Table 2.
Studies of the toxicity mechanisms of e-cigarette.
| Toxicity Mechanism | Cells/Animals | E-Cigarette Model | Exposure Method | Toxicity Findings | Reference |
|---|---|---|---|---|---|
| Inflammation response Oxidative stress |
NHBE cells Human 3D bronchial epithelial tissue |
PG/VG: 70:30 Nicotine: 2% Flavors: flavorless |
Incubation with media containing e-liquids for 24 h | Decreased cell viability, increase in G-CSF, CXCL1, and IL-8 and levels of GSH and ROS | [68] |
| Inflammation response | BEAS-2B cells | Lounge model designed with 2.8 Ω coil and 3.6 V power supply PG/VG: 65:35 Nicotine: 0 and 16 mg/mL Flavors: blond tobacco, chlorophyll mint, and unflavored |
Air–liquid interface for 8 or 48 min (35 mL puff volume, 2 s draw, 60 s puff interval) | Low increase in IL-6 | [69] |
| Inflammation response Oxidative stress |
H292 cells HFL1 cells C57BL/6J mice |
Refillable ENDS with 2.2 Ω Nicotine: 0 and 16 mg/mL Flavors: classic tobacco, cinnamon roll, grape vape, American tobacco, etc. |
Air–liquid interface for 5, 10, and 15 min (a puff of 3–4 s, 30 s puff interval) | Decreased cell viability, increase in IL-6 and IL-8, promotion of OX/ROS generation, and lung inflammation in mice | [70] |
| Inflammation response Oxidative stress Apoptosis |
Human alveolar macrophages | Second-generation END with 650 mAh battery and 1.8 Ω coil PG/VG: 50:50 Nicotine: 0 and 36 mg/mL Flavors: flavorless |
Incubation with media containing e-cigarette vapor condensate for 24 h | Decreased cell viability, increased apoptosis, increased ROS production and levels of IL-6, TNF-α, CXCL8, MCP-1, and MMP-9 | [71] |
| Inflammation response DNA damage |
Bronchial epithelial cells 16HBE cells |
JUUL® e-cigarette Nicotine: 5% Flavors: Virginia tobacco and menthol |
Air–liquid interface for 30 min (55 mL puff volume, 4 s draw, 30 s puff interval) | Decreased cell viability, increase in IL-6, IL-8, and 8-OHdG | [72] |
| Inflammation response | BALB/c mice | Four different varieties of e-cigarette (Mt. Baker Vapor, Lynden, WA, USA) Nicotine: 0 and 12 mg/mL Flavors: American Tobacco |
Whole-body exposure for 8 weeks | Increase in pulmonary inflammation and responsiveness to methacholine | [73] |
| Inflammation response | C57BL/6J mice | PG/VG: 1:1 Nicotine: 0 and 18 mg/mL Flavors: tobacco blend |
Whole-body exposure for 3 days or 4 weeks | Increase in BALF cellularity, levels of IL-1β, IL-6, pulmonary inflammation, and responsiveness to methacholine | [74] |
| Inflammation response | C57BL/6 mice CD-1 mice |
E-liquid was placed in a standard tank (1.8 Ω) with a rechargeable battery (3.4 V) PG/VG: 50:50 Nicotine: 24 mg/mL Flavors: flavorless |
Nose-only inExpose system exposure for 3–6 months | Increase in circulating inflammatory cytokines | [75] |
| Oxidative stress DNA damage |
HFL-1 cells | Lorillard Blu Classic Tobacco E-cigarette Nicotine: 16 mg/mL Flavors: classic tobacco |
Air–liquid interface for 5, 10, 15, or 20 min (a puff of 3–4 s, 30 s puff interval) | Increase in mtROS, nuclear DNA fragmentation, and decrease in stability of an electron transport chain (ETC) complex IV subunit | [76] |
| Oxidative stress | BEAS-2B cells | Second-generation “Lounge” model with a 2.8 Ω nichrome coil and 4.6 W power supply and third-generation “ModBox” model with a 0.5 Ω Kanthal coil PG/VG: 65:35 Nicotine: 16 mg/mL Flavors: blond tobacco |
Air–liquid interface for 40, 80, and 120 puffs (55 mL puff volume, 2 s draw, 30 s puff interval) | Increase of GSSG/GSH ratio at higher power settings | [10] |
| Oxidative stress DNA damage |
B6C3F1 mice | PG/VG: 1:1 Nicotine: 0, 12, and 24 mg/mL Flavors: flavorless |
Whole-body exposure for 8 weeks | Increase in 8-OHdG | [77] |
| Oxidative stress | Acellular ROS assay | PG/VG: 1:1 Nicotine: 0%–6.8% Flavors: tobacco, minty fruit, fruity, minty/cool (iced), desserts, and drinks/beverages |
Incubation with media containing of e-cigarette vapor condensate for 15 min | Increase in ROS | [78] |
| Oxidative stress | BEAS-2B cells | JUUL® pod Nicotine: 5% Flavors: menthol and Virginia tobacco |
Air–liquid interface for 30 min (55 mL puff volume, 3 s draw, 30 s puff interval) | Change of mitochondrial bioenergetics and decrease in mitochondrial respiration | [79] |
| Oxidative stress | MG-63 cells | Mister-E-Liquid and Vape Dudes PG/VG: 1:1 Nicotine: 0 mg/mL Flavors: flavorless and cinnamon |
Incubation with media containing e-cigarette vapor condensate for 24 or 48 h | Decreased cell viability, increase in ROS | [80] |
| Oxidative stress Inflammation response |
U937 cells Mono Mac 6 cells |
Nicotine: 0 mg/mL Flavors: strawberry zing, café latte, pineapple coconut, cinnamon roll, etc. |
Incubation with media containing of e-cigarette vapor condensate for 24 h | Decreased cell viability, increase in ROS and IL-8 | [81] |
| DNA damage | Human epithelial normal bronchial cells (Nuli1) Human premalignant dysplastic oral mucosal keratinocyte cells (POE9n) |
Brands NJoy and eGo-T PG/VG: 50:50 Nicotine: 0, 12, and 18 mg/mL Flavors: traditional tobacco and desert sands |
Incubation with media containing of e-cigarette vapor condensate for 2 weeks (1 h per day) | Increase in 8-oxo-dG and ROS, decrease in the expression of ERCC1 and OGG1 | [82] |
| DNA damage Oxidative stress Apoptosis |
HUVEC cells | Brands Blu, Vuse, Green Smoke, and NJoy Nicotine: 2.4%, 4.5%, and 4.8% Flavors: tobacco |
Incubation with media containing e-cigarette vapor condensate for 24 or 72 h | Decreased cell viability, increase in DNA damage, apoptosis, and ROS | [83] |
| DNA damage | BEAS-2B cells UROtsa cells FVBN mice |
Brand NJoy PG/VG: 50:50 Nicotine: 10 mg/mL |
Whole-body exposure for 12 weeks and cell exposure for 1 h | Increase in γ-OH-PdG and O6-MedG, decrease in the expression of repair proteins XPC and OGG1/2 | [84] |
| DNA damage | Sprague Dawley rats | Brand Essential cloud with a 2000 mAh battery and 2 Ω coil Nicotine: 18 mg/mL Flavors: red fruit |
Whole-body exposure for 4 weeks | Increase in the free radical content, 8-OHdG, and DNA fragmentation | [85] |
| Apoptosis | Human primary gingival fibroblasts | Brand EMOW Nicotine: 12 mg/mL Flavors: smooth Canadian tobacco |
Incubation with media containing e-cigarette vapor condensate for 24 h | Decrease in cell density and altered cell morphology, increase in cell apoptosis | [86] |
| Apoptosis | Human primary gingival epithelial cells | Brand EMOW Nicotine: 12 mg/mL Flavors: smooth Canadian tobacco |
Air–liquid interface for 1, 2, or 3 days with 15 min per day (5 s draw, 30 s puff interval) | Increase in cell apoptosis and caspase-3 activity | [87] |
| Epithelial–mesenchymal transition | A549 cells | Nicotine: 48 mg/mL Flavors: menthol and tobacco |
Incubation with media containing e-cigarette vapor condensate for 3–4 days | Acquisition of a fibroblast-like morphology, loss of cell-to-cell junctions, internalization of E-cadherin, increased motility, and upregulation of EMT markers | [88] |
| Transcriptomic changes | NHBE cells | No mention | Air–liquid interface for 6 or 24 h | Inducement of significant transcriptomic changes, increase in expression of ribosomal protein genes, change of ribosomal RNA transcription and protein synthesis | [89] |
| Transcriptomic changes | NHBE cells | E-cigarette liquid Nicotine: 0% or 2.4% |
Incubation with media containing e-cigarette vapor condensate for 48 h | Change of microRNA expression profiling and increase in expression of multiple miRNAs | [90] |
| Transcriptomic changes | iPSC-EC cells | Vape Dudes E-cigarette PG/VG: 50:50 Nicotine: 24 mg/mL Flavors: menthol |
Incubation with media containing e-cigarette vapor condensate for 24 h | Change of expression profiling of lncRNAs and mRNAs | [91] |