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

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

“…Important conclusions were that the EpiOcular-EIT and the SkinEthic HCE EIT test methods were able to predict the immediate disruptive effects to the corneal epithelium (corneal opacity), and they were also able to identify chemicals that are classified based on the persistence of the effects at day 21 and or due in part to conjunctival effects (Kandarova et al 2018b;Van Rompay et al 2018). The combination of in vitro 3D corneal epithelial test methods (EpiOcular-EIT and SkinEthic HCE EIT) and ex vivo BCOP LLBO test method grouped with physicochemical analysis in a two-step, bottom-up approach was shown to be applicable for neat liquid materials and resulted in improved specificity (Alépée et al 2019). Currently, there are no internally agreed-upon performance standards available to evaluate these testing strategies but these methods offer the possibility of being able to distinguish Cat 1 and Cat 2 materials.…”

Performance Statistics of Defined Approaches for Eye Hazard Identification of Non-Surfactant Liquids to Distinguish Between the Three United Nations Globally Harmonized System Categories

“…C osmetics Europe developed two defined approaches (DAs) for classification and labeling of chemicals according to the United Nations Globally Harmonized System (UN GHS). [1][2][3] These DAs are DAL-1 for non-surfactant liquids combining physicochemical properties, reconstructed human cornea-like epithelium (RhCE) test method (OECD test guideline [TG] 492), and bovine corneal opacity and permeability (BCOP) test method (OECD TG 437); and DAL-2 for non-surfactant liquids combining short time exposure (STE) test method (OECD TG 491) and BCOP test method (OECD TG 437). [4][5][6] In both DAs, the BCOP laser lightbased opacitometer (LLBO) is used, as described within the OECD TG 437.…”

“…This approach for DAL-1 is shown in Figure 1, which combines four physicochemical properties of the liquid test substances with the results of two in vitro test methods (RhCE and BCOP LLBO). 2 Physicochemical property exclusion rules based on water solubility (<0.02 mg/mL) or a combination of octanol-water partition coefficient (LogP >1), vapor pressure (>3 mm Hg), and surface tension (ST <30 dyne/cm) are used in a first step to identify liquid chemicals with no serious eye damage or eye irritation potential. Liquids for which the exclusion rules are not met are evaluated based on an RhCE test method in Step 2.…”

“…liquids that are positive with the RhCE test methods are correctly identified based on the physicochemical property exclusion rules. 2 DAL-2, shown in Figure 3, describes the combination of STE test method and the BCOP LLBO test method in a bottom-up approach. 3 The STE test method is used to identify liquid chemicals with no serious eye damage or eye irritation potential (No Cat.…”

“…2, and No Cat., underprediction, overprediction, false negative (FN) rate, and false positive (FP) rate for DAL-1 and DAL-2 were published by Alépée and coauthors. 2,3 At the time the DAs were developed, no international agreed performance criterion was available to assess their predictive capacity. Therefore, the criteria that were set during the CONsortium for in vitro Eye Irritation testing strategy (CON4EI) project were used initially to develop DAL-1 and DAL-2.…”