Abstract: Physiologically-based kinetic models leverage mechanistic knowledge on human physiology and chemicals characteristic to model their absorption, distribution, metabolism and excretion. Therefore, these models enable the linking of the external exposure to internal tissue and blood concentrations in time. There are 2 manners in which physiologically-based kinetic models are being integrated in next generation risk assessment approaches. One approach is to use in vitro data, such as hepatic clearance and oral absorption, for parameterizing physiologically-based kinetic models. The second approach is to use the physiologically-based kinetic models to extrapolate from an in vitro effect concentration to the corresponding in vivo exposure. This last approach is essential for utilizing in vitro data for in vivo hazard characterization. These quantitative in vitro-in vivo extrapolation approaches can be tailored for different mode-of-action-ontologies. These approaches on how to integrate physiologically-based kinetic modelling in next generation risk assessment will be discussed in this presentation.