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Application of Mechanistic Data in Risk Assessment: Exposure Alignment and Evidence Integration
Citation:
Jarabek, A. Application of Mechanistic Data in Risk Assessment: Exposure Alignment and Evidence Integration. Advancing New Alternative Methods for Tobacco Harm Reduction, Durham, NC, October 18 - 22, 2021.
Impact/Purpose:
Invited presentation in a session hosted by NICEATM and CORESTA (Centre de Coopération pour les Recherches Scientifiques Relatives au Tabac/Cooperation Centre for Scientific Research Relative to Tobacco) . Participants include FDA, NICEATM, PSCI and PNNL in addition to EPA. Impact will be technology transfer of current work wiht OCSPP on in vitro to in vivo extrapolation (IVIVE) and integrated approaches to testing and assessment (IATA) for inhalation exposures.
Description:
Risk assessment relies on integration of available and relevant evidence across several data streams by necessity. While systematic review can identify relevant data, approaches for integration are still needed. Conceptual constructs for source-to-outcome modeling based on the aggregate exposure pathway (AEP) and adverse outcome pathway (AOP) frameworks can provide a mechanistic scaffold for evidence integration to include application of novel approach methods (NAMs). Based on the conceptual construct, this presentation highlights the critical role of dosimetry models to provide exposure alignment across experimental platforms and illustrates impact with two recent integrated approaches to testing and assessment (IATA) under TSCA Section 5 for evaluation of new chemical substances. Both IATA formalized a role for NAMs. These IATA demonstrate how consideration of physicochemical properties and NAMs aimed at key events of AOPs create context for evaluation of the need and strategy for higher-tiered testing based on mechanistic responses, dosimetry, and exposure information.