This application utilizes disciplines of Basic Biomedicine, Epidemiology, Ecology, and Engineering to assess the impact of hazardous waste exposure on human health. The Biomedical portion of the Program Project seeks to develop methods for detecting human chemical exposure in vivo. This program Project focuses on assays that can be performed using blood, hair follicle cells, and noninvasive sampling methods useful for monitoring human exposure. In the early stages of the Program Project, rats will be utilized for assessing the specificity, sensitivity, and validity of the methods for monitoring in vivo exposure. The following model toxic agents will be utilized: a) benzene; b) chloroform; c) 2,4,5,2',4',5' hexachlorobiphenyl; d) trichloroethylene; 3) cadmium chloride; f) potassium chromate; g) methylmercuric chloride; and h)nickel acetate. The following tests will be examined as indices of exposure: a) basal and TPA- induced H2O2 formation in neutrophils; b) immune function assays on B and T cells; c) crosslinks with antibodies; e) examination of DNA repair and mutagenesis in lymphocytes in the absence and presence of a test dose of UV; f) examination of mutagenic metabolites in blood and detection of DNA adducts with antibodies; g) assays of neurobehavior; and h) the hair follicle cells as indicators of exposure. The Biomedical components are complemented by an Exposure, Analytical Chemistry and Statistics Core and by a Human Core. The Human Core will provide epidemiological support to the individual components in order to develop, validate, and apply exposure assays in studies involving humans. The Engineering components will calculate the mean and the probability distribution of the dose of chemicals to humans and aquatic organisms from Superfund sites. The Ecology components of the Program Project are involved in trying to understand how Superfund chemicals enter the food chain and how bacteria may alter the Superfund chemicals in our environment. Collectively, these studies, which attempt to predict and assess the uptake of Superfund toxic chemicals to humans, are strongly integrated with the biomedical assays which measure exposure. The results of all these approaches will yield a better understanding of the potential threat of Superfund chemicals to human health.
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