t richloroethylene and Cancer

Trichloroethylene (TCE) was for many decades the solvent of choice for cleaning and vapor degreasing of metal parts, and has been commonly used in several other industrial applications. Since the early 1970s, however, concern over potential risks of cancer and other health effects among TCE-exposed workers, coupled with its documented environmental release through air and wastewater emissions, has led to a decline in its use. Strong evidence of carcinogenicity has come from experimental research, with TCE shown to induce tumors in kidney, liver, lung, testes, and hematopoietic tissue in rodents (1). The evidence from occupational epidemiologic studies has been less clear, although a recent meta-analysis of published cohort and case-control findings supports an association with kidney cancer and more limited evidence of association with liver cancer and non-Hodgkin lymphoma (NHL) (2). In October 2012, an expert review panel at the International Agency for Research on Cancer (IARC) upgraded the classification of TCE to known human carcinogen (group 1) (3), largely based on findings related to kidney cancer. In this issue of the Journal, Hansen et al. report new findings from an updated analysis of three cohorts of TCE-exposed workers, with additional follow-up of 10 to 15 years of cancer incidence for each cohort (4). A unique strength of these cohorts, located in Denmark, Sweden, and Finland, is that exposure to TCE among workers was confirmed from past measurements of urinary trichloroacetic acid (U-TCA), a major metabolite of TCE and a biomarker of recent exposure. In a combined analysis of all 5553 exposed workers, the investigators observed statistically significant elevated standardized incidence ratios (SIRs) for cancers of the liver (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervix (2.31; 95% CI = 1.32 to 3.75), but not for kidney cancer (1.01; 95% CI = 0.70 to 1.42). A statistically significant association with NHL was observed for men (SIR = 1.55; 95% CI = 1.06 to 2.20) but not women (SIR = 0.63; 95% CI = 0.23 to 1.37), with inconclusive results overall (SIR = 1.26; 95% CI = 0.89 to 1.73). In internal analyses, evidence of an exposure-response relationship with mean U-TCA was found only for cervical cancer. However, given the short half-life of U-TCA of 35–70 hours (5), the large proportion