Incorporating integrated testing strategy (ITSv1) defined approach into read-across (RAx) in predicting skin sensitization potency: ITSv1-based RAx

Abstract

Recently, due to regulatory and ethical demands, new approach methodologies (NAMs), defined approaches (DAs), and read-across (RAx) have been used in the risk assessment of skin sensitization. Integrated testing strategy (ITS)v1 DA, adopted in OECD Guideline No. 497, can be used for skin sensitization potency categorization. However, ITSv1 DA alone is not used for further refinement of the potency prediction based on EC3 (the estimated concentration that produces a stimulation index of 3 in murine local lymph node assay) values. Moreover, there is no explicit approach to incorporating NAM/DA data into RAx to fill the data gap of EC3 values with high confidence. This study developed a strategy incorporating ITSv1 DA into RAx to predict skin sensitization potency: ITSv1-based RAx. To examine the reliability of this novel strategy, a case study with lilial, a fragrance material, was performed. Based on ITSv1-based RAx, the skin sensitization potency of lilial was determined by extrapolating the EC3 value of 9.5% for the suitable analogue bourgeonal, which was close to the historical EC3 value of 8.6%. The result suggested that the strategy can refine the prediction of EC3 values with high confidence and be useful for the risk assessment of skin sensitization.

Keywords: Defined approach (DA); Integrated testing strategy (ITS); Next generation risk assessment (NGRA); Read-across (RAx); Skin sensitization.