Validation of a Human In Vitro Vaginal Irritation Test

DESCRIPTION (provided by applicant): Exposure of female reproductive tract to the various chemical agents contained within spermicides, medicaments, microbicides, feminine hygiene and other vaginal care products (VCP) can cause inflammation or tissue damage and thus endanger the health of women. Perturbation of the vaginal epithelium by VCP can also increase the risk of acquiring sexually transmitted infections including HIV-1. Current vaginal irritation/toxicity tests are primarily performed using animal models which are time consuming and costly. Furthermore, results from the most commonly used rabbit vaginal toxicity model do not always correlate with human responses. To date, no validated, human in vitro vaginal irritation method exists. This research project will develop such a test method. Phase I research will prevalidate MatTek's organotypic vaginal-ectocervical (VEC) tissue model for use in identifying potential hazard of existing or newly developed VCP. In vitro assays will include tissue viability, structural damage, barrier function, and cytokine release measurements. Parallel experiments will be performed in an acute rabbit vaginal irritation assay using a well defined set of model test materials. Correlation of the in vivo and in vitro data will result in the development of a sensitive and reliable in vitro vaginal irritation test method. During Phase II, the test method will undergo formal validation in a multi-center, GLP study. A prevalidated in vitro vaginal organotypic tissue model for assessing the irritation potential of chemicals/ formulations will have far reaching application in industries involved in vaginal care products, microbicides, spermicides, and other feminine hygiene and topical pharmaceutical products. Evaluation of irritancy levels is important to minimize hazards in women exposed to topically applied products. The proposed human tissue based assay will provide a sensitive and specific time-efficient method to screen a large number of chemicals/formulations at a reduced cost.