Skin Corrosion in the regulatory hazard classification and labeling context is defined as the production of irreversible damage to skin, generally evident as necrosis through the epidermis and into the dermis, following a defined chemical exposure. The In Vitro Skin Corrosion Test is an in vitro, non-animal test designed to identify those chemicals and mixtures capable of inducing skin corrosion (UN GHS Category 11), and in some cases to partially subcategorize corrosives into UN GHS Sub-Categories 1A or 1B-and-1C (ie., the current test methods do not effectively discriminate between UN GHS Sub-Categories 1B and 1C).
1 United Nations (UN) Globally Harmonized System (GHS) of Classification and Labelling of Chemicals
This test method is useful for regulatory classification and labeling of chemicals and mixtures, and depending upon the regulatory jurisdiction and framework the test results may be used as standalone or to support a weight of evidence approach. Since skin corrosion in vivo typically results from rapid chemical-induced cell damage, this test method provides a mechanistically-relevant measurement of cell viability in reconstructed human epidermis (RhE) tissues after a single topically-applied chemical treatment, relative to negative control-treated tissues.
IIVS has extensive expertise with a wide variety of reconstructed skin-based protocols. IIVS staff members participated in the original validation study management that led to the adoption of the OECD Test Guideline 431: In Vitro Skin Corrosion: Reconstructed Human Epidermis Test Method (TG 431).
NOTE: since this test method does not discriminate among any non-corrosive categories, a non-corrosive prediction by this test method should be followed up with a test for potential skin irritation, using any of the validated Skin Irritation Test (SIT) methods, including the In Vitro Skin Irritation Test using a Reconstructed Human Epidermis (RhE) Model.
A variety of other protocols are available to evaluate for potential skin irritation across a spectrum of irritation and corrosion responses to support product development, product stewardship, candidate formulation selection and other non-regulatory applications, and can provide a rank ordering of skin irritation potential. A variety of protocols allow for evaluation of mild formulations such as Time-to-Toxicity ET50 Screening protocol, Cytokine Expression Assay for Mild Products and for moderate to corrosive products and mixtures In Vitro Skin Irritation / Corrosion Screen.
If full corrosive Sub-Categorization is essential and to discriminate between UN GHS Sub-Categories 1B and 1C, the Corrositex Membrane Barrier Time Monitor may be used.
3-D reconstructed human epidermis (RhE) models such as the EpiDerm (MatTek Corp.), epiCS (CellSystems), LabCyte EPI-MODEL (Japan Tissue Engineering Co., Ltd. ), and EpiSkin and SkinEthic RHE (EpiSkin SA) are organotypic in vitro models of human epidermis which can be utilized in a variety of assays to evaluate the dermal irritation, corrosivity, cytotoxicity, phototoxicity, and/or anti inflammatory potential of test materials. Viability of the tissues is determined using the vital dye MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The reduction of MTT in test material-treated tissues is expressed as a percentage relative to negative control-treated cultures.
The EpiDerm, epiCS, LabCyte EPI-MODEL, and EpiSkin and RHE tissue models are made from human epithelial cells, which are cultured on specially designed cell culture inserts. The cells differentiate to form a fully differentiated epidermis, complete with a functional stratum corneum (see picture below). An advantage of using 3-D RhE tissues is that test materials are applied topically, at full formulation strength, without dilution, so that most forms of test materials can be applied to the cultures in the same manner as occurs in vivo.