title: The usefulness of the validated SkinEthic™ RHE test method to identify skin corrosive UN GHS subcategories.
abstract: The SkinEthic™ Reconstructed Human Epidermis (RHE) test method has been adopted within the context of OECD TG 431 for distinguishing corrosive and non-corrosive chemicals. The EU CLP classification system requires subcategorising of corrosive chemicals into the three UN GHS subcategories 1A, 1B and 1C. Since the SkinEthic™ RHE method was originally validated to discriminate corrosives from non-corrosives, the present study was undertaken to investigate its usefulness to discriminate skin corrosive UN GHS subcategories. In total 84 substances were tested in three independent runs and two prediction models (PM) were assessed, representing a pre-defined validated prediction model (PM-A) and an alternative one defined post-hoc (PM-B). The results obtained with both PM were reproducible, as shown by the ⩾92.9% concordance of classification between runs for discriminating corrosives versus non-corrosives, and the ⩾85% concordance for discriminating the GHS subcategories versus non-corrosives. Moreover results confirmed a high sensitivity of the SkinEthic™ RHE method to predict corrosives (94.9%) and good specificity (⩾73.7%) independent of the PM applied. Regarding the identification of UN GHS corrosive subcategories, PM-A resulted in 86.1% correct classifications of the GHS subcategory 1A. When using the PM-B, the identification of GHS subcategory 1B-and-1C substances improved, with 63.4% correct sub-categorisation. If considering the 30 reference chemicals as recommended in the recently revised OECD TG 431 (2013), PM-A and PM-B achieved 78.9% and 83.3% accuracy respectively for the identification of GHS subcategories and non-corrosives. They correctly predicted 90% of GHS subcategory 1A and 80% of GHS non-corrosive substances independent of the PM used. In conclusion, the SkinEthic™ RHE test method is highly reproducible and sensitive for discriminating corrosive from non-corrosive substances. Furthermore it allows reliable identification of skin corrosive GHS subcategory 1B-and-1C substances using the PM-A and PM-B, and of GHS subcategories 1A using the PM-B. Due to its high sensitivity, the test method provides high safety standards for skin corrosion testing.
authors.affiliation: L'Oréal Research & Innovation, Aulnay Sous Bois, France. Electronic address: nalepee@rd.loreal.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Alépée
authors.affiliation: SkinEthic Laboratories, Gerland, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Robert
authors.affiliation: SkinEthic Laboratories, Gerland, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Tornier
authors.affiliation: L'Oréal Research & Innovation, Aulnay Sous Bois, France.
authors.forename: José
authors.initials: J
authors.lastname: Cotovio
mesh_terms: D000826:Animal Testing Alternatives; D002424:Caustics / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D006801:Humans; D015203:Reproducibility of Results; D012871:Skin Diseases / Q000139:chemically induced*; D023422:Skin Irritancy Tests / Q000379:methods
chemical_list: D002424:Caustics
keywords: (Sub)category 1A 1B 1C; 3 D Reconstructed Human Epidermis; OECD Test Guideline 431; Regulation on the Transport of Dangerous Goods; Skin corrosion; SkinEthic RHE