EPIVAGINAL TISSUE MODEL FOR PRECLINICAL SCREENING OF SINGLE OR REPEAT EXPOSURE TO VAGINALLY APPLIED CHEMICALS/FORMULATIONS.

• TR Number: 656

A predictive test system for assessing the vaginal irritation potential of chemicals and formulations will have far reaching application in the testing of feminine care products. The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation/inflammation which can make women susceptible to infections such as HIV-1 and HSV-2. Hence, chemical or therapeutic agent induced vaginal irritation is a public health concern. In the current study, we investigated whether the highly differentiated EpiVaginalTM tissue of normal human vaginal/ectocervical cells could be used as a non-animal alternative for the FDA approved rabbit vaginal irritation (RVI) assay.  The tissue was exposed to 1X (24 hr) or 4X (1 hr/day for 5 days) to 12 test articles (TA).  Tissue viability (MTT assay), barrier disruption (measured by trans-epithelial electrical resistance, TEER and sodium fluorescein (FL) leakage), and inflammatory cytokine release (IL-1α, IL-1β, IL-6, and IL-8) were examined.   Two irritating TA, benzalkonium chloride (BZK) and nonoxynol 9 (N9), reduced tissue viability to100% in the 1X test. 4 other non-irritating TA and vaginal fluid simulant (pH = 4.2) had minimal effects on these parameters.  Assay reproducibility was confirmed by testing using 3 different production lots