Opportunities and Challenges of Physiologically Based Kinetic Model-based Quantitative In Vitro to In Vivo Extrapolation in a Next Generation Risk Assessment Paradigm
Registration is required for this free webinar
Hosted by the SOT Risk Assessment and Biological Modeling Specialty Sections
Physiologically based kinetic (PBK) model-based quantitative in vitro-in vivo extrapolation (QIVIVE) links in vitro effect concentrations to human bioequivalent external doses, making it central to next generation risk assessment (NGRA) and the move away from animal testing. Generic, population-based PBK modelling platforms are a welcome development, as they streamline and standardize QIVIVE for NGRA by providing ready-to-use, quality-controlled model structures and physiological databases, enabling rapid simulations across chemicals and populations and facilitating easier review and regulatory uptake. Yet their implementation still faces several important scientific bottlenecks, including poor prediction of the kinetics of chemicals that are lipophilic, are transporter substrates or undergo enterohepatic circulation. This RASS/BMSS webinar presents research on PBK model-based QIVIVE from three research programmes, the Dutch VHP4Safety project, the EU Horizon Europe PARC partnership and the EU Horizon 2020 ONTOX project, which together aim to tackle these bottlenecks. Case studies focus on (developmental) neurotoxicity and nephrotoxicity and include organophosphate pesticides, per- and polyfluoroalkyl substances (PFAS) and mycotoxins, illustrating the integration of PBK models with (quantitative) adverse outcome pathways and human biomonitoring studies.
Speaker
Nynke I. Kramer, PhD
Toxicology Chair Group
Wageningen University, Wageningen, The Netherlands