Comparison of Toxicological Profiles of Benzalkonium Chloride and POLYQUAD®: An Experimental Study

Abstract

Purpose: : The aim of the present study was to compare, in vivo on a rat model, two different preservatives–benzalkonium chloride (BAC) and POLYQUAD® (PQ–1)–using new experimental approaches.

Methods: : Thirty eyes of 15 male Lewis rats were used in this study. Rats were randomly divided into five groups instilled twice a day for 11 days with eye drops containing different concentrations of preservatives, 0.1% BAC, 0.5% BAC, 0.1% PQ–1, 0.5% PQ–1, and balanced salt solution as a control. The ocular surface toxicity of these two preservatives was investigated using new in vivo experimental approaches. Slit lamp examination, the fluorescein test, the red phenol test, impression cytology, and in vivo corneal confocal microscopy were used to evaluate the rat ocular surface after preservative instillation. Histology sections and immunohistochemistry were also used to confirm these results.

Results: : Compared to PQ–1, BAC consistently and dramatically altered the corneoconjunctival surface as evaluated by slit lamp examination, the fluorescein test, impression cytology, in vivo confocal microscopy, and histology. The 0.5% BAC solution also significantly decreased tear production compared to the control. Although 0.5% PQ–1 significantly decreased goblet cell density in comparison to the control eyes and some abnormalities were observed with in vivo confocal microscopy, no statistically significant differences were observed between the two groups using the tear production test, slit–lamp and fluorescein evaluation, or histology.

Conclusions: : Using an acute rat model of ocular toxicity by comparing preservatives at high concentrations, we demonstrated in vivo that high doses of PQ–1 were much less toxic than BAC. In vivo confocal microscopy and impression cytology are new promising experimental approaches for studying the rat corneoconjunctival surface, particularly in the field of ocular surface toxicity.

Keywords: ocular irritancy/toxicity testing • pathology: experimental • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)