Lactic Acid Salts of Nicotine Potentiate the Transfer of Toxic Metals into Electronic Cigarette Aerosols.

The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals.

Toxic Metals in Liquid and Aerosol from Pod-Type Electronic Cigarettes.

High-quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g., e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling and aerosol trapping materials are essential to generate accurate quantitative metal data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from three manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55-mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn and 463 ng/10 puffs for Pb. Our results showed some metal delivery from all the products examined and highly variable metal levels between manufacturer, brand and package.

A gas chromatography-mass spectrometry method for quantifying squalane and squalene in aerosol emissions of electronic cigarette, or vaping, products.

Numerous chemicals of unknown inhalational toxicity have been measured in electronic cigarette, or vaping, products (EVPs). In addition, little is known about the liquid-to-aerosol transmission and deliveries of these chemicals, including oil-like terpenes such as squalene (SQE) and squalane (SQA). To provide information on the aerosol deliveries of these compounds from EVPs, we developed and validated a quantitative method to measure squalene and squalane in EVP aerosol emissions. Validation parameters include measurement repeatability (SQA and SQE %RSD <6%), intermediate precision (SQA: %RSD 11%, SQE: %RSD 17%), accuracy (SQA: 86-107%, SQE: 104-113%), matrix effects, method robustness, and analyte stability. Limits of detection were 6.06 ng/mL puffed air volume for both squalene and squalane. The method was used to measure squalene and squalane in aerosol emissions of 153 EVPs associated with case patients from a recent outbreak of e-cigarette, or vaping, product use associated lung injury (EVALI). The EVPs analyzed were organized into nicotine, cannabidiol, and tetrahydrocannabinol products by the percentage of nicotine, cannabidiol, and tetrahydrocannabinol in total particulate matter after vaping. In case-associated tetrahydrocannabinol products the detection rates and mean concentrations were 82.4% and 33.0 ng/mL puffed air for squalene and 4.41% and 7.80 ng/mL puffed air for squalane.

Analysis of Toxic Metals in Aerosols from Devices Associated with Electronic Cigarette, or Vaping, Product Use Associated Lung Injury.

Research gaps exist in toxic metals characterization in e-cigarette, or vaping, products (EVPs) as these analytes typically have low concentrations and most standard aerosol trapping techniques have high metals background. An additional complication arises from differences in the EVP liquid formulations with nicotine products having polar properties and non-nicotine products often being non-polar. Differences in polar and non-polar matrices and the subsequent aerosol chemistries from various EVPs required modifications of our previously reported nicotine-based EVP aerosol method. Validation and application of the expanded method, suitable for both hydrophobic and hydrophilic aerosols, are reported here. The metals analyzed for this study were Al, Cr, Fe, Co, Ni, Cu, Cd, Sn, Ba, and Pb. The method limits of detection for the modified method ranged from 0.120 ng/10 puffs for Cd to 29.3 ng/10 puffs for Al and were higher than reported for the previous method. Results of the analyses for metals in aerosols obtained from 50 EVP products are reported. Cannabinoid based EVP aerosols were below reportable levels, except for one sample with 16.08 ng/10 puffs for Cu. Nicotine-based EVP results ranged from 6.72 ng/10 puffs for Pb to 203 ng/10 puffs for Sn. Results of the analyses for these metals showed that aerosols from only 5 of the 50 devices tested had detectable metal concentrations. Concentrations of toxic elements in the aerosols for nicotine-based EVP aerosol metal concentration ranges were consistent with previously published results of aerosol analyses from this class of devices.

Toxic Metal-Containing Particles in Aerosols from Pod-Type Electronic Cigarettes.

The popularity of electronic cigarettes (electronic nicotine delivery systems or ENDS) has grown rapidly over the past decade. With the continued evolution of ENDS, and the arrival of newer replaceable pod devices on the market, it is prudent to examine their emissions to help determine potential health risks to the user. Metal-containing particles were examined in aerosol from several pod-based devices from three manufacturers that offer flavored liquids in their respective products. Previous ENDS metal emissions studies focused on the total toxic metal concentrations in aerosols and have suggested that the principal sources are oxidized internal metal components that are in contact with the liquid. Most metal oxides have limited solubility, and it is likely that some metal content in ENDS aerosol may present as particles rather than dissolved forms. Examining the composition and number of particles in the ENDS aerosols is important because inhaled metal oxide particles cause pulmonary inflammation. Chronic inhalation of ENDS aerosol may lead to inflammatory cell activation in the lungs. Therefore, this study was designed to measure metal oxide particle concentrations and sizes in ENDS aerosols from select pod-based systems. Aerosol samples were generated with pod liquids (tobacco, mint or menthol) from devices produced by three manufacturers using CORESTA Recommended Method 81 parameters with a high-purity fluoropolymer aerosol trap. Particle sizes for chromium, iron, nickel, copper, zinc, tin and lead oxides were measured in triplicate using single particle inductively coupled plasma-mass spectrometry and dynamic light scattering. A novel aspect of these measurements included using dual element particle analysis to infer particle source component material. Particle concentrations in aerosols from the devices were variable between devices and from pod to pod, ranging from no detectable chromium- and zinc-containing particles in aerosol from some pods to 222,000 lead containing particles per 10 puffs from individual pods.

Analysis of Toxic Metals in Electronic Cigarette Aerosols Using a Novel Trap Design.

Since 2006 the domestic popularity and sales of electronic cigarettes (i.e., electronic nicotine delivery systems or ENDS) have grown rapidly. Although the constituents of the aerosol produced by ENDS have been previously investigated, differences in puff regimens and aerosol trapping schema in published literature often complicate result comparisons and data interpretation. As the ENDS product designs continue to evolve, there is a critical need to develop and validate robust methodologies for laboratory testing, appropriate aerosol generation and trapping media required for accurate determinations of ENDS aerosol metals deliveries. A simple, high metals purity, fluoropolymer trap was developed and validated that meets standard machine puffing regimen (CORESTA Recommended Method 81) specifications and exhibits negligible acid extractable metal backgrounds. Using a standard machine puffing regimen in combination with a fluoropolymer condensation trap, aerosol was generated and collected from select ENDS devices for analysis of chromium, nickel, copper, zinc, cadmium, tin, and lead with triple quadrupole inductively coupled plasma mass spectrometry. Devices tested spanned a range of commercial products, including flavored variants of JUUL pods, refillable tank systems, rechargeable cartridges, and single-use ENDs devices. Results showed that for aerosols generated under a fixed puffing regimen (50 puffs/collection), metal concentrations ranged from below the detection limits (LOD) to 614 ng copper and 339 ng zinc per 10 puffs. Cadmium concentrations were below LOD for all devices tested. Device specific aerosol levels of Sn and Pb ranged from below LOD to low nanogram levels. Cr and Ni were transported in aerosols at levels equivalent to, or slightly higher than in mainstream cigarette smoke using a standard smoking regimen. The generally lower levels of specific metals, Cd and Pb, transmitted in ENDS aerosols compared to mainstream cigarette smoke reflect possible reduction of harm for smokers who substitute the use of ENDS as cessation devices in place of smoking cigarettes.

Analysis of Toxic Metals in Liquid from Electronic Cigarettes.

As the technology of electronic nicotine delivery systems (ENDS), including e-cigarettes, evolves, assessing metal concentrations in liquids among brands over time becomes challenging. A method for quantification of chromium, nickel, copper, zinc, cadmium, tin, and lead in ENDS liquids using triple quadrupole inductively coupled plasma mass spectrometry was developed. The method's limits of detection (LODs) were 0.031, 0.032, 3.15, 1.27, 0.108, 0.099, 0.066 µg/g for Cr, Ni, Cu, Zn, Cd, Sn, and Pb respectively. Liquids analyzed were from different brands and flavors of refill bottles or single-use, rechargeable, and pod devices from different years. Scanning electron microscopy with energy dispersive spectroscopy further evaluated the device components' compositions. Refill liquids before contacting a device were below lowest reportable levels (LRL) for all metals. Copper and zinc were elevated in liquids from devices containing brass. Cadmium was

Electrothermal Vaporization-QQQ-ICP-MS for Determination of Chromium in Mainstream Cigarette Smoke Particulate.

Chromium is transported in mainstream tobacco smoke at very low concentrations. However, when chromium is deposited too deeply in the lungs for mucociliary clearance, or is in a particle that is too large to pass directly through tissues, it bioaccumulates in the lungs of smokers. It is important to determine the concentrations of chromium that are transported in mainstream smoke. Several reliable studies have resulted in reports of chromium concentrations in smoke particulate that were below limits of detection (LODs) for the instruments and methods employed. In this study, electrothermal vaporization-triple quad-inductively coupled plasma-mass spectrometry (ETV-QQQ-ICP-MS) was chosen for determination of chromium concentrations in mainstream smoke because of the high sensitivity of ETV combined with QQQ-ICP-MS. The smoke from five reference, quality control, and commercial cigarettes was analyzed using ETV-QQQ-ICP-MS with isotope dilution for quantitative determination of chromium. The method LOD was sufficiently low that chromium concentrations in mainstream smoke could indeed be determined. The chromium concentrations in the smoke particulate were between 0.60 and 1.03 ng/cigarette. The range of chromium concentrations was at or below previously reported LODs. Determination of the oxidation state of the chromium transported in mainstream smoke would also be important, in consideration of the fact that both chromium(III) and chromium(VI) oxidation states cause inhalation toxicity, but chromium(VI) is also a carcinogen. It was possible to separate the oxidation states using ETV-QQQ-ICP-MS. However, determination of individual species at the levels found in mainstream smoke particulate matter was not possible with the present method.

Characterization of SPECTRUM Variable Nicotine Research Cigarettes.

OBJECTIVE: To provide researchers an extensive characterization of the SPECTRUM variable nicotine research cigarettes. METHODS: Data on cigarette physical properties, nicotine content, harmful and potentially harmful constituents in the tobacco filler was compiled. RESULTS: Data on physical properties, concentrations of menthol, nicotine and minor alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, ammonia, and toxic metals in the filler tobacco for all available varieties of Spectrum research cigarettes are provided. The similarity in the chemistry and physical properties of SPECTRUM cigarettes to commercial cigarettes renders them acceptable for use in behavioral studies. Baseline information on harmful and potentially harmful constituents in research tobacco products, particularly constituent levels such as minor alkaloids that fall outside typical ranges reported for commercial, provide researchers with the opportunity to monitor smoking behavior and to identify biomarkers that will inform efforts to understand the role of nicotine in creating and sustaining addiction. CONCLUSIONS: Well characterized research cigarettes suitable for human consumption are an important tool in clinical studies for investigating the physiological impacts of cigarettes delivering various levels of nicotine, the impact of reduced nicotine cigarettes on nicotine addiction, and the relationship between nicotine dose and smoking behavior.

Triple Quad-ICP-MS Measurement of Toxic Metals in Mainstream Cigarette Smoke from Spectrum Research Cigarettes.

We previously reported toxic metal concentrations in the mainstream smoke from 50 varieties of commercial cigarettes available in the USA using quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). However, efforts to continue producing high quality data on select mainstream cigarette smoke constituents demand continued improvements in instrumentation and methodology and application of the methodology to cigarettes that differ in design or construction. Here we report a new application of 'triple quad'-ICP-MS instrumentation to analyze seven toxic metals in mainstream cigarette smoke from the Spectrum variable nicotine research cigarettes. The Spectrum cigarettes are available for research purposes in different configurations of low or conventional levels of nicotine, mentholated or nonmentholated, and tar delivery ranges described as 'low tar' or 'high tar'. Detailed characterizations of specific harmful or potentially harmful constituents delivered by these research cigarettes will help inform researchers using these cigarettes in exposure studies, cessation studies and studies related to nicotine addiction or compensation.

High-Throughput Determination of Mercury in Tobacco and Mainstream Smoke from Little Cigars.

A method was developed that utilizes a platinum trap for mercury from mainstream tobacco smoke, which represents an improvement over traditional approaches that require impingers and long sample preparation procedures. In this approach, the trapped mercury is directly released for analysis by heating the trap in a direct mercury analyzer. The method was applied to the analysis of mercury in the mainstream smoke of little cigars. The mercury levels in little cigar smoke obtained under Health Canada Intense smoking machine conditions ranged from 7.1 × 10(-3) to 1.2 × 10(-2) mg/m(3). These air mercury levels exceed the chronic inhalation minimal risk level corrected for intermittent exposure to metallic mercury (e.g., 1 or 2 h per day, 5 days per week) determined by the Agency for Toxic Substances and Disease Registry. Multivariate statistical analysis was used to assess associations between mercury levels and little cigar physical design properties. Filter ventilation was identified as the principal physical parameter influencing mercury concentrations in mainstream little cigar smoke generated under ISO machine smoking conditions. With filter ventilation blocked under Health Canada Intense smoking conditions, mercury concentrations in tobacco and puff number (smoke volume) were the primary physical parameters that influenced mainstream smoke mercury concentrations.