In Vitro Systems Toxicology Assessment of Exposure to Aerosol from a Carbon Heated Tobacco Product as Compared with Exposure to Cigarette Smoke: The Impact on Nasal and Small Airway Epithelial Culture

August 20, 2017

Anita R. Iskandar, Yannick Martinez, Carole Mathis, Patrice Leroy, Florian Martin, Alan Sewer, Laura Ortega Torres, Shoaib Majeed, Keyur Trivedi, Stefan Frentzel, Emmanuel Guedj, Celine Merg, Ashraf Elamin, Nikolai V. Ivanov, Manuel C. Peitsch, Julia Hoeng

Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland (part of Philip Morris International group of companies)

The aim of the study is the characterization of the 3R4F smoke and CHTP1.2 aerosol in the Vitrocell 24/48® exposure system including the measurements of nicotine in the diluted 3R4F smoke and THS2.2 aerosol. Cytotoxicity was assessed, concentrations of pro-inflammatory mediators were measured, mRNA microarrays and the histological analysis were done.

The poster was presented at the 10th World Congress on Alternatives and Animal Use in the Life Sciences, Seattle, Washington, USA.

Toxicological assessment of tobacco products should provide relevant indication of the health risk for humans. Advances in tissue engineering have allowed the development of in vitro organotypic cultures with an air-liquid interface, thus permitting a direct exposure to inhaled chemicals. Using human organotypic nasal and small airway epithelial cultures, this study assessed the impact of an aerosol from a carbon heated tobacco product (CHTP) 1.2—a candidate modified-risk tobacco product (MRTP)*—compared with cigarette smoke (CS) at similar nicotine levels. Various endpoints including cytotoxicity, histology, ciliary beating function, cytochrome P450 1A1/1B1 activity, and secreted pro-inflammatory mediators, were complemented by a systems biology analysis of the transcriptomes to assess the exposure impact at different post-exposure time points. The overall data demonstrate a substantially reduced biological impact of CHTP1.2 aerosol exposure compared with CS in both nasal and small airway cultures.

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