18B.6 Health effects of heated tobacco products

Last updated: May 2024           

Suggested citation: Winnall, WR & Greenhalgh, EM. 18B.6 Health effects of heated tobacco products. In Greenhalgh EM, Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2024. Available from  https://www.tobaccoinaustralia.org.au/chapter-18-e-cigarettes/indepth-18b-non-combustible-cigarettes/18b-6-health-effects-of-heated-tobacco-products

 

Heated tobacco products are touted by their manufacturers as harm reduction products despite a lack of evidence for this claim. Although numerous toxic chemicals are present at lower levels in heated tobacco emissions than cigarette smoke, the long-term health effects of heated tobacco use have not been measured. There is evidence that heated tobacco products are addictive and have short term effects on health, such as increased heart rate and blood pressure (see InDepth 18B.6.3), possible liver damage (see InDepth 18B.6.7), and safety issues due to accidental ingestion of tobacco sticks (see InDepth 18B.6.10). There are also concerning signs of lung damage, which may lead to long term lung disease (see InDepth 18B.6.4), and biomarkers of harm that may lead to cancer in long-term users (see InDepth 18B.6.5).

This section discusses the evidence for the health effects of exposure to heated tobacco product emissions under the following topics:

Estimating the health risks from use of heated tobacco products

Addiction to heated tobacco products

Cardiovascular effects of heated tobacco products

Effects of heated tobacco products on respiratory health

Cancer risk for users of heated tobacco products

Effects of heated tobacco products on pregnancy and reproductive health

Possible liver toxicity with use of heated tobacco products

Other possible health effects of heated tobacco products

Health effects of exposure to secondhand emissions from heated tobacco products

Safety issues with use of heated tobacco products

Over half the studies of the health risks of heated tobacco products have been funded by the manufacturers of the products. Manufacturers researching their own or competitor products have a conflict of interest that can bias their findings and interpretations.1 In this section, only studies by independent (non-tobacco industry) researchers are presented, unless stated.

18B.6.1 Estimating the health risks from use of heated tobacco products

Heated tobacco products produce a smoky emission at a lower temperature than burning cigarettes do. These emissions contain many of the toxic constituents found in cigarette smoke (see InDepth 18B.5). Since the long-term health effects of heated tobacco use is unknown, due to the recency of introduction of heated tobacco products into the market, some studies have used indirect approaches to estimate the relative risks of health effects. These approaches include using toxicology data from individual chemicals, measuring biomarkers of exposure (see InDepth 18B.5.6), biomarkers of potential harm or the effects of heated tobacco on animals or cells grown in laboratories.

Because some constituents are found at lower levels, and because some biomarkers of exposures and harm also appear at lower levels, tobacco companies argue that heated tobacco products are less harmful than conventional cigarettes (see details below). However, it is also the case that some toxic constituents appear at higher levels than in cigarettes (see InDepth 18B.5.4). Data on constituents and biomarkers do not directly measure the health effects of heated tobacco use, and the accuracy of predictions of harm based on this information is uncertain.

Toxicology approaches

Toxicology information has been used to predict the risk of disease from heated tobacco use. These studies have many limitations, such as:

  • Many studies were performed by the tobacco industry testing its own products, with an obvious conflict of interest.
  • Most studies have compared the emissions of heated tobacco to cigarette smoke rather than to ambient air, therefore the potential for harm of heated tobacco use for non-smokers are rarely estimated.
  • Many studies focus on chemicals in the FDA’s list of harmful and potentially harmful constituents of tobacco, whilst not measuring other harmful chemicals that may be present in the emissions of heated tobacco products.2

Analysis of the toxic chemicals present in heated tobacco emissions has shown that many are present at lower levels compared to cigarette smoke, as detailed in InDepth 18B.5 and Table 18B.5.1.

Independent studies have integrated information such as known risks from individual toxic chemicals, their doses, routes of exposure, frequency and duration of exposure. One such study estimated a lifetime cancer risk for use of heated tobacco as similar to, but slightly lower than that of cigarette use.3 A risk was also calculated for non-cancer diseases, estimating that heated tobacco use was approximately 2/3rds as risky as cigarette use.3 For heated tobacco, most of this non-carcinogenic risk was predicted to come from relatively high levels of acrolein gas, a respiratory and cardiovascular toxicant.3 These studies predicted an increased risk of health effects (both cancer and non-cancerous) from heated tobacco products that is higher than acceptable, based on the extent of exposure to chemicals, but not as high as that for cigarettes. However, toxicological studies are limited in that they provide a theoretical estimation of risk, but no direct measure of health effects of these products. Whether reduced exposure among those that switch from smoking to using heated tobacco will lead to meaningful reductions in human health risks is yet to be established.4

Despite the limitations of predicting health effects based on toxicology, the reduced exposure levels from heated tobacco have been used by tobacco companies to gain access to markets with claims of harm reduction. In the US, the Food and Drug Administration (FDA) supported findings of the presence of harmful and potentially harmful compounds (HPHC) in the emissions of heated tobacco products, albeit at significantly lower levels than that found in cigarette smoke.5 The FDA found that the IQOS (a popular brand of heated tobacco product manufactured by Philip Morris International) emissions contain several probable or possible carcinogenic chemicals that are unique to IQOS or present in higher levels than in conventional cigarette smoke. IQOS emissions also contain 15 other chemicals that are possibly genotoxic (causing DNA mutations that may cause cancer) and 20 more compounds that have potential health effects. However, in its 2019 authorisation of the sale of IQOS in the US, the FDA concluded that because the products produce fewer or lower levels of some toxic chemicals than combustible cigarettes, their introduction to the market is appropriate from a public health perspective.6 This decision has been criticised by public health groups, who note that the presence of these toxic compounds likely pose significant health risks7 and argue that Philip Morris failed to produce adequate evidence of public health benefits of IQOS and therefore failed to meet the rigorous public health standards that are detailed in the law.

Biomarkers of exposure and potential harm

Another method for estimating risk is to measure biomarkers in people who use heated tobacco products compared to non-users or those who use other tobacco products. Biomarkers of exposure, which can be used to test for exposure to specific chemicals and in different regions of the body, are discussed in InDepth 18B.5.6 and summarised in Table 18B.5.1. These biomarkers measure exposure to individual chemicals only, not overall risk. Biomarkers of potential harm (BoPH) may be more meaningful for predicting health effects. These biomarkers can be measured in users of heated tobacco products to detect damage done by exposure to all the chemicals in tobacco products, which may lead to disease. Examples of these measures include measures of inflammation, white blood cells counts, oxidative stress (cellular damage that can lead to cancer and other diseases) and artery stiffness.8 Detection of these markers in the bodies of tobacco users can be early warning signs, as well as finding the possible underlying damage that may lead to disease in the long term. However, BoPH may also be affected by exposure to other sources of pollution, complicating the interpretation of results. BoPH are discussed below in the relevant sections.

Cellular damage and health effects in animals

Experiments exposing animals and cells grown in laboratories to emissions from heated tobacco products have shown deleterious changes that are consistent with the development of tobacco-associated diseases. Damage to DNA at specific genes may signal a future risk of cancer. Inflammation and oxidative damage, as well as reduced clearance of infections may predict long-term lung diseases or cardiovascular diseases. Although this evidence does not directly demonstrate that users of heated tobacco products will have a greater risk of disease, the early signs of damage in cells and animals remain concerning. Specific animal and laboratory experiments are described in some of the sections below, where relevant.

18B.6.2 Addiction to heated tobacco products

Heated tobacco products contain nicotine, the highly addictive component of tobacco. Evidence indicates that these products are addictive: they contain and deliver similar levels of nicotine to cigarettes,9, 10 users report perceptions of addictiveness11 and they report reductions of nicotine cravings and withdrawal symptoms after use of heated tobacco.12-17

In general, the higher dose of nicotine and the more rapidly it is delivered to the brain, the higher the likelihood of nicotine dependence.18 There is evidence that heated tobacco emissions contain levels of nicotine similar to or just lower than those in cigarette smoke.19, 20 A systematic review estimated that the amount of nicotine in mainstream IQOS aerosol ranged from 57% to 83% of cigarette smoke based on tobacco industry and independent studies.10 Nicotine flux, defined as the rate of nicotine emission per second, contributes to addiction. As for cigarettes and e-cigarettes, the nicotine flux from heated tobacco products varies widely per product (ranging from 5.8 to 58.3 μg/s).9 In one study, Philip Morris’s IQOS products generally had a higher nicotine flux than (BAT’s) glo.9

The heated tobacco device’s limitations may also affect users’ levels of exposure. A study of IQOS users found that they speed up their ‘puff rate’ in order to inhale more nicotine because the heat stick only lasts for six minutes, potentially increasing their intake of nicotine and other harmful chemicals.21

Use of heated tobacco is able to suppress cravings for nicotine or cigarettes.12-17 In smokers who abstained overnight, use of heated tobacco was able to significantly reduce cigarette craving, and was considered as rewarding/satisfying and slightly preferred over e-cigarettes.22 One study showed that, although total nicotine delivery was higher in the usual brand cigarettes, heated tobacco products were able to reduce smoking cravings and withdrawal symptoms in smokers.14 Another study found that users of heated tobacco products reported greater perceived addictiveness than users of e-cigarettes.11 Heated tobacco users also showed signs of nicotine dependence when tested for the time before first use after waking.23 Exclusive daily cigarette smokers and dual users of heated tobacco plus daily cigarettes had the highest prevalence of nicotine dependence relative to exclusive non-daily cigarette smokers in one study from Japan.23 Exclusive heated tobacco user also had higher levels of nicotine dependence than non-daily cigarette smokers.23

There are a lack of quality studies and a lack of independent studies on the effectiveness of heated tobacco products as a cessation aid for smoking.24 Studies indicate that few people who smoke opt to completely replace cigarettes with heated tobacco products. See InDepth 18B.7.2 for more information.

18B.6.3 Cardiovascular effects of heated tobacco products

Since heated tobacco products have only recently come to market, there have been no long-term studies of cardiovascular disease risk for people who use them. Short term studies show that use of heated tobacco is followed by increases in heart rate, blood pressure and markers of damage and reduced function of the cardiovascular system, as described below. Unfortunately, most of these studies examined these effects in smokers, who already have an increased risk of cardiovascular disease. Only a few studies have recruited non-smokers or occasional smokers. 

Short-term cardiovascular effects

A study of people who used heated tobacco products found increases in heart rate and blood pressure, and small but significant decreases in blood oxygen saturation by five minutes after use.25 These effects are consistent with the effects of nicotine, and were similar to those seen in users of e-cigarettes and conventional cigarettes in the same study. Increases in blood pressure and heart rate after use by non-users (occasional smokers) was seen in a study from Sweden,26 and also in smokers in three other studies.27-29 The Swedish study also found adverse effects on vascular function such as increased arterial stiffness and platelet thrombus formation, which are both risk factors for the development of atherosclerosis (the underlying damage that contributes to many types of cardiovascular disease).26 Two studies of smokers29, 30 and two studies of occasional smokers30, 31 also found increases in arterial stiffness after use of heated tobacco products.28, 29 Inflammation and damage to blood vessels (endothelial dysfunction) has been detected in smokers after one use of heated tobacco.8, 27

Cardiovascular function in smokers who switch to heated tobacco products

Studies of people who switch from cigarettes to heated tobacco products aim to predict whether use of the latter may reduce harm compared to continued cigarette smoking. These studies mostly do not compare to non-users, so the extent of harm reduction compared with quitting all nicotine/tobacco products is unclear.

An independent study measured markers of cardiovascular health including heart function, vascular function (circulation to the body) and artery stiffness in smokers who switched to heated tobacco use for one month. Each of these markers of cardiovascular health was improved after one month.32

A large longitudinal study of people who quit smoking in South Korea compared cardiovascular outcomes for those who quit all nicotine products compared to those who switched from smoking to heated tobacco or e-cigarettes.33 In this study, people who switched to the non-combusted tobacco alternatives were considered as one group. Quitting smoking was associated with a lower incidence of cardiovascular disease compared to continued smoking. Compared with quitting all nicotine products, people who switched to either heated tobacco or e-cigarettes had a higher risk of cardiovascular disease. Unfortunately, this study design doesn’t allow for a direct comparison between switching to heated tobacco product use and continued smoking.33

18B.6.4 Effects of heated tobacco products on respiratory health

People who use heated tobacco products risk developing respiratory conditions caused by their regular inhalation of toxic chemicals. The recent introduction of heated tobacco products means that long term respiratory conditions are not yet expected to have arisen in its users. To predict the risks of heated tobacco use, researchers have studied its effects on animals and cells grown in laboratories, as well as the early signs of damage in users that precede serious respiratory diseases. There are concerning signs of lung damage and reduced lung function in users of heated tobacco.34-36

Numerous studies on this subject have been conducted by the tobacco industry. Only data from independent researchers is presented here.

COPD

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating lung disease caused by smoking (see Section 3.2.4.1). Since heated tobacco products have not been on the market for long, the risks of COPD for heated tobacco users cannot be directly measured. Both tobacco industry and independent studies have examined the early types of damage that may underlie the risk of COPD from use of heated tobacco products. Most of this data comes from animal studies or studies of cells grown in laboratories, so its use in predicting risk of COPD is limited. A detailed review of the literature on the early signs of immunological changes consistent with COPD found conflicting data regarding the effects of heated tobacco produced compared to conventional cigarettes.37 Some studies in animals and laboratory-grown cells showed similar immunological changes from heated tobacco compared to cigarette smoke extract exposure, whereas others found that heated tobacco had lesser effects than cigarette smoke. The authors concluded that more long-term studies are necessary to examine the effects of heated tobacco products on COPD.37

For cigarette smokers with COPD, those who successfully cease smoking on average have a small improvement in lung function and less age-related decline in lung function than continuing smokers. One small clinical study has provided some evidence of improvements in disease course after smokers with COPD switched to heated tobacco products. However, one of the authors of this study has links with the tobacco industry.38

Lung function and other markers of respiratory health

Lung function can be detected in tests such as spirometry. Reduced lung function can be a sign of COPD, asthma or other type of lung disease. A reduction in lung function such as airway obstruction, can be an early warning sign of a serious lung disease.

Former smokers who use heated tobacco products had a greater risk of airway obstruction than those who abstained, in study of almost 3,000 people from Japan.39 In this study, people who currently used heated tobacco products only, were 2.32 times more likely to have airway obstruction than non-tobacco users. However, over 90% of these heated tobacco users were former smokers. To address the issue of previous smoking affecting airway obstruction, the authors analysed outcomes for all the former smokers in their sample. Former smokers who currently used heated tobacco were 1.42 times more likely to have airway obstruction compared to former smokers who abstained from all tobacco. In people who ceased smoking for over five years ago, the risk of airway obstruction was almost double if they currently used heated tobacco, compared to continual abstainers.39  These comparisons strengthen the evidence that heated tobacco product use can lead to airway obstruction in former smokers.

A study comparing non-smokers and smokers found similar signs of reduced lung function for both groups soon after using one heated tobacco product.34 Exhaled carbon monoxide was increased by at least two-fold in each group. Oxygen saturation was reduced and some other markers of poor lung function were increased, whilst others were steady. The authors concluded that while the changes were small in terms of major clinical importance, the lack of difference between the effects of heated tobacco and cigarettes raised safety concerns for long term exposure.34 Another study of occasional smokers found reduced lung function after heated tobacco exposure, which was similar in extent to that seen after a conventional cigarette.30

Mucociliary clearance is a process that protects the lungs from polluting particles by sweeping them out of the airways. Exposure to cigarette smoke reduces the rate of this process. One study of mucociliary clearance in users of heated tobacco products found no difference in the clearance rate compared to non-smokers, but significant differences compared to smokers.35

Other respiratory conditions

Among younger users of heated tobacco products, findings of a large-scale survey demonstrated that use of IQOS increased the risk of multimorbidity of asthma and allergic rhinitis and atopic dermatitis in Korean adolescents.40

A large cross-sectional study of students in Hong Kong asked if they had respiratory symptoms for three consecutive months in the past 12 months.36 While 16.3% of all students reported respiratory symptoms, this was higher in smokers (31.1%) and exclusive heated tobacco users (33.5%). Although this cross-sectional study design means it cannot be used to assign a cause to these respiratory symptoms, it does indicate that using heated tobacco instead of smoking cigarettes may not be associated with a reduction in respiratory symptoms.36

Two cases of a rare respiratory disease called acute eosinophilic pneumonia have been described that followed uptake of heated tobacco product use. These diseases involves fever, shortness of breath, and cough.41, 42

Respiratory health in smokers who switch to heated tobacco products

In 2016, Philip Morris International (PMI) submitted an application to the US FDA (Food and Drug Administration) for a designation of IQOS as a ‘modified risk tobacco product’ on the bases of their own data on pulmonary and immune toxicities. Ultimately this request was denied, although IQOS was approved for marketing with a ‘reduced exposure’ designation (see InDepth 18B.6.1 above).43 An independent study examining the data presented by PMI in this application showed that it actually supported significant pulmonary toxicology in IQOS users.44 The authors found that the analysis of PMI’s results was flawed, and that once this analysis was optimised, there was no evidence for PMI’s claim of improvement in pulmonary inflammation or pulmonary function in cigarette smokers who switched to IQOS compared to those who continued smoking.44

Animal studies

In an animal experiment, mice were exposed to heated tobacco emissions for eight weeks, resulting in respiratory inflammation characterised by immune cell infiltrates, decreased antioxidant activity and damage to the lining of the lungs.45 The extent of this inflammation and damage was no different to that produced in mice exposed to cigarette smoke. When subject to bacterial respiratory infection, the exposed mice had reduced bacterial clearance, similar to that seen in cigarette smoke exposed mice.45 These experiments indicate that heated tobacco emissions can cause inflammation and inhibit clearance of bacterial infections in the lungs, but studies of humans are necessary for confirmation. An emphysema-like lung damage and inflammation was also seen in mice exposed to heated tobacco emissions for six months (two 30 minute sessions per day, five days a week for six months).46

Exposure of mice to IQOS emissions for 24 weeks resulted in lower lung function and lung tissue damage.47 The mice were exposed to IQOS emissions for two 30 minute sessions per day, five days a week for 24 weeks. Damage seen in these mice included reduced forced expiration volume (indicating poorer lung function), collagen deposition (indicating tissue damage) in the lungs and increase in signs of inflammation.47

18B.6.5 Cancer risk for users of heated tobacco products

The cancer risks of heated tobacco product use are currently unknown and difficult to predict. Cancer has a long latency period, and due the recent introduction of heated tobacco products there is no long-term epidemiological data on the risk of cancer for users. Many heated tobacco users may be current or former smokers, which will make epidemiological studies on the risks of cancer more complicated.

As described in InDepth 18B.5.3.2 and Table 18B.5.1, users of heated tobacco products are exposed to many carcinogens (cancer-causing chemicals), mostly at lower levels than those in cigarette smoke but higher levels than in e-cigarette emissions and ambient air. Although the long-term risks from this exposure cannot be directly measured, there are concerning results from biomarkers of exposure and damage, and from animal and laboratory studies that indicate a potential risk of cancer for heated tobacco users.

Predicting cancer risk from biomarker and toxicological studies

To predict the risk of cancer, biomarkers can be measured from users of tobacco products.  Biomarkers of exposure (BoE) to specific chemicals and biomarkers of potential harm, (BoPH; indicating damage that may lead to disease), have been used by the tobacco industry and independent researchers to study the risk of disease in the users of these products (see InDepth 18B.5.6 and 18B.6.1). However, only a subset of BoE and BoPH are relevant for predicting the risk of cancer.

A systematic review evaluated all BoE and BoPH measured in trials of heated tobacco products for their appropriateness in predicting lung cancer risk.48 These trials in humans were a mix of independent and tobacco industry research. The authors found that 16 out of a total of 82 biomarkers would be informative for lung cancer risk. These BoE included metabolites (chemicals modified by human cellular processes) of known carcinogens such as 1,3-butadiene. The BoPH harm that were relevant to lung cancer risk included white blood cell counts and measures of lung function (spirometry). Of these 16 biomarkers that predict lung cancer risk, three significantly improved for smokers who switched to heated tobacco use, whereas the remaining 13 did not improve upon switching. These data show that: 1) many trials are using biomarkers that are inappropriate for predicting lung cancer risk, and 2) the most relevant biomarkers mostly showed no improvement for smokers switching to heated tobacco products. Biomarker studies, therefore, do not strongly support a reduction in the risk of lung cancer for people who switch from cigarettes to heated tobacco products. This review also found a lack of trials of lung cancer biomarkers that included non-smokers.48

A study that measured volatile organic compounds, carbon monoxide, nicotine and tar used toxicology methods to calculate lifetime cancer risk for users of a heated tobacco product (as described above).3 The lifetime cancer risk for the heated tobacco was estimated to be similar to, but slightly lower than that for cigarette use.3 Unsurprisingly, publications from the tobacco industry estimate a larger reduction in lifetime cancer risk from heated tobacco compared with cigarettes.49

Studies in animals and laboratory-grown cells

Experiments using animals and cell samples from humans that are grown in laboratories have been used to study the effects of exposure to tobacco products. The results can indicate the potential for damage that may lead to cancer.

A study of oral cells (from the lining of the human mouth) grown in the laboratory showed that heated tobacco emissions were able to cause DNA damage (a risk for cancer) and inhibit DNA repair mechanisms that protect from cancer formation. The effects of emissions from heated tobacco products were similar to those from cigarette smoke in this experiment.50 Similarly, a study of human bronchial cells showed that exposure to heated tobacco emissions lead to damage, such as oxidative stress and genetic lesions, consistent with the causes of cancer. This damage was not as severe as that from cigarettes but more severe than from e-cigarette use.51 A study of lung cells grown in the laboratory showed that heated tobacco emissions 1) altered gene expression (the use of genes), and 2) changed epigenetic methylation (a modification of DNA that does not alter the sequence). Both changes were consistent with a risk for cancer development. The effects of heated tobacco exposure in this study were not as severe as those for conventional cigarette exposure.52

An animal study of exposure used rats that were exposed to IQOS emissions for four weeks (eight tobacco sticks per day, never exceeding the three hours per day of exposure).53 This study found a number of concerning changes that may increase the risk of lung cancer, including: activation of lung enzymes that activate carcinogens, increases in reactive radicals (which can be carcinogenic); promotion of oxidative and gene level DNA damage, and stimulation of a cellular signalling pathway that is involved in tobacco smoke-induced cancer progression. Overall, these results showed that IQOS exposure leads to lung damage and promotion of cellular processes that increase cancer risk in animals.53 Studies in humans are required to assess these risks regarding lung cancer in IQOS users.

18B.6.6 Effects of heated tobacco products on pregnancy and reproductive health

Exposure to nicotine and other toxic chemicals from tobacco emissions can be particularly harmful during pregnancy.54 There is some preliminary evidence that birth outcomes such as birth weight and preterm birth are affected by use of heated tobacco by pregnant women. However, this evidence all comes from cross-sectional studies, and longitudinal studies are necessary to establish use of heated tobacco as a cause of these poor outcomes.

A cross-sectional study in Japan tracked birth outcomes for over 5,000 pregnancies. Of these, 106 pregnant women were users of heated tobacco but no other tobacco or nicotine products. Of these pregnancies, 5.7% resulted in a small for gestational age (SGA) birth, compared with an average of 2.7% for the whole group. After adjusting for socioeconomic status and other variables, the odds of an SGA birth were increased 2.5-fold for sole users of heated tobacco, which was higher than that for conventional cigarette users (1.95-fold).55 Longitudinal studies are needed to confirm this increase in risk.

A study from Italy showed that pregnant users of heated tobacco were more likely than non-users/non-smokers to experience preterm birth.56 Measures such as ultrasound evaluations, biochemical tests and APGAR scores (for assessing acute response to birth) found no other differences between these groups. However, there were significant differences in the demographics of the groups of people who chose to use heated tobacco versus abstain – such as in lower school attendance and higher unemployment for the heated tobacco users.56

A cross-sectional survey found that infants of women who used heated tobacco products during pregnancy had twice the prevalence of allergies, such as asthma, rhinitis (nasal inflammation), conjunctivitis (eye inflammation) or dermatitis (skin rash).57 The same authors found that prevalence of heated tobacco use in pregnant women was as high as 10%, with many being former smokers.58 Lower birthweight and higher prevalence of hypertensive disorders of pregnancy were found for heated tobacco users. Again, this cross-sectional data needs to be confirmed in longitudinal studies that adjust for potential confounding variables such as history of smoking.58

18B.6.7 Possible liver toxicity with use of heated tobacco products

A study of rats exposed to heated tobacco emissions has shown abnormalities in their livers.59 In this study, rats were exposed to IQOS emissions five days a week for four weeks, at the rate of four sticks per day. This exposure resulted in changes to the rat liver consistent with impaired liver function.59 Signs of liver toxicity are also found in human studies. An analysis of the data from human studies provided by Philip Morris International (PMI) in their application to the FDA to market IQOS found some evidence of liver toxicity.60 These data came from preclinical studies conducted by PMI and clinical studies of five and 90 days of exposure to IQOS and IQOS menthol. The results of these trials indicate increases in levels of toxicity in users of IQOS compared to conventional cigarette smokers and non-smokers.60 PMI dispute this finding.61

18B.6.8 Other possible health effects of heated tobacco products

A cross-sectional study in Japan found that exclusive heated tobacco users have a higher odds of having prediabetes and diabetes compared to never smokers. The strength of association for heated tobacco users were comparable to that for people who smoke cigarettes. Prospective studies are needed to determine whether heated tobacco use could be causing diabetes.62

A cross-sectional study from South Korea found an association between use of heated tobacco plus exposure to secondhand cigarette smoke with suicidal ideation, suicidal plans and suicide attempts. However, current use of heated tobacco products was not associated with these suicidal effects.63

Results from a Japanese study of firefighters showed that use of heated tobacco products was associated with a reduction in the amount of secreted saliva. These people also had reduced secretion of two salivary enzymes that have anti-microbial activity. These results indicate that use of heated tobacco may lead to abnormalities in the saliva.64

A case study from the Ukraine described a patient with an oral condition called verrucous leukoplakia of the red border, which arose soon after use of IQOS.65

18B.6.9 Health effects of exposure to secondhand emissions from heated tobacco products

Heated tobacco products are a weaker indoor pollution source than conventional cigarettes (see InDepth 18B.5.5); however, the magnitude of their health impacts on bystanders is not well understood. To date, the studies conducted in humans have used a cross-sectional design, meaning that no conclusions regarding causation can be made.

Numerous studies demonstrate that some toxic components increased above background air levels with the use of heated tobacco products, but much higher increases in these toxic components occurring followed the use of conventional cigarettes (see InDepth 18B.5.5).10, 19, 20, 66-69 These secondhand emissions from heated tobacco can be inhaled by people who are in the vicinity of these products during use, potentially contributing to health effects. Two independent studies concluded that despite emissions being lower than from combustible cigarettes, exposure to dangerous fine particles when heated tobacco products are used indoors does occur, and, likely, a high proportion of the inhaled particles from second hand smoke reaches the alveoli of bystanders, deep in their lungs.70, 71

Research conducted in Japan found that among never smokers who had been exposed to secondhand heated tobacco emissions, nearly half reported at least one acute symptom, although these symptoms were not severe.72 A study assessed the short-term symptoms arising after exposure to secondhand emissions from heated tobacco.73 This cross-sectional data came from an internet-based survey of 11,000 people in Japan. Of those exposed to secondhand cigarette smoke, 57% reported one or more symptoms (sore throat, cough, asthma attack, chest pain, eye pain, nausea, headache or other) compared with 39% of those exposed to secondhand heated tobacco emissions. Nausea was the most commonly reported symptom.73 In this study, the participants were a mix of non-smokers, smokers and heated tobacco users. A similar survey found that exposure to secondhand heated tobacco emissions was associated with respiratory symptoms.74 Non-smokers exposed to these emissions had a 1.49-fold increased risk of asthma or asthma-like symptoms and 1.44-fold increased risk of persistent cough, compared to unexposed people. This data is cross-sectional; therefore, it could not be concluded that heated tobacco exposure caused these effects. However, this study is part of a larger longitudinal study that will provide these results in time.74

18B.6.10 Safety issues with use of heated tobacco products

One safety issue of heated tobacco products is unintended exposure to the tobacco sticks through ingestion of these products, such as by young children. Unlike cigarettes, some of the tobacco sticks for IQOS have small metal components used for heating, which may constitute an additional risk if ingested.

A study of calls to a toxicological information centre in Czechia (between 2012 and 2018) reported nine calls regarding exposure to the refills of heated tobacco products and noted that they contained 5 milligrams of nicotine. Unfortunately, the exposure route and adverse effects from these exposures were indiscernible from the report.75

A case study from Japan detailed the experience of a seven-year-old who ingested a tobacco stick made by Philip Morris. Surgery was required to remove a sharp metal micro-blade from her small intestine.76 Metal micro-blades from tobacco sticks were also ingested by a 10-month old and an 18-month old from Italy.77

A case report from Japan details the experience of a man who ingested eight tobacco stick refills for a heated tobacco product.78 He was treated by gastric lavage (stomach pumping) to remove the undigested tobacco, with an estimated 100 mg of nicotine. 

Relevant news and research

For recent news items and research on this topic, click here(Last updated May 2024)

References

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