Local toxicity of benzalkonium chloride in ophthalmic solutions following repeated applications

Abstract

-We performed repeated toxicity studies of benzalkonium chloride (BAK)-containing vehicles of ophthalmic solutions in monkeys and rabbits to assess the local toxicity of BAK after repeated applications on the ocular surface. Local toxicity of BAK was evaluated by toxicity studies in which a 0.01% BAK-containing vehicle was applied twice/day for 52 weeks, 4 times/day for 39 weeks, or 6 times/day for 13 weeks, or in which a 0.005% BAK-containing vehicle was applied 6 times/day for 52 weeks or twice/day for 4 weeks in monkeys. Local toxicity of BAK was also evaluated where a 0.01% BAK-containing vehicle was applied 6 times/day for 6 weeks, or a 0.005% BAK-containing vehicle was applied twice/day for 39 weeks or 8 times/day for 4 weeks in rabbits. These doses were chosen because BAK is generally used at concentrations up to 0.01% in ophthalmic solutions. The BAK-containing vehicle did not cause ophthalmological changes suggestive of irritation, allergy, or corneal damage. We also did not observe any histopathological changes in the eyeball, eyelid, lacrimal gland, and nasal cavity, with repeated applications of BAK for up to 52 weeks, up to 8 times/day, or at concentrations up to 0.01%, in monkeys and rabbits. Our results suggest that BAK in concentrations up to 0.01% in ophthalmic solution is non-toxic to the eyeball, its accessory organs, and the nasal cavity after long repeated applications.

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

“…For in vitro cell studies, the BAC levels in culture media were much less than those in the in vivo animal experiments and as low as 0.0003% in some studies [33,34]. In studies involving animal models in which dry eye and toxicity tests were frequently conducted, the concentration of BAC that was topically applied varied case by case from 0.01% to 0.5%, with lower concentrations corresponding to longer durations of observation [35,36]. However, 0.2% BAC was frequently administered to dry eye models.…”

Tacrolimus Loaded Cationic Liposomes for Dry Eye Treatment

“…Benzalkonium chloride is detrimental to corneal epithelium cells and could decrease the tear film break up time, especially in the patients with long-period administration (Meloni et al, 2019). However, Okahara and Kawazu (2013) found that when installing eye drops with .005% and .01% benzalkonium chloride, there was no obvious change on the ocular surface after 52-week administration. In our study, the administration time of commercial FK506 eye drops is short.…”

Comparison of Haptic and Biometric Properties, Bacterial Load, and Student Perception of Fixative Solutions: Formaldehyde Versus Chilean Conservative Fixative Solution with and without Formaldehyde in Pig Kidneys

“…Since the bacterial load did not vary between the different solutions, from the microbiological point of view the solutions are interchangeable. This is because formaldehyde chCFS and formaldehyde‐free chCFS have benzalkonium chloride which acts as a sporicidal, disinfectant, and antiviral agent (Okahara and Kawazy., 2013; Leal et al, 2018).…”