THE EPIOCULAR PREDICTION MODEL: AN ACCURATE, REPRODUCIBLE IN VITRO MEANS OF ASSESSING OCULAR IRRITANCY POTENTIAL.

The EpiOcular™ tissue model (OCL-200) is an organotypic model of the human corneal epithelium (HCE) cultured from normal human keratinocytes using serum free medium. Paraffin embedded, H&E stained histological cross sections show the structure of EpiOcular closely parallels that of the HCE; large nucleated basal cells lie beneath 5-6 stratified cell layers which progressively flatten out, ending with a highly squamous, non-keratinized layer at the culture’s apical surface. During 1996 and 1997, 47 and 82 lots, respectively, of the OCL-200 model were produced and monitored using the MTT assay. The common surfactant, 0.3% Triton X-100, was used as a positive control and the Effective Time 50 values (time of exposure after which viability is reduced to 50%, or ET 50) was determined for each lot of tissue. The ET-50 average of 24.9 + 6.3 (+ 1 standard deviation) minutes for 1996 (n=47 lots) was not statistically different (p = 0.043) than the 1997 average of 22.9 + 4.7 minutes (n = 81 lots). Stability of the EpiOcular model for international shipment was probed using these standard quality control tests following packaging and storage of the tissue for 4 days; both positive and negative controls and histology of the tissue remained constant over this time period. Interlaboratory testing conducted in 3 testing labs also demonstrated the stability of the tissue following shipment. Coefficients of variation (c.v.) for three materials tested in three laboratories were all below 10%. ET-50 values for 19 water-soluble chemicals from the ECETOC database were measured using 4 separate lots of EpiOcular tissue. The resultant ET-50 values were correlated to Draize rabbit eye scores (r = 0.90) and a prediction model was constructed. Next, a set of 41 materials including final formulation shampoos, off-the-shelf cosmetic/personal care products, and surfactants, for which Draize data were available, were tested and their respective ET-50’s were determined. Based on the prediction model, the predicted Draize and the actual Draize scores were compared; a correlation coefficient, r = 0.86, was obtained. Thus, the EpiOcular tissue model appears to be a reproducible and accurate in vitro means of reducing and/or replacing in vivo, animal-based ocular irritancy testing.

Basal cells, Chemicals, Chemicals, water soluble, Corneal epithelium, Corneal epithelium models, Cosmetic Personal Care Products, Shampoo(s), Cosmetics, Draize prediction model, Draize scores, Draize tests, Endpoints, MTT, EpiOcular, Eye irritation, MTT, MTT ET-50 tissue viability assay, MTT assay, Ocular irritancy testing, Ocular irritation, Ocular irritation testing, Personal care products, Pre-validation, Prediction model, Prevalidation, Quality control tests, Reproducibility, Reproducible, Surfactants, Triton X-100, Validation, Viability