Article pubs.acs.org/est
Flavoring Chemicals and Aldehydes in E‑Cigarette Emissions Skylar Klager,† Jose Vallarino,† Piers MacNaughton,† David C. Christiani,† Quan Lu,† and Joseph G. Allen*,† †
Harvard T.H. Chan School of Public Health, 401 Park Drive Boston, Massachusetts 02215, United States S Supporting Information *
ABSTRACT: Regulations on e-cigarettes in the U.S. do not provide guidelines on the chemical content of e-cigarette liquids. We evaluated emissions of aldehydes and flavoring chemicals in e-cigarette vapor under typical usage conditions. We selected 24 e-cigarette flavors from the top selling disposable e-cigarette brands. E-cigarettes were connected to a pump drawing air for two second puffs with sixty-second intervals between puffs. The vapor was analyzed for the presence of aldehydes using high-performance liquid chromatography-ultraviolet detector and for the presence of flavoring chemicals with gas chromatography and an electron capture detector. All e-cigarette emissions tested contained at least one aldehyde and/or flavoring chemical on either the FEMA “High Priority Chemicals” or FDA Harmful and Potentially Harmful Constituents lists when sampled at typical usage conditions. Diacetyl, a known respiratory hazard, along with acetoin, were the most prevalent of the flavoring chemicals in e-cigarette vapor, being found in more than 60% of samples. The presence of propionaldehyde, acetaldehyde and formaldehyde were correlated, corroborating previous work suggesting thermal degradation as a pathway for aldehyde generation in e-cigarette vapors. Median formaldehyde concentrations of 626 μg/m3 in e-cigarette vapor exceed the ACGIH maximum concentrations allowable for workers of 370 μg/m3.
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and flavorings dissolved in a propylene glycol and/or glycerol vehicle.9,10 The glycerol and propylene glycol base is the major constituent of e-cigarette liquid, comprising approximately 80− 97% of the e-cigarette liquid by weight.11 When a user draws air through the e-cigarette, the liquid in an e-cigarette is heated, creating an aerosol that is inhaled. The flavoring compounds, propylene glycol, and glycerol in e-cigarette liquids are approved by the FDA and found on the Generally Recognized as Safe (GRAS) list.12 However, GRAS chemicals are tested and approved for ingestion only, not for inhalation. The GRAS approved flavoring compound diacetyl that is used to create savory, sweet, and fruit flavors is known to produce severe respiratory diseases upon inhalation and has been identified in e-cigarette aerosol in numerous studies.13−16 Diacetyl gained notoriety over 15 years ago due to the development of disease in factory workers who inhaled diacetyl during microwave popcorn production.17 Inhalation of diacetyl observed in this occupational health study was linked to the development of obliterative bronchiolitis (colloquially termed “popcorn lung”), an irreversible, life-threatening lung disease.18 The National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH) have since implemented
INTRODUCTION The e-cigarette product market has expanded in recent years, with nearly 500 brands and 7,700 flavors of electronic cigarettes (“e-cigarettes”) currently available in the U.S.1 E-cigarette use is observed among all age groups. A 2014 survey by the Center for Disease Control (CDC) estimates 3.7% of adults currently use e-cigarettes, whereas 16% of high school youths were ecigarette users in 2015.2,3 A study conducted in 2016 shows that among middle school aged children, nearly 30% indicated having tried e-cigarettes, with 17% classified as current users.4 Until May of 2016, unregulated e-cigarettes were widely available to minors. Implementation of new Food and Drug Administration (FDA) regulations on e-cigarettes requires a nicotine-warning label and a ban on the sale of e-cigarette products to adolescents under the age of 18.5 However, the new FDA regulations do not propose guidelines for e-cigarette ingredients. The novelty of e-cigarettes leaves little primary research available to properly evaluate the risks associated with e-cigarette ingredients and components. Reported differences between the chemical composition of e-cigarette liquid and the aerosol inhaled by consumers creates an additional need for identifying exposures under typical use conditions.6−8 An e-cigarette is a battery-operated nicotine delivery device consisting of a heating chamber and a liquid-containing cartridge. The devices can be purchased with cartridges that are disposed of once empty or as vaporizers with a refillable tank that allows users to create their own mixtures and flavors of e-cigarette fluid. E-cigarette liquids are composed of nicotine © 2017 American Chemical Society
Received: Revised: Accepted: Published: 10806
May 2, August August August
2017 11, 2017 17, 2017 17, 2017 DOI: 10.1021/acs.est.7b02205 Environ. Sci. Technol. 2017, 51, 10806−10813
Article
Environmental Science & Technology
Scheme 1. Proposed Mechanisms of Aldehyde Formation from the Pyrolysis and Oxidation of (A) Glycerol and (B) Propylene Glycol during Vaporization of E-Cigarette Liquid
occupational exposure limits to diacetyl.19 As awareness about the dangers of diacetyl grew, the food industry began using flavoring alternatives to diacetyl that create similar flavor profiles. Subsitutes for diacetyl include acetoin, 2,3-pentanedione, 2,3-heptanedione, 2,3-hexanedione, and 3,4-hexanedione. Inhalation of these chemicals has been shown to also cause respiratory hazards such as bronchial fibrosis, increases in the proinflammatory cytokine IL-6, and altered gene expression and ion transport.20−23 The Flavoring and Extract Manufacturers Association (FEMA) identified diacetyl, acetoin, 2,3pentanedione, 2,3-heptanedione, 2,3-hexanedione, and 3,4hexanedione as chemicals of “high priority” in respiratory health research.24 Aldehyde chemicals can also be used as flavoring compounds in food manufacturing. Multiple research groups have detected aldehydes in e-cigarette aerosols, including formaldehyde, acetaldehyde, acrolein, crotonaldehyde, and butyraldehyde.7,11,25−30 Both the FDA and FEMA identified aldehydes with potential for adverse health effects. FEMA lists acetaldehyde, benzaldehyde, isobutyraldehyde, propionaldehyde, and valeraldehyde, all aldehydes used in flavoring compounds, as chemicals of “high priority”.24 The FDA’s Harmful and Potentially Harmful Constituent list identifies acetaldehyde, formaldehyde, and crotonaldehyde as aldehydes of interest.31 Exposures to aldehydes in both the FEMA and FDA lists are implicated in noncancerous effects such as airway constriction, eye irritation, damage to airway epithelium, and alterations in gene expression.32−36 Formaldehyde and acetaldehyde carry the additional risk of carcinogenicity; the International Agency for Research on Cancer (IARC) designates formaldehyde as carcinogenic to humans and acetaldehyde as possibly carcinogenic to humans, while the EPA considers both probable human carcinogens.37−39 Formaldehyde and acetaldehyde are of particular interest due to having “ceiling limits” in occupational workplaces in which air concentrations of these chemicals cannot exceed a certain threshold for any part of the work day.40 According to ACGIH, both formaldehyde and acetaldehyde are known to cause upper respiratory tract and eye irritation.40 Chemical analysis of e-cigarette liquid and
aerosol have identified a wide range of additional compounds, including volatile organic compounds (VOCs), nitrosamines, metals and nanoparticles.11,26,41−45 Flavoring compounds cannot fully account for the presence of all aldehydes in e-cigarette vapor, particularly that of formaldehyde and acetaldehyde. Thermal decomposition of propylene glycol and glycerol are known to produce formaldehyde, propionaldehyde, and acetaldehyde as byproducts.46 A proposed explanation for the presence of formaldehyde and acetaldehyde in e-cigarette vapor is the pyrolysis and oxidation of propylene glycol and glycerol induced by the vaporization of the e-cigarette liquid upon use, as detailed in Scheme 1.6,7,14,30,47 Brand of e-cigarette, ratios of propylene glycol to glycerol vehicles, and amount of power applied to the ecigarette coil have been attributed to differing levels of aldehydes produced in e-cigarette vapor.7,11,25,28,29,48,49 Researchers recently observed that unflavored e-cigarette liquid generated “cleaner” vapor chemical profiles with lower aldehyde concentrations than flavored e-cigarette liquids.50 These findings propose thermal decomposition of flavoring compounds as an alternative, or more likely additional, mechanism for the presence of aldehydes in e-cigarette vapor.50 The goal of our research was to quantify the chemicals, including aldehydes, present in e-cigarette vapor under conditions representative of the behavior of an average ecigarette user, with special attention to those chemicals on the FDA’s Harmful and Potentially Harmful Constituent List and FEMA’s chemicals of “high priority”. We selected disposable and rechargeable battery e-cigarette models with disposable liquid cartridges from brands that hold a large portion of the market. These e-cigarette models cannot have their heating coil altered to generate heating conditions favorable for dry puff.
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MATERIALS AND METHODS Product Selection. We selected e-cigarettes based upon the most popular and easily accessible brands. The highest grossing e-cigarette brands were assumed to be a proxy for popularity and consumer use, providing the most likely exposure scenario to the average disposable e-cigarette consumer. A 2015 market report identified the top e-cigarette
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DOI: 10.1021/acs.est.7b02205 Environ. Sci. Technol. 2017, 51, 10806−10813
Article
Environmental Science & Technology Table 1. Flavoring Chemical Summary Information for Each E-Cigarette Testeda flavoring chemical concentration (μg/m3) brand
flavor
acetoin
diacetyl
2,3-heptanedione
2,3-hexanedione
2,3-pentanedione
3,4-hexanedione
A A A A A A A A A A A A B B C C C C C D D D D D D D
Java Jolt Vivid Vanilla Pina Colada Classic Tobacco Magnificent Menthol Cherry Crush Java Jolt Vivid Vanilla Peach Schnapps Cherry Crush Vivid Vanilla Pina Colada Classic Menthol Vanilla Bean Pomegranate Menthol Gold Tobacco Bold Tobacco Mint Crema Berry Berry Chai Original Tobacco Original Tobacco
