Advancing NAM Data into Evidence Integration for Inhalation Risk Assessment: Integrated Approaches to Testing and Assessment (IATA)
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There is increasing interest in replacing tests using laboratory animals with human cell-based, biochemical, or computational methods to predict chemical toxicity for regulatory decision making, with a focus on novel approach methods (NAMs) comprised of in vitro assays. To best support the integration of these new types of data into assessment workflows, case studies based on integrated approaches to testing and assessment (IATAs) provide a means by which all relevant and reliable information about a chemical is used to answer a defined hazard characterization question. This can be especially challenging for inhalation exposures, however, as different experimental platforms vary by both exposure system (e.g., direct liquid application versus air liquid interface) and cell system (e.g., epithelial cell line, 3D tissue explants) that influence characterization of delivered dose and inferences regarding effects. This presentation will present how elucidating mechanistic factors along an exposure-dose-response construct can help create needed clarity on important parameters necessary for coherent evidence integration in an IATA. For example, considerations of in vivo dynamics such as proximal to distal distribution of inhaled reactive gases can be used to guide the choice of exposure and cell systems, while the parallelogram approach proven to be useful for interspecies extrapolation can be used to verify dose predictions to improve in vitro to in vivo extrapolation (IVIVE). The need for data templates to ensure adequate meta data are captured on assays and the role of developing best practices and reporting standards to ensure results are repurposed appropriately in risk assessment applications will also be discussed.