In Silico Simulation of Dermal Xenobiotic Metabolism and Skin Sensitisation

Understanding the xenobiotic's journey once in the skin is imperative for the use of topically appliedcosmetics and pharmaceuticals. Beyond solely permeation, the skin is an organ capable of manyfunctions which can a ect the application. Reactions in the skin can transform the xenobiotics andalter the bioavailability. The aim is to better combine the knowledge and data from the di erentelds thereby closing the gaps in the modelling of skin's complex functionality as a transdermaldelivery pathway. The purpose of this work is to develop an in silico dermal permeation model withthe capabilities of simulating metabolism and skin sensitisation. These biological functionalitiesare implemented using reactions applied to the required domains in skin. This implementationrelies on the mechanistic knowledge of the reactions. The model has been applied in several casestudies to demonstrate the capabilities of the model and provides quantitative comparison to theexperimental results. After calibration of parameters, the model has provided a predictive outputcomparable to ex vivo data. The tting has provided insight into the main impacting parametersin the model, and improved the translation of ex vivo scenario data to in silico modelling. Thismodel has acted as a platform for a range of experimental data formats, from a variety of di erentresearch areas