Development of a defined approach for eye hazard identification of solid chemicals according to the three UN GHS categories
Main Article Content
Abstract
Currently there are two OECD-adopted defined approaches (DA) for eye hazard identification of non-surfactant liquids (OECD TG 467). The current study aimed to develop a DA for eye hazard identification of solid chemicals according to the three UN GHS categories (Cat.1, Cat. 2, No Cat.): the DAS. The DAS combines two test methods described in OECD TG 437 and TG 492. The DAS was developed based on in-depth statistical analysis of a database on solids containing in vitro and historically curated in vivo Draize eye test data. The performance of the DAS was assessed by comparing the predictions with the classification based on in vivo Draize eye test data, on the one hand, and with the performance criteria established by the OECD expert group, on the other hand. In a first tier of the DAS, the SkinEthic™ HCE EIT method (TG 492) is used to distinguish No Cat. from classified substances. For classified substances, the BCOP LLBO method (TG 437) is used to identify Cat. 1, and the remaining solids are predicted Cat. 2. In summary, 77.4% Cat. 1 (N=31), 52.3% Cat. 2 (N=18), and 70.0% of No Cat. (N=60) solids were correctly identified compared to the classification based on the Draize eye test. The percentage of correct predictions met the minimum OECD performance values of 75% Cat. 1, 50% Cat. 2, and 70% No Cat., and the percentage of mispredictions was below the established maximum values. Therefore, inclusion of the DAS in OECD TG 467 has been achieved.
Plain language summary
Defined approaches combine information from different non-animal testing methods in a specific way and interpret the results according to a fixed procedure. Such defined approaches are already available as full replacements of animal testing to assess the eye hazard of liquid chemicals (OECD Test Guideline 467). This study used two OECD-adopted in vitro methods, based on human cells and corneas from cattle, to create a defined approach that can be used for solid chemicals. The performance of the procedure was assessed against data from previous animal tests for 109 solid chemicals. The results have already led to this defined approach being adopted by the OECD TGs programme for inclusion in TG 467. With the adoption of the new defined approach, non-animal human relevant strategies are now available for eye hazard assessment of liquids and solids, reducing the need for animal testing.
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s).
Adriaens, E., Verstraelen, S., Desprez, B. et al. (2021). Overall performance of bovine corneal opacity and permeability (BCOP) laser light-based opacitometer (LLBO) test method with regard to solid and liquid chemicals testing. Toxicol In Vitro 70, 105044. doi:10.1016/j.tiv.2020.105044
Alépée, N., Leblanc, V., Adriaens, E. et al. (2016). Multi- laboratory validation of SkinEthic HCE test method for testing serious eye damage/eye irritation using liquid chemicals. Toxicol In Vitro 31, 43-53. doi:10.1016/j.tiv.2016.02.014
Alépée, N., Adriaens, E., Abo, T. et al. (2019a). 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. Toxicol In Vitro 59, 100-114. doi:10.1016/j.tiv.2019.04.011
Alépée, N., Adriaens, E., Abo, T. et. al. (2019b). Development of a defined approach for eye irritation or serious eye damage for liquids, neat and in dilution, based on cosmetics Europe analysis of in vitro STE and BCOP test methods. Toxicol In Vitro 57, 154-163. doi:10.1016/j.tiv.2019.02.019
Alépée, N., Adriaens, E., Abo, T. et al. (2023). Development of a defined approach for eye hazard identification of chemicals having surfactant properties according to the three UN GHS categories. Toxicol In Vitro 89, 105576. doi:10.1016/j.tiv.2023.105576
Barroso, J., Alépée, N., Cole at al. (2014). The EURL ECVAM – Cosmetics Europe Prospective Validation Study of Reconstructed Human Cornea-Like Epithelium (RhCE)-Based Test Methods for Identifying Chemicals Not Requiring Classification and Labelling for Serious Eye Damage/Eye Irritation – Validation. doi:10.2787/41680
Barroso, J., Pfannenbecker, U., Adriaens, E. et al. (2017). Cosmetics Europe compilation of historical serious eye damage/eye irritation in vivo data analysed by drivers of classification to support the selection of chemicals for development and evaluation of alternative methods/strategies: The Draize eye test Reference Database (DRD). Arch Toxicol 91, 521-547. doi:10.1007/s00204-016-1679-x
ICCVAM (2006). Background Review Document: Current Status of in Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants: Bovine Corneal Opacity and Permeability Test Method. (NIH Publ. No. 06-4512).
Kandarova, H., Letasiova, S., Adriaens, E. et al. (2018). CON4EI: EpiOcular™ eye irritation test (EpiOcular™ EIT) for hazard identification and labelling of eye irritating chemicals. Toxicol In Vitro 49, 21-33. doi:10.1016/j.tiv.2017.07.002
OECD (2019). Guidance Document on Integrated Approaches to testing and assessment (IATA) for serious eye damage and eye irritation. OECD Series on Testing and Assessment, No. 263. OECD Publishing, Paris. https://www.oecd.org/chemicalsafety/testing/series-testing-assessment-publications-number.htm
OECD (2021). Test No. 494: Vitrigel-Eye Irritancy Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9f20068a-en
OECD (2022a). Test No. 492B: Reconstructed Human Cornea-like Epithelium (RHCE) Test Method for Eye Hazard Identification. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/0d603916-en
OECD (2022b). Test No. 467: Defined Approaches for Serious Eye Damage and Eye Irritation. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/28fe2841-en
OECD (2022c). Supporting Document for Evaluation and Review of Test Guideline 467 on Defined Approaches (DAs) for Serious Eye Damage / Eye Irritation, OECD Environment, Health and Safety Publications. Series on Testing and Assessment, No 354. OECD Publishing, Paris. https://www.oecd.org/chemicalsafety/testing/seriesontestingandassessmenttestingforhumanhealth.htm
OECD (2023a). Test No. 405: Acute Eye Irritation/Corrosion. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264185333-en
OECD (2023b). Test No. 492: Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264242548-en
OECD (2023c). Test No. 437: Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264203846-en
OECD (2023d). Test No. 491: Short Time Exposure In Vitro Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264242432-en
OECD (2023e). Test No. 438: Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264203860-en
OECD (2023f). Test No. 460: Fluorescein Leakage Test Method for Identifying Ocular Corrosives and Severe Irritants. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/9789264185401-en
OECD (2023g). Test No. 496: In vitro Macromolecular Test Method for Identifying Chemicals Inducing Serious Eye Damage and Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. doi:10.1787/970e5cd9-en
UN (2023). United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Tenth revised edition. ST/SG/AC.10/30/Rev.10. New York and Geneva: United Nations. https://unece.org/sites/default/files/2023-07/GHS%20Rev10e.pdf
Van Rompay, A. R., Alépée, N., Nardelli, L. et al. (2018). CON4EI: SkinEthic™ human corneal epithelium eye irritation test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals. Toxicol In Vitro 49, 11-20. doi:10.1016/j.tiv.2017.06.012
Van Rompay, A. R., Adriaens, E. and Verstraelen S. (2020). Laser light-based opacitometer ‘Peira LLBO 180’: A new and validated opacitometer for use in the bovine corneal opacity and permeability (BCOP) eye irritation test method. MethodsX 7, 101085. doi:10.1016/j.mex.2020.101085
Verstraelen, S., Maglennon, G., Hollanders, K. et al. (2017). CON4EI: Bovine corneal opacity and permeability (BCOP) test for hazard identification and labelling of eye irritating chemicals. Toxicol In Vitro 44, 122-133. doi:10.1016/j.tiv.2017.06.028
Yang, H., Kim, D. E., Jang, W. H. et al. (2017). Prevalidation trial for a novel in vitro eye irritation test using the reconstructed human cornea-like epithelial model, MCTT HCE™. Toxicol In Vitro 39, 58-67. doi:10.1016/j.tiv.2016.11.010