title: Sub-categorisation of skin corrosive chemicals by the EpiSkin™ reconstructed human epidermis skin corrosion test method according to UN GHS: revision of OECD Test Guideline 431.
abstract: The EpiSkin™ skin corrosion test method was formally validated and adopted within the context of OECD TG 431 for identifying corrosive and non-corrosive chemicals. The EU Classification, Labelling and Packaging Regulation (EU CLP) system requires the sub-categorisation of corrosive chemicals into the three UN GHS optional subcategories 1A, 1B and 1C. The present study was undertaken to investigate the usefulness of the validated EpiSkin™ test method to identify skin corrosive UN GHS Categories 1A, 1B and 1C using the original and validated prediction model and adapted controls for direct MTT reduction. In total, 85 chemicals selected by the OECD expert group on skin corrosion were tested in three independent runs. The results obtained were highly reproducible both within (>80%) and between (>78%) laboratories when compared with historical data. Moreover the results obtained showed that the EpiSkin™ test method is highly sensitive (99%) and specific (80%) in discriminating corrosive from non-corrosive chemicals and allows reliable and relevant identification of the different skin corrosive UN GHS subcategories, with high accuracies being obtained for both UN GHS Categories 1A (83%) and 1B/1C (76%) chemicals. The overall accuracy of the test method to subcategorise corrosive chemicals into three or two UN GHS subcategories ranged from 75% to 79%. Considering those results, the revised OECD Test Guideline 431 permit the use of EpiSkin™ for subcategorising corrosive chemicals into at least two classes (Category 1A and Category 1B/1C).
authors.affiliation: L'Oréal Research & Innovation, Aulnay Sous Bois, France. Electronic address: nalepee@rd.loreal.com.
authors.forename: N
authors.initials: N
authors.lastname: Alépée
authors.affiliation: L'Oréal Research & Innovation, Aulnay Sous Bois, France.
authors.forename: M H
authors.initials: MH
authors.lastname: Grandidier
authors.affiliation: L'Oréal Research & Innovation, Aulnay Sous Bois, France.
authors.forename: J
authors.initials: J
authors.lastname: Cotovio
mesh_terms: D000826:Animal Testing Alternatives; D002424:Caustics / Q000633:toxicity*; D004396:Coloring Agents; D004817:Epidermis / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D015203:Reproducibility of Results; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology; D023422:Skin Irritancy Tests / Q000379:methods* / Q000592:standards; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D002424:Caustics; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; BLR; Between-laboratory reproducibility; ECHA; ECVAM Scientific Advisory Committee; ESAC; EU; EU CLP; EU DSD; EU Dangerous Substances Directive; EpiSkin; European Chemicals Agency; European Union; European Union System of Classification of Chemicals implemented in the EU Classification, Labelling and Packaging Regulation; MTT; NSC; Non-Specific Colour; OD; OECD; OECD Test Guideline 431; Optical Density; Organisation for Economic Co-operation and Development; PM; REACH; Reconstructed human Epidermis; Registration, Evaluation, Authorisation and Restriction of Chemicals; RhE; SCVS; SD; SOP; Skin Corrosion Validation Study; Skin corrosion; Standard Deviation; Standard Operating Procedure; Sub-categorisation 1A 1B/1C; TER; TG; Test Guidelines; Transcutaneous Electrical Resistance; UN GHS; UN Regulation on the Transport of Dangerous Goods; UN TDG; United Nations Globally Harmonised System; WLR; prediction model; within-laboratory reproducibility