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Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE) . Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based(More)
BACKGROUND In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. OBJECTIVES We summarized the key findings and scientific issues regarding the human health effects of(More)
Physiologically based Pharmacokinetic (PBPK) models are used for predictions of internal or target dose from environmental and pharmacologic chemical exposures. Their use in human risk assessment is dependent on the nature of databases (animal or human) used to develop and test them, and includes extrapolations across species, experimental paradigms, and(More)
BACKGROUND The Ramazzini Institute (RI) has completed nearly 400 cancer bioassays on > 200 compounds. The European Food Safety Authority (EFSA) and others have suggested that study design and protocol differences between the RI and other laboratories by may contribute to controversy regarding cancer hazard findings, principally findings on lymphoma/leukemia(More)
Bromochloromethane (BCM) is a volatile compound and a by-product of disinfection of water by chlorination. Physiologically based pharmacokinetic (PBPK) models are used in risk assessment applications. An updated PBPK model for BCM is generated and applied to hypotheses testing calibrated using vapor uptake data. The two different metabolic hypotheses(More)
Cytochrome P450-dependent oxidation and glutathione (GSH)-dependent conjugation are the primary routes of metabolism of haloalkanes. Using rat liver microsomes and cytosol, we investigated the metabolism of two halopropanes found on the U.S. Environmental Protection Agency Contaminant Candidate List, 1,3-dichloropropane (1,3-DCP) and 2,2-dichloropropane(More)
The health risk assessment from exposure to a particular agent is preferred when the assessment is based on a relevant measure of internal dose (e.g., maximal concentration of an active metabolite in target tissue) rather than simply the administered dose or exposure concentration. To obtain such measurements, the relevant biology, physicochemical(More)
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