16 September 2020

Mark Bentley, Manager Project Management & Knowledge Integration, is in charge of multiple complex, multidisciplinary projects requiring cross-functional organization and coordination within R&D and with external partners. Mark's presentation uncovers what we know about the chemistry of IQOS aerosol.

My name is Mark Bentley. I've been with Philip Morris for 12 years, and primarily my focus, while I've been here, is an interest in chemical screening of aerosol and cigarette smoke and looking at the differences between the two using a technique that we call untargeted screening. 

Markus and Tom will have already described to you the differences in the physical characteristics between a heated tobacco aerosol and cigarette smoke, and I'm going to describe to you that we also observe significant chemical differences between the aerosol and cigarette smoke. Now cigarette smoke is known to contain more than 6,000 chemical constituents, and within these 6,000, there are over 100 which have been classified as harmful and potentially harmful constituents, and these are toxicants that are considered to be linked with disease causation in smokers.  

From this list of more than 100 HPHC, various governments and regulatory bodies have compiled priority lists of toxicants that require measurement in cigarette smoke. The most comprehensive list is by the FDA and their list of 93 constituents. 

At Philip Morris, we have analyzed using targeted methods the concentrations of these 93 constituents in cigarette smoke versus heated tobacco aerosol depending on which priority list we consider. Whether it's the World Health Organization list of 9 priority toxicants which are mandated for reduction in cigarette smoke, or we consider the full FDA 93 list, between 90 and 95 percent reductions are observed for these constituents in heated tobacco aerosol compared to cigarette smoke.

The targeted analysis of the FDA 93 list of harmful and potentially harmful constituents was integral to our MRTP authorization. When we heat tobacco, and we don't burn it, we cannot discount the possible formation of other toxicants.  

In order to look for the presence of any other toxicants that could be present in heated tobacco aerosol compared to cigarette smoke, we apply a technique that's known as untargeted screening. Here, we are looking for everything that's present within the matrix, and we don't exclude anything at all. We apply multiple analytical methods that are complementary, and they have been designed to cover the entire chemical space associated with cigarette smoke and heated tobacco aerosol.  

We can apply the untargeted screening in two ways: we can apply it simply as a screening approach whereby we look for everything, and in this situation, we apply a reporting threshold. The alternative approach is untargeted differential screening, and here we don't apply a threshold, but we just look for differences between cigarette smoke and heated tobacco aerosol and then identify compounds which are higher in heated tobacco aerosol compared to cigarette smoke.  

We are applying untargeted screening to the evaluation of a heated tobacco aerosol, and when we apply this threshold, we cover 99.8% of what we are measuring. We have demonstrated that over 80% of the aerosol is attributable to the particulate phase. Talking about numbers, including water, nicotine, and glycerine, we have determined that there are 532 chemical constituents present in the aerosol of a heated tobacco product. Depending upon the variant of the heated tobacco stick that we use, the numbers vary slightly, and in comparison, we estimate that there are approximately ten-fold higher numbers of constituents present in cigarette smoke.  

The cigarette comparator that we have used, the 3R4F reference cigarette, is an unflavored product, so it doesn't have any flavoring added to the tobacco matrix. With heatsticks, there is a flavoring system and blend differences in the tobacco are incorporated, which will be quite different with the 3R4R reference cigarette. If we take for example the regular stick which does contain a flavor system, if we compare the concentrations in the aerosol versus the 3R4F cigarette smoke, we can see that there are 51 compounds which are higher in the heated tobacco aerosol compared to cigarette smoke, and an additional three compounds which are unique in the aerosol of the heated tobacco product.  

Now, these 3 compounds are most likely attributable to the flavor system that has been added because we know from the chemical compounds they are likely to be flavor compounds. For the compounds, a toxicological evaluation was performed, and the levels were not considered to have presented any additional hazard compared to cigarette smoke.  

So, by applying a combination of both targeted and untargeted analyses to the aerosol of a heated tobacco product and cigarette smoke, I can confidently say that we understand the composition of these aerosols. The FDA have also commented that the yields of potential carcinogens, respiratory toxicants, and reproductive, and developmental toxicants are significantly lower in heated tobacco aerosol compared to combusted cigarette smoke.   

Thank you for your time. 

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