Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)Board on Environmental Studies and Toxicology
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Trichloroethylene, a solvent widely used as a degreasing agent, is a common contaminant of air, soil, and water at manufacturing facilities, military installations, and hundreds of waste sites around the country. Several animal studies and human population (epidemiologic) studies show that trichloroethylene is associated with several health effects, including cancer. To help protect people from potential health effects of exposure to contaminants, risk assessments are conducted to guide policy and risk management decisions. However, there are several scientific issues that make risk assessments difficult and controversial. At the request of an interagency group composed of the U.S. Department of Defense, Department of Energy, Environmental Protection Agency (EPA), and the National Aeronautics and Space Administration, this National Research Council report offers independent guidance on scientific issues related to assessing health risks of trichloroethylene. The report provides detailed findings with regard to what the available studies show about various health effects and how to strengthen various aspects of the risk assessment. The report concludes that, because information on carcinogenic risk and other health hazards from exposure to trichloroethylene has strengthened since 2001 and because so many people are exposed to the chemical, federal agencies should finalize their risk assessment with currently available data so that risk management decisions can be made expeditiously.
- Assuming a mitogenic mode of action for dichloroacetic acid as a rodent liver carcinogen, genotypic species differences between mice and humans suggest that humans would be much less susceptible to liver carcinogenesis.
- Evidence from animal and epidemiologic studies suggests that several reproductive and developmental toxicity end points may be associated with trichloroethylene exposure, including infertility in males and females, impaired fetal growth, and cardiac teratogenesis.
- Evidence from experimental, mechanistic, and epidemiologic studies supports the conclusion that trichloroethylene is a potential kidney carcinogen.
- Information on response variability among humans is required in addition to mode-of-action information to clarify the shape of the low dose-response curve in humans. The mode of action for trichloroethylene as a kidney carcinogen remains unclear and likely involves multiple pathways. None of the existing epidemiologic data is suitable as a primary means of quantifying cancer risks.
- It is not known which human enzymatic isoforms are most efficient at disposing of trichloroethylene and its metabolites.
- Multiple mechanisms appear to contribute to the neurotoxic action of trichloroethylene, and further study is needed to elucidate them more precisely.
- None of the currently available PBPK models considers all possible routes of exposure to trichloroethylene (e.g., dermal) or dose metrics for all potential health end points (e.g., neurotoxicity, teratogenicity). Thus, it is appropriate to consider dose metrics generated from PBPK modeling along with other dose metrics that have been used in the past.
- Pulmonary cancer does not appear to be a critical end point in assessing human health risks to trichloroethylene.
- Studies in genetically susceptible rodents have shown that trichloroethylene exacerbates underlying autoimmune disease, and supporting information comes from multiple human studies of scleroderma and exposures to organic solvents. The metabolites and the mode of action involved have not been elucidated, but a role for chloral has been implicated in mouse models.
- The available data indicate that toxic effects of trichloroethylene are likely to change in the presence of exposure to other chemicals, including its metabolites and similar metabolites of other toxicants.
- The committee found that the evidence on carcinogenic risk and other health hazards from exposure to trichloroethylene has strengthened since 2001. Hundreds of waste sites in the United States are contaminated with trichloroethylene, and it is well documented that individuals in many communities are exposed to the chemical, with associated health risks.
- There remains a lack of direct evidence that alterations in the VHL gene initiate renal tumors, but the alterations, especially in protein expression, might contribute to tumor progression.