THE EPIOCULAR PREDICTION MODEL – A REPRODUCIBLE IN VITRO MEANS OF ASSESSING OCULAR IRRITANCY POTENTIAL.

• TR Number: 167
• Authors: Klausner, M., Sennott, H.A., Breyfogle, B., Makwana, A., Kubilus, J. Mattek Corp., Ashland, MA, USA.

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. 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, Triton X-l00 (0.3%), 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 minutes (+ 1 standard deviation) for 1996 (n=47 lots) was not statistically different (p < 0.05) 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. Interlaboratory testing also confirmed the reproducibility of the tissue. Coefficients of variation (c.v.) for 3 materials tested in 3 laboratories were all below 10%. ET-50 values were measured for 19 water-soluble chemicals from the ECETOC database and 41 materials including final formulation shampoos, off-the-shelf cosmetic/personal care products, and surfactants. Draize data for these materials were correlated to ET-50 values and a prediction model was constructed: Draize = 4.735+l01.65/(ET-5O)^0.5 (correlation coefficient, r = 0.90). Thus, the EpiOcular tissue model is reproducible and appears to be an accurate in vitro means of predicting in vivo ocular irritancy.