China’s First Progress Report on Potentially Harmful Ingredients in E-Cigarettes Released

The first domestic progress report on the research on possible harmful components of e-cigarettes was released. E-cigarettes, also known as e-nicotine delivery systems, are products that atomize e-cigarette liquid through an atomizer to deliver nicotine and/or other substances to the respiratory system [1]. In recent years, e-cigarettes have developed rapidly. The report of the Seventh Conference of the Parties to the World Health Organization Framework Convention on Tobacco Control (FCTC)[2] shows that global expenditure on e-cigarettes in 2015 was US$10 billion; of which the United States and the United Kingdom accounted for 56% and 12% respectively, and China, France, Germany, Italy and Poland together accounted for 21%, with each country contributing 3% to 5%); In addition, the proportion of young people under the age of 20 using e-cigarettes has increased year by year. From 2013 to 2015, the number of non-smoking young people using e-cigarettes in Florida and Poland increased by 5 times and 8 times respectively, with the usage rates reaching 6.9% and 13% respectively [2].

In terms of regulatory supervision of e-cigarettes, some countries/regions have not yet clarified the classification of e-cigarettes, their legal status is unclear, and legal supervision is not uniform; Some countries/regions have taken certain measures to supervise, such as completely banning e-cigarettes, or controlling e-cigarettes in the form of tobacco products, consumer goods, medical products or other products. However, most of the countries or regions currently carrying out supervision are at the legal level, and there are few specific technical requirements. The raw materials, production processes and products used for the production of smoking equipment and cigarette liquids are not fully controlled, and their quality and safety cannot be effectively guaranteed [3]. At present, risk research on e-cigarettes mainly focuses on the analysis of harmful components in cigarette liquids and aerosols, and there are few comparative studies on harmful substances in mainstream cigarette smoke. This paper collects, classifies, compares and analyzes the risk research literature and relevant regulations on chemical components in cigarette liquids, smoking articles and aerosols at home and abroad in recent years, and expounds the current status of risk research on chemical components in e-cigarettes, providing reference for e-Cigarette safety research.

1 Electronic cigarette liquid

Chemical risks in cigarette liquids mainly include inaccurate labeling of nicotine content, aldehyde and ketone compounds, volatile compounds, tobacco-specific nitrosamines and metal elements.

1.1 Inaccurate labeling of nicotine content

A total of 16 documents reported the inconsistency between the nicotine content in smoke liquid and the label, involving 544 samples. See Table 1 for details. It can be seen that the nicotine content on the label is quite different from the actual content, and the deviation range is-100%~105%. For example, Cheah et al.[9] tested the nicotine content of 20 cigarette bombs, of which one labeled the nicotine content of 6mg/cigarette bomb, with a detection value of 12.3 mg/cigarette bomb, and one labeled the nicotine content of 24mg/cigarette bomb, with a detection value of only 3mg/cigarette bomb; Goneewicz et al.[15] tested a cigarette liquid labeled as pure nicotine, with a nicotine content of only 150.3 mg/mL.

1.2 aldehydes and ketones

Low-molecular aldehyde compounds are a class of harmful substances that have a strong irritating effect on the respiratory system, especially formaldehyde, acetaldehyde, acetone, acrolein, o-methylbenzaldehyde, and propionaldehyde [20]; among them, formaldehyde and acetaldehyde are classified by IARC as Class 1 and Class 2B carcinogens respectively [21]. XPD90 -300-2: Requirements and Experimental Methods Related to Electronic Cigarette Liquids issued by the French Standardization Institute (AFNOR), the Guidelines for the Production, Import, Testing and Identification of E-Cigarette, Cigarette Liquids, Electronic hookah and Direct Related Products issued by the British Standardization Institute (BSI) and the Electronic Cigarette Liquids Manufacturing Standards Association (AEMSA) all clearly prohibit the addition of formaldehyde, acetaldehyde, acrolein to cigarette liquids [22-24]; In addition, the U.S. Food and Drug Administration (FDA) also requires attention to the above three aldehyde compounds in cigarette liquids [25]. Vincent et al.[26] used LC-UV/MS to detect aldehyde compounds in 42 samples from 14 brands: formaldehyde content was 0.1 - 9.0 g/g (detection rate was 100%); acetaldehyde content was 0.05 - 10.2 g/g (detection rate was 100%); acrolein was detected in 3 samples, with the contents of 0.18 g/g, 0.21 g/g and 1.03 g/g. Lim et al.[27] used headspace solid phase microextraction and GC-MS to detect the contents of formaldehyde, acetaldehyde and acrolein in 225 cigarette liquids. Among them, the formaldehyde content was 0.02 - 10.09 mg/L (average value was 2.16 mg/L, detection rate was 92%), and the acetaldehyde content was 0.10 - 15.63 mg/L (average value was 4.98 mg/L, detection rate was 100%). No acrolein was detected in all samples. Chen Gang et al.[28] used HPLC to determine the contents of formaldehyde, acetaldehyde and acrolein in 48 cigarette liquids. The detection rates were 87.5%, 97.9% and 8.3%, respectively, and the highest contents were 1.2 mg/L, 1.69 mg/L and 9.45 mg/L respectively.# p#pagination title #e#

Although 2,3-butanedione is allowed to be added to food as a food additive, studies have shown that 2,3-butanedione may deposit in the lungs after being heated and inhaled into the lungs, causing obstruction, exacerbating respiratory inflammation, and in severe cases, forming popcorn lungs [2,29]. Because 2,3-pentanedione is similar in structure to 2,3-butanedione and can produce fragrance, cigarette liquid was once added as a substitute for 2,3-butanedione; but subsequent animal experiments with 2,3-pentanedione showed that the safety risks of inhaling 2,3-butanedione are consistent with inhaling 2,3-butanedione 122 China Tobacco Journal Acta Tabacaria Sinica 2018 Vol. 24 No. 3 ketone [30,31]. The above-mentioned standards in France, the United Kingdom and the United States all prohibit the addition of 2,3-butanedione and 2,3-pentanedione to cigarette liquids [22-25]. Visser et al.[32] detected 2,3-butanedione in 183 tobacco liquids, and was detected in 34 samples, with the highest concentration reaching 5591 g/mL. Farsalinos et al.[30] analyzed the contents of 2,3-butanedione and 2,3-pentanedione in 159 smoke liquids and found: (1) 45 samples contained both 2,3-butanedione and 2,3-pentanedione, 73 samples contained one of them, and neither was detected in 41 samples;(2) 110 samples contained 2,3-butanedione, with a median concentration of 29 g/mL, and a content range of 10 - 170 g/mL;(3) 53 samples contained 2,3-pentanedione, with a median concentration of 44 g/mL, and a content range of 7 - 172 g/mL. 1.3 volatile compounds

Few research documents on volatile compounds in smoke liquids have been collected. Han Shulei et al.[33] established a GC-MS method for the determination of 18 VOCs in smoke liquid, and analyzed 55 smoke liquid samples and found that the detection rates of 2-butanone, benzene, ethylbenzene, o-xylene, and p, m-xylene were all greater than 80%. Due to the attractiveness of menthol, the Fourth Conference of the Parties (COP4) of the FCTC recommended that all parties ban the addition of menthol in cigarettes [34]. The European Union's New Tobacco Products Directive 2014/40/EU Directive on Coordinating Laws, Regulations and Administrative Provisions on the Production, Display and Sale of Tobacco and Related Products in Member States also prohibits the addition of menthol in cigarettes (transition period until May 20, 2020)[35]. The FDA has also carried out relevant research on the addiction of pepper-type cigarettes [36], therefore, menthol is included in the cigarette liquid component analysis list recommended in the FDA's e-cigarette market application guide (draft)[25].—“”“” Christoph et al.[14] used GC-MS to scan 28 smoke liquids and found a total of 141 volatile compounds, and 12 samples contained menthol.

1.4 tobacco-specific nitrosamines

Tobacco-specific nitrosamines (TSNAs) include N-nitrosonoricotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosoneonicotine (NAT) and N-nitrosoanabasine (NAB), of which NNN and NNK are listed as Class 1 carcinogens by IARC [37]. Six papers involved the analysis of TSNAs, with a total of 170 smoke liquid samples. See Table 2 for details: All the papers were determined by LC-MS/MS method, but the results varied greatly. Some were all detected, some were not detected, and some were only detected by individual indicators. For example, Kim et al.[39] tested the content of TSNAs in 105 cigarette liquids sold in the Korean market, including NNN concentrations of 0.34 - 60.08 g/L (detection rate 64.8%), NNK concentrations of 0.22 - 9.84 g/L (detection rate 88.6%), NAB concentrations of 0.11 - 11.11 g/L (detection rate 54.3%), and NAT concentrations of 0.09 - 62.19 g/L (detection rate 75.2%). Schober et al.[38] tested 6 smoke liquid samples, but neither NNN nor NNK were detected, and the highest concentrations of NAT and NAB were 0.38 ng/mL and 0.22 ng/mL respectively. Lagesen et al.[40] analyzed the content of TSNAs in cigarette shells with nicotine content of 0 mg, 6 mg, 11 mg and 16 mg and found that as the content of nicotine increased, the content of TSNAs also increased. The content of TSNAs in 16 mg cigarette shells was 8.18 ng/cigarette shell.

1.5 metal elements

Williams et al.[42] used SEM-EDS and other methods to analyze the oil storage wool of the cigarette bomb and detected elements such as Sn, Cu and Ni, but did not quantify it. Catherine et al.[43] used ICP-MS to analyze the metal elements in five cigarettes. Cd, Cr, Pb, Mn and Ni were all detected. The Cd content was 0.137 - 755 g/L, the Cr content was 41.5 - 16900 g/L, the Pb content was 3.53 - 4870 g/L, the Mn content was 11.8 - 31500 g/L, and the Ni content was 13.7 - 72700 g/L. Among them, Ni and Cr may originate from the migration of heating wires made of nickel-chromium alloy. Fan Meijuan et al Research Progress on the Risk of Chemical Components in E-Cigarettes 123 #p #Page Title #e#

1.6 other components

The analysis list of cigarette liquid components recommended in the draft e-cigarette market application guidance issued by the FDA also includes ethylene glycol and diethylene glycol [25]. Christoph et al.[14] used GC-FID to analyze ethylene glycol in 28 smoke liquids. The content was detected in 13 samples, with a content of 1% to 76%, with an average value of 26%, and a median value of 5%. One of the samples contained as high as 76%, and ethylene glycol may be used as a solvent instead of glycerol and propylene glycol. Vincent et al.[26] used GC-MS to analyze ethylene glycol and diethylene glycol in 42 smoke liquids and found that the detection rate of ethylene glycol was 73.8%, and the content was 2.19 - 66.97 g/g; The detection rate of diethylene glycol was 21.4%, and the content was 0.6 - 4.0 g/g; although ethylene glycol and diethylene glycol in smoke liquids were detected, they were below the limit required by regulations (the FDA stipulates that the limit for ethylene glycol in glycerol is 620 g/g[44]; the 2007 version of the United States Pharmacopeia stipulates that the limit for diethylene glycol is 1 mg/g[45]). Vincent et al. believed that it may be caused by pollutants in production raw materials. In 2009, the U.S. FDA's Center for Drug Evaluation and Research asked Westenberger et al.[12] to evaluate the nicotine content and other harmful substances in a total of 16 cigarette bombs from 2 brands. They found that diethylene glycol was detected in one cigarette bomb sample, with a content close to 1%.

In addition, Christoph et al.[14] analyzed 28 tobacco liquids: (1) 4 samples contained coumarin, which is prohibited by the German Tobacco Act from being added to cigarettes; and (2) 4 samples contained acetamide, which is classified as a Class 2B carcinogen by the IARC [21]. Wang Chao et al.[46] used solid phase supported liquid-liquid extraction and GC-MS to determine 16 polycyclic aromatic hydrocarbons in 13 smoke liquid samples, including naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, fluorene, phenanthrene and anthracene. Xiao Weiqiang et al.[47] analyzed that the ammonia content in 12 tobacco liquid samples was 0.244~1.65 g/g. In addition, there have been reports that drugs such as amino-tadalafil (Viagra analog) and rimonabant (a weight-loss drug banned in the United States) have been detected in some cigarette liquids [48].

2 E-cigarette aerosols

Glycerol, propylene glycol or a mixture of the two are commonly used solvents in smoke liquids, usually accounting for about 90% of the mass of the smoke liquid, and they account for a large proportion of aerosols [49]. Animal experiments have shown that inhalation of propylene glycol aerosol is safe, but it has a water-absorbing function and may cause dryness in the smoker's mouth and throat [26]; glycerol is a generally recognized safe substance and can be added to food [50]. However, heating glycerol and propylene glycol to a certain temperature can produce harmful aldehydes and ketones [50]. At present, the main risks involved in aerosol research include nicotine release and stability, aldehyde compounds, volatile compounds, metal elements and tobacco-specific nitrosamines. In addition, this part also compares the harmful components in e-cigarette aerosols and cigarette smoke.

2.1 nicotine

Research on nicotine in aerosols includes two parts: nicotine release amount and nicotine release stability.

(1) Nicotine release. See Table 3 for studies on nicotine release from aerosols. Goniewicz et al.[4] conducted a quantitative analysis of the nicotine release in 16 samples, and smoked according to the parameters of aspiration time (1.8 0.9) s, aspiration interval (1013) s, and aspiration volume (7068) mL. The nicotine content in 20 groups of aerosols with a total of 300 mouthfuls was 0.5 - 15.4 mg. In order to verify Goneewicz's method, Westenberger et al.[12] used three samples to test, with a suction volume of 100 mL, and the nicotine content in the aerosol was 26.8 - 43.2 g/mouth, that is, 8.04 - 13.0 mg/300 mouth, which was consistent with Goneewicz's results. In order to verify the nicotine release stability of different batches of e-cigarettes, Goneewicz et al.[19] selected 6 e-cigarettes for repeated testing, with a maximum content of 15 mg/300 mouthfuls, which is consistent with previous results. Goniewicz et al.[4] found that for smoke liquids with medium nicotine content (21 - 26 mg/mL) and high nicotine content (27 - 36 mg/mL), the nicotine release amount has little correlation with nicotine content; but it is closely related to working voltage, heating wire type, and air inlet size and location.

(2) nicotine release stability. The unstable release of nicotine from e-cigarettes may cause consumers to inhale excessive nicotine, so relevant regulations pay attention to the stability of nicotine release. 2014/40/EU stipulates that the nicotine release from e-cigarettes should be stable and consistent [35]. The relevant requirements and experimental methods for XP D90-300-3 releases issued by AFNOR stipulate that the nicotine release from e-cigarettes should be stable and consistent. If each e-cigarette is smoked continuously for 3 groups (20 puffs/group), the relative average deviation of nicotine release should be less than 25%[51]. Farsalinos et al.[41] compared the nicotine release stability of three cigarette cartridge e-cigarettes and four liquid-extended e-cigarettes: the nicotine release amount of the cigarette cartridge was 1.01 - 3.01 mg/20 bites, and the RSDs in the sample were 5.5%-12.5%. The liquid-extended e-cigarettes were 2.72 - 10.61 mg/20 bites, and the RSDs in the sample were 3.7%-6.5%. Therefore, Farsalinos et al. believed that the liquid-extended e-cigarettes have higher nicotine release stability than the cigarette cartridge e-cigarettes.# p#pagination title #e#

2.2 aldehyde compound

There are many studies on aldehyde compounds in aerosols, mainly including the study of aldehyde compound content and influencing factors. See Table 4 for details.

(1) The content of aldehyde compounds in the aerosol. A total of 408 samples were collected for the study on the content of aldehyde compounds in aerosols. The detection rate of aldehyde compounds was high, such as formaldehyde was detected in all samples. Goniewicz et al.[52] measured aldehyde compounds in 12 samples. The formaldehyde content was 3.2 0.8~56.1 1.4 g/150 samples (detection rate 100%), the acetaldehyde content was 2.0 0.1~13.6 2.1 g/150 samples (detection rate 100%), the acrolein content was N.D~41.9 3.4 g/150 samples (detection rate 91.67%), and the o-methylbenzaldehyde content was 1.3 0.8~7.1 0.4 g/150 samples (detection rate 100%).

(2) Study on the influencing factors of aldehyde compounds in aerosols. Leon et al.[53] investigated the effects of smoke liquid formulation and working voltage on the content of aldehyde compounds produced and found that: (1) propylene glycol is easier to decompose than glycerol to produce low-molecular aldehyde compounds;(2) the higher the working voltage, the higher the working temperature of the atomizer, the more smoke liquid is consumed per puff, and the higher the content of aldehyde compounds produced; when the voltage is increased from 3.2V to 4.8V, the content of formaldehyde, acetaldehyde and acetone increases by 4 to 200 times;(3) No acrolein was detected in any of the 13 samples, which was inconsistent with the results of other studies, probably due to different detection limits and the small number of suction ports (30 in total). Otmar et al.[54] studied the relationship between output power and aldehyde compound content: when the output power increased from 5W to 15W, the formaldehyde and acetaldehyde contents increased by 12.8 times and 7.5 times respectively. When the power is 20 W, the formaldehyde content is 1559.9 423.3 ng/mouth, the acetaldehyde content is 348.4 84.6 ng/mouth, and the acrolein content is 2.5 0.8 ng/mouth. Wang et al.[55] analyzed the effect of glycerol and propylene glycol in the formulation of cigarette liquid on the production of aldehyde compounds under certain temperature conditions: when the atomization temperature is 215℃, both glycerol and propylene glycol produce a large amount of formaldehyde and acetaldehyde; When the temperature is 270℃, the cigarette liquid containing glycerol produces acrolein; when the temperature is 318℃, 1mg of glycerol produces 21.1 3.80 g of formaldehyde, 2.40 0.99 g of acetaldehyde, and 0.80 0.50 g of acrolein;1mg of propylene glycol produces 2.03 0.80 g of formaldehyde, 2.35 0.87 g of acetaldehyde and trace amounts of acrolein.

2.3 volatile compounds

The research on volatile compounds includes two parts: aerosols and environmental smoke. See Table 5 for details.

(1) Volatile compounds in aerosols. Lagesen et al.[40] analyzed the volatile compounds in each puff (suction volume 38 mL): p, m-xylene 0.18 ppm, propylene glycol 32 ppm, styrene 0.29 ppm. Goniewicz et al.[52] analyzed 11 volatile compounds, only toluene and p, m-xylene were detected, and the contents were 0.2~6.3 g/150 (detection rate 83.3%) and 0.1~0.2 g/150 (detection rate 83.3%) respectively.

(2) Volatile compounds in environmental smoke. Pellegrino, Schober and Schripp et al.[8, 36, 58] studied the impact of e-cigarette aerosols on environmental smoke, which all showed that after smoking e-cigarettes, the content of volatile organic compounds in the environmental test chamber increased, mainly propylene glycol, glycerol and nicotine. Schober et al.[36] studied the impact of smoking e-cigarettes on indoor air quality: increased concentrations of 11 volatile compounds, including aroma compounds such as benzyl alcohol and menthol. Schripp et al.[58] found that the content of glycerol diacetate (solvent for aroma substances) and aroma substances in the environmental chamber increased. Pellegrino et al.[8] also discovered fragrances such as damasone, 5-methyl-2-furfural and pyrazine.

2.4 metal elements

Metallic elements not only appear in smoke liquids, but also elements such as Cd, Ni, Pb, Cr, and Si are found in aerosols. See Table 6 for details. Goniewicz et al.[52] conducted quantitative analysis of 12 elements in aerosols. Only Cd, Ni and Pb were detected, and the Cd content was N.D.~ 0.22 0.16 g/150 mouths (detection rate 91.67%), Ni content 0.11 0.05~0.29 0.08 g/150 mouths (detection rate 100%), and Pb content 0.03 0.03~0.57 0.28 g/150 mouths (detection rate 100%). Williams et al.[42] measured the content of 21 elements in cigarette e-cigarette aerosols, among which the elements with higher content were Na (4.18 g/10 mouths), B (3.83 g/10 mouths), Si (2.24 g/10 mouths), Ca (1.03 g/10 mouths), Fe (0.52 g/10 mouths), Al (0.394 g/10 mouths), Pb (0.017 g/10 mouths), Cr (0.007 g/10 mouths) and Ni (0.005 g/10 mouths). La gesen et al.[40] tested As, Sb, Cd, Cr, Co, Cu, Pb, Mn and Ni in cigarette e-cigarette aerosols, but none of them were detected;La gesen et al. believed that the number of samples that might be tested was small and limited.# p#pagination title #e#

2.5 tobacco-specific nitrosamines

The research on TSNAs in e-cigarette aerosols includes two parts: the content of TSNAs in aerosols, the relationship between TSNAs in smoke liquid and TSNAs in aerosols. See Table 7 for details.

(1) TSNAs content in aerosols. Goniewicz et al.[52] detected trace amounts of TSNAs in aerosols, including NNN content 1.1 - 28.3 ng/150 mouths (detection rate 75%), and NNK content 0.8 - 4.3 ng/150 mouths (detection rate 75%). The literature reported the content of TSNAs in a certain brand of e-cigarette aerosols with four different flavors. The NAT content ranged from 2 to 5 ng/L, and NNN, NNK and NAB were all below the limit of quantification (limit of quantification 2 ng/L)[59].

(2) The relationship between TSNAs in smoke liquid and TSNAs in aerosol. Farsalinos et al.[41] studied the relationship between TSNAs in smoke liquid and TSNAs in aerosols. By adding certain concentrations of NNN, NAT, NAB and NNK to smoke liquid, it was detected that there was no statistical difference between the concentration of TSNAs in aerosol and the concentration of TSNAs added in smoke liquid, and there was a significant correlation (r=0.83, p 0.001). Therefore, it is recommended to evaluate the content of TSNAs in aerosol by analyzing the content of TSNAs in smoke liquid, without testing the content of TSNAs in aerosol. Young et al.[60] analyzed the content of TSNAs in 50 e-cigarette aerosols and found that e-cigarettes do not produce TSNAs during working. The TSNAs in the aerosols are the original transfer of TSNAs in the smoke liquid, which is consistent with Farsalinos 'conclusion.

2.6 Comparison of harmful components in e-cigarette aerosols and cigarette smoke

Under normal use of e-cigarettes, some harmful substances in aerosols are usually lower or much lower than mainstream cigarette smoke, but some unique harmful substances, such as glyoxal, are also produced [2]. In addition, it is reported in the literature that under normal use experimental conditions, the content of some elements (such as Pb, Cr and Ni) and formaldehyde in e-cigarette aerosols is equal to or higher than that in mainstream cigarette smoke [2,42,54].

Visser et al.[32] systematically compared the harmful components in e-cigarette aerosols and cigarette smoke: the contents of TSNAs, acetaldehyde, acrolein, benzene, toluene, Cd and Pb in mainstream smoke are 400 times, 35 times, 4 times, 40 times, 1500 times, 155 times and 3.5 times that of aerosol respectively; but the formaldehyde content in aerosol is three times that of mainstream cigarette smoke. Lauterbach et al.[61] compared the release of harmful substances in the mainstream smoke of an e-cigarette aerosol and a cigarette: the release of nicotine in the aerosol was 2.5% of that of mainstream smoke, and the release of other harmful components was 98% less than that of cigarettes. Goniewicz et al.[52] smoked 12 e-cigarettes according to the smoking parameters of a smoking capacity of 70 mL, a smoking time of 1.8 seconds, and a smoking interval of 10 seconds. They compared the harmful substances in e-cigarette aerosol and cigarette mainstream smoke. The results showed that the harmful substances in cigarette mainstream smoke were 9 to 450 times that in e-cigarette aerosol, and the Cd, Ni and Pb contents in the aerosol were equivalent to those in mainstream smoke. Williams et al.[42] compared the elements in aerosols and mainstream smoke: (1) There are three elements contained in aerosols alone (Si: 2.24 g/10 mouth, B: 3.83 g/10 mouth and Ca:1.03 g/10 mouth);(2) There are 4 kinds of elements with high aerosol content in common between the two (Na:4.18 g/10 mouth, Fe:0.52 g/10 mouth, Al:0.394 g/10 mouth and Ni:0.005 g/10 mouth), there are 5 elements with equivalent content (Cu:0.203 g/10 mouth, Mg:0.066 g/10 mouth, Pb:0.017 g/10 mouth, Cr:0.007 g/10 mouth and Zn:0.002 g/10 mouth). Research by Otmar et al.[54] showed that when the output voltage is 4.8V, the formaldehyde content is 25 g/15 puffs, which is equivalent to mainstream cigarette smoke.

3 Electronic cigarette smoking equipment

The safety of smoking equipment is an important part of the quality and safety of e-cigarette products. During storage and working of e-cigarettes, the oil guide cord, heating wire, liquid storage tube, air duct, liquid storage cotton, inside of the nozzle, etc. are in direct contact with the cigarette liquid and aerosol, and the outside of the nozzle is in direct contact with the oral cavity. Hazardous substances in the material may migrate into the cigarette liquid, aerosols and oral cavity, increasing consumer health risks. XPD90 -300-1 released by AFNOR: Progress in risk research on chemical components in electronic cigarettes such as Fan Meijuan and others 127 Smoking equipment related requirements and experimental method requirements: The nozzles and storage tubes of electronic cigarettes should not release toxic or allergenic substances; If the material of the nozzles and storage tubes is polyvinyl chloride, polystyrene, ABS resin, polycarbonate, polyoxymethylene or styrene-acrylonitrile polymer, migration tests of each polymer monomer should be carried out [62].

So far, there has been no literature report on the migration test of various components of smoking sets. Studies have been carried out that have shown that elements in smoking equipment may migrate into aerosols. The median values of Cr, Cu, Zn, Sn, and Pb in 183 cigarette liquids detected by Visser et al.[32] were: <5.0 ng/mL,<5.0 ng/mL, 28 ng/mL,<5.0 ng/mL and <5.0 ng/mL, respectively, and the median values of element content in aerosols were: 6.7 ng/mouth, 2.1 ng/mouth, 1.7 ng/mouth, 1.1 ng/mouth, and 0.59 ng/mouth, respectively. Based on data reported in the literature [32], it is estimated that according to the conversion of 3 L of cigarette liquid [63] consumed for one puff of e-cigarette, 1 mL of cigarette liquid requires about 333 puffs. The median values of Cr, Cu, Zn, Sn and Pb content in the aerosol generated by consuming 1 mL of cigarette liquid are: 2233 ng, 700 ng, 5667 ng, 367 ng, and 197 ng respectively, which are much higher than the content in the cigarette liquid [31]. Therefore, the above elements may originate from the migration of smoking equipment materials. Williams et al.[38] analyzed the elements in the aerosol produced by cigarette bomb-type electronic cigarettes. Sn, Ag, Fe, Ni, Al, Si, Ca, Mg, etc. were detected. Williams et al. believed that Sn may come from the solder joints in the cigarette bombshell, other metal elements (such as Cu, Ni, Ag) may come from wires or other metal components in the cigarette shell, and Si, Ca, Al, Mg may come from glass fibers migrating in the oil guide cord.# p#pagination title #e#

4 Summary

At present, e-cigarettes are growing rapidly around the world, but at this stage, there are few risk studies on the chemical components in e-cigarettes. The harmful components in cigarette liquids, the release of harmful components in aerosols, and the migration of high-risk substances in smoking equipment have not yet been fully understood. It is recommended to improve them from the following aspects: (1) Standardize standard cigarette liquids for experimental research, such as determining the mass ratio of glycerol, propylene glycol, nicotine, water and aroma substances;(2) Establish a unified standard analysis method for smoke liquids and aerosols to guide the analysis of harmful component content in smoke liquids, aerosol capture and release;(3) Carry out safety evaluation research on smoking equipment materials to assess the safety risks of harmful migrants.

Although some reportsE-cigarettes are harmfulThere are fewer types and lower content than those in mainstream cigarette smoke, but there are also toxic substances that cause discomfort to the respiratory and cardiovascular systems. Long-term use may increase the risk of chronic lung disease, cardiovascular disease and some other diseases related to smoking.[2]. At this stage, there are not enough studies to quantify the relative risks of e-cigarettes and cigarettes, and a large number of e-cigarettes toxicological evaluations and epidemiological studies are still needed to scientifically, objectively and comprehensively evaluate the safety differences between e-cigarettes and cigarettes.