| Perinatal Immunotoxicity: Why Adult Exposure Assessment Fails to Predict Risk Rodney R. Dietert and Michael S. Piepenbrink Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA Abstract
Recent research has pointed to the developing immune system as a remarkably sensitive toxicologic target for environmental chemicals and drugs. In fact, the perinatal period before and just after birth is replete with dynamic immune changes, many of which do not occur in adults. These include not only the basic maturation and distribution of immune cell types and selection against autoreactive lymphocytes but also changes designed specifically to protect the pregnancy against immune-mediated miscarriage. The newborn is then faced with critical immune maturational adjustments to achieve an immune balance necessary to combat myriad childhood and later-life diseases. All these processes set the fetus and neonate completely apart from the adult regarding immunotoxicologic risk. Yet for decades, safety evaluation has relied almost exclusively upon exposure of the adult immune system to predict perinatal immune risk. Recent workshops and forums have suggested a benefit in employing alternative exposures that include exposure throughout early life stages. However, issues remain concerning when and where such applications might be required. In this review we discuss the reasons why immunotoxic assessment is important for current childhood diseases and why adult exposure assessment cannot predict the effect of xenobiotics on the developing immune system. It also provides examples of developmental immunotoxicants where age-based risk appears to differ. Finally, it stresses the need to replace adult exposure assessment for immune evaluation with protocols that can protect the developing immune system. Key words: allergy, atopy, autoimmunity, children's health, developmental immunotoxicology, immune balance, immunoglobulin E, perinatal risk, safety testing. Environ Health Perspect 114:477-483 (2006) . doi:10.1289/ehp.8566 available via http://dx.doi.org/ [Online 16 November 2005]
Address correspondence to R.R. Dietert, Department of Microbiology and Immunology, C5-135 Veterinary Medical Center, College of Veterinary Medicine, Cornell University, North Tower Rd., Ithaca, NY 14853 USA. Telephone: (607) 253-4015. Fax: (607) 253-3384. E-mail: rrd1@cornell.edu Support of the authors for research on this topic, including partial salary recovery, was provided by grants or contracts from the National Institute of Environmental Health Sciences [Superfund Basic Research and Education Program via the U.S. Environmental Protection Agency (EPA) ], the American Chemistry Council (ACC) , the U.S. EPA, and the U.S. Department of Agriculture (USDA) . The ACC and the USDA provided salary support for M.S.P. Research support for R.R.D. during the past 5 years has been from the ACC and the USDA (Developmental Immunotoxicology) and from the USDA and New York State (Environment and Breast Cancer) . Received 8 August 2005 ; accepted 15 November 2005.
The full version of this article is available for free in HTML or PDF formats. |
