Introduction: Trichloroethylene (TCE) is a common water contaminant and continues to be used in the workplaces of many developing countries. It causes kidney cancer and possibly non-Hodgkin lymphoma and liver cancer. However, the underlying pathophysiology of TCE-induced cancer is not well understood. To evaluate biological responses to TCE, we conducted a cross-sectional molecular epidemiology study of workers exposed to TCE and unexposed controls and applied non-targeted metabolomics analysis. Methods: We studied 80 healthy workers that used TCE and 95 comparable unexposed controls in Guangdong, China. The TCE-exposed workers had a median 8-hour time weighted average personal air exposure of 12 ppm (range: 0.4 to 230 ppm), with almost all workers having exposure under the current U.S. OSHA Permissible Exposure Limit of 100 ppm. Metabolomics analysis of plasma samples was conducted by ultra-high resolution mass spectrometry Results: Metabolic features associated with TCE exposure included known TCE metabolites and additional unidentified chlorinated compounds. TCE exposure was also associated with multiple alterations in endogenous metabolism, including changes in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Specific metabolite associations with TCE exposure included uric acid, glutamine, cystine, methylthioadenosine, taurine and chenodeoxycholic acid, consistent with immunosuppressive, hepatotoxic and nephrotoxic effects that have been related to TCE. There were also correlations between multiple metabolites and additional exposure, immunologic, and nephrotoxic biomarkers that had been measured previously. Conclusion: Untargeted high-resolution metabolomics correlated occupational exposure to TCE with internal dose and metabolic responses, providing new insights into molecular mechanisms of TCE-related disease.
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