Practical approaches to adverse outcome pathway development and weight-of-evidence evaluation as illustrated by ecotoxicological case studies.

Adverse outcome pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and depend largely on the intended use or motivation for development and data availability. The present review describes 4 ecotoxicological AOP case studies, developed for different purposes. In each situation, creation of the AOP began in a manner determined by the initial motivation for its creation and expanded either to include additional components of the pathway or to address the domains of applicability in terms of chemical initiators, susceptible species, life stages, and so forth. Some general strategies can be gleaned from these case studies, which a developer may find to be useful for supporting an existing AOP or creating a new one. Several web-based tools that can aid in AOP assembly and evaluation of weight of evidence for scientific robustness of AOP components are highlighted. Environ Toxicol Chem 2017;36:1429-1449.