Overview on current status of alternative methods and testing approaches for skin corrosion testing

Abstract

The area of skin corrosion represents one of the pioneering areas for the validation of alternative test methods, in which replacement alternatives have been validated and adopted in the regulation as early as 2000 in the European Union and in 2004 at the OECD level. Current internationally agreed approaches recommend the use of Integrated Approach for Testing and Assessment (IATA) that allow to replace or minimize to the extent possible the use of in vivo animal testing while ensuring human safety (OECD Guidance document No. 203, 2014). The IATA comprises in a sequential way (1) the use of existing information, physico-chemical properties and non-testing methods, (2) a weight-of-evidence evaluation of the existing data and (3) if needed, the conduct of prospective testing. When combined within tiered testing strategies in either a top-down or a bottom-up approach for predicting the potential skin irritation and corrosion hazard of a test chemical, the currently validated and adopted in vitro methods for skin irritation and corrosion can replace the traditional in vivo Draize rabbit test (OECD, OECD guidelines for the testing of chemicals No. 404, 2015). According to the United Nations Globally Harmonized System (UN GHS) for classification, skin corrosives are classified as category 1, and where required by a competent authority (and in case data are sufficient), in one of the three subcategories 1A, 1B and 1C (UN, Globally harmonized system of classification and labelling of chemicals (GHS), 2015). Another system used to classify corrosive substances is described in the UN model regulations for the transport of dangerous goods, in which packaging groups are assigned to skin corrosives (referred to as PG I, II and III) (UN, Volume I - Part 2. Classification, 2015). Skin corrosion effects as defined by the UN GHS classification system and by the UN transport packaging groups can be predicted by the following scientific valid in vitro test methods that have been internationally adopted: The rat skin transcutaneous electrical resistance (TER) test (OECD guidelines for the testing of chemicals No. 430, 2015), which allows discriminating skin corrosives from non-corrosives but does not allow subcategorization of corrosive effects. The reconstructed human epidermal (RhE) models (OECD guidelines for the testing of chemicals No. 431, 2016) including the commercially available EpiSkin™ Standard Model (SM), the EpiDerm™ Skin Corrosion Test (SCT), the SkinEthic™ RhE and the epiCS® test method. In addition to discriminating corrosives from non-corrosives, these test methods also allow the discrimination between subcategory 1A and a combination of subcategories 1B-and-1C but were not adopted for the discrimination between subcategories 1B and 1C due to the limited data set of well-known in vivo corrosive subcategory 1C chemicals.