ArticleToxicological sciences : an official journal of the Society of Toxicology2011
In vitro screening for population variability in chemical toxicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Quantitative estimates of inter-individual variability for new approach methodologies-based systemic safety toolbox using a population-based human in vitro model.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Identification of functional genetic components modulating toxicity response to PFOS using genome-wide CRISPR screens in HepG2/C3A cells.Archives of toxicology · 2026Article
- Identification of Functional Genetic Components Modulating Toxicity Response to PFOS using Genome-wide CRISPR Screens in HepG2/C3A cells.bioRxiv : the preprint server for biology · 2025Article
- Hepatocytes derived from human induced pluripotent stem cells: Towards establishing anCurrent research in toxicology · 2025Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- Interindividual Differences in DNA Adduct Formation and Detoxification of 1,3-Butadiene-Derived Epoxide in Human HapMap Cell Lines.Chemical research in toxicology · 2020Article
- Methods for evaluating variability in human health dose-response characterization.Human and ecological risk assessment : HERA · 2019Article
- Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population.Toxicology · 2018Review
- The Impact of Novel Assessment Methodologies in Toxicology on Green Chemistry and Chemical Alternatives.Toxicological sciences : an official journal of the Society of Toxicology · 2018Review
- Bridging the Data Gap FromFrontiers in public health · 2018Review
- The US Federal Tox21 Program: A strategic and operational plan for continued leadership.ALTEX · 2018Article
- The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions.Environmental health perspectives · 2016Review
- In vitro screening for population variability in toxicity of pesticide-containing mixtures.Environment international · 2015Article
- Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making.Environmental health perspectives · 2015Review
- Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study.Environmental health perspectives · 2015Article
- Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse.Environmental health perspectives · 2014Article
- FutureTox: building the road for 21st century toxicology and risk assessment practices.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- A cellular genetics approach identifies gene-drug interactions and pinpoints drug toxicity pathway nodes.Frontiers in genetics · 2014Article
- Addressing human variability in next-generation human health risk assessments of environmental chemicals.Environmental health perspectives · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d'Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility.
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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.