Application of mechanistic data in risk assessment: exposure alignment and evidence integration
Risk assessment relies on integration of evidence across several data streams by necessity. Conceptual constructs for source-to-outcome modeling based on aggregate exposure pathway (AEP) and adverse outcome pathway (AOP) frameworks can provide a mechanistic scaffold for evidence integration to now include application of new approach methods (NAMs). Based on the conceptual construct, this presentation will discuss the critical role of dosimetry models to provide exposure alignment across experimental platforms and illustrate impact by two recent integrated approaches to testing and assessment (IATA) under the Toxic Substances Control Act (TSCA) that formalized a role for NAMs. The IATA demonstrate how consideration of physicochemical properties and NAMs aimed at key events (KEs) of AOPs create context for evaluation of the need and strategy for higher-tiered testing based on mechanistic responses, dosimetry, and exposure information.