Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene (2010) / Chapter Skim
Currently Skimming:
1 Introduction
1 Introduction
Pages 16-23
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 16... ...
has classified tetrachloroethylene as a hazardous air pollutant under the Clean Air Act, a toxic pollutant under the Clean Water Act, a contaminant under the Safe Drinking Water Act, a hazardous waste under the Resource Conservation and Recovery Act, and a hazardous substance under the Comprehensive Environmental Response, Compensation, and Liability Act. EPA's Integrated Risk Information System (IRIS)
|
From page 17... ...
The committee was asked to evaluate whether the key studies underlying the draft IRIS assessment were of requisite quality, reliability, and relevance to support the derivation of the RfD, RfC, and oral and inhalation unit risks; to evaluate whether the scientific uncertainties in EPA's risk assessment were adequately described and, where possible, quantified; and to identify research that could reduce the uncertainties given the current understanding of human health effects associated with tetrachloroethylene exposure. During the study course of the project, EPA submitted specific questions for the committee to address.
|
From page 18... ...
2. Characterization of Uncertainties -- the noncancer assessment considers uncertainty on the basis of extrapolation from laboratory animals to humans, variations in response within experimental species, human variation, and database deficiencies; the noncancer RfC and RfD are based on a specific neurotoxicity effect; EPA also presents reference values based on other effects to illustrate the dose dependence of the multiple observed toxicities.
|
From page 19... ...
3. Development of the inhalation unit risk and oral slope factor -- EPA's draft unit-risk estimate relies on choices of tumor type, point of departure, and low-dose extrapolation that aim to provide a "reasonable upper bound estimate" of risk; because the draft assessment judged that there was no strong basis for preferring one physiologically-based pharmacokinetic model over another, a range of tetrachloroethylene unit-risk estimates calculated with three PBPK models is given.
|
From page 20... ...
Choice of Dose Metrics for Various Toxic Outcomes, PBPK Modeling, and Interspecies Scaling Approaches Exposure to tetrachloroethylene results in the production of several metabolic products. The parent compound is used as the dose metric for neurotoxic effects, and the rate of formation of total metabolites in humans is used for cancer effects.
|
From page 21... ...
The committee and staff examined the reference lists included in EPA's draft assessment, major epidemiologic studies, review articles, and major compilations for relevant citations. Smaller targeted literature searches were performed to identify pertinent older literature and papers on specific topics and to gather general background information.
|
From page 22... ...
In the last decade, a continually evolving framework for considering weight of evidence for hypothesized modes of action and their human relevance has been developed and widely incorporated in guidance and risk assessments for individual chemicals by national and international agencies, including EPA. The framework is relevant to consideration of mechanistic data on both cancer and noncancer effects and sets the stage for informing dose-response relationships through consideration of hypothesized modes of action in the context of key events and their relevance to humans (for example, see Meek 2008)
|
From page 23... ...
Chapter 2 provides a brief overview of the toxicokinetics of tetrachloroethylene because understanding how the body handles tetrachloroethylene is critical for understanding its effects in the later chapters focused on specific organ systems. Chapter 3 presents an evaluation of the neurotoxic effects of tetrachloroethyelene; such effects were the basis of EPA's derivation of the RfC and RfD for tetrachloroetheylene, so the review focuses on evaluating the strengths and weaknesses of available studies and their utility in deriving reference values.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.