title: Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study.
abstract: OBJECTIVE
  The aim of this study was to compare, in vivo on a rat model, two different preservatives- benzalkonium chloride (BAC) and polyquaternium-1 (PQ-1)-using new experimental approaches.
  
  
  METHODS
  Thirty (30) 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 (BSS) 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 examined 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, and some abnormalities were observed with in vivo confocal microscopy, no statistically significant differences were observed between these 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 to studying the rat corneoconjunctival surface, particularly in the field of ocular surface toxicity.
authors.affiliation: Department of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, and INSERM U598, Cordeliers Biomedical Institute, University of Paris 5, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Labbé
authors.forename: Aude
authors.initials: A
authors.lastname: Pauly
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.forename: Françoise
authors.initials: F
authors.lastname: Brignole-Baudouin
authors.forename: Chantal
authors.initials: C
authors.lastname: Martin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Warnet
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D019793:Fluorescein / Q000378:metabolism; D015590:Fluorophotometry; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009883:Ophthalmic Solutions / Q000633:toxicity; D010637:Phenolsulfonphthalein / Q000378:metabolism; D011108:Polymers / Q000633:toxicity*; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013666:Tears / Q000378:metabolism
chemical_list: D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011108:Polymers; D011310:Preservatives, Pharmaceutical; C058655:polyquaternium 1; D010637:Phenolsulfonphthalein; D019793:Fluorescein