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A physiologically based pharmacokinetic (PBPK) model for trichloroethylene (TCE) in the male Long-Evans (LE) rat was needed to aid in evaluation of neurotoxicity data collected in this rodent stock. The purpose of this study was to develop such a model with the greatest possible specificity for the LE rat. The PBPK model consisted of 5 compartments: brain,(More)
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic member of a class of planar and halogenated chemicals. Improvements in exposure assessment of TCDD require scientific information on the distribution of TCDD in target tissues and cellular responses induced by TCDD. Since 1980, several physiologically based pharmacokinetic (PBPK) models for TCDD(More)
Strategies are needed for assessing the risks of exposures to airborne toxicants that vary over concentrations and durations. The goal of this project was to describe the relationship between the concentration and duration of exposure to inhaled trichloroethylene (TCE), a representative volatile organic chemical, tissue dose as predicted by a(More)
We have developed a comprehensive, Bayesian, PBPK model-based analysis of the population toxicokinetics of trichloroethylene (TCE) and its metabolites in mice, rats, and humans, considering a wider range of physiological, chemical, in vitro, and in vivo data than any previously published analysis of TCE. The toxicokinetics of the "population average," its(More)
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has dose-dependent tissue distribution because of induction of CYP1A2, a TCDD-binding protein, in the liver. Induction requires transcriptional activation of the CYP1A2 gene product by TCDD and the Ah receptor. An empirical model for dose-dependent distribution (Carrier et al., 1995, Toxicol. Appl. Pharmacol. 131,(More)
Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term(More)
Chloroform (CHCl3) is a near-ubiquitous environmental contaminant, a by-product of the disinfection of drinking water sources and a commercially important compound. Standards for safe exposure have been established based on information defining its toxicity, which is mediated by metabolites. The metabolism of CHCl3 is via cytochrome P-450 2E1(More)
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)
Risk assessments often must consider exposures that vary over time or for which the exposure duration of concern differs from the available data, and a variety of extrapolation procedures have been devised accordingly. The present experiments explore the relationship(s) between exposure concentration (C) and time (t) to investigate procedures for assessing(More)
The relationship between the concentration of trichloroethylene (TCE) in the brain and changes in brain function, indicated by the amplitude of steady-state pattern-elicited visual evoked potentials (VEP), was evaluated in Long-Evans rats. VEPs were recorded from visual cortex following stimulation of the eyes and, thus, reflect the function of the afferent(More)