Chapter 8 - Nervous System

Abstract

Neuropathology remains the benchmark to detect neurotoxicity in animal toxicology studies. Along with neurobehavioral endpoints, morphological changes are used to identify or characterize neurotoxicity during routine safety assessments of regulated products in general commerce. General principles and methods underlying meaningful evaluation of neurotoxicity include strategic study design, collective analyses of multiple endpoints and integrative data analysis based on an understanding of neuroanatomy, neurophysiology, mechanisms of toxicity, and responses to neurotoxic injury within the nervous system. The narratives were written with the practicing toxicologic pathologist in mind to highlight aspects specific to the susceptibility of the nervous system to toxicants as well as the specificity of neurotoxicants to various components within the nervous system. This chapter provides an overview of basic neuroanatomy, neurophysiology, various methodological approaches in the evaluation of neurotoxicity, known mechanisms of neurotoxic injury, and responses to neurotoxic injury with a focus of morphological aspects encompassing neuropathology. A brief synopsis of regulatory perspectives impacting neuropathology evaluation in the context of potential neurotoxicity is included.