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- tobacco
- addictiveness
- additives
- cigarettes
- cigars
- smoking
- toxicity
- characterising flavour
- facilitated inhalation
- combustion products
The EU Tobacco Products Directive
The European Commission’s Tobacco Products Directive 2014/40/EU (TPD)1 came into force in 2014 and lays out rules governing the manufacture, presentation and sale of tobacco and related products, including cigarettes, roll-your-own tobacco, cigars, cigarillos, smokeless tobacco, electronic cigarettes and herbal products for smoking. It strengthens the rules regarding the reporting on ingredients contained in tobacco products and regulates permissible additives (or levels thereof) to improve the functioning of the internal market while guaranteeing a high level of public health. Articles 6 and 7 specifically focus on additivesi to tobacco products. More in detail article 7 lists prohibition of specific tobacco products, among which
tobacco products with a characterising flavour (Art 7 (1))
tobacco products containing the following additives2 (Art 7 (6)):
vitamins or other additives that create the impression that a tobacco product has a health benefit or presents reduced health risks;
caffeine or taurine or other additives and stimulant compounds that are associated with energy and vitality;
additives with colouring properties for emissions;
for tobacco products for smoking, additives that facilitate inhalation or nicotine uptake;
additives that have carcinogenic, mutagenic and reproductive toxicity (CMR) properties in unburnt form.
tobacco products containing additives in quantities that increase the toxic or addictive effect, or the CMR properties of a tobacco product at the stage of consumption to a significant or measurable degree (Art 7 (9)).
In line with Article 6 of the TPD, more stringent reporting obligations, in the form of comprehensive studies, will apply for additives placed on a priority list to be adopted by the European Commission, taking into account the intended use of the products concerned and examining in particular the emissions resulting from the combustion process involving the additive concerned.
The studies shall also examine the interaction of that additive with other ingredients contained in the products concerned. The results of these studies will help Member States and the Commission in their enforcement efforts regarding Article 7 of the TPD, which specifically concerns the regulation of ingredients used in tobacco products.
SCENIHR’s mandate to provide scientific advice on a list of priority additives
Article 6 of the Directive calls on the Commission to develop and update a priority list of at least 15 additives contained in cigarettes and roll-your-own tobacco (the first products to which these provisions will apply) by May 2016. The Commission mandated its independent Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) to provide scientific advice to the Commission in identifying additives that fulfil the criteria set out in Article 6 and could be put on the priority list (questions 1 and 2 of the Term of Reference (ToR)). The mandate also asked the Committee to provide advice on the type and criteria for comprehensive studies that should be requested from manufacturers to assess the relevance of the individual additives considering inter alia the knowledge gaps identified and the interaction of the additive with other additives/ingredients as well as the most suitable methodologies to be used to carry out those studies (question 3 of the ToR). This paper deals with the answers to questions 1 and 2, compiled in the first of the two opinions to be adopted.
Based on scientific evidence and other relevant information currently available the SCENIHR was asked to identify – for each category separately – those additives that fall/are suspected to fall within the scope of the following categories:
contributing to the toxicity or addictiveness of the products concerned/increasing the toxicity or addictiveness of any of the products concerned to a significant or measurable degree;
resulting in a characterising flavour;
facilitating inhalation or nicotine uptake;
leading to the formation of substances that have CMR properties/increasing the CMR properties in any of the products concerned (cigarettes/roll-your-own) to a significant or measurable degree.
As far as possible, the SCENIHR was asked to identify the most commonly used additives by weight or number and to consider further properties (eg, interaction with other ingredients—see full opinion for details).2
Although the amount of each single additive in a specific tobacco product is generally low, the number of additives used by tobacco product manufacturers is high; as an example it has been reported that additives account for 10% by weight in cigarette on the US market. Therefore, regulating additives in tobacco products comes is of relevance for protecting human health. Additives may be used to improve taste (eg, sugars, cocoa and liquorice), reduce smoke harshness (eg, humectants such as glycerol and propylene glycol) and generate product sensory characteristics using flavours (eg, sweeteners). The flavours are added to tobacco leaves to provide a specific and standardised taste, which makes it unique and recognisable among the large variety of available brands, as well as to compensate and mask variation of tobacco maintaining over time the specific taste of a certain product.
Approach
To carry out its task, the SCENIHR considered inter alia several lists of additives from the European Union Member States, from other jurisdictions (eg, USA, Canada, and Brazil) as well as from data published by industry and for practical reasons decided to use the comprehensive list from the Netherlands (containing 1260 compounds) as a typical example as verified in light of data submitted by other Member States. Most of the additives included in the SCENIHR suggested list belong to those frequently used in the other available sources considered.
This high number of additives used in tobacco products was narrowed down to approximately 100 compounds on the basis of two criteria: the frequency of detection in different brands and the amounts used in cigarettes. Following the assessment of SCENIHR, this number was further reduced to 55 additives based on the aforementioned properties (contributing to/increasing the toxicity or addictiveness of the products concerned, resulting in a characterising flavour, facilitating inhalation or nicotine uptake, leading to the formation of substances that have CMR properties/increasing CMR properties of the products concerned). Although the SCENIHR was aware of the outcome of the EU project ‘Public Information Tobacco Control' (PITOC), compounds indicated as relevant by the Project were not included on the list a priori. This way allowed an independent selection, after which the SCENIHR noticed that additives selected independently by the PITOC project were also included in the proposed list of the 55 chemicals selected by the SCENIHR. The only exception was Carob bean extract, which was a posteriori added to the ‘first screening’ list, including a total of 56 additives.
There was scant toxicological information regarding these additives, and the available information was often limited to the oral route of exposure, especially for flavouring substances that are used by the food industry, or, to a lesser degree, to the dermal route, for substances that are also commonly used in cosmetic products. Because there was little data on their kinetic behaviour or inhalation toxicity, it was difficult, if not impossible, to make route-to-route extrapolation. Therefore one of the major gap was related to the lack of inhalation toxicity studies, representing the most relevant ones for the additives in tobacco products, which are either transferred to inhaled smoke in pure form or are combusted and converted via pyrolysis into potentially toxic products.
Considering the possible detrimental health effects due to exposure to additives, a general scarcity of information was observed on exposure to the additive in unburnt form and even on the combustion reactions’ products, since data on pyrolysis obtained in the actual condition of use are scant.
For most tobacco additives, direct information about their possible contribution to addictiveness and characterising flavours does not exist, although information can often be derived from the mode of action of the additive (eg, addictiveness can be related to increased nicotine bioavailability or to local anaesthetic effects facilitating the inhalation of tobacco smoke).
The selection of the priority list was based on unfavourable toxicological characteristics of the compounds in their unburnt form or of pyrolysis products and/or based on possible available information about attractiveness and addictiveness. The selection was therefore based on their hazard profile; as a consequence a full risk assessment was not carried out. A data sheet was prepared for each chemical, containing the most relevant information and the related references; it also includes a paragraph describing the reasons for inclusion into the priority list.
Considering that each of the tobacco additives (and combustion products) is only one among the massive number of other chemicals contained in cigarette smoke, additive effects or reactions with other compounds are likely to occur but cannot be adequately evaluated.
Results
48 single chemicals identified by SCENIHR as relevant for the priority list
Despite these limitations, the SCENIHR was able to come up with 30 entries corresponding to chemicals/groupsii of chemicals for a total of 48 single chemicals selected from the initial list of 56 compounds list and thus to fulfil its mandate of providing a list of minimum 20 and maximum 30 additives that are suitable/recommended to be added to the priority list of additives in line with Article 6 of TPD 2014/40/EU, as specified in the ToR. The compounds were selected mainly based on hazard identification having or being suspected to have one or more of the above-mentioned properties (bullet point A-D), including toxicity in unburned form, facilitating inhalation or increasing nicotine uptake (which may contribute to addictiveness), having characterising flavour (one of the factors potentially contributing to attractiveness) and formation of toxic chemicals after combustion.
Some additives may fall into several of these four categories.
On the basis of these criteria:
17 substances were identified because they fall or are suspected to fall in the category: toxic in unburnt form, among which six are suspected of CMR potential.
14 substances were identified because they are suspected of facilitating inhalation or of increasing nicotine uptake.
19 substances were identified because they show a characterising flavour, a factor potentially contributing to attractiveness.
20 substances were identified because they are known or suspected of forming irritant, toxic and/or CMR chemicals after combustion.
See Box 1 for list of priority chemicals.
List of priority chemicals (in alphabetical order) as suggested by the SCENIHR.
Acetanisole
Aliphatic gamma-lactones (including 8 members: gamma-Valerolactone, gamma-Hexalactone, gamma-Heptalactone, gamma-Octalactone, gamma-Nonalactone, gamma-Decalactone, gamma-Undecalactone, gamma-Dodecalactone)
Ammonium compounds
Benzaldehyde
Benzoic acid and sodium benzoate (2 members)
Benzyl alcohol
Caramel colours
Carob bean extract
Cellulose
Cocoa
β-Damascone
Diacetyl
2-Furfural
Geraniol
Glycerol
Guar gum
Guaiacol
Linalool
Liquorice
Maltol
Menthol
Natural extracts (including 4 members: fenugreek, rum, plum extract, fig extract)
Phenylacetic acid
Piperonal
Ranking the additives
Within the list SCENIHR was asked to ‘indicate as far as possible rankings of additives and provide an explanation for its ranking’. In the absence of a full-risk assessment an attempt to rank the selected additives was given, in a few cases based on hazard information (qualitative approach) but in most cases based on their ranking in frequency and amount used in tobacco products.2
The six substances in the list for which the carcinogenic/genotoxic potential could not be ruled out were ranked highest on the suggested list because the TPD in its Article 7 foresees the prohibition of additives that have CMR properties in unburnt form. Although the degree of uncertainty in their toxicity was estimated to be different, it was impossible to quantitatively rank them on the basis of their CMR potential (giving rise to comparable concern); therefore their prioritisation was based on available data concerning their content and frequency of use (see table 1).
Prioritisation of additives based on their content and frequency of use
The first data requirement for these additives would be to define their CMR potential in their unburnt form. If they tested positive, no further testing would be needed, because that alone would cause them to be banned according to the TPD. If CMR properties in unburnt form were excluded, the possibility to give rise to toxic chemicals after combustion should be verified and considered similar to the other additives falling in more than one of the above-mentioned categories.
In addition to these six chemicals, menthol, one of the most commonly used tobacco additives worldwide, was also considered to belong in the ‘high-priority group’, as a wide body of evidence is available to indicate the presence of characterising flavour, as well as a complex pharmacological action (including anaesthetic effects, facilitation of deeper inhalation and higher nicotine exposure), characteristics which tobacco additives should not have according to the TPD. However, further data are needed to elucidate the dose–response relationship to determine whether the described effects are relevant at the actual exposure levels as an additive in ‘non’ menthol brands of tobacco products.
The possibility of forming CMR compounds after combustion identified a second group including sugars, sugar-containing additives (caramel colours, rum, natural extracts such as fenugreek, plum extract, carob bean extracts, guar gum) and cellulose.
All the remaining selected additives (including among others, humectants as propylene glycol, sorbitol and glycerol, cocoa, liquorice, linalool, vanillin) are categorised in the third group. SCENIHR considered that it was not possible to rank them on the basis of their specific hazard profile. The possible criteria used for their prioritisation are listing them with respect to their content/frequency ranking or possible combination of more than one of four characteristics provided for in Article 6.
The full list and details about how and why single compounds were proposed can be found in the opinion.
SCENIHR also noted that for some substances in the priority list several structural analogues exist (with similar physico-chemical characteristics). If substances on the list are substituted by structural analogues, it should be considered that they may (or may not) have similar or even higher potential hazardous characteristics. In case the analogue do not rank high in use or frequency or are not presently used as additive in tobacco products, they were not included in the current priority list, but this does not mean they can be seen as safe.
The second concern is related to derived natural products, for which different forms exist depending on specific extraction process and fractions, each one corresponding to different CAS numbers. As an example cocoa is marketed as cocoa extract, cocoa powder, cocoa butter, cocoa shells, cocoa distillate, cocoa hulls, etc. For all these products it is not clear to what extent the toxicological profile of the different forms of natural compounds can be compared.
On 18 May 2016, the Commission adopted the Commission Implementing Decision (EU) 2016/787 laying down a priority list of additives contained in cigarettes and roll-your-own tobacco subject to enhanced reporting obligationsii, identifying 15 chemicals among those listed in the SCENIHR opinion.
A second opinion, to be published later this year, is intended to provide advice on the development of guidelines for types of studies and their criteria that should be requested by manufacturers to assess the relevance of the individual additives.
See the full opinion2 for further details.
iAccording to the TPD 2014/40/EU (see Article 2 (23)), ’additive' means a substance, other than tobacco, that is added to a tobacco product, a unit packet or to any outside packaging.
iiSome chemicals with very similar structures (ie, aliphatic gamma-lactones, including eight members) and/or properties (eg, weak acids, including eight members) were grouped together.
iii http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016D0787&from=EN
What this paper adds
The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) identified a list of 48 single chemicals relevant for the priority list of additives used in tobacco products. Within the list, SCENIHR attempted to indicate as far as possible rankings of additives and provide an explanation for its ranking.
Footnotes
Contributors The Opinion is a result of a joint work and therefore individual contributions cannot be identified. Recommendations to the European Commission implementing a priority list of additives that should have more stringent reporting requirements: the opinion of the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR).
Competing interests None to be declared.
Provenance and peer review Not commissioned; internally peer reviewed.
Collaborators Members of the SCENIHR: Michelle Epstein, Igor Emri, Philippe Hartemann, Peter Hoet, Norbert Leitgeb, Luis Martínez Martinez, Ana Proykova, Luigi Rizzo, Eduardo Rodriguez-Farré, Lesley Rushton, Konrad Rydzynski, Theodoros Samaras, Emanuela Testai and Theo Vermeire.