title: Benzalkonium chloride causes colposcopic changes and increased susceptibility to genital herpes infection in mice.
abstract: BACKGROUND
  Colposcopy is widely used in clinical microbicide safety testing but not in preclinical small animal studies. Endoscopic colposcopy could be employed in small animals allowing colposcopy to be used as one component in a multifactorial safety testing paradigm.
  
  
  METHODS
  We conducted dose-response studies in mice using 2%, 0.2%, or 0.02% benzalkonium chloride (BZK) as the test compound, and using multiple safety end points that included endoscopic colposcopy, susceptibility to vaginal HSV-2 infection, histology, and entry of inflammatory cells into the vagina.
  
  
  RESULTS
  Animals treated with 0.2% or higher BZK experienced vaginal toxicities detectable by all tests used including colposcopy. In contrast, 0.02% BZK produced no significant changes except by histology in which a significant thinning of the vaginal epithelium was seen.
  
  
  CONCLUSIONS
  Endoscopic colposcopy detected microbicide-elicited changes in the mouse vagina with similar sensitivity to the other endpoints used in these studies and would appear to be useful as part of a multifactorial microbicide safety testing paradigm in mice.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Biomedical Engineering, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Vincent
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bell
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Johnston
authors.forename: Rachael
authors.initials: R
authors.lastname: Stegall
authors.forename: Gracie
authors.initials: G
authors.lastname: Vargas
authors.forename: Alai
authors.initials: A
authors.lastname: Tan
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Stanberry
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenthal
authors.forename: Gregg N
authors.initials: GN
authors.lastname: Milligan
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D003127:Colposcopy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D051379:Mice; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects / Q000473:pathology* / Q000821:virology*
chemical_list: D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds