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Integration of New Approach Methodologies for Prospective Selection of Chemicals for Additional Study (Physicians Committee for Responsible Medicine (PCRM)/New Approach Methodology (NAM) Use for Regulatory Application (NURA) May 2022)
Citation:
Paul-Friedman, K. Integration of New Approach Methodologies for Prospective Selection of Chemicals for Additional Study (Physicians Committee for Responsible Medicine (PCRM)/New Approach Methodology (NAM) Use for Regulatory Application (NURA) May 2022). PCRM Online Webinar: DyNAMic Discussions: The Future is Already Here, NA, Webinar, May 20, 2022. https://doi.org/10.23645/epacomptox.20037902
Impact/Purpose:
Presenting to the PCRM/NURA-sponsored webinar, "DyNAMic Discussions: The Future is Already Here" about approaches to transition toward NAM-based chemical safety assessment. Online webinar series with Physicians Committee for Responsible Medicine (PCRM)/New Approach Methodology (NAM) Use for Regulatory Application (NURA) May 2022
Description:
Use of new approach methodologies (NAMs), including high-throughput, in vitro bioactivity data, in setting a point-of-departure (POD) has the potential to accelerate the pace of human health risk assessments. Combining hazard and exposure predictions as a bioactivity:exposure ratio (BER) for use in risk-based prioritization of substances that may not have a complete data profile represents a prospective approach to employing new approach methodologies (NAMs). Further, NAMs may provide some support for derivation of bioactivity flags, i.e. potential hazards that are of concern for further mechanism-based screening and/or hazard prediction. In this work we describe the first phase of an effort conducted via the Accelerating the Pace of Chemical Risk Assessment initiative, a consortium of international toxicologists and regulatory scientists. This prospective case study involves generation of NAM data for 200 chemicals, with the primary objective of developing reusable and adaptable approach for prioritization of chemicals for additional short-term studies in rats using a combination of the BER and bioactivity-based flags for indication of putative endocrine, developmental, neurological, and immune suppressive effects. Multiple hazard data streams, including targeted biochemical and cell-based assays, high-throughput transcriptomics, and high-throughput phenotypic profiling data, will be used to inform hazard and risk indications, along with generic high-throughput toxicokinetic models parameterized with chemical-specific data. The goal of this case study is to enable regulatory scientists from different international contexts to develop efficient approaches for chemical management, while possibly reducing the need for animal studies by identifying key areas for hazard characterization. This work demonstrates the feasibility, and continuing challenges, of using toxicodynamic and toxicokinetic NAMs in screening level safety assessment. This abstract does not necessarily reflect U.S. EPA, Health Canada, EFSA, ECHA, A*STAR, or JRC policy.
URLs/Downloads:
DOI: Integration of New Approach Methodologies for Prospective Selection of Chemicals for Additional Study (Physicians Committee for Responsible Medicine (PCRM)/New Approach Methodology (NAM) Use for Regulatory Application (NURA) May 2022)
NURA_DYNAMIC_DISCUSSION_INTEG_OF_NAMS_PROSPECTIVE_SELECTION_CHEMS_20MAY2022.PDF (PDF, NA pp, 2252.509 KB, about PDF)