ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Adverse outcome pathway development II: best practices.
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In one paragraph
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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
95 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The Transcriptome of the Zebrafish Embryo After Chemical Exposure: A Meta-Analysis.Toxicological sciences : an official journal of the Society of Toxicology · 2017Pooled it
- Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework.Risk analysis : an official publication of the Society for Risk Analysis · 2015Pooled it
- Unveiling toxicological adverse outcomes: toward construction and simulation of large-scale networks.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- HIDmap: a physiology-based map of human immune system development to support animal-free research and regulatory innovation.Frontiers in immunology · 2026Article
- Inhibitory binding to plastoquinone B site on D1 protein of photosystem II leading to decreased population growth rate via disruption of cellular energy metabolism.Frontiers in plant science · 2026Review
- Adverse Outcome Pathways Applied to Space Radiation Research.Environmental and molecular mutagenesis · 2025Review
- Long-term treatment with carbamazepine restores cognitive abilities in a mouse model of KCNQ2 developmental and epileptic encephalopathy.Epilepsia open · 2025Article
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Adverse Outcome Pathway and Machine Learning to Predict Drug Induced Seizure Liability.ACS chemical neuroscience · 2025Article
- Cumulative risk assessment as the pathway to public health protection for behavioral neurotoxicity.Neurotoxicology · 2025Review
- Adverse Outcome Pathways Mechanistically Describing Hepatotoxicity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- An adverse outcome pathway for cigarette smoke-mediated oxidative stress in plaque formation.Frontiers in toxicology · 2025Review
- Current Challenges to Align Inflammatory Key Events in Animals and Lung Cell ModelsChemical research in toxicology · 2024Review
- Leveraging integrative toxicogenomic approach towards development of stressor-centric adverse outcome pathway networks for plastic additives.Archives of toxicology · 2024Article
- New approach methodologies (NAMs) for theFrontiers in toxicology · 2024Review
- Sublethal effects of early-life exposure to common and emerging contaminants in birds.Current research in toxicology · 2024Article
- Cell proliferation and carcinogenesis: an approach to screening for potential human carcinogens.Frontiers in oncology · 2024Article
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35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Daniel L Villeneuve*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium villeneuve.dan@epa.gov.
Doug Crump*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Natàlia Garcia-Reyero*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Markus Hecker*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Thomas H Hutchinson*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Carlie A LaLone*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Brigitte Landesmann*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Teresa Lettieri*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Sharon Munn*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Malgorzata Nepelska*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Mary Ann Ottinger*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Lucia Vergauwen*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Maurice Whelan*US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS 39762, School of the Environment and Sustainability and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada SK S7N 5B3, School of Biological Sciences, University of Plymouth, Plymouth, Devon, PL4 8AA, UK, Water Resources Center, University of Minnesota, St. Paul, MN 55108, European Commission, Joint Research Centre, Via E. Fermi 2749, 21027 Ispra, Italy, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium *US EPA Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, Environment Canada, Ecotoxicology and Wildlife Health Division, Ottawa, Ontario, Canada K1A 0H3, Institute for Genomics, Biocompu
Funding
No grant is acknowledged in the PubMed record.
Abstract
Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.
Indexed as
Databases, FactualModels, BiologicalAnimalsBiomedical ResearchHumansToxicologyadverse outcome pathwayextrapolationknowledgebasepredictive toxicologyregulatory toxicology
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