title: Influence of alkyl chain length of benzalkonium chloride on acute corneal epithelial toxicity.
abstract: 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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uematsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kumagami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimoda
authors.forename: Mao
authors.initials: M
authors.lastname: Kusano
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
mesh_terms: 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
chemical_list: D001548:Benzalkonium Compounds