VALIDATION OF THE BOVINE CORNEAL OPACITY-PERMEABILITY ASSAY AS A PREDICTOR OF OCULAR IRRITATION POTENTIAL.
In Vitro Toxicol 1994;7(3):283-90.
The author's task was to develop an approach to assessing ocular irritation, with minimal use of animals, so that it could be applied inhouse for worker safety testing.
The centerpiece of the multifaceted approach was the bovine corneal opacity and permeability (BCOP) assay, a test that measures opacity and cell sheet integrity in a target tissue: the cornea. Initial studies indicated that the BCOP gave an overall concordance with in vivo data of 85%. Two specific findings were that although suspensions could be tested, hydroscopic compds. tended to float on the exposure medium and adequate exposures could not be obtained; and that some compounds caused irritation in animals only after a delay of 24-72 hrs, and these could not be detected in vitro.
The BCOP method proved to be easily transferable, with good reproducibility in a small interlaboratory study. Overall concordance was approximately 83% among the six participants. Some slight modifications were made to the assay based on the results of this study, and a larger interlaboratory study was begun in order to broaden further experience and to attempt to define other areas of potential difficulty. Twelve labs participated in evaluating 52 diverse chemicals, and interlaboratory variability was quite low. Concordance was approximately 80%, with the false-negative and false-positive rate dependent upon the in vivo classification system generally in use at a particular lab.
In a comparison study in which 36 pharmaceutical manufacturer intermediates from 11 companies were all tested in the BCOP and 6 other assays, the BCOP was found to be among the most accurate tests. A tiered approach, combining results from other assays with the BCOP data, did not appear to provide an enhanced predictive value. Based on this body of data, it was considered that the BCOP assay is valid for the specific purposes and for the types of chemicals included in the studies (i.e., mainly pharmaceutical intermediates and raw materials).