The definite components in the e-liquid include propylene glycol, glycerol, nicotine (either included or not), and essence. Han, S.L. et al. determined the contents of the main components in 51 kinds of E-cigarette e-liquid. It was found that 1,2-propylene glycol and glycerol were the main solvents in most of E-cigarette e-liquids, with the content ranging between 75% and 95% . Although 1,2-propylene glycol and glycerol are widely used in the food, pharmaceutical and cosmetic industries, they are also food additives approved by the European Union . Although they are considered safe for oral use, propylene glycol will be converted into propylene oxide during aerosol inhalation, and propylene oxide is classified as a Class 2B carcinogen by the International Agency for Cancer Research. In addition, the glycerol will be converted to acrolein, which causes stimulation of the upper respiratory tract . A short-term exposure study showed that 5 min of E-cigarette use resulted in a significant increase in airway resistance . Another study found that with exposure to E-cigarette smoke, the number of free radicals in the lungs would increase significantly, indicating that E-cigarettes caused the development of oxidative stress in the lung. The content of 8-hydroxy-2-deoxyguanosine in the lungs also increased significantly. The 8-hydroxy-2-deoxyguanosine is widely used as a biomarker to assess oxidative stress and carcinogenicity . Goniewicz, M.L. et al. found four kinds of toxic substances, including carbonyl compounds, volatile organic compounds (VOCs), tobacco-specific nitrosamines (TSNAS), and heavy metals in the analysis of E-cigarette smoke . In addition, the essence, nicotine, and aerosol particles generated by electronic devices are harmful to the health .(1)For the carbonyl compounds, the heating of glycerol will produce harmful aldehydes related to temperature, including formaldehyde, acetaldehyde and acrolein. These three compounds were identified in almost all of the examined E-cigarettes . The study of Gassee, F.R. et al. showed that the mixture of the above three compounds produced more sensory stimuli than those of a single compound . Among them, formaldehyde was categorized as a Class 1 carcinogen in 2006. Acrolein stimulates the nasal cavity, damages the lungs and the inner walls of the blood vessels, and is a major factor leading to cardiovascular disease. Chronic inhalation of acrolein inhibits circulation of endothelial progenitor cells and promotes atherosclerosis, which accelerates the rate of hardening of the aorta by 1.6 times . Ambrus, J.L. et al. also confirmed the presence of acrolein, toxic substances and mutagenic compounds in E-cigarette smoke. It was found that the carcinogenic metabolic enzymes in rats exposed to E-cigarette smoke increased significantly, inducing a greater carcinogenic risk of carcinogens in E-cigarette smoke .(2)Nicotine is the addictive component of tobacco. It induces adverse effects during pregnancy and contributes to the progress of cardiovascular disease. Although nicotine itself is not a carcinogen, it functions as a “tumor promoter”. Nicotine is involved in neurodegeneration and other malignant diseases. Therefore, the use of nicotine in children, adolescents, pregnant women and women of reproductive age should be treated with great caution, due to the effects of nicotine on the brain . The effects of nicotine on the cardiovascular system will be elaborated in the following chapters.(3)Volatile organic compounds (VOCs) include toluene and meta xylene. In the study of Czogala, J. et al. almost all of the detected smokes contained toluene . In the study of Goniewicz, M.L. et al. toluene and meta xylene were detected in almost all sample smokes. These VOCs are irritating to the skin and mucous membrane, and have an anesthetic effects on the central nervous system, as well as having certain carcinogenicity .(4)N′-nitrosonornicotine (NNN), 4-(methylonitrosoamino)-1-(3-pirydyl)-l-butanone (NNK) and N′-nitrosoanatabine (NAT) are the three most representative tobacco-specific nitrosamines (TSNAS) in E-cigarettes. Kim, H.J. et al. tested the content of TSNAS in e-liquid samples. There were various kinds of TSNAS tested in 105 samples, among which the maximum concentration of NAT reached 62.19 ug/L, significantly exceeding the requirement for cigarette companies . Nitrosamines have strong carcinogenicity. Moreover, both nitrosamine and the polycyclic aromatic hydrocarbon benzopyrene can interact with DNA. These produced additives interfere DNA replication and the duplicated DNA produces purine free sites and triggers gene mutations . The chemical mixture in the smoke of the E-cigarette will cause chromosome division, and may cause damage to mitotic spindles or filaments, thereby inducing mutations .(5)Heavy metals include lead, nickel, cadmium, and so on. In 2013, Williams, M. et al. found heavy metals such as tin, nickel, lead, chromium and other nanoparticles in the smoke of E-cigarettes . The inhaled heavy metal nanoparticles can be deposited in the alveoli, inducing lung damage and leading to cough, dyspnea, chest pain, pulmonary edema, acute respiratory failure, as well as carcinogenicity, nephrotoxicity, and neurotoxicity . For example, tin is cytotoxic to human lung fibroblasts . In 2017, Williams, M. et al. continued to study the electronic flue gas sol. They selected 36 kinds of elements to detect, of which 35 kinds were detected in the electronic flue gas sol, while there were only 15 kinds of heavy metals detected in traditional cigarettes. These elements contain a variety of heavy metals, and the concentration is usually higher than that of traditional cigarette smoke . The content of lead and chromium is equal to that of traditional cigarette smoke. Especially the nickel content is much higher than that of traditional cigarettes . However, we still do not know the effects of inhaling heavy metal particles in aerosol on health.(6)There are studies that have investigated the cytotoxicity of the essence in E-cigarettes. Bahl, V. et al. used MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assays to test the cytotoxicity of e-liquids. The results showed that some e-liquids were cytotoxic to human embryonic stem cells and mouse neural stem cells, and that the composition and concentration of chemical components played an important role. In addition, more evidences confirmed that the chemical properties and the concentration of essence added to the e-liquid, rather than the nicotine alone, are much more harmful . Farsalinos, K.E. et al. used MTT tests to study the in vitro toxicity of the e-liquid of 20 E-cigarettes. The results showed that some electronic smoke liquid had a toxic effect on cardiac muscle cells after heating and atomizing, which would cause disease. The evidence indicated that the ingredients involved in the progress of diseases were related to the production process adopted by the liquid tobacco production company, as well as the flavor components added to cater to the public’s preference . Cinnamylaldehyde and diacetyl are approved flavorings in food, but they will affect people’s health when inhaled . Zeng, W.L. et al. collected tobacco smoke by cell culture medium, and studied the effect of smoke on the relative proliferation rate of Chinese hamster ovary cells (CHO cells) by MTT. The results showed that the relative proliferation rate of flue gas trapping liquid on CHO cells was 10 times higher than that of a 3R4F-reference-cigarette at 100% smoke concentration .