Prior work evaluating health effects from hazardous waste has been plagued by crude measures of human exposures, low doses, and small sample sizes. Data on background levels of contaminants are largely lacking, so that the differential between ostensibly """"""""exposed; and """"""""unexposed"""""""" communities is essentially unknown. Concomitantly, much work on biomarkers has been removed real-world human exposure scenarios. The proposed research will attempt to tackle each of these problems. In the first funding period, the epidemiology core conducted feasibility analyses to lay the basis for field studies that would implement improved exposure assessment and measure biomarkers developed by other projects in this program. In the upcoming funding period, the epidemiology effort will be directed to supporting, complementing and extending the work of the main projects. Specifically, in conjunction with Project #3 , the epidemiology core will conduct field studies to (a) assess feasibility of self-administered devices for collection of breath, urine, tapwater, and indoor air monitor samples in large-scale studies of benzene and pentachlorophenol, respectively, (b) generate data on background variability of body burdens and protein adducts from exposures to benzene and pentachlorophenol, and (c) determine factors that influence such variability, including point sources of contamination and workplace in addiction to background factors such as sociodemograhic, geographic, lifestyle and home characteristics. In conjunction with Project #2, this core will (a) provide epidemiologic input to the selection of subjects and samples for studies of hprt mutations in T-lymphocytes, glycophorin A mutations in red blood cells and presence of mutant p21ras oncoproteins in sera from workers with high vinyl-chloride exposure, (b) link findings on these biomarkers for chemically-induced genetic alterations with the occupational exposure histories to evaluate the relations with dose and time-since-exposure, and (c) evaluate the pathways of vinyl chloride-induced carcinogenesis in nested case-control analyses by relating work exposure data to development of liver angiosarcomas, incorporating the data on biomarkers generated by Project #2. Conceptual themes underlying the work of the epidemiology core include; the background distribution of the biomarkers, i.e., sensitivity at low doses, and expected levels among the unexposed, or at least those with apparently minimal exposure; interindividual variability and intraindividual variability in both concentrations of these compounds in human tissue and in biomarkers of protein and DNA damage; and the relationships among time of exposure, dose, and the measured alterations.
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