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.

STUDY DESIGN:

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.

CONCLUSION:

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: Kathleen L Vincent, Brent A Bell, Rebecca K Johnston, Rachael Stegall, Gracie Vargas, Alai Tan, Lawrence R Stanberry, Susan L Rosenthal, Gregg N Milligan, Massoud Motamedi, Nigel Bourne
• Journal: Sexually transmitted diseases (Sex Transm Dis) Vol. 37 Issue 9 Pg. 579-84 (Sep 2010) ISSN: 1537-4521 [Electronic] United States
• PMID: 20803781 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Infective Agents, Local
• Benzalkonium Compounds

Topics

• Administration, Intravaginal
• Animals
• Anti-Infective Agents, Local (administration & dosage, adverse effects, pharmacology)
• Benzalkonium Compounds (administration & dosage, adverse effects, pharmacology)
• Colposcopy (methods)
• Dose-Response Relationship, Drug
• Female
• Herpes Genitalis (immunology, pathology, virology)
• Herpesvirus 2, Human (pathogenicity)
• Mice
• Treatment Outcome
• Vagina (drug effects, pathology, virology)