Analytical Assessment of e-Cigarettes

From Contents to Chemical and Particle Exposure Profiles

Konstantinos E. Farsalinos,I. Gene Gillman,Stephen S. Hecht,Riccardo Polosa,Jonathan Thornburg

• Publisher: Elsevier
• Year: 2016
• ISBN:
  9780128112427
• Topic: Physical Sciences
• Subtopic: Analytic Chemistry

A volume in the Emerging Issues in Analytical Chemistry series, Analytical Assessment of E-Cigarettes: From Contents to Chemical and Particle Exposure Profiles addresses the many issues surrounding electronic cigarettes in an unprecedented level of scientific detail. The plethora of product devices, formulations, and flavors, combined with the lack of industry standards and labeling requirements, quality control, and limited product oversight, has given rise to public concern about initiation of use and potential for adverse exposure and negative long-term health outcomes. This volume discusses how analytical methods can address these issues and support the manufacturing, labeling, distribution, testing, regulation, and monitoring for consistency of products with known chemical content and demonstrated performance characteristics.

The book begins with the background on aerosol drug delivery services and e-cigarettes, constituents of nicotine-containing liquid dosing formulations, typical use scenarios and associated aerosol emissions, and chemical exposures and pharmacological and toxicological effect profiles, and then continues with descriptions of the analytical methods used to characterize the chemicals in formulations and emissions from e-cigarettes, including their stability, physical particle-size distribution and thermal degradation under commonly employed conditions of use.

Analytical methods enabling detection of biomarkers of exposure and harm in complex biological matrices are discussed, with an emphasis on constituents or emissions of current medicinal interest or with potential to produce harm. Opportunities and challenges for analytical chemistry in supporting the continued development and use of safe and consistent dosage formulations as alternatives to tobacco products are also explored, with a concluding section describing an analytical approach to a risk-benefit assessment of e-cigarette use on human health.

The Emerging Issues in Analytical Chemistry series is published in partnership with RTI International and edited by Brian F. Thomas. Please be sure to check out our other featured volumes: Thomas, Brian F. and ElSohly, Mahmoud. The Analytical Chemistry of Cannabis: Quality Assessment, Assurance, and Regulation of Medicinal Marijuana and Cannabinoid Preparations, 9780128046463, December 2015. Hackney, Anthony C. Exercise, Sport, and Bioanalytical Chemistry: Principles and Practice, 9780128092064, March 2016.Tanna, Sangeeta and Lawson, Graham. Analytical Chemistry for Assessing Medication Adherence, 9780128054635, April 2016.Rao, Vikram; Knight, Rob; and Stoner, Brian. Sustainable Shale Oil and Gas: Analytical Chemistry, Biochemistry, and Geochemistry Methods, 9780128103890, September 2016.

• Discusses the chemistry and physics involved in aerosol production, inhalation, deposition, chemical exposure, and effect assessment
• Contains current information and state-of-the-science methods on e-cigarette emissions, exposures, and harm assessment
• Offers an authoritative, objective perspective from five of the most well-recognized scientists in their areas of expertise who have no personal stake in the e-cigarette industry or the opposition
• Includes a foreword written by Dr. Neal Benowitz

Chapter 1

Introduction to e-Cigarettes

K.E. Farsalinos

Abstract

e-Cigarettes represent alternative-to-smoking products which produce a visible aerosol that the user inhales. They simulate the psychobehavioral aspects of smoking dependence and deliver the chemical component of the smoking dependence, nicotine. Their intended use, from a public health perspective, is for harm reduction. Thus they could be used for abstention or reduction of tobacco consumption, to prevent relapse to smoking, and to avoid smoking initiation. There is, however, the possibility that they will be used as a new habit, even among nonsmokers. e-Cigarettes are very diverse, with different design, functional, and performance characteristics. This complicates research. The chemistry of e-Cigarettes, especially of the aerosol, is of particular importance in understanding the implications from use. The following chapters will address the analytical aspects of the aerosol, the assessment of biomarkers of exposure, the chemical aspects that could be the focus of regulation, and the risk assessment of use.

Keywords

e-Cigarettes; tobacco harm reduction; nicotine; smoking; aerosol; chemistry

Introduction

e-Cigarettes were recently invented and developed as an alternative-to-smoking method of nicotine intake. They are electronic devices with three main parts: a battery, an atomizer composed of a wick and metal coil, and a liquid (“e-liquid”) stored inside the atomizer. The function is to aerosolize the liquid, producing a visible aerosol which the user inhales. This is achieved by heating the metal coil inside the atomizer by an electrical current from the battery. e-Cigarettes are commonly called electronic nicotine-delivery devices (ENDS). However, because they can be used with non-nicotine e-liquids, the term ENDS is inaccurate and does not represent the whole spectrum of e-Cigarette devices and use patterns.

Invention and Evolution of e-Cigarettes

e-Cigarettes were invented by Hon Lik, a pharmacist from China. The initial patent was filed in 2004 in China and in 2005 in the United States Patent Office (application number 10/587,707).¹ The patent was published in 2007. The principle of e-Cigarette function, the evaporation of liquid and delivery of aerosol to the user, can be tracked back to patents published decades earlier. In 1930, a patent was published by the US Patent Office describing an electric vaporizer “for holding medicinal compounds which are electrically or otherwise heated to produce vapors for inhalation.”² Another patent in 1934 described a therapeutic apparatus that was “adapted for transforming volatile liquid medicaments into vapors or into mists of exceedingly fine particles.”³ A similar patent was published in 1936.⁴ These cases referred to vaporization for therapeutic applications. However, a patent filed by Herbert A. Gilbert and published in 1965 was titled “Smokeless non-tobacco cigarette” and described a battery-operated device “to provide a safe and harmless means for and method of smoking by replacing burning tobacco and paper with heated, moist, flavored air.”⁵

The term e-Cigarette includes a very diverse line of products, with different design, functional, and performance characteristics. Although there is still no consensus on terminology, the products available on the market are mainly of three types (Fig. 1.1).⁶

1. First-generation (“cigalike”) devices have similar size, shape, and appearance as tobacco cigarettes. They consist of a small lithium battery and a cartomizer. The battery can be either disposable (discarded after being discharged) or rechargeable. The cartomizer is a specific type of atomizer, consisting of a sponge-like polyfil (polyester fiber) material which is soaked with the liquid. There is no tank where the liquid is stored. Usually, cartomizers are prefilled with liquid; however, empty cartomizers are also available, which can be refilled with any liquid of choice. These were the first e-Cigarettes released to the market.

2. Second-generation devices consist of a rechargeable lithium battery of larger size and cylindrical shape, resembling a large pen. These are called eGo-type batteries. The atomizer is refillable and has a tank design, with a storage space for the liquid and a transparent window so that the user can see the level of the liquid. Initially, the whole atomizer had to be discarded after several milliliters of liquid consumption, but in the last few years they have been available with removable heads so that the resistance and wick parts are replaced and the body retained. This significantly reduced the cost of use and resulted in the development of more advanced products.

3. Third-generation devices, called “mods” or “advanced personal vaporizers” (APVs), consist of a large-capacity lithium battery with an integrated circuit that allows the user (“vaper”) to adjust the energy (wattage) delivered to the atomizer. They usually have either a cylindrical or a box-like shape. They can be combined with either second-generation atomizers or rebuildable atomizers, where the consumers can prepare a custom setup of resistance and wick. Most of these atomizers have a tank-type design, but there is a distinct group of “dripper” atomizers which have no storage space; the user introduces the liquid from the mouthpiece at regular intervals to keep the wicking material wet.

Figure 1.1 Types of e-Cigarettes. First generation: (A) disposable cigalike; (B) rechargeable cigalike and replacement prefilled cartomizers. Second generation: (C) eGo-type battery; (D) tank-type atomizers; (E) tank-type atomizer with replacement coil and wick head. Third generation: (F) box-shape variable-wattage battery device; (G) tank-type atomizer with replacement head; (H) rebuildable atomizer.

Another proposed classification is open versus closed systems, referring to the ability or not to refill the atomizer with liquid. However, closed systems can be modified and refilled. Furthermore, this classification is not indicative of different functional and performance characteristics and is of limited value for the understanding of consumers about the potential of the devices.

Since the initial introduction of e-Cigarettes to the market, new products have evolved rapidly. Cigalike devices, resembling the tobacco cigarette in shape, form, weight, and function, have low aerosol volume production⁷ and low nicotine delivery potential.^8,9 This was evident from surveys of dedicated users, which showed preference for newer generation e-Cigarettes.^10–12 The newer devices produce more sensory satisfaction¹¹ and more nicotine delivery and absorption,⁹ very close to the delivery rate and level of tobacco cigarettes.¹³ There has also been progress in construction materials, especially for atomizers. Current atomizers use pyrex glass and stainless steel instead of plastics and other metals, while the wicking material is cotton instead of silica¹⁴; still, no research has determined whether these developments are accompanied by fewer harmful emissions in the aerosol. A wide variety of liquids are available, with thousands of flavors¹⁵ and different nicotine content (including non-nicotine liquids). The main ingredients of the liquids are the humectants propylene glycol and glycerol, as well as flavoring compounds. The latter are either natural extracts or synthetically produced substances and are, in most cases, approved and generally recognized as safe for ingestion.

Tobacco Harm Reduction and e-Cigarettes

Harm reduction is the strategy, policy, and philosophy of reducing risk and thus the morbidity and mortality associated with an action or condition. Widely known examples are needle and syringe exchange programs and opioid substitution therapy for intravenous drug users to reduce the risk of blood-borne infectious diseases such as hepatitis and HIV.^16,17 These approaches have been actively endorsed by authorities such as the World Health Organization¹⁸ and have been integrated into the legislation of several countries.¹⁹ They have proven to be cost-effective and to reduce risk and improve quality of life.²⁰ Beyond that, the philosophy of harm reduction is strongly endorsed in everyday social activities, with characteristic examples being the use of seat belts in cars, helmets for motorcycles, and condoms in sexual activities.

Tobacco harm reduction seeks to decrease the net damage to health associated with the use of combustible tobacco products. It provides alternative sources of nicotine to smokers who are unable or unwilling to quit tobacco and nicotine entirely. It is based on the concept that “smokers smoke for nicotine but die from tar,” expressed by British tobacco addiction researcher Michael A.H. Russell,²¹ referring to combustion products and toxins other than nicotine which are present in smoke. Although nicotine itself may not be absolutely harmless, several studies evaluating the effects of non-combustible nicotine products have shown that it is highly unlikely to contribute significantly to smoking-related cancer and cardiovascular disease.^22–26 Russell proposed a harm reduction approach in 1974.²⁷ He realized the high dependence-producing potency and the broad appeal of the effects of nicotine on smokers and recognized that “the goal of abstinence and the abolition of all smoking are unrealistic and doomed to fail.” A few years later, smokeless tobacco products were proposed as harm reduction agents.^28,29 Since then, several studies have shown that their use can reduce some smoking-related diseases. The most characteristic case is in Sweden, where tobacco use prevalence in males is high but is mostly Scandinavian snus use rather than smoking. As a result, Sweden has the lowest death rates from cancer and cardiovascular disease among European Union countries.³⁰ Recently, major health organizations such as the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency have accepted long-term nicotine therapy for harm reduction in smokers.^31–33

Smoking dependence is not solely attributed to nicotine. The sensorimotor aspects and rituals of the smoking act have an important role.^34,35 e-Cigarettes are the only products in the current arsenal that replicate the rituals along with nicotine delivery. As such, they produce harm reduction in three ways: allowing smokers to quit, helping former smokers avoid relapse, and preventing non-smokers from initiating smoking. From a public health perspective, e-Cigarettes should be only used as a harm reduction product. However, they may also be used as a new habit by never-smokers or people not intending to smoke tobacco cigarettes. Population studies have shown that regular use of e-Cigarettes occurs mostly among smokers and former smokers, supporting the argument that they are used for harm reduction. However, experimentation is observed at increasing rates among non-smokers, and this should be continuously monitored to assess if they become regular users, consume nicoti...