ArticleEnvironment international2015
In vitro screening for population variability in toxicity of pesticide-containing mixtures.
Article in Environment international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- 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
- Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility.bioRxiv : the preprint server for biology · 2025Article
- 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
- Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.Human genomics · 2024Review
- 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
- New approach methodologies to address population variability and susceptibility.Human genomics · 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
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- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Methods for evaluating variability in human health dose-response characterization.Human and ecological risk assessment : HERA · 2019Article
- Multi-dimensional in vitro bioactivity profiling for grouping of glycol ethers.Regulatory toxicology and pharmacology : RTP · 2019Article
- Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population.Toxicology · 2018Review
- Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures - an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides - in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitro-to-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard from complex environmental mixtures. Additionally, such an approach yields testable hypotheses regarding potential toxicity mechanisms.
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What OpenQuestion holds
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.