Next-generation risk assessment in cosmetic safety: Moving from the frameworks and case studies to wide Adoption

phenotyping to derive Bioactivity-Exposure Ratios (BERs) for risk characterization. Numerous case studies across diverse chemical types, including coumarin, benzophenone-4, caffeine, and benzyl salicylate, have demonstrated NGRA's utility for making protective safety decisions without animal data. These examples highlight critical considerations that need to be addressed in NGRA, including metabolite assessment, dose metric selection, and quantitative uncertainty characterization. While like-for-like replacement of all animal tests remains unachievable, NGRA provides a scientifically robust pathway for protective assessments where an absence of systemic effects is the primary goal, particularly for cosmetic ingredients. The challenge now lies in harmonizing methodologies, building regulatory confidence in these approaches, and evolving institutional structures to enable routine NGRA implementation across global regulatory regimes.