Corneal toxicity studies in rabbits and dogs with hydroxyethyl cellulose and benzalkonium chloride.

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Durand-Cavagna G, Delort P, Duprat P, Bailly Y, Plazonnet B, Gordon LR

Corneal toxicity studies in rabbits and dogs with hydroxyethyl cellulose and benzalkonium chloride.

Fundam Appl Toxicol. 1989 Oct;13(3):500-8.

PubMed ID
2612782 [ View in PubMed
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Abstract

Hydroxyethyl cellulose (HEC) is used as a viscosity-enhancing agent in ophthalmic formulations to prolong corneal contact time and increase intraocular drug levels. Benzalkonium chloride (BAK) is the preservative most frequently used in ophthalmic formulations. Corneal epithelial changes were seen by slit lamp and light microscopic examination in rabbits but not dogs after multiple instillations of an ophthalmic vehicle containing 0.01% BAK and 0.5% HEC. Microscopically, there was sloughing of superficial epithelial cells and a slight loss of polarity of the basal cells. Formulations with 0.01% BAK and HEC, at concentrations between 0.3 and 0.8%; caused these changes but not with BAK or HEC alone. It was concluded that hydroxyethyl cellulose increased the viscosity and prolonged the contact time of BAK with cornea resulting in corneal epithelial damage in the rabbit. Physiological and anatomical features of the rabbit combined with the increased contact time were concluded to favor these changes in this species. The results confirm that the rabbit is a sensitive and unique species in studies of ocular toxicity of drugs.

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