Development of a defined approach for eye irritation or serious eye damage for neat liquids based on cosmetics Europe analysis of in vitro RhCE and BCOP test methods. (September 2019)

• Record Type: Journal Article
• Authors: Alépée, N.; Adriaens, E.; Abo, T.; Bagley, D.; Desprez, B.; Hibatallah, J.; Mewes, K.; Pfannenbecker, U.; Sala, À.; Van Rompay, A.R.; Verstraelen, S.; McNamee, P.
• Is Part Of: Toxicology in vitro. Volume 59(2019)
• Page Start: 100
• Page End: 114
• Publication Date: 2019-09
• Subjects: Serious eye damage and eye irritation -- in vitro test methods -- Physicochemical properties -- Defined approach -- IATA -- Draize eye reference database; BCOP Bovine Corneal Opacity and Permeability -- CAS RN Chemical Abstracts Service Registry Number -- Cat. 1 UN GHS classification for chemicals causing irreversible effects on the eye/serious damage to the eye -- Cat. 2 UN GHS classification for chemicals causing reversible effects on the eye/eye irritation, sub-categorised in 2A (irritant to eyes, eye effects are not fully reversible within 7 days of observation) and 2B (mild irritant to eyes, eye effects fully reversible within 7 days of observation) -- CEFIC European Chemical Industry Council -- CO Corneal Opacity -- CON4EI CONsortium for in vitro Eye Irritation testing strategy -- DA defined approach -- DRD Draize eye test Reference Database -- ECHA European Chemicals Agency -- EIT eye irritation test -- EITL eye irritation test liquids -- EU CLP EU Classification, Labelling and Packaging regulation -- EIT Eye Irritation Test -- EIVS Eye Irritation Validation Study -- EURL ECVAM European Union Reference Laboratory for Alternatives to Animal Testing -- FN(R) false negative (rate) -- FP(R) false positive (rate) -- GD guidance document -- HCE human corneal epithelium -- IATA Integrated Approach on Testing and Assessment -- LS lipid solubility -- LLBO laser light-based opacitometer -- LogP octanol-water partition coefficient -- MP melting point -- MW molecular weight -- No Cat. chemicals not classified for serious eye damage or eye irritation under GHS/EU CLP -- NPV negative predictive value -- OECD Organisation for Economic Co-operation and Development -- OFG Organic Functional Group -- PC principal component -- PCA principal component analysis -- PPV positive predictive value -- QSAR quantitative structure-activity relationships -- REACH Registration Evaluation & Restriction of Chemicals -- RhCE reconstructed human cornea-like epithelium -- ST surface tension -- STE short time exposure -- TG test guideline -- TS testing strategy -- UN GHS United Nations Globally Harmonized System of Classification and Labelling of Chemicals -- VP vapor pressure -- WS water solubility; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2019.04.011
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The focus of Cosmetics Europe's ocular toxicity programme is on development of testing strategies and defined approaches for identification of ocular effects of chemicals in the context of OECD's Guidance Document on an Integrated Approach on Testing and Assessment (IATA) for Serious Eye Damage and Eye Irritation. Cosmetics Europe created a comprehensive database of chemicals for which in vitro data are available with corresponding historical in vivo Draize eye data and physicochemical properties. This database allowed further exploration of the initially proposed strategies from the CON4EI project and to identify opportunities for refinement. One key outcome of this project is that combining in vitro test methods (RhCE and BCOP LLBO) with physicochemical properties in a two-step Bottom-Up approach applicable to neat liquids, resulted in an improvement of the specificity, without reducing the sensitivity, when compared to the combination of in vitro methods alone. The Bottom-Up approach proposed here for neat liquids correctly predicted 58.3% (EpiOcular™ EIT followed by BCOP LLBO) to 62.6% (SkinEthic™ HCE EIT followed by BCOP LLBO) of No Cat., 59.1% to 68.7% of Cat. 2, and 76.5% of Cat. 1. Incorporating specific physicochemical properties with this Bottom-Up approach increased the correct identification of No Cat. neat liquids to between 72.7% and 79.7%. Highlights: Develop defined approach (DA) for assessment of serious eye damage/eye irritation Development of exclusion rules for physicochemical properties to identify No Cat. Proposed DA's: 2 combinations of RhCE test methods with the BCOP LLOB Incorporation of physicochemical property exclusion rules with DA's improve their specificity.