Science Inventory

Retrospective Clinical Evaluation for the Development of Reference Chemical Lists

Citation:

Ponder, J., M. Singal, K. Sullivan, AND Nancy C. Baker. Retrospective Clinical Evaluation for the Development of Reference Chemical Lists. 10th Annual Meeting of the American Society for Cellular and Computational Toxicology (ASCCT), Virtual, Virtual, October 12 - 14, 2021. https://doi.org/10.23645/epacomptox.17704352

Impact/Purpose:

Presentation to the 10th Annual Meeting of the American Society for Cellular and Computational Toxicology (ASCCT) October 2021. This is work on a project for respiratory sensitisation.

Description:

As new approach methodologies (NAMs) continue to be developed and adopted, an ongoing barrier for in vitro cell and tissue culture assays is the process of validation. A major advantage of human cell and tissue culture models is the ability to improve the accuracy of translation of results from the research bench to real-world scenarios. However, limitations emerge during validation stages when gathering prospective clinical data is not an option, especially for hazardous chemicals. Therefore, practical approaches to develop and maintain the most clinically relevant data for comparison are needed. To this end, information from case studies can be evaluated retrospectively to identify and characterize the hazards associated with chemical use in real-world conditions. Herein we describe such an approach for the identification of respiratory sensitizers, in which we utilized the EPA-developed Abstract Sifter literature review tool and standardized search terms to maximize the retrieval of publications relevant to respiratory chemical allergy or asthma in humans. This approach successfully identified over twenty compounds as known respiratory sensitizers based on well-defined clinical diagnostic criteria. This output will be used along with other available data to establish a reference list of respiratory sensitizers, irritants, and non-sensitizers, to update existing risk assessment approaches and evaluate the accuracy of new approaches for this key endpoint. Overall, this approach provides an exemplary method to evaluate and apply human clinical data as part of the weight-of-evidence towards establishing reference chemical lists. This abstract does not necessarily represent U.S. EPA policy.