Our work in the field of toxicokinetics aims to improve our understanding of how substances behave when applied to the skin and potentially enter into the systemic circulation. Specifically, our research addresses a multitude of toxicokinetic parameters to estimate internal dosage in relation to external exposure. This requires data on consumer exposure and the use of in silico and physiologically based pharmacokinetic (PBPK) models to help predict the systemic concentration of the chemical in relation to dermal exposure. The generation of in vitro administration, distribution, metabolism and excretion (ADME) data to support in silico and PBPK models may also be needed at this stage. Our work will be split into several projects:
- Using a multi-organ chip, we will investigate the skin and liver-specific metabolism of chemicals after single and repeated dermal and systemic exposure.
- To assess topical exposure, we will determine how a chemical penetrates the skin and is then transformed by the skin by using measured skin bioavailability parameters and in silico tools.
- We will develop a toolbox of assays to measure in vitro ADME parameters that will help us to predict systemic exposure.
- We will develop an internal threshold of toxicological concern (TTC) using the TTC concept and the prediction of internal exposure.
- We will use a PBPK modelling specifically adapted for exposure to cosmetics, integrating ADME parameters and applying as proof of concept through case studies.
- We will use quantitative in vitro – in vivo extrapolation and in vitro kinetics to predict relevant concentrations of chemicals.