In the preparation of this chapter, the author read approximately 150 peer-reviewed publications and a large number of recent conference proceedings. Two things became apparent: (1) electronic nicotine delivery systems (ENDS) are evolving rapidly as manufacturers innovate, and the peer-reviewed literature does not adequately reflect products on the market. (2) Published findings of analytical testing and analysis of ENDS tend to show thermal decomposition products at either very low or very high levels, with little agreement in the middle. To address the first issue, recent conference proceedings are cited to fill gaps in the literature. The second issue is addressed only when required to highlight differences in testing methodologies. The objective is primarily to explain the results and implications of ENDS aerosol testing. Definitive advice on the choice and appropriateness of particular test methods must await further developments.

All current ENDS deliver nicotine in the form of a heated aerosol commonly comprised of propylene glycol (PG), glycerin (GLY), water, and flavoring. The modern ENDS arose from a 2003 invention by Chinese pharmacist Lik Honbut the concept of delivering nicotine in a heated PG or GLY aerosol has been around since at least 1960. Technical challenges, including battery technology, delayed commercialization until the 21st century. ENDS are increasingly popular, with millions of users in the United States and Europe,3(cid:1)5 and are often a replacement for combustible cigarettes.6 The aerosol is called a vapor, and usage is called vaping. This is inaccurate, because “vapor” refers to a gaseous state, while the aerosol from ENDS is a complex suspension of fine particles, not pure gas phase vapor compounds. The ENDS aerosol is a complex mixture containing semiliquid particulate matter along with gas phase compounds. Unlike combustible cigarette smoke, ENDS aerosol does not contain true particulate matter. It is produced by atomization of the liquid and not through combustion of carbon-based material, as in smoking a combustible cigarette. The aerosol is typically generated by heating the liquid with a small gauge metal wire in contact with a heat-resistant material containing the liquid. Two main types of atomizers are currently used. Devices with a separate wick to transfer the liquid from a reservoir to the heating coil are called clearomizers or atomizers. Those that integrate the heating coilintotheliquid chamberare calledcartomizers. In all devices,aerosol is delivered for inhalation into the user’s respiratory tract.7 Most of the aerosol is retained by the respiratory tract, and any not retained is exhaled into the environment.8 ENDS come in a variety of shapes and sizes, from small devices that resemble a conventional combustible cigarette and are called cigalikes, to much larger devices called personal vaporizers, mods, or advanced devices. The larger devices visually have more in common with other electronic devices than with combustible cigarettes. ENDS have been commercialized in various forms and designs but all have similar physical and operational characteristics: a battery, a liquid reservoir, and an atomizer. The size of the product and amount of aerosol that can be delivered without recharging the battery are driven by the capacity of the battery. Small cigalikes can deliver the contents of a single, prefilled cartridge of around 1mL of liquid on a single charge. Larger devices can deliver the contents of 5(cid:1)40mL before recharging. Table 2.1 gives the characteristics of common ENDS, including the chronological generation of each product, which is often cited in the literature.

The term “mods” has several meanings in the peer-reviewed literature and by end users. The original meaning sprang from the end user modifications to improve performance, such as the once common practice of constructing devices using flashlight bodies and large capacity batteries. It has also been used incorrectly to describe any variable voltage or variable power ENDS. It now means atomizers and tanks that can be modified by the end user and will be so used here. A cigalike operateswhen the user draws air throughit, which triggers an airflow sensor and activates a battery that powers an atomizer to produce an aerosol from liquid in the cartomizer (Fig. 2.1). Advanced devices function in much the same way except that power is applied to the atomizer coil only when a button is depressed by the user.

Current cigalikes are integrated cartomizer devices that contain the atomizer and liquid in one unit. The liquid reservoir is comprised of an adsorbent material that transfers the liquid to a wick wrapped by the heating coil. The wicking material is usually silica based but may be other materials. The adsorbent material in the cartomizer also helps tocontain the liquid and prevent leaks (Fig. 2.2).

Figure2.2DiagramofcartomizerusedincigalikeENDS.(1)Batteryconnecter,(2and3)nonresistancewires, (4)resistanceheatingwire,(5)liquidreservoirwithabsorbentmaterial (6)aerosolexit,and(7)mouthend. The power supply unit and tank-based atomizer are available from many suppliers and are usually interchangeable, allowing the user to select different vendors for the two components. Fig. 2.3 is a diagram of a rechargeable, variable power, temperature-controlled power supply unit. One type of refillable tank-based atomizer is the clearomizer. It is usually cylindrical in shape with a clear plastic or glass tank and a separate wick, usually silica, that transfers the liquid from the tank to the heating coil. A clear tank allows the user to see the level of liquid. The wick may be placed at either the top or bottom of the tank (Fig. 2.4, Tanks A and B). Top coil tanks require longer wicks and thus have poor liquid-wicking rates, are more prone to dry puffing, and are limited in the maximum power that can be applied. Another type of refillable is the cartomizer. It too is usually cylin- drical, with a clear plastic or glass tank containing a replaceable atomizer coil. The liquid is transferred directly from the tank to the cartomizer containing the coil (Figure 2.4, Tank C). The coil may be oriented horizontally or vertically. The wicking material can be made from a variety of materials, including silica, polyfill, cotton, or other heat-resistant absorbent material. Since the cartomizer must be in contact with the liquid, it is usually placed at the bottom of the tank. Because of the use of very short wicks and direct contact with the liquid, cartomizer tanks have good liquid-wicking rates, are less prone to dry puffing, and are available in a wide variety of power ranges.

Refillable atomizers that allow for user customization are commonly called “mods.” They may include rebuildable atomizers (RBAs), which allow the user to select and assemble the wick and coil materials instead of using commercially produced atomizers. RBAs are of two main categories: rebuildable tank atomizers (RTAs) and rebuildable dripping ato- mizers (RDAs). RTAs are similar in design to clearomizers in that a wick transfers the liquid from the tank to the coil. They are very customizable and offer many wicking and coil materials. RDAs are devices where the liquid is added or “dripped” by the user directly onto the coil and wick. These devices do not contain a tank. Because the amount of liquid is small, they are prone to overheat during active puffing due to a lack of liquid supply to the coil. Very few studies have been conducted on RDAs, but the limited research indicates that they may produce significant thermal decomposition products during normal use.9 Given the range of configurations that can be made by the consumer and thus their nonstandard design, mods will not be covered in detail here. Another design feature of ENDS is temperature regulation of the atomizer coil. Nontemperature-regulated devices use Nichrome or Kanthal wires because their physical properties, including resistance, stay relatively consistent with changing temperature. This simplifies control and allows for direct-battery and variable voltage devices. However, starting in 2010, devices began to use onboard processors for software-controlled output power and direct wattage control.

Variable wattage devices can put out consistent vapor even if the resistance of the heating coil changes. Temperature-limiting and temperature-controlled ENDS use heating wires that undergo significant, repeatable changes in resistance when the temperature changes. Typical materials are pure nickel, pure titanium, and stainless steel. The resistance of the wire is an intrinsic property that varies only with temperature, so there is no time lag as happens with an external sensor. A resistance-based temperature-controlled device can react to changes in temperature as fast as the controller can sample the resistance of the coil, often hundreds or thousands of times per second. The measured resistance of the atomizer coil can be used to determine coil temperature, as shown in Fig. 2.5, using the mathematical formula R 5R ½11αðT 2T Þ(cid:3), where R and T are the resis measured ref actual ref ref reftance of the conductor material at a reference temperature, usually 20(cid:4)C, and α is the temperature coefficient of resistance for the conduc- tor. As of 2016, it is estimated that half of all new large ENDS have some form of temperature control or temperature limiting. However, because of the increased technical sophistication that current implementations require of the user and the relative scarcity of temperature sensing consumables and atomizers, fewer than 20% of devices that are temperature capable are routinely used in a temperature-controlled mode. This percentage is expected to rise as devices become more user friendly. Further information on this technology and its regulatory perspective is provided in Chapter 5. The increasing popularity of ENDS is causing concern among public health groups and regulators, given the lack of oversight on these products. In part, this is due to the fact that ENDS manufacturers generally do not provide analytical testing information on device perfor- mance or other information such as yield, production of thermal decomposition products, and batch to batch reproducibility. Further, the media and scientific publications tend to regard ENDS as a general class, while a wide range of products are available on the retail market, often with liquid, batteries, and tank selected by consumers from different suppliers. The scientific literature has shown large performance differences across the range of available ENDS. The impact on nicotine yield and public health is not known.10 The following sections of this chapter review the available information on the composition of liquids, common contaminants, aerosol production, and compounds of concern that might be present in the aerosol, with emphasis on methods to detect and quantitate.

Nicotine in liquids

Almost all ENDS deliver nicotine. Unlike in tobacco products that include the whole leaf, the amount of added nicotine via ENDS is controlled by the producer of the liquid. Nicotine content is communicated to the consumer in several ways. Prefilled devices may list total nicotine amount or the nicotine concentration of the liquid in units of mg/mL, mg/gram, or percent nicotine by weight. Refill liquids typically list mg/mL or percent nicotine by volume. The yield of aerosol among ENDS varies from less than 2mg/puff to over 40mg/puff, depending on the type of device and power level. Nicotine in commercial liquids and prefilled devices varies from 3mg/mL on the low end to 50mg/mL on the very high end. Three to 6mg/mL nicotine-containing liquids are commonly used in highest yielding ENDS and 25(cid:1)50mg/mL in lower yielding prefilled cigalikes. By matching nicotine liquid content to device yield, consumers are exposed to a narrower range of nicotine amount per puff than might be obvious from the range of nicotine content available on the market. Use of a 50mg/mL liquid would be very unpleasant in a high-yielding fourth-generation ENDS but acceptable in a cigalike. However, the level listed on the labels of ciga- like cartridges and refill solutions is often significantly different from measured values.11(cid:1)20 The Salt Lake County Health Department21 recently tested the amount of nicotine in 153 liquid samples from local retail shops and reported that 61% differed by at least 10% from the labeled content, with discrepancies that ranged from 88% less to 840% more than stated. Of the 33 samples that listed the nicotine amount as zero, 1 contained 7.35mg/mL. Given the number of reports that have found that nicotine content in the refill liquids or prefilled devices does not match the labeled amounts, it appears that a large percentage of commercial products are not accurately labeled. Table 2.2 summarizes historical nicotine test results for refill solutions; there appears to be little improvement over time in the accuracy of labeling.

However, several industry groups do have standards in place that mandate the nicotine content in refill liquids. The American E-Liquid Manufacturing Standards Association (AEMSA)24 and the Electronic Cigarette Trade Association of Canada (ECTA)25 require that their members produce and test liquids within a tolerance level of 610% of their labeled nicotine content. Production of refill liquids falling under European Union26 or US Food and Drug (FDA)27 regulation will also likely require mandatory nicotine analyses. There are currently no standardized analysis methods for nicotine in liquids. Several have been used: nonaqueous titrations,24,28 high-performance liquid chromatography (HPLC),14liquid