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University of North Carolina-Chapel Hill

Superfund Research Program

Environmental Fate and Human Exposure to Carcinogens

Center Director: James A. Swenberg
Grant Number: P42ES005948
Funding Period: 1992-2018

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Summary (1995-2000)

The objective of this program is to expand the scientific foundation necessary to generate biologically-based risk assessments for several specific chemicals found at waste sites on the National Priorities List. Due to widespread potential for human exposure, the following specific chemicals have been selected for study: vinyl chloride (VC), pentachlorophenol (PCP), benzene, 2,6-dinitrotoluene (DNT), 1,1,2-trichloroethylene, 1,1,2,2- tetrachloroethylene, 1,1,2-trichloroethane, chloroform, carbon tetrachloride, and selected polycyclic aromatic hydrocarbons (PAHs). The program consists of seven integrated research projects (three biomedical, four nonbiomedical), scientific cores on chemistry, epidemiology, and training, as well as outreach and administrative cores.

As a means to fulfill the objectives of the program, certain specific aims were established. One specific aim is primarily focussed on identifying and establishing dose-response relationships for the critical mechanisms related to the induction of mutations and cancer. Another aim of the program is to develop methods for identifying sensitive populations to assess if they are at greater or lesser risk than the general population to selected chemicals. An epidemiological study is being conducted so as to determine in vivo somatic mutation frequencies and mutational spectra in workers occupationally exposed to vinyl chloride. These mutation frequencies will then be related to exposure levels, metabolic genotypes, and DNA repair capacities, in order to develop biomarkers of human susceptibility.

In order to further examine the factors related to human exposure to carcinogenic chemicals, the development and use of ultrasensitive biomarkers has surfaced as another aim of this program. Two of the individual biomedical projects are specifically concentrating on the isolation and application of DNA or protein adducts as biomarkers of exposure or effective dose. Such biomarkers are being designed for identification and quantification of exposure to selected chemicals and on how their levels are modulated in animal tissues. Once validated, these markers will have subsequent application to human studies.

Regarding the nonbiomedical aspect of this program, a primary specific aim is directed toward the study of the degradation and fate of the above listed chemicals. Studies are being conducted to determine the relative toxicity of specific degradation by-products as compared to the parent compounds. One project is concentrating on the kinetics of bacterial degradation of high molecular weight PAHs. A related project is assessing the fate of degraded PAHs in the soil. Two other projects are evaluating mass transfer phenomena in heterogeneous multiphase subsurface systems, and then applying stochastic analysis to approximate human and ecological exposure to certain contaminants, particularly non-aqueous phase liquids (NAPL).

The program's training core provides quality interdisciplinary instruction for pre- and post-doctoral fellows in environmental sciences by combining coursework, group activities, seminars and research experiences in environmental health sciences, hydrogeological engineering, and microbial ecology. The trainees conduct basic research in the individual projects and cores, take courses and attend seminars designed to foster greater understanding of biomedical, ecological, and engineering aspects of hazardous waste management, and participate in numerous workshops and discussion groups related to Superfund issues. The program's outreach core disseminates information to target audiences such as other university researchers, industry researchers, US and state government regulatory agency personnel, and consultants, who use and apply basic research findings. The University of North Carolina is collaborating with the Institut National de la Sante et de la Recherche Medicine and Harvard University in their research efforts.

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