Characterization of mass distribution in a biomimetic aerosol exposure system.

OBJECTIVE: Lack of biomimicry in geometry and flow conditions of emissions systems for analytical testing and biological exposure has led to fundamental limitations, including a poor understanding of dose delivered to specific airway locations. This work characterizes mass distribution of a JUUL® brand e-cigarette in a Biomimetic Aerosol Exposure System (BAES). MATERIALS AND METHODS: A combination of mass balance, direct measurements, and inferences based on direct measurements were used to characterize regional and local dose as a function of system flow path configuration and emissions topography profile. RESULTS: Doses produced by the emissions topography profile with only puffing were significantly different from profiles with clean air inhalation following puffs. Mass characterization results support that dose can be manipulated using flow path geometry. Local and regional deposition was mapped throughout the system. DISCUSSION AND CONCLUSIONS: We estimate the fraction of yield to the mouth deposited at several locations throughout the system for a variety of puffing and respiration topographies and show that emissions topography profile and system flow path geometry affect dose. This work provides proof-of-concept for assessing mass distribution as a function of aerosol generator (e-cigarette product), user airway geometry, and inhalation and puffing topography.

Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"

Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system-a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide.

Effect of third-party components on emissions from a pod style electronic cigarette.

Electronic nicotine delivery systems (ENDS) have been associated with a dramatic increase in youth becoming addicted to nicotine following decades-long decline in cigarette smoking uptake. The United States Food and Drug Administration, Center for Tobacco Products (FDA/CTP) is responsible for regulating devices and consumable materials associated with ENDS. State and federal regulations regarding flavoring compounds in ENDS liquids (e-liquids) may be circumvented when vendors market refillable reservoirs side-by-side with noncompliant e-liquids. This study investigated the effect of third-party refillable versus manufacturer-supplied single-use reservoirs on total particulate matter (TPM) and nicotine emissions. The maximum TPM yield per puff was 5.6 times higher for the third-party (Blankz) reservoir (12.4 mg/puff) in comparison with the manufacturer's (JUUL) reservoir (2.2 mg/puff), whereas the maximum TPM concentration was over 7 times higher for third party (0.200 mg/ml) versus manufacturer (0.028 mg/ml) pod. The third-party pod was tested with nicotine concentrations ranging from 0% to 4%. The mass ratio of nicotine present in the aerosol (mg Nic/mg TPM) was found to be approximately the same as the mass ratio of the e-liquid (mg Nic/mg e-liquid) for both pods and all 3 nicotine laden e-liquids tested. Toxicant exposure may increase when consumers use third-party pods with ENDS devices. Refillable reservoirs are a significant barrier to regulatory restrictions on potentially toxic additives to e-liquids. It is recommended FDA/CTP require emissions characterization of third-party reservoirs used with each ENDS they are compatible with and should be required to demonstrate no increased potential toxicant exposure in comparison with manufacturer-provided reservoirs.

Nominal Operating Envelope of Pod and Pen Style Electronic Cigarettes.

Many Electronic Nicotine Delivery Systems (ENDS) employ integrated sensors to detect user puffing behavior and activate the heating coil to initiate aerosol generation. The minimum puff flow rate and duration at which the ENDS device begins to generate aerosol are important parameters in quantifying the viable operating envelope of the device and are essential to formulating a design of experiments for comprehensive emissions characterization. An accurate and unbiased method for quantifying the flow condition operating envelope of ENDS is needed to quantify product characteristics across research laboratories. This study reports an accurate, unbiased method for measuring the minimum and maximum aerosolization puff flow rate and duration of seven pod-style, four pen-style and two disposable ENDS. The minimum aerosolization flow rate ranged from 2.5 to 23 (mL/s) and the minimum aerosolization duration ranged from 0.5 to 1.0 (s) across the ENDS studied. The maximum aerosolization flow rate was defined to be when the onset of liquid aspiration was evident, at flow rates ranging from 50 to 88 (mL/s). Results are presented which provide preliminary estimates for the effective maximum aerosolization flow rate and duration envelope of each ENDS. The variation in operating envelope observed between ENDS products of differing design by various manufacturers has implications for development of standardized emissions testing protocols and data reporting required for regulatory approval of new products.

A Comparison between Cigarette Topography from a One-Week Natural Environment Study to FTC/ISO, Health Canada, and Massachusetts Department of Public Health Puff Profile Standards.

Standardized topography protocols for testing cigarette emissions include the Federal Trade Commission/International Standard Organization (FTC/ISO), the Massachusetts Department of Health (MDPH), and Health Canada (HC). Data are lacking for how well these protocols represent actual use behavior. This study aims to compare puff protocol standards to actual use topography measured in natural environments across a range of cigarette brands. Current smokers between 18 and 65 years of age were recruited. Each participant was provided with a wPUM™ cigarette topography monitor and instructed to use the monitor with their usual brand cigarette ad libitum in their natural environment for one week. Monitors were tested for repeatability, and data were checked for quality and analyzed with the TAP™ topography analysis program. Data from n = 26 participants were analyzed. Puff flow rates ranged from 17.2 to 110.6 mL/s, with a mean (STD) of 40.4 (21.7) mL/s; durations from 0.7 to 3.1 s, with a mean (STD) of 1.5 ± 0.5 s; and volumes from 21.4 to 159.2 mL, with a mean (STD) of 54.9 (29.8) mL. Current topography standards were found to be insufficient to represent smoking across the wide range of real behaviors. These data suggest updated standards are needed such that emissions tests will provide meaningful risk assessments.