ArticleToxicological sciences : an official journal of the Society of Toxicology2020
A Rat Liver Transcriptomic Point of Departure Predicts a Prospective Liver or Non-liver Apical Point of Departure.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Review on Predictive Models and Integration Strategies for Holistic Impact Assessment of Chemicals and Materials.Environmental science & technology · 2026Review
- Dose-response assessment of dipentyl phthalate effects on testosterone production and morphogenesis of late-gestation fetal rat testis.Environment international · 2025Article
- Bioinformatic workflows for deriving transcriptomic points of departure: current status, data gaps, and research priorities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- 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
- Article
- Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.Archives of environmental contamination and toxicology · 2024Article
- Transcriptomic point of departure determination: a comparison of distribution-based and gene set-based approaches.Frontiers in genetics · 2024Article
- Integrating gene expression and splicing dynamics across dose-response oxidative modulators.Frontiers in genetics · 2024Article
- Article
- The Effect of Historical Data-Based Informative Prior on Benchmark Dose Estimation of Toxicogenomics.Chemical research in toxicology · 2023Article
- A tiered testing strategy based on in vitro phenotypic and transcriptomic data for selecting representative petroleum UVCBs for toxicity evaluation in vivo.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- A value of information framework for assessing the trade-offs associated with uncertainty, duration, and cost of chemical toxicity testing.Risk analysis : an official publication of the Society for Risk Analysis · 2023Article
- Editorial:Frontiers in toxicology · 2023Article
- From vision toward best practices: EvaluatingFrontiers in toxicology · 2023Article
- A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.Toxicology in vitro : an international journal published in association with BIBRA · 2022Review
- A microRNA or messenger RNA point of departure estimates an apical endpoint point of departure in a rat developmental toxicity model.Birth defects research · 2022Article
- Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- A computational system for Bayesian benchmark dose estimation of genomic data in BBMD.Environment international · 2022Article
- Case study: Targeted RNA-sequencing of aged formalin-fixed paraffin-embedded samples for understanding chemical mode of action.Toxicology reports · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying a toxicity point of departure (POD) is a required step in human health risk characterization of crop protection molecules, and this POD has historically been derived from apical endpoints across a battery of animal-based toxicology studies. Using rat transcriptome and apical data for 79 molecules obtained from Open TG-GATES (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) (632 datasets), the hypothesis was tested that a short-term exposure, transcriptome-based liver biological effect POD (BEPOD) could estimate a longer-term exposure "systemic" apical endpoint POD. Apical endpoints considered were body weight, clinical observation, kidney weight and histopathology and liver weight and histopathology. A BMDExpress algorithm using Gene Ontology Biological Process gene sets was optimized to derive a liver BEPOD most predictive of a systemic apical POD. Liver BEPODs were stable from 3 h to 29 days of exposure; the median fold difference of the 29-day BEPOD to BEPODs from earlier time points was approximately 1 (range: 0.7-1.1). Strong positive correlation (Pearson R = 0.86) and predictive accuracy (root mean square difference = 0.41) were observed between a concurrent (29 days) liver BEPOD and the systemic apical POD. Similar Pearson R and root mean square difference values were observed for comparisons between a 29-day systemic apical POD and liver BEPODs derived from 3 h to 15 days of exposure. These data across 79 molecules suggest that a longer-term exposure study apical POD from liver and non-liver compartments can be estimated using a liver BEPOD derived from an acute or subacute exposure study.
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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.