Skin sensitisation prediction using read-across, an illustrative next generation risk assessment (NGRA) case study for vanillin

Abstract

Skin sensitisation is a key adverse human health effect to be addressed in the safety assessment of cosmetic ingredients. Regulatory demands and scientific progress have led to the development of a Next Generation Risk Assessment (NGRA) framework, relying on the use of New Approach Methodologies (NAM) Defined Approaches (DA) and read-across instead of generating animal data. This case study illustrates the application of read-across for the prediction of the skin sensitisation potential of vanillin at the hypothetical use concentration of 0.5% in a shower gel and face cream. A three-step process was applied to select the most suitable analogues based on their protein reactivity, structural characteristics, physicochemical properties, skin metabolism profile and availability of skin sensitisation data. The applied read-across approach predicted a weak skin sensitiser potential for vanillin corresponding with a Local Lymph Node Assay EC3 value of 10%. Based on this EC3 value a point of departure of 2500 μg/cm2 was derived, resulting in an acceptable exposure level (AEL) of 25 μg/cm2. Because the consumer exposure levels (CEL) for the face cream (13.5 μg/cm2) and shower gel (0.05 μg/cm2) scenarios were lower than the AEL, the NGRA concluded both uses as safe.