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Jane Adams,¹ Stan Barone Jr.,² Anthony LaMantia,³ Rossanne Philen,⁴ D.C. Rice,⁵ Linda Spear,⁶ and Ezra Susser⁷

¹Department of Psychology, University of Massachusetts-Boston, Boston, Massachusetts, USA; ²Neurotoxicology Division, Cellular and Molecular Toxicology Branch, National Health Effects Environmental Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ³Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA; ⁴Environmental Hazards Epidemiology Section, National Center for Environmental Heath, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁵National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, D.C., USA; ⁶Department of Psychology, Center for Developmental Psychobiology, Binghamton University, Binghamton, New York, USA; ⁷Division of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, New York, USA

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. Key words: abnormal neurological development, behavioral teratology, behavioral testing methodology, delayed neurotoxicity, developmental disorders, developmental neurotoxicology, environmental health, neurobiological substrates of function, neuronal plasticity. -- Environ Health Perspect 108(suppl 3) :535-544 (2000) .

http://ehpnet1.niehs.nih.gov/docs/2000/suppl-3/535-544adams/abstract.html