Developing a Repeated Exposure Regimen Using a Buccal Epithelium-Fibroblast Tissue Model

• TR Number: 1103
• Authors: Cao, X., Molignano, J., Farcas, M.T., Oldach, J., Gutierrez, M.M.
• Keywords: EpiOral-FT ORL-300-FT, oral tobacco products, Kentucky 1R6F reference cigarettes, CRP2.1 moist snuff smokeless tobacco, complete artificial saliva CAS, LDH, IL-6, IL-8, repeat exposure, histology, H&E
• Materials Tested: oral tobacco products, Kentucky 1R6F reference cigarettes, CRP2.1 moist snuff smokeless tobacco
• Institution: Altria Client Services LLC, 601 E. Jackson St., Richmond, VA 23219, USA, MatTek Corporation, 200 Homer Ave, Ashland, MA 01721

Background: 

Oral tobacco products (OTPs) are considered potentially reduced-risk alternatives to traditional combustible cigarettes within the tobacco harm reduction paradigm. However, their mechanistic toxicity profiles, particularly local effects on oral tissues, remain insufficiently characterized. Current mechanistic assays have largely focused on single exposure designs, which are limited in their ability to capture the potential cumulative biological effects associated with repeated use, a pattern more representative of real-world consumer use behavior. Therefore, evaluating repeated exposure is an essential step toward addressing this knowledge gap and achieving a better understanding of oral tissue responses relevant to human outcomes. In this preliminary study, we established a feasible approach for conducting up to five repeated exposures using a human buccal epithelium-fibroblast co-culture tissue model (ORL-300 FT, Mattek Corporation, MA, USA)