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An electrically-heated smoking system, also known as a heated tobacco product or heat-not-burn tobacco product (HnB), uses an electric heating element^[1] to char tobacco,^[2]^{[unreliable medical source?]} at a lower temperature than a conventional cigarette.^[3] The result is a smoke that contains nicotine, other chemicals, and particulates.^[1] These products may match some of the behavioral aspects of smoking.^[4] Some tobacco companies claim these products are less harmful to consumers than other types of cigarettes, but there is no reliable evidence to support these claims.^[3]^[5]

Some of these products take loose-leaf tobacco in a heated chamber; others require product-specific cigarettes.^[6]^[1] Products heating cigarettes using an external heat source first came to market in 1988, however they were not a commercial success.^[3] These products are being introduced by large tobacco companies.^[7]

Health effects

There is not enough research to evaluate the level of harm of these products.^[8] A 2016 Cochrane review found that it was unclear whether using these products instead of conventional cigarettes would "substantially alter the risk of harm".^[9] Also in 2016, the WHO noted that some scientists believe these products to be as harmful as traditional cigarettes, and stated that no convincing evidence had been presented for industry claims of lowered risk and health benefits. Independent research is not available to support these claims; they are based on industry-funded research.^[5] Independent 2018 reanalysis of data from industry research has found deficiencies and omissions in the evidence used to support the industry's claims.^[10]^{[unreliable medical source?]}^[11]^{[unreliable medical source?]}^[12]^{[unreliable medical source?]}

Action on Smoking and Health stated in 2016 that due to "the tobacco industry's long record of deceit" regarding the health risks involving smoking, it is important to conduct independent studies into the health effects of these products.^[13]

The effects of second-hand exposure are unknown.^[1]

Addiction and quitting

Such products are believed to be just as addictive as conventional cigarettes.^[14]^{[failed verification]} Nearly half of people using these products had never used conventional cigarettes,^[15] according to a small survey done in Italy.^[16] This has caused concern that the products might cause nicotine addiction rather than reduce harm to those who already smoke.^[15]^[17]

There is not enough evidence to know if HnB products help with quitting smoking.^[18] In one manufacturer-led study, smokers using Hnb products mostly did not stop using regular cigarettes; they mostly used both, although the HnB products were supplied to them for free.^[10]^{[unreliable medical source?]} Even assuming that the new products are less risky than older cigarettes, there is not thought to be any possibility of a risk reduction among these dual users, who make up 69% of all users.^[17]

Nicotine delivery

Tests of smokers switching to the most common HnB products show that they take deeper, longer puffs at shorter intervals.^[17]^: 90 Users experience a sudden, sharp peak in blood nicotine levels, which rise just as abruptly, and just as high, as in the peak from a regular cigarette.^[19]^: 90 However, a HnB cigarette delivers slightly less nicotine overall than a regular cigarette;^[19]^: 90 blood nicotine drops more quickly after smoking it.^[20]

Sharper peaks in blood nicotine levels cause greater addictiveness.^[21] Blood nicotine levels drop fairly rapidly, halving every 1-2 hours, causing mild withdrawal within tens of minutes. Nicotine withdrawal causes deteriorating mood, driving craving for nicotine consumption.^[22] Smoking trial volunteers switching to exclusive use of an HnB cigarette product, after an initial adjustment period, usually smoked more cigarettes than the control arm, while reporting that they were less satisfying and rewarding than regular cigarettes.^[17]^{: 93–94, Table 8}

Pregnancy

There is no information on the effects of smoking HnB devices during pregnancy, as of 2018.^[18] However, they are nicotine-containing products.^[1] Nicotine harms brain development, in the fetus^[23] and infant.^[24]

Nature and function

Nicotine is released from tobacco heated above 140°C.^[25] Heating tobacco causes pyrolysis; organic material breaks down, releasing most of the substances found in regular cigarette smoke.^[26]^[2]^{[unreliable medical source?]} At higher temperatures, the carbon increasingly combines with atmospheric oxygen, releasing carbon monoxide and carbon dioxide.^[26]^{[unreliable medical source?]} It is possible to heat to a temperature hot enough to cause pyrolysis, but not hot enough to oxidize and release the carbon.^[26]^{[unreliable medical source?]} This ancient process is called charring,^[2]^{[unreliable medical source?]} and the carbon-rich residue is called char.^[27]^{[unreliable medical source?]}

HnB products vary, but the main brands heat to temperatures of 340-180 Celsius,^[28]^{: Table 4} which is hot enough to char.^[26]^{[unreliable medical source?]} ^[2]^{[unreliable medical source?]} The composition of the smoke is changed by lower temperatures: levels of some substances fall, while levels of others rise.^[11]^{[unreliable medical source?]} While the nicotine is the main addictive component in tobacco, some pyrolysis products of tobacco are thought to reinforce addiction (such as acetaldehyde, norharman, and harman).^[29]^[30]^[relevant?]

These products are marketed as "heat-not-burn"^[31] and "smoke-free".^[32] However, independent researchers explicitly disagree with the claim that they are smokeless,^[33]^[34]^{[unreliable medical source?]}^[35]^[36] arguing that^[37]^{[unreliable medical source?]} the emitted aerosol is smoke,^{[original research?]} as it contains pyrolysis products,^[17] and they commonly^[38]^{[unreliable medical source?]}^[36] call it "smoke".^[36]^{[failed verification]} Prior to 2016, Phillip Morris did the same.^[17] Independent research has also disputed the claim that the products are "heat-not-burn" devices.^[2]^[39]^{[neutrality is disputed]}

The three main products have a time limit, so that a cigarette must be smoked within 3.5 - 10 minutes.^[40] This is not technically necessary, but causes more variable levels of blood nicotine, increasing addictiveness.^[40]

History

Steam Hot One, a Japanese variant of the Eclipse made by Japan Tobacco.

Philip Morris' Heatbar pictured without a specifically designed cigarette.

The first commercial heat-not-burn product was the R.J. Reynolds Premier,^[41] a smokeless cigarette launched in 1988 and described as difficult to use.^[42] Many smokers disliked the taste.^[43] It was shaped like a traditional cigarette, and when heated the smoldered charcoal moved past processed tobacco containing more than 50 percent glycerin to create a smoke including aerosolized nicotine.^[44] It did require some combustion.^[45] In 1989,^[46] after spending $325 million,^[47] R.J. Reynolds pulled it from the market months later after organisations recommended to the US Food and Drug Administration (FDA) to restrict it or classify it as a drug.^[48]

The Premier product concept went on to be further developed and re-launched as Eclipse^[46] in the mid-1990s,^[49] and was available in limited distribution as of 2015.^[50] Reynolds American stated that the Revo was a "repositioning" of its Eclipse.^[51] R.J. Reynolds' Revo was withdrawn in 2015.^[50]

Philip Morris International (PMI) launched a cigarette in 1998 that was placed into an electronic heating device as Accord.^[52] The battery-powered product was the size of a pager.^[53] The product was marketed as "low-smoke". Ads claiming reduced risk were drafted, but never released; an attempt was made to get the Surgeon General of the United States to endorse it without requiring long-term studies on its health effects. Few people started using the Accord, and almost all users also continued to use regular cigarettes. The Accord was discontinued in 2006, eight years after it came on the market.^[54]

In 2007 PMI launched the Heatbar,^[55] which was nearly identical to the Accord.^[54] The Heatbar was around the size of a mobile phone and was said to heat specifically designed cigarettes rather than burning them.^[56] The only benefit was to lower second-hand smoke, which lead to Heatbar being discontinued.^[57] Heatbar did not obtain any significant user reception.^[58] Accord and Heatbar are predecessors of PMI's current heat-not-burn tobacco products.^[59]

The ubiquitousness of electronic cigarettes and growing dissatisfaction with not providing a throat-hit may present an opportunity for heat-not-burn tobacco products.^[3] These products are currently being introduced by large tobacco companies.^[7] PMI anticipates a future without traditional cigarettes, but campaigners and industry analysts call into question the probability of traditional cigarettes being dissolved, by either e-cigarettes or other products like iQOS.^[60]

Products

Electrically-heated cigarette system. a) Charger (left) and cigarette holder (right), b) low-temperature cigarette (left) and holder with cigarette inserted (right), c) Disassembled holder, with heating element visible (left) and the holder's lid (right)

The products are designed to be similar their conventional counterparts.^[51] A tobacco stick along with a heating element will provide the user a choice across the different heat-not-burn tobacco products available.^[51]^{[clarification needed]} Another type of heat-not-burn tobacco product is the loose-leaf tobacco vaporizer that entails putting loose-leaf tobacco into a chamber, which is electrically heated using an element.^[6]

3T

The 3T from Vapor Tobacco Manufacturing was launched in December 2014.^[61] The product employs a patented, aqueous system whereby desired components are extracted into water.^[62] The liquid is mixed with glycerin and aerosolized producing a smoke without combustion by an electronic heating system.^[62] Their organic liquids are made from organic tobacco, organic glycerin, and water.^[61]

Glo

In 2016 British American Tobacco (BAT) launched a heat-not-burn product called glo in Japan.^[63] glo is battery-powered.^[63] It uses a heating element with a tobacco stick.^[51] In May 2017 they released i-glo in Canada.^[64] The glo iFuse debuted in Romania by BAT in 2015.^[51] It uses a cartridge with a tobacco stick and a flavored nicotine liquid.^[51] Bonnie Herzog, a senior analyst at Wells Fargo Securities stated that the proposed acquisition of R. J. Reynolds by BAT in 2016 would let them catch up in the technology competition.^[65]

IQOS

The introduction of IQOS was announced on June 26, 2014.^[66] Although it is marketed as a novel product, it is very similar to the "Accord" product released by the same company in 1998; however, the IQOS cigarettes have more nicotine, less tar, and more tobacco. They are heated to a lower temperature, and the kit costs about US$40 more in 2018 dollars.^[54] The product is marketed by Philip Morris International (PMI) under the Marlboro and Parliament brands.^[67]

Initially launched in 2014 in Nagoya, Japan and Milan, Italy, IQOS is being gradually rolled out to other countries.^[68] By end of 2016 it was available in over 20 countries, with expansion plans into several more in 2017 as manufacturing capacity increases.^[69] PMI has projected that when 30 billions units are sold, iQOS would increase profits by $700 million.^[70] To date, the company claims that total investments made in the development and assessment of these products have exceeded $3 billion.^[71] Phillip Morris spent €500 million on iQOS in 2016 alone.^[72]

iQOS consists of a charger around the size of a mobile phone and a holder that looks like a pen.^[73] The disposable tobacco stick, which looks somewhat like a short cigarette, has been dipped in propylene glycol,^[74] is inserted into the holder which then heats it to temperatures up to 350 °C.^[52] The smoke released contains nicotine and other chemicals.^[4] The amount of nicotine provided may be a little strong for light cigarette smokers.^[75] Users have reported less smell and odour on clothing.^[45] The smoke generated by iQOS contains substances from pyrolysis and thermogenic degradation that are identical to the constituents found in traditional tobacco cigarette smoke.^[74] A 2017 review found "little research on what substances are released after the device heats the tobacco-based paste. The physical effects on users are also not yet known."^[76]

One independent study of the iQOS criticized Phillip Morris, saying "Dancing around the definition of smoke to avoid indoor-smoking bans is unethical" and called for more independent research, saying "Smokers and non-smokers need accurate information about toxic compounds released in IQOS smoke. This information should come from sources independent of the tobacco industry".^[74] After the study was published, the heads of the three Swiss universities where the authors worked received letters from Phillip Morris, accusing the authors of faulty methodology, and subsequently the researchers were not willing to talk to a journalist.^[33] JAMA Internal Medicine, which published the study, described the letters as unusual and smacking of intimidation.^[33] Phillip Morris also published an online academic counter-argument.^[33]

In December 2016, PMI submitted a multi-million page application^[72] to the US FDA for iQOS to be authorized as a modified risk tobacco product.^[77] The FDA reviewed Phillip Morris's data, some independent studies, including the May 2017 Swiss paper about toxic compounds in iQOS smoke mentioned above, a December 2017 amendment to the application by Phillip Morris on the same topic, and the FDA's own laboratory testing data.^[78]

In January 2018, the FDA advisory panel ruled that Phillip Morris had not shown that their product cut health risks;^[79] the panel also "expressed concerns about the lack of data" on risk relative to cigarettes.^[80] The Campaign for Tobacco-Free Kids criticized the product, saying that it looks like the e-cigarettes which children use the most.^[34] IQOS is marketed in stores and packaging which resemble those of high-end smartphones, a strategy expected to appeal to youth by associating it with their interests in new technology.^[81]

PMI intends to convert its customers in Japan to using heat-not-burn products.^[82] iQOS is sold as an alternative to cigarettes.^[83] PMI states that they understand that its iQOS product will be as addictive as tobacco smoking.^[13] iQOS is sold with a warning that the best option is to avoid tobacco use altogether.^[84]

iSmoke OneHitter

iSmoke OneHitter by iSmoke was launched in 2015.^[85] It can be used as a loose-leaf tobacco vaporizer.^[86] It has a chamber that can be filled with up to 800-milligrams of tobacco.^[86]

Korea Tobacco & Ginseng Corporation

Korea Tobacco & Ginseng Corporation announced on 8 June 2017 that they will launch a heat-not-burn tobacco product in September 2017.^[87]

Pax 2

PAX Labs, formerly known as Ploom,^[88] sells PAX vaporizers.^[89] In 2010 they launched Ploom, a butane-powered product used for the heating tobacco or botanical products.^[90] Later models replaced butane heating with an electric system.^[91] After its initial partnership with Japan Tobacco was abandoned, the company became known as Pax Labs.^[92] The Pax 2 uses loose-leaf tobacco.^[51] The surface of the Pax 2 remains cool, while the oven heats to temperatures up to 455 °F.^[93] It has four temperature options.^[93]

Ploom Tech

In January 2016 Japan Tobacco (JT) released Ploom TECH.^[94] JT's Ploom has been withdrawn from the US.^[51] The Ploom brand, however, remained with JT and the product itself has been replaced with a different product called Ploom Tech, in which an aerosol passes through a capsule of granulated tobacco leaves.^[95] The capsules are aluminum.^[17] Sales are being expanded throughout Japan in 2017.^[96] They intend to spend $500 million to increase their heated tobacco manufacturing capacity by late 2018.^[97]

V2 Pro

V2 originally released their vaporizer line named V2 Pro in July 2014.^[98] The initial product was named Series 3.^[98] Series 3 comes with 3 cartridges including a loose-leaf cartridge, which heats the material by conduction.^[99] It comes with a battery and USB changer, among other things.^[99] Pro Series 3X also by V2 can be used with dry material.^[100] It has three different air flow options that can be adjusted with a slight turn of the mouthpiece.^[100] Series 7 comes with a loose-leaf cartridge, among other things.^[101] Series 7 lets the user change the temperature by using a single button.^[98]

Regulations

Tobacco companies have used these products to seek exemptions and relaxations of existing tobacco control policies.^[102]

"There is concern that heat-not-burn tobacco will skirt local ordinances that prevent smoking in public areas," Mitchell H. Katz, director of the Los Angeles County Health Agency, wrote in 2017.^[103] Action on Smoking and Health stated in 2016 that "unless and until independent evidence shows that IQOS and similar products are substantially less harmful than smoking then these products should be regulated in the same way as other tobacco products."^[13] Tobacco control activist Stanton Glantz stated that the US FDA should halt new tobacco products until tobacco companies stop selling traditional cigarettes.^[104] As of 2016^[update], 19 countries have permitted the sale of iQOS.^[74]

In the US, these products fall under the jurisdiction of the Food and Drug Administration,^[6] which is reviewing them as of 2018.

Advertisement for the iQOS, but not iQOS' tobacco stick, is unregulated under the European Union Tobacco Products Directive.^[51] In Italy, taxes, smoking bans, ad bands, and health warnings have all been scaled back from what is required of conventional cigarettes; for instance, the warning labels required are less than half as large, and do not have to include images.^[105]

Heat-not-burn tobacco products are not restricted for sale in Israel by the Ministry of Health.^[106] However, after intervention by three voluntary organizations, they are now taxed at the same rate as other cigarettes.^[107]

Ploom and iQOS are governed by the Tobacco Industries Act regulations as tobacco products in Japan.^[108] Nicotine e-cigarettes are illegal in Japan, and rare, while IQOS cigarettes made up nearly 5% of tobacco sales in October 2016.^[109] The Liberal Democratic Party will deliberate over increasing the tax rate for heat-not-burn tobacco products in April 2018.^[110]

Electronic tobacco products using dry material are regulated as e-cigarettes in South Korea by the Ministry of Health and Welfare.^[111] Korea regulates e-cigarettes differently than traditional cigarettes for tax reasons.^[112] As a result, iQOS are taxed at a decreased rate, compared to the 75% incurred on normal cigarettes.^[112] Emerging tobacco products are banned in Singapore by the Ministry of Health.^[113]

After iQOS launched a marketing campaign in New Zealand, the Ministry of Health, which has the authority to regulate nicotine products, stated that the refill sticks are not legal for sale in New Zealand.^[114] Rapid negotiation between politicians and the tobacco industry about legalization, and regulation as a consumer product rather than a medical treatment, followed, in a process the New Zealand Medical Journal called "alarming".^[115]

References

^ ^a ^b ^c ^d ^e "Heated tobacco products (HTPs) information sheet". World Health Organization. 2018. In order to produce the nicotine-infused vapor, HTPs heat tobacco up to 350°C (lower than 600°C as in conventional cigarettes) using battery-powered heating-systems... Currently, there is also insufficient evidence on the potential effects of second-hand emissions produced by HTPs.
^ ^a ^b ^c ^d ^e Davis, Barbara; Williams, Monique; Talbot, Prue (2018). "IQOS: Evidence of pyrolysis and release of a toxicant from plastic". Tobacco Control: tobaccocontrol-2017-054104. doi:10.1136/tobaccocontrol-2017-054104 (inactive 31 October 2018). PMID 29535257. Charring due to pyrolysis (a form of organic matter thermochemical decomposition) was observed in the tobacco plug after use. When the manufacturer's cleaning instructions were followed, both charring of the tobacco plug and melting of the polymer-film filter increased. Headspace analysis of the polymer-film filter revealed the release of formaldehyde cyanohydrin at 90°C, which is well below the maximum temperature reached during normal usage. {{cite journal}}: Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: DOI inactive as of October 2018 (link)
^ ^a ^b ^c ^d Caputi, TL (24 August 2016). "Heat-not-burn tobacco products are about to reach their boiling point". Tobacco Control. 26 (5): 609–610. doi:10.1136/tobaccocontrol-2016-053264. PMID 27558827.
^ ^a ^b Bentley, Guy (15 March 2017). "Heat-Not-Burn Tobacco: The Next Wave Of A Harm-Reduction Revolution". Forbes.
^ ^a ^b "Further development of the partial guidelines for implementation of Articles 9 and 10 of the WHO FCTC" (PDF). World Health Organization. 12 July 2016. pp. 5–6. As previously discussed, products that heat rather than burn are claimed to be less harmful than traditional cigarettes, although these claims of risk reduction are based on industry-funded studies. Independent studies should be conducted to investigate these claims. Convincing evidence has yet to be provided for the claims of risk reduction and health benefits of products that heat rather than burn tobacco [37]. Some scientists consider these heated tobacco products to be just as harmful as conventional cigarettes[38].
^ ^a ^b ^c Lopez, Alexa A; Hiler, Marzena; Maloney, Sarah; Eissenberg, Thomas; Breland, Alison B (2016). "Expanding clinical laboratory tobacco product evaluation methods to loose-leaf tobacco vaporizers". Drug and Alcohol Dependence. 169: 33–40. doi:10.1016/j.drugalcdep.2016.10.005. PMC 5140724. PMID 27768968.
^ ^a ^b Neo Chai Chin (2 March 2017). "Heated tobacco products just as bad as cigarettes: Amy Khor". Today (Singapore newspaper). Mediacorp.
^ "Alternatieve tabaksproducten: harm reduction?" (PDF). Netherlands National Institute for Public Health and the Environment. 2016. pp. 1–66.
^ Lindson-Hawley, Nicola; Hartmann-Boyce, Jamie; Fanshawe, Thomas R.; Begh, Rachna; Farley, Amanda; Lancaster, Tim (2016). "Interventions to reduce harm from continued tobacco use". Cochrane Database of Systematic Reviews. 10: CD005231. doi:10.1002/14651858.CD005231.pub3. PMID 27734465.
^ ^a ^b McKelvey, Karma; Popova, Lucy; Kim, Minji; Lempert, Lauren Kass; Chaffee, Benjamin W.; Vijayaraghavan, Maya; Ling, Pamela; Halpern-Felsher, Bonnie (2018). "IQOS labelling will mislead consumers". Tobacco Control. 27 (Suppl 1): s48–s54. doi:10.1136/tobaccocontrol-2018-054333. PMID 30158208.
^ ^a ^b St.Helen, Gideon; Jacob Iii, Peyton; Nardone, Natalie; Benowitz, Neal L. (2018). "IQOS: Examination of Philip Morris International's claim of reduced exposure". Tobacco Control. 27 (Suppl 1): s30–s36. doi:10.1136/tobaccocontrol-2018-054321. PMID 30158205.
^ Moazed, Farzad; Chun, Lauren; Matthay, Michael A.; Calfee, Carolyn S.; Gotts, Jeffrey (2018). "Assessment of industry data on pulmonary and immunosuppressive effects of IQOS". Tobacco Control. 27 (Suppl 1): s20–s25. doi:10.1136/tobaccocontrol-2018-054296. PMID 30158203.
^ ^a ^b ^c "ASH reaction to new Philip Morris IQOS 'heat not burn' product". Action on Smoking and Health. 30 November 2016.
^ Pieper, Elke; Mallock, Nadja; Henkler-Stephani, Frank; Luch, Andreas (2018). "Tabakerhitzer als neues Produkt der Tabakindustrie: Gesundheitliche Risiken" (PDF). Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 61 (11): 1422–1428. doi:10.1007/s00103-018-2823-y. PMID 30284624. Der Nikotingehalt in den Emissionen des Tabakerhitzers ist vergleichbar mit dem konventioneller Zigaretten. Daher ist von einem vergleichbaren Sucht- und Abhängigkeitspotenzial auszugehen... dass Tabakerhitzer den irreführenden Eindruck eines nahezu unbedenklichen Tabakkonsums wecken könnten und neben den verbleibenden, substanziellen Schadstoffemissionen auch ein hohes Suchtpotenzial bergen... The nicotine content in the emissions of the tobacco heater is comparable to that of those of conventional cigarettes. It is therefore taken that there is a comparable potential for addiction and dependence... as tobacco heaters can create the misleading impression of being a nearly harmless form of tobacco consumption, despite their substantial remaining emissions of harmful substances and the high addictive potential (Wikipedian's translation)
^ ^a ^b Liu, Xiaoqiu; Lugo, Alessandra; Spizzichino, Lorenzo; Tabuchi, Takahiro; Gorini, Giuseppe; Gallus, Silvano (2018). "Heat-Not-Burn Tobacco Products Are Getting Hot in Italy". Journal of Epidemiology. 28 (5): 274–275. doi:10.2188/jea.JE20180040. PMC 5911679. PMID 29657258. These trends may be of concern, since we have previously shown that nearly half of Italian IQOS users (45%) and over half of the people interested in IQOS (51%) are never smokers. Therefore, such a product may represent, at least in Italy, a gateway for nicotine addiction among never smokers rather than a harm reduction substitution for current smokers
^ Liu, Xiaoqiu; Lugo, Alessandra; Spizzichino, Lorenzo; Tabuchi, Takahiro; Pacifici, Roberta; Gallus, Silvano (26 January 2018). "Heat-not-burn tobacco products: concerns from the Italian experience". Tobacco Control: tobaccocontrol-2017-054054. doi:10.1136/tobaccocontrol-2017-054054.
^ ^a ^b ^c ^d ^e ^f ^g Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092.}}
^ ^a ^b Li, Gerard; Saad, Sonia; Oliver, Brian G.; Chen, Hui (1 August 2018). "Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome". Toxics. 6 (3): 43. doi:10.3390/toxics6030043. ISSN 2305-6304. PMC 6160993. PMID 30071638. There is insufficient evidence on the efficacy of heat-not-burn tobacco on smoking cessation. Neither is there information on the potential impact of maternal inhalation of heat-not-burn tobacco smoke during pregnancy on fetal outcomes, all of which require urgent attention.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Le pic plasmatique est atteint en 6/7 minutes pour la cigarette et le tabac chauffé. Pour les produits non mentholés, le pic est à 13,82 ng/mL avec la cigarette, 14,30 ng/mL et 11,53 ng/mL avec la THS2.2 et 4,8 ng/mL avec la gomme nicotinique 2 mg, alors que les aires sous la courbe sont respectivement de 24,66 ng*h/mL avec la cigarette, 23,75 et 19,92 ng*h/mL avec la THS2.2 et 14,88 ng*h/mL avec la gomme non mentholée. Ainsi, la THS2.2 apporte un peu moins de nicotine qu'une cigarette, mais plus qu'une gomme... "The [blood] plasma peak is attained in 6-7 minutes for both the cigarette and the heated tobacco. For non-metholated products,the peak is 13.82 ng/mL for the cigarette, 14.30 ng/mL and 11.53 ng/mL with the THS2.2 [IQOS] and 4.8 ng/mL with the 2 mg nicotine gum, while the areas under the curve [of plotted blood-nicotine levels] are 24.66 ng*h/mL with the cigarette, 23.75 and 19.92 ng*h/mL with the THS2.2, and 14.88 ng*h/mL with non-menthol gum, respectively. Thus the THS2.2 supplies a bit less nicotine than a cigarette, but more than the gum" (Wikipedian's translation)}}
^ trivial calculation from previous reference; if one peak has a smaller under-curve area than another, and the left sides of the peaks are the same, the smaller-area peak must be narrower, and thus steeper on the other side
^ Ziedonis, Douglas; Das, Smita; Larkin, Celine (2017). "Tobacco use disorder and treatment: new challenges and opportunities". Dialogues in Clinical Neuroscience. 19 (3): 271–280. ISSN 1294-8322. PMID 29302224. Retrieved 10 February 2019. When nicotine or tobacco is administered orally (nicotine-replacement therapy [NRT] medication, dissolvable tobacco, tobacco chew, snuff, etc), absorption is slow and takes 10 to 15 minutes. When nicotine is inhaled as smoke, it quickly reaches the alveoli of the lungs, and within 11 seconds of a puff, reaches the brain through the blood stream and crossing the blood-brain barrier... In dependent smokers, repeated exposure to nicotine peaks can desensitize nAChRs so that they are less responsive, requiring a smoker to smoke more. In contrast, nicotine replacement patches release a stable amount of nicotine in the blood, eliminating peaks and alleviating dependence... Whereas plasma nicotine sharply peaks within 5 minutes of cigarette use, NRTs offer a more steady delivery of nicotine, thereby satisfying but not reinforcing.
^ Ziedonis, Douglas; Das, Smita; Larkin, Celine (2017). "Tobacco use disorder and treatment: new challenges and opportunities". Dialogues in Clinical Neuroscience. 19 (3): 271–280. ISSN 1294-8322. PMID 29302224. Retrieved 10 February 2019. Nicotine's short half-life of 1 to 2 hours leads to withdrawal symptoms of irritability, frustration, anxiety, difficulty concentrating, restlessness, depressed mood, insomnia, increased appetite, weight gain, and cravings... smoking cessation leads to significant reductions in anxiety, depression, and stress in both psychiatric and nonpsychiatric populations
^ England, Lucinda J.; Kim, Shin Y.; Tomar, Scott L.; Ray, Cecily S.; Gupta, Prakash C.; Eissenberg, Thomas; Cnattingius, Sven; Bernert, John T.; Tita, Alan Thevenet N.; Winn, Deborah M.; Djordjevic, Mirjana V.; Lambe, Mats; Stamilio, David; Chipato, Tsungai; Tolosa, Jorge E. (31 December 2010). "Non-cigarette tobacco use among women and adverse pregnancy outcomes". Acta Obstetricia et Gynecologica Scandinavica. 89 (4): 454–464. doi:10.3109/00016341003605719. ISSN 1600-0412. PMC 5881107. PMID 20225987. The use of any products containing nicotine likely will have adverse effects of fetal neurological development.
^ Jenssen, Brian P.; Walley, Susan C.; McGrath-Morrow, Sharon A. (12 December 2017). "Heat-not-Burn Tobacco Products: Tobacco Industry Claims No Substitute for Science". Pediatrics. 141 (1). doi:10.1542/peds.2017-2383. ISSN 1098-4275. PMID 29233936. Retrieved 10 February 2019. Additionally, the IQOS smoke had nicotine levels similar to levels in conventional cigarette smoke. Nicotine, the highly addictive substance found in tobacco, is unsafe to youth and harms infant and adolescent brain development, as has been summarized in a recent report from the US Surgeon General.
^ Forster, Mark; Liu, Chuan; Duke, Martin (16 April 2015). "An experimental method to study emissions from heated tobacco between 100-200°C". Chemistry Central Journal. 9: 20. doi:10.1186/s13065-015-0096-1. PMC 4418098. PMID 25941536.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b ^c ^d St.Helen, Gideon; Jacob Iii, Peyton; Nardone, Natalie; Benowitz, Neal L (2018). "IQOS: Examination of Philip Morris International's claim of reduced exposure". Tobacco Control. 27 (Suppl 1): tobaccocontrol–2018–054321. doi:10.1136/tobaccocontrol-2018-054321. PMID 30158205. PMI's MRTP application fails to address the important question of whether the aerosol generation process for IQOS produces toxic substances not found in the smoke of combustible cigarettes, which could have been answered through non-targeted chemical analysis. Combustible tobacco cigarettes reach about 900°C during a puff and smoulder at about 400°C between puffs.[23] The burning process, substances emitted and their levels vary at different temperatures.[38] Distillation, the process during which nicotine and aromas are transferred from tobacco to smoke, occurs below 300°C; pyrolysis occurs at about 300°C–700°C, entails the decomposition of biopolymers, proteins, and other organic materials and generates the majority of substances emitted in smoke; and combustion occurs above 750°C and results in the generation of carbon dioxide, CO and water.[38] HeatSticks are heated to a maximum of 350°C,[19] a temperature sufficient to enable pyrolytic decomposition of some organic materials. Formation of toxic volatile organic compounds, including formaldehyde, acetaldehyde and acrolein, via dehydration and oxidation of the humectants, propylene glycol and glycerin, have been reported in e-cigarette aerosols at similar temperatures as IQOS.[39–42] In addition, flavouring chemicals in e-cigarettes undergo thermal degradation and contribute significantly to levels of toxic aldehydes emitted in e-cigarette aerosol.[43] Since the constituents of HeatSticks may be different from that of combustible cigarettes, including flavourants and additives, it is plausible that the IQOS aerosol may contain substances not present in tobacco smoke.
^ Sharma, Ramesh K.; Wooten, Jan B.; Baliga, Vicki L.; Martoglio-Smith, Pamela A.; Hajaligol, Mohammad R. (13 February 2002). "Characterization of char from the pyrolysis of tobacco". Journal of Agricultural and Food Chemistry. 50 (4): 771–783. ISSN 0021-8561. PMID 11829644.
^ Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. ... alors que les premiers tabacs chauffés l'étaient à plus de 500 °C, la THS2.2 est chauffée à 340 °C, la THP1.0 à 240 °C et la Ploom ® à 180 °C "...while the first heated tobacco products were [heated] at over 500 °C, the THS2.2 [IQOS version] is heated to 340 °C, the THP1.0 to 240 °C, and Ploom® to 180 °C" (Wikipedian's translation)
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^ ^a ^b "FDA Panel Gives Qualified Support To Claims For 'Safer' Smoking Device". NPR.org. Retrieved 4 June 2018.
^ Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. R. Auer [36] , un scientifique suisse indépendant dans une lettre au JAMA Internal Medecine , a provoqué la fureur de PMI [37—39] en affirmant que le produit produisait de la fumé... "R. Auer, a Swiss independent scientist, wrote a letter in JAMA Internal Medicine, which provoked the fury of PMI by affirming that the product produced smoke" (Wikipedian's translation)
^ ^a ^b ^c Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Cette étude comme d'autres confirme que les émissions de ces produits contiennent des particules solides et que la THS2.2 n'est pas un produit « non fumé » , mais bien « un nouveau produit du tabac fumé »... This study, like others, confirms that the emissions of these products contain solid particles, and that THS2.2 [IQOS, see legend of Table 4] is not a "smoke=free" product, but indeed "a new smoked tobacco product". (Wikipedian's translation; note that this systematic review paper also painstakingly attributes the papers it reviews to either independent academics or nicotine-industry-funded ones, see Table 1)
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^ Mallock, Nadja; Böss, Lisa; Burk, Robert; Danziger, Martin; Welsch, Tanja; Hahn, Harald; Trieu, Hai-Linh; Hahn, Jürgen; Pieper, Elke; Henkler-Stephani, Frank; Hutzler, Christoph; Luch, Andreas (2018). "Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks". Archives of Toxicology. 92 (6): 2145–2149. doi:10.1007/s00204-018-2215-y. ISSN 0340-5761. PMC 6002459. PMID 29730817., and sources therein
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^ ^a ^b Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Le tabac chauffé a lui été concu pour obliger le fumeur à prendre la dose de nicotine en quelques minutes (de 3,5 minutes à 10 minutes) avant que le dispositif ne s'arrête obligatoirement. Ce mode de fonctionnement de tabac chauffé permet de maintenir des pics de nicotine et une up régulation des récepteurs nicotiniques qui, en semultipliant et se désensibilisant, maintiennent un niveau très élevé de dépendance nicotinique. Alors que la vape est concue pour être un produit de sortie du tabac, le tabac chauffé est concu pour être un produit de maintien en dépendance nicotinique, voire d'entrée en tabagisme, donc un produit concu pour maintenir ou augmenter les profits de l'IT. "Heated tobacco has been designed to oblige the smoker to take the dose of nicotine within a few minutes (3.5 to 10 minutes) before the dispenser forcibly stops. This heated-tobacco operating pattern permits the maintenance of peaks of nicotine, and upregulation of the nicotine receptors, which, in multiplying and becomeing less sensitive, maintain a very high level of nicotine dependence. Where vaping is designed as a tobacco-exit product, heated tobacco is designed as a product for the maintenance of nicotine dependence, and indeed of entry into tobaccoism; it is a product designed to maintain or augment the profits of the tobacco industry." (Wikipedian's translation)
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[WHO2018-1] "Heated tobacco products (HTPs) information sheet". World Health Organization. 2018. In order to produce the nicotine-infused vapor, HTPs heat tobacco up to 350°C (lower than 600°C as in conventional cigarettes) using battery-powered heating-systems... Currently, there is also insufficient evidence on the potential effects of second-hand emissions produced by HTPs.

[char-2] Davis, Barbara; Williams, Monique; Talbot, Prue (2018). "IQOS: Evidence of pyrolysis and release of a toxicant from plastic". Tobacco Control: tobaccocontrol-2017-054104. doi:10.1136/tobaccocontrol-2017-054104 (inactive 31 October 2018). PMID 29535257. Charring due to pyrolysis (a form of organic matter thermochemical decomposition) was observed in the tobacco plug after use. When the manufacturer's cleaning instructions were followed, both charring of the tobacco plug and melting of the polymer-film filter increased. Headspace analysis of the polymer-film filter revealed the release of formaldehyde cyanohydrin at 90°C, which is well below the maximum temperature reached during normal usage. {{cite journal}}: Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: DOI inactive as of October 2018 (link)

[Cap2016-3] Caputi, TL (24 August 2016). "Heat-not-burn tobacco products are about to reach their boiling point". Tobacco Control. 26 (5): 609–610. doi:10.1136/tobaccocontrol-2016-053264. PMID 27558827.

[Bentley2017-4] Bentley, Guy (15 March 2017). "Heat-Not-Burn Tobacco: The Next Wave Of A Harm-Reduction Revolution". Forbes.

[WHO2016-5] "Further development of the partial guidelines for implementation of Articles 9 and 10 of the WHO FCTC" (PDF). World Health Organization. 12 July 2016. pp. 5–6. As previously discussed, products that heat rather than burn are claimed to be less harmful than traditional cigarettes, although these claims of risk reduction are based on industry-funded studies. Independent studies should be conducted to investigate these claims. Convincing evidence has yet to be provided for the claims of risk reduction and health benefits of products that heat rather than burn tobacco [37]. Some scientists consider these heated tobacco products to be just as harmful as conventional cigarettes[38].

[LopezHiler2016-6] Lopez, Alexa A; Hiler, Marzena; Maloney, Sarah; Eissenberg, Thomas; Breland, Alison B (2016). "Expanding clinical laboratory tobacco product evaluation methods to loose-leaf tobacco vaporizers". Drug and Alcohol Dependence. 169: 33–40. doi:10.1016/j.drugalcdep.2016.10.005. PMC 5140724. PMID 27768968.

[Chin2017-7] Neo Chai Chin (2 March 2017). "Heated tobacco products just as bad as cigarettes: Amy Khor". Today (Singapore newspaper). Mediacorp.

[RIVM2016-8] "Alternatieve tabaksproducten: harm reduction?" (PDF). Netherlands National Institute for Public Health and the Environment. 2016. pp. 1–66.

[pmid27734465-9] Lindson-Hawley, Nicola; Hartmann-Boyce, Jamie; Fanshawe, Thomas R.; Begh, Rachna; Farley, Amanda; Lancaster, Tim (2016). "Interventions to reduce harm from continued tobacco use". Cochrane Database of Systematic Reviews. 10: CD005231. doi:10.1002/14651858.CD005231.pub3. PMID 27734465.

[effects-10] McKelvey, Karma; Popova, Lucy; Kim, Minji; Lempert, Lauren Kass; Chaffee, Benjamin W.; Vijayaraghavan, Maya; Ling, Pamela; Halpern-Felsher, Bonnie (2018). "IQOS labelling will mislead consumers". Tobacco Control. 27 (Suppl 1): s48–s54. doi:10.1136/tobaccocontrol-2018-054333. PMID 30158208.

[constituents-11] St.Helen, Gideon; Jacob Iii, Peyton; Nardone, Natalie; Benowitz, Neal L. (2018). "IQOS: Examination of Philip Morris International's claim of reduced exposure". Tobacco Control. 27 (Suppl 1): s30–s36. doi:10.1136/tobaccocontrol-2018-054321. PMID 30158205.

[12] Moazed, Farzad; Chun, Lauren; Matthay, Michael A.; Calfee, Carolyn S.; Gotts, Jeffrey (2018). "Assessment of industry data on pulmonary and immunosuppressive effects of IQOS". Tobacco Control. 27 (Suppl 1): s20–s25. doi:10.1136/tobaccocontrol-2018-054296. PMID 30158203.

[ASH2016-13] "ASH reaction to new Philip Morris IQOS 'heat not burn' product". Action on Smoking and Health. 30 November 2016.

[Germany_risks-14] Pieper, Elke; Mallock, Nadja; Henkler-Stephani, Frank; Luch, Andreas (2018). "Tabakerhitzer als neues Produkt der Tabakindustrie: Gesundheitliche Risiken" (PDF). Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 61 (11): 1422–1428. doi:10.1007/s00103-018-2823-y. PMID 30284624. Der Nikotingehalt in den Emissionen des Tabakerhitzers ist vergleichbar mit dem konventioneller Zigaretten. Daher ist von einem vergleichbaren Sucht- und Abhängigkeitspotenzial auszugehen... dass Tabakerhitzer den irreführenden Eindruck eines nahezu unbedenklichen Tabakkonsums wecken könnten und neben den verbleibenden, substanziellen Schadstoffemissionen auch ein hohes Suchtpotenzial bergen... The nicotine content in the emissions of the tobacco heater is comparable to that of those of conventional cigarettes. It is therefore taken that there is a comparable potential for addiction and dependence... as tobacco heaters can create the misleading impression of being a nearly harmless form of tobacco consumption, despite their substantial remaining emissions of harmful substances and the high addictive potential (Wikipedian's translation)

[Italy-15] Liu, Xiaoqiu; Lugo, Alessandra; Spizzichino, Lorenzo; Tabuchi, Takahiro; Gorini, Giuseppe; Gallus, Silvano (2018). "Heat-Not-Burn Tobacco Products Are Getting Hot in Italy". Journal of Epidemiology. 28 (5): 274–275. doi:10.2188/jea.JE20180040. PMC 5911679. PMID 29657258. These trends may be of concern, since we have previously shown that nearly half of Italian IQOS users (45%) and over half of the people interested in IQOS (51%) are never smokers. Therefore, such a product may represent, at least in Italy, a gateway for nicotine addiction among never smokers rather than a harm reduction substitution for current smokers

[16] Liu, Xiaoqiu; Lugo, Alessandra; Spizzichino, Lorenzo; Tabuchi, Takahiro; Pacifici, Roberta; Gallus, Silvano (26 January 2018). "Heat-not-burn tobacco products: concerns from the Italian experience". Tobacco Control: tobaccocontrol-2017-054054. doi:10.1136/tobaccocontrol-2017-054054.

[systematic_review-17] ^ ^a ^b ^c ^d ^e ^f ^g Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092.}}

[pregnancy-18] Li, Gerard; Saad, Sonia; Oliver, Brian G.; Chen, Hui (1 August 2018). "Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome". Toxics. 6 (3): 43. doi:10.3390/toxics6030043. ISSN 2305-6304. PMC 6160993. PMID 30071638. There is insufficient evidence on the efficacy of heat-not-burn tobacco on smoking cessation. Neither is there information on the potential impact of maternal inhalation of heat-not-burn tobacco smoke during pregnancy on fetal outcomes, all of which require urgent attention.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[systematic_review_nic_peak-19] Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Le pic plasmatique est atteint en 6/7 minutes pour la cigarette et le tabac chauffé. Pour les produits non mentholés, le pic est à 13,82 ng/mL avec la cigarette, 14,30 ng/mL et 11,53 ng/mL avec la THS2.2 et 4,8 ng/mL avec la gomme nicotinique 2 mg, alors que les aires sous la courbe sont respectivement de 24,66 ng*h/mL avec la cigarette, 23,75 et 19,92 ng*h/mL avec la THS2.2 et 14,88 ng*h/mL avec la gomme non mentholée. Ainsi, la THS2.2 apporte un peu moins de nicotine qu'une cigarette, mais plus qu'une gomme... "The [blood] plasma peak is attained in 6-7 minutes for both the cigarette and the heated tobacco. For non-metholated products,the peak is 13.82 ng/mL for the cigarette, 14.30 ng/mL and 11.53 ng/mL with the THS2.2 [IQOS] and 4.8 ng/mL with the 2 mg nicotine gum, while the areas under the curve [of plotted blood-nicotine levels] are 24.66 ng*h/mL with the cigarette, 23.75 and 19.92 ng*h/mL with the THS2.2, and 14.88 ng*h/mL with non-menthol gum, respectively. Thus the THS2.2 supplies a bit less nicotine than a cigarette, but more than the gum" (Wikipedian's translation)}}

[20] trivial calculation from previous reference; if one peak has a smaller under-curve area than another, and the left sides of the peaks are the same, the smaller-area peak must be narrower, and thus steeper on the other side

[use_disorder_peaks-21] Ziedonis, Douglas; Das, Smita; Larkin, Celine (2017). "Tobacco use disorder and treatment: new challenges and opportunities". Dialogues in Clinical Neuroscience. 19 (3): 271–280. ISSN 1294-8322. PMID 29302224. Retrieved 10 February 2019. When nicotine or tobacco is administered orally (nicotine-replacement therapy [NRT] medication, dissolvable tobacco, tobacco chew, snuff, etc), absorption is slow and takes 10 to 15 minutes. When nicotine is inhaled as smoke, it quickly reaches the alveoli of the lungs, and within 11 seconds of a puff, reaches the brain through the blood stream and crossing the blood-brain barrier... In dependent smokers, repeated exposure to nicotine peaks can desensitize nAChRs so that they are less responsive, requiring a smoker to smoke more. In contrast, nicotine replacement patches release a stable amount of nicotine in the blood, eliminating peaks and alleviating dependence... Whereas plasma nicotine sharply peaks within 5 minutes of cigarette use, NRTs offer a more steady delivery of nicotine, thereby satisfying but not reinforcing.

[use_disorder_withdrawal-22] Ziedonis, Douglas; Das, Smita; Larkin, Celine (2017). "Tobacco use disorder and treatment: new challenges and opportunities". Dialogues in Clinical Neuroscience. 19 (3): 271–280. ISSN 1294-8322. PMID 29302224. Retrieved 10 February 2019. Nicotine's short half-life of 1 to 2 hours leads to withdrawal symptoms of irritability, frustration, anxiety, difficulty concentrating, restlessness, depressed mood, insomnia, increased appetite, weight gain, and cravings... smoking cessation leads to significant reductions in anxiety, depression, and stress in both psychiatric and nonpsychiatric populations

[23] England, Lucinda J.; Kim, Shin Y.; Tomar, Scott L.; Ray, Cecily S.; Gupta, Prakash C.; Eissenberg, Thomas; Cnattingius, Sven; Bernert, John T.; Tita, Alan Thevenet N.; Winn, Deborah M.; Djordjevic, Mirjana V.; Lambe, Mats; Stamilio, David; Chipato, Tsungai; Tolosa, Jorge E. (31 December 2010). "Non-cigarette tobacco use among women and adverse pregnancy outcomes". Acta Obstetricia et Gynecologica Scandinavica. 89 (4): 454–464. doi:10.3109/00016341003605719. ISSN 1600-0412. PMC 5881107. PMID 20225987. The use of any products containing nicotine likely will have adverse effects of fetal neurological development.

[no_substitute-24] Jenssen, Brian P.; Walley, Susan C.; McGrath-Morrow, Sharon A. (12 December 2017). "Heat-not-Burn Tobacco Products: Tobacco Industry Claims No Substitute for Science". Pediatrics. 141 (1). doi:10.1542/peds.2017-2383. ISSN 1098-4275. PMID 29233936. Retrieved 10 February 2019. Additionally, the IQOS smoke had nicotine levels similar to levels in conventional cigarette smoke. Nicotine, the highly addictive substance found in tobacco, is unsafe to youth and harms infant and adolescent brain development, as has been summarized in a recent report from the US Surgeon General.

[25] Forster, Mark; Liu, Chuan; Duke, Martin (16 April 2015). "An experimental method to study emissions from heated tobacco between 100-200°C". Chemistry Central Journal. 9: 20. doi:10.1186/s13065-015-0096-1. PMC 4418098. PMID 25941536.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[constituents_pyrolysis_quote-26] St.Helen, Gideon; Jacob Iii, Peyton; Nardone, Natalie; Benowitz, Neal L (2018). "IQOS: Examination of Philip Morris International's claim of reduced exposure". Tobacco Control. 27 (Suppl 1): tobaccocontrol–2018–054321. doi:10.1136/tobaccocontrol-2018-054321. PMID 30158205. PMI's MRTP application fails to address the important question of whether the aerosol generation process for IQOS produces toxic substances not found in the smoke of combustible cigarettes, which could have been answered through non-targeted chemical analysis. Combustible tobacco cigarettes reach about 900°C during a puff and smoulder at about 400°C between puffs.[23] The burning process, substances emitted and their levels vary at different temperatures.[38] Distillation, the process during which nicotine and aromas are transferred from tobacco to smoke, occurs below 300°C; pyrolysis occurs at about 300°C–700°C, entails the decomposition of biopolymers, proteins, and other organic materials and generates the majority of substances emitted in smoke; and combustion occurs above 750°C and results in the generation of carbon dioxide, CO and water.[38] HeatSticks are heated to a maximum of 350°C,[19] a temperature sufficient to enable pyrolytic decomposition of some organic materials. Formation of toxic volatile organic compounds, including formaldehyde, acetaldehyde and acrolein, via dehydration and oxidation of the humectants, propylene glycol and glycerin, have been reported in e-cigarette aerosols at similar temperatures as IQOS.[39–42] In addition, flavouring chemicals in e-cigarettes undergo thermal degradation and contribute significantly to levels of toxic aldehydes emitted in e-cigarette aerosol.[43] Since the constituents of HeatSticks may be different from that of combustible cigarettes, including flavourants and additives, it is plausible that the IQOS aerosol may contain substances not present in tobacco smoke.

[char_character-27] Sharma, Ramesh K.; Wooten, Jan B.; Baliga, Vicki L.; Martoglio-Smith, Pamela A.; Hajaligol, Mohammad R. (13 February 2002). "Characterization of char from the pyrolysis of tobacco". Journal of Agricultural and Food Chemistry. 50 (4): 771–783. ISSN 0021-8561. PMID 11829644.

[systematic_review_smoke-28] Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. ... alors que les premiers tabacs chauffés l'étaient à plus de 500 °C, la THS2.2 est chauffée à 340 °C, la THP1.0 à 240 °C et la Ploom ® à 180 °C "...while the first heated tobacco products were [heated] at over 500 °C, the THS2.2 [IQOS version] is heated to 340 °C, the THP1.0 to 240 °C, and Ploom® to 180 °C" (Wikipedian's translation)

[Bruijnzeel2012-29] Bruijnzeel, Adrie W. (2012). "Tobacco addiction and the dysregulation of brain stress systems". Neuroscience & Biobehavioral Reviews. 36 (5): 1418–1441. doi:10.1016/j.neubiorev.2012.02.015. PMC 3340450. PMID 22405889.

[30] Hoffman, A. C.; Evans, S. E. (2013). "Abuse Potential of Non-Nicotine Tobacco Smoke Components: Acetaldehyde, Nornicotine, Cotinine, and Anabasine". Nicotine & Tobacco Research. 15 (3): 622–632. doi:10.1093/ntr/nts192. PMID 22990226.

[marketing-31] Staal, Yvonne CM; van de Nobelen, Suzanne; Havermans, Anne; Talhout, Reinskje (28 May 2018). "New Tobacco and Tobacco-Related Products: Early Detection of Product Development, Marketing Strategies, and Consumer Interest". JMIR Public Health and Surveillance. 4 (2): 60–6. doi:10.2196/publichealth.7359. ISSN 2369-2960. PMC 5996176. PMID 5996176.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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[systematic_review_independent-35] Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. R. Auer [36] , un scientifique suisse indépendant dans une lettre au JAMA Internal Medecine , a provoqué la fureur de PMI [37—39] en affirmant que le produit produisait de la fumé... "R. Auer, a Swiss independent scientist, wrote a letter in JAMA Internal Medicine, which provoked the fury of PMI by affirming that the product produced smoke" (Wikipedian's translation)

[systematic_review_like_others-36] Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Cette étude comme d'autres confirme que les émissions de ces produits contiennent des particules solides et que la THS2.2 n'est pas un produit « non fumé » , mais bien « un nouveau produit du tabac fumé »... This study, like others, confirms that the emissions of these products contain solid particles, and that THS2.2 [IQOS, see legend of Table 4] is not a "smoke=free" product, but indeed "a new smoked tobacco product". (Wikipedian's translation; note that this systematic review paper also painstakingly attributes the papers it reviews to either independent academics or nicotine-industry-funded ones, see Table 1)

[37] Auer, Reto; Cornuz, Jacques; Berthet, Aurélie (2017). "Perplexing Conclusions Concerning Heat-Not-Burn Tobacco Cigarettes—Reply". JAMA Internal Medicine. 177 (11): 1699–1700. doi:10.1001/jamainternmed.2017.5861. PMID 29114801.

[38] Mallock, Nadja; Böss, Lisa; Burk, Robert; Danziger, Martin; Welsch, Tanja; Hahn, Harald; Trieu, Hai-Linh; Hahn, Jürgen; Pieper, Elke; Henkler-Stephani, Frank; Hutzler, Christoph; Luch, Andreas (2018). "Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks". Archives of Toxicology. 92 (6): 2145–2149. doi:10.1007/s00204-018-2215-y. ISSN 0340-5761. PMC 6002459. PMID 29730817., and sources therein

[strategy-39] Bialous, Stella A.; Glantz, Stanton A. (2018). "Heated tobacco products: Another tobacco industry global strategy to slow progress in tobacco control". Tobacco Control. 27 (Suppl 1): s111–s117. doi:10.1136/tobaccocontrol-2018-054340. PMC 6202178. PMID 30209207.

[systematic_review_timelimit-40] Dautzenberg, B.; Dautzenberg, M.-D. (11 November 2018). "[Systematic analysis of the scientific literature on heated tobacco]". Revue Des Maladies Respiratoires. doi:10.1016/j.rmr.2018.10.010. ISSN 1776-2588. PMID 30429092. Le tabac chauffé a lui été concu pour obliger le fumeur à prendre la dose de nicotine en quelques minutes (de 3,5 minutes à 10 minutes) avant que le dispositif ne s'arrête obligatoirement. Ce mode de fonctionnement de tabac chauffé permet de maintenir des pics de nicotine et une up régulation des récepteurs nicotiniques qui, en semultipliant et se désensibilisant, maintiennent un niveau très élevé de dépendance nicotinique. Alors que la vape est concue pour être un produit de sortie du tabac, le tabac chauffé est concu pour être un produit de maintien en dépendance nicotinique, voire d'entrée en tabagisme, donc un produit concu pour maintenir ou augmenter les profits de l'IT. "Heated tobacco has been designed to oblige the smoker to take the dose of nicotine within a few minutes (3.5 to 10 minutes) before the dispenser forcibly stops. This heated-tobacco operating pattern permits the maintenance of peaks of nicotine, and upregulation of the nicotine receptors, which, in multiplying and becomeing less sensitive, maintain a very high level of nicotine dependence. Where vaping is designed as a tobacco-exit product, heated tobacco is designed as a product for the maintenance of nicotine dependence, and indeed of entry into tobaccoism; it is a product designed to maintain or augment the profits of the tobacco industry." (Wikipedian's translation)

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 HnB products vary, but the main brands heat to temperatures of 340-180 Celsius,<ref name="systematic_review_smoke">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub |issn=1776-2588|quote=''... alors que les premiers tabacs chauffés l’étaient à plus de 500 °C, la THS2.2 est chauffée à 340 °C, la THP1.0 à 240 °C et la Ploom ® à 180 °C''  "...while the first heated tobacco products were [heated] at over 500 °C, the THS2.2 [IQOS version] is heated to 340 °C, the THP1.0 to 240 °C, and Ploom® to 180 °C" (Wikipedian's translation)''}}</ref>{{rp|Table 4}} which is hot enough to char.<!--temperatures hot enough to release smoke, but not most of the carbon--><ref name=constituents_pyrolysis_quote/>{{MEDRS|date=January 2019}}<!-- source is a secondary review of a single multimillion-page source containing many primary studies--> <ref name="char"/>{{MEDRS|date=January 2019}} The composition of the smoke is changed by lower temperatures: levels of some substances fall, while levels of others rise.<ref name=constituents>{{cite journal |doi=10.1136/tobaccocontrol-2018-054321 |pmid=30158205 |title=IQOS: Examination of Philip Morris International's claim of reduced exposure |journal=Tobacco Control |volume=27 |issue=Suppl 1 |pages=s30–s36 |year=2018 |last1=St.Helen |first1=Gideon |last2=Jacob Iii |first2=Peyton |last3=Nardone |first3=Natalie |last4=Benowitz |first4=Neal L. }}</ref>{{MEDRS|date=January 2019}} While the nicotine is the main addictive component in tobacco, some pyrolysis products of tobacco are thought to reinforce addiction (such as [[acetaldehyde]], [[norharman]], and [[Harmane|harman]]).<ref name=Bruijnzeel2012>{{cite journal |doi=10.1016/j.neubiorev.2012.02.015 |pmid=22405889 |pmc=3340450 |title=Tobacco addiction and the dysregulation of brain stress systems |journal=Neuroscience & Biobehavioral Reviews |volume=36 |issue=5 |pages=1418–1441 |year=2012 |last1=Bruijnzeel |first1=Adrie W. }}</ref><ref>{{cite journal |doi=10.1093/ntr/nts192 |pmid=22990226 |title=Abuse Potential of Non-Nicotine Tobacco Smoke Components: Acetaldehyde, Nornicotine, Cotinine, and Anabasine |journal=Nicotine & Tobacco Research |volume=15 |issue=3 |pages=622–632 |year=2013 |last1=Hoffman |first1=A. C. |last2=Evans |first2=S. E. }}</ref>{{relevance-inline|date=January 2019}}<!-- relevant as explains use of higher temperatures; can cite that these are found in smoke from these products if needed--->
-These products are marketed as "heat-not-burn"<ref name="marketing">{{cite journal |last1=Staal |first1=Yvonne CM |last2=van de Nobelen |first2=Suzanne |last3=Havermans |first3=Anne |last4=Talhout |first4=Reinskje |title=New Tobacco and Tobacco-Related Products: Early Detection of Product Development, Marketing Strategies, and Consumer Interest |journal=JMIR Public Health and Surveillance |date=28 May 2018 |volume=4 |issue=2 |pages=60–6 |doi=10.2196/publichealth.7359 |pmid=5996176 |pmc=5996176 |issn=2369-2960}}</ref><!--Source does not say they are "marketed" as heat-not-burn. Source says they are called heat-not-burn products.{{FV|date=January 2019}} --> and "smoke-free".<ref name=prohibited>{{Cite news| issn = 1170-0777| title = Tobacco company charged over importing prohibited product| work = NZ Herald| accessdate = 6 June 2018| date = 18 May 2017| url = https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11858402}}</ref> However, independent researchers explicitly disagree with the claim that they are smokeless,<ref name=better_query/><ref name=npr_FDA>{{Cite web| title = FDA Panel Gives Qualified Support To Claims For 'Safer' Smoking Device| work = NPR.org| accessdate = 4 June 2018| url = https://www.npr.org/sections/health-shots/2018/01/25/580213742/fda-panel-gives-qualified-support-to-claims-for-safer-smoking-device}}</ref>{{MEDRS|date=January 2019}}<!--journalistic sources are best for claims of who said what --><ref name="systematic_review_independent">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub |issn=1776-2588|quote=''R. Auer [36] , un scientifique suisse indépendant dans une lettre au JAMA Internal Medecine , a provoqué la fureur de PMI [37—39] en affirmant que le produit produisait de la fumé''... "R. Auer, a Swiss independent scientist, wrote a letter in JAMA Internal Medicine, which provoked the fury of PMI by affirming that the product produced smoke" (Wikipedian's translation)}}</ref><ref name="systematic_review_like_others">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub |issn=1776-2588|quote=''  Cette étude comme d’autres confirme que les émissions de ces produits contiennent des particules solides et que la THS2.2 n’est pas un produit « non fumé » , mais bien « un nouveau produit du tabac fumé »''... This study, like others, confirms that the emissions of these products contain solid particles, and that THS2.2 [IQOS, see legend of Table 4] is not a "smoke=free" product, but indeed "a new smoked tobacco product". '' (Wikipedian's translation; note that this systematic review paper also painstakingly attributes the papers it reviews to either independent academics or nicotine-industry-funded ones, see Table 1)''}}</ref> arguing that<ref>{{cite journal |doi=10.1001/jamainternmed.2017.5861 |pmid=29114801 |title=Perplexing Conclusions Concerning Heat-Not-Burn Tobacco Cigarettes—Reply |journal=JAMA Internal Medicine |volume=177 |issue=11 |pages=1699–1700 |year=2017 |last1=Auer |first1=Reto |last2=Cornuz |first2=Jacques |last3=Berthet |first3=Aurélie }}</ref>{{MEDRS|date=February 2019}}<!--medref not needed for attribution of statement --> the emitted [[aerosol]] is smoke, as it contains [[pyrolysis]] products,<ref name="systematic_review"/> and they commonly<ref>{{cite journal |last1=Mallock |first1=Nadja |last2=Böss |first2=Lisa |last3=Burk |first3=Robert |last4=Danziger |first4=Martin |last5=Welsch |first5=Tanja |last6=Hahn |first6=Harald |last7=Trieu |first7=Hai-Linh |last8=Hahn |first8=Jürgen |last9=Pieper |first9=Elke |last10=Henkler-Stephani |first10=Frank |last11=Hutzler |first11=Christoph |last12=Luch |first12=Andreas |title=Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks |journal=Archives of Toxicology |date=2018 |volume=92 |issue=6 |pages=2145–2149 |doi=10.1007/s00204-018-2215-y |pmid=29730817 |pmc=6002459 |issn=0340-5761}}, and sources therein</ref>{{MEDRS|date=January 2019}}<ref name="systematic_review_like_others"/> call it "smoke".<ref name="systematic_review_like_others"/><!-- Please provide verification on talk page. {{FV|date=January 2019}} --> Prior to 2016, Phillip Morris did the same.<ref name="systematic_review"/> Independent research has also disputed the claim that the products are "heat-not-burn" devices.<ref name="char"/><ref name=strategy>{{cite journal |doi=10.1136/tobaccocontrol-2018-054340 |pmid=30209207 |pmc=6202178 |title=Heated tobacco products: Another tobacco industry global strategy to slow progress in tobacco control |journal=Tobacco Control |volume=27 |issue=Suppl 1 |pages=s111–s117 |year=2018 |last1=Bialous |first1=Stella A. |last2=Glantz |first2=Stanton A. }}</ref>{{POV-statement|date=January 2019}}
+These products are marketed as "heat-not-burn"<ref name="marketing">{{cite journal |last1=Staal |first1=Yvonne CM |last2=van de Nobelen |first2=Suzanne |last3=Havermans |first3=Anne |last4=Talhout |first4=Reinskje |title=New Tobacco and Tobacco-Related Products: Early Detection of Product Development, Marketing Strategies, and Consumer Interest |journal=JMIR Public Health and Surveillance |date=28 May 2018 |volume=4 |issue=2 |pages=60–6 |doi=10.2196/publichealth.7359 |pmid=5996176 |pmc=5996176 |issn=2369-2960}}</ref><!--Source does not say they are "marketed" as heat-not-burn. Source says they are called heat-not-burn products.{{FV|date=January 2019}} --> and "smoke-free".<ref name=prohibited>{{Cite news| issn = 1170-0777| title = Tobacco company charged over importing prohibited product| work = NZ Herald| accessdate = 6 June 2018| date = 18 May 2017| url = https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11858402}}</ref> However, independent researchers explicitly disagree with the claim that they are smokeless,<ref name=better_query/><ref name=npr_FDA>{{Cite web| title = FDA Panel Gives Qualified Support To Claims For 'Safer' Smoking Device| work = NPR.org| accessdate = 4 June 2018| url = https://www.npr.org/sections/health-shots/2018/01/25/580213742/fda-panel-gives-qualified-support-to-claims-for-safer-smoking-device}}</ref>{{MEDRS|date=January 2019}}<!--journalistic sources are best for claims of who said what --><ref name="systematic_review_independent">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub |issn=1776-2588|quote=''R. Auer [36] , un scientifique suisse indépendant dans une lettre au JAMA Internal Medecine , a provoqué la fureur de PMI [37—39] en affirmant que le produit produisait de la fumé''... "R. Auer, a Swiss independent scientist, wrote a letter in JAMA Internal Medicine, which provoked the fury of PMI by affirming that the product produced smoke" (Wikipedian's translation)}}</ref><ref name="systematic_review_like_others">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub |issn=1776-2588|quote=''  Cette étude comme d’autres confirme que les émissions de ces produits contiennent des particules solides et que la THS2.2 n’est pas un produit « non fumé » , mais bien « un nouveau produit du tabac fumé »''... This study, like others, confirms that the emissions of these products contain solid particles, and that THS2.2 [IQOS, see legend of Table 4] is not a "smoke=free" product, but indeed "a new smoked tobacco product". '' (Wikipedian's translation; note that this systematic review paper also painstakingly attributes the papers it reviews to either independent academics or nicotine-industry-funded ones, see Table 1)''}}</ref> arguing that<ref>{{cite journal |doi=10.1001/jamainternmed.2017.5861 |pmid=29114801 |title=Perplexing Conclusions Concerning Heat-Not-Burn Tobacco Cigarettes—Reply |journal=JAMA Internal Medicine |volume=177 |issue=11 |pages=1699–1700 |year=2017 |last1=Auer |first1=Reto |last2=Cornuz |first2=Jacques |last3=Berthet |first3=Aurélie }}</ref>{{MEDRS|date=February 2019}}<!--medref not needed for attribution of statement --> the emitted [[aerosol]] is smoke,{{OR}} as it contains [[pyrolysis]] products,<ref name="systematic_review"/> and they commonly<ref>{{cite journal |last1=Mallock |first1=Nadja |last2=Böss |first2=Lisa |last3=Burk |first3=Robert |last4=Danziger |first4=Martin |last5=Welsch |first5=Tanja |last6=Hahn |first6=Harald |last7=Trieu |first7=Hai-Linh |last8=Hahn |first8=Jürgen |last9=Pieper |first9=Elke |last10=Henkler-Stephani |first10=Frank |last11=Hutzler |first11=Christoph |last12=Luch |first12=Andreas |title=Levels of selected analytes in the emissions of "heat not burn" tobacco products that are relevant to assess human health risks |journal=Archives of Toxicology |date=2018 |volume=92 |issue=6 |pages=2145–2149 |doi=10.1007/s00204-018-2215-y |pmid=29730817 |pmc=6002459 |issn=0340-5761}}, and sources therein</ref>{{MEDRS|date=January 2019}}<ref name="systematic_review_like_others"/> call it "smoke".<ref name="systematic_review_like_others"/>{{FV|date=February 2019}} Prior to 2016, Phillip Morris did the same.<ref name="systematic_review"/> Independent research has also disputed the claim that the products are "heat-not-burn" devices.<ref name="char"/><ref name=strategy>{{cite journal |doi=10.1136/tobaccocontrol-2018-054340 |pmid=30209207 |pmc=6202178 |title=Heated tobacco products: Another tobacco industry global strategy to slow progress in tobacco control |journal=Tobacco Control |volume=27 |issue=Suppl 1 |pages=s111–s117 |year=2018 |last1=Bialous |first1=Stella A. |last2=Glantz |first2=Stanton A. }}</ref>{{POV-statement|date=January 2019}}
 The three main products have a time limit, so that a cigarette must be smoked within 3.5 - 10 minutes.<ref name="systematic_review_timelimit"/> This is not technically necessary, but causes more variable levels of blood nicotine, increasing addictiveness.<ref name="systematic_review_timelimit">{{cite journal |last1=Dautzenberg |first1=B. |last2=Dautzenberg |first2=M.-D. |title=[Systematic analysis of the scientific literature on heated tobacco] |journal=Revue Des Maladies Respiratoires |date=11 November 2018 |doi=10.1016/j.rmr.2018.10.010 |pmid=30429092 |url=https://www.sciencedirect.com/science/article/pii/S0761842518303632?via%3Dihub|issn=1776-2588|quote=''Le tabac chauffé a lui été concu pour obliger le fumeur à prendre la dose de nicotine en quelques minutes (de 3,5 minutes à 10 minutes) avant que le dispositif ne s’arrête obligatoirement. Ce mode de fonctionnement de tabac chauffé permet de maintenir des pics de nicotine et une ''up régulation'' des récepteurs nicotiniques qui, en semultipliant et se désensibilisant, maintiennent un niveau très élevé de dépendance nicotinique. Alors que la vape est concue pour être un produit de sortie du tabac, le tabac chauffé est concu pour être un produit de maintien en dépendance nicotinique, voire d’entrée en tabagisme, donc un produit concu pour maintenir ou augmenter les profits de l’IT.'' "Heated tobacco has been designed to oblige the smoker to take the dose of nicotine within a few minutes (3.5 to 10 minutes) before the dispenser forcibly stops. This heated-tobacco operating pattern permits the maintenance of peaks of nicotine, and upregulation of the nicotine receptors, which, in multiplying and becomeing less sensitive, maintain a very high level of nicotine dependence. Where vaping is designed as a tobacco-exit product, heated tobacco is designed as a product for the maintenance of nicotine dependence, and indeed of entry into tobaccoism; it is a product designed to maintain or augment the profits of the tobacco industry." (Wikipedian's translation)''}}</ref>