2026 CONVENTION
In vitro assessment of chemical-induced skin sensitization responses through Nrf2-ARE pathway activation
Consumer products contain diverse chemicals such as preservatives, fragrances, antioxidants, and solvents, that may induce adverse biological responses through signaling pathways. Understanding chemical-mediated modulation of intracellular stress responses is important for pharmacological and toxicological evaluation. The KeratinoSens™ assay provides a mechanistic approach to assess skin sensitization potential by measuring activation of the antioxidant response element (ARE)-dependent pathway associated with chemical-induced cellular responses. In this study, 32 consumer product-associated chemicals were evaluated using the KeratinoSens™ assay. Cells were exposed to a concentration range of 0.98 to 2000 μM, and ARE-dependent luciferase induction (Imax), EC1.5 values, and cytotoxicity were assessed. Benzisothiazolinone showed strong ARE activation (EC1.5=2.95 μM, Imax=5.25-fold). Several fragrance-related compounds also induced Nrf2-ARE activation, including hexyl cinnamal (EC1.5=16.55 μM), geraniol (EC1.5=58.81 μM), bronopol (EC1.5=103.65 μM), and triplal (EC1.5=262.94 μM). Most chemicals showed limited or no significant ARE induction. Cytotoxicity profiles varied among compounds, highlighting the importance of integrating viability with pathway activation. These findings present the use of KeratinoSens™ as a mechanistic pharmacological and toxicological platform for characterizing chemical-induced stress responses and prioritizing compounds for safety evaluation.