Assessing the Human Health Risks of Trichloroethylene Key Scientific Issues (2006) / Chapter Skim
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1 Introduction
1 Introduction
Pages 15-24
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to review and provide advice on the key scientific issues raised.
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The committee was asked to highlight issues critical to the development of an objective, realistic, and scientifically balanced trichloroethylene health risk assessment. The focus was to be on hazard characterization and mode of action for trichloroethylene toxicity, possible approaches to synthesize epidemiologic data in informing the hazard characterization of trichloroethylene, differential susceptibility in different subpopulations or life stages, the evidence for effects from trichloroethylene exposures alone compared with that for effects from mixtures of chemicals that include trichloroethylene, physiologically based pharmacokinetic modeling, dose-response assessment, and quantitative assessment of cancer and noncancer risks.
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The delineation of interspecies and intraspecies pharmacokinetic differences can provide insights into how laboratory animal and epidemiologic data might reveal overall human health risks and the basis for individual differences in susceptibility. Furthermore, physiologically based pharmacokinetic models can quantify the relationship between external measures of exposure and internal measures of a toxicologically relevant dose.
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Trichloroethylene concentrations measured in ambient air at various U.S. locations are provided in Table 1-1.
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Arrows with broken lines indicate other possible steps in forming dichloroacetic acid. Abbreviations: CYP, cytochrome P-450; DCA, dichloroacetic acid; DCVC, S-(1,2-dichlorovinyl)
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estimates that between 9% and 34% of drinking water supply sources tested in the United States contain some trichloroethylene. Example concentrations of trichloroethylene found in effluents, surface water, rainwater, groundwater, and drinking water are presented in Table 1-3.
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of Concentrations, µg/L Water Type Samples) Year Mean Median Range Reference Industrial U.S.
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Chapters 4, 5, 6, 7, and 8 evaluate the key issues regarding liver toxicity and cancer, reproductive and developmental toxicity, neurotoxicity, respiratory tract toxicity and cancer, and immunotoxicity, respectively. While these chapters are divided by target organ site, it is important to
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Physiologically based pharmacokinetic models are evaluated in Chapter 11, and guidance is provided on future directions for model development. Finally, Chapter 12 considers issues related to dose-response assessment and quantitative assessment of risk.
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