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Rodney R. Dietert,¹ Ruth A. Etzel,² David Chen,³ Marilyn Halonen,⁴ Steven D. Holladay,⁵ Annie M. Jarabek,⁶ Kenneth Landreth,⁷ David B. Peden,⁸ Kent Pinkerton,⁹ Ralph J. Smialowicz,¹⁰ and Tracey Zoetis^11,*

¹Department of Microbiology and Immunology and Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York, USA; ²Epidemiology and Risk Assessment Division, Food Safety and Inspection Service, Washington, D.C., USA; ³Office of Children's Health Protection, U.S. Environmental Protection Agency, Washington, D.C., USA; ⁴Respiratory Sciences, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona, USA; ⁵Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg, Virginia, USA; ⁶National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ⁷Department of Microbiology and Immunology, West Virginia University Medical Center, MBR Cancer Center, Morgantown, West Virginia, USA; ⁸Center for Environmental Medicine and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; ⁹Department of Anatomy, Physiology and Cell Biology, University of California at Davis, Davis, California, USA; ¹⁰National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ¹¹Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA

Abstract

Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment. Key words: children's health, developmental exposure, developmental immunotoxicity, respiratory toxicity, risk assessment, windows of vulnerability.
-- Environ Health Perspect 108(suppl 3) :483-490 (2000) .

http://ehpnet1.niehs.nih.gov/docs/2000/suppl-3/483-490dietert/abstract.html