Assessing the Adverse Effects of Environmental Hazards

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The identification of potential environmental hazards has outpaced the ability to set safety and exposure standards. One limitation has been the lack of tools to translate environmental concentrations of various compounds to human exposures and adverse effects. Only now have practical methods been developed and validated to monitor the fate and transport, human exposure and adverse effects to human health. The present proposal addresses the later two issues. The first objective of this Project will be to screen selected environmental contaminants for adverse effects on the human placenta. A primary cell culture of human trophoblast cells will be used to determine if compounds of interest from other projects are candidates for more intense investigations as determined by their ability to target placenta cells in vitro. This system has been successfully used for dioxin and bromodichloromethane and provides an incisive method for evaluating potential placental toxicants. The compounds to be investigated will be selected based on the results of other subprojects in which human exposures and potential adverse effects, respectively, have been documented. The second objective will follow up the positive in vitro results with in vivo experiments using nonhuman primate animal model. These in vivo studies will confirm the previous in vitro results and verify the target of toxicity in a human-relevant animal model. The third and fourth objectives are to adapt existing biomarker immunoassays to an automated platform and develop new biomarker assays in conjunction with Dr. Denison's project and the analytical chemistry Core. The new biomarkers for development, inhibin and activin, have been selected based on our perceived need to have a complete surveillance of human reproductive health and these hormones play pivotal roles in the regulation of gonadal function. New algorithms and data reduction methods will also be developed in conjunction with Core B. This Project will also collaborate with Project 8 in the development of new assay platforms for future development. The current automation of the biomarker assays will increase throughput, decrease costs and simplify standardization. The fifth objective is to apply existing biomarker assays to population-based studies of human reproductive health in other Superfund Projects. Taken together this project bridges most of the other projects and cores with a focus on human reproductive health at both the individual and population level.