OPEN SCIENCE, SEPTEMBER 2020

      The fundamental difference between cigarette smoke and heated tobacco product aerosol

      In our second ever Open Science event, we decided to focus on one of the biggest problems with cigarettes: burning. By exploring the science behind heating rather than burning tobacco, we discussed how this approach reduces harmful chemicals in the aerosol of our leading heated tobacco product (HTP), the tobacco heating system (THS), commercialized as IQOS.

      Burning is the main problem with cigarettes

      Many people believe that cigarette smoke and heated tobacco product aerosol are the same, but they are not. In fact they are very different. Both fall under the category of aerosols, but how they are formed and what they're made of set them far apart from each other. Reducing and controlling the temperature is the key to avoid burning the tobacco, and thus to avoid creating smoke. 

      It's the burning, or combustion, of tobacco that creates cigarette smoke and generates high levels of harmful chemicals. By heating instead of burning tobacco, we can avoid creating smoke and thus many of those harmful chemicals, and the levels of those chemicals that are present may be significantly reduced.

       

      PMI research on heated tobacco products aerosol

      Our scientists have studied the aerosol of our leading heated tobacco product in depth, comparing it against cigarette smoke at each step along the way. Those findings have been published in two reports already on PMI Science:

      Event details

      Cigarette smoke vs HTP aerosol

      In September 2020, we hosted our second webinar focused on our latest research initiatives. The event was conducted via our Open Science platform, providing participants with opportunities to interact directly with our scientists through live Q&A sessions.

       

      Choose one of the links below to watch the presentations by our scientists:

      Open Science Speakers
      smoke vs aerosol

      The difference between cigarette smoke and smoke-free product aerosol

      Dr. Markus Nordlund explains that there are substantial differences between cigarette smoke and the aerosols formed by smoke-free products. The smoke generated from the combustion of a cigarette contains solid particles or soot, liquid droplets, and thousands of chemicals, out of which about 100 are identified by health authorities to be harmful and potentially harmful. Whereas the aerosol formed by heating tobacco at lower temperatures is much less complex and contains no solid particles - it's not smoke. Importantly, smoke-free products are not risk free.

      Hi, my name is Markus Nordlund. I’m a physicist by training, and I have a PhD in fluid mechanics. I’ve been working for Philip Morris for more than 12 years, in the area of aerosol physics and combustion science. I’m currently leading the scientific and medical affairs activities here at Philip Morris. 

      Today, I’m going to talk to you about the difference between smoke and an aerosol. This is particularly important to distinguish when we talk about smoke-free products, when usually what comes out from the products looks very similar – a sort of a cloud shaped form.

      In order to do so, it’s very important to understand: what is an aerosol? An aerosol is a suspension of solid and/or liquid particles in a gas, usually air. What makes an aerosol visible is actually the light scattering through these particles, that makes it look like a cloud when it comes out. There are many different types of aerosols that come from various physical or thermal processes and, depending on what generates the aerosols, the composition of the aerosol becomes very different.

      Common examples of such aerosol that are formed from vaporization/condensation processes are clouds for example in the sky, or mist, fog, or steam, where you have water vapor cooling down until it forms liquid droplets. Cigarette smoke contains solid particles, or soot, and liquid droplets. And it contains thousands of chemicals, out of which 100 or so are recognized by health authorities to be harmful and potentially harmful. The smoke particles are generated from the high temperature processes happening during combustion.

      Now, it’s really the high-temperature processes that generate these chemicals. But while smoke is an aerosol, it’s very important to realize that not all aerosols are smoke. If you have an aerosol generated by low temperature processes, like vaporization, it generates a liquid-based aerosol when these vapors are cooled down to form droplets. When you either heat tobacco or a liquid, you vaporize an aerosol former, typically propylene glycol or glycerol, and these are the fundamental differences between the smoke from a cigarette containing solid particles and thousands of chemicals, compared to aerosols that are generated from smoke-free products that contain much less chemicals and liquid droplets.

      To summarize: while smoke is an aerosol, not all aerosols are smoke. Smoke contains solid particles and thousands of chemicals that are generated at high temperatures when a material combusts, whereas an aerosol that is formed at lower temperatures from vaporization/condensation is much less complex than cigarette smoke and no solid particles are generated. This is why it’s so important for smoke-free products to avoid combustion, as it’s combustion that generates smoke.  

      My colleagues will talk a little bit more about combustion and also what’s in the aerosol, and also how the aerosol affects the surroundings when the products are used. 

      Thank you for your attention.

      Combustion

      Why is the absence of combustion so important?

      Dr. Tom McGrath shares with us the reasons why the absence of combustion in smoke-free products is an important feature of their design. In this video, Dr. McGrath explains the nature of combustion reactions, and specifically those that occur in cigarettes where tobacco is burned at significantly higher temperatures. He then describes how smoke-free products are designed to prevent combustion from occurring, thereby having the potential to significantly reduce the levels of harmful and potentially harmful constituents compared with cigarette smoke for adults who switch. 

      Hello everybody, my name is Tom McGrath. I’m a scientist by training, I have a PhD in Chemistry. I’ve studied the design, development, and research into smoke-free alternatives for the last 10 years. Today, I’m going to talk about combustion, and why it’s very important that we eliminate it. As Markus has explained: combustion reactions, due to the high temperatures involved, lead to the generation of smoke and ash, and to the emission of harmful and potentially harmful constituents. A combustion process and its characteristics are very well known in the fields of combustion science and fire safety. It can be defined as the oxidative reaction of a fuel that is fast enough to release heat and light usually in the form of a glow or a flame.

      Everyday combustion reactions, such as burning fossil fuels, wood, candles, and the tobacco in a cigarette are seldom complete combustion processes, and incomplete combustion products are actually formed.  

      Most of us are very familiar with examples of flaming combustion, but in a cigarette when the tobacco is set on fire, we have a smoldering combustion process or a flameless combustion process. If we look at a cigarette and the tobacco being the fuel, the combustion reaction can be set up when the tobacco is heated at temperatures above 400 °C for an oxidative reaction to occur. So, the oxidant in this case would be the oxygen in air, and the source of the heat that raises the temperature of the tobacco would be a match or an actual lighter. Once this combustion reaction sets in, the temperature at the tip of the cigarette is greater than 600 °C, and when air is drawn through the tip of a cigarette, the temperature rises above 850 °C. To put this in perspective, this is about 4 times hotter than a frying pan.

      In designing a portfolio of smoke-free alternatives, it is very important that we eliminate combustion, and that we control the temperature to which a solid matrix such as tobacco, or a liquid matrix such as an e-liquid, are actually heated.  With our heat control technology, we are able to raise the temperature of tobacco sufficiently to release nicotine and flavors, but also low enough that we avoid combustion.  

      So, what evidence do we have to support the absence of combustion in our smoke-free products? 

      • When air is drawn into the tobacco heating system, instead of it increasing as would be the case in a combustion process, the temperature of the tobacco decreases. 
      • If you were to take away the source of energy in the system, in this case turn the heater off, you see a rapid decrease in the temperature of the system.  
      • As there are no combustion reactions, the tobacco in the tobacco stick is not consumed to ash and to generate smoke, but actually remains intact.
      • Analysis of the aerosol that’s generated from the tobacco heating system shows that it is absent of combustion-derived solid particles. 
      • When you don’t have air or you do not have an oxidant, you cannot have combustion. Operating the tobacco heating system in an atmosphere of nitrogen, i.e., the absence of oxygen, yields very similar results as when the experiments are run in air, showing that the tobacco heating system is independent, in fact, of the atmosphere around it.

      So why is this important? Scientific studies have shown that as the temperature of the tobacco increases, the levels of harmful and potentially harmful constituents also increase. So, by eliminating combustion and reducing the temperature at with the tobacco is heated to, we will significantly reduce the overall levels of harmful and potentially harmful constituents. In the tobacco heating system aerosol, the levels of these harmful and potentially harmful constituents are on average reduced by 90-95% compared to cigarette smoke.  

      So, to sum up: elimination of combustion is a fundamental foundation in the heat-not-burn principle. By heating tobacco to temperatures below combustion, we are able to reduce significantly the levels of harmful and potentially harmful constituents.  

      I just want to take the opportunity to thank everybody for their time.

      Aerosol chemistry

      What do we know about the chemicals in the aerosol of heated tobacco products?

      Mark Bentley presents the approach taken by PMI to characterize the aerosol produced by THS. By using targeted methods aimed at measuring the concentrations of harmful chemicals in the product aerosol, we observe an average reduction between 90 and 95 % for these selected constituents in the aerosol of our leading heated tobacco product compared with cigarette smoke. Mr. Bentley also explains the difference between targeted and untargeted screening, and how the latter is used to detect the presence of any other potential toxicants, including any compounds that may be unique to the THS and what further studies are done in these cases.

      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 HPHCs, 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 from the 3R4F 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.

      Independent research

      What do independent studies say about our leading heated tobacco product?

      In this video, Dr. Maurice Smith reviews some independent studies focusing on the emissions from our leading HTP. Conducted in various countries, these studies aimed to identify harmful and potentially harmful constituents, as well as particulate matter and well-known toxicants like benzene, butadiene, and carbonyl compounds. Our HTP is shown to be associated with significantly lower emissions of all the compounds targeted. Dr. Smith also reviews the types of data that were considered by the United States Food and Drug Administration in their authorization of our claims for reduced exposure, confirming that our HTP is fundamentally different from cigarettes. 

      Hello, I’m Maurice Smith. I’m a toxicologist by background and experience. I currently work in the Scientific and Medical Affairs team, where we provide scientific support for communications about the benefits of transitioning away from conventional cigarette products. We always publish studies in peer-reviewed journals’ to ‘We always publish our studies in peer-reviewed journals, and I think that’s essential to be transparent and to get the general acceptance of our science, both the quality and the breadth of the science. But of course, we have received criticism that most of the studies have been performed by Philip Morris or have been funded by Philip Morris. That is no longer the case because, as we’ve rolled out our products in a number of markets, that encourages other scientists, independent scientists, to study our products as well.  

      So, what I want to do then is look at a few examples of these, to see how they support the reduced impact of our reduced-risk products. We have to look at the studies very carefully to see whether they corroborate our own findings or challenge our own findings, and this obviously contributes to the general scientific understanding of our product range.

      So first, we see a paper by a Chinese group that have taken IQOS and compared that with a conventional reference cigarette, and really what they show is that you do see substantial reductions in the emissions of harmful and potentially harmful smoke constituents. What they also did was to perform some simulated pyrolysis experiments, where they took the tobacco from IQOS, but also took tobacco from conventional cigarettes and heated it under the same conditions. In that circumstance, they found similar emissions from either IQOS tobacco or a combustible cigarette tobacco, and this confirms that it really is the combustion that causes the emission of harmful constituents. It has nothing to do with any special ingredients or special formulation of IQOS tobacco. 

      Let’s have a look at another paper, from the German Federal Institute for Risk Assessment (BFR), where they also looked at IQOS emissions. So, they performed analytical experiments, and compared against a market basket of conventional cigarettes from existing publications. Again, what they were able to show was that certainly the yields of carbonyl compounds—formaldehyde, acetaldehyde etc.—were reduced by 80 to 96%, compared to conventional cigarette brands, and for other well-known toxicants in cigarette smoke: benzene, butadiene, etc, were also reduced by 97 to 99%, much lower than you find in conventional cigarettes.

      Now when you take those reduced emission data, it’s interesting to understand whether that is likely to result in reduced risk for smokers who make the switch to reduced-risk products such as the IQOS. So, at the Dutch National Institute for Public Health and the Environment, the RIVM, a group there developed some innovative but still conservative approaches to risk assessment to compare two products. In this case, they used IQOS and conventional cigarettes as an example. The authors concluded that overall, if you consume IQOS instead of cigarettes, that would be associated with a substantial increase in life expectancy compared to continued smoking for the subgroup of smokers who would die from cancer. However, the authors also suggest the health impact will be greatest for habitual smokers who switch at a young age. There is an important point the authors also made that of course switching to IQOS can lead to risk reduction, but these products such as IQOS are not risk free. And there is a negative health impact expected to remain from consuming heated tobacco products as compared to total abstinence, so quitting is still clearly the best option.

      A very recent study from Italy looking at the impact of IQOS and another heated tobacco product, Glo, and compared to an e-cigarette, Juul, where they, in a controlled environment with enforced smoking sessions—standardized smoking sessions—tested the amount of particulate material that was detectable in the room environment. Overall, they were able to show that the heated tobacco products and e-cigarettes yielded significantly lower levels of particulate material. There were significant differences among the non-combusting products. The IQOS was associated with a significantly lower burden of emissions for monitored fractions of particulate material, including total particulate material. 

      So, the non-combusted products have significantly less intense and less persistent effects on indoor pollution in comparison with conventional cigarettes, with a quantitative estimate suggesting a lower effect with IQOS. This is an important topic, and I think it shows that because these are liquid droplets being generated by IQOS as well as the e-cigarettes, that these do not persist in the same way as the solid particulate materials that are generated by cigarette smoke. 

      If we then look at how all of these types of data were considered by the United States Food and Drug Administration in their recent authorization of our claims for reduced exposure, they confirm that our claim based on the available evidence to-date that: 

      •  The IQOS system heats tobacco but does not burn it.  
      •  This significantly reduces the production of harmful and potentially harmful chemicals 
      • Switching completely from conventional cigarettes to the IQOS system significantly reduces your body’s exposure to harmful and potentially harmful chemicals. 

      They didn’t authorize reduced-risk claims at this time but did recognize that measurable and substantial reductions in morbidity and mortality among individual tobacco users is reasonably likely to be seen in subsequent studies. This authorization confirmed that IQOS is fundamentally different from cigarettes and offers a much better alternative to continued smoking. 

      And with that, I’d just like to say thank you. Thank you very much.

      Indoor air quality

      What is the impact of IQOS aerosol on indoor air?

      In this video, Dr. Catherine Goujon-Ginglinger shines a light on indoor air quality and the studies conducted for our leading HTP. She first explains the parameters involved in assessing indoor air quality before moving into PMI’s research to quantify not only on the level of pollutants attributed to the use of the smoke-free product, but also to determine the composition of the resulting environmental aerosol. She futher reminds us of the importance of having a representative set of pollutants to be measured such as markers of combustion, carbonyls, or volatile organic compounds, which are known as major pollutants in air. Finally, we look at the results of a study on pollutants in indoor air: the levels of pollutants released when cigarettes were smoked was much higher than when our leading HTP was used instead.

      My name is Catherine Goujon. I am a scientist by background, organic chemist by background, and I’m working in Philip Morris for 20 years. My current position is Manager, Chemistry Research in Product Research.  

      Let me first explain the key features when we are talking about indoor air quality. Indoor air quality is not influenced only by the level of pollutant in air, but also by any parameter influencing the comfort of occupants, such as temperature or humidity. In fact, reasons for bad indoor air quality are mainly due to outdoor or indoor pollution, and inappropriate ventilation. So, an acceptable indoor air quality is considered where pollutants are not reaching critical level of exposure, and where people do not express dissatisfaction.  

      Looking at the composition of aerosol generated during use of heated products, we can reasonably expect significant drop of pollutant indoor compared to combustion products, such as cigarettes. That’s why we have initiated research on indoor air quality.

      Environmental tobacco smoke, or ETS, is composed of mainstream smoke exhaled by the user and side stream smoke, which is the smoke generated from the lit head of the cigarette. This is contributing to 70-80% of the whole smoke. ETS is a primary source of pollution of cigarettes. On the contrary, emission from aerosol exhaled by the adult consumer will be the source of pollution for the smoke-free products.  

      The aim of our research in indoor air quality is to quantify the differences, not only on the level of pollutants attributed to the use of the smoke-free product, but also to determine the composition of the resulting environmental aerosol. The level of pollutants is compared to guidelines whenever existing, and equally importantly, the knowledge generated is bringing key information to consumers when they decide to use tobacco products at home, for example, and want to understand the differences between cigarettes and smoke-free products indoors.

      Just to be crystal clear, the research provides context and an understanding in places or environments where tobacco use may be allowed. 

      From literature, we know that measuring one pollutant is not enough to get a good idea of indoor air quality. That’s why it’s important to have a representative set of pollutants to measure such as markers of combustion, carbonyls, or volatile organic compounds, which are known as major pollutants in air. We confirmed this statement conducting an assessment under the same conditions on tea lights, incense, or cigarettes. We were able to detect markers of combustion, but also most of the known pollutants when incense or cigarettes were used.  

      On the other hand, when we look at the results for twelve sticks of IQOS, we see a very different picture. In fact, only two pollutants are above background: nicotine and acetaldehyde. And both of them are far below the level of cigarettes, and far below the threshold for existing indoor air quality guidelines. 

      By conducting such fundamental research, it helps pondering the impact of smoke-free products indoors. 

      Thank you for your time.

      Q&A from Open Science, September 2020

      Here are a few of the most asked questions from our September Open Science event, along with our answers to those questions from the sessions.

      We look at the different studies being published, and assess the study design, the methods, the test products, and the scientific approach. Because it's all important to understanding the results.

      The easiest way to look at this question about the toxicity of the Tobacco Heating System (THS) aerosol is to look at the FDA conclusions based on our scientific dossier. The FDA received all of our toxicological studies. These studies looked at the complete aerosol that is generated by THS. This aerosol includes the propylene glycol and the glycerin. In the end, the FDA concluded that overall, there was a lower toxic potential for THS despite the fact that there may be increases in some of the chemicals.

      These two specific compounds, which are used to form the aerosol in e-cigarettes and THS, have been very well studied. It is important that these are of the appropriate chemical grade, and that any heating that takes place of these compounds is controlled. So, an e-cigarettes using a high-power setting, could heat the e-liquid at quite high temperatures, which could generate compounds like glycidol, which is a known toxin. But the levels of these compounds are extremely low in devices that are operating properly. So, it's unlikely that this is a major issue for THS and we would direct people to have a look at the recent review by UK Committee on Toxicity, where they reviewed e-cigarettes.

      The fact is that both THS and e-cigarettes emit aerosols that are both generated in the absence of combustion. These aerosols are not smoke, as there is no combustion. Aerosol droplets are instead formed from the vapors of the aerosol former, which is glycerol, that is evaporated from the tobacco during the heating. When the vapor of this aerosol former later cools down, it condenses to form liquid droplets.

      The very same process of vaporization and condensation happens in e-vapor products. There are aerosol formers in the e-liquid: propylene glycol and glycerol. Both are vaporized when the liquid is heated by the heating element. In the same way as for heated tobacco products, these vapors form an aerosol when they cool down and condense into liquid droplets. Both of the aerosols are liquid-based aerosol, containing fewer and lower levels of harmful and potentially harmful constituents compared to the smoke from combusted products, which contain thousands of chemicals and solid particles because it is the combustion that generates these solid particles.

      I would like to emphasize the similarities between those two products. As there is no combustion in either product, they do not generate sidestream smoke. When these products are being used there are only a few components that are present in air above the levels of background, and it can be attributed to the exhaled aerosol of these products.

      More importantly, because there is no combustion, those products will not generate smoke, and therefore do not produce second-hand smoke. In the air, we can measure a small level of glycerin and/or propylene glycol and nicotine, and for THS, we also saw a small level of acetaldehyde.

      Although e-cigarettes are a category of products, we have conducted studies with different types of e-cigarettes, rechargeable, tank-refillable products, etc., so we have a broad view of how they affect indoor air quality.

      See more from our Open Science events

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      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.