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      Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

      research-article
      1 ,
      BMC Public Health
      BioMed Central
      Vaping, e-cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit

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          Abstract

          Background

          Electronic cigarettes (e-cigarettes) are generally recognized as a safer alternative to combusted tobacco products, but there are conflicting claims about the degree to which these products warrant concern for the health of the vapers (e-cigarette users). This paper reviews available data on chemistry of aerosols and liquids of electronic cigarettes and compares modeled exposure of vapers with occupational safety standards.

          Methods

          Both peer-reviewed and “grey” literature were accessed and more than 9,000 observations of highly variable quality were extracted. Comparisons to the most universally recognized workplace exposure standards, Threshold Limit Values (TLVs), were conducted under “worst case” assumptions about both chemical content of aerosol and liquids as well as behavior of vapers.

          Results

          There was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures. The vast majority of predicted exposures are < <1% of TLV. Predicted exposures to acrolein and formaldehyde are typically <5% TLV. Considering exposure to the aerosol as a mixture of contaminants did not indicate that exceeding half of TLV for mixtures was plausible. Only exposures to the declared major ingredients -- propylene glycol and glycerin -- warrant attention because of precautionary nature of TLVs for exposures to hydrocarbons with no established toxicity.

          Conclusions

          Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces. However, the aerosol generated during vaping as a whole (contaminants plus declared ingredients) creates personal exposures that would justify surveillance of health among exposed persons in conjunction with investigation of means to keep any adverse health effects as low as reasonably achievable. Exposures of bystanders are likely to be orders of magnitude less, and thus pose no apparent concern.

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          Most cited references17

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          Metal and Silicate Particles Including Nanoparticles Are Present in Electronic Cigarette Cartomizer Fluid and Aerosol

          Background Electronic cigarettes (EC) deliver aerosol by heating fluid containing nicotine. Cartomizer EC combine the fluid chamber and heating element in a single unit. Because EC do not burn tobacco, they may be safer than conventional cigarettes. Their use is rapidly increasing worldwide with little prior testing of their aerosol. Objectives We tested the hypothesis that EC aerosol contains metals derived from various components in EC. Methods Cartomizer contents and aerosols were analyzed using light and electron microscopy, cytotoxicity testing, x-ray microanalysis, particle counting, and inductively coupled plasma optical emission spectrometry. Results The filament, a nickel-chromium wire, was coupled to a thicker copper wire coated with silver. The silver coating was sometimes missing. Four tin solder joints attached the wires to each other and coupled the copper/silver wire to the air tube and mouthpiece. All cartomizers had evidence of use before packaging (burn spots on the fibers and electrophoretic movement of fluid in the fibers). Fibers in two cartomizers had green deposits that contained copper. Centrifugation of the fibers produced large pellets containing tin. Tin particles and tin whiskers were identified in cartridge fluid and outer fibers. Cartomizer fluid with tin particles was cytotoxic in assays using human pulmonary fibroblasts. The aerosol contained particles >1 µm comprised of tin, silver, iron, nickel, aluminum, and silicate and nanoparticles (<100 nm) of tin, chromium and nickel. The concentrations of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concentrations in conventional cigarette smoke. Many of the elements identified in EC aerosol are known to cause respiratory distress and disease. Conclusions The presence of metal and silicate particles in cartomizer aerosol demonstrates the need for improved quality control in EC design and manufacture and studies on how EC aerosol impacts the health of users and bystanders.
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            Evaluation of Electronic Cigarette Use (Vaping) Topography and Estimation of Liquid Consumption: Implications for Research Protocol Standards Definition and for Public Health Authorities’ Regulation

            Background: Although millions of people are using electronic cigarettes (ECs) and research on this topic has intensified in recent years, the pattern of EC use has not been systematically studied. Additionally, no comparative measure of exposure and nicotine delivery between EC and tobacco cigarette or nicotine replacement therapy (NRTs) has been established. This is important, especially in the context of the proposal for a new Tobacco Product Directive issued by the European Commission. Methods: A second generation EC device, consisting of a higher capacity battery and tank atomiser design compared to smaller cigarette-like batteries and cartomizers, and a 9 mg/mL nicotine-concentration liquid were used in this study. Eighty subjects were recruited; 45 experienced EC users and 35 smokers. EC users were video-recorded when using the device (ECIG group), while smokers were recorded when smoking (SM-S group) and when using the EC (SM-E group) in a randomized cross-over design. Puff, inhalation and exhalation duration were measured. Additionally, the amount of EC liquid consumed by experienced EC users was measured at 5 min (similar to the time needed to smoke one tobacco cigarette) and at 20 min (similar to the time needed for a nicotine inhaler to deliver 4 mg nicotine). Results: Puff duration was significantly higher in ECIG (4.2 ± 0.7 s) compared to SM-S (2.1 ± 0.4 s) and SM-E (2.3 ± 0.5 s), while inhalation time was lower (1.3 ± 0.4, 2.1 ± 0.4 and 2.1 ± 0.4 respectively). No difference was observed in exhalation duration. EC users took 13 puffs and consumed 62 ± 16 mg liquid in 5 min; they took 43 puffs and consumed 219 ± 56 mg liquid in 20 min. Nicotine delivery was estimated at 0.46 ± 0.12 mg after 5 min and 1.63 ± 0.41 mg after 20 min of use. Therefore, 20.8 mg/mL and 23.8 mg/mL nicotine-containing liquids would deliver 1 mg of nicotine in 5 min and 4 mg nicotine in 20 min, respectively. Since the ISO method significantly underestimates nicotine delivery by tobacco cigarettes, it seems that liquids with even higher than 24 mg/mL nicotine concentration would be comparable to one tobacco cigarette. Conclusions: EC use topography is significantly different compared to smoking. Four-second puffs with 20–30 s interpuff interval should be used when assessing EC effects in laboratory experiments, provided that the equipment used does not get overheated. Based on the characteristics of the device used in this study, a 20 mg/mL nicotine concentration liquid would be needed in order to deliver nicotine at amounts similar to the maximum allowable content of one tobacco cigarette (as measured by the ISO 3308 method). The results of this study do not support the statement of the European Commission Tobacco Product Directive that liquids with nicotine concentration of 4 mg/mL are comparable to NRTs in the amount of nicotine delivered to the user.
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              Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke.

              Tobacco-specific nitrosamines are a group of carcinogens that are present in tobacco and tobacco smoke. They are formed from nicotine and related tobacco alkaloids. Two of the nicotine-derived nitrosamines, NNK and NNN, are strong carcinogens in laboratory animals. They can induce tumors both locally and systemically. The induction of oral cavity tumors by a mixture of NNK and NNN, and the organospecificity of NNK for the lung are particularly noteworthy. The amounts of NNK and NNN in tobacco and tobacco smoke are high enough that their total estimated doses to long-term snuff-dippers or smokers are similar in magnitude to the total doses required to produce cancer in laboratory animals. These exposures thus represent an unacceptable risk to tobacco consumers, and possibly to non-smokers exposed for years to environmental tobacco smoke. The permission of such high levels of carcinogens in consumer products used by millions of people represents a major legislative failure. Indeed, the levels of tobacco-specific nitrosamines in tobacco are thousands of times higher than the amounts of other nitrosamines in consumer products that are regulated by government authorities. Although the role of tobacco-specific nitrosamines as causative factors in tobacco-related human cancers cannot be assessed with certainty because of the complexity of tobacco and tobacco smoke, several lines of evidence strongly indicate that they have a major role, especially in the causation of oral cancer in snuff-dippers. Epidemiologic studies have demonstrated that snuff-dipping causes oral cancer. NNK and NNN are quantitatively the most prevalent known carcinogens in snuff, and they induce oral tumors when applied to the rat oral cavity. A role for NNK in the induction of lung cancer by tobacco smoke is likely because of its organospecificity for the lung. Tobacco-specific nitrosamines may also be involved in the etiology of tobacco-related cancers of the esophagus, nasal cavity, and pancreas. Because they are derived from nicotine, and therefore should be associated only with tobacco, tobacco smoke and other nicotine-containing products, tobacco-specific nitrosamines as well as their metabolites and macromolecular adducts should be ideal markers for assessing human exposure to, and metabolic activation of, tobacco smoke carcinogens. Ongoing research has demonstrated the formation of globin and DNA adducts of NNK and NNN in experimental animals. Sensitive methods for the detection and quantitation of these adducts in humans would provide an approach to assessing individual risk for tobacco-related cancers.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Contributors
                Journal
                BMC Public Health
                BMC Public Health
                BMC Public Health
                BioMed Central
                1471-2458
                2014
                9 January 2014
                : 14
                : 18
                Affiliations
                [1 ]Department of Environmental and Occupational Health, School of Public Health, Drexel University, Nesbitt Hall, 3215 Market St. Floor 6, Office 614, Philadelphia, PA 19104, USA
                Article
                1471-2458-14-18
                10.1186/1471-2458-14-18
                3937158
                24406205
                d3b13af3-a765-430e-9f74-af07cb4bad59
                Copyright © 2014 Burstyn; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 August 2013
                : 2 January 2014
                Categories
                Research Article

                Public health
                vaping,e-cigarettes,tobacco harm reduction,risk assessment,aerosol,occupational exposure limit

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