A Practical Approach, Second Edition=Ronald D. Ho.pdf

1080 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONAPPENDIX C-7*SPECIES COMPARISON OF ANATOMICAL ANDFUNCTIONAL IMMUNE SYSTEM DEVELOPMENTMichael P. Holsapple 1,4 , Lori J. West 2 and Kenneth S. Landreth 31ILSI Health and Environmental Sciences Institute (HESI), Washington, DC;2The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada;3Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV.4Address All Correspondence to: Michael P. Holsapple, Ph.D., Executive Director, ILSI Health and EnvironmentalSciences Institute, One Thomas Circle, NW, Ninth Floor, Washington, DC 20005-5802, PH: 202-659-3306, FAX:202-659-3617. Email: mholsapple@ilsi.orgIntroductionIn recent years, there has been increasing regulatory pressure to protect children’s health becauseit is suspected that immature populations may be at greater risk for chemically induced toxicity.Congress enacted two statutes in 1996, the FOOD QUALITY PROTECTION ACT (FQPA) andthe SAFE DRINKING WATER ACT (SDWA). FQPA stated that “when establishing, . . . a tolerance. . . of a pesticide residue on food, EPA must perform s separate assessment for infants and children. . .”; and the SDWA “requires that EPA conduct studies to identify subpopulations, such as infants,children, pregnant women . . . that may be more susceptible than the general population . . .”. In1997, presidential Executive Order #13045 was issued which emphasized the following, “eachFederal Agency shall make it a high priority to identify and assess environmental health risks andsafety risks that may disproportionately affect children and ensure that its policies, programs,activities and standards address disproportionate risk to children that result from environmentalhealth risks or safety risks . . . ”.Interestingly, a review of the available literature in virtually any area of health-related toxicologyindicated that an overwhelming proportion of previous research and testing had been directed towardexposure of adults as opposed to children (Dietert et al., 2000). As the number of studies in younganimals has begun to increase to address this regulatory pressure, it is already clear that there aremany challenges to the design, conduct and interpretation of these new data.Components of the immune system have not traditionally been emphasized as potential targetorgans in standard developmental and reproductive toxicity (DART) protocols. Moreover, althoughimmunotoxicology has evolved as a science to the point where several regulatory agencies havecrafted guidelines to address the immunotoxic potential of both drugs and non-drug chemicals,these protocols are generally performed in young adult animals, principally either rats or mice.Developmental immunotoxicology is predicated around the possibility that the immune system mayexhibit unique susceptibility during its ontological development that may not be seen if data is onlyacquired in adults. It is important to emphasize at the onset, that there are currently no validatedor widely accepted methods for evaluating the effects of a drug or chemical on the developingimmune system. Nonetheless, because of concerns over children’s health issues, specifically thepossibility that the very young are uniquely susceptible to chemical perturbation, governmentalregulators are beginning to ask for information about potential effects on the developing immunesystem.* Source: Holsapple, M. P., West, L. J., and Landreth, K. S., Species comparison of anatomical and functional immunesystem development, Birth Defects Research, Part B: Developmental and Reproductive Toxicology, 68, 321-334, 2003.© 2006 by Taylor & Francis Group, LLC