Citation:

Perkins, E., N. Garcia-Reyero, S. Edwards, C. Wittwehr, Dan Villeneuve, D. Lyons, AND G. Ankley. The Adverse Outcome Pathway: A conceptual framework to support toxicity testing in the 21st century. Chapter 1, Computational Systems Toxicology: Discovering and Using the Toxicological Blueprint of Active Substances. Springer Science + Business Media, New York, NY, , 1-26, (2015).

Impact/Purpose:

The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their metabolites that can lead to adverse effect. The aim of the book is to share the vision of international initiatives aimed at characterizing toxicity pathways and provide the reader with an overview of the most relevant systems toxicology resources and computational approaches to evaluate large molecular datasets, which organized into meaningful biological networks, lead to mechanistic insights of potential toxic effects essential for safety assessment. This chapter outlines the important role of the adverse outcome pathway (AOP) concept as an important framework for implementing the NRC vision. This chapter disseminates a vision for the role of AOPs in 21st century toxicity testing, the history and evolution of the AOP concept, and considerations for developing and disseminating AOPs via a common knowledgebase, to the computational toxicology audience the book is geared toward. As such, it aids on-going EPA efforts to engage the broader scientific community in the development and application of AOPs in research and risk-based decision-making.

Description:

The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their metabolites that can lead to adverse effect. The aim of the book is to share the vision of international initiatives aimed at characterizing toxicity pathways and provide the reader with an overview of the most relevant systems toxicology resources and computational approaches to evaluate large molecular datasets, which organized into meaningful biological networks, lead to mechanistic insights of potential toxic effects essential for safety assessment. This chapter outlines the important role of the adverse outcome pathway (AOP) concept as an important framework for implementing the NRC vision. This chapter disseminates a vision for the role of AOPs in 21st century toxicity testing, the history and evolution of the AOP concept, and considerations for developing and disseminating AOPs via a common knowledgebase, to the computational toxicology audience the book is geared toward. As such, it aids on-going EPA efforts to engage the broader scientific community in the development and application of AOPs in research and risk-based decision-making.

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