Benzalkonium chloride causes colposcopic changes and increased susceptibility to genital herpes infection in mice.
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.
Vincent
Kathleen L
KL
Department of Obstetrics and Gynecology, Center for Biomedical Engineering, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Bell
Brent A
BA
Johnston
Rebecca K
RK
Stegall
Rachael
R
Vargas
Gracie
G
Tan
Alai
A
Stanberry
Lawrence R
LR
Rosenthal
Susan L
SL
Milligan
Gregg N
GN
Motamedi
Massoud
M
Bourne
Nigel
N
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*
D000891:Anti-Infective Agents, Local; D001548:Benzalkonium Compounds