Influence of alkyl chain length of benzalkonium chloride on acute corneal epithelial toxicity.
OBJECTIVE
To evaluate acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) homologs with different alkyl chain lengths using an in vivo electrophysiological method.


METHODS
BAC homologs with C12, C14, and C16 alkyl chain lengths were used at concentrations of 0.0025%, 0.005%, and 0.01%, respectively. Cytotoxicity of BAC homologs on the normal rabbit corneal epithelial cells was examined by using a WST-1 assay. Corneal transepithelial electrical resistance (TER) was measured in living Japanese white rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. TER changes were then evaluated after a 60-second exposure to these BAC homologs. Morphological changes in corneal epithelium after exposure to the BAC homologs were examined using scanning electron microscopy. The antimicrobial activity of BAC homologs against Escherichia coli was also assessed.


RESULTS
All BAC homologs caused cytotoxicity and corneal barrier dysfunction in a concentration-dependent manner. However, the degree of corneal toxicity differed among the BAC homologs. Based on cytotoxicity and TER measurement, C14-BAC caused the greatest corneal impairment followed in order of severity by mixed BAC/C16-BAC and C12-BAC. Scanning electron microscopy images indicated an intact corneal epithelium after exposure to 0.005% C12-BAC, whereas 0.005% C14-BAC damaged the epithelium. There were no remarkable differences noted in the antimicrobial activity among the BAC homologs.


CONCLUSIONS
Acute corneal epithelial toxicity induced by BAC homologs depends on the alkyl chain length. Thus, the use of C12-BAC instead of commercially available BAC is potentially safer for patients undergoing ophthalmological pharmacotherapy.
Uematsu
Masafumi
M
Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
Kumagami
Takeshi
T
Shimoda
Kenichiro
K
Kusano
Mao
M
Teshima
Mugen
M
Sasaki
Hitoshi
H
Kitaoka
Takashi
T
D000818:Animals; D001548:Benzalkonium Compounds / Q000737:chemistry* / Q000633:toxicity*; D017097:Electric Impedance; D055724:Electrophysiological Phenomena; D004847:Epithelial Cells / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D011817:Rabbits
D001548:Benzalkonium Compounds