EpiSkin Acute Dermal Toxicity Testing Strategy - OECD TG 404 Acute Dermal Toxicity Testing Strategy Combining the Use of the EpiSkin Validated Test Methods

The ability to produce irreversible or reversible alterations to the skin at the site of contact is part of the guidance based facts used for the identification of corrosive and skin irritant chemicals. During the skin corrosion validation study of the EpiSkin test method, some in vivo corrosives were identified as non corrosives in vitro. Since under classification of chemicals may be due to non specific reduction of MTT , interference corrections were performed on 5 chemicals detected as direct MTT reducers indicating the need to adapt the EpiSkin skin corrosion test method by including specific controls. Similarly controls for coloring substance should be used.

A stepwise testing strategy (Top down and Bottom-Up) for the prediction of skin irritation and then skin corrosion was proposed using the validated EpiSkin test methods to support the ongoing revision of the OECD test guidelines TG404 and TG431. Based on the validation study, EpiSkin test method is able to distinguish Cat.1A from Cat. 1B/C corrosives (UN GHS , essential for transportation and goods regulation). The testing strategy was applied to more than 60 substances (from the ECVAM validation studies) covering in vivo in vitro main skin irritation classes.

Among 15 chemicals identified by NICEATM/ICCVAM as having a high tendency for misclassification, 12 were correctly predicted as skin corrosives while 3 others in vitro non corrosive were finally predicted as irritating. Among the unquestionable corrosive substance of the set, none was classified as “non irritating” while some over prediction was observed. According to TG test strategy suggesting the combination of in silico tools, physico-chemical parameters, in vitro corrosion and irritation, it was demonstrated that misclassification becomes minimal. These 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 used for hazard assessment.