CON4EI: Development of serious eye damage and eye irritation testing strategies with respect to the requirements of the UN GHS/EU CLP hazard categories

摘要

The main objective of the CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project (2015-2016) was to develop tiered, non-animal testing strategies for serious eye damage and eye irritation assessment in relation to the most important drivers of classification. The serious eye damage and eye irritation potential of a set of 80 chemicals was identified based on existing in vivo Draize eye test data and testing was conducted using the following eight alternative test methods: BCOP (Bovine Corneal Opacity and Permeability) + histopathology, BCOP-LLBO (BCOP Laser Light-Based Opacitometer), ICE (Isolated Chicken Eye) + histopathology, STE (Short Term Exposure), EpiOcular (TM) EIT (EpiOcular Eye Irritation Test), EpiOcular (TM) ET-50 (EpiOcular (TM) Time-to-toxicity), SkinEthic (TM) HCE EIT (SkinEthic (TM) Human Corneal Epithelial Eye Irritation Test), and SMI (Slug Mucosal Irritation). Project management decided to not include the ICE data in this project since the execution showed relevant, and not predictable, deviations from Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 438 and Guidance Document 160. At this stage, the outcome of these deviations has not been fully assessed. In addition to these alternative test methods, the computational models Toxtree and Case Ultra were taken into account. This project assessed the relevance of these test methods, their applicability domains and limitations in terms of 'drivers of classification', and their strengths and weaknesses. In this way, methods were identified that fit into a tiered-testing strategy for serious eye damage/eye irritation assessment to distinguish United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) Category 1 (Cat 1) chemicals from non-Cat 1 chemicals and address the gap namely distinguish between Category 2 (Cat 2) and Cat 1 chemicals.