Trichloroethylene (TCE, CASRN 79-01-6) is a volatile, chlorinated alkene used mainly as an intermediate for hydrofluorocarbon production and as a degreaser for metal parts, although its use as a degreaser has decreased in the United States since the 1970s. People are exposed in workplaces that produce or use TCE as a degreaser or solvent, and from drinking contaminated water and breathing contaminated air.
The National Toxicology Program (NTP) conducted a cancer hazard assessment of TCE, focusing on three types of cancer kidney cancer, non-Hodgkin lymphoma (NHL), and liver cancer. NTP used systematic review methods to identify studies, evaluate study quality, integrate evidence across studies, and integrate evidence across data streams (human, animal, and mechanistic data). Using established criteria, NTP reached conclusions regarding the strength of the evidence for each of the three cancer types and on the recommended listing status of trichloroethylene in the Report on Carcinogens.
Results and discussion
Epidemiological studies provide evidence of a causal relationship between exposure to TCE and kidney cancer based on consistent evidence of increased risk of kidney cancer across studies with different study designs, geographical areas, and occupational settings. Kidney cancer risk increased with increasing level or duration of TCE exposure in some individual studies and across studies. Exposure to TCE by inhalation or gavage caused kidney tumors in rats. TCE most likely causes kidney cancer by its metabolism in the kidney to genotoxic and cytotoxic GSH-conjugation-derived metabolites (or their systemic delivery to the kidney).
Non-hodgkin lymphoma (NHL)
Epidemiological studies provide limited evidence that TCE exposure causes NHL, based on positive associations in several studies and evidence for increased risk of NHL across studies combined in two meta-analyses. However, alternative explanations for the associations, such as chance or confounding, cannot reasonably be ruled out. Exposure to TCE by inhalation or gavage caused lymphoma in mice. TCE causes immunomodulation in both people and animals, and immunomodulation is linked to NHL; however, the potential association between trichloroethylene-induced immune effects and lymphoma has not been tested directly in either humans or animals.
Epidemiological studies of TCE in humans were inconsistent and the overall data were considered inadequate. Exposure to TCE by inhalation or gavage caused lymphoma in mice.
NTP cancer hazard conclusion
The NTP cancer hazard evaluation was the basis for changing the listing status of TCE from reasonably anticipated to known to be a human carcinogen in the 14th edition of the Report on Carcinogens based on sufficient evidence of carcinogenicity from studies in humans. This conclusion is based on epidemiological studies showing that TCE causes kidney cancer in humans, together with supporting evidence from toxicological, toxicokinetic, and mechanistic studies demonstrating the biological plausibility of its carcinogenicity in humans.
National Toxicology Program (NTP). 2015. Report on Carcinogens monograph on trichloroethylene. Research Triangle Park, NC: National Toxicology Program. RoC Monograph 05. https://doi.org/10.22427/ROC-MGRAPH-5