The Adverse Outcome Pathway: A Multifaceted Framework Supporting 21^st Century Toxicology

The adverse outcome pathway (AOP) framework serves as a knowledge assembly, interpretation, and communication tool designed to support the translation of pathway-specific mechanistic data into responses relevant to assessing and managing risks of chemicals to human health and the environment. As such, AOPs facilitate the use of data streams often not employed by risk assessors, including information from in silico models, in vitro assays and short-term in vivo tests with molecular/biochemical endpoints. This translational capability can increase the capacity and efficiency of safety assessments both for single chemicals and chemical mixtures. Our mini-review describes the conceptual basis of the AOP framework and aspects of its current status relative to use by toxicologists and risk assessors, including four illustrative applications of the framework to diverse assessment scenarios.