mutations in the VHL gene should be determined. The potential of specific missense mutations in the VHL gene contributing to tumor initiation and progression should be determined.
Although correlation of VHL mutations to trichloroethylene exposure and renal cell cancer are persuasive, the findings need to be validated in other populations and geographic areas. Because many risk factors for renal cell carcinoma generate mutation spectra similar to that of trichloroethylene, coexposure to trichloroethylene with other risk factors needs to be seriously considered and accounted for in future epidemiologic studies.
Mechanistic studies should include field studies of populations exposed to trichloroethylene to assess the range of metabolic pathways used and relative amounts of metabolites from each pathway as a function of exposure intensity and enzymatic genotypes. This information will greatly help in the interpretation and extrapolation of information from rodents to humans.
Additional studies of nephrotoxicity in workers exposed occupationally to trichloroethylene should be performed. It is important that actual exposures are measured and not estimated using biological markers that are subject to large interindividual differences.
No analytic community studies were included in the committee’s assessment of kidney cancer. Given the importance of contamination of water supplies by trichloroethylene, it is important that sufficiently robust studies (with sufficient statistical power and exposure assessments) be conducted in the general population where such exposures might be occurring.
Any follow-up epidemiologic study must have a wide range of exposures, preferably to the range of the Vamvakas and Henschler studies to provide an anchor in that range where effects were seen. There may be opportunities for studies of populations in developing countries in Asia and Eastern Europe, where high exposures to trichloroethylene may not have been controlled. Strong, quantitative exposure assessments will be critical for these studies to be useful for resolving the remaining dose-response issues.