Cited by 2,734Environmental Toxicology and EcotoxicologyAnimal testing and alternativesAgricultural safety and regulations

Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment

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Ankley, Gerald T., Bennett, Richard S., Erickson, Russell J., Hoff, Dale J., Hornung, Michael W., Johnson, Rodney D., Mount, David R., Nichols, John W. +5 more·2009·Environmental Toxicology and Chemistry

Abstract

Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk—effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations. Here we discuss a framework designed for this purpose, the adverse outcome pathway (AOP). An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. The practical utility of AOPs for ecological risk assessment of chemicals is illustrated using five case examples. The examples demonstrate how the AOP concept can focus toxicity testing in terms of species and endpoint selection, enhance across-chemical extrapolation, and support prediction of mixture effects. The examples also show how AOPs facilitate use of molecular or biochemical endpoints (sometimes referred to as biomarkers) for forecasting chemical impacts on individuals and populations. In the concluding sections of the paper, we discuss how AOPs can help to guide research that supports chemical risk assessments and advocate for the incorporation of this approach into a broader systems biology framework. Environ. Toxicol. Chem. 2010;29:730–741. © 2009 SETAC

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  • The AOP concept was designed as a conceptual framework for sequential organization of the molecular initiating event, connected with the adverse outcome via a series of key events.

    “the concept of adverse outcome pathways (AOP) was designed as a conceptual framework for the sequential organization of the molecular initiating event (MIE), connected with the adverse outcome (AO) via a series of KEs (Ankley et al., 2010).”

    From In Vitro research Reproducibility: Keeping up High Standards (2019) · cites this paper as Ankley et al., 2010

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  1. G.T. Ankley et al. 15528618, 2010, 3, Downloaded from https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.34
  2. by Readcube (Labtiva Inc.), Wiley Online Library on [01/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License laevis: Two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD). Toxicol Sci 88:60-72.
  3. Wheeler JR, Gimeno S, Crane M, Lopez-Juez E, Morritt D. 2005. Vitellogenin: A review of analytical methods to detect (anti)estrogenic activity in fish. Toxicol Mech Methods 15:293-306.
  4. Kleinow KM, Nichols JW, Hayton WL, McKim JM, Barron MG. 2008. Toxicokinetics in fishes. In Di Giulio R, Hinton D, eds, The Toxicology of Fishes. Taylor & Francis, New York, NY, USA, pp 55-152.
  5. Erickson RJ, Nichols JW, Cook PM, Ankley GT. 2008. Bioavailability of chemicals in the aquatic environment. In Di Giulio R, Hinton D, eds, The Toxicology of Fishes. Taylor & Francis, New York, NY, USA, pp 9-54. Adverse outcome pathways in ecological risk assessment Environ. Toxicol. Chem. 29, 2010

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Authors
Ankley, G. T., Bennett, R. S., Erickson, R. J., Hoff, D. J., Hornung, M. W., Johnson, R. D., Mount, D. R., Nichols, J. W., Russom, C. L., Schmieder, P. K., Serrrano, J. A., Tietge, J. E., & Villeneuve, D. L.
Affiliations
Environmental Protection Agency (US)
Corresponding author
Ankley, Gerald T.
Venue
Environmental Toxicology and Chemistry
Published
2009-11-09
Volume
29
Issue
3
Pages
730-741
ISSN
  • 0730-7268 (ISSN-L)
  • 1552-8618
OpenAlex
W2000089305
Cited by
2,734
References
2
Citations by year
2026: 243 · 2025: 188 · 2024: 206 · 2023: 208 · 2022: 192 · 2021: 192 · 2020: 212 · 2019: 212 · 2018: 206 · 2017: 196 · 2016: 190 · 2015: 171 · 2014: 126 · 2013: 89 · 2012: 59
FWCI
4.02
Type
journal article
Language
en
Open access
Locations
  • Environmental Toxicology and Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Agricultural safety and regulations
Keywords
adverse outcome pathways, environmental risk assessment, ecotoxicology, molecular initiating events, biomarkers, mixture effects, systems biology, population effects
MeSH terms
Animals, Humans, Receptors, Estrogen, Research, Vitellogenesis, Dermatitis, Phototoxic, Receptors, Aryl Hydrocarbon, Risk Assessment, Systems Biology, Stupor, Ecotoxicology

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