ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Assessing Toxicokinetic Uncertainty and Variability in Risk Prioritization.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed.
- Incorporating a dermal absorption route into high throughput toxicokinetic modeling.Journal of exposure science & environmental epidemiology · 2026Article
- Scientific Opinion on waiving of the dog studies in the regulatory process of agrochemicals approval.EFSA journal. European Food Safety Authority · 2026Article
- Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Uncertainty-aware machine learning to predict non-cancer human toxicity for the global chemicals market.Nature communications · 2026Article
- Extrapolation steps in quantitativeCurrent research in toxicology · 2026Review
- Comparative Evaluation of Toxicity End Points in Unicellular Bioassays for Environmental Pollutant Assessment.Environmental science & technology · 2025Article
- Reference library for suspect screening of environmental toxicants using ion mobility spectrometry-mass spectrometry.Communications chemistry · 2025Article
- Cross-species comparisons of plasma binding and considerations for data evaluation.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
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- Community-Engaged Research and the Use of Open Access ToxVal/ToxRef In Vivo Databases and New Approach Methodologies (NAM) to Address Human Health Risks From Environmental Contaminants.Birth defects research · 2024Article
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- TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment.EFSA journal. European Food Safety Authority · 2023Article
- Cutting-edge computational chemical exposure research at the U.S. Environmental Protection Agency.Environment international · 2023Review
- Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.Chemical research in toxicology · 2023Article
- Article
- HExpPredict:Environmental health perspectives · 2023Article
- Practical application of the interim internal threshold of toxicological concern (iTTC): a case study based on clinical data.Archives of toxicology · 2023Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
High(er) throughput toxicokinetics (HTTK) encompasses in vitro measures of key determinants of chemical toxicokinetics and reverse dosimetry approaches for in vitro-in vivo extrapolation (IVIVE). With HTTK, the bioactivity identified by any in vitro assay can be converted to human equivalent doses and compared with chemical intake estimates. Biological variability in HTTK has been previously considered, but the relative impact of measurement uncertainty has not. Bayesian methods were developed to provide chemical-specific uncertainty estimates for 2 in vitro toxicokinetic parameters: unbound fraction in plasma (fup) and intrinsic hepatic clearance (Clint). New experimental measurements of fup and Clint are reported for 418 and 467 chemicals, respectively. These data raise the HTTK chemical coverage of the ToxCast Phase I and II libraries to 57%. Although the standard protocol for Clint was followed, a revised protocol for fup measured unbound chemical at 10%, 30%, and 100% of physiologic plasma protein concentrations, allowing estimation of protein binding affinity. This protocol reduced the occurrence of chemicals with fup too low to measure from 44% to 9.1%. Uncertainty in fup was also reduced, with the median coefficient of variation dropping from 0.4 to 0.1. Monte Carlo simulation was used to propagate both measurement uncertainty and biological variability into IVIVE. The uncertainty propagation techniques used here also allow incorporation of other sources of uncertainty such as in silico predictors of HTTK parameters. These methods have the potential to inform risk-based prioritization based on the relationship between in vitro bioactivities and exposures.
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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.