Defining neurotoxicity in a decision-making context

Neurotoxicity is one of several noncancer endpoints used by regulatory agencies in risk assessment. At the US EPA, neurotoxicity is defined as an adverse change in the structure and/or function of the central and/or peripheral nervous system measured at the neurochemical, behavioral, neurophysiological or anatomical levels. Adverse effects include alterations that diminish an organism's ability to survive, reproduce or adapt to the environment. Generally, a weight-of-evidence approach is used to evaluate observed effects. There is, for example, a high level of concern for persistent changes in the function or structure of the nervous system, while transient changes must be evaluated using further criteria. Compensatory changes resulting from cell death might represent activation of repair capacity and, since this could decrease future potential adaptability, reversibility is viewed with concern. In general, equal weight is given to chemicals that directly or indirectly affect the nervous system. Finally, effects on the nervous system must be compared to those on other organ systems to help rule out non-specific changes in neurobiological measures.