The Comparative Immunotoxicity of Five Selected Compounds Following Developmental or Adult Exposure

Abstract

It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. Although not established absolutely, it is generally believed that development constitutes a period of increased immune system susceptibility to xenobiotics, since adverse effects may occur at lower doses and/or immunomodulation may be more persistent, thus increasing the relative risk of xenobiotic exposure to the immunologically immature organism. To address this issue, a brief overview of immune maturation in humans is provided to demonstrate that functional immaturity alone predisposes the young to infection. Age-dependent differences in the immunotoxic effects of five diverse compounds, diethylstilbestrol (DES), diazepam (DZP), lead (Pb), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and tributyltin oxide (TBTO), which have undergone adult and developmental immunotoxicity testing in rodents, are then reviewed, as are human data when available. For all five chemicals, the developing immune system was found to be at greater risk than that of the adult, either because lower doses produced immunotoxicity, adverse effects were more persistent, or both.

This review was prepared by members of the Immunotoxicology Workgroup, under Interagency Agreement DW75991101 between the U.S. Environmental Protection Agency's Office of Children's Health Protection and the Health Effects Laboratory Division of the National Institute for Occupational Safety and Health (NIOSH). Members of the workgroup not included as authors are Drs. Dori Germolec (National Institute of Environmental Health Sciences, National Toxicology Program), Christine Park, Michael Kashon, and Laura Blanciforti (NIOSH, Health Effects Laboratory Division). Special thanks to Drs. Katherine Anitole, Linda Birnbaum, Ralph Smialowicz, Ron Ward, Mike Holsapple, and John Armstrong for reviewing the manuscript, and to Dr. Bob Sonawane (EPA/ORD/NCEA) for helping to organize this effort.

This report has been reviewed by the U.S. Environmental Protection Agency and the National Institute of Occupational Safety and Health and approved for publication. Approval does not signify that the contents reflect the views of the agencies.