Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

Abstract

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

Hepatocellular carcinoma and the risk of occupational exposure

“…In fact, it has been proved that TCE is able to bind PPAR [128][129][130][131][132] . RAD51 is a eukaryote gene.…”

Female Breast Cancer and Electrical Manufacturing: Results of a Nested Case‐control Study

“…Moreover, chronic exposure to chlorinated alkanes and alkines, including trichloroethylene, seemed to be related to an increase in mammary cancers in female mice 25) , and in vitro and in vivo studies failed to demonstrate that trichloroethylene had genotoxic activity, while dichlorovinylcysteine (a trichloroethylene metabolite) was observed to induce DNA damage in mammalian cells in vitro and in vivo 26) . These results, along with the carcinogenic activity of trichloroethylene in other sites (i.e, the kidney and probably liver and non-Hodgkin lymphomas) 27,28) , seem to suggest a similar situation for female breast cancer too.…”

Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and Perchloroethylene: Key Similarities, Differences, and Data Gaps

“…PCE-associated chronic nephropathy, including karyomegaly, occurs in rats (National Toxicology Program, 1977, 1986) of both sexes after chronic exposure. Renal injury associated with TCE or PCE exposure is probably mediated through GSH5conjugative metabolites (i.e., DCVG/TCVG and DCVC/TCVC) Lash et al, 2014;Rusyn et al, 2014).…”