Deliverable 6.3 - Integration of in silico and in vitro data in PBPK modeling for risk assessment of food- and non-food-borne chemicals using the Euromix toolbox

Physiologically‐based toxicokinetic (PTPK) models are important tools for in vitro to in vivo or interspecies extrapolations in health risk assessment of food‐borne and non‐food borne chemicals. We present here the results obtained on nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants) when increasingly complex levels of parametrization are applied a generic PBPK model implemented in the Euromix toolbox, MCRA 9. At the first stage high‐throughput parameter estimates were used. In a second stage we introduced parameter values estimated using other QSAR models and then combined the latter with parameters from in vitro methods. The results show that parameterisation plays a capital role in the output of the PBPK model, and that in many cases of chronic exposure, the PBPK model can be summarized by an external to internal dose factor, and that interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform