This guideline provides an in vitro skin irritation test method using a Reconstructed Human Epidermis (RhE) model to distinguish skin irritating substances from non-irritating ones. The method involves the topical application of a test substance to a three-dimensional RhE model, followed by the measurement of cell viability using the MTT assay. This guideline details the test principle, limitations, procedures, acceptance criteria, and reporting requirements. It applies to solids, liquids, semi-solids, and waxes. This version has been revised to remove the EpiSkin™ model, which has been discontinued.