Adverse outcome pathway explained

An adverse outcome pathway (AOP) is structured representation of biological events leading to adverse effects and is considered relevant to risk assessment.^{[1] [2]} The AOP links in a linear way existing knowledge along one or more series of causally connected key events (KE) between two points — a molecular initiating event (MIE) and an adverse outcome (AO) that occur at a level of biological organization relevant to risk assessment. The linkage between the events is described by key event relationships (KER) that describe the causal relationships between the key events. AOPs are important for expanding the use of mechanistic toxicological data for risk assessment and regulatory applications with recent applications in further disciplines such as climate science.^{[3] [4] [5]}

Background

In 2012, the Organisation for Economic Co-operation and Development (OECD) launched a new programme on the development of adverse outcome pathways. A guidance document describes in detail how AOPs are to be developed, reviewed, agreed and published at the OECD level.^[6] The AOP development and reviewing workflow is intended to take place via a web-based IT management tool: the Adverse Outcome Pathway Knowledge Base (AOP-KB)^[7] which is currently still under development. It is the wiki-based, user-friendly tool providing open-source interface for collaborative sharing of established AOPs and building new AOPs. The AOP-KB gives the scientific community the possibility to enter, share and discuss their AOP-related knowledge at one central point of information.The AOP-KB allows for building AOPs by entering and then linking information about MIEs, KEs, AOs and Chemical Initiators.Knowing that pathway elements are not necessarily unique to a single AOP, value is added to existing knowledge by facilitating the re-use of MIE, KE and AO information in multiple AOPs, which prevents redundancy and make the collective knowledge about those entities available in all AOPs in which they appear.

The AOP-KB is a combination of individually developed applications, synchronised and orchestrated in a way that gives users the possibility to capture, review, browse and comment on AOPs shared by the AOP stakeholder community.

The AOP-KB project is an Organisation for Economic Co-operation and Development initiative, which is executed as close collaboration between the Joint Research Centre of European Commission, the United States Environmental Protection Agency and the Engineer Research and Development Center of United States Army Corps of Engineers for the purpose of the Organisation for Economic Co-operation and Development's programme on the development of AOPs ^[8]

The AOP has also been recently applied to better understand the effects of climate related stressors, further expanding the potential of AOPs to other scientific disciplines

More recent developments have focused on the analysis of AOP networks^[9] and the quantification of KERs with a view to developing mathematical models of AOPs, sometimes referred to as quantitative AOPs.^[10]

Scientific workshops held for advancing the concept of AOP:

• 2013
  • January 23–25, Baltimore, USA Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology:Liver Toxicity Mode-of-Action^[11]
• 2014
  • March 2–7, Somma Lombardo, Italy Advancing Adverse Outcome Pathways (AOP) for Integrated Toxicology and Regulatory Applications ^[12]
  • August 24, Prague, Czech Republic AOPs 101: The How and Why of Development and Use ^[13]
  • September 3–5, Bethesda, USA Adverse Outcome Pathways: From Research to Regulation workshop held by NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Physicians Committee for Responsible Medicine. Materials from the workshop, including links to the plenary session videocasts and summaries of the breakout group discussions, are available on the NTP website^[14]

External links

• AOP KB Homepage
• OECD Adverse Outcome Pathways, Molecular Screening and Toxicogenomics Programme on the development of AOPs
• European Commission's Joint Research Centre
• Adverse Outcome Pathways: From Research to Regulation
• NTP Interagency Center for the Evaluation of Alternative Toxicological Methods

Notes and References

1. Book: ((National Research Council; Division on Earth and Life Studies; Board on Environmental Studies and Toxicology; Institute for Laboratory Animal Research; Committee on Toxicity Testing and Assessment of Environmental Agents)) . Toxicity testing in the 21st century : a vision and a strategy. 2007. The National Academic Press. Washington. 978-0-309-15173-3.
2. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, Tietge JE, Villeneuve DL . 6 . Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment . Environmental Toxicology and Chemistry . 29 . 3 . 730–741 . March 2010 . 20821501 . 10.1002/etc.34 . 26011816 . free .
3. Kramer VJ, Etterson MA, Hecker M, Murphy CA, Roesijadi G, Spade DJ, Spromberg JA, Wang M, Ankley GT . 6 . Adverse outcome pathways and ecological risk assessment: bridging to population-level effects . Environmental Toxicology and Chemistry . 30 . 1 . 64–76 . January 2011 . 20963853 . 10.1002/etc.375 . 40565681 . free .
4. Book: Cronin M, Madden J. In silico toxicology principles and applications. Chapter 14:Adverse Outcome Pathways: A Way of Linking Chemical Structure to in Vivo Toxicological Hazards. Issues in Toxicology. 2010. 346–371. Royal Society of Chemistry. Cambridge. 10.1039/9781849732093-00346. 978-1-84973-209-3. Schultz TW. 2014-09-16. 2014-11-29. https://web.archive.org/web/20141129093239/http://pubs.rsc.org/en/content/chapter/bk9781849730044-00346/978-1-84973-004-4/unauth#!divRelatedContent&chapters. dead.
5. Ducker J, Falkenberg LJ . 2020 . How the Pacific Oyster Responds to Ocean Acidification: Development and Application of a Meta-Analysis Based Adverse Outcome Pathway. . Frontiers in Marine Science . 7 . 597441 . 10.3389/fmars.2020.597441. free .
6. Web site: The Development of AOPs. oecd.org . OECD.
7. Web site: Adverse Outcome Pathway Knowledge Base (AOP-KB).
8. Web site: Adverse Outcome Pathways, Molecular Screening and Toxicogenomics. OECD.
9. Spinu N, Bal-Price A, Cronin MT, Enoch SJ, Madden JC, Worth AP . Development and analysis of an adverse outcome pathway network for human neurotoxicity . Archives of Toxicology . 93 . 10 . 2759–2772 . October 2019 . 31444508 . 10.1007/s00204-019-02551-1 . 201283568 . free .
10. Paini A, Campia I, Cronin MT, Asturiol D, Ceriani L, Exner TE, Gao W, Gomes C, Kruisselbrink J, Martens M, Meek ME, Pamies D, Pletz J, Scholz S, Schüttler A, Spînu N, Villeneuve DL, Wittwehr C, Worth A, Luijten M . 6 . Towards a qAOP framework for predictive toxicology - Linking data to decisions . Computational Toxicology . 21 . 100195 . February 2022 . 35211660 . 8850654 . 10.1016/j.comtox.2021.100195 .
11. Willett C, Caverly Rae J, Goyak KO, Minsavage G, Westmoreland C, Andersen M, Avigan M, Duché D, Harris G, Hartung T, Jaeschke H, Kleensang A, Landesmann B, Martos S, Matevia M, Toole C, Rowan A, Schultz T, Seed J, Senior J, Shah I, Subramanian K, Vinken M, Watkins P . 6 . Building shared experience to advance practical application of pathway-based toxicology: liver toxicity mode-of-action . Altex . 31 . 4 . 500–519 . 2014 . 24535319 . 4779550 . 10.14573/altex.1401281 .
12. Advancing Adverse Outcome Pathways (AOP) for Integrated Toxicology and Regulatory Applications . Workshop . Somma Lombardo, Italy . March 2014 . 16 September 2014. https://archive.today/20141119010731/https://aopkb.org/saop/workshops/somma.html. 19 November 2014. dead. dmy-all.
13. Web site: AOPs 101: The How and Why of Development and Use. 17 September 2014.
14. Web site: Adverse Outcome Pathways: From Research to Regulation. NTP. 16 September 2014.