LIGHT-MICROSCOPIC COMPARISON OF SURFACTANT-INDUCED EYE IRRITATION IN RABBITS AND RATS AT 3 HOURS AND RECOVERY DAY-35/

Limited information exists on the pathologic changes occurring with su rfactant-induced ocular irritation in the context of accidental human exposures and animal tests used to assess for such irritation. The pur pose of this study was to begin to characterize the pathologic changes that occur with surfactants in the context of standard animal tests a nd compare the response in rats to that in rabbits. Representative ani onic, cationic, and nonionic surfactants causing slight to severe ocul ar irritation were directly applied to the corneas of rabbits and rats at a dose of 10 mu l. Eyes and eyelids of each animal were macroscopi cally examined for signs of irritation beginning 3 hr after dosing and periodically until recovery or day 35. Eyes and eyelids from animals in each group were collected for microscopic examination after 3 hr an d at recovery or day 35. Microscopically, all of the surfactants cause d erosion, denudation, and/or necrosis of the conjunctival and corneal epithelium in rabbits and rats. Necrosis of keratocytes was observed in rabbits and rats treated with the severely irritating cationic surf actant and in rats treated with anionic surfactants that were mildly i rritating and moderately irritating. Corneal endothelial changes were observed in rabbits and rats with only the cationic surfactant. Change s in eyes of rabbits and rats that had not recovered by day 35 include d decreased prominence of goblet cells, conjunctivalization of the cor neal epithelium, neovascularization and fibrosis of the cornea, and pr esence of devitalized stroma. Overall, the changes in rabbits and rats were similar and suggest that the rat may be used as a surrogate for the rabbit in studies to understand better mechanisms of surfactant-in duced eye irritation.