This chapter presents a review of published data and new data collected by RTI International to provide the reader a perspective on the sources and external factors that influence the magnitude of exposure to e-Cigarette vapor.The author reviewed over 100 published articles from the e-Cigarette, conventional cigarette, and aerosol science fields. Articles were selected that have data to help advance our understanding of user, secondary, and tertiary exposures. Although the cited literature in this chapter is limited, the number of published papers focused on e-Cigarette vapor exposures continues to increase annually. As such,the literature review was limited to those published before August 1, 2016. A note on terminology: Vapors includes both the particles and gases produced by an e-Cigarette. Particles and aerosols are used synonymously following the definition by Hinds: “An aerosol is defined in its simplest form as a collection of solid or liquid particles in a gas.”1

A note on terminology: Vapors includes both the particles and gases produced by an e-Cigarette. Particles and aerosols are used synonymously following the definition by Hinds: “An aerosol is defined in its simplest form as a collection of solid or liquid particles in a gas.”

Introduction

This chapter discusses the physical and chemical changes in e-Cigarette vapor during inhalation and exhalation by the user. The vapor properties span aerosol and gas phases, and the chemical concentration. These factors influence the nicotine and flavoring dose received by the user and exhaled leading to secondhand exposure. The physical and chemical processes will be supported by published theortical and empirical evidence plus new findings from current research. How the user and device profile influences the chemical and physical properties of the produced vapors is discussed in Chapter 2. Although that is briefly mentioned in this chapter to add supplemental information, the reader should refer to Chapter 2 for details. The toxicological and physiological impacts of e-Cigarette vapors are discussed in Chapter 4.

e-Cigarette Constituent Apprortionment

e-Cigarette liquids(e-liquids) are chemical complex. The main ingredients by mass are a carrier liquid (typically propylene glycol [PG] and/ or vegetable glycerin [VG], water, and nicotine. Each liquid is then customized with a unique combination of flavorings, perseratives, and artifical colors selected by the manufacturer. How these ingredients apportion from the liquid into the aerosol and gas phases during e-Cigarette use has not been extensively studied.

Table 3.1 gives the available gas(cid:1)particle apportionment data for selected e-liquid ingredients. In general, the apportionment of the constituents between the particle and gas phases is dependent on the vapor pressure of each constituent. A chemical with a higher vapor pressure will be more volatile and more likely to prefer the gas phase once heated by the e-Cigarette device. The polar volatile compounds, however, will partition between the gas and particle phases because the PG/VG carriers are humectants. Their affinity for polar compounds will retain a portion of the ingredients in the particle phase. The limited data available indicate that the food preservatives BHA and BHT are only present in the particle phase.

Measurement Methods

Methods for measuring the concentration and composition of e-Cigarette vapors, both particles and gases, fall into two categories. Real-time methods provide temporally resolved data useful for tracking the evolution of the vapor’s physical and chemical properties over time. Integrated methods provide a time-averaged measurement of vapor properties, which is useful for quantifying trace components with concentrations below the detection limit of real-time instrumentation. Different techniques are used for the aerosol and gas phase measurements. Not all of these methods are applicable for measuring aerosol and gas phase constituents, characterizing chemical and physical changes that occur in a simulated user’s respiratory system, and potential secondhand exposure. This section summarizes available methods and operating techniques. There are numerous books and journal articles that provide detailed theoretical and practical information about these methods.

Aerosol Instrumentation

Aerosol measurement methods that quantify the particle concentration, size distribution, and chemical composition are available. Certain methods can measure one or more of these characteristics either in real time or as a time-integrated average. Particle concentration can be expressed as a number per unit volume or a mass per unit volume. Although either number or mass concentration is the principle measurement, one can be calculated from the other if the particle diameter and density are known or assumed.

Real-Time Aerosol Instruments

These are used frequently to characterize the particle concentration and size distributions produced by e-Cigarettes.4(cid:1)6 Table 3.2 describes the various methods. These devices are preferred because they provide a large quantity of data quickly, temporal resolution being on the order of seconds. High temporal resolution is useful for understanding how the particle physical characteristics produced by a device or e-liquid evolve over time. Another advantage is that most types of real-time instruments generate data that spans a wide range of sizes classified into many discrete bins to provide a continuous measure of the size distribution. If these instruments are used properly, they also yield accurate and precise data. Proper use means the user must be aware of potential measurement artifacts. A potential artifact unique to e-Cigarette particles results from their highly volatile nature. Devices that operate under vacuum or high flow conditions may cause the liquid particles to evaporate during measurement, reducing the measured size distribution. The magnitude of the error depends on the volatility, surface tension and relative composition of the semivolatiles in the aerosol particles. For example, differential mobility analyzer (DMA) measurements can have a negative bias of 10(cid:1)35% under certain operating conditions.7

Given the volatility, high concentration, and short puff duration of e-Cigarette aerosol, researchers may be tempted to set their DMA toa low sheath flow and fast scan rate in order to measure the complete size distribution from a single puff. However, these DMA operating conditions promote evaporation and will maximize the negative bias in the measured particle size distribution.7 A simple procedure to minimize the evaporation within a DMA is to take advantage of the fact that DMAs internally recycle the air flow (called sheath air) required for proper operation. Measurement of the particle size distribution after sampling multiple puffs to establish a steady-state PG:VG vapor concentration in the sheath air will minimize the negative bias in the size distribution.

Many instruments also are unable to accurately measure the extremely high particle concentrations emitted directly from an e-Cigarette. An accurate measurement requires careful dilution of the aerosol to reduce the concentration without promoting evaporation. A properly operated commercially available or customized dilution system will minimize evaporation by establishing a steady-state PG:VG vapor concentration within the diluter.

Integrated Aerosol Instruments

These collect the particles on a substrate or collection media for subsequent mass or chemical analysis. A variety of particle collection media are available. The most common are glass fiber filters, membrane filters, and polyurethane foam (PUF). CORESTA Method No. 81 and Health Canada Test Method T-115 specify glass fiber substrates because the methods were originally developed for conventional tobacco smoke collection in a laboratory system. Membrane filters are available in various materials for laboratory or field studies. A commonly used material for aerosol sampling is polytetrafluorethylene (PTFE) because it is chemically inert (i.e., will not react with the collected particles), hydrophobic, and not subject to accumulation of electrostatic charge. PUF is not commonly used for general aerosol measurements. However, the high mass fraction of organic aerosoline-Cigarette vapors increases the versatility of PUF, because the total mass and the speciated organic mass can be measured as described in Gas Phase Methods. The sampler can capture all particles on a single substrate or use impaction to inertially separate the particles by their size for collection on one or more substrates. There are numerous single stage filter holders available that collect all the particles or have an impaction stage to collect a subfraction of the aerosol.8 The CORESTA methods, for example, collect all particles. Alternatively, a PM sampler will 2.5collect essentially 100% of all particles with aerodynamic diameters smaller than 2.5um. A cascade impactor has multiple stages that collect all particles between the lower and upper aerodynamic sizes. The number of size separation stages determines the resolution of the measured mass size distribution. Like the real-time aerosol instruments, the integrated devices are subject to sample collection artifacts. Again, the most common artifact when sampling e-Cigarette emissions is evaporation of the volatile components. The air velocity through the filter, referred to as the face velocity, drives the evaporation of the volatile components. A higher face velocity promotes evaporation. Face velocities greater than 10cm/second cause significant evaporative losses.9 For comparison, CORESTA Recommended Method 81 specifies a face velocity of 0.2cm/second to minimize evaporative losses. Similarly, the pressure drop across cascade impactor stages, especially stages designed to collect submicrometer particles, can cause evaporation.10 If evaporative losses are suspected, a PUF filter or sorbent tube placed downstream from the filter is recommended to capture the gases. The most common analytical method performed on filter substrates is gravimetric analysis using a high precision microbalance (61ug) to determine the total mass of the particles collected. Because of the volatile nature of e-Cigarette aerosols, storage of collected filters in a 4 Crefrigerator is recommended. Also, because the aerosols contain a high(cid:3) water fraction, equilibration of the filters for 24 hours at 23 C and 35% relative humidity (RH) prior to preweight and postweight measurements will account for water absorption on the filter media. Other analytical methods can quantify metal and organic species contents. The methods selected will depend on whether or not multiple analyses are desired and the desired minimum detection limit (MDL). Metals can be quantified by x-ray fluorescence (nondestructive), atomic absorption (destructive), or inductively coupled mass spectrometry (destructive). The organic species, including nicotine and flavors, can be chemically extracted from the filter substrate for analysis by gas chromatography and liquid chromatography. collect essentially 100% of all particles with aerodynamic diameterssmaller than 2.5um. A cascade impactor has multiple stages that collect all particles between the lower and upper aerodynamic sizes. The number of size separation stages determines the resolution of the measured mass size distribution. Like the real-time aerosol instruments, the integrated devices are subject to sample collection artifacts. Again, the most common artifact when sampling e-Cigarette emissions is evaporation of the volatile components. The air velocity through the filter, referred to as the face velocity, drives the evaporation of the volatile components.

A higher face velocity promotes evaporation. Face velocities greater than 10cm/second cause significant evaporative losses.9 For comparison, CORESTA Recommended Method 81 specifies a face velocity of 0.2cm/second to minimize evaporative losses. Similarly, the pressure drop across cascade impactor stages, especially stages designed to collect submicrometer particles, can cause evaporation.10 If evaporative losses are suspected, a PUF filter or sorbent tube placed downstream from the filter is recommended to capture the gases.

The most common analytical method performed on filter substrates is gravimetric analysis using a high precision microbalance (61ug) to determine the total mass of the particles collected. Because of the volatile nature of e-Cigarette aerosols, storage of collected filters in a 4 C refrigerator is recommended. Also, because the aerosols contain a hig(cid:3) water fraction, equilibration of the filters for 24 hours at 23 C and 35% relative humidity (RH) prior to preweight and postweight measurements will account for water absorption on the filter media. Other analytical methods can quantify metal and organic species contents. The methods selected will depend on whether or notmultiple analyses are desired and the desired minimum detection limit (MDL). Metals can be quantified by x-ray fluorescence (nondestructive), atomic absorption (destructive), or inductivelycoupled mass spectrometry (destructive). The organic species, including nicotine and flavors, can be chemically extracted from the filter substrate for analysis by gas chromatography and liquid chromatography