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Biology subjects

Pankow, J. F.

Publications and source records attributed to Pankow, J. F..

4 recordsLinked to original sources

Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes

Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants ("Watermelon Ice," "Blueberry Ice," "Green Mint," and "Polar Mint") were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescent microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13 - 19 mg/mL) were lower than many 4th generation e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44 - 100%. SURGE fluids and aerosols had four dominant flavor chemicals (> 1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were < 100 based on consumption of 1 - 2 SURGE cigarettes/day. Replacing the heating coil with a sonicator did not eliminate chemicals, including aldehydes, in aerosols or diminish toxicity in comparisons between SURGE and other pod products. The high concentrations of nicotine, WS-23, flavor chemicals, and aldehydes and the cytotoxicity of SURGE aerosols do not support the hypothesis that aerosols from u-cigarettes are less harmful than those from e-cigarettes.

pharmacology and toxicology↗

Tracking the Movement of Electronic Cigarette Flavor Chemicals and Nicotine from Refill Fluids to Aerosol, Lungs and Exhale

Electronic cigarettes (ECs) have been linked to lung diseases, including COVID-19, with little understanding of exposure, retention, and exhalation of EC aerosol chemicals. Here, flavor chemicals and nicotine were quantified in two refill fluids, their transfer efficiency to EC aerosols was determined, exhalation by human participants was measured, and chemical retention was modeled. Nicotine transferred well to aerosols irrespective of topography; however, transfer efficiencies of flavor chemicals depended on the chemical, puff volume, puff duration, pump head, and EC power. Participants could be classified as "mouth inhalers" or "lung inhalers" based on their retention and exhale of flavor chemicals and nicotine. Only mouth inhalers exhaled sufficient concentrations of flavor chemicals and nicotine to contribute to chemical deposition on environmental surfaces. These data help distinguish two types of EC users, add to our knowledge of chemical exposure during vaping, and provide information useful in treating EC-related diseases and regulating EC use.

pharmacology and toxicology↗

Menthol in Electronic Cigarettes: A Contributor to Respiratory Disease?

Menthol is widely used in tobacco products. This study compared the effects of menthol on human bronchial epithelium using submerged cultures, a VITROCELL(R) cloud chamber that provides air liquid interface (ALI) exposure without solvents or heating, and a Cultex ALI system that delivers aerosol equivalent to that inhaled during vaping. In submerged culture, menthol significantly increased calcium influx and mitochondrial reactive oxygen species (ROS) via the TRPM8 receptor, responses that were inhibited by a TRPM8 antagonist. VITROCELL(R) cloud chamber exposure of BEAS-2B monolayers increased mitochondrial protein oxidation, expression of the antioxidant enzyme SOD2, activation of NF-{kappa}B, and secretion of inflammatory cytokines (IL-6 and IL-8). Proteomics data collected following ALI exposure of 3D EpiAirway tissue in the Cultex showed upregulation of NRF-2-mediated oxidative stress, oxidative phosphorylation, and IL-8 signaling. Across the three platforms, menthol adversely effected human bronchial epithelium in a manner that could lead to respiratory disease. O_FIG O_LINKSMALLFIG WIDTH=115 HEIGHT=200 SRC="FIGDIR/small/988006v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@b86c96org.highwire.dtl.DTLVardef@1e12bd2org.highwire.dtl.DTLVardef@4008corg.highwire.dtl.DTLVardef@c01cad_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract. Mechanism of action of menthol on human bronchial epithelium.Three in vitro platforms were used to study the effect of menthol on bronchial epithelium. In submerged culture (using BEAS-2B cells), menthol produced rapid calcium influx followed by an increase in oxidative stress and inflammatory cytokines. ALI exposure of BEAS-2B cells to unheated menthol in a cloud chamber caused activation of an inflammatory transcription factor (NF-{kappa}B) and oxidative stress. Proteomics analysis of human EpiAirway tissues exposed at the ALI to heated menthol EC aerosols identified changes in the expression of proteins involved in oxidative stress and in an inflammatory response. C_FIG

cell biology↗

Toxicity of JUUL Fluids and Aerosols Correlates Strongly with Nicotine and Some Flavor Chemical Concentrations

While JUUL electronic cigarettes (ECs) have captured the majority of the EC market with a large fraction of their sales going to adolescents, little is known about their cytotoxicity and potential effects on health. The purpose of this study was to determine flavor chemical and nicotine concentrations in the eight currently marketed pre-filled JUUL EC cartridges (\"pods\") and to evaluate the cytotoxicity of the different variants (e.g., \"Cool Mint\" and \"Creme Brulee\") using in vitro assays. Nicotine and flavor chemicals were analyzed using gas chromatography/mass spectrometry in pod fluid before and after vaping and in the corresponding aerosols. 59 flavor chemicals were identified in JUUL pod fluids, and three were >1 mg/mL. Duplicate pods were similar in flavor chemical composition and concentration. Nicotine concentrations (average 60.9 mg/mL) were significantly higher than any EC products we have analyzed previously. Transfer efficiency of individual flavor chemicals that were >1mg/mL and nicotine from the pod fluid into aerosols was generally 35 - 80%. All pod fluids were cytotoxic at a 1:10 dilution (10%) in the MTT and neutral red uptake assays when tested with BEAS-2B lung epithelial cells. Most aerosols were cytotoxic in these assays at concentrations >1%. The cytotoxicity of aerosols was highly correlated with nicotine and ethyl maltol concentrations and moderately to weakly correlated with total flavor chemical concentration and menthol concentration. Our study demonstrates that: (1) some JUUL flavor pods have high concentrations of flavor chemicals that may make them attractive to youth, and (2) the concentrations of nicotine and some flavor chemicals (e.g. ethyl maltol) are high enough to be cytotoxic in acute in vitro assays, emphasizing the need to determine if JUUL products will lead to adverse health effects with chronic use.

pharmacology and toxicology↗