The science of flavour in tobacco products

6.1. Introduction

Most conventional, traditional and new or emerging tobacco products, including cigarettes, cigars, cigarillos, smokeless tobacco products (including snus), waterpipe tobacco and e-cigarettes with nicotine (also known as electronic nicotine delivery systems – ENDS) and without nicotine (also known as electronic non-nicotine delivery systems ENNDS) contain flavourings. Broadly defined, flavour is the sensory experience produced when something is ingested or inhaled through the mouth (1). Tobacco itself imparts a flavour (e.g. “natural tobacco” flavour), which depends on the type of tobacco and the curing process (2), and many, if not most, products include added flavours. Some flavourings are derived from natural products, such as cocoa, liquorice, honey and sucrose, while other are created synthetically, such as pyrazines for chocolate flavour and sucralose for sweetness. In the context of tobacco product regulation, flavours that are present at levels that impart a strong non-tobacco smell or taste are considered “characterizing”. While use of the term “characterizing” is much debated and it is not used worldwide, the European Union Tobacco Product Directive (3) defined a characterizing flavour as a:

clearly noticeable smell or taste other than one of tobacco, resulting from an additive or combination of additives, including, but not limited to, fruit, spice, herb, alcohol, candy, menthol or vanilla, which is noticeable before or during the consumption of the tobacco product.

The FDA does not directly define “characterizing flavours” but used the following language in guidance on the flavoured cigarette ban in 2009 (4):

“… a cigarette or any of its component parts (including the tobacco, filter, or paper) from containing as a constituent (including a smoke constituent) or additive, an artificial or natural flavor (other than tobacco or menthol) or an herb or spice, including strawberry, grape, orange, clove, cinnamon, pineapple, vanilla, coconut, liquorice, cocoa, chocolate, cherry, or coffee, that is a characterizing flavor of the tobacco product or tobacco smoke.”

The tobacco industry has introduced flavours into tobacco products to increase the appeal of tobacco products. It is believed that flavours are added to these products to reduce their harshness, increase their appeal and improve their palatability. Further, the display of the names or graphic representations of flavours on packaging and advertising materials may enhance the attractiveness of a product.

We provide here a brief overview of the epidemiology of use of flavoured tobacco and nicotine products worldwide and perceptions of these products. We also discuss technological innovations that have been applied to flavoured products, including how they enhance appeal. We provide a general overview of the sensory processes underlying the perception of flavour, known pharmacological targets for flavour chemicals and evidence on the potential toxicity of flavours. Throughout, implications for research and regulation are highlighted.

6.2. Epidemiology of use of flavoured tobacco and nicotine products

Flavoured tobacco and nicotine products are used throughout the world. While there is limited systematic evidence about the availability and use of these products, preferences and use are often specific to countries and regions. For example, in Indonesia and other south Asian countries, traditional clove cigarettes (kretek), which contain clove pieces, oils and flavours, are highly popular. In India, spiced smokeless tobacco (pan masala, gutka) is used, which contains tobacco mixed with food spices and oils, flavourings, betel nut and other ingredients. Hookah smoking, which originated in India and the Middle East and is now increasingly popular among young people in Europe and north America, involves use of heavily flavoured, sweetened tobacco, known as maassel.

The tobacco industry has long used flavours in tobacco products as a marketing strategy (5), including towards young people (6). For example, in the USA in 2013, the flavoured form of non-cigarette tobacco products comprised 52.3% “cigarette-sized cigars”, 81.3% “cigar wraps” (“blunt wraps”, “tobacco wraps” and “wraps”), 55.1% moist snuff, 86.1% shisha and 81.5% dissolvable tobacco products (e.g. Ariva, Camel Orb/Sticks) (7). A longitudinal study of market trends showed that the presence of flavours accounted for 59.4% of the growth in smokeless tobacco sales between 2005 and 2011 (8). More recently introduced nicotine-containing e-cigarettes are now available in many flavours (9, 10).

Surveys indicate high rates of flavoured tobacco use, although there is little systematic evidence on the use of these products throughout the world. The National Adult Tobacco Survey in the USA in 2013–2014 revealed that an estimated 10.2 million e-cigarette users (68.2%), 6.1 million hookah users (82.3%), 4.1 million cigar smokers (36.2%) and 4.0 million smokeless tobacco users (50.6%) had used flavoured products in the past 30 days (11). The addition of multiple flavours (menthol/mint, clove/spice/herb, fruit, alcohol, candy/chocolate/other sweet flavours) was also assessed. The most prevalent flavours used by type of tobacco product were: smokeless tobacco: menthol/mint (76.9%); hookah: fruit (74.0%); cigars, cigarillos, filtered little cigars: fruit (52.4%), candy, chocolate and other sweet flavours (22.0%) and alcohol (14.5%); e-cigarettes: fruit (44.9%), menthol/mint (43.9%) and candy, chocolate and other sweet flavours (25.7%); and pipes: fruit (56.6%), candy, chocolate and other sweet flavours (26.5%) and menthol/mint (24.8%) (11). In Poland, 26% of female smokers and 10.5% of male smokers reported current use of flavoured cigarettes (menthol, vanilla or other flavour) according to an analysis of data from the Global Adult Tobacco Survey conducted in 2009–2010 (12).

Flavoured tobacco products are very popular among young people (13–15). In a nationally representative sample of Canadian young people who used a variety of tobacco products (cigarettes, pipes, cigars, cigarillos, bidis, smokeless tobacco, hookah, blunts, roll-your-own cigarettes), 52% reported using flavoured products (16). Similarly, evidence from a national survey conducted in Poland showed that younger smokers were more likely to use flavoured cigarettes (12). Evidence from the Population Assessment of Tobacco Health study (15), a longitudinal national survey conducted in the USA, indicated that use of flavoured tobacco products was highest (80%) among children aged 12–17 years, 73% among tobacco users aged 18–24 years and lowest in users aged ≥ 65 years (29%). Most of the children (81%) and young adults (86%) and only 54% of adults aged ≥ 25 years reported that their first product had been flavoured. Furthermore, first use of a flavoured tobacco product was associated with a higher prevalence of current tobacco use among young people and adults.

Summary: future regulations on flavoured products should consider the significant differences in the availability (marketing and access) and use of flavoured tobacco by country and by demographic group. Unfortunately, current surveillance tools may be inadequate for monitoring use of these products. For example, the Global Youth Tobacco Survey (17), an important global tool for monitoring tobacco use by young people, does not request information specifically about flavoured tobacco use. In the Global Adult Tobacco Survey (18), use of flavoured and unflavoured tobacco is investigated only for waterpipe tobacco, and information about flavoured cigarettes can be obtained only by analysing text responses about the brand of cigarette smoked. To address this information gap, additional questions about flavoured and unflavoured products could be added to iterations of these surveys. Surveillance tools should also assess different use of flavours. Given that menthol is often regulated separately from other flavours, it would be advisable that questions distinguish menthol or mint from other flavours.

6.3. Flavoured products: perceptions, experimentation, uptake and regulation

There is a general perception that flavoured tobacco products are less harmful than other tobacco products (15, 19–21). Favourable perceptions of flavoured tobacco and nicotine products were recorded among both users and non-users of a wide range of products (e.g. cigars, e-cigarettes, hookah, kreteks, bidis and smokeless tobacco) (22). Flavoured non-menthol tobacco products (hookahs, little cigars and cigarillos, e-cigarettes) were perceived to be less harmful than cigarettes (20).

Perhaps not surprisingly, the presence of flavours in tobacco and nicotine products is associated with greater willingness to experiment with these products (20, 23, 24), an important consideration for young people. The availability of flavours has been associated with initiation of use of a variety of tobacco products, including hookah, e-cigarettes and cigars (25–27). The presence of flavours may also promote a move from experimentation to regular use; the presence of more flavours in e-cigarettes was associated with greater frequency of e-cigarette use among adolescents but not among adults (28). Further, advertising for sweet and fruit flavours was shown to activate brain reward areas in young adults and to interfere with recall of health warnings (29). For example, adolescents in the USA who had tried flavoured tobacco were almost three times more likely to be current cigarette smokers than those who had not tried these products (30), and more than 80% of current tobacco or nicotine users reported that they had first used a flavoured product (15).

In order to reduce appeal, experimentation and uptake, many countries have regulated flavoured tobacco products, as summarized by the Tobacco Legal Control Consortium (31). Some countries ban cigarettes with characterizing flavours, other than menthol (for example in European Union countries), while others have extended the ban to flavours in other tobacco products, e.g. the USA, Canada (little cigars, blunt wraps) and Ethiopia (all products). Several countries have enacted legislation also banning menthol as a flavour additive in cigarettes and other tobacco products. For example, Turkey has banned the addition of menthol at any level and of any menthol derivatives (e.g. mint); and Canada has finalized a ban on the addition of any menthol in cigarettes, blunt wraps and most cigars sold on the Canadian market. Canada has also banned the use of any promotional materials, including packaging that depicts the e-liquid containing confectionery, desserts, cannabis, soft drinks or energy drink flavours.

Summary: both the presence of specific flavours in tobacco and nicotine products and the presence of flavour descriptors on packaging and in advertising have been linked to the appeal and uptake of tobacco and nicotine products, particularly among young people. Given these associations, many countries have regulated flavoured tobacco products. In view of differences in the timing and specificities of regulations in different countries and local ordinances, there is an opportunity for surveillance research (for example, within the International Tobacco Control project or other surveillance systems) to study the impact of regulations on the uptake of tobacco by youth, tobacco sales and use patterns and the subsequent response from the tobacco industry to the regulations.

6.4. A brief history of the development of flavoured tobacco by the tobacco and e-cigarette industry

The tobacco industry has been at the forefront in integrating flavour science and technology to increase product appeal and marketability. An early example is the addition of saccharin to chewing tobacco in the 1890s by the Reynolds Tobacco Company. This high-potency artificial sweetener replaced the more expensive sugar and increased the product’s shelf life and uniformity. The industry continued to improve tobacco breeding, selection, curing and manufacturing methods to control the harshness of tobacco smoke, added fillers, casings, humectants (moisteners) and designed wrapper papers and filter systems to improve appeal and the uniformity of flavour delivery.

For decades, tobacco companies have been the major consumers of cocoa and liquorice on the world market. Both are added to cigarette tobacco as casings, not to dominate the flavour experience but to increase taste fullness and reduce the harshness of smoke. In contrast, menthol in menthol cigarettes is a characterizing flavour, an added non-tobacco flavour listed on the product label, which dominates the flavour experience (32). Menthol cigarettes were first marketed in the USA in the 1920s, and they remain popular. Many cigarettes that are not labelled as mentholated may also contain low levels (33), which may be sufficient to enhance the appeal of the product (34).

While most early products contained natural flavours, including menthol extracted from mint, fruit extracts and natural terpenes and aldehydes, the increasing demand of the tobacco industry for standardized flavourings and the limited supply from natural sources prompted suppliers to develop and optimize chemical synthetic processes to deliver bulk amounts of key flavourings. For example, most of today’s menthol supply is produced by three major chemical companies that developed procedures for stereo-selective synthesis or purification of L-menthol, the minty, cooling form of menthol (35). Similarly, chemicals in non-menthol products, including vanillin (vanilla flavour), pyrazines (coffee and chocolate flavourings), aldehydes such as benzaldehyde (a berry and candy flavouring) and many other tobacco flavourings are chemically synthesized, often from petrochemical hydrocarbon precursors (35). Modern flavoured tobacco products contain finely tuned mixtures of purified and recombined flavourings to create characterizing flavours, which are marketed after exhaustive testing by industry flavour panels and consumer volunteers.

Flavourings are usually added to tobacco products in the tobacco casing, sprayed on tobacco in humectants, in the filter and in the foil liner of tobacco packaging. The tobacco and flavour industries continue to introduce new flavours and flavour delivery systems to diversify products and increase their appeal. For example, the introduction of flavour capsules within the filter has resulted in a new category of cigarettes that release bursts of flavour when the filter is pressed. Cigarettes with a menthol capsule were first introduced in 2007 in Japan, then in 2008 in Europe and the USA and in 2011–2012 in Australia and Mexico (36). Most capsules in products contain menthol, but they may also contain aldehydes or other flavour chemicals to create flavours like spearmint, lemon mint, apple mint and strawberry mint (37). Some brands contain two flavour capsules, one containing menthol and the other a tangy, fruity flavour or more menthol. The capsules can be crushed individually, giving the user control over the dual flavour experience. The presence of flavour capsules was shown to enhance the appeal of cigarettes to young people (37).

After the ban on cigarettes with characterizing flavours (except for mentholated products) in some countries, the industry quickly developed alternative flavoured products, such as small cigars, some of which share the basic design of cigarettes and have tobacco in the wrapping paper. Flavoured small cigars are highly popular among young people. Patents filed by the tobacco industry describe innovative techniques for the application and enrichment of flavourings, specifically sweeteners, to cigar wrapping papers and mouthpieces to ensure that the product is perceived as sweet. In one study, high levels of saccharin and other synthetic high-intensity sweeteners were found in many popular small cigars or cigarillos on the United States market. Saccharin levels were especially high in the mouth sections and tips of the small cigars, with a sweetness intensity exceeding that of sugar (38). Small cigars of all flavour categories, regardless of whether they were labelled as sweet, contained saccharin (39, 40).

Tobacco industry patents also describe the use of recombinant, sweet taste-stimulating proteins like thaumatin, which is 2000 times sweeter than table sugar, as sweeteners and of synthetic menthol derivatives as innovative cooling agents. After the ban on menthol cigarettes in Canada, the tobacco industry began marketing cigarettes without menthol in packaging with designs almost identical to those of previously marketed menthol cigarettes, signalling the same cool freshness (41). It is unclear whether these cigarettes contain cooling additives to replace menthol. Many of the smokeless tobacco products found in Asia (e.g. zarda, quiwam, gutkha, khaini) contain flavour chemicals (42, 43). Novel smokeless tobacco products have also been introduced in several countries, including snus (previously marketed only in Sweden) and new varieties of moist snuff. Snus and snuff are sold in many flavours, including menthol/mint, cherry, vanilla and strawberry, and it has been suggested that the significant rise in sales of moist snuff is related to the introduction of flavours (8, 44). Newly marketed snus products have also been found to contain very high levels of sucralose (Splenda^®), a synthetic high-intensity sweetener that tastes more like sugar than saccharin, which is still used in snuff (45).

Flavoured waterpipe tobacco (maassel), is a sweetened, flavoured form of tobacco manufactured by fermentation of tobacco with molasses, glycerol and fruit essence. It is the preferred form of tobacco used in waterpipes, especially by adolescents and young adults (46).

E-cigarettes and ENDS, which appeared on the market in 2004, in Europe in 2006 and in the USA in 2007, are available in an ever-expanding range of e-liquid flavours, and the customized flavour and nicotine combinations are attractive to users. These products electrically heat and vaporize e-liquids and are available in a variety of devices, including cigarette-like products, vape or hookah pens, advanced devices known as “mods” or personal vaporizers and more discrete pod-devices like JUUL. In 2013–2014, 466 brands of e-cigarette were available online, with over 7000 unique flavour names; 242 new flavours were added each month (9). By 2016–2017, the number had doubled to over 15 000 flavours and flavour combinations (10). The counterbalancing effects of flavour options on promoting a switch from combustibles to e-cigarettes or ENDS against increasing the risk for uptake among young people is a hotly debated topic.

Summary: the tobacco and now the e-cigarette industry is constantly introducing innovative additives, such as flavourings and sweeteners, to increase the appeal of tobacco products, including waterpipes, smokeless tobacco, e-cigarettes and ENDS. Regulatory surveillance to detect and follow such product manipulations is critical to curtail the appeal of tobacco products.

6.5. Sensory systems that contribute to flavour

To understand the appeal of flavours in tobacco products, it is important to understand the role of the sensory components that contribute to the experience of flavour. The senses of taste and smell (olfaction) play the largest role in flavour perception; however, flavour also includes sensations of temperature, touch and chemaesthesis (i.e. sensations that are produced by chemical stimulation of the senses of temperature, touch and pain) (47).

Taste: the sense of taste derives from taste buds located on the tongue and soft palate, which provide the sensations of sweetness, saltiness, sourness, bitterness and savoury. Because of the bitter taste of nicotine (48), bitterness is a dominant quality of the flavour of tobacco. The addition of flavours to tobacco products may serve to mask the bitter taste and improve flavour and appeal.

Olfaction: the sense of smell provides information not only about odours in the environment (orthonasal olfaction) but also about odours emanating from the mouth and airways (retronasal olfaction), which contribute significantly to the flavour of tobacco products. An opening at the rear of the nasal cavity that is connected to the back of the oral cavity (49, 50) allows odours from products that are taken into or inhaled through the mouth to stimulate olfactory receptors during exhalation.

Temperature: temperature can contribute to the flavour of tobacco in at least two ways: directly, via sensations of warmth and heat produced by combustible or heated tobacco products, and indirectly, by modulating the rate of release of volatile flavour molecules that are sensed by retronasal olfaction.

Touch: in tobacco smoking, touch provides the oral “feel” of cigarettes, cigars, pipes and mouthpieces during smoking or vaping as well as the texture of smokeless tobacco products in the mouth. Touch also senses changes in oral mucosal surfaces such as dryness and astringency (51) that can be caused by inhaled or oral tobacco products.

Chemaesthesis: in addition to evoking tastes and smells, some chemicals can produce sensations of temperature, touch or pain by stimulating receptors in the mucous membranes that normally respond to either weak or strong (noxious) mechanical or thermal stimulation (47). Chemaesthesis plays a key role in the flavour of tobacco products, including the harshness of nicotine, acrolein and other chemical irritants in tobacco smoke and the coolness and “burning” cold sensations of menthol.

Interactive effects of flavour: a defining characteristic of flavour is integration of its multisensory components into coherent perceptions in the mouth. A particularly important interaction is the referral of retronasal odours to the mouth (52, 53), which leads to mislabelling of odours as tastes, most commonly for odours that have taste-like qualities, such as “sweet” odours like vanilla, cherry and strawberry (54). This is important, because it means that characterizing flavours often emerge as a seamless combination of sensations evoked by multiple, interacting sensory systems.

Flavour constituents of tobacco and e-cigarette products can also be important for their masking or inhibitory effects, such as masking a bitter taste by a sweet taste (55). Some studies have found evidence that sweeteners also suppress pain, particularly in infants (56, 57). Sweeteners are present in smokeless tobacco products, for example, at levels that exceed those in confectionery products (45). Patents filed by the tobacco industry describe procedures for adding artificial sweeteners to cigar wrappings and mouthpieces to ensure that the consumer perceives the product as sweet. Similarly, the appeal of mentholated products owes much to the appeal of their cool, minty flavour, but menthol also has analgesic effects that can reduce the sensory irritation and harshness of nicotine (34, 58) and other constituents of tobacco smoke (59) and smokeless tobacco products (58, 60, 61).

Summary: the multimodal, integrative characteristics of flavour make it an important contributor to the appeal of tobacco products, ranging from essential tactile and thermal qualities in the mouth and throat to both taste and olfactory constituents in chemically derived characterizing flavours. While regulating individual well-known flavouring ingredients such as menthol and artificial sweeteners could have a straightforward effect on the appeal of tobacco products, interactions among flavour constituents designed to heighten appeal through combined sweetness or mechanisms like masking and analgesia pose more difficult problems for designing regulatory strategies. As flavour perception integrates sensory experience and is subjective, both human sensory testing and chemical analysis will be required to identify “the concentrations above which an additive will impart a characterizing flavor” (3) or increase the appeal of a product by masking aversive tastes or sensations. For products in which the flavour is perceptible but ambiguous, labelling may serve to boost the perception and identification of the flavour.

6.6. Flavour receptors: a new science of flavour sensing and coding

Molecular, genetic, pharmacological and behavioural approaches have revolutionized flavour research, including the discovery of flavouring receptors. Olfactory receptors, also called odorant receptors, were identified first in nerve endings in the nasal olfactory epithelium. These receptors play a dominant role in the retronasal sensing of volatile flavourings in tobacco and nicotine products. Taste receptors were identified in the taste papillae of the tongue and palate. Humans have a single sweet taste receptor made up of two protein subunits (TAS1R2 and TAS1R3) that bind sugars such as sucrose (table sugar) and, with much greater affinity, artificial high-potency sweeteners, such as saccharin and sucralose. Bitter taste receptors, the TAS2R receptors, of which humans express 38 different versions, signal the presence of potentially poisonous chemicals and are probably involved in the perception of nicotine and other tobacco alkaloids as bitter. The presence of polymorphisms of the gene encoding a human bitter receptor, TAS2R38, has been linked with menthol cigarette smoking, suggesting perhaps that smokers who are more sensitive to bitter tastes may use menthol to mask the bitter taste of nicotine or cigarette smoke (62, 63).

Receptors that mediate the chemaesthetic properties of flavours and other tobacco constituents, the transient receptor potential (TRP) ion channels, are located on nerves that transmit noxious and innocuous chemical, mechanical and thermal stimuli from the oral and nasal passages and airways. TRPA1 is the receptor for noxious aldehydes in tobacco smoke, eliciting burning and irritating sensations. TRPA1 also mediates the irritating effects of nicotine and flavouring aldehydes such as cinnamaldehyde and benzaldehyde, present in many fruity flavours. TRPM8 is the receptor for menthol and mediates its cooling and soothing effects. Experiments in mice indicated that TRPM8 is essential for the suppression of the irritating and aversive effects of tobacco smoke and nicotine by menthol (60, 64).

Summary: with more knowledge about flavour receptors and their pharmacology, the flavour industry can use molecular and pharmacological approaches to develop new, highly optimized flavour receptor modulators. These include novel sweet taste enhancers, bitter blockers (to reduce bitter taste), savoury (non-glutamate) taste enhancers and novel cooling agents. Several are approved as food additives, and more are in development. The tobacco industry has experimented with synthetic cooling agents that activate the menthol receptor, TRPM8, with a less minty odour, reduced irritancy and greater stability. The identification of flavouring receptors may provide an opportunity to regulate flavourings on the basis of their receptor-mediated pharmacological and behavioural effects in humans and animal model systems. For example, instead of regulating an individual flavour, such as menthol, which can be substituted quickly by alternative cooling agents, regulators could decide instead to control all TRPM8 receptor agonists in tobacco as a receptor-specific flavouring class.

6.7. Toxicological effects of flavours

While legislation and regulations vary by country, in many, inclusion of flavours as food additives requires scientific premarket review. In the European Union, flavouring additives are regulated by the European Food Safety Authority. In the USA, the FDA has designated the generally recognized as safe (GRAS) classification for food additives, in which stakeholders submit data on safety, which is reviewed for the intended use of a flavouring. The GRAS declaration for use of a flavour in confectionery products does not, however, automatically apply to its use in tobacco products, especially products that are inhaled, including cigarettes, cigars, hookah and electronic cigarettes. For example, cinnamaldehyde, the GRAS cinnamon flavouring widely used in baked goods and confectionaries, is added at very high concentrations to some electronic cigarette fluids (65). In toxicological studies, vapours from these liquids damaged lung epithelial cells and caused pulmonary inflammation in mice (66). Other sweet flavours, including characterizing banana and cherry flavours, were also found to damage cells and expose e-cigarette users to benzaldehyde, a key component of many berry flavour mixes, with known toxic effects on the respiratory system (67, 68). Diacetyl, a flavour chemical commonly found in buttery flavours, also has a well-known toxic effect on respiration (69, 70). Flavour chemicals can react with solvents and other components of e-liquids to form irritant compounds with unknown toxicological effects (71).

Despite these concerns, some manufacturers of e-cigarette and ENDS have used GRAS labelling in their advertising, implying that the flavourings in their liquids are safe because they were previously approved for addition to food. Such health claims were strongly refuted by the Flavor and Extracts Manufacturing Association, a body of the United States flavour industry that submitted GRAS applications to the FDA, which stated that use of flavouring in e-cigarettes is not considered an intended use (72).

The lack of a regulatory process for evaluating the safety of flavouring agents is also a limitation for tobacco products such as snus, snuff and flavoured cigars, cigarettes and hookah tobacco, which may result in ingestion or inhalation of toxic levels of flavourings situations by consumers. For example, analytical studies showed that wintergreen-flavoured snuff products can expose regular users to levels of the wintergreen flavouring, methyl salicylate, that exceed the acceptable daily intake determined by the Food and Agriculture Organization of the United Nations and WHO for food by 12 times (73). Smokeless tobacco products (including zarda, quiwam, gutka and khaini varieties) have been found to have high levels of flavour chemicals such as eugenol, coumarin, camphor and diphenyl ether (43). Some snus products contain such high levels of sweeteners that regular use might exceed the recommended daily consumption of sugar if users consume other sweetened products at the same time (45).

There is little information about the fate of flavourings in combusted tobacco products (cigarettes, cigars, hookah) or heated nicotine solutions (as in e-cigarettes). The tobacco industry reported no major differences in the levels of toxic constituents in the smoke of menthol capsules or kretek (clove) cigarettes and in equivalent cigarettes without flavouring (74, 75); however, any toxic effects of flavours may have been masked by the overwhelming contributions of the other toxic constituents of cigarettes. In other studies, increased levels of VOCs were found in the smoke of flavoured cigarettes, and industry documents provide evidence that the industry knew about the carcinogenicity of some types of flavoured cigarettes (76, 77). In these studies, only the main smoke constituents (such as TSNAs and PAHs) were measured; the specific chemical products resulting from combusted flavourings were not examined. Analysis of the chemical fate of e-cigarette flavourings may provide information on the toxicity of flavours. When high-voltage settings are used in e-cigarettes, exposure to flavourings increases, and the levels of oxidation products such as formaldehyde exceed toxic levels. As cigarettes, cigars and hookah tobacco burn at higher temperatures than vapour-producing e-cigarettes, the possibility that larger amounts of flavouring oxidation products and other toxic chemical species may be formed is a concern. Evidence obtained for e-liquid flavours suggests that flavour chemicals can have toxic effects (65, 78, 79).

Summary: regulations to specify acceptable levels of flavourings depend on the type of tobacco product, the level at which the flavouring is delivered to the consumer’s oral and respiratory systems and the potential for chemical changes during storage, heating and combustion. The chemical fate of flavourings, especially when heated at high temperatures, should be investigated further. This may result in the addition of flavourings and their chemical products to the lists of HPHCs curated by national regulators such as the FDA and in TobReg reports on toxicants in tobacco products. Future regulation of tobacco products might require specific reporting of the levels and toxicity of flavour chemicals.

6.8. Conclusions

Critical questions remain about the role of flavours in the appeal of and addiction to tobacco and nicotine products. Surveillance should be conducted worldwide to assess the use of flavoured tobacco products and also perceptions about the appeal and addictive potential of flavoured and unflavoured products. Flavours and sweeteners are chemicals that can be appealing independently and can also increase the use of tobacco products by enhancing the palatability of nicotine and other bitter or harsh constituents. A flavour like menthol may do this by pharmacologically attenuating the aversive effects of exposure to nicotine (e.g. cough, harshness, heat), and the presence of menthol in cigarettes is probably associated with increased rates of initiation of and progression to regular cigarette smoking, development of addiction and difficulty in quitting smoking (80). Much less is known about whether and how other flavour constituents influence preferences for and use of tobacco and nicotine products.

As flavours are complex and subjective, testing of flavoured tobacco and nicotine products for their appeal will require human behavioural and toxicological evaluations, in combination with chemical analyses. Methods for determining the presence and levels of flavourings should be based on what is delivered to the consumer (e.g. in smoke or vapour) and should also be used to determine potential changes in flavourings during storage, heating and combustion. Both the appeal and toxicity of flavourings should be evaluated. While it is important to determine the optimal doses of flavours that produce these effects, it is also important to understand the influence of the concentrations of flavours. All this information should be used to further refine the definition of a “characterizing flavour”.

Surveillance and testing methods will have to keep up with the constant innovations of the tobacco industry designed to enhance the appeal of flavoured tobacco products, including use of new synthetic compounds and strategic placement of flavouring molecules in tobacco products. Declaration of flavourings and their concentrations on tobacco product labels should be considered. Additionally, regulatory work will have to contend with alternative marketing strategies introduced by the tobacco industry to deal with regulations on flavours, such as manipulation of packaging to continue to convey brand features associated with flavours (41).

Future regulations should account for the possibility that some flavours and flavour constituents, like sweeteners, are also positively reinforcing in themselves and, when combined with nicotine, might enhance the rewarding effects of low-dose nicotine and promote a transition to higher levels of nicotine, leading to addiction. Experimental evidence and monitoring of these complex issues will be crucial to ensure that regulations are designed to reduce the appeal and addictive potential of tobacco products. Better understanding of the science of flavours and how they enhance the appeal and addictive potential of tobacco products will be required to regulate these molecules.

6.8.1. Recommended priorities for research

• Systematically monitor the global epidemiology of flavoured conventional, traditional, new and emerging tobacco and nicotine products.

• Identify flavour chemicals, their reaction products and their concentrations in tobacco and nicotine products and in aerosols, vapours and smoke.

• Determine how depiction of flavours on product packaging and in marketing alter public perceptions and the appeal of tobacco and nicotine products, especially among young people.

• Evaluate whether the presence of specific flavours and their concentrations in tobacco and nicotine products alters their appeal and abuse potential.

• Among smokers, investigate the role of the availability of flavoured products as a motive for switching to less harmful tobacco products (relative to the degree of harm reduction).

• Determine the toxicity and health effects of various concentrations of inhaled flavour chemicals and their metabolites and adducts.

• Monitor the use of alternative chemical moieties to replace prohibited flavours, and determine their appeal, toxicity and health effects.

6.8.2. Recommended policies

• Consider obtaining systematic global evidence on the use of flavoured tobacco and e-cigarette and ENDS products.

• Consider banning the use of flavours, including menthol, in harmful combusted products.

• Consider limiting the levels, number of and/or specific flavours allowed in tobacco and nicotine products for which there is evidence of modified or reduced risk, to reduce initiation by young people and support cessation of use of combusted tobacco products.

• Consider requiring that the types and concentrations of flavour chemicals in various products be listed among the product constituents.