1,1,2-Trichloroethylene (TCE) is an important
solvent that is widespread in the environment. We have reviewed carcinogenicity data from seven bioassays with regard to renal injury and renal
tumors. We report a consistent but low incidence of renal tubule
carcinoma in male rats. Epidemiology studies on workers exposed to TCE (and other chlorinated
solvents) indicate a weak association between high-level exposure and
renal cancer. There appears to be a threshold below which no renal injury or carcinogenicity is expected to arise. TCE is not acutely nephrotoxic to rats or mice, but subchronic exposure to rats produces a small increase in urinary markers of renal injury. Following chronic exposure, pathological changes (toxic
nephrosis and a high incidence of cytomegaly and karyomegaly) were observed. The basis for the chronic renal injury probably involves bioactivation of TCE. Based on the classification by E. A. Lock and G. C. Hard (2004, Crit. Rev. Toxicol. 34, 211-299) of chemicals that induce renal tubule
tumors, we found no clear evidence to place TCE in category 1 or 2 (chemicals that directly or indirectly interact with renal
DNA), category 4 (direct cytotoxicity and sustained tubule cell regeneration), category 5 (indirect cytotoxicity and sustained tubule cell regeneration associated with
alpha2u-globulin accumulation), or category 6 (exacerbation of spontaneous chronic progressive nephropathy). TCE is best placed in category 3, chemicals that undergo conjugation with GSH and subsequent enzymatic activation to a reactive species. The implication for human risk assessment is that TCE should not automatically be judged by linear default methods; benchmark methodology could be used.