ChemSkin DB 2.0: a comprehensive reference chemical database for skin corrosion and irritation

We previously developed ChemSkin DB listing 100 reference chemicals to aid the development of new approach methodologies (NAMs) for skin irritation. However, ChemSkin DB is insufficient for NAMs addressing the full spectrum of skin hazards, i.e., skin corrosion and irritation. To address this gap, ChemSkin DB was expanded with 134 reference chemicals to ChemSkin DB 2.0 as a harmonized reference database aligning skin corrosion and irritation data with UN GHS criteria. A total of 234 unique substances were consolidated and assigned to reference categories under a precautionary decision framework. ChemSkin DB 2.0 contains normalized in vivo metrics and model-specific in vitro viability values obtained with OECD TG 431 and 439 In Vitro Skin Corrosion and Irritation Tests: Reconstructed Human Epidermis (RhE) Test Methods, ensuring transparency and regulatory traceability. Especially, performance evaluation demonstrated substantial agreement across OECD TG 431 RhE models for corrosion identification. In contrast, OECD TG 439 irritation RhE models showed moderate to substantial agreement, with variability in specificity linked to the single-threshold structure of irritation classification. Chemical category stratification further revealed chemical class-dependent performance patterns across both endpoints, highlighting the influence of mechanistic diversity on model reliability. Collectively, ChemSkin DB 2.0 provides a severity-stratified, regulatory-aligned reference resource that supports transparent model development and evaluation, and improved consistency in skin hazard assessment.