NAMs-Decisions Center: New Approach Methods for Decisions on Industrial and Consumer-Use Chemicals

About This Grant

PROJECT SUMMARY The NAMs Decisions Center is a multidisciplinary team of scientists, engineers, modelers, and educators working to integrate New Approach Methodologies (NAMs) into regulatory decision-making for chemical safety assessment. The primary goal of the Center is to develop defined approaches for using mature combinatorial in vitro and in silico NAMs to enhance read-across methods, reducing reliance on animal testing. A key challenge in replacing traditional animal tests is proving sufficient similarity between chemicals, which is required for regulatory acceptance of read-across approaches. A systematic review of over 1,100 industry-proposed read- across adaptations submitted to the European Chemicals Agency (ECHA) found that only 8% were accepted, primarily due to insufficient toxicokinetic and toxicodynamic data—gaps that NAMs could help fill. To address this, the Center proposes five Specific Aims. Aim 1: Center Management and International Integration, will ensure effective governance through an Internal Steering Committee and guidance from an External Advisory Committee with international representation from regulatory agencies, industry and NGOs. Aim 2: Developing Population-Based NAMs for Read-Across, will be focused on improving read-across approaches using population-based in vitro and in silico NAMs. This work will include complex in vitro models for gut permeability, liver metabolism, and renal clearance, population variability studies using human-derived cell panels, ion mobility spectrometry-mass spectrometry as a rapid tool for toxicokinetics, toxicodynamic variability assessment with human lymphoblast cell lines, these will be combined into population-toxicokinetics/toxicodynamics NAMs. Three pilot projects focused on Center-relevant studies will be also included. Aim 3: NAMs Technology Development and Commercialization, will consist of three cores: Administrative Core will provide Center oversight, Data Management & Bioinformatics Core will be responsible for data integration and biostatistics support, and NAMs Resources Core will include resources for Device Fabrication and Transcriptomics. Aim 4: NAMs Qualification and Regulatory Acceptance, will ensure the robustness and reproducibility of the individual and combinatorial NAMs. With expertise in regulatory qualification, this Aim will help facilitate regulatory acceptance of Center- developed NAMs-based approaches. Aim 5: Training, Outreach, and Stakeholder Engagement, will conduct Ethical, Legal, and Social Implications (ELSI) research (identify stakeholder concerns, clarify validation expectations, and refine communication strategies), workforce development & training (create NAMs education materials for high-school/college students, regulators, industry professionals, and academics), and Community Engagement (encourage regulatory adoption through targeted workshops and read-across case studies). Overall, the NAMs Decisions Center aims to revolutionize chemical safety assessments by integrating NAMs into defined read-across approaches. By accelerating chemical evaluations and reducing reliance on animal testing, this initiative will make a significant impact on public health and regulatory decision-making.