Development of in vitro skin corrosion test using KeraSkin™

Skin corrosion and irritation are critical local toxicological endpoints associated with chemical exposure. OECD has approved the use of the Reconstructed Human Epidermis (RhE) model, KeraSkin™, as me-too in vitro skin irritation test of OECD Test Guideline (TG) 439. Here, we explored the applicability of KeraSkin™ as a me-too test method for in vitro skin corrosion test OECD TG 431, to expand its validated use beyond skin irritation test. Thirty reference chemicals, including Category 1A, 1B/1C, and non-corrosive substances as described in OECD TG 431 performance standards (PS), were tested. Test chemicals were applied for 3 or 60 min, and cell viability (CV) was measured using MTT assay. Classification criteria were based on viability thresholds, wherein <15% at 3 min indicates Category 1A corrosives, ≥15% at 3 min and <15% at 60 min, Category 1B/1C, and ≥50% at 3 min and ≥15% at 60 min indicates non-corrosives. The KeraSkin™ skin corrosion test demonstrated reliable predictive capacity with 100% sensitivity, 70% specificity, 90% accuracy (corrosive/non-corrosive), and 76.7% sub-category accuracy in the predictive capacity assessment using 30 chemicals, which satisfies the accuracy criteria of OECD TG 431 PS. Collectively, we demonstrated that KeraSkin™ can be a reliable in vitro model for skin corrosion test, expanding the availability of validated non-animal methods for global chemical safety assessment. Further full validation test is underway for the approval of the KeraSkin™ skin corrosion test for a me-too test method of OECD TG 431.