ArticleEnvironmental health perspectives2014
Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse.
Article in Environmental health perspectives, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Reducing uncertainty in dose-response assessments by incorporating Bayesian benchmark dose modeling and in vitro data on population variability.Risk analysis : an official publication of the Society for Risk Analysis · 2025Article
- Comparing computational times for simulations when using PBPK model template and stand-alone implementations of PBPK models.Frontiers in toxicology · 2025Article
- Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.Annual review of pharmacology and toxicology · 2025Review
- Renal Glutathione: Dual roles as antioxidant protector and bioactivation promoter.Biochemical pharmacology · 2024Review
- Low-dose inhalation exposure to trichloroethylene induces dopaminergic neurodegeneration in rodents.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment.Environmental health : a global access science source · 2023Review
- Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.Regulatory toxicology and pharmacology : RTP · 2022Article
- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- Quantitative Characterization of Population-Wide Tissue- and Metabolite-Specific Variability in Perchloroethylene Toxicokinetics in Male Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Engineering synthetic breath biomarkers for respiratory disease.Nature nanotechnology · 2020Article
- PBPK modeling of impact of nonalcoholic fatty liver disease on toxicokinetics of perchloroethylene in mice.Toxicology and applied pharmacology · 2020Article
- Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.Chemical research in toxicology · 2019Article
- Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains.Toxicology · 2018Article
- Incorporation of the glutathione conjugation pathway in an updated physiologically-based pharmacokinetic model for perchloroethylene in mice.Toxicology and applied pharmacology · 2018Article
- Beyond the RfD: Broad Application of a Probabilistic Approach to Improve Chemical Dose-Response Assessments for Noncancer Effects.Environmental health perspectives · 2018Article
- Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population.Toxicology · 2018Review
- Population-based dose-response analysis of liver transcriptional response to trichloroethylene in mouse.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Advancing chemical risk assessment decision-making with population variability data: challenges and opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Applying a Global Sensitivity Analysis Workflow to Improve the Computational Efficiencies in Physiologically-Based Pharmacokinetic Modeling.Frontiers in pharmacology · 2018Article
- Characterization of inter-tissue and inter-strain variability of TCE glutathione conjugation metabolites DCVG, DCVC, and NAcDCVC in the mouse.Journal of toxicology and environmental health. Part A · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundQuantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.
objectivesWe evaluated the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study.
methodsWe used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and 1 hybrid mouse strains to calibrate and extend existing physiologically based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). We used a Bayesian population analysis of interstrain variability to quantify variability in TCE metabolism.
resultsConcentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation were less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production were less variable (2-fold range) than DCA production (5-fold range), although the uncertainty bounds for DCA exceeded the predicted variability.
conclusionsPopulation PBPK modeling of genetically diverse mouse strains can provide useful quantitative estimates of toxicokinetic population variability. When extrapolated to lower doses more relevant to environmental exposures, mouse population-derived variability estimates for TCE metabolism closely matched population variability estimates previously derived from human toxicokinetic studies with TCE, highlighting the utility of mouse interstrain metabolism studies for addressing toxicokinetic variability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.