381 © 2008, Japanese Society for Alternatives to Animal Experiments Application of a systems biology approach for skin allergy risk assessment

We have developed an in silico model of skin sensitization induction to characterise and quantify the contribution of each pathway to the overall biological process; through this analysis we have developed a rationale for the interpretation and potential integration of in vitro test data for risk assessment purposes. The mouse local lymph node assay (LLNA) is now in widespread use for the evaluation of skin sensitization potential. Recent changes in EU legislation [i.e. 7th Amendment to the EU Cosmetics Directive] have made developing non-animal approaches to provide the data for skin sensitization risk assessment a key business need. Several in vitro assays have already been developed for the prediction of skin sensitization; however these are based on measuring a few pathways within the overall biological process and our understanding of the relative contribution of these individual pathways to skin sensitization induction is limited. To address this knowledge gap and thereby guide further in vitro assay development, a "systems biology" approach has been used to construct a computer-based mathematical model of the induction of skin sensitization, in collaboration with Entelos Inc. Biological mechanisms underlying the induction phase of skin sensitization are represented by non-linear ordinary differential equations, defined using qualitative an