Flavouring substances in e-cigarettes: updated assessment of safrole, sucralose and menthol

1 Subject of the assessment

In the present reassessment, the BfRshort forGerman Federal Institute for Risk Assessment examined whether there is new scientific evidence on the flavouring substances menthol, safrole and sucralose with regard to their use in e-cigarettes.

2 Results

1. Safrole

The substance 5-allylbenzo[1,3]dioxole (safrole), CAS No. 94-59-7 is harmonised under the CLP Regulation as a category 2 mutagenic substance and a category 1B carcinogenic substance and is therefore prohibited in e-cigarettes and refill containers in accordance with Annex 2 point 4. a) of the German Tobacco Products Ordinance.

2. Sucralose

In its 2019 opinion on the sweetener sucralose in foodstuffs, the BfRshort forGerman Federal Institute for Risk Assessment already pointed out that the substance decomposes at temperatures above 120°C and forms harmful chlorine compounds such as chloropropanoles [1].

There are now also studies that show decomposition in the liquid when heated in an e-cigarette [2,3]. The formation of chloropropanole derivatives was shown here, for example. In the study, the number of puffs had a greater influence on the formation of chlorinated components than the influence of temperature at operating temperatures of over 200 °Cshort fordegrees Celsius. In another study, it was found that the formation of aldehydes such as propanal, acetaldehyde, glycolaldehyde and acrolein as well as formaldehyde hemiacetals, which can release formaldehyde, increases when an e-liquid containing sucralose (0.24% w/w or more) is vaporised [4].

It should be noted that in one study, the tested concentrations of sucralose (1–7% w/w) were higher than the concentrations in commercially available liquids of 0.1–0.5% w/w [5]. However, sucralose is also used by consumers themselves as a “do-it-yourself” sweetener.

3. Menthol

Menthol is a frequently used flavour in liquids. It not only occurs in menthol-flavoured liquids, but is also contained in low concentrations in many other commercially available liquids to round off the flavour. Due to activation of thermosensitive receptors, menthol has a cooling effect in the region of the tongue and oral cavity[6-8]. It also has a local anaesthetic effect, as it blocks pain receptors [7]. The effects can alleviate irritation in the oral cavity and throat. In animal experiments, for example, reduced defence reactions against irritating components of tobacco smoke were found, which were mediated by the cold receptor TRPM8 [9]. Activation of the TRPM8 receptor is the central physiological mechanism of action [10]. In sensitive people, menthol can also suppress the cough stimulus triggered by certain chemicals such as capsaicin [11].

A study from 2016 shows that menthol alleviates the irritating sensory effects of liquids with high nicotine content [12]. Although there is currently a lack of studies that would prove increased inhalation or nicotine uptake when vaping e-cigarettes containing menthol, the existing data suggests that menthol and other TRPM8-activating substances make it easier to start vaping, even with e-cigarettes with high nicotine levels.

There is also current evidence that menthol in liquids leads to an increased release of micro- and submicron particles when consuming e-cigarettes. This is associated with poorer lung function in smokers who use tobacco and e-cigarettes at the same time (dual use) [13].

Menthol is also contained in medicines and numerous other products that are considered to be beneficial to health. There are a large number of menthol-containing medicines on the market that are recommended for inhalative treatment of colds. These products claim to have properties such as eliciting relaxation, facilitating coughing, and providing relief. Thus, the impression that menthol has health benefits may also be created when using liquids containing menthol.

Despite current studies on reduced health hazards of e-cigarettes compared to conventional tobacco cigarettes and the described assistance in quitting smoking [14,15], the protection of minors is an important aspect, especially with regard to fruity flavourings and those with a menthol taste. There is evidence that menthol, even in very low concentrations, can increase the attractiveness of e-cigarettes to adolescents [16]. For example, a study from 2022 shows widespread use of menthol and fruit-flavoured e-cigarettes among adolescents and young adults in the United States [17].

This should be viewed particularly critically, as the increased attractiveness could encourage continued consumption and the transition to higher, addictive nicotine levels. This is particularly true in combination with higher menthol concentrations, as found in commercial liquids.

3 References

[1] BfRshort forGerman Federal Institute for Risk Assessment Süßstoff Sucralose: Beim Erhitzen von Lebensmitteln können gesundheitsschädliche Verbindungen entstehen. www.bfr.bund.de/cm/343/suessstoff-sucralose- beim-erhitzen-von-lebensmitteln-koennen-gesundheitsschaedliche-verbindungen- entstehen.pdf.

[2] El-Hage, Rachel, et al.short foret alii (lat. "and others") "Toxic emissions resulting from sucralose added to electronic cigarette liquids." Aerosol Science and Technology 53.10 (2019): 1197-1203.

[3] Moser, Daniel, et al.short foret alii (lat. "and others") "Quantification and cytotoxicity of degradation products (chloropropanols) in sucralose containing e-liquids with propylene glycol and glycerol as base." Toxicology and Applied Pharmacology 430 (2021): 115727.

[4] Duell, Anna K., et al.short foret alii (lat. "and others") "Sucralose-enhanced degradation of electronic cigarette liquids during vaping." Chemical research in toxicology 32.6 (2019): 1241-1249.

[5] Schlappack, Tobias, et al.short foret alii (lat. "and others") "Ambient mass spectrometry and near-infrared spectroscopy–a direct comparison of methods for the quantification of sucralose in e-liquids." Analytical Methods 15.20 (2023): 2448-2455.

[6] Eccles, R. "Menthol and related cooling compounds." Journal of Pharmacy and Pharmacology 46.8 (1994): 618-630.

[7] Kahnert, S., et al.short foret alii (lat. "and others") "Wirkungen von Menthol als Zusatzstoff in Tabakprodukten und die Notwendigkeit einer Regulierung." Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz 55.3 (2012): 409-415.

[8] Kamatou, Guy PP, et al.short foret alii (lat. "and others") "Menthol: a simple monoterpene with remarkable biological properties." Phytochemistry 96 (2013): 15-25.

[9] Willis, Daniel N., et al.short foret alii (lat. "and others") "Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants." The FASEB Journal 25.12 (2011): 4434.4 / 5© BfRshort forGerman Federal Institute for Risk Assessment | Aromen in E-Zigaretten | Mitteilung vom 4. Dezember 2024

[10] McKemy, David D., Werner M. Neuhausser, and David Julius. "Identification of a cold receptor reveals a general role for TRP channels in thermosensation." Nature 416.6876 (2002): 52-58.

[11] Millqvist, Eva, Ewa Ternesten-Hasséus, and Mats Bende. "Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough." Respiratory medicine 107.3 (2013): 433-438.

[12] Rosbrook, Kathryn, and Barry G. Green. "Sensory effects of menthol and nicotine in an e-cigarette." Nicotine & Tobacco Research 18.7 (2016): 1588-1595.

[13] Chandra, Divay, et al.short foret alii (lat. "and others") "Electronic cigarette menthol flavoring is associated with increased inhaled micro and sub-micron particles and worse lung function in combustion cigarette smokers." Respiratory Research 24.1 (2023): 1-11.

[14] Yayan, Josef, et al.short foret alii (lat. "and others") "Comparative systematic review on the safety of e-cigarettes and conventional cigarettes." Food and Chemical Toxicology (2024): 114507.

[15] Auer, Reto, et al.short foret alii (lat. "and others") "Electronic Nicotine-Delivery Systems for Smoking Cessation." New England Journal of Medicine 390.7 (2024): 601-610.

[16] Krishnan-Sarin, Suchitra, et al.short foret alii (lat. "and others") "Studying the interactive effects of menthol and nicotine among youth: an examination using e-cigarettes." Drug and Alcohol Dependence 180 (2017): 193-199.

[17] Chaffee, Benjamin W., et al.short foret alii (lat. "and others") "Preferences, use, and perceived access to flavored e- cigarettes among United States adolescents and young adults." Drug and alcohol dependence reports 3 (2022): 100068.