Figures
- FIGURE 1
E-cigarette models. a) First generation; b) second generation; c) third generation; d) fourth generation.
- FIGURE 2
Inflammatory responses elicited by e-liquid vaping. E-liquid vaping results in recruitment of immune cells to the site of exposure, i.e. nasal and throat epithelial cells. Tissue macrophages are among the first lines of defence activated by exposure to e-cigarette vapours. Activated macrophages participate in phagocytosis and release pro-inflammatory cytokines such as interleukin (IL)-6, IL-10, IL-1β, etc. a) In turn, these cytokines lead to B-cell and T-cell differentiation and participate in downstream signalling mechanisms. b) IL-6 mediated activation of the JAK–STAT (Janus tyrosine kinase/signal transducer and activator of transcription) pathway is one such downstream pathway that is known to be activated by the action of e-vapours. IL-6 production by exposure to e-vapours causes STAT3 phosphorylation which further elicits production of other cytokines and chemokines, and, most importantly promotes neutrophil adhesion and migration into the lungs. c) Neutrophil migration into the tissue results in release of neutrophil elastase and matrix metallopeptidase-9, which in turn causes tissue destruction in emphysematous lungs and chronic obstructive pulmonary disease. d) Furthermore, neutrophils release various cytokines and chemokines such as tumour necrosis factor (TNF)-α, IL-10 and IL-1β, which activate p38 and nuclear factor (NF)-кB mediated signalling pathways that might result in inflammation or apoptosis. e) Exposure to e-vapours further results in release of β-defensins by epithelial cells. β-defensins have antimicrobial actions and participate in eliciting an inflammatory response; however, production of the SPLUNC1 (short palate, lung and nasal epithelium clone 1) protein known to induce innate immunity in airway epithelial cells is lowered on exposure to e-vapours. ICAM: intercellular adhesion molecule.
Tables
- TABLE 1
Four generations of e-cigarettes
1st generation 2nd generation 3rd generation 4th generation Remarks Open/closed system Closed Open Open Open An open system is manufactured with a clearomiser which is manually filled with e-liquid
A closed system is prefilled with e-liquid which is directly attached to the batteryDesign Cig-a-like Pens/laser pointer Tank-style devices, also called “mods” Tank-style with better regulatory features: “regulated mods” The design of e-cigarettes has become more complex over time
Currently available devices are larger and come with temperature controlsCartridge refill No Refill Refillable Refillable Refillable Voltage ∼3.7–4.2 V ∼3.7–6 V ∼6–8 V ∼3–8 V with variable wattage (1–75 W) High voltage results in heating, which causes release of toxic compounds that have health implications Battery type and capacity Brushed steel battery eGO-style battery; lithium-ion battery ICR lithium-ion or IMR lithium-ion battery Lithium-polymer battery (Li-Po) Most of these battery packs can short-circuit and may cause explosions Brands VAPESTICK, Vype Disposable, Aer Disposable and NJOY Blu+, Eonsmoke, VaporFi Rocket, Apollo vTube 4.0 and VaporFi Pro II VaporFi, Halo, Mig Vapor and KangerTech V2, JUUL Vapor, South Beach Smoke, Diamond Series, Vapor Shark ICR: LiCoO2 cathode; IMR: LiMn2O4 cathode.
- TABLE 2
Chemical constituents of e-liquid and e-cigarette aerosols
Amount in e-liquids/e-cigarette aerosol Amount in conventional tobacco cigarette Permissible limit Toxic effect Molecular mechanism of toxicity Acetaldehyde 0.10–15.63 mg·L−1 (refill solution) [68] or
2.0±0.1–13.6±2.1 µg per 150 puffs [69]680 µg per
cigarette [70]45–270 ppm for 1 h (AEGL and NAC) [71] Eye, skin and respiratory tract irritation on acute exposure
Coughing, erythema, pulmonary oedema and necrosis on higher exposures
Probable carcinogen based on animal and human cancer studies [72, 73]Readily binds to protein and DNA, forming damaging adducts and impairing normal function and enzyme activity [74, 75] Acetone 2.9 mg·m−3 [76] or
0.16 ppm per 38-mL puff [77]287 µg per
cigarette [70]750–1000 ppm per 8-h work shift as per OSHA guidelines [78] Respiratory irritant in small quantities; nausea, CNS depression and cardiorespiratory failure in large amounts [78, 79] Metabolism in high amounts is not possible, leading to its accumulation and toxicity [78] Acrolein ND to 41.9±3.4 µg per 150 puffs [69] 60–140 µg per
cigarette [70, 80]0.1 ppm per 8 h as per OSHA guidelines [81] Highly toxic even in small quantities
Respiratory and cardiovascular toxicant
Possible carcinogen [79, 81]Highly reactive, leading to DNA and protein adduction, endoplasmic reticulum stress, membrane damage, mitochondrial disruption, oxidative stress and immune dysfunction [82] Cadmium ND 0.103 µg per
cigarette [70]5 µg·m−3 of air for 8 h as per OSHA guidelines [83] Chronic inhalation causes pulmonary changes with obstructive damage
Toxicity leads to renal dysfunction
Associated with teratogenicity in animals, but limited data on humans [84, 85]
Classified as a carcinogen, showing association with lung and prostate cancers [86]Has a long biological half-life (∼15–20 years)
Interacts with DNA
repair machinery, acts as a catalyst for ROS production, increases lipid peroxidation and induces apoptosis in cellular systems [87, 88]Chromium (Cr) 0.007 µg per 10 puffs [28] 0.0042 µg per
cigarette [70]5 µg·m−3 of air [89] Acute exposure causes fever, nausea, vomiting, diarrhoea; chronic exposures may cause irritation, nasal ulcers and perforations
Lung cancer is a major long-term effect [70, 79]Most of the toxicity is attributable to chromium(IV). Chromium(IV) is readily soluble and under physiological conditions, can produce reactive intermediates, hydrogen peroxide and GSH, which can attack DNA, protein and membrane lipids [90] Formaldehyde 0.02–10.09 mg·L−1 refill solution [68] or
3.2±0.8–56.1±1.4 µg per 150 puffs [69]20–100 µg per
cigarette [70, 80]0.75 ppm per 8-h work shift as per OSHA guidelines [91] Potent respiratory stimulant causing irritation, cough, wheezing, significant respiratory inflammation, pneumonia and bronchitis on exposure
Has been recognised as a carcinogen
Has more toxic effects on children compared to adults
Known to cause neurological symptoms upon high-level exposure [70, 79, 91]Highly reactive electrophilic reagent that can easily attach to neutrophilic biological targets, leading to formation of harmful adducts and ROS [92] Nicotine 0–87.2 mg·mL−1 refill solution or
0.3±0.2–8.7±1.0 mg per 150 puffs [93]1.0–1.5 mg per
cigarette [80]0.5 mg·m−3 skin [94] Nausea, vomiting, increased salivation, bronchorrhea, hyperpnoea, hypertension, tachycardia, vasoconstriction, headache, restlessness, etc.
Causes developmental defects
Addictive [94, 95]Mechanism not fully understood, but toxicity attributed to oxidative damage, lipid peroxidation and DNA adduct formation [96] N-Nitrosamines ND to 28 µg per 150 puffs [69] 0.019–72 µg per cigarette [70] 0.3 ng·m−3 [97] Carcinogen [70] Forms diazonium or oxynium ions which cause alkylating DNA
Activates various oxidative damage and radical scavenging pathways [98]Toluene ND to 6.3±1.5 µg per 150 puffs [69] 72.8 µg per
cigarette [70]200 ppm (300–500 ppm for a maximum 10 min per 8-h shift, as per OSHA guidelines) [99] Neurotoxicity including headache, nausea, euphoria, depression, cognitive impairment, etc. [100] Rapidly absorbed, has high affinity for lipids and crosses the blood–brain barrier
Metabolises to form hippurate ions resulting in metabolic acidosis and hypokalaemia
Has been found responsible for increased production of dopamine [101]Lead 0.03±0.03–0.57±0.28 µg per 150 puffs [69] 0.00128 µg per
cigarette [70]50 µg·m−3 per 8 h (NIOSH) [102] Neurotoxin, cardiotoxin, behavioural changes and developmental changes [103] Causes oxidative stress and ionic imbalance [104] AEGL: acute exposure guideline level; NAC: National Advisory Committee; OSHA: Occupational Safety and Health Administration; CNS: central nervous system; ND: not determined; ROS: reactive oxygen species; GSH: glutathione; NIOSH: National Institute for Occupational Safety and Health.
Jump To
- Article
- Abstract
- Abstract
- Introduction
- Materials and methods
- Product engineering of e-cigarette devices
- Toxicological profile of e-liquids and e-cig aerosols
- Immunological effects of e-cig use
- Vaping: is it safe for health?
- Regulations imposed on the use of e-cigs
- Future directions and conclusions
- Footnotes
- References
- Figures & Data
- Info & Metrics