Arsenic is a carcinogen, a Superfund toxic compound, and a common drinking-water contaminant. The Environmental Protection Agency (EPA) has identified 1,300 sites on its National Priorities List (NPL) and arsenic has been found in at least 781 of these sites in the USA. Exposure may occur by a variety of pathways including inhalation of dusts in air, ingestion of contaminated soil or water, or through the food chain. The primary mode of exposure in non-occupationally exposed populations is drinking-water contamination from either alluvial deposits or industrial contamination. The precise relation of arsenic to cancer has not been established at low exposure levels. In addition, arsenic toxicokinetics in humans remains poorly understood. Thus, we propose to assess exposure and skin-lesion risk, as well as arsenic dosimetrics in a population with a wide range of arsenic exposure via drinking-water contamination. The proposal builds upon a small study in which a case-control study has been initiated. This proposal will use the necessary resources to analyze biomarkers of exposure and susceptibility and for statistical analyses of both a case-control study of skin lesions and a repeated-measures biomarker dosimetry study. The proposed studies in Bangladesh will assess this risk in a population with a wide range of exposures - from low to very high. Together, these data will add substantially to the existing risk assessment information by elucidating both early and late outcomes alter arsenic exposure, and the influence of susceptibility traits at all levels of exposure. This project is relevant to the overall aims of NIEHS in several ways: First, we will examine a range of health effects of an important environmental carcinogen. Second, we will define human biomarkers of exposure, early effects, and genetic susceptibility to arsenic exposure. Third, we will examine exposure-response relationships for arsenic-induced non-malignant skin lesions as well as for skin cancers.
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