Immune System Maturity and Sensitivity to Chemical 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. The immune system continues to mature after birth, and functional immaturity accounts for much of the increased susceptibility in the young. 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. Data from published reports were compared to determine whether age and developmental stage at exposure influence the immunotoxic effects of diethylstilbestrol (DES), diazepam (DZP), lead (Pb), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and tributyltin oxide (TBTO). These compounds were chosen for comparison based on the fact that each had been studied fairly extensively, resulting in a significant number of peer-reviewed publications. Based on lowest-observed-adverse-effect level (LOAEL) values for all five compounds, the developing immune system was found to be at greater risk than that of the adult, either because lower doses induced immunotoxicity, adverse effects were more persistent, or adverse effects were reported following developmental, but not adult, exposure.

We thank Drs. Ralph Smialowicz, Linda Birnbaum, and Jamie DeWitt for reading the manuscript and providing helpful suggestions. 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).

This article was prepared from a talk presented at the 2005 Toxicology and Risk Assessment Conference, Fairborn, OH. A more detailed version of this article was published in the Journal of Toxicology and Environmental Health, Part B.

This report was 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.

Notes

We thank Drs. Ralph Smialowicz, Linda Birnbaum, and Jamie DeWitt for reading the manuscript and providing helpful suggestions. 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).

This article was prepared from a talk presented at the 2005 Toxicology and Risk Assessment Conference, Fairborn, OH. A more detailed version of this article was published in the Journal of Toxicology and Environmental Health, Part B.

This report was 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.

Tributyltin oxide (TBTO). 1997. CASRN 56-25-9. Integrated Risk Information System, U.S. Environmental Protection Agency. September 1