Applicability of the U-SENS™ assay for assessing skin sensitization potential of agrochemical active ingredients and formulations.

Skin sensitization testing is essential for the regulatory classification of agrochemicals, including active ingredients (AIs) and formulations. Although several alternative methods have been developed, their application to agrochemicals remains limited. In particular, the performance of the U-SENS™ assay, which addresses key event three (dendritic cell activation) of the adverse outcome pathway, has not yet been evaluated for these products. This study assessed the U-SENS™ applicability to predict the sensitization potential of agrochemical formulations and their AIs. Twelve formulations and nine AIs with known in vivo data were tested following OECD TG 442E. Moreover, in silico analyses were conducted to identify protein binding alerts (PBAs) and potential (a)biotic products mechanistically support the in vitro results. The assay showed balanced accuracies of 72% for formulations and 65% for AIs, comparable to previous reports for other chemical classes. Most non-sensitizing AIs lacked PBAs and metabolites, consistent with their negative U-SENS™ results, while in vivo sensitizers exhibited PBAs in the parent compound or metabolites. These findings provide preliminary evidence that U-SENS™ may contribute to the assessment of skin sensitization potential in agrochemicals. However, further studies including a wider range of substances and additional key events are required to better define its applicability domain and improve classification reliability.