ArticleEnvironmental health perspectives2017
Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population.
Article in Environmental health perspectives, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Derivation of ultrasound and electrocardiogram cardiac reference ranges for Mus musculus using the collaborative cross and identification of new cardiac models.BMC cardiovascular disorders · 2025Article
- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Article
- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.Regulatory toxicology and pharmacology : RTP · 2022Article
- Intra- and Inter-Species Variability in Urinary N7-(1-Hydroxy-3-buten-2-yl)guanine Adducts Following Inhalation Exposure to 1,3-Butadiene.Chemical research in toxicology · 2021Article
- 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
- Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice.Archives of toxicology · 2021Article
- Gene-by-environment interactions in Alzheimer's disease and Parkinson's disease.Neuroscience and biobehavioral reviews · 2019Review
- Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene.Environmental health perspectives · 2019Article
- Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.Chemical research in toxicology · 2019Article
- Long-Term Combinatorial Exposure to Trichloroethylene and Inorganic Arsenic in Genetically Heterogeneous Mice Results in Renal Tubular Damage and Cancer-Associated Molecular Changes.G3 (Bethesda, Md.) · 2019Article
- Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population.G3 (Bethesda, Md.) · 2019Article
- Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy.The Journal of allergy and clinical immunology · 2019Article
- Variable outcomes of human heart attack recapitulated in genetically diverse mice.NPJ Regenerative medicine · 2019Article
- Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains.Toxicology · 2018Article
- Metabolism and Toxicity of Trichloroethylene and Tetrachloroethylene in Cytochrome P450 2E1 Knockout and Humanized Transgenic Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Incorporation of the glutathione conjugation pathway in an updated physiologically-based pharmacokinetic model for perchloroethylene in mice.Toxicology and applied pharmacology · 2018Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEvaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics.
objectiveWe quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure.
methodsMale mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC (1,000 mg/kg) or vehicle (Alkamuls-EL620) and euthanized at various time points (n = 1/strain/time). Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed.
resultsSignificant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude (~8-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPARα)-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among
conclusionsUsing the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788.
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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.