Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Nov;91(11):3697-3707.
doi: 10.1007/s00204-017-2020-z. Epub 2017 Jun 28.

Adverse outcome pathways: a concise introduction for toxicologists

Mathieu Vinken  1 , Dries Knapen  2 , Lucia Vergauwen  2   3 , Jan G Hengstler  4 , Michelle Angrish  5 , Maurice Whelan  6
Affiliations
Review

Adverse outcome pathways: a concise introduction for toxicologists

Mathieu Vinken et al. Arch Toxicol. 2017 Nov.

Abstract

Adverse outcome pathways (AOPs) are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology, and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use AOPs, have been published in the last few years. The present paper provides a synopsis of the main principles related to the AOP framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology.

Keywords: Adverse outcome pathway; Ecotoxicology; Risk assessment; Toxicology.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Modules of the AOP-KB. The e.AOP.portal can be reached at http://aopkb.org, the AOP Wiki at http://aopwiki.org, Effectopedia at http://effectopedia.org and the AOP Xplorer at http://datasciburgoon.github.io/aopxplorer. The OECD “Harmonized Template 201: Intermediate effects” can be found at https://www.oecd.org/ehs/templates/harmonised-templates-intermediate-effects.htm.
Figure 2
Figure 2
Generic AOP structure, in this case applied to human toxicology, spread over different levels of biological organization and fed by different types of information.
Figure 3
Figure 3
AOP development process and potential applications in toxicology and risk assessment. There are no clear boundaries between the different stages of development or levels of completeness (i.e. putative AOP, formal AOP and quantitative AOP). These terms rather reflect a continuum of development and in most cases it is not possible to assign specific applications to a specific category. Instead, the applicability of a given AOP most often depends on a case by case determination of fit-for-purpose.
Figure 4
Figure 4
AOP from covalent protein binding leading to skin sensitization in human (https://aopwiki.org/aops/40).
Figure 5
Figure 5
AOP from aromatase inhibition leading to reproductive dysfunction in fish (https://aopwiki.org/aops/25).
See this image and copyright information in PMC

References

    1. Ankley GT, Bencic DC, Cavallin JE, Jensen KM, Kahl MD, Makynen EA, Martinovic D, Mueller ND, Wehmas LC, Villeneuve DL. Dynamic nature of alterations in the endocrine system of fathead minnows exposed to the fungicide prochloraz. Toxicol Sci. 2009;112:344–353. - PubMed
    1. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrrano JA, et al. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010;29:730–741. - PubMed
    1. Ashikaga T, Yoshida Y, Hirota M, Yoneyama K, Itagaki H, Sakaguchi H, Miyazawa M, Ito Y, Suzuki H, Toyoda H. Development of an in vitro skin sensitization test using human cell lines: the human cell line activation test (h-CLAT): I. optimization of the h-CLAT protocol. Toxicol In Vitro. 2006;20:767–773. - PubMed
    1. Basketter DA, White IR, McFadden JP, Kimber I. Skin sensitization: implications for integration of clinical data into hazard identification and risk assessment. Hum Exp Toxicol. 2015;34:1222–1230. - PubMed
    1. Becker RA, Ankley GT, Edwards SW, Kennedy SW, Linkov I, Meek B, Sachana M, Segner H, Van Der Burg B, Villeneuve DL, Watanabe H, et al. Increasing scientific confidence in adverse outcome pathways: application of tailored Bradford-Hill considerations for evaluating weight of evidence. Regul Toxicol Pharmacol. 2015;72:514–537. - PubMed

LinkOut - more resources