ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Evaluating In Vitro-In Vivo Extrapolation of Toxicokinetics.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 142 citations in OpenAlex.
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- Reference library for suspect screening of environmental toxicants using ion mobility spectrometry-mass spectrometry.Communications chemistry · 2025Article
- Informatics for toxicokinetics.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- The environmental neuroactive chemicals list of prioritized substances for human biomonitoring and neurotoxicity testing: A database and high-throughput toxicokinetics approach.Environmental research · 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
- Characterizing chlorotriazine effects in cancer-relevant high-throughput screening assays.Frontiers in toxicology · 2025Article
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- In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters.Archives of toxicology · 2024Article
- Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.Regulatory toxicology and pharmacology : RTP · 2024Article
- Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening.Frontiers in toxicology · 2024Review
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- New approach methodologies in human regulatory toxicology - Not if, but how and when!Environment international · 2023Review
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- A regression analysis using simple descriptors for multiple dermal datasets: Going from individual membranes to the full skin.Journal of applied toxicology : JAT · 2023Article
- Closing the gap between in vivo and in vitro omics: using QA/QC to strengthen ex vivo NMR metabolomics.NMR in biomedicine · 2023Review
- Machine learning and artificial intelligence in physiologically based pharmacokinetic modeling.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
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Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more under-estimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks.
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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.