Behavioral Outcome as a Primary Organizing Principle for Mechanistic Data in Developmental Neurotoxicity

Abstract

There is a vast and growing quantity of mechanistic data showing changes from exposure to chemical agents, due in part to a preponderance of mechanistic studies and in vitro high-throughput technologies. Particularly challenging is the interpretation of mechanistic data for determining neurotoxic risk from developmental exposure. Brain development occurs through plastic processes, homeostatic disruption, iterative adaptation, and “learning” at a mechanistic level, all of which suggest changes in mechanisms that may be indistinguishable from “neurotoxic” processes. The central tenet of neuroscience, that behavior reflects central nervous system function, suggests a basis for organizing our interpretation of mechanistic effects. Behavior may serve as an organizing principle that draws our attention to, and marks the significance of, one or more salient mechanisms within and across developmental stages. In this chapter, we explain the rationale for this approach, define its assumptions, and provide examples of this approach.