Determination of the environmental fate and tissue distribution of trichloroethylene and its metabolites
Dixon, Amy Melissa
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Trichloroethylene (TCE) is a volatile organic compound commonly found in drinking water supplies as a result of its widespread use as a metal degreaser and dry cleaning solvent. Dichloroacetic acid (DCA) is found in drinking water as a by-product of the chlorination disinfection process and is also a metabolite of TCE formed via the cytochrome P450 oxidative pathway. Exposure to TCE and DCA is of concern, because the two compounds have been shown to cause cancer in laboratory animals. However, doses of TCE and DCA typically given in animal studies are much higher than the levels to which individuals are exposed to environmentally. Efforts to determine the potential carcinogenicity of the two compounds and the extent of DCA formation from TCE in vivo have been hindered by difficulty with developing reliable analytical methods. Uncertainty in results obtained from methods using derivitizing reagents containing sulfuric acid have arisen, because sulfuric acid has been shown to convert up to 80% of TCA (another metabolite of TCA) to DCA. This uncertainty has led to doubts as to whether DCA is formed from TCE in vivo. Chapter 1, the introduction, describes the layout of the dissertation and reviews methods currently in the literature for the analysis of TCE and DCA and two additional metabolites of TCE, trichloroacetic acid (TCA) and chloral hydrate (CH). Also included in this chapter are means by which to improve analytical methods for TCE and its metabolites. An optimized method for the determination of TCE by SPME-GC/MS is presented in Chapter 2. Methods for the analysis of DCA by HILIC-LC/MS/MS are presented for drinking water (Chapter 3) and rat blood and tissues (Chapter 4). All of the methods reported in Chapters 2-4 do not require derivitization of the analytes, and should thus mimimize uncertainty in results due to conversion of TCA to DCA. Chapter 4 presents a method for quantitating DCA in biological samples that is proven to not convert TCA to DCA and demonstrates that DCA is formed in vivo as a metabolite of TCE.