The electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).
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Effect of the heating process on aerosol composition. Main harmful effects documented. Several compounds detected in e-cigarette aerosols are not present in e-liquids and the device material also seems to contribute to the presence of metal and silicate particles in the aerosols. The heating conditions especially on humectants, flavourings and the low-quality material used have been identified as the generator of the new compounds in aerosols. Some compounds generated from humectants (propylene glycol and glycerol) and flavourings, have been associated with clear airways impact, inflammation, impairment of cardiovascular function and toxicity. In addition, some of them are carcinogens or potential carcinogens
In this line, a study compared the acute impact of CS vs. e-cigarette vaping with equivalent nicotine content in healthy smokers and non-smokers. Both increased markers of oxidative stress and decreased NO bioavailability, flow-mediated dilation, and vitamin E levels showing no significant differences between tobacco and e-cigarette exposure (reviewed in [20]). Inasmuch, short-term e-cigarette use in healthy smokers resulted in marked impairment of endothelial function and an increase in arterial stiffness (reviewed in [20]). Similar effects on endothelial dysfunction and arterial stiffness were found in animals when they were exposed to e-cigarette vapor either for several days or chronically (reviewed in [20]). In contrast, other studies found acute microvascular endothelial dysfunction, increased oxidative stress and arterial stiffness in smokers after exposure to e-cigarettes with nicotine, but not after e-cigarettes without nicotine (reviewed in [20]). In women smokers, a study found a significant difference in stiffness after smoking just one tobacco cigarette, but not after use of e-cigarettes (reviewed in [20]).
Other compounds that have been detected in aerosols include acetamide, a potential human carcinogen [5], and some aldehydes [69], although their levels were minimal. Interestingly, the existence of harmful concentrations of diethylene glycol, a known cytotoxic agent, in e-liquid aerosols is contentious with some studies detecting its presence [4, 68, 70,71,72], and others finding low subtoxic concentrations [73, 74]. Similar observations were reported for the content ethylene glycol. In this regard, either it was detected at concentrations that did not exceed the authorised limit [73], or it was absent from the aerosols produced [4, 71, 72]. Only one study revealed its presence at high concentration in a very low number of samples [5]. Nevertheless, its presence above 1 mg/g is not allowed by the FDA [73]. Figure 1 lists the main compounds detected in aerosols derived from humectant heating and their potential damaging effects. It would seem that future studies should analyse the possible toxic effects of humectants and related products at concentrations similar to those that e-cigarette vapers are exposed to reach conclusive results.
The range of e-liquid flavours available to consumers is extensive and is used to attract both current smokers and new e-cigarette users, which is a growing public health concern [6]. In fact, over 5 million middle- and high-school students were current users of e-cigarettes in 2019 [75], and appealing flavours have been identified as the primary reason for e-cigarette consumption in 81% of young users [76]. Since 2016, the FDA regulates the flavours used in the e-cigarette market and has recently published an enforcement policy on unauthorised flavours, including fruit and mint flavours, which are more appealing to young users [77]. However, the long-term effects of all flavour chemicals used by this industry (which are more than 15,000) remain unknown and they are not usually included in the product label [78]. Furthermore, there is no safety guarantee since they may harbour potential toxic or irritating properties [5].
Other important components in the aerosols include silicate particles from the fiberglass wicks or silicone [89,90,91]. Many of these products are known to cause abnormalities in respiratory function and respiratory diseases [89,90,91], but more in-depth studies are required. Interestingly, the battery output voltage also seems to have an impact on the cytotoxicity of the aerosol vapours, with e-liquids from a higher battery output voltage showing more toxicity to A549 cells [30].
Interestingly, most of these reports linking COVID-19 harmful effects with smoking or vaping, are based on their capability of increasing the expression of angiotensin-converting enzyme 2 (ACE2) in the lung. It is well known that ACE2 is the gate for SARS-CoV-2 entrance to the airways [106] and it is mainly expressed in type 2 alveolar epithelial cells and alveolar macrophages [107]. To date, most of the studies in this field indicate that current smokers have higher expression of ACE2 in the airways (reviewed by [108]) than healthy non-smokers [109, 110]. However, while a recent report indicated that e-cigarette vaping also caused nicotine-dependent ACE2 up-regulation [42], others have revealed that neither acute inhalation of e-cigarette vapour nor e-cigarette users had increased lung ACE2 expression regardless nicotine presence in the e-liquid [43, 110].
Although honey is recognized as high-quality food, it is more vulnerable to adulteration, mislabeling, and unethical mixing with cheaper and low-grade honey, sugars, and other substances. Moreover, due to its limited availability, proved therapeutic and healing properties, and the increased population concerns regarding their health, there is a rising demand for the natural food product. This increased economic value would make honey a vulnerable adulteration target [12]. Moreover, while honey is a well-known high nutritional value food, it can also be toxic naturally by transferring plant toxins such as pyrrolizidine alkaloids, or because of adulterants that are added into the pure honey by mankind to gain economic profits [13]. Food adulteration has been a major concern for consumers, as it does not only decrease the quality of food products but also results in several adverse health effects. Authentic testing of food and the toxicology of adulterants is required for a value assessment to assure consumer protection against fraudulent activities. According to the regulation set by Alimentarius [1], consumers have the right to receive truthful information about the food that they are going to consume. It has also mentioned that honey should not have any added ingredients, any foreign matter, flavor, aroma, or taint absorbed from foreign substances during processing and storage, nor any removal of a particular constituent. Moreover, honey should not be heated or processed to such an extent that its essential composition is changed and its quality impaired. Although honey adulteration is a serious issue worldwide that requires several actions to be solved, there is currently a lack of an effective method to regulate the adulterated honey production [14]. In addition, honey adulteration is a key factor in the honey price fluctuation on the market. Several actions, locally and internationally, have been taken to detect fraud and solve the problem, but there is no actual solution to control the production of adulterated honey [15].
The adverse health impact of honey adulteration on consumers may lead to increased blood sugar, followed by the release of the insulin hormone and type II diabetes, abdominal weight gain and obesity, a rise in the blood lipid levels, and high blood pressure [32]. Furthermore, adulterants can affect internal organs, potentially causing a fatty liver [13], acute and chronic kidney injury [33] and elevate visceral fat pads and total body fat, which can lead to death [12,15].
The symptoms of acute vitamin A toxicity include headache, blurred vision, dizziness, vertigo, nausea, vomiting, and reduced motor coordination secondary to intracranial hypertension. Other symptoms reported are skin peeling, weight loss, and fatigue [10,135]. These toxic effects are usually the result of excessive ingestion of dietary vitamin A supplements. However, regular intake of liver, although generally not a problem in areas with retinol deficiency, can also cause toxicity owing to its high content of vitamin A [10,136].
Acrylamide can form naturally from chemical reactions in certain types of starchy foods, after cooking at high temperatures. Some foods with higher levels of acrylamide include French fries, potato chips, foods made from grains (such as breakfast cereals, cookies, and toast), and coffee. 2ff7e9595c
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