Current and emerging new approach & methodologies for skin hazard assessment

The animal tests including Rabbit Draize test and Guinea Pig Maximization Test have served as the standard tests to evaluate skin hazards for decades but they face limitations due to poor concordance with human responses and ethical concerns. Recently, global regulatory shifts, such as the FDA Modernization Act 3.0, are accelerating the paradigm shift toward non-animal New Approach Methodologies (NAMs). Consequently, the establishment of novel test platforms capable of precisely mimicking the human physiological environment beyond simple 2D human cell models and standardized 3D Reconstructed Human Epidermis (RhE) has emerged as an essential challenge. This review summarizes current standard non-animal test methods to evaluate skin irritation/corrosion, sensitization, and phototoxicity, and comprehensively and systemically classified new technology trends-organoids, skin-on-a-chip and in silico-by major skin hazard endpoints. Furthermore, we analyzed the opportunities and challenges in the regulatory acceptance of these technologies, in an effort to provide an insight into the direction for future skin hazard evaluation.