Verification of a Quantitative Risk Assessment Approach for Skin Sensitization Using EC1.6 Derived From LLNA: BrdU-ELISA With Medical Devices.

Quantitative risk assessment (QRA) is a practical approach for establishing acceptable exposure levels (AELs) and estimating the risks of skin sensitizers in consumer and medical products; however, its verification using actual exposure condition remains limited. In this study, we verified the QRA approach based on EC1.6 values derived from local lymph node assay (LLNA): BrdU-ELISA by leveraging contrasting clinical reports regarding isobornyl acrylate (IBOA), a known sensitizer, in two generations of continuous glucose monitors (CGMs). This study compared the original FreeStyle Libre, associated with reported incidences of allergic contact dermatitis (ACD) caused by IBOA, and the next-generation FreeStyle Libre 2, for which no such cases have been reported. The point of departure (POD; μg/cm2) was determined from a reliable EC1.6 value, and the AEL was subsequently derived using composite safety factors. For the original FreeStyle Libre, the estimated dermal exposure level of IBOA was approximately 17-fold greater than the AEL, consistent with documented ACD incidences. Conversely, IBOA level in the FreeStyle Libre 2 was below the limit of quantification (LOQ). Even under conservative LOQ-based assumptions, the estimated dermal exposure level of IBOA was approximately 1/70 of the AEL, aligning with the clinical absence of sensitization. These results demonstrate that the QRA approach using EC1.6 values effectively discriminates between products that do and do not cause ACD, supporting the validity and reliability of the QRA approach. This study highlights the importance of combining reliable hazard data with realistic exposure assessments to manage skin sensitization risks and inform safer product development.