© 1992 Oxford University Press
research-article |
Assessment of Cytotoxicity Assays as Predictors of Ocular Irritation of Pharmaceuticals
*Merck Sharp and Dohme Research Laboratories West Point, PA;
Merck Sharp and Dohme-Chibret Laboratoires Riom, France
Received April 15, 1991; accepted November 1, 1991
We have evaluated the use of cytotoxicity assays in vitro as an alternative to predicting ocular irritation potential in animals. Three different measures of cytotoxicity—leucine incorporation into protein, MTT dye reduction, and neutral red uptake—were measured in a presumed target cell, corneal epithelial cells from rabbit, as well as in a nontarget cell, V79 (Chinese hamster lung fibroblasts). An ICSO value was determined for each endpoint in one or both target cells for a series of 27 commercially available compounds and 56 in-house materials from a variety of chemical classes (carbonitriles, imidazoles, substituted benzenes, aromatic acids, peptides, phenols, esters, etc.). Analysis of the data by Spearman p rank correlation and Pearson's correlation indicated that none of the endpoint-target cell combinations used here accurately predicts in vivo irritation potential for this group of compounds. The MTT dye reduction endpoint gave the best overall correlation, regardless of target cell, but still had a correlation coefficient below –0.5. We conclude that the measurement of cytotoxicity is of limited value as an alternative assay for the classes of materials studied here.