第492号试验：用于识别不需要对眼睛刺激或严重眼睛损伤进行分类和标签的化学物质的重建人角膜样上皮（RhCE）试验方法

OECD/OCDEYou are free to use this material subject to the terms and conditions available athttp://www.oecd.org/termsandconditions/OECD GUIDELINE FORTHETESTING OF CHEMICALSReconstructed Human Cornea-Like Epithelium (Rhce) Test Method ForIdentifying Chemicals Not Requiring Classification And Labelling For EyeIrritation Or Serious Eye DamageSerious eye damage refers to the production of tissue damage in the eye, or serious physicaldecay of vision, which is not fully reversible, occurring after exposure of the eye to a test chemical, asdefined by the United Nations Globally Harmonized System of Classification and Labelling of Chemicals(UN GHS) (1). Also according to UN GHS, eye irritation refers to the production of changes in the eye,which are fully reversible, occurring after exposure of the eye to a test chemical. Test chemicals inducingserious eye damage are classified as UN GHS Category 1, while those inducing eye irritation are classifiedas UN GHS Category 2. Test chemicals not classified for eye irritation or serious eye damage are definedas those that do not meet therequirements for classification as UN GHS Category 1 or 2 (2A or 2B) i.e.,they are referred to as UN GHS No Category.The assessment of serious eye damage/eye irritation has typically involved the use of laboratoryanimals (OECD Test Guideline (TG) 405; adopted in 1981 and revised in 1987, 2002, 2012 and 2017) (2).The choice of the most appropriate test method and the use of this Test Guideline should be seen in thecontext of the OECD Guidance Document on an Integrated Approaches on Testing and Assessment(IATA) for Serious Eye Damage and Eye irritation (3).This Test Guideline describes an in vitro procedure allowing the identification of chemicals(substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damagein accordance with UN GHS. It makes use of reconstructed human cornea-like epithelium (RhCE) whichclosely mimics the histological, morphological, biochemical and physiological properties of the humancorneal epithelium. Four other in vitro test methodshave been validated, considered scientifically valid andadopted as OECD Test Guidelines (TGs) 437 (4), 438 (5), 460 (6) and 491 (7) to address the human healthendpoint serious eye damage or no classification.Four validated test methods using commercially available RhCE models are included in this TestGuideline. Validation studies for assessing eye irritation/serious eye damage have been conducted(8)(9)(10)(11)(12)(13)(14)(15) using the EpiOcular™Eye Irritation Test (EIT), the SkinEthic™HumanCornealEpithelium (HCE) EIT, the LabCyte CORNEA-MODEL24 EIT and the MCTT HCETMEIT. Each ofthese methods makes use of commercially available RhCE tissue constructs as test system, two of themare referred to in the following text as the Validated Reference Methods–EpiOcular™EIT (VRM1) andSkinEthic™HCE EIT (VRM2), respectively. From their validation studies and their independent peerreview (10)(13)(16)(17) it was concluded that EpiOcular™EIT, SkinEthic™HCE EIT, LabCyte CORNEA-MODEL24 EIT, and the MCTT HCETMEIT are able to correctly identify chemicals (both substances andmixtures) not requiring classification and labelling for eye irritation or serious eye damage according to UN 492Adopted:14 June2019Corrected: 25 June 2024 ©OECD, (2024)INTRODUCTION 1.2.3.4. OECD/OCDE2GHS (1), and the test methods were recommended as scientifically valid for that purpose. Annexes II-VIIprovide a synopsis of the important elements of the test methods, as well as flowcharts providing guidanceThe test method(s) described in this Test Guideline cannot be used on their ownto replace the invivo Draize eye test to predict acrossthe full range of serious eye damage/eye irritation responsesfordifferent chemical classes.It is therefore recommended to make use of alternative testing strategies suchas those described in TG 467 and 492B to address the required ranges of irritation potential.Strategiccombinations of several alternative test methods within (tiered) testing strategies such as the Bottom-Up/Top-Down approach may be able to fully replace the Draize eye test (19). The Bottom-Up approach isdesigned to be used when, based on existing information, a chemical is expected not to cause sufficienteye irritation to require a classification, while the Top-Down approach is designed to be used when, basedon existing information, a chemicalis expected to cause serious eye damage. The EpiOcular™EIT,SkinEthic™HCE EIT, LabCyte CORNEA-MODEL24 EIT, and MCTT HCETMEIT are recommended toidentify chemicals that do not require classification for eye irritation or serious eye damage according toUN GHS (UN GHS No Category) (1) without further testing, within a testing strategy such as the Bottom-Up/Top-Down approach suggested by Scott et al. e.g., as an initial step in a Bottom-Up approach or asone of the last steps in a Top-Down approach. However, the EpiOcular™EIT, SkinEthic™HCE EIT,LabCyte CORNEA-MODE