A Critical Evaluation of Predicting Ocular Irritancy Potential from an in Vitro

Appl. Toxicol 12,281-290. Numerous in vitro cytotoxicity assays have been proposed as poten-tial alternatives to the Draize eye irritancy test. The results reported, based upon the rank correla-tion of ocular irritancy with cytotoxicity, have been encouraging. However, direct calibration of in vivo to in vitro data utilizing several categories of chemicals has not been reported. This study evaluated the use of m vitro cytotoxicity data for predicting the ocular irritancy potential of 24 chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics). BALB/c 3T3 cells were grown overnight, then exposed for 30 min to at least four different concentrations of each chemical (expressed as volume percentage). Linear regression analysis of the log concentration versus percentage of control growth was used to calculate the concentra-tion of toxicant that inhibited the normal growth rate by 50 % (GI50). The rank ordering of cytotoxicity based upon the GI50s was surfactants> aromatics> alcohols> ketones or acetates. The larger molecular weight representative of each series (i.e., 2-ethyl-l-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances. The GI50 values were then directly calibrated against in vivo ocular irritancy quantitated as percentage corneal swelling following exposure of rabbits to the same test chemicals. A significant linear correlatio