How does the HPHC profile differ between cigarettes and PMI's THS?

What other HPHCs does PMI measure in our heated tobacco product aerosols besides the WHO 9?

PMI screens for a wide number of other HPHCs in addition to those listed on the WHO 9. Various priority lists of smoke toxicants in mainstream cigarette smoke have been proposed by different health authorities for the evaluation of commercially marketed cigarettes. These lists contain categories of constituents linked to the serious health effects of smoking, including carcinogens, respiratory, developmental, reproductive and cardiovascular toxicants, and constituents linked to addiction. 

HPHCs mandated for reporting are generally consistent across regulatory authorities, however, with the exception of Health Canada, specific test methods had not been defined or validated at the time these lists were developed. To enable accurate comparisons of the HPHC levels in THS aerosol and cigarette smoke, PMI established the PMI 58 list. This list comprises constituents for which analytical protocols were well established and widely available at the time.

The PMI 58 list contains:

• All constituents required for reporting by different regulatory authorities, including the HPHCs which are subject to reporting on the U.S. Food and Drug Administration’s (FDA’s) abbreviated list of 18 HPHCs in mainstream cigarette smoke.
• The 44 constituents on the Health Canada list.
• All 39 smoke constituents identified as priority toxicants and proposed for reporting by TobReg.
• Additional HPHCs identified in mainstream cigarette smoke and deemed relevant by PMI for product evaluation. 

Since the initial development of the PMI 58 list, we have also studied the levels of constituents in THS aerosol according to the U.S. FDA’s list of 93 HPHCs. The FDA 93 was initially published in 2012 and contains 93 compounds or classes of compounds covering toxicants linked to diseases such as cancer and cardiovascular disease, among others, for which testing methods have now been defined.

What does the totality of evidence show for our leading heated tobacco product?  

Overall, our results show significant reductions in the levels of HPHCs emitted by THS aerosol compared with cigarette smoke. Looking at the different lists, the average levels of HPHCs measured in the aerosols of both THS 2.2 and THS 3.0 were reduced by 90% to 95% compared with those found in the smoke of a reference cigarette.

We have also published a study measuring levels of HPHCs on the FDA’s list of 93 HPHCs (FDA 93) for regular and menthol THS 2.2. Aside from nicotine, anabasine, and polonium-210 (which was near the limit of detection), the average reduction in the levels of HPHCs in the aerosol of THS compared with smoke from a reference cigarette was >91.6% (regular) and >92.2% (menthol). This indicates that the reduction in levels of HPHCs is not impacted by the nature of the flavor system.

In addition to these targeted studies, PMI also conducts untargeted screening to determine whether any new or unexpected chemical compounds are present in THS aerosol. The comprehensive chemical characterization of THS aerosol using untargeted analytical screening methods revealed that a total of 532 chemical constituents are present at concentrations ≥ 100 ng/heated tobacco unit. This is compared with more than 4,800 chemicals found in cigarette smoke. Only a minority of compounds in THS aerosol were present at concentrations exceeding those measured in cigarette smoke.

The compounds that were found to be significantly higher in THS aerosol than cigarette smoke were submitted for toxicological evaluation. While four compounds were subsequently highlighted to be of potential toxicological concern, the levels of these four compounds were very low, and the U.S. FDA concluded that the “…potential effects are outweighed by the substantial decrease in the number and levels of HPHCs found in [combusted cigarettes].”

Are the HPHC levels in PMI's oral products and e-vapor aerosols also lower than cigarette smoke?

PMI's findings demonstrate that our e-vapor aerosols and oral products contain fewer and lower levels of HPHCs, compared with cigarette smoke.

Results from scientific testing indicate that PMI’s e-vapor products can generate up to 99% fewer harmful chemicals (excluding nicotine) than cigarettes, although this does not equate to a 99% reduction in risk. This is an average reduction of 99% in levels of the HPHCs based on the WHO 9 list.

Separate studies have demonstrated that PMI’s oral nicotine pouches generally contain fewer and lower levels of almost all the toxicants measured, with many falling below their limits of quantification.

In one such study, researchers screened seven oral nicotine-delivery products, including nicotine replacement therapy (NRT) products and PMI’s nicotine pouches, commercialized as ZYN, for 43 HPHCs potentially present in tobacco products. Only four HPHCs tested were measurable in nicotine pouches, and the pouch products tested showed no presence of nitrosamines or polycyclic aromatic hydrocarbons. Overall, the HPHC profile in nicotine pouches was similar to that of NRT products tested.

What methods does PMI use to measure constituents?

In testing smoke constituents, PMI uses the intense machine-smoking protocol proposed by Health Canada. This mimics an intense puffing topography and has been adopted by a number of other health regulatory bodies.

Are the reductions in HPHCs released by our smoke-free products a possible indicator of a reduction in harm?

For adult smokers who would otherwise continue to smoke, the reduction in the levels of HPHCs emitted or released by our smoke-free products showcase the potential for these products to reduce the risk of harm associated with cigarette smoking. It is also important to remember that, while a reduction in HPHC levels can be an indicator of reduced toxicity, it does not alone prove harm reduction.

This is why PMI conducts a stepwise assessment program to scientifically substantiate the reduction in harm through further studies such as toxicological assessments, product use studies, clinical trials, and long-term assessments. Based on the totality of evidence gathered so far, PMI smoke-free products, while not risk free, have been demonstrated to be a better choice for adult smokers who would otherwise continue smoking cigarettes, with potential benefits for public health.