Predicting points of departure and potency categories for fragrance ingredients by integrating OECD in vitro models.

Continuous potency assessment is crucial for conducting quantitative risk assessment (QRA) of sensitizers. Quantitative regression models, based on in vitro methods, have been developed to calculate points of departure for use in skin sensitization QRA. These models calculate a point of departure as a predicted value for Local Lymph Node Assay (LLNA) EC3 or potency value (PV), integrating data from the kinetic Direct Peptide Reactivity Assay (kDPRA), KeratinoSens (KS) assay, and human Cell Line Activation Test (h-CLAT). The goal of this study was to determine how in vitro predicted EC3s and PVs compare to published reference data. In vitro data were combined in point of departure regression models to predict EC3s and PVs. These points of departure were then grouped into sensitization potency categories, such as extreme, strong, moderate, weak, very weak, or non-sensitizer, as previously described. Trends in potency distribution and high concordance between predicted EC3 and PV categories and published potency categories were observed. Furthermore, the median absolute fold-misprediction ranged between 1.8 and 2.5 for models predicting EC3 and between 1.7 and 3.4 for those predicting PVs. These regression models are a promising animal alternative for determining sensitization quantitative potency for fragrance ingredients, thereby facilitating QRA.