Combustion, Emissions and Toxicological Studies

17 September 2024

CHAPTER 4 . OUR SMOKELESS SCIENCE

Combustion, Emissions and Toxicological Studies
How the products work

Cigarette smoke is an extremely complex and hazardous aerosol. It contains more than 7,500 individual chemicals, of which 150 are known to be harmful and more than 60 are known carcinogens.^[1,2,3]

"Combustion equals complexity. Our Smokeless Products are shown not to combust. Without combustion our Smokeless Products have fewer chemicals present in their aerosols/extractions. The chemicals that are present are often greatly reduced compared to those found in cigarette smoke."

Dr Sandra Costigan

Head of Analytical and Preclinical Research, Global Life Sciences

Sign up for more exclusive the Omni™ content

Access full Omni™

Smoke is formed when a cigarette is lit and its tobacco and paper combusts (burns). This process happens at temperatures of up to 950°C and combustion will continue if there is enough tobacco (fuel) and oxygen available. If there is insufficient fuel, oxygen or heat, combustion will not occur.^[4]

Our Smokeless Products do not combust

For our Oral Tobacco Products and Oral Nicotine Pouches, the absence of combustion is self-evident with how they are consumed in the absence of heat. Our Vapour Products and Heated Products utilise controlled heating as part of their operation. Vapour Products have a metal coil/trace that heats the e-liquid to no more than 200°C to deliver an aerosol. Heated Products heat plant-based (tobacco leaf or non-tobacco leaf) material to no more than 300°C. These temperatures are low enough to avoid both ignition and burning and neither Vapour Products nor Heated Products produce smoke.

For our Heated Products we utilise a multistep approach to confirm the absence of combustion. These steps include determining the temperature profile of the Heated Product’s heater and consumable during use; measurement of combustion markers e.g. carbon monoxide; and mapping the thermal degradation of our Heated Product consumables.

Through mapping the thermal degradation of our Heated Product consumables via Thermogravimetric Analysis (TGA), we can determine at what temperature combustion will occur. TGA allows us to incrementally heat our Heated Product consumable from room temperature up to 1000°C whilst we monitor its mass. We complete this assessment in the presence and absence of oxygen, comparing the differences in mass loss to determine at what point combustion occurs. Thermal degradation mapping of our Heated Product consumables has demonstrated that combustion occurs at above 450°C, when significant mass loss is observed in the presence of oxygen but not in the absence of oxygen (Figure 1).^[5] When there is no oxygen, combustion cannot occur. When there is oxygen, combustion occurs above 450°C.

Figure 1. Thermogravimetric Analysis of our Heated Product consumable in the presence (in air) and absence (in nitrogen) of oxygen

Fewer and lower levels of harmful chemicals

When tobacco is combusted the aerosol, smoke, produced is incredibly complex with >7,500 individual chemicals present, of which 150 chemicals are known to be harmful, and >60 are known carcinogens.^[1,2,3] With no combustion, the aerosols of our Heated Products and Vapour Products are significantly simpler than cigarette smoke.

Our Heated Products heat a consumable of natural material (tobacco leaf or non-tobacco leaf), which is why its aerosol is the most complex of our Smokeless Products. However, the total number of chemicals in our Heated Product aerosols is approximately >10 times less than in cigarette smoke and their concentrations are significantly reduced.^[6,7,8]

Our Vapour Products contain no tobacco. The e-liquid that comprises high-quality materials is heated to form an aerosol. As a result, our Vapour Product aerosols consist predominantly of the e-liquid ingredients and are >100 times less complex than cigarette smoke.^[9,10]

Our Oral Tobacco Products and Oral Nicotine Pouches also have significantly lower levels of chemicals present in their extractions than cigarette smoke. As they contain tobacco, our Oral Tobacco Products have a more complex extraction compared to our Oral Nicotine Pouches. Our Oral Nicotine Pouches are like our Vapour Product e-liquids in that they comprise solely high-quality materials. Of all our Smokeless Products, Oral Nicotine Pouches have the lowest number of chemicals present in their extractions.^[12]

This consolidated picture illustrates the visual difference in aerosol complexity for Heated Products (bottom right) and Vapour Products (top right) compared to cigarette smoke (bottom left) and air (top left).^[11]Approximately 10 puffs of each product and the discolouration of the laboratory filter pad is greatest with the most complex aerosol, cigarette smoke.

Figure 2. Laboratory Filter Pads

Our Smokeless Products have >90% fewer toxicants^#

In 2008, the World Health Organization recommended the reduction of nine chemicals (‘toxicants’) in cigarette smoke.^[13] In our Smokeless Products, on average, these nine toxicants are reduced by 90-95% for Heated Products,^[6]99% for Vapour Products,^[10] and >99% for Oral Nicotine Pouches.^[12] (Figure 3)

Figure 3. Average % reductions of nine toxicants in our Smokeless Products^#

Figure 4. Our Smokeless Products have fewer chemicals in their aerosols/extractions. Combustion = Complexity

Less toxic than cigarette smoke

Cigarette smoke is toxic. With fewer chemicals generated in the aerosols and extractions of our Smokeless Products, we use regulatory toxicology in vitro tests to understand if this translates to a reduction in toxicity. The regulatory toxicology in vitro tests we employ allow us to assess four types of toxicological endpoints:

01 Mutagenicity:

The ability to cause permanent, typically negative, changes to a cell or organism by altering the structure of its DNA.

02 Genotoxicity:

The ability to damage the genetic information within a cell causing mutations, which may lead to cancer.

03 Cytotoxicity:

The level at which something is toxic to a cell.

04 Cell Stress:

The level at which cells are stressed and/or die through exposure to a chemical/chemicals.

We have compared the toxicity of our Smokeless Products to the toxicity of cigarette smoke. For each Smokeless Product we have observed substantial reductions across all four regulatory toxicology in vitro tests (Figure 5).^[14-26]

Figure 5. Smokeless Product reductions in genotoxicity, cytotoxicity and cell stress^#

Footnotes

# Comparison with smoke from a scientific standard reference cigarette (approximately 9 mg tar) in terms of the average of the 9 harmful components the World Health Organization recommends to reduce in cigarette smoke.

^ Oral Tobacco Products operate at ambient temperature but placed here as number of chemicals in its extract are in the 100s.

References

[1] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Tobacco Smoke and Involuntary Smoking (No. 83). World Health Organization and International Agency for Research on Cancer, 2004. Available at: https://www.ncbi.nlm.nih.gov/books/NBK316407/

[2] Jenkins, R.A., et al., Mainstream and sidestream smoke, In The chemistry of environmental tobacco smoke: composition and measurement (2nd ed). CRC Press, 2000. p. 49-75 DOI: 10.1201/9781482278651

[3] Rodgman, A. and Perfetti, T.A., The chemical components of tobacco and tobacco smoke. CRC press, 2008. DOI: 10.1201/9781420078848

[4] Baker, R.R., A review of pyrolysis studies to unravel reaction steps in burning tobacco. J Anal Appl Pyrolysis, 1987. 11: p 555-573. DOI: 10.1016/0165-2370(87)85054-4

[5] Eaton, D., et al., Assessment of tobacco heating product THP1.0. Part 2: product design, operation and thermophysical characterisation. Regul Toxicol Pharmacol, 2018. 93: p. 4-13. DOI: 10.1016/j.yrtph.2017.09.009

[6] Forster, M., et al., Assessment of novel tobacco heating product THP1.0. Part 3: Comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions. Regul Toxicol Pharmacol, 2018. 93: p. 14-33. DOI: 10.1016/j.yrtph.2017.10.006

[7] Savareear B., et al., Non-targeted analysis of the particulate phase of heated tobacco product aerosol and cigarette mainstream tobacco smoke by thermal desorption comprehensive two-dimensional gas chromatography with dual flame ionisation and mass spectrometric detection. J Chromatogr A, 2019. 1603: p. 327-337. DOI: 10.1016/j.chroma.2019.06.057

[8] Savareear, B., et al., Headspace solid-phase microextraction coupled to comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry for the analysis of aerosol from tobacco heating product. J Chromatogry A, 2017. 1520: p. 135-142. DOI: 10.1016/j.chroma.2017.09.014

[9] Margham, J., et al., Chemical composition of aerosol from an e-cigarette: a quantitative comparison with cigarette smoke. Chem Res Toxicol, 2016. 29(10): p. 1662-1678. DOI: 10.1021/acs.chemrestox.6b00188

[10] Pinto, M.I., et al., Chemical characterisation of the vapour emitted by an e-cigarette using a ceramic wick-based technology. Sci Rep, 2022. 12(1):16497. DOI: 10.1038/s41598-022-19761-w

[11] Dalrymple, A., et al., Assessment of enamel discoloration in vitro following exposure to cigarette smoke and emissions from novel vapor and tobacco heating products. Am J Dent, 2018. 31(5): p. 227-233. Available at: https://pubmed.ncbi.nlm.nih.gov/30346667/

[12] Azzopardi, D., et al., Chemical characterization of tobacco-free “modern” oral nicotine pouches and their position on the toxicant and risk continuums. Drug Chem Toxicol, 2022. 45(5): p. 2246-2254. DOI: 10.1080/01480545.2021.1925691

[13] WHO, The Scientific Basis of Tobacco Product Regulation. WHO Press, 2008. https://iris.who.int/bitstream/handle/10665/43997/TRS951_eng.pdf

[14] Jaunky, T., et al., Assessment of tobacco heating product THP1.0. Part 5: In vitro dosimetric and cytotoxic assessment. Regul Toxicol Pharmacol, 2018. 93: p. 52-61. DOI: 10.1016/j.yrtph.2017.09.016

[15] Taylor, M., et al., Assessment of novel tobacco heating product THP1.0. Part 6: a comparative in vitro study using contemporary screening approaches. Regul Toxicol Pharmacol, 2018. 93: p. 62-70. DOI: 10.1016/j.yrtph.2017.08.016

[16] Thorne, D., et al., Assessment of novel tobacco heating product THP1.0. Part 7: Comparative in vitro toxicological evaluation. Regul Toxicol Pharmacol, 2018. 93: p. 71-83. DOI: 10.1016/j.yrtph.2017.08.017

[17] Murphy, J., et al., Assessment of tobacco heating product THP1.0. Part 9: The placement of a range of next-generation products on an emissions continuum relative to cigarettes via pre-clinical assessment studies. Regul Toxicol Pharmacol, 2018. 93: p. 92-104. DOI: 10.1016/j.yrtph.2017.10.001

[18] Goodall, S., et al., Evaluation of behavioural, chemical, toxicological and clinical studies of a tobacco heated product glo™ and the potential for bridging from a foundational dataset to new product iterations. Toxicol Rep, 2022. 9: p. 1426-1442. DOI: 10.1016/j.toxrep.2022.06.014

[19] Taylor, M., et al., E-cigarette aerosols induce lower oxidative stress in vitro when compared to tobacco smoke. Toxicol Mech Methods, 2016. 26(6): p. 465-476. DOI: 10.1080/15376516.2016.1222473

[20] Thorne, D., et al., The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100. Mutat, 2016. 812: p. 29-38. DOI: 10.1016/j.mrgentox.2016.10.005

[21] Azzopardi, D., et al., Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicol Mech Methods, 2016. 26(6): p. 477-491. DOI: 10.1080/15376516.2016.1217112

[22] Bishop, E., et al., An in vitro toxicological assessment of two electronic cigarettes: E-liquid to aerosolisation. Curr Res Toxicol, 2024. 6:100150. DOI: 10.1016/j.crtox.2024.100150

[23] Bishop, E., et al., A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro. Toxicol Lett, 2023. 380: p. 1-11. DOI: 10.1016/j.toxlet.2023.03.006

[24] Bishop, E., et al., An approach for the extract generation and toxicological assessment of tobacco-free ‘modern’ oral nicotine pouches. Food Chem Toxicol, 2020. 145:111713. DOI: 10.1016/j.fct.2020.111713

[25] East, N., et al., A screening approach for the evaluation of tobacco-free ‘modern oral’ nicotine products using Real Time Cell Analysis. Toxicol Rep, 2021. 8: p. 481-488. DOI: 10.1016/j.toxrep.2021.02.014

[26] Yu, F., et al., Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts. Mutat, 2024. 895: p. 503738. DOI: 10.1016/j.mrgentox.2024.503738