ArticleEnvironmental health perspectives2015
Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study.
Article in Environmental health perspectives, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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.
The trial behind it
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
72 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
- Natural variation suggests candidate genes underlying Caenorhabditis elegans susceptibility to diverse toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Natural variation suggests candidate genes underlyingbioRxiv : the preprint server for biology · 2025Article
- 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
- 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
- Therapeutic Bioactivities and Chemical Composition Analysis of Rhizome Oleoresin ofCombinatorial chemistry & high throughput screening · 2025Article
- Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.Human genomics · 2024Review
- Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.Human genomics · 2024Article
- Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.Regulatory toxicology and pharmacology : RTP · 2024Article
- Invited Perspective: Uneven Progress Addressing Population Variability in Human Health Risk Assessment.Environmental health perspectives · 2024Article
- Mapping Interindividual Variability of Toxicodynamics Using High-Throughput Transcriptomics and Primary Human Hepatocytes from Fifty Donors.Environmental health perspectives · 2024Article
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- Advancing probabilistic risk assessment by integrating human biomonitoring, new approach methods, and Bayesian modeling: A case study with the mycotoxin deoxynivalenol.Environment international · 2023Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
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- 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
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12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
backgroundUnderstanding of human variation in toxicity to environmental chemicals remains limited, so human health risk assessments still largely rely on a generic 10-fold factor (10½ each for toxicokinetics and toxicodynamics) to account for sensitive individuals or subpopulations.
objectivesWe tested a hypothesis that population-wide in vitro cytotoxicity screening can rapidly inform both the magnitude of and molecular causes for interindividual toxicodynamic variability.
methodsWe used 1,086 lymphoblastoid cell lines from the 1000 Genomes Project, representing nine populations from five continents, to assess variation in cytotoxic response to 179 chemicals. Analysis included assessments of population variation and heritability, and genome-wide association mapping, with attention to phenotypic relevance to human exposures.
resultsFor about half the tested compounds, cytotoxic response in the 1% most "sensitive" individual occurred at concentrations within a factor of 10½ (i.e., approximately 3) of that in the median individual; however, for some compounds, this factor was > 10. Genetic mapping suggested important roles for variation in membrane and transmembrane genes, with a number of chemicals showing association with SNP rs13120371 in the solute carrier SLC7A11, previously implicated in chemoresistance.
conclusionsThis experimental approach fills critical gaps unaddressed by recent large-scale toxicity testing programs, providing quantitative, experimentally based estimates of human toxicodynamic variability, and also testable hypotheses about mechanisms contributing to interindividual variation.
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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 Socratic graph.