THE EPIOCULAR PREDICTION MODEL: A REPRODUCIBLE IN VITRO MEANS OF ASSESSING OCULAR IRRITANCY POTENTIAL.
- TR Number: 176
- Authors: Klausner1, M., Sheasgreen1, J., Breyfogle1, B., Sennott1, H., Liebsch2, M., Kubilus1, J. 1Mattek Corp., Ashland, MA 01721, USA, 2ZEBET, 12277 Berlin, Germany.
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. Haematoxylin and Eosin stained histological sections show the structure of EpiOcular to closely parallel that of the HCE. During 1998, 85 lots of OCL-200 were produced and monitored using the MTT assay. The common surfactant, Triton X-100 (0.3%), was used as a positive control and the Effective Time-50 values (time of exposure after which viability is reduced to 50% [ET50]) were determined for each lot of tissue. The 1998 ET50 average of 25.2 ± 5.6 minutes (± 1 standard deviation) was not significantly different (p > 0.75) than the 1996 average of 24.9 ± 6.3 minutes (n = 47 lots), the first year of commercial production. ET50 values were measured for 19 water-soluble chemicals from the ECETOC database and 41 cosmetic or personal care products/ingredients. Draize data for these materials were correlated to ET50 values and a prediction model was constructed: Draize = -4.74 + 101.7/ (ET50) ^ 0.5 (correlation coefficient, r = 0.90). Stability of the EpiOcular model for international shipment was probed by shipping the tissue to ZEBET in Germany. A plot of the predicted Draize in the two laboratories gave r = 0.94; plotting predicted versus actual Draize scores gave r = 0.90 and r = 0.94, for Mattek and ZEBET, respectively. Thus, the EpiOcular tissue model is reproducible and appears to be an in vitro means of accurately predicting in vivo ocular irritancy.