Abstract
Understanding the xenobiotic's journey once in the skin is imperative for the use of topically applied
cosmetics and pharmaceuticals. Beyond solely permeation, the skin is an organ capable of many
functions which can a ect the application. Reactions in the skin can transform the xenobiotics and
alter the bioavailability. The aim is to better combine the knowledge and data from the di erent
elds thereby closing the gaps in the modelling of skin's complex functionality as a transdermal
delivery pathway. The purpose of this work is to develop an in silico dermal permeation model with
the capabilities of simulating metabolism and skin sensitisation. These biological functionalities
are implemented using reactions applied to the required domains in skin. This implementation
relies on the mechanistic knowledge of the reactions. The model has been applied in several case
studies to demonstrate the capabilities of the model and provides quantitative comparison to the
experimental results. After calibration of parameters, the model has provided a predictive output
comparable to ex vivo data. The tting has provided insight into the main impacting parameters
in the model, and improved the translation of ex vivo scenario data to in silico modelling. This
model has acted as a platform for a range of experimental data formats, from a variety of di erent
research areas.