Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography–mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition

Chronic e-cigarette exposure alters the human bronchial epithelial proteome

Rationale: E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown. Objectives: To determine the effects of chronic vaping on pulmonary epithelia. Methods: We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers) and obtained bronchial brush biopsies and lavage samples from these subjects for proteomic investigation. We further employed in vitro and murine exposure models to support our human findings. Measurements and Main Results: Visual inspection by bronchoscopy revealed that vaper airways appeared friable and erythematous. Epithelial cells from biopsy samples revealed approximately 300 proteins that were differentially expressed in smoker and vaper airways, with only 78 proteins being commonly altered in both groups and 113 uniquely altered in vapers. For example, CYP1B1 (cytochrome P450 family 1 subfamily B member 1), MUC5AC (mucin 5 AC), and MUC4 levels were increased in vapers. Aerosolized PG/VG alone significantly increasedMUC5AC protein in human airway epithelial cultures and in murine nasal epithelia in vivo.We also found that e-liquids rapidly entered cells and that PG/VG reduced membrane fluidity and impaired protein diffusion. Conclusions: We conclude that chronic vaping exerts marked biological effects on the lung and that these effects may in part be mediated by the PG/VG base. These changes are likely not harmless and may have clinical implications for the development of chronic lung disease. Further studies will be required to determine the full extent of vaping on the lung

Runaway electron beam control

Post-disruption runaway electron (RE) beams in tokamaks with large current can cause deep melting of the vessel and are one of the major concerns for ITER operations. Consequently, a considerable effort is provided by the scientific community in order to test RE mitigation strategies. We present an overview of the results obtained at FTU and TCV controlling the current and position of RE beams to improve safety and repeatability of mitigation studies such as massive gas (MGI) and shattered pellet injections (SPI). We show that the proposed RE beam controller (REB-C) implemented at FTU and TCV is effective and that current reduction of the beam can be performed via the central solenoid reducing the energy of REs, providing an alternative/parallel mitigation strategy to MGI/SPI. Experimental results show that, meanwhile deuterium pellets injected on a fully formed RE beam are ablated but do not improve RE energy dissipation rate, heavy metals injected by a laser blow off system on low-density flat-top discharges with a high level of RE seeding seem to induce disruptions expelling REs. Instabilities during the RE beam plateau phase have shown to enhance losses of REs, expelled from the beam core. Then, with the aim of triggering instabilities to increase RE losses, an oscillating loop voltage has been tested on RE beam plateau phase at TCV revealing, for the first time, what seems to be a full conversion from runaway to ohmic current. We finally report progresses in the design of control strategies at JET in view of the incoming SPI mitigation experiments