New Techniques for Toxicological Assessment Highlighted

A comprehensive overview of Philip Morris International (PMI)’s extensive development and assessment program for Reduced-Risk-Products (RRPs) has been presented and discussed at the recent American College of Toxicology (ACT) Annual Meeting in Baltimore, MD, USA.^1-3 Through a series of oral presentations, posters and Q&A sessions, a team of PMI scientists shared details of the Tobacco Heating System 2.2 (THS), a new technology that heats tobacco without burning it, thereby reducing or eliminating the formation of many of the harmful or potentially harmful compounds (HPHCs) that are produced by cigarettes.

“This is the first time we have shared and discussed such a thorough compendium of THS research at a major international toxicology conference,” said Dr Nikolai Ivanov, Manager of Research Technologies, Biomedical Research, PMI. “From product development to in vitro, in vivo and clinical studies, we have been able to demonstrate the depth and breadth of our assessment program to date and our plans for future research. We have also been able to raise awareness of the extensive sbv IMPROVER platform, which through a series of open events and challenges invites external scrutiny of our scientific methods and results.”

Amongst the highlights of the research presented was a comparison of the biological effects of long-term exposure of human bronchial epithelial cells to either THS aerosol or cigarette smoke.¹ Multiple endpoints were explored (e.g., proliferation, DNA damage, oxidative stress, tissue repair) and cells were also collected regularly for systems toxicological analysis. Cigarette smoke was found to result in an increase in DNA damage after four weeks of exposure. Similar effects were not observed with THS aerosol at comparable, or even five times higher, concentrations of nicotine.

Another study of note analyzed reductions in exposure of selected smoke constituents in individuals switching to menthol THS (mTHS), or observing smoking abstinence, in comparison to continued smoking of menthol cigarettes.² Individuals were assessed for five days in clinical confinement followed by 85 days in an ambulatory setting. The study demonstrated that switching from menthol cigarettes to mTHS resulted in reductions in exposure to HPHCs. Furthermore, the levels of these reductions were found to be close to those observed following smoking abstinence.

“Not only are we demonstrating the potential of THS aerosol to present less risk of harm in comparison to cigarette smoke across a range of studies, we have also shown how we are developing exciting new techniques and technologies for toxicological assessment,” said Dr Julia Hoeng, Director of Systems Toxicology, Biomedical Research, PMI. “These include the use of human cells grown in three-dimensional culture systems, which has the potential to reduce the need for in vivo testing, advanced systems toxicology techniques with unprecedented predictive capabilities, and next generation sequencing to shed new light on the genetic basis of commonly used toxicological assays.”

The data presented at the ACT Annual Meeting will contribute to a package of evidence that will be submitted to the U.S. Food and Drug Administration (FDA) for their appraisal of the risk-reduction potential of THS. THS is one of a portfolio of RRPs which are undergoing development and assessment at PMI. RRPs are products with the potential to reduce individual risk and population harm in comparison to cigarettes, and through technological innovation and rigorous scientific assessment, PMI is leading a full-scale effort to ensure that they ultimately replace cigarettes.⁴

References

1. van de Toorn, M. et al. Comparison of the biological effects of long-term exposure of human bronchial epithelial cells to total particulate matter from 3R4F cigarette smoke or aerosol from the candidate modified risk tobacco product (cMRTP) THS2.2. ACT 37th Annual Meeting, November 6–9, 2016, Marriott Waterfront Baltimore, Baltimore, MD, USA.

2. Ivanov, N.V. Evaluation of the Tobacco Heating System 2.2: a candidate modified risk tobacco product. ACT 37th Annual Meeting, November 6–9, 2016, Marriott Waterfront Baltimore, Baltimore, MD, USA.

3. Battey, J. et al. Genomic analysis of L5178Y tk+/- cells and their induced tk-/- mutant colonies. ACT 37th Annual Meeting, November 6–9, 2016, Marriott Waterfront Baltimore, Baltimore, MD, USA.

4. Philip Morris International, 2016. United Nations Global Compact Communication on Progress 2015. Available online at: https://www.unglobalcompact.org/participation/report/cop/create-and-submit/active/245741