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02639_4 Concordance between different in vitro culture models designed to predict vaginal irritation and/or toxicity Patricia Watts* The aim of this study was to examine concordance between different in vitro culture models designed to predict vaginal irritation and/or toxicity. For that purpose 5 agents (KY Jelly, SLS, N9 and silicones 300CP and D5 were tested using ME180 vaginal epithelial cells, reconstructed epidermal and vaginal models (EPI-200 and VEC-100, from MatTek Corporation), and cervical and epidermal tissue explants. Measured parameters included percent viability in the MTT reduction assay, with ED50 determination, and extracellular release of proinflammatory and chemotactic cytokines (inc IL-1_, IL-6, IL-8, TNF-_, GM-CSF, MIP-1_, MIP-1_, MCP-1, RANTES, and Eotaxin) after topical application of compound for 2 or 24 h. Silicone products did not cause any toxicity (to any system) following overnight exposure to a 10% dose. Epithelial cells (single cell layers) were more sensitive to toxic effects of N9 and SLS (10X) than multilayered epithelium. Explant cultures (skin & cervix) showed similar results to multilayered epithelial cultures (eg 0.028% (Cx) vs 0.047% (VEC-100) for SLS. Cytotoxic reagents modified cytokine production, specifically causing a suppression of IL-6, IL-8 and MCP-1 secretion. Silicones and KY Jelly had no effect on cytokine production. These data show good correlation between different culture models and suggest that assessment of both toxicity and cytokine production may be predictive of in vivo irritation. Miss Patricia Watts |
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