The In vitro SkinEthic RHE Skin Corrosion as a Reference Test Method in the Acute Testing Strategy

Skin irritation and skin corrosion refer to localized toxic effects resulting from a topical exposure of the skin to a substance. The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) define skin irritation as "the production of reversible damage» and skin corrosion as "irreversible damage” to the skin following the application of a substance. A number of validated, non-animal methods to determine skin corrosion and irritation are available. As such, the SkinEthic Reconstructed Human Epidermis (RHE) test method has been adopted within the context of OECD TG 431 (skin corrosion) and OECD TG 439 (skin irritation).

Updated approaches to the use of tiered and integrated testing strategies for predicting skin corrosion/irritation potential without the use of animals are discussed in the present study. Illustration is provided by combining both SkinEthic RHE skin corrosion and irritation test methods for evaluating the stepwise testing strategy (Top down and Bottom-Up approaches).

All 50 reference chemicals listed in either OECD TG431 or 439 were evaluated in both skin irritation and corrosion SkinEthic RHE validated methods.

Amongst the 22 known in vivo corrosive chemicals, 95% were correctly predicted as corrosives. Therefore those 21 chemicals were also defined as irritants. The substances were well classified by using the top-down approach which consists of conducting primarily skin corrosion test method.

Considering the non irritant chemicals, 100% (10/10) of the correctly classified in vitro irritants were also identified as non corrosives. Thus, when applying the bottom-up approach, the GHS classification of those substances was accurately defined by performing the skin irritation evaluation.

In conclusion, the results suggest that testing strategy is not a strict sequence and that stepwise procedure, weight of evidence and testing should be considered as acceptable approaches to structure relevant information of the substance used for hazard assessment.