approaches for detecting and managing neurotoxic risk generally regard any substantial toxicant-induced change in neural chemistry, function, or structure as harmful (i.e., adverse). Neurotoxicant-induced injury may appear as an acute illness or death, typically pointing to severe disruption in CNS function, or structure-associated with a high-dose exposure. Alternatively, early declines in neurological function (i.e., premature senescence) and/or the quality of life often follow chronic and low-level neurotoxicant exposure. The practice of toxicologic neuropathology requires an integrated understanding of comparative neurobiology (the major likenesses and dissimilarities among species, strains, ages, and genders) and correlative neurobiology (the relationship among neural structure, function, and chemistry) as well as a solid grasp of neurotoxicant classes, targets, and mechanisms.