Project Summary (2000-2006)

Organochlorine solvents are common contaminants of groundwater and drinking water supplies and, therefore, pose a particularly important long-term health hazard to humans. Of the many organochlorine solvents, vinyl chloride poses the greatest threat to humans because it is highly prevalent, a common metabolite of many organochlorine solvents (e.g., TCE, DCE), and tentatively linked with long-term neurological dysfunction and brain cancer. The identification of biomarkers to determine the relative health risk associated with human exposure to vinyl chloride is a high priority of the EPA and a long-term objective of this proposal. Currently, researchers are identifying the neurotoxic and neuro-oncogenic mechanisms of vinyl chloride and using these as tools or biomarkers for risk assessment. The major metabolite of vinyl chloride monomer is chloracetaldehyde (CAA), a known human and rodent genotoxin with neurotoxic, mutagenic, and oncogenic properties. Previous work indicates that other alkylating agents similar to CAA (e.g., methylazoxymethanol, MAM) are neurotoxic, damage DNA, perturb DNA repair, and are mutagenic; researchers hypothesize that CAA induces its neurotoxic and mutagenic effects by a similar mechanism. Experiments are examining the relationship between the formation of ethenobase DNA adducts and neurotoxicity or mutations. Findings from these studies are expected to provide important information about the neurotoxic and mutagenic mechanisms of vinyl chloride.