Comparison of preservative-induced toxicity on monolayer and stratified Chang conjunctival cells.
Preservatives are used in ocular medications to prevent microbial contamination. The use of benzalkonium chloride (BAC), the most widely used preservative in ocular medications, has been scrutinized with a number of studies indicating its toxicity to monolayer cultures of corneal and conjunctival epithelial cells. The purpose of this study was to evaluate and compare the toxicity of BAC and other preservatives and common components of ocular formulations on monolayer and stratified air-lifted cultures of Chang conjunctival cells. Air-lifting Chang cells grown on transwell filters increased stratification as assessed by transepithelial electrical resistance and histology. Unlike monolayer cultures in which ocular medications containing BAC caused near complete loss of cell viability, stratified, air-lifted cultures were not affected by the presence of BAC in ocular medications with up to 30-min exposures. Stratification shifted the dose-response curve to the right for benzalkonium chloride, thimerosal, chlorhexidine digluconate, potassium sorbate and EDTA. These results demonstrate that stratification significantly affects cell viability of Chang conjunctival cells in response to preservatives and additives of ophthalmic preparations.
Drug Safety Research and Development, Pfizer Inc., 10646 Science Center Drive, San Diego, CA 92121, USA. gina.yanochko@pfizer.com
Gina M
GM
Yanochko
Su
S
Khoh-Reiter
Mark G
MG
Evans
Bart A
BA
Jessen
D001548:Benzalkonium Compounds / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000633:toxicity; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000633:toxicity; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D013011:Sorbic Acid / Q000633:toxicity; D013849:Thimerosal / Q000633:toxicity; D018675:Toxicity Tests
D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D013849:Thimerosal; D004492:Edetic Acid; C010882:chlorhexidine gluconate; D002710:Chlorhexidine; D013011:Sorbic Acid