A Scientific Argument Against the 16-Compound Restrictive List and for Expanded Flavouring

Provisions Including Natural Tobacco Extracts

Submission to the Responsible Regulatory Department of Estonia

Executive Summary

The proposed regulation restricts tobacco-flavoured e-liquid formulations to 16 specified flavouring

compounds. This submission argues on scientific, sensory, and public-health grounds that this list is structurally

incapable of recreating the flavour profile of cured tobacco or tobacco smoke, and that its implementation will

undermine rather than advance smoking cessation objectives.

We argue that firstly, tobacco flavour is an emergent property of thousands of trace constituents. As

Rodgman and Perfetti (2013) documented, tobacco and tobacco smoke contain over 5,500 identified chemical

constituents spanning terpenoids, esters, norisoprenoids, pyrazines, furanones, organic acids, phenolics, lactones,

and Maillard reaction products. The sensory experience smokers recognise as 'tobacco' arises from the integrated

contribution of these compounds at trace concentrations not from a handful of synthetic isolates.

Secondly, natural tobacco extracts provide the full authentic flavour spectrum and should be permitted.

Tobacco extracts (NETs) contain the complete volatile and semi-volatile profile of cured tobacco leaf. They are

already used commercially in e-liquids and offer the only viable pathway to a genuinely tobacco-like flavour.

Lastly, such restrictive ingredient list will only hamper our company’s honest goals. ENVA was founded for

one reason: to help people who smoke cigarettes find a realistic alternative they can actually stick with. We know

from years of research and from the experiences of our own customers that the single hardest thing about

switching from combustible cigarettes is the sensory gap. A product that doesn't satisfy what a smoker expects

tobacco to taste like is a product they abandon and when they abandon it, they go back to smoking.

The proposed regulation restricts tobacco flavoured e-liquid formulations to 16 specified flavouring

compounds. This submission argues on scientific, sensory, and public-health grounds that this list is structurally

incapable of recreating the flavour profile of cured tobacco or tobacco smoke, and that its implementation will

undermine rather than advance smoking cessation objectives.

Our recommendation: Expand the permitted list to include natural tobacco extracts and additional

compound classes genuinely present in tobacco (pyrazines, phenolics, maltol, furaneol, vanillin, menthol), with

concentration-based controls rather than follow the misguided restrictive list set precedent by Netherland’s

regulatory body.

We believe our approach aligns with the purpose of Directive 2014/40/EU. The Directive restricts

characterizing flavors because they attract non-users, especially youth. A product that tastes like tobacco is only

relevant to people who already use tobacco; a product that tastes like mango or cotton candy is relevant to

everyone. We want our product to be relevant only to existing adult smokers looking for an alternative. We really

appreciate your time to take into our considerations and are available to answer any questions you may have.

Part 1: The Chemical Architecture of Tobacco Flavour

1.1 The Scale of Tobacco's Chemical Complexity

Tobacco is not a simple botanical. Rodgman & Perfetti's The Chemical Components of Tobacco and Tobacco

Smoke (2nd ed., CRC Press, 2013) documents over 5,500 identified constituents in tobacco and its smoke. These

span a remarkable diversity of chemical classes which can be summarised in the table below:

Chemical Class Representative Compounds Sensory Contribution

Terpenoids & norisoprenoids α-Ionone, β-ionone, damascones,

damascenones, neophytadiene

Floral, fruity, woody, green

Pyrazines 2,6-Dimethylpyrazine,

2-ethyl-5-methylpyrazine,

trimethylpyrazine, acetylpyrazine

Roasted, nutty, toasted, earthy

Phenolics Guaiacol, 4-methylguaiacol,

phenol, cresols, eugenol

Smoky, medicinal, spicy, clove-like

Furanones & pyranones Maltol, ethyl maltol, furaneol,

cyclotene

Sweet, caramel, burnt sugar

Pyridines Pyridine, 3-ethylpyridine,

3-acetylpyridine, nicotyrine

Tobacco-like, burnt, roasted

Organic acids Acetic acid, isovaleric acid,

hexanoic acid

Sour, cheesy, sharp

Amadori compounds Fructose-proline,

fructose-asparagine

Odourless precursors to pyrazines,

furans

Critically, the sensory impact of these compounds is governed not merely by presence but by odour activity

values (OAV) the ratio of concentration to odour threshold. A compound present at parts-per-billion can dominate

the aroma if its threshold is low enough. Guaiacol, for example, has an odour threshold of approximately 0.021

mg/L in water; 2,6-dimethoxyphenol (the phenolic on the permitted list) has a threshold of approximately 1.85

mg/L, approximately 88 times less potent. Replacing guaiacol with 2,6-dimethoxyphenol is not a like-for-like

substitution.

1.2 The Maillard Reaction: The Thermal Engine of Tobacco Aroma

Tobacco flavour does not exist in the raw leaf. It is created through two sequential processes. First, curing and

aging, enzymatic and non-enzymatic reactions between the leaf's sugars (25–50% dry weight), amino acids (12–25%

nitrogenous content), and lipids produce Amadori compounds, Strecker aldehydes, and norisoprenoids. Second,

combustion/pyrolysis at 600–900°C in the burning zone, these precursors undergo Maillard reactions,

caramelisation, and thermal cracking to generate the heterocyclic volatiles (pyrazines, pyridines, furans, phenols)

that define smoke aroma.

Amadori compounds, odourless intermediates accounting for 2–3% of tobacco dry weight, are particularly

important. Their thermal degradation produces 'large amounts of flavour-related products, including aroma-active

aldehydes, ketones, acids, pyrazines, pyridines, and other odorants' (Li et al., 2024). The permitted list contains no

Amadori compounds, no pyrazines, and no Maillard-reaction products.

1.3 The Pyrazine Triad and Roasted Character

Wu et al. (2026), analysing cigar tobacco smoke, identified what they term the 'pyrazine triad'

(methyl-pyrazine, 2,6-dimethyl-pyrazine, and 2-ethyl-5-methyl-pyrazine) as the chemical engine of 'roasted

almond and toasted bread aromas, establishing the dominant charred nutty character.' These compounds exhibit

direct transfer efficiencies of 40–50× from leaf to smoke, meaning they are thermally generated in large quantities

during smoking.

The proposed list contains zero pyrazines. Pyrazines are: naturally present in roasted coffee, chocolate, nuts,

and bread; formed from the Maillard reaction between amino acids and sugars, a reaction central to all heated

food; GRAS flavouring compounds widely used in the food industry; and essential to the 'roasted' and 'nutty'

dimensions of tobacco smoke. Without pyrazines, any e-liquid will lack the roasted, toasted, earthy backbone

that smokers associate with tobacco smoke.

Part 2: The Case for Natural Tobacco Extracts (NETs)

2.1 What NETs Are and How They Work

Natural Extract of Tobacco (NET) e-liquids use cured tobacco leaf that is macerated, steeped, or extracted to

transfer the leaf's native volatile and semi-volatile compounds into the e-liquid base. The extract contains native

compounds such as norisoprenoids, terpenoids, and Maillard products already formed during curing (pyrazines,

furans, pyrroles, Amadori compounds).

The extract provides the integrated, balanced profile that 16 isolated synthetic compounds cannot replicate.

2.2 Why NETs Were Excluded (And Why That Reason Is Insufficient)

The Pennings methodology, the methodology Netherlands regulators based their ingredient list on, excluded

all plant extracts at Criterion 3: 'Flavouring ingredients that are mixtures defined as a distillation or extraction

product from plant material are excluded. The composition of such substances... is not consistent as it depends on

the composition of the plant source material... It is therefore not possible to establish conclusively through

analytical chemical research whether an e-liquid contains a particular extract.'

The concern is that analytical laboratories cannot verify whether an e-liquid contains 'tobacco extract' versus

'cocoa extract' because both are complex mixtures. This problem is solvable through: certificate-of-analysis

requirements (quantifying key marker compounds); nicotine and alkaloid fingerprinting (tobacco extracts contain

characteristic alkaloid profiles); and exclusion of non-tobacco plant extracts (permit only Nicotiana species

extracts).

The analytical challenge should be put onto the manufacturers to prove their case and compliance. When

regulators ban NETs, they force manufacturers to attempt the impossible: recreating a 5,500-compound botanical

profile from 16 synthetic molecules.

Part 3: The Consequence — What Happens When E-Cigarettes Cannot

Satisfy Smokers

3.1 Evidence from Flavour Ban Evaluations

Studies such as Rubenstein et al. (2025) conducted a laboratory choice task with 88 adult dual users. When

the only e-cigarette available was tobacco-flavoured, participants chose combustible cigarettes more often. We

see this problem too often in regions that have banned other flavours. Our goal at ENVA is to recreate authentic

tobacco flavours derived from NETs to hopefully convince users that have would have gone back to combustible

cigarettes to choose the less harmful product.

Our product that is aimed to faithfully recreate the sensation of taste of a tobacco cigarette is only aimed for

adult smokers to present them with a reduced harm alternative that they use on the daily. Such flavours are only

relevant to our target users as they are not attractive to users that are looking for sweet and fruity flavours.

Part 4: A Proposed Science-Based Alternative

The goal of tobacco-flavour regulation should be to permit formulations that provide sensory satisfaction

equivalent to combustible tobacco for adult smokers seeking to switch; do not create distinctively sweet, fruity, or

candy-like flavours that appeal to youth; are based on compounds genuinely present in tobacco or tobacco smoke;

and are manufactured with quality controls and concentration limits.

First, permit natural tobacco extracts. Tobacco extracts derived from Nicotiana tabacum or Nicotiana rustica

should be permitted under standardised conditions.

Second, expand the synthetic compound list to include authentic tobacco constituents. Pyrazines, phenolics,

furanones, vanillin derivatives, pyridines, lactones, and traditional casing ingredients (cocoa, licorice extracts)

should be permitted with concentration caps.

Third, maintain prohibitions on youth-appeal flavours. Fruit-flavour isolates, candy and dessert profiles,

bubblegum, cotton-candy, and high-concentration sweeteners should remain prohibited. Pyrazines and guaiacol

are no more appealing to youth than 3-ethylpyridine or isovaleric acid. In fact, pyrazines and phenolics are harsh,

bitter, and astringent at concentrations that would be used in tobacco e-liquids.

DECLARITION

We respectfully request that the governing body review this submission in accordance with the principles

established in Directive 2014/40/EU and the Estonian Tobacco Act, and we are available to provide any additional

information or clarification that may be required. We are happy to provide samples of our product for your expert

panels to judge whether our products only produce tobacco flavors.

Key Peer-Referenced Citations:

1. European Parliament and the Council of the European Union. Directive 2014/40/EU of the European

Parliament and of the Council of 3 April 2014 on the approximation of the laws, regulations and

administrative provisions of the Member States concerning the manufacture, presentation and sale of

tobacco and related products and repealing Directive 2001/37/EC. European Union. 2014 Apr 29.

https://health.ec.europa.eu/system/files/2016-11/dir_201440_en_0.pdf

2. Rodgman A, Perfetti T. The Chemical Components of Tobacco and Tobacco Smoke, Second Edition. CRC

Press; 2013.

https://www.researchgate.net/publication/294261056_The_Chemical_Components_of_Tobacco_and_To

bacco_Smoke_Second_Edition

3. Li W, et al. The dynamics of microbial community structure and metabolic function in different parts of

cigar tobacco leaves during air-curing. Frontiers in Microbiology; 2024.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11669699/

4. Wu X, et al. Formation and transfer patterns of key aroma compounds in cigar tobacco. Food Bioscience;

2026. https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2026.1755255/full

5. Rubenstein D, et al. Restricting choice of e-cigarette flavor and device type increases choices for

combustible cigarettes. Drug and Alcohol Dependence. 2025;320.

https://pubmed.ncbi.nlm.nih.gov/41343944/

Authorisation and Sign-Off

This submission is prepared by our lab scientist and researcher in response to the public consultation on proposed

restrictions to e-liquid flavouring compounds. The signatory confirms that the information provided herein is

accurate to the best of our knowledge, and that this submission represents our genuine scientific and regulatory

position.

Shenzhen GreenSound High-tech Co., Ltd. 2026-July-28

Signature: Signature:

_______________________________________________ _______________________________________________

Chenbo Wang Jason Tian

Regulatory and Compliance Manager Head of European Market

A Scientific Argument Against the 16-Compound Restrictive List and for Expanded Flavouring

Provisions Including Natural Tobacco Extracts

Submission to the Responsible Regulatory Department of Estonia

Executive Summary

The proposed regulation restricts tobacco-flavoured e-liquid formulations to 16 specified flavouring

compounds. This submission argues on scientific, sensory, and public-health grounds that this list is structurally

incapable of recreating the flavour profile of cured tobacco or tobacco smoke, and that its implementation will

undermine rather than advance smoking cessation objectives.

We argue that firstly, tobacco flavour is an emergent property of thousands of trace constituents. As

Rodgman and Perfetti (2013) documented, tobacco and tobacco smoke contain over 5,500 identified chemical

constituents spanning terpenoids, esters, norisoprenoids, pyrazines, furanones, organic acids, phenolics, lactones,

and Maillard reaction products. The sensory experience smokers recognise as 'tobacco' arises from the integrated

contribution of these compounds at trace concentrations not from a handful of synthetic isolates.

Secondly, natural tobacco extracts provide the full authentic flavour spectrum and should be permitted.

Tobacco extracts (NETs) contain the complete volatile and semi-volatile profile of cured tobacco leaf. They are

already used commercially in e-liquids and offer the only viable pathway to a genuinely tobacco-like flavour.

Lastly, such restrictive ingredient list will only hamper our company’s honest goals. ENVA was founded for

one reason: to help people who smoke cigarettes find a realistic alternative they can actually stick with. We know

from years of research and from the experiences of our own customers that the single hardest thing about

switching from combustible cigarettes is the sensory gap. A product that doesn't satisfy what a smoker expects

tobacco to taste like is a product they abandon and when they abandon it, they go back to smoking.

The proposed regulation restricts tobacco flavoured e-liquid formulations to 16 specified flavouring

compounds. This submission argues on scientific, sensory, and public-health grounds that this list is structurally

incapable of recreating the flavour profile of cured tobacco or tobacco smoke, and that its implementation will

undermine rather than advance smoking cessation objectives.

Our recommendation: Expand the permitted list to include natural tobacco extracts and additional

compound classes genuinely present in tobacco (pyrazines, phenolics, maltol, furaneol, vanillin, menthol), with

concentration-based controls rather than follow the misguided restrictive list set precedent by Netherland’s

regulatory body.

We believe our approach aligns with the purpose of Directive 2014/40/EU. The Directive restricts

characterizing flavors because they attract non-users, especially youth. A product that tastes like tobacco is only

relevant to people who already use tobacco; a product that tastes like mango or cotton candy is relevant to

everyone. We want our product to be relevant only to existing adult smokers looking for an alternative. We really

appreciate your time to take into our considerations and are available to answer any questions you may have.

Part 1: The Chemical Architecture of Tobacco Flavour

1.1 The Scale of Tobacco's Chemical Complexity

Tobacco is not a simple botanical. Rodgman & Perfetti's The Chemical Components of Tobacco and Tobacco

Smoke (2nd ed., CRC Press, 2013) documents over 5,500 identified constituents in tobacco and its smoke. These

span a remarkable diversity of chemical classes which can be summarised in the table below:

Chemical Class Representative Compounds Sensory Contribution

Terpenoids & norisoprenoids α-Ionone, β-ionone, damascones,

damascenones, neophytadiene

Floral, fruity, woody, green

Pyrazines 2,6-Dimethylpyrazine,

2-ethyl-5-methylpyrazine,

trimethylpyrazine, acetylpyrazine

Roasted, nutty, toasted, earthy

Phenolics Guaiacol, 4-methylguaiacol,

phenol, cresols, eugenol

Smoky, medicinal, spicy, clove-like

Furanones & pyranones Maltol, ethyl maltol, furaneol,

cyclotene

Sweet, caramel, burnt sugar

Pyridines Pyridine, 3-ethylpyridine,

3-acetylpyridine, nicotyrine

Tobacco-like, burnt, roasted

Organic acids Acetic acid, isovaleric acid,

hexanoic acid

Sour, cheesy, sharp

Amadori compounds Fructose-proline,

fructose-asparagine

Odourless precursors to pyrazines,

furans

Critically, the sensory impact of these compounds is governed not merely by presence but by odour activity

values (OAV) the ratio of concentration to odour threshold. A compound present at parts-per-billion can dominate

the aroma if its threshold is low enough. Guaiacol, for example, has an odour threshold of approximately 0.021

mg/L in water; 2,6-dimethoxyphenol (the phenolic on the permitted list) has a threshold of approximately 1.85

mg/L, approximately 88 times less potent. Replacing guaiacol with 2,6-dimethoxyphenol is not a like-for-like

substitution.

1.2 The Maillard Reaction: The Thermal Engine of Tobacco Aroma

Tobacco flavour does not exist in the raw leaf. It is created through two sequential processes. First, curing and

aging, enzymatic and non-enzymatic reactions between the leaf's sugars (25–50% dry weight), amino acids (12–25%

nitrogenous content), and lipids produce Amadori compounds, Strecker aldehydes, and norisoprenoids. Second,

combustion/pyrolysis at 600–900°C in the burning zone, these precursors undergo Maillard reactions,

caramelisation, and thermal cracking to generate the heterocyclic volatiles (pyrazines, pyridines, furans, phenols)

that define smoke aroma.

Amadori compounds, odourless intermediates accounting for 2–3% of tobacco dry weight, are particularly

important. Their thermal degradation produces 'large amounts of flavour-related products, including aroma-active

aldehydes, ketones, acids, pyrazines, pyridines, and other odorants' (Li et al., 2024). The permitted list contains no

Amadori compounds, no pyrazines, and no Maillard-reaction products.

1.3 The Pyrazine Triad and Roasted Character

Wu et al. (2026), analysing cigar tobacco smoke, identified what they term the 'pyrazine triad'

(methyl-pyrazine, 2,6-dimethyl-pyrazine, and 2-ethyl-5-methyl-pyrazine) as the chemical engine of 'roasted

almond and toasted bread aromas, establishing the dominant charred nutty character.' These compounds exhibit

direct transfer efficiencies of 40–50× from leaf to smoke, meaning they are thermally generated in large quantities

during smoking.

The proposed list contains zero pyrazines. Pyrazines are: naturally present in roasted coffee, chocolate, nuts,

and bread; formed from the Maillard reaction between amino acids and sugars, a reaction central to all heated

food; GRAS flavouring compounds widely used in the food industry; and essential to the 'roasted' and 'nutty'

dimensions of tobacco smoke. Without pyrazines, any e-liquid will lack the roasted, toasted, earthy backbone

that smokers associate with tobacco smoke.

Part 2: The Case for Natural Tobacco Extracts (NETs)

2.1 What NETs Are and How They Work

Natural Extract of Tobacco (NET) e-liquids use cured tobacco leaf that is macerated, steeped, or extracted to

transfer the leaf's native volatile and semi-volatile compounds into the e-liquid base. The extract contains native

compounds such as norisoprenoids, terpenoids, and Maillard products already formed during curing (pyrazines,

furans, pyrroles, Amadori compounds).

The extract provides the integrated, balanced profile that 16 isolated synthetic compounds cannot replicate.

2.2 Why NETs Were Excluded (And Why That Reason Is Insufficient)

The Pennings methodology, the methodology Netherlands regulators based their ingredient list on, excluded

all plant extracts at Criterion 3: 'Flavouring ingredients that are mixtures defined as a distillation or extraction

product from plant material are excluded. The composition of such substances... is not consistent as it depends on

the composition of the plant source material... It is therefore not possible to establish conclusively through

analytical chemical research whether an e-liquid contains a particular extract.'

The concern is that analytical laboratories cannot verify whether an e-liquid contains 'tobacco extract' versus

'cocoa extract' because both are complex mixtures. This problem is solvable through: certificate-of-analysis

requirements (quantifying key marker compounds); nicotine and alkaloid fingerprinting (tobacco extracts contain

characteristic alkaloid profiles); and exclusion of non-tobacco plant extracts (permit only Nicotiana species

extracts).

The analytical challenge should be put onto the manufacturers to prove their case and compliance. When

regulators ban NETs, they force manufacturers to attempt the impossible: recreating a 5,500-compound botanical

profile from 16 synthetic molecules.

Part 3: The Consequence — What Happens When E-Cigarettes Cannot

Satisfy Smokers

3.1 Evidence from Flavour Ban Evaluations

Studies such as Rubenstein et al. (2025) conducted a laboratory choice task with 88 adult dual users. When

the only e-cigarette available was tobacco-flavoured, participants chose combustible cigarettes more often. We

see this problem too often in regions that have banned other flavours. Our goal at ENVA is to recreate authentic

tobacco flavours derived from NETs to hopefully convince users that have would have gone back to combustible

cigarettes to choose the less harmful product.

Our product that is aimed to faithfully recreate the sensation of taste of a tobacco cigarette is only aimed for

adult smokers to present them with a reduced harm alternative that they use on the daily. Such flavours are only

relevant to our target users as they are not attractive to users that are looking for sweet and fruity flavours.

Part 4: A Proposed Science-Based Alternative

The goal of tobacco-flavour regulation should be to permit formulations that provide sensory satisfaction

equivalent to combustible tobacco for adult smokers seeking to switch; do not create distinctively sweet, fruity, or

candy-like flavours that appeal to youth; are based on compounds genuinely present in tobacco or tobacco smoke;

and are manufactured with quality controls and concentration limits.

First, permit natural tobacco extracts. Tobacco extracts derived from Nicotiana tabacum or Nicotiana rustica

should be permitted under standardised conditions.

Second, expand the synthetic compound list to include authentic tobacco constituents. Pyrazines, phenolics,

furanones, vanillin derivatives, pyridines, lactones, and traditional casing ingredients (cocoa, licorice extracts)

should be permitted with concentration caps.

Third, maintain prohibitions on youth-appeal flavours. Fruit-flavour isolates, candy and dessert profiles,

bubblegum, cotton-candy, and high-concentration sweeteners should remain prohibited. Pyrazines and guaiacol

are no more appealing to youth than 3-ethylpyridine or isovaleric acid. In fact, pyrazines and phenolics are harsh,

bitter, and astringent at concentrations that would be used in tobacco e-liquids.

DECLARITION

We respectfully request that the governing body review this submission in accordance with the principles

established in Directive 2014/40/EU and the Estonian Tobacco Act, and we are available to provide any additional

information or clarification that may be required. We are happy to provide samples of our product for your expert

panels to judge whether our products only produce tobacco flavors.

Key Peer-Referenced Citations:

1. European Parliament and the Council of the European Union. Directive 2014/40/EU of the European

Parliament and of the Council of 3 April 2014 on the approximation of the laws, regulations and

administrative provisions of the Member States concerning the manufacture, presentation and sale of

tobacco and related products and repealing Directive 2001/37/EC. European Union. 2014 Apr 29.

https://health.ec.europa.eu/system/files/2016-11/dir_201440_en_0.pdf

2. Rodgman A, Perfetti T. The Chemical Components of Tobacco and Tobacco Smoke, Second Edition. CRC

Press; 2013.

https://www.researchgate.net/publication/294261056_The_Chemical_Components_of_Tobacco_and_To

bacco_Smoke_Second_Edition

3. Li W, et al. The dynamics of microbial community structure and metabolic function in different parts of

cigar tobacco leaves during air-curing. Frontiers in Microbiology; 2024.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11669699/

4. Wu X, et al. Formation and transfer patterns of key aroma compounds in cigar tobacco. Food Bioscience;

2026. https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2026.1755255/full

5. Rubenstein D, et al. Restricting choice of e-cigarette flavor and device type increases choices for

combustible cigarettes. Drug and Alcohol Dependence. 2025;320.

https://pubmed.ncbi.nlm.nih.gov/41343944/

Authorisation and Sign-Off

This submission is prepared by our lab scientist and researcher in response to the public consultation on proposed

restrictions to e-liquid flavouring compounds. The signatory confirms that the information provided herein is

accurate to the best of our knowledge, and that this submission represents our genuine scientific and regulatory

position.

Shenzhen GreenSound High-tech Co., Ltd. 2026-July-28

Signature: Signature:

_______________________________________________ _______________________________________________

Chenbo Wang Jason Tian

Regulatory and Compliance Manager Head of European Market