ArticleToxicological sciences : an official journal of the Society of Toxicology2021
A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- AOP Report: Aryl Hydrocarbon Receptor Activation Leads to Early-Life Stage Mortality via Sox9 Repression-Induced Craniofacial and Cardiac Malformations.Environmental toxicology and chemistry · 2023Pooled it
- A high-throughput method to computationally develop candidate adverse outcome pathways in humans: a proof of concept with insecticides and Parkinson's Disease.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Cadmium Exposure and Osteoporosis: A Spatially Contextualized Adverse Outcome Pathway Integrating Epidemiology, Toxicogenomics and Transcriptomics.Biological trace element research · 2026Article
- Mass Spectrometry Proteomics: A Key to Faster Drug Discovery.Journal of medicinal chemistry · 2026Review
- The FAIR AOP roadmap for 2025: Advancing findability, accessibility, interoperability, and re-usability of adverse outcome pathways.Computational toxicology (Amsterdam, Netherlands) · 2025Article
- Computational tools and data integration to accelerate vaccine development: challenges, opportunities, and future directions.Frontiers in immunology · 2025Review
- Article
- AOP Report: Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia.Current research in toxicology · 2025Article
- A developmental neurotoxicity adverse outcome pathway (DNT-AOP) with voltage gate sodium channel (VGSC) inhibition as a molecular initiating event (MiE).EFSA journal. European Food Safety Authority · 2024Article
- Building an Adverse Outcome Pathway network for COVID-19.Frontiers in systems biology · 2024Article
- Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.Frontiers in toxicology · 2024Article
- The adverse outcome pathway for breast cancer: a knowledge management framework bridging biomedicine and toxicology.Discover oncology · 2023Review
- Adverse outcome pathway for pregnane X receptor-induced hypercholesterolemia.Archives of toxicology · 2023Review
- Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.EFSA journal. European Food Safety Authority · 2023Article
- Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations.Environmental research · 2023Review
- Development of a data-driven approach to Adverse Outcome Pathway network generation: a case study on the EATS-modalities.Frontiers in toxicology · 2023Article
- Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19.Journal of clinical medicine · 2022Review
- Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways.Journal of clinical medicine · 2022Review
- Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.Redox biology · 2022Review
- Natural language processing in toxicology: Delineating adverse outcome pathways and guiding the application of new approach methodologies.Biomaterials and biosystems · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adverse outcome pathway (AOP) framework provides a practical means for organizing scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. It has reached wide acceptance as a tool to aid chemical safety assessment and regulatory toxicology by supporting a systematic way of predicting adverse health outcomes based on accumulated mechanistic knowledge. A major challenge for broader application of the AOP concept in regulatory toxicology, however, has been developing robust AOPs to a level where they are peer reviewed and accepted. This is because the amount of work required to substantiate the modular units of a complete AOP is considerable, to the point where it can take years from start to finish. To help alleviate this bottleneck, we propose a more pragmatic approach to AOP development whereby the focus becomes on smaller blocks. First, we argue that the key event relationship (KER) should be formally recognized as the core building block of knowledge assembly within the AOP knowledge base (AOP-KB), albeit framing them within full AOPs to ensure regulatory utility. Second, we argue that KERs should be developed using systematic review approaches, but only in cases where the underlying concept does not build on what is considered canonical knowledge. In cases where knowledge is considered canonical, rigorous systematic review approaches should not be required. It is our hope that these approaches will contribute to increasing the pace at which the AOP-KB is populated with AOPs with utility for chemical safety assessors and regulators.
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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.