? Trichloroethylene (TCE), a commonly used industrial solvent and environmental contaminant, has been classified as a rodent carcinogen and a probable human carcinogen (Group 2A). In the U.S., TCE production reached several hundred million pounds a year over the last decade, and 60% of the hazardous waste sites on the U.S. Environmental Protection Agency (EPA) National Priority List are contaminated with TCE. EPA is currently conducting a comprehensive risk assessment of TCE in order to determine toxicity and carcinogenicity in humans. No controlled epidemiologic study of high-level oral exposure to TCE has been published to-date. We propose to plan a complex epidemiologic investigation of a cohort, orally exposed to high levels of TCE up to fifty years. Ecologic studies have investigated drinking water contamination with organic solvents, including TCE; however, this study is unique in that TCE is virtually the only contaminant. ? ? Beginning in 1951, TCE was used at a manufacturing plant in Beaverton, OR, and subsequently discarded onto the ground next to a well that produced drinking water for the employees. Over the course of fifty years, over 13,000 individuals were exposed to 1500 pg/I of TCE in their drinking water Exposure stopped in 1998 when it was discovered that the drinking water was contaminated. An electronic database of former employees has been established that we will use to identify recently diagnosed cancer patients by linking the employee database with the population-based cancer registries in Oregon and Washington. We anticipate to also enroll 200 randomly selected cancer-free controls from this cohort and frequency, and match them to cancer cases by recovering the same controls for analysis of each different cancer type. We will ascertain exposure history and other risk factors in subjects with and without cancer through a mailed questionnaire and determine potential associations between TCE exposure and these cancer types. While the sample size of nested case control studies for rare cancers is not expected to have sufficient statistical power, this pilot study will validate the enrollment procedures and collect important TCE exposure data from subjects with potentially rapidly fatal cancers. Because of the urgent nature of this epidemiologic investigation, we will also collect biological samples for future susceptibility studies of TCE detoxification pathways in order to validate the laboratory methods. ? ?
