Posters

      Systems toxicological evaluation of a heat-not-burn tobacco product in a 90-day OECD inhalation study in comparison to cigarette smoke

      Kogel, U.; Xiang, Y.; Wong, E. T.; Boue, S.; Martin, F.; Guedj, E.; Hayes, A. W.; Peitsch, M. C.; Vanscheeuwijck, P.; Hoeng, J.

      Conference date
      Mar 17, 2016
      Conference name
      Society of Toxicology (SOT) 2016
      Link to more information
      Topic
      Summary

      A 90-day rat inhalation study was performed in accordance with OECD test guideline 413 to characterize potential adverse effects caused by subchronic exposure to the Tobacco Heating System (THS) 2.2 aerosol, a heat-not-burn tobacco product, and to compare with those induced by the smoke generated from the reference cigarette 3R4F. Sprague Dawley rats were exposed for a period of 13 weeks to filtered air, three concentrations of mainstream 3R4F smoke (8, 15, 23 μg/l nicotine), or THS2.2 aerosol (15, 23, 50 μg/l nicotine). The evaluation of all OECD recommended endpoints indicated that aerosol from the THS2.2 caused a significantly reduced systemic and respiratory tract toxicity in comparison with cigarette smoke. The response of OECD endpoints may be only detectable after substantial damage. Therefore, the OECD endpoints were augmented with omics analysis generated from respiratory nasal epithelial (RNE) and lung tissue. Transcriptome analysis resulted in more than 3900 differential expressed genes (DEGs) in the RNE of male rats after 3R4F exposure, but in none after THS2.2 exposure. Gene set enrichment analysis using the KEGG database showed very few significant enrichment in THS2.2 groups. One gene set cluster was found that showed similar high enrichment as in the 3R4F groups. Processes belonged to amino acids, lipids and xenobiotics metabolism. Approximately 800 and 1300 DEGs were detected in lung tissue of male and female rats exposed to 3R4F, respectively. 17 DEGs were found in the lung tissue from THS2.2 exposed female rats. Ingenuity pathway analysis linked those genes to cellular movement and inflammatory responses. Overall, transcriptomics analysis showed a reduced response of THS2.2 on respiratory tissues compared with mainstream cigarette smoke.

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.