Physiologically-based Pharmacokinetic (PBPK) Model of TiO_2 Nanoparticles' Bio-distribution in Rat Tissues

摘要

The emerging of nanotechnology has increasingly gained expansions and applications in various materials science research and development. However, the exposure to nanoparticles and engineered nanomaterials can lead to adverse biological effects because the small sizes of nanoparticles can enter the human body and deposit in the organs or translocate from the intake area to the secondary organs and can cause inflammation. One of the most used nanoparticles is TiO_2, which is commonly found in skin care and household products. It is still unclear how TiO_2 nanoparticles are remained in human bodies after exposing. In the present study, we develop a physiologically-based pharmacokinetic (PBPK) model to predict the bio-distribution of TiO_2 concentrations in rat tissues. The model is validated with an existing in-vivo study in rats. We also extend our PBPK model to predict cell death caused by TiO_2 nanoparticles in the rat liver using a dose-response model. The dose-response model accounts for the interplay between the cellular accumulation of TiO_2 due to cell's particle uptake and the dilution of TiO_2 due to cell division. Our developing framework, which can be scaled-up to understand the effects in human system, has a potential to provide the health risk data and to help regulate the human exposure to TiO_2 nanoparticles.