Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules

Abstract

IntroductionSkin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense) that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage.ResultsThe key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with ‘High’ reliability scoring), DEREK (accuracy = 72.73% and CCR = 71.44%) and TOPKAT (accuracy = 60.00% and CCR = 61.67%). Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%), the coverage was very low (only 10 out of 77 molecules were predicted reliably).ConclusionsOwing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing.

A Perspective and a New Integrated Computational Strategy for Skin Sensitization Assessment

“…Computational approaches for the prediction of skin sensitization potential have recently garnered much attention. ,,, Despite obvious advantages and recent successes, computational approaches have yet to receive acceptance for regulatory use. As obvious from this paper, we strongly promote the substitution of current methods by computational tools, and we will continue to improve our Bayesian model as well as advocate for its use in regulatory purposes.…”