Case study on the evaluation of skin sensitization for 23 selected fragrance ingredients using a defined approach based on OECD Guideline 497.

Abstract

Twenty-three single-ingredient substances, selected from materials labeled as allergens in cosmetic fragrances, were assessed for skin sensitization potential using a defined approach (DA) based on the OECD Guideline 497 Integrated Testing Strategy version 2 (ITSv2). According to the ITSv2, skin hypersensitivity data for these selected substances were integrated. In chemico data (from the Direct Peptide Reactivity Assay, DPRA) and in vitro data (from the human Cell Line Activation Test, h-CLAT) were obtained from existing databases, while in silico data were generated via the automated workflow of the OECD QSAR Toolbox. The DA for skin sensitization, which combines QSAR predictions with DPRA and h-CLAT test results, categorized 17 substances, including 2-benzylideneheptanal, as "Sensitizers"; 5 substances, including 4-methoxybenzyl alcohol, as "Inconclusive"; and citronellol alone was categorized as "Not Classified." The outcomes from the Local Lymph Node Assay (LLNA) for substances identified as skin sensitizers by the DA method demonstrated similar classification patterns to those from DA. These results underscore the necessity of integrating comprehensive in vitro, in chemico, and in silico data for accurate evaluation of potential skin sensitizers. This case study could aid in enhancing the safety assessments of potential skin sensitizers using DA; however, final categorization is subject to validation by regulatory authorities.