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ASSESSING RISKS TO THE DEVELOPING IMMUNE SYSTEM
Impact/Purpose:
The objective of this research is to provide EPA with predictive tools for prioritization and enhanced interpretation of exposure, hazard identification and dose-response information. This research will aid in the determination of whether the developing immune system exhibits greater susceptibility to chemical perturbation compared to that of the fully mature immune system. As such, it will provide OPPTS with important information relative to the potential increased susceptibility of the developing immune system to perinatal pesticide exposure, as well as to identify the more sensitive and predictive immune function endpoints for assessment of developmental immunotoxicity.
Description:
There is no standardized laboratory animal testing approach to assess the potential toxicity of chemicals to the developing immune system. The goal of this research is to apply a panel of in vivo, ex vivo and in vitro assays to determine whether the developing (i.e., prenatal, neonatal and/or post-weaning/juvenile periods of development) immune system of the rat exhibits increased susceptibility to immunosuppressive chemicals compared to the adult. The assays employed include, but are not limited, to the following: cell-mediated delayed-type hypersensitivity response; humoral antibody response; innate natural killer cell activity; flow cytometric phenotype analysis; and cytokine message profiles. This research will employ a known immunosuppressive agent to accomplish the following: 1) determine the effective dose that produces immunosuppression in rats treated during the stages of development identified above; 2) determine whether chemical exposure during these developmental stages suppresses immune function at comparable or lower doses than adult exposure; and 3) identify the critical developmental windows during which chemical exposure produces immediate and/or persistent immunosuppression.