Development of quantitative model of a local lymph node assay for evaluating skin sensitization potency applying machine learning CatBoost

Abstract

The estimated concentrations for a stimulation index of 3 (EC3) in murine local lymph node assay (LLNA) is an important quantitative value for determining the strength of skin sensitization to chemicals, including cosmetic ingredients. However, animal testing bans on cosmetics in Europe necessitate the development of alternative testing methods to LLNA. A machine learning-based prediction method can predict complex toxicity risks from multiple variables. Therefore, we developed an LLNA EC3 regression model using CatBoost, a new gradient boosting decision tree, based on the reliable Cosmetics Europe database which included data for 119 substances. We found that a model using in chemico/in vitro tests, physical properties, and chemical information associated with key events of skin sensitization adverse outcome pathway as variables showed the best performance with a coefficient of determination (R2) of 0.75. In addition, this model can indicate the variable importance as the interpretation of the model, and the most important variable was associated with the human cell line activation test that evaluate dendritic cell activation. The good performance and interpretability of our LLNA EC3 predictable regression model suggests that it could serve as a useful approach for quantitative assessment of skin sensitization.