1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, United States
2 Emory University, Division of Pulmonary, Allergy and Critical Care Medicine
3 University of California at Berkeley, Division of Environmental Health Sciences, School of Public Health
4 Institute for Risk Assessment Sciences, Utrecht University, Division of Environmental Epidemiology
5 Guangdong Medical Laboratory Animal Center, Guangzhou, China
6 Guangdong Poison Control Center, Guangzhou, China
7 University of Washington
8 Seoul National University, Graduate School of Public Health
9 Tufts University, Department of Civil and Environmental Engineering
Occupational exposure to trichloroethylene (TCE) has been linked to kidney cancer and is suspected to cause non-Hodgkin lymphoma and liver cancer. However, TCE’s mode of action for development of these diseases in humans is not well understood. Non-targeted metabolomics analysis of plasma obtained from 80 TCE exposed workers and 95 controls were completed by ultra-high resolution mass spectrometry. Biological responses to TCE exposure was determined, with metabolic changes and plasma TCE metabolites evaluated by exposure-dose response and pathway enrichment. Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulfur amino acid and bile acid biosynthesis pathways. Metabolic perturbations were consistent with immunologic alterations, hepatotoxicity, and nephrotoxicity. High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure related disease etiology.