Adverse outcome pathway networks I: Development and applications

Abstract

Copyright © 2018 The Authors. Based on the results of a SETAC-sponsored Horizon Scanning exercise focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two papers has been developed to begin exploring these concepts. In the present paper (part I), derivation of AOP networks is considered in the context of how it differs from development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary paper (part II). Finally, we present a number of case studies that illustrate concepts underlying development, analysis and application of AOP networks. The concepts described in this paper, and in its companion paper focused on AOP network analytics, are intended to serve as a starting point for further development of the AOP network concept, but also to catalyze AOP network development and application by the different stakeholder communities. This article is protected by copyright. All rights reserved.