Introduction to e-Cigarettes
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 inaccu- rate and does not represent the whole spectrum of e-Cigarette devices and use patterns.
What is it:  ENDS contains three main parts: (1) A battery (2) An atomizer composed of a wick and metal coil (3) A liquid (“e-liquid”) stored inside the atomizer.
For-What: The function is to aerosolize the liquid, producing a visible aerosol which the user inhales.
How to : This is achieved by heating the metal coil inside the atomizer by an electrical current from the battery.
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). 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.” 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.” A similar patent was published in 1936. 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.” 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：
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 dispoable. First generation: (A) disposable cigalike; (B) rechargeable replacement prefilled cartomizers.
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 serveral milliters of liquid consumption, but in the last few years they have been availabe 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.
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.
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.
Analytical Assessment of e-Cigarettes
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 production and low nicotine delivery potential. This was evident from surveys of dedicated users, which showed preference for newer generation e-Cigarettes. The newer devices produce more sensory satisfaction and more nicotine delivery and absorption, very close to the delivery rate and level of tobacco cigarettes. 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 silica; 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 flavors 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. These approaches have been actively endorsed by authorities such as the World Health Organization and have been integrated into the legislation of several countries. They have proven to be cost-effective and to reduce risk and improve quality of life. 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, 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. Russell proposed a harm reduction approach in 1974. 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 reduc- tion agents. 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. 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.Smoking dependence is not solely attributed to nicotine. The sensorimotor aspects and rituals of the smoking act have an important role.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 nicotine-containing e-Cigarettes, or transition to smoking. There has been an exponential increase in e-Cigarette awareness and use over the last few years.As expected, this has attracted the interest of researchers, public health, governments, and regulators.
Research on E-cigarettes
Intense research on all aspects related to e-Cigarettes, including chemistry, toxicology, clinical effects, and population effects, is ongoing. e-Cigarettes are complex products. Liquids have many ingredients, particularly flavoring compounds. Although no chemical was specifically synthesized or developed to be used in e-Cigarettes, and almost all compounds used are approved for human consumption, their safety has been mostly assessed for ingestion. With e-Cigarettes, the liquid is subject to heating and evaporation, resulting in the emission of an aerosol. The aerosol is inhaled instead of ingested, which leads to direct lung exposure and fast absorption directly into the arterial circulation, bypassing the first-pass metabolism in the liver. The atomizers, where the liquid is stored, have several metal and plastic components, and there may be interaction between these and the liquids, resultingin emission of harmful substances. The heating process and the aerosol yield are highly dependent on the design and structure of the atomizer and the energy delivered from the battery. The huge variability of e-Cigarette devices and liquids makes evaluation of the aerosol composition complex.
Chemical evaluation is a vital step in the assessment of many consumer products. It is important for informing consumers about the potential benefits and risks of exposure and informing regulators to make appropriate decisions to ensure quality and safety. In the case of e-Cigarettes, the chemistry of the emitted aerosol is critical; this is what the user inhales. Obviously, there is overlap between liquid composition and aerosol emissions, but the heating process can result in the de novo formation of chemicals not present in the liquid formulation. The following chapters will discuss analytical aspects of the aerosol, assessment of biomarkers of exposure, regulatory decisions that could ensure the quality of products, and risk assessment, especially for smokers who make the partial or complete switch to e-Cigarettes. Research is continuously evolving and progressing, and the chapters will address current knowledge and future prospects.
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