pH and the potential irritancy of douche formulations to the vaginal mucosa of the albino rabbit and rat

Kaminsky, M.; Willigan, Donald A.

doi:10.1016/s0278-6915(82)80247-0

Cited by 21 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The exclusion of lactic acid, as well as possibly other vaginal compounds, from the experimental protocol might have led to results that were of limited relevance to the true in vivo situation. Similarly, the vaginal pH of laboratory mice, rats and rabbits is between 6.5 and 7.5 (Kaminsky & Willigan, 1982; Meysick & Garber, 1992) and devoid of Lactobacillus , substantially different from that of women. This calls into question the applicability to the human situation of studies performed on the lower genital tract in animal models.…”

Section: Discussionmentioning

confidence: 99%

Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide

Witkin

Alvi

Bongiovanni

et al. 2011

FEMS Immunol Med Microbiol

View full text Add to dashboard Cite

Lactic acid is the predominant acid present in the vagina. We evaluated the consequences of lactic acid, at physiological levels present in the vagina, on cytokine responses of peripheral blood mononuclear cells (PBMCs) obtained from 10 individuals in the presence or absence of bacterial lipopolysaccharide. Preincubation of PBMCs in 15 mM lactic acid before the addition of lipopolysaccharide resulted in a 246% mean increase in interleukin-23 (IL-23) secretion over that released in the presence of lipopolysaccharide alone (P = 0.0068). The lipopolysaccharide-induced production of tumor necrosis factor-a, IL-6, IL-10 and IL-12 was unaffected by lactic acid. IL-23 stimulation was not observed if the lactic acid was neutralized before its addition to the culture medium or if hydrochloric acid was substituted for lactic acid. In the absence of lipopolysaccharide, lactic acid did not stimulate the production of IL-23 or any of the other cytokines. The increase in IL-23 production was proportional to the lactic acid concentration over a 15-60 mM range. We conclude that at body sites characterized by lactic acid accumulation, such as in the human vagina, exposure to gram-negative bacteria results in selective IL-23 production, leading to a subsequent preferential stimulation of the Th17 T lymphocyte pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide

Witkin

Alvi

Bongiovanni

et al. 2011

FEMS Immunol Med Microbiol

View full text Add to dashboard Cite

show abstract

“…important variables affecting the data collected. In addition, due to differential sensitivity of various animal species to topically applied test agents, the toxicological endpoints seem to differ (Kaminsky and Willigan, 1982;Gray et al, 1984). The lack of a specific, sensitive, reliable, reproducible, and physiologically relevant animal model has severely hindered the efforts to conduct standardized, controlled research on spermicide/microbicide preclinical development.…”

Section: Introductionmentioning

confidence: 99%

A Study of the Potential of the Pig as a Model for the Vaginal Irritancy of Benzalkonium Chloride in Comparison to the Nonirritant Microbicide PHI-443 and the Spermicide Vanadocene Dithiocarbamate

D’Cruz

Erbeck²,

Uckun

2005

Toxicol Pathol

View full text Add to dashboard Cite

A porcine model was established to test the mucosal toxicity potential of a thiophene thiourea (PHI-443)-based anti-HIV microbicide and a vanadocene-based spermicide, vanadocene dithiocarbamate (VDDTC) in comparison to benzalkonium chloride (BZK). Nine domestic pigs (Duroc) in nonestrus stage received a single intravaginal application of 2% BZK, 2% PHI-443, or 0.1% VDDTC-containing gel. At various times after gel application, cell differentials and levels of inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-γ , and TNF-α) in cervicovaginal lavage (CVL) fluid were monitored by flow cytometry and ELISA, respectively. Eight pigs were exposed intravaginally to a gel with and without BZK or VDDTC for 4 consecutive days and vaginal tissues were scored histologically for inflammation using a new scoring system. Only CVL fluid from pigs exposed to BZK showed a significant increase of IL-1β, IL-8, and also IL-18 production when compared to the controls, PHI-443 or VDDTC-treated groups. Maximum levels of BZK-induced IL-1β (100-fold), IL-8 (2,500-fold), IL-18 (80-fold), and IFN-γ (10-fold) were found at 24 hours. In the in vivo porcine vaginal irritation model, increased levels of vaginal IL-1β, IL-8, and IL-18 were associated with histological changes consistent with vaginal inflammation. These results demonstrate that key cervicovaginal inflammatory cytokines are useful in vivo biomarkers for predicting the mucosal toxicity potential of vaginal products in the physiologically relevant and sensitive porcine model.

show abstract

“…Even if the consequences of the administration of vaginal formulations presenting undesirable pH is not readily assessable, it is well known that increased vaginal pH is associated with the presence or favoring of bacterial vaginosis, trichomoniasis or mixed infections [ 27 ]. Outcomes of low pH are even less understood, but animal data suggest that values of three or less are unacceptable for human use [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective

et al. 2014

View full text Add to dashboard Cite

Vaginal lubricants are widely used by women to help solve intercourse difficulties or as enhancers, but recent reports raise questions about their safety. Twelve commercially available gel products were tested for pH value, pH buffering capacity, osmolality and cytotoxicity relevant to vaginal delivery. Obtained data were analyzed in light of the recent Advisory Note by the World Health Organization (WHO) for personal lubricants to be concomitantly used with condoms. Results showed that most products do not comply with pH and osmolality recommended standards, thus posing a potential hazard. Four products presented values of osmolality around three-times higher than the maximum acceptable limit of 1200 mOsm/kg. In vitro cell testing further identified substantial cytotoxicity even at 1:100 dilutions for three products, contrasting with no significant effect of up to at least a 1:5 dilution of a Universal Placebo gel. However, no direct correlation between these last results and pH or osmolality was found, thus suggesting that the individual toxicity of specific formulation components plays an important role in the outcome of a particular product. Although further assessment is required, these results highlight potential safety issues related to the formulation of commercially available vaginal lubricants.

show abstract

pH and the potential irritancy of douche formulations to the vaginal mucosa of the albino rabbit and rat

Cited by 21 publications

References 1 publication

Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide

Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide

A Study of the Potential of the Pig as a Model for the Vaginal Irritancy of Benzalkonium Chloride in Comparison to the Nonirritant Microbicide PHI-443 and the Spermicide Vanadocene Dithiocarbamate

Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective

Contact Info

Product

Resources

About