Abstract
This paper summarizes the deliberations of a work group charged with addressing specific questions relevant to risk estimation in developmental neurotoxicology. We focused on eight questions. a) Does it make sense to think about discrete windows of vulnerability in the development of the nervous system? If it does, which time periods are of greatest importance? b) Are there cascades of developmental disorders in the nervous system? For example, are there critical points that determine the course of development that can lead to differences in vulnerabilities at later times? c) Can information on critical windows suggest the most susceptible subgroups of children (i.e., age groups, socioeconomic status, geographic areas, race, etc.)? d) What are the gaps in existing data for the nervous system or end points of exposure to it? e) What are the best ways to examine exposure-response relationships and estimate exposures in vulnerable life stages? f) What other exposures that affect development at certain ages may interact with exposures of concern? g) How well do laboratory animal data predict human response? h) How can all of this information be used to improve risk assessment and public health (risk management)? In addressing these questions, we provide a brief overview of brain development from conception through adolescence and emphasize vulnerability to toxic insult throughout this period. Methodological issues focus on major variables that influence exposure or its detection through disruptions of behavior, neuroanatomy, or neurochemical end points. Supportive evidence from studies of major neurotoxicants is provided.