A COLLABORATIVE EVALUATION OF 7 ALTERNATIVES TO THE DRAIZE EYE IRRITATION TEST USING PHARMACEUTICAL INTERMEDIATES

Much of the data which have been generated on in vitro alternatives to the Draize eye irritation test have dealt with compounds within a spe cific chemical class or product category. However, in the pharmaceutic al industry, it is often necessary to evaluate materials which are not related in structure or properties. It was thus decided to evaluate a diverse series of chemicals in seven in vitro methods for estimating ocular irritation. Thirty-seven test materials were chosen to represen t a broad range of pH, solubility, and in vivo irritation potential. A ssays were chosen to include as many different types of end points as practical. The group of assays was composed of TOPKAT (assessing struc ture-activity relationships), bovine corneal opacity-permeability (BCO -P; corneal opacity/toxicity), Eytex (protein coagu lation), neutral r ed uptake (cytotoxicity), MTT in living dermal equivalent (cytotoxicit y), Microtox (cytotoxicity in bacteria), and CAMVA (inflammation/toxic ity). The results of the study indicated that, in general, the cytotox icity end points did not correlate well with the in vivo data. The BCO -P, CAMVA, and Eytex assays had the best overall concordance (88.9, 75 .8, and 75.0%, respectively) with this set of compounds. Estimation of irritation potential based on structure-activity (TOPKAT) was possibl e for only approximately 50% of the compounds; however, the assay show ed 100% sensitivity (i.e., no false negatives), but low specificity (i .e., negatives correctly identified only 54.5% of the time). These dat a suggest that for screening of chemicals of diverse structure and pro perties, the more mechanism-based assays, as opposed to general cytoto xicity assays, hold more promise and should be further evaluated. (C) 1995 society of Toxicology.