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PRE-VALIDATION OF RECONSTRUCTED EPIVAGINAL TISSUE MODEL TO SCREEN IRRITATION POTENTIAL OF CHEMICALS.
Ayehunie, S., Cannon, C., LaRosa, K., Hayden, P., and Klausner, M.
MatTek Corporation, Ashland, MA, USA.
Presented at Society of Toxicology Meeting, (2009).
Summary:
This study by scientists at MatTek Corp. demonstrated how MatTek's EpiVaginal in vitro human cervico-vaginal tissue equivalent can be used to accurately measure vaginal mucosa irritation/inflammation potential and therefore should be considered as an in vitro alternative test for the rabbit vaginal irritation assay.
The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that can cause irritation/inflammation and make women susceptible to infections such as HIV-1 and HSV-2. Hence, chemical/formulation or therapeutic agent induced vaginal irritation should be a concern for toxicologists. Traditionally, testing of such materials has been performed using the rabbit vaginal irritation (RVI) assay.
In the current study, MatTek scientists investigated using the human cell derived, organotypic EpiVaginal™ tissue as a non-animal alternative.
The EpiVaginal tissue was exposed to single application of six chemicals at three concentrations and the effects on tissue viability (MTT assay), barrier disruption measured by trans-epithelial electrical resistance, (TEER) and sodium fluorescein (NaFl) leakage, and inflammatory cytokine release (IL-1á, IL-1â, IL-6, and IL-8) were examined.
When compared to untreated controls, two irritating test articles, benzalkonium chloride and nonoxynol 9, had the following effects: a) tissue viability was reduced to <40%, b) TEER was reduced to <60%, c) NaFl leakage increased by 11-24%, and d) IL-1á and IL-1â release increased by >100%.
Four other non-irritating materials had minimal effects on these parameters.
Assay reproducibility was confirmed by testing the chemicals using three different production lots and by using tissues derived from cells of three different donors; coefficients of variation were < 10% and <12%, respectively.
In conclusion, decreases in MTT and TEER and increases in NaFl permeability and IL-1á and IL-1â release appear to be useful endpoints for preclinical toxicity screening of chemicals and formulations and should be considered as an in vitro alternative test for the current rabbit vaginal irritation assay.
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EpiVaginal Data Sheet
EpiVaginal Specifications
EpiVaginal Technical References
Applications: Cytokine expression/analysis, Inflammation - vaginal, Irritation - vaginal, Personal care products, Validation - in vitro tissue models
Keywords: EpiVaginal, Estradiol receptor, Histology, IL-1a, IL-1b, IL-6, IL-8, Irritation, Sodium fluorescein (NaFl) leakage, Tissue viability, Trans-epithelial electrical resistance (TEER), VEC-100, VEC-100-FT, Vaginal irritation
Materials Tested: Benzalkonium chloride, Benzocaine, Miconazole nitrate, Nonoxynol 9, Polydimethylsiloxane, Providine iodide |
