Article Text


Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective
  1. Nuan Ping Cheah1,
  2. Norman Wee Lin Chong2,
  3. Jing Tan1,
  4. Faridatul Akmam Morsed1,
  5. Shen Kuan Yee2
  1. 1Cigarette Testing Laboratory, Applied Sciences Group, Health Sciences Authority, Singapore
  2. 2Tobacco Regulation Branch, Health Products Regulation Group, Health Sciences Authority, Singapore
  1. Correspondence to Dr Nuan Ping Cheah, Cigarette Testing Laboratory, Applied Sciences Group, Health Sciences Authority, 11 Outram Road, Singapore 169078, Singapore; cheah_nuan_ping{at}


Objective Many electronic nicotine delivery systems (ENDS) are marketed as safer tobacco alternative products or effective cessation therapies. ENDS samples were evaluated for design features, including nicotine and glycols content. This could be useful in developing a legal framework to handle ENDS.

Methods Identification of the nicotine, glycerol and propylene glycol (PPG) contents was conducted using gas chromatography mass spectrometry with quantification performed using flame ionisation techniques.

Results Varying nicotine amounts were found in ENDS cartridges which were labelled with the same concentration. Chemicals such as PPG and glycerol were found to be present in the nicotine-containing liquid of the cartridges. ENDS varied in their contents and packaging information. Limited information was available on the contents of nicotine and other chemicals present in a variety of ENDS sampled.

Conclusions Based on samples tested in this study, many contain misleading information on product ingredients. The results show poor consistency between actual nicotine content analysed on ENDS cartridges and the amount labelled. These findings raise safety and efficacy concerns for current and would-be recreational users or those trying to quit smoking.

Statistics from


Electronic nicotine delivery systems (ENDS), commonly called electronic cigarettes, e-cigarettes or vapourisers, are typically battery-operated devices that are designed and used in the same manner as a conventional cigarette but claimed to rapidly deliver nicotine to its users without exposure to harmful carcinogens and toxicants. Alternative versions include electronic cigars and shisha pipes.1

An ENDS product usually consists of a cartridge, heating element, lithium battery and light-emitting diode (LED) light which emits a reddish light when puffed (figure 1). Nicotine refill cartridges are available in different concentrations ranging from zero nicotine, low and mid-range doses (eg, 6–8 mg/ml and 10–14 mg/ml respectively), to high and extra-high doses (eg, 16–18 mg/ml and 24–36 mg/ml respectively).2 The concentration labels are often printed on the e-liquid bottle or cartridge.

Figure 1

‘eGo’ manufactured by JOYE Technology, China. The design of the eGo electronic cigarette differs from conventional designs that resemble conventional cigarettes, purportedly to allow the user to vape more discretely in public. Although its shape is closer to that of a cigar, the black rubberised exterior and silver/gold finishing makes this design less similar to a tobacco product. Another unique feature of this design is the presence of a button, which allows users to activate the atomiser without initiating the first puff (

Without the need for combustion or tobacco, such devices heat up compounds typically composed of propylene glycol (PPG) (a known irritant when inhaled or ingested) and nicotine, which is vapourised as a mist, providing the sensory and visual sensation of exhaling ‘smoke’. Manufacturers often offer such compounds with varying levels of nicotine and assorted flavours.

Studies done by the US Food and Drug Administration3–7 have shown that ENDS may pose health risks to its users as they may contain toxic chemicals and other impurities. Moreover, the amounts of nicotine stated on the nicotine cartridges did not match with the result of laboratory analysis, raising concerns about their quality and safety.7

To further understand the ENDS product, a sample of different types of ENDS products was tested and the content of its main chemicals, nicotine and glycols, is presented and discussed.


Sample and standard preparation

The sale of ENDS is prohibited in Singapore. The Immigration and Checkpoints Authority of Singapore provided the samples used in this study from its seizure operations conducted between October 2010 and March 2011. Seizures are made from individuals who attempt to carry in ENDS via border checkpoints or at parcel screening facilities when individuals attempt to import ENDS via internet purchases.

ENDS reviewed in this study were obtained from seizure samples. A total of 20 variants of ENDS cartridge were analysed. Each brand was evaluated on design, nicotine content and labelling information (table 1).

Table 1

Product and labelling information of 20 variants of electronic nicotine delivery system (ENDS) cartridges seized by Singapore Customs

Determination of nicotine, PPG and glycerol was carried out using organic solvent extraction followed by detection by gas chromatography. The extraction steps are described in detail by Trehy et al.3 In addition, the completeness of the extraction of the studied analyte was re-examined by re-extracting five of the studied cartridges (E-vaporizer—16 mg; Smoker Haven; Smoking Everywhere—Med 11 mg; V2CIGS—Red-12 and Fifty-One—6 mg). The re-extracted solution was found to have non-detectable amounts of nicotine, PPG and glycerol (ie, below the detection level of the method). We obtained recovery between 80% and 90% using the laboratory fortified matrix with known concentration between the low and high levels of all three chemicals studied (nicotine, PPG and glycerol). The detection limits for this method were 0.02 mg for nicotine, 0.5 mg for PPG and 0.5 mg for glycerol. A series of standard solutions were prepared by dissolving reference standards in methanol. The correlation coefficient of the calibration curve (R2) was >0.995. The analysis was conducted in triplicate (ie, test on three cartridges per product) per brand.

Materials and instrument

The standard of nicotine (99.7%) was obtained from Merck Chemicals. Glycerol (99.5%) and PPG (99.5%) were from Sigma-Aldrich. Other chemicals and solvents used were of analytical or high-performance liquid chromatography grade. Gas chromatography with flame ionisation detector (Agilent 6890 N Series) was used to quantify the content of nicotine, PPG and glycerol in ENDS. A J&W DB-Wax capillary column coated with a 1 μm thick polyethylene glycol (30 m×0.53 mm) was used for the analysis. Each compound was identified using the same instrument with mass spectrometer detection.


The vast majority of the 20 brands of ENDS provided information on the health impact of ENDS use and the risk of nicotine addiction (table 1). All 20 brands of ENDS evaluated in this study were marketed as safer and healthier alternatives to conventional smoking, or as smoking cessation aids.

Twelve brands included some form of health caution, with a warning for users who are under 18 years, pregnant or who have a heart condition, diabetes, high blood pressure or asthma. Only two brands provided a warning on nicotine addiction.

Seventeen products were found to contain detectable amounts of nicotine (table 2). Four of the 20 brands sampled were found to contain nicotine even though these products claimed to be nicotine free. Across the 20 products, nicotine content ranged up to 15.3 mg per cartridge, PPG content ranged up to 1020 mg per cartridge and glycerol content ranged from 19.4 to 1020 mg per cartridge. In 16 of the 20 brands sampled, actual nicotine content did not correspond to the amount that the cartridge purported to contain.

Table 2

Nicotine, propylene glycol (PPG) and glycerol content of 20 variants of electronic nicotine delivery system (ENDS) cartridges, seized by Singapore Customs

Two products contained a very high level of glycerol (w/w): e-joy with 374 mg and Fifty-One with 827 mg (labelled as 6 mg). Eighteen products were found to contain more than 100 mg of PPG per cartridge.

Polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamine compounds were not found in the ENDS cartridges in this study. This is expected as tobacco-specific nitrosamines are mostly formed during the ageing, curing and fermentation of tobacco, whereas PAHs are smoke compounds formed due to incomplete combustion of organic materials. Descriptions and illustrations of four ENDS products are included in figures 1–5.

Figure 2

‘SGS electronic cigarette’ manufactured by Wiwin Industry Co, China. The packaging of the SGS electronic cigarette very closely resembles the Marlboro conventional cigarette packaging. The design and colour of the battery and cartridge closely resemble a typical cigarette. The amber light-emitting diode which lights up during puff inhalation also adds to the illusion of smoking. Although there is no evidence to show that any conventional cigarette company has a stake in this product, the red chevron design of the packaging (which serves as a charger for the electronic cigarette battery) resembles similar branding of a conventional cigarette brand. (No independent marketing website found at time of print.)

Figure 3

‘Tattoo’ manufactured by Smoke Free Electronic Cigarettes, China. While its mechanism is no different from other brands of electronic cigarettes, its branding is unique. Touting to be inspired by designs of a famous US tattoo artist, Ed Hardy, its ‘Tattoo’ branding could arguably be geared towards the younger target audience. Its marketing strategies include packaging the product in collectable tattoo designed boxes with messages like ‘Take control of your life! No more letting other people tell you when or where you can smoke!’ and ‘Join the smoke free electronic cigarette revolution! Be bold! Be unique! Be you!’ Available in black, white, gold, silver, red and pink, it may be argued that certain colour schemes may attract particular consumer populations, such as young women (

Figure 4

‘Super eGo’ manufactured by E-Cig Technology Inc, China. The Super eGo claims to offer different battery amperages. Stronger batteries are claimed to provide users with longer-lasting use, be able to provide deeper inhalation and higher nicotine ‘hits’ compared with other brands of ENDS. Variants come in three-piece or two-piece formats. The three-piece formats are made up of the battery, atomiser and cartridge whereas the two-piece formats are made up of the battery and cartomiser. The cartomiser serves as the replaceable integrated combination of the atomiser and cartridge. The two-piece format aims to appeal to users who find cleaning and replacing faulty atomisers inconvenient (

Figure 5

‘E-pipe’ manufactured by E-Cig Technology Inc, China. A variant design from the e-cigarette, which could appeal to a niche target audience of pipe users, the E-pipe contains the basic components of its e-cigarette peer: the battery, atomiser, cartridge and the additional inhaler mouth piece which comes in contact with the lips. The E-pipe also contains a red light-emitting diode which activates during puffing, adding to the illusion of smoking a conventional pipe (


Labelling of constituents and health information on the 20 brands of ENDS sampled was inadequate. About half of the sampled brands did not label the nicotine amounts on the packaging and did not provide any health caution on risks of nicotine use, particularly to at-risk subpopulations like pregnant women and minors. The majority of the brands sampled were found to have inaccurate nicotine labelling and did not give the amount of nicotine on the individual cartridge wrapper, consistent with previously published work.8 Future regulation of ENDS should determine appropriate warnings on the risks and harm associated with nicotine exposure due to inhalation and mishandling. In addition, our findings show that there is significant difference in the nicotine content across ENDS of the same concentration label. There are brand-to-brand and cartridge-to-cartridge variations. ENDS that contain low amounts of nicotine may have the potential to serve as a starting point for would-be tobacco users.9 High concentrations of nicotine in ENDS may pose other risks. For example, an estimated level of 10 mg nicotine can be fatal to children.10 The effectiveness of nicotine delivery in such devices is still in question, with competing views on the use of such products as gateways to tobacco use9 or as cessation aids, like nicotine replacement therapy.11 ,12

Due to its odourless and smokeless delivery system, the e-cigarette can be used in non-smoking areas, as suggested by some ENDS product inserts. This has the potential to allow people to satisfy the smoking urge despite being in areas where smoking is prohibited.

The presence of a high amount of glycols (PPG and glycerol) in great quantities in these devices raises another concern. PPGs, the main liquid found in the cartridge, is a non-toxic chemical widely used as humectants in food products and as additives in asthma inhalers and nebulisers. Unlike inhalers or nebulisers, the e-cigarette device consists of a heating component and the heating of glycols (PPGs or glycerols) generates various carbonyls which are toxic to the users.13 ,14

There are additional safety concerns associated with these products. Carbonyls such as acetaldehyde (0–14 mg/m3), formaldehyde (0–97 mg/m3), acrolein (0–9.3 mg/m3), glyoxal (0–42 mg/m3) and methylglyoxal (0–38 mg/m3) have been detected in the air generated from electronically heated cigarettes.15 Methylglyoxal, the most mutagenic of all aldehydes, is known to inhibit formaldehyde metabolism, thus enhancing formaldehyde-inducing cytotoxicity.16 High concentrations of short-chain aldehydes such as formaldehyde, acetaldehyde and acrolein are produced during the heating of ENDS. Formaldehyde, a chemical used in wood preservation and embalming, is classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) and is suspected to be the cause of various diseases (IARC 2006). Acetaldehyde is known to contribute to tobacco's addictive properties.17 ,18 The safety of the combination substances that are delivered to the lungs by ENDS has not been evaluated for either short-term or long-term use, making toxicological evaluation challenging.

The current study is limited to the 20 ENDS products confiscated from the Immigration and Checkpoints authority, and thus may not be a conclusive representation of all other ENDS products on the market. Evaluation of the ENDS products is limited to the content of the electronic cigarette cartridges.


In the realm of public health, more knowledge on the toxicological effects and risk assessment of ENDS is needed. These novelty tobacco-related products may not fit neatly under conventional classifications of pharmaceutical or tobacco products. This may pose a challenge for many regulatory bodies to regulate these products within existing laws.

While the current attention on traditional tobacco products is important, it is also necessary to focus on novelty products like ENDS, which may encourage maintenance of tobacco usage behaviour and slow down the impact of national smoking control programmes.

Tobacco control policy makers and professionals are seriously urged to find ways to address the gap in the scientific understanding and the legal framework of such products, as this gap may impede efforts at curbing tobacco use.

What this study adds

  • While the marketing and product ranges of electronic nicotine delivery systems (ENDS) have grown in recent years, questions on the safety and efficacy of these products as cessation tools have not been fully addressed. Preliminary tests by the US Food and Drug Administration found varying levels of nicotine, carcinogens and diethylene glycol in some samples, highlighting concerns on quality control and potential toxicity to users. Trtchounian's examination of six brands of ENDS suggested a lack of adequate labelling and raised questions on quality control. Our study of 20 brands of ENDs provides further data on inconsistencies in the amount of nicotine found in cartridges compared with the labelling and the pervasiveness of misleading information on product labelling and packaging. This supports the current literature and regulators’ concerns of questionable safety and quality of ENDS and highlights the need for more research to help regulators make empirically based policy decisions.


The authors would like to thank the Health Sciences Authority for supporting this project. The authors thank Dr Reinskje Talhout and the anonymous reviewers for their constructive comments and suggestions.


View Abstract


  • Contributors NPC handled the conceptualisation, analysis and interpretation of the quantitative aspects of ENDS constituents. NPC wrote the toxicological section and integrated all information gathered in this paper. NC handled the acquisition, qualitative review of ENDS samples and packaging information, and assisted NPC in the drafting, revision and approval of the final version of the paper. JT organised the analytical and chemical analysis section. FAM analysed, tabulated and interpreted the chemical part of the work. SKY provided writing assistance and technical advice on the regulatory aspects of the paper. All the named authors contributed substantially to the writing of this paper. NPC, NC and the rest of the authors approve the concept, approach and the final version of this paper.

  • Funding This study was funded by ASG Research Fund (ASG07/10), Health Sciences Authority, Singapore.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Additional unpublished information and data are available to the editorial team and reviewers upon request.

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