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Finding Synergies for 3Rs – Toxicokinetics and Read-Across: Report from an EPAA Partners’ Forum

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners’ Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. An important hurdle to PBK modelling is a lack of toxicokinetic data. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetic parameters required for read-across; case studies exemplifying how toxicokinetics data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools; and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to create a database of toxicokinetic tools that assist risk assessment.