from the conferences organized by TANGER Ltd. provisional website
Toxicity of any substance is determined by its physico-chemical properties and tissue exposure. In the case of nanoparticles (NPs), the relevant properties include the size, aspect ratio, surface charge, chemical composition etc.; the tissue exposure represents the NPs’ concentration and exposure duration. The HISENTS project aims to develop a platform of integrated modules for nanotoxicity screening. The PBPK model is an integral part of the platform as it provides information on the tissue exposure to nanomaterials via their ADME (absorption, distribution, metabolism, and excretion) behaviour. For this reason, a simple perfusion rate-limited PBPK model requiring only one NP-specific parameter per tissue was developed. The model treats all tissues as well-stirred compartments and the rate of NP exchange is only limited by the tissue perfusion. The model was calibrated against in vivo data for nano-TiO2 and, despite its simplicity, gave a reasonable agreement between predicted and measured NPs concentrations in the tissues. The main advantage of the model is that the biodistribution of NPs is described using only thermodynamic parameters (partition coefficients) which can be estimated from equilibrium responses of the individual modules.Keywords: nanotoxicity, pharmacokinetics, modelling
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