TY - JOUR
AU - Kośmider,, Leon
AB - Abstract Introduction Electronic cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes. This study aimed to assess whether the generated aerosols from ECs contain lower amount of cadmium (Cd) and lead (Pb) than cigarette smoke and to detect any changes in exposure to Cd and Pb among cigarette smokers who switched completely or partially to EC. Methods EC aerosols and cigarette smoke were generated, and the determination of Cd and Pb in trapped samples and e-liquids was performed by the electrothermal atomic absorption spectrometry method. A cross-sectional, group-based survey was carried out using 156 volunteers classified into groups of nonsmokers, EC-only users, dual EC users-cigarette smokers, and cigarette-only smokers. Using electrothermal atomic absorption spectrometry, blood Cd and Pb levels were measured, and the results were compared by analysis of covariance. Results Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals were present in the remaining e-liquid from tanks used for vapor generation. The geometric mean blood Cd concentration adjusted for age and sex was 0.44 (95% confidence interval = 0.37 to 0.52) µg/L in the EC-only users, which was significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual users of 1.38 (1.11 to 1.72). The blood Pb geometric mean differed significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9 (13.6 to 18.6). Conclusion The study revealed that smokers who completely switched to ECs and quit smoking conventional cigarettes may significantly reduce their exposure to Cd and probably Pb. Implications Switching to EC use is associated with a rapid and substantial decrease in the exposure to carcinogenic Cd. Exposure to Pb is probably also decreased but may be overshadowed by other factors. The study provides empirical data based not only on the analysis of generated aerosol but also on biological indicators of recent exposure—that is, the concentrations of Cd and Pb in blood, indicating EC as a potential harm-reduction device, especially regarding Cd exposure. However, in this case, dual EC use-cigarette smoking provides doubtful benefits. Introduction Cadmium (Cd) and lead (Pb) are heavy metals, which can pose significant negative effects on human health. Their toxicity has been the subject of many studies and is well documented. Both metals may induce numerous adverse health effects. Long-term exposure to Cd results in chronic intoxication, which may manifest mainly as obstructive pulmonary disease and renal tubular disease. There may also be effects on the cardiovascular, skeletal, and reproductive systems.1 Chronic exposure to Pb is linked to adverse effects on the central and peripheral nervous system, the kidneys, and hematological, cardiovascular, reproductive, and immunological systems.1,2 According to the classification by the International Agency for Research on Cancer, Cd and inorganic Pb compounds are classified as Category 1 and 2A carcinogens, respectively. At present, exposure to Cd and Pb in the general population occurs mainly by ingestion and, in to a lesser extent, as a result of inhalation of contaminated air. However, a significant increase in Cd and Pb exposure is caused by tobacco smoke. Both Cd and Pb are present in tobacco in relatively high concentrations that vary between 0.28–4.5 µg/g and 0.28–5.79 µg/g for Cd and Pb, respectively.1 In addition, the transfer of both metals to smoke during tobacco smoking is one of the highest among all metals contained in tobacco, and according to various literature sources, up to 69%–90% of Cd and 24%–60% of Pb passes into the smoke.3 The Food and Drug Administration included Cd and Pb in the list of 93 most harmful and potentially harmful constituents in tobacco products and tobacco smoke as a carcinogen, reproductive or development toxicant (Cd and Pb), respiratory toxicant (Cd), and cardiovascular toxicant (Pb).4 Because of exposure to tobacco smoke, a higher concentration of Cd and Pb is found in smokers’ blood than in nonsmokers’ blood. Ten years of studies within the National Health and Nutrition Examination Studies5 showed that the geometric mean (GM) of Pb in the blood of smokers (aged 19–34 years) was approximately 60% higher than that in the blood of nonsmokers. Tobacco smoking causes the highest Cd body burden in the general population and in similar age groups (20–39 years), the GM of Cd concentration in the blood of smokers was three to four times higher than that in nonsmoking individuals.6 Electronic cigarettes (ECs), which have been introduced on the market for at least a decade, are considered a less harmful alternative to conventional cigarettes. To date, many studies have shown that the amount of toxicants contained in e-liquids and aerosols is significantly lower than in tobacco smoke, and those, which are present, are mostly in the lower concentration.7–10 Nevertheless, it should be noted that for some the toxicants’ levels were found to be comparable with combustible cigarettes. For example, formaldehyde intake for ECs can be even higher than for mainstream tobacco smoke.10–12 However, some of these findings have been challenged through replication studies, which found substantially lower aldehyde emissions than previously reported.13,14 Williams et al.15 found that the concentrations of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concentrations in conventional cigarette smoke. In their more recent investigation, aerosols from disposable ECs and electronic hookahs were more abundant in the total number of different elements than conventional tobacco smoke and some of them were found to be present in significantly higher concentrations.16 The heavy metals such as Cd, Pb, Ni, Sn, Cu, and Cr were detected in both, e-liquids and generated aerosols.7,15–20 Toxicological assessment of EC is still controversial. The report of the Public Health of England showed that ECs have 5% of the risk of tobacco cigarettes.21 Similarly, the Royal College of Physicians concluded in its own report that the availability of EC has been beneficial to UK public health.22 However, according to the World Health Organization report, there are insufficient studies to assess the relative health risk quantifiably compared with smoked tobacco products.23 A similar opinion presents the Report of the Surgeon General stating that the health effects and potentially harmful doses of heated and aerosolized constituents of EC liquids, including solvents, flavorants, and toxicants, are not completely understood.24 Thus, many authorities await the continuation of studies that aim to evaluate the health effects related to the use of EC based on the examination of the EC user population.25–27 Considering the negative influence of Cd and Pb on health, we attempted to assess their possible emissions from an EC and the level of exposure among smokers who completely or partially switched from conventional cigarettes to EC. Subjects and Methods Study Subjects During the study, 156 volunteers (77 men and 79 women) were enrolled whose age was between 19 and 39 years. The volunteers were divided into four groups: smokers who smoked cigarettes for at least 2 years, dual users who smoked conventional cigarettes for at least 2 years and used EC for at least 6 months, EC users who used EC for at least 6 months and were former smokers with minimum duration of smoking cessation of 6 months and who directly switched from combustible cigarettes to EC after smoking for at least 2 years, and never-smokers. The smoking status was verified by measuring exhaled carbon monoxide in the morning hours before the examination. The questionnaire involved questions regarding the amount and years of smoking and/or amount of e-liquids used a day, type of liquids (nicotine content and flavoring), and used EC device. The characteristics of the studied population is presented in Table 1. Almost all participants lived in Sosnowiec city (comprising 240 000 inhabitants) and the vicinity located in southern Poland. They declared that they were not occupationally exposed to Cd and Pb, and their living area was not close to significant point emission sources of heavy metals. In the questionnaire, the participants were also asked in general, concerning the consumption of certain products containing a high amount of Cd and Pb (shellfish, cereals, roots, tubers, and vegetables such as salads, radish, beetroot, spinach, parsley, and carrot).28,29 There was no significant difference in the ingestion of these products between groups during the month preceding the examinations. On this basis, we assumed that environmental exposure to Cd and Pb was similar across the studied population. The study design was approved by the Bioethics Committee of the Institute of Occupational Medicine and Environmental Health in Sosnowiec. Table 1. Characteristic of Study Participants Characteristic Nonsmokers (n = 51) EC users (n = 48) Dual EC users-cigarette smokers (n = 29) Cigarette-only smokers (n = 28) p Male/female (n) 23/28 24/24 17/12 13/15 .29 Age (years) 30.2 (21–39) 29.5 (22–39) 26.2 (18–35) 28.1 (21–39) .032 BMI (kg/m2) 22.8 (18.6–29.1) 25.0 (19.3–34.9) 24.3 (19.5–34.3) 23.7 (19.4–28.9) .073 Blood cadmium (µg/L) 0.32 (0.13–0.76) 0.45 (0.17–0.93) 1.27 (0.40–5.31) 1.39 (0.49–3.76) <.001 Blood lead (µg/L) 11.7 (5–25) 14.1 (8–30) 14.2 (7–26) 15.2 (6–32) .042 Cigarettes per day, (n) NA NA 8.8 (5.7) 14.7 (4.5) <.001 E-liquid per day (mL) NA 2.7 (1.7) 1.7 (0.8) NA <.001 Characteristic Nonsmokers (n = 51) EC users (n = 48) Dual EC users-cigarette smokers (n = 29) Cigarette-only smokers (n = 28) p Male/female (n) 23/28 24/24 17/12 13/15 .29 Age (years) 30.2 (21–39) 29.5 (22–39) 26.2 (18–35) 28.1 (21–39) .032 BMI (kg/m2) 22.8 (18.6–29.1) 25.0 (19.3–34.9) 24.3 (19.5–34.3) 23.7 (19.4–28.9) .073 Blood cadmium (µg/L) 0.32 (0.13–0.76) 0.45 (0.17–0.93) 1.27 (0.40–5.31) 1.39 (0.49–3.76) <.001 Blood lead (µg/L) 11.7 (5–25) 14.1 (8–30) 14.2 (7–26) 15.2 (6–32) .042 Cigarettes per day, (n) NA NA 8.8 (5.7) 14.7 (4.5) <.001 E-liquid per day (mL) NA 2.7 (1.7) 1.7 (0.8) NA <.001 Geometric mean (5th–95th percentile), arithmetic mean (SD). EC = electronic cigarette; e-liquid = electronic cigarette liquid; BMI = body mass index; NA = not applicable. View Large Table 1. Characteristic of Study Participants Characteristic Nonsmokers (n = 51) EC users (n = 48) Dual EC users-cigarette smokers (n = 29) Cigarette-only smokers (n = 28) p Male/female (n) 23/28 24/24 17/12 13/15 .29 Age (years) 30.2 (21–39) 29.5 (22–39) 26.2 (18–35) 28.1 (21–39) .032 BMI (kg/m2) 22.8 (18.6–29.1) 25.0 (19.3–34.9) 24.3 (19.5–34.3) 23.7 (19.4–28.9) .073 Blood cadmium (µg/L) 0.32 (0.13–0.76) 0.45 (0.17–0.93) 1.27 (0.40–5.31) 1.39 (0.49–3.76) <.001 Blood lead (µg/L) 11.7 (5–25) 14.1 (8–30) 14.2 (7–26) 15.2 (6–32) .042 Cigarettes per day, (n) NA NA 8.8 (5.7) 14.7 (4.5) <.001 E-liquid per day (mL) NA 2.7 (1.7) 1.7 (0.8) NA <.001 Characteristic Nonsmokers (n = 51) EC users (n = 48) Dual EC users-cigarette smokers (n = 29) Cigarette-only smokers (n = 28) p Male/female (n) 23/28 24/24 17/12 13/15 .29 Age (years) 30.2 (21–39) 29.5 (22–39) 26.2 (18–35) 28.1 (21–39) .032 BMI (kg/m2) 22.8 (18.6–29.1) 25.0 (19.3–34.9) 24.3 (19.5–34.3) 23.7 (19.4–28.9) .073 Blood cadmium (µg/L) 0.32 (0.13–0.76) 0.45 (0.17–0.93) 1.27 (0.40–5.31) 1.39 (0.49–3.76) <.001 Blood lead (µg/L) 11.7 (5–25) 14.1 (8–30) 14.2 (7–26) 15.2 (6–32) .042 Cigarettes per day, (n) NA NA 8.8 (5.7) 14.7 (4.5) <.001 E-liquid per day (mL) NA 2.7 (1.7) 1.7 (0.8) NA <.001 Geometric mean (5th–95th percentile), arithmetic mean (SD). EC = electronic cigarette; e-liquid = electronic cigarette liquid; BMI = body mass index; NA = not applicable. View Large EC Used by the Study Subjects Participants from the EC group used 12 different brands of second-generation (44 individuals) and third-generation (four individuals) ECs. The nicotine concentrations of e-liquid used were as follows: 0.1%–0.4% (two individuals); 0.6%–0.9% (15 individuals); 1.0%–1.5% (14 individuals); 1.6%–2.4% (15 individuals); and greater than 2.4% (two individuals). Among the six groups of flavorings, most of the individuals used fruit taste (21 individuals) followed by tobacco taste (11 individuals), menthol taste (eight individuals), and tea/coffee taste (six individuals). Participants from the dual-user group used eight different brands of second-generation (26 individuals) and third-generation (three individuals) ECs. The nicotine concentrations of e-liquid used were as follows: 0.1%–0.4% (two individuals); 0.6%–0.9% (13 individuals); 1.0%–1.5% (15 individuals); 1.6%–2.4% (15 individuals); and greater than 2.4% (one individual). Among the seven groups of flavorings, most of the individuals used fruit taste (11 individuals) followed by tobacco taste (seven individuals) and menthol taste (seven individuals). EC Devices and E-Liquid Filling for Emission Measurement The second-generation Ego-3 battery (3.4 V with voltage stabilization) was used most popularly among the participants in our study. We examined four tank systems (two CE4 systems with a top atomizer and two CE5 systems with a bottom atomizer) and convenience samples of 18 e-liquids. Each EC tank was filled, rotated a few times to ensure the homogeneous distribution of the contents, and stored for at least 24 hours in the dark at room temperature at a horizontal position before the experiment. Each was used for a single brand of e-liquid. The batteries were fully charged before the experiment and were replaced after the charge level reached half of the maximum value, which was signaled by the red diode on the battery. Aerosol/Smoke Generation and Analysis Aerosol from ECs was generated using a smoking machine Palaczbot (Technical University of Lodz, Poland; Supplementary Figure 1). The puff volume was validated using a Soap Bubble Flow Meter R 24.01 (Borgwaldt, Germany). The difference between the average puff volumes was ±5%. We used puffing topography utilized in our previous study: puff volume = 70 mL, puff duration = 1.8 seconds, and puff interval = 17 seconds.30 Each series of vapor generation (15 puffs) was repeated four times (60 total puffs per e-liquid) with 15-minute intervals between each series. Aerosol (60 puffs) was collected in round-bottomed flasks (1000 mL) containing 10 mL of 10% (v/v) nitric acid (Baker Instra-Analyzed). The inner walls of the flask were moistened by the solution and the tube of gas washing bottle head ended just above it. The aerosol was gathered at the bottom of flask without bubbling to prevent violent spreading and escaping of the aerosol from the flask. After each series, aerosol was allowed to deposit on the walls and in the liquid and was completely dissolved in an absorption solution by gently swirling. Similarly, blank samples of room air were prepared at the beginning and end of the analysis session. Efficiency was assessed by placing the membrane filter on the outlet and checked it for metals’ content after aerosol collection (the details later). All the results for filter were under detection limit. Similarly, no presence of nicotine was shown on the glass filters (Borgwaldt, 44 mm diameter) mounted on the outlet in a series of separate experiments, in which nicotine was measured following the Cooperation Centre for Scientific Research Relative to Tobacco method. Smoke was generated using the 3R4f reference cigarettes under ISO parameters and was collected on two connected in series membrane filters with a 0.8-µm pore size and 37-mm diameter (Millipore). The combined filters were mineralized using concentrated nitric acid and 30% hydrogen peroxide (Baker Analyzed) in closed perfluoroalkoxy vessels followed by the dilution to 10 mL of volume. The membrane (Mix Cellulose Esters) filters are commonly used in air monitoring to collect particulates and characterized by very low blank sample results. To verify the collection efficiency of the filters, the test was carried out with three filters in series. Negligible or undetectable level of metals was found on the third filter, indicating enough efficiency for quantitative collection of the Cd and Pb presented in the smoke. All the samples were stored in 15-mL Falcon vials and were analyzed for the metal content by electrothermal atomic absorption spectrometry (Perkin Elmer 4100ZL) using optimized time–temperature program parameters. For Cd and Pb, the limit of detection (LOD) was 0.0002 and 0.001 µg/15 puffs and 0.001 and 0.005 µg/cigarette, respectively. Determination of Cd and Pb in E-Liquids Both e-liquids from new closed bottles and remaining e-liquids from tank used for aerosol generation were analyzed for the metals’ content in the same fashion. The samples of the remaining e-liquid were obtained within a week following aerosol generation. An aliquot of e-liquid was diluted 10 times with 0.8 M nitric acid and then was analyzed by electrothermal atomic absorption spectrometry using optimized time–temperature program parameters. When the concentration exceeded the calibration range, the solution was appropriately diluted to achieve a concentration within the calibration curve. The LOD was 0.50 µg/L and 0.01 mg/L for Cd and Pb, respectively. Determination of Cd and Pb Levels in the Blood Blood for Cd and Pb level determination was collected from a cubital vein on the morning after the 12-hour fast after the last meal. Cd and Pb levels in the blood were determined by atomic absorption spectrometry using electrothermal atomization and Zeeman type background correction (PerkinElmer 4100ZL). Blood samples for analyses were deproteinized using 0.8 M nitric acid mixed with blood at 8:5 and 4:1 ratios to determine the Cd and Pb levels, respectively. Calibration was performed using standard solutions prepared in bovine blood. All samples were run in duplicate. The detection limits of Cd and Pb were 0.10 and 3 µg/L, respectively, and the precision values of the results expressed as the coefficients of variation were 5.4% and 4.4%, respectively. The Laboratory of the Institute of Occupational Medicine and Environmental Health regularly participates in proficiency testing in the field of Cd and Pb examination in the blood (Lead and Multielement Proficiency), meeting the requirements of the program organizers. Statistical and Mathematical Calculation The calculations were performed using STATISTICA V 9.1 StatSoft (2010). As appropriate, the GM with 5th–95th percentiles, range, or arithmetic mean with standard deviation were chosen for the presentation of characteristics and measures distributed across specified groups of data. The initial between-group differences in the means and proportions were tested by the Kruskal–Wallis rank test and F test, respectively. Analysis of covariance was used to compare the adjusted values of the metals in blood, and significant differences between groups were assessed using post hoc analysis (Tukey test for unequal sample size). Due to the nonnormal distribution of data, the values were natural log transformed to the approximate normal distribution. Analysis was controlled by age, sex, and body mass index as a priori covariance; however, the final body mass index was found not to be significant and was excluded in the final models similar to age in case of the model for Pb in the blood. The results were considered significant at p less than .05. Results A description of the study population and summaries of the blood analysis results are presented in Table 1. All the sample levels were above the method detection limit of each the elements in the blood. Figure 1 presents the distribution of Cd and Pb concentrations measured in the blood of participants. The GM (with 95% confidence intervals) blood Cd concentrations adjusted for age and sex were 0.31 (0.26 to 0.36); 0.44 (0.37 to 0.52); 1.38 (1.11 to 1.72), and 1.44 (1.16 to 1.78) µg/L in the nonsmokers, EC users, dual users, and smokers, respectively. Post hoc analysis revealed that significant differences were observed between nonsmokers and EC users (p = .026), and between nonsmokers or EC users and dual users or smokers (p < .001). In the same study groups, the GM (95% confidence intervals) blood Pb concentrations adjusted for sex were 11.9 (10.6 to 13.3); 14.2 (12.5 to 16.0); 13.9 (11.9 to 16.2), and 15.9 (13.6 to 18.6) µg/L. The concentrations of Pb in the blood were significantly different only between the nonsmokers and smokers groups (p = .043). Figure 1. View largeDownload slide Blood cadmium (a) and lead (b) levels by group (crude data). Horizontal bars = medians. p values for differences between the cigarette-only smokers and other groups (Tukey test for unequal sample size including significant covariates); ns = nonsignificant; EC = electronic cigarette. Figure 1. View largeDownload slide Blood cadmium (a) and lead (b) levels by group (crude data). Horizontal bars = medians. p values for differences between the cigarette-only smokers and other groups (Tukey test for unequal sample size including significant covariates); ns = nonsignificant; EC = electronic cigarette. The metal concentration in the remaining e-liquids originating from a particular tank system, unused e-liquids, and aerosols is provided in Table 2. Cd was not detectable in all aerosols analyzed and was quantified in 3R4f reference cigarette emission in many times higher levels comparing to studied EC aerosols per puff basis. Pb was only sporadically detected (three cases) in EC aerosols and was detected in 3R4f reference cigarette emission, which was approximately three times higher than the highest value obtained for EC emission per puff basis. All the blank room/air sample results did not reach the LOD of the analysis methods. Table 2. Concentration of Cadmium and Lead in Nicotine Liquids and Electronic Cigarette Aerosols/Smoke Tank system/ cigarette Number of liquids/ cigarettes tested Remained e-liquid after vaporization in tanks E-liquid in bottle Aerosol/smoke Pb (mg/L) Cd (µg/L) Pb (mg/L) Cd (µg/L) Pb (µg/15 puffs or cigarette) Cd (µg/15 puffs or cigarette) CE4(1) 5 0.22‒29.26 <0.50‒46.46 <0.01 <0.50 <0.001 <0.0002 CE5(2) 8 0.04‒34.64 <0.50‒32.66 <0.01 <0.50 <0.001‒0.003 <0.0002 CE4(3) 2 0.08‒3.35 <0.50‒1.61 <0.01 <0.50 <0.001 <0.0002 CE5(4) 3 1.14‒17.84 <0.50‒13.07 <0.01 <0.50 <0.001‒0.003 <0.0002 3R4f 3 — — — — 0.009 (0.002) 0.056 (0.001) Tank system/ cigarette Number of liquids/ cigarettes tested Remained e-liquid after vaporization in tanks E-liquid in bottle Aerosol/smoke Pb (mg/L) Cd (µg/L) Pb (mg/L) Cd (µg/L) Pb (µg/15 puffs or cigarette) Cd (µg/15 puffs or cigarette) CE4(1) 5 0.22‒29.26 <0.50‒46.46 <0.01 <0.50 <0.001 <0.0002 CE5(2) 8 0.04‒34.64 <0.50‒32.66 <0.01 <0.50 <0.001‒0.003 <0.0002 CE4(3) 2 0.08‒3.35 <0.50‒1.61 <0.01 <0.50 <0.001 <0.0002 CE5(4) 3 1.14‒17.84 <0.50‒13.07 <0.01 <0.50 <0.001‒0.003 <0.0002 3R4f 3 — — — — 0.009 (0.002) 0.056 (0.001) Range or arithmetic mean (SD). Cd = cadmium; Pb = lead; e-liquid = electronic cigarette liquid. View Large Table 2. Concentration of Cadmium and Lead in Nicotine Liquids and Electronic Cigarette Aerosols/Smoke Tank system/ cigarette Number of liquids/ cigarettes tested Remained e-liquid after vaporization in tanks E-liquid in bottle Aerosol/smoke Pb (mg/L) Cd (µg/L) Pb (mg/L) Cd (µg/L) Pb (µg/15 puffs or cigarette) Cd (µg/15 puffs or cigarette) CE4(1) 5 0.22‒29.26 <0.50‒46.46 <0.01 <0.50 <0.001 <0.0002 CE5(2) 8 0.04‒34.64 <0.50‒32.66 <0.01 <0.50 <0.001‒0.003 <0.0002 CE4(3) 2 0.08‒3.35 <0.50‒1.61 <0.01 <0.50 <0.001 <0.0002 CE5(4) 3 1.14‒17.84 <0.50‒13.07 <0.01 <0.50 <0.001‒0.003 <0.0002 3R4f 3 — — — — 0.009 (0.002) 0.056 (0.001) Tank system/ cigarette Number of liquids/ cigarettes tested Remained e-liquid after vaporization in tanks E-liquid in bottle Aerosol/smoke Pb (mg/L) Cd (µg/L) Pb (mg/L) Cd (µg/L) Pb (µg/15 puffs or cigarette) Cd (µg/15 puffs or cigarette) CE4(1) 5 0.22‒29.26 <0.50‒46.46 <0.01 <0.50 <0.001 <0.0002 CE5(2) 8 0.04‒34.64 <0.50‒32.66 <0.01 <0.50 <0.001‒0.003 <0.0002 CE4(3) 2 0.08‒3.35 <0.50‒1.61 <0.01 <0.50 <0.001 <0.0002 CE5(4) 3 1.14‒17.84 <0.50‒13.07 <0.01 <0.50 <0.001‒0.003 <0.0002 3R4f 3 — — — — 0.009 (0.002) 0.056 (0.001) Range or arithmetic mean (SD). Cd = cadmium; Pb = lead; e-liquid = electronic cigarette liquid. View Large Cd was not detected in e-liquids from a few tanks, whereas Pb was detected in all liquids taken from the tanks in relatively high concentrations. For the same brand of tank system, the concentration of metals varied in a very wide range and differs nearly up to 1000 times in the highest point. By contrast, Pb and Cd were not detected in any e-liquid taken from the unused, closed bottles. Discussion EC users inhaling aerosol generated by the EC device are potentially exposed to toxic and carcinogenic metals. Among them are Cd and Pb, which are also present in tobacco smoke, one of the main sources of exposure to these metals among smokers. On the market, various EC devices and a variety of flavors are available. Four years ago, these levels were estimated to be 460 and 7600, respectively.31 Currently, there is a wide range of these types of products, and it is not surprising that the concentration of metals determined in the liquid varied in a broad range. Hess et al.32 analyzed the liquid from 10 cartridges from 5 brands and found that the concentration of Cd was within 0.1–255 µg/L, and the concentration of Pb was within 3.2–4870 µg/L. Such wide differences cannot be only a result of contaminated liquids but due to the direct contact of the liquid with the device components made from metals.20,33,34 It was also confirmed in our study that nicotine liquids not contaminated by Cd and Pb showed the presence of both metals after the tank systems were filled and used. After partial e-liquid evaporation due to puffing sessions, the levels of Cd and Pb were in the range less than LOD—46.46 µg/L and 40–34 640 µg/L, respectively. It was also found that tanks of the same brand filled with different liquids varied in the levels of the studied metals and that their transfer was not linked to the concentration of metals in the liquid from the tank. The cause may be related to the composition and quality of the metal parts (alloys and joins) used in the EC devices as also liquid constituents resulting for example in a different pH. Another possible reason for this finding is the possibility of problems with consistent production and possible difference in materials from one batch to the other. Although, it should be mentioned that the used atomizer systems are largely outdated and almost unavailable in the European Union market due to the fact that they are not Tobacco Product Directive (TPD) compliant, perhaps excluding requirements regarding capacity (<2 mL). However, most importantly for exposure assessment, the transfer of both metals to aerosol seemed to be minimal. Considering the exposure of EC users to the metals, there is a need to consider their levels in aerosol that is inhaled and enters the body. To date, reports involving this issue are sparse, and the data presented are divergent (Table 3). There are a few reasons for this: the studies were conducted using e-liquids with different nicotine concentrations, flavorings, and manufacturers; different EC models and brands were used for aerosol generation that may vary in heating element and other metal components. Obviously, their direct contact with liquid may lead to metal release and contamination, which may take place especially in prefilled cartomizers, which are filled with liquid since production and thus the contact between liquid and metal parts exists for a long time (even for months). This is expected to increase corrosion and thus metal detection in the liquid extracted from prefilled cartomizers. At least the topography parameters used for aerosol generation, as factors influencing metal transfer rates of elements, were different among performed studies. Table 3. Reported Values for Cadmium and Lead in Aerosols/Smoke Study Subject of study Reported contents Reported contents in cigarette smoke Comments of aerosol heavy metal determination (object of study, LOD, puffing parameters, method of analysis) Cd Pb Cd Pb Laugesen35 Aerosol ND (µg/300 puffs) ND (µg/300 puffs) — — One sample of aerosol from nicotine refill cartridge; CdLOD <0.01 ppm; PbLOD < 0.01; 38 and 58 mL puffs; ICP–MS Goniewicz et al.7 Aerosol 0.01–0.22 µg/150 puffs 0.03–0.57 µg/150 puffs — — Samples of aerosol from 12 cartridges of different EC brands; Cd and Pb detected in 11 and 12 brands, respectively; 150 puffs, 70 mL puffs with a 1.8-s duration; ICP–MS Williams et al.15 Aerosol NI 0.017 µg/10 puffs — 0.017–0.98a µg/cig Aerosol generated from cartomizer; 60 puffs with a 4.3-s duration (not volume data); ICP–OES Williams et al.16 Aerosol/smoke NI <0.002–0.162 µg/10 puffs NI NI Aerosol generated from disposable EC/electronic hookah; 60 puffs with a 4.3-s duration, 12.9–81.7 mL; ICP–OES Margham et al.9 Aerosol/smoke 0.082 ng/puff 0.230 ng/puff 8.81 ng/puff 2.47 ng/puff One sample cartomizer; 100 puffs, 55 mL puffs with a 3-s duration; ICP-MS; 3R4F smoke reference Mikheev et al.36 Aerosol ND ND — — Samples of seven aerosol-generated liquids with seven different flavors; 75 puffs, 74 mL puffsb with a 4.3-s duration; ICP–MS Palazzolo et al.20 Aerosol/smokec BDL BDL 0.08 µg/15 puffs 0.01 µg/cig One sample aerosol generated from liquid; 45 puffs, 33.6 mL puffs with a 5-s duration; ICP–MS; smoke from conventional Marlboro cigarettes This work Aerosol <0.0002 µg/15 puffs <0.0001–0.005 µg/15 puffs 0.056 µg/cig 0.009 µg/cig Sample of 18 aerosol from 18 refill liquid and 10 clearomizer, Cd and Pb detected in 0 and 3 samples, respectively; 60 puffs, 70 mL, 1.8 s; Cd LOD = 0.0002 µg/15 puffs, LOD Pb = 0.001 µg/15 puffs; ETAAS; smoke from reference cigarettes 3R4F Study Subject of study Reported contents Reported contents in cigarette smoke Comments of aerosol heavy metal determination (object of study, LOD, puffing parameters, method of analysis) Cd Pb Cd Pb Laugesen35 Aerosol ND (µg/300 puffs) ND (µg/300 puffs) — — One sample of aerosol from nicotine refill cartridge; CdLOD <0.01 ppm; PbLOD < 0.01; 38 and 58 mL puffs; ICP–MS Goniewicz et al.7 Aerosol 0.01–0.22 µg/150 puffs 0.03–0.57 µg/150 puffs — — Samples of aerosol from 12 cartridges of different EC brands; Cd and Pb detected in 11 and 12 brands, respectively; 150 puffs, 70 mL puffs with a 1.8-s duration; ICP–MS Williams et al.15 Aerosol NI 0.017 µg/10 puffs — 0.017–0.98a µg/cig Aerosol generated from cartomizer; 60 puffs with a 4.3-s duration (not volume data); ICP–OES Williams et al.16 Aerosol/smoke NI <0.002–0.162 µg/10 puffs NI NI Aerosol generated from disposable EC/electronic hookah; 60 puffs with a 4.3-s duration, 12.9–81.7 mL; ICP–OES Margham et al.9 Aerosol/smoke 0.082 ng/puff 0.230 ng/puff 8.81 ng/puff 2.47 ng/puff One sample cartomizer; 100 puffs, 55 mL puffs with a 3-s duration; ICP-MS; 3R4F smoke reference Mikheev et al.36 Aerosol ND ND — — Samples of seven aerosol-generated liquids with seven different flavors; 75 puffs, 74 mL puffsb with a 4.3-s duration; ICP–MS Palazzolo et al.20 Aerosol/smokec BDL BDL 0.08 µg/15 puffs 0.01 µg/cig One sample aerosol generated from liquid; 45 puffs, 33.6 mL puffs with a 5-s duration; ICP–MS; smoke from conventional Marlboro cigarettes This work Aerosol <0.0002 µg/15 puffs <0.0001–0.005 µg/15 puffs 0.056 µg/cig 0.009 µg/cig Sample of 18 aerosol from 18 refill liquid and 10 clearomizer, Cd and Pb detected in 0 and 3 samples, respectively; 60 puffs, 70 mL, 1.8 s; Cd LOD = 0.0002 µg/15 puffs, LOD Pb = 0.001 µg/15 puffs; ETAAS; smoke from reference cigarettes 3R4F NI = not identified; ND = not detectable; BDL = below detection limit; LOD = limit of detection; Cd = cadmium; Pb = lead; EC = electronic cigarette; ETAAS = electrothermal atomic absorption spectrometry; ICP-MS = inductively coupled plasma mass spectrometry; ICP-OES = inductively coupled plasma optical emission spectrometry. aLiterature data. bCalculated from flow rate and duration puff. cAccumulation of the trace metals on mixed cellulose ester membranes exposed to EC-generated aerosol and cigarette smoke. View Large Table 3. Reported Values for Cadmium and Lead in Aerosols/Smoke Study Subject of study Reported contents Reported contents in cigarette smoke Comments of aerosol heavy metal determination (object of study, LOD, puffing parameters, method of analysis) Cd Pb Cd Pb Laugesen35 Aerosol ND (µg/300 puffs) ND (µg/300 puffs) — — One sample of aerosol from nicotine refill cartridge; CdLOD <0.01 ppm; PbLOD < 0.01; 38 and 58 mL puffs; ICP–MS Goniewicz et al.7 Aerosol 0.01–0.22 µg/150 puffs 0.03–0.57 µg/150 puffs — — Samples of aerosol from 12 cartridges of different EC brands; Cd and Pb detected in 11 and 12 brands, respectively; 150 puffs, 70 mL puffs with a 1.8-s duration; ICP–MS Williams et al.15 Aerosol NI 0.017 µg/10 puffs — 0.017–0.98a µg/cig Aerosol generated from cartomizer; 60 puffs with a 4.3-s duration (not volume data); ICP–OES Williams et al.16 Aerosol/smoke NI <0.002–0.162 µg/10 puffs NI NI Aerosol generated from disposable EC/electronic hookah; 60 puffs with a 4.3-s duration, 12.9–81.7 mL; ICP–OES Margham et al.9 Aerosol/smoke 0.082 ng/puff 0.230 ng/puff 8.81 ng/puff 2.47 ng/puff One sample cartomizer; 100 puffs, 55 mL puffs with a 3-s duration; ICP-MS; 3R4F smoke reference Mikheev et al.36 Aerosol ND ND — — Samples of seven aerosol-generated liquids with seven different flavors; 75 puffs, 74 mL puffsb with a 4.3-s duration; ICP–MS Palazzolo et al.20 Aerosol/smokec BDL BDL 0.08 µg/15 puffs 0.01 µg/cig One sample aerosol generated from liquid; 45 puffs, 33.6 mL puffs with a 5-s duration; ICP–MS; smoke from conventional Marlboro cigarettes This work Aerosol <0.0002 µg/15 puffs <0.0001–0.005 µg/15 puffs 0.056 µg/cig 0.009 µg/cig Sample of 18 aerosol from 18 refill liquid and 10 clearomizer, Cd and Pb detected in 0 and 3 samples, respectively; 60 puffs, 70 mL, 1.8 s; Cd LOD = 0.0002 µg/15 puffs, LOD Pb = 0.001 µg/15 puffs; ETAAS; smoke from reference cigarettes 3R4F Study Subject of study Reported contents Reported contents in cigarette smoke Comments of aerosol heavy metal determination (object of study, LOD, puffing parameters, method of analysis) Cd Pb Cd Pb Laugesen35 Aerosol ND (µg/300 puffs) ND (µg/300 puffs) — — One sample of aerosol from nicotine refill cartridge; CdLOD <0.01 ppm; PbLOD < 0.01; 38 and 58 mL puffs; ICP–MS Goniewicz et al.7 Aerosol 0.01–0.22 µg/150 puffs 0.03–0.57 µg/150 puffs — — Samples of aerosol from 12 cartridges of different EC brands; Cd and Pb detected in 11 and 12 brands, respectively; 150 puffs, 70 mL puffs with a 1.8-s duration; ICP–MS Williams et al.15 Aerosol NI 0.017 µg/10 puffs — 0.017–0.98a µg/cig Aerosol generated from cartomizer; 60 puffs with a 4.3-s duration (not volume data); ICP–OES Williams et al.16 Aerosol/smoke NI <0.002–0.162 µg/10 puffs NI NI Aerosol generated from disposable EC/electronic hookah; 60 puffs with a 4.3-s duration, 12.9–81.7 mL; ICP–OES Margham et al.9 Aerosol/smoke 0.082 ng/puff 0.230 ng/puff 8.81 ng/puff 2.47 ng/puff One sample cartomizer; 100 puffs, 55 mL puffs with a 3-s duration; ICP-MS; 3R4F smoke reference Mikheev et al.36 Aerosol ND ND — — Samples of seven aerosol-generated liquids with seven different flavors; 75 puffs, 74 mL puffsb with a 4.3-s duration; ICP–MS Palazzolo et al.20 Aerosol/smokec BDL BDL 0.08 µg/15 puffs 0.01 µg/cig One sample aerosol generated from liquid; 45 puffs, 33.6 mL puffs with a 5-s duration; ICP–MS; smoke from conventional Marlboro cigarettes This work Aerosol <0.0002 µg/15 puffs <0.0001–0.005 µg/15 puffs 0.056 µg/cig 0.009 µg/cig Sample of 18 aerosol from 18 refill liquid and 10 clearomizer, Cd and Pb detected in 0 and 3 samples, respectively; 60 puffs, 70 mL, 1.8 s; Cd LOD = 0.0002 µg/15 puffs, LOD Pb = 0.001 µg/15 puffs; ETAAS; smoke from reference cigarettes 3R4F NI = not identified; ND = not detectable; BDL = below detection limit; LOD = limit of detection; Cd = cadmium; Pb = lead; EC = electronic cigarette; ETAAS = electrothermal atomic absorption spectrometry; ICP-MS = inductively coupled plasma mass spectrometry; ICP-OES = inductively coupled plasma optical emission spectrometry. aLiterature data. bCalculated from flow rate and duration puff. cAccumulation of the trace metals on mixed cellulose ester membranes exposed to EC-generated aerosol and cigarette smoke. View Large The data presented in Table 2 indicate that the amount of Cd and Pb in the aerosol is many times lower (often <LOD) that in main stream tobacco smoke. According to Margham et al.,9 the concentration of Cd and Pb in the aerosol is over 100 and over 10 times lower, respectively, compared with tobacco smoke. An exception is the study by Williams et al.15 in which the authors compared the results of the Pb concentration in aerosols and indicate that its level of Pb in aerosol may be equal to the level of Pb in tobacco smoke. It is noteworthy to add that low-quality ECs of 1-generation was tested in this study. Among 11 brands of disposable ECs and electronic hookahs in turn, which were tested in their more recent survey, Pb was identified in the aerosol of only two brands of disposable electronic hookahs.16 The lower concentration of Cd and Pb in the EC aerosol than in tobacco smoke implicates changes in the EC user exposure to both toxic metals. It may be hypothesized that switching from conventional cigarettes to ECs will decrease the risk of exposure to Cd and Pb. Because Cd and Pb in the blood reflects a particularly recent exposure level, the examinations of EC users and dual users, conducted in our study, confirm the hypothesis. It was found that quitting smoking to use ECs leads to a rapid and significant decrease in the level of Cd in the blood of EC users, nearly to the level of nonsmoking individuals (Figure 1a). Small, but significant differences between nonsmokers and EC users occur; however, blood Cd levels also tend to reflect cumulative exposure in environmentally exposed subjects and were found to be higher in former smokers than in nonsmokers.37 A small and not significant decrease in the blood Cd concentrations in dual users compared with smokers indicates that reducing smoking to use ECs does not lead to a substantial decrease in exposure to Cd in contrast to completely switching from conventional cigarettes to ECs. This finding confirms that in an earlier report showing that only completely replacing conventional cigarettes by ECs may probably decrease adverse health effects associated with cigarette smoking.26,38,39 However, it should be mentioned that the difference in smoking consumption between dual users and smokers was below 50%; it is possible that larger reductions in consumption (eg, in a dual user smoking from 20 to 2 or 3 cigarettes per day) could affect exposure to Cd. Instead, the mean concentration of Pb in the blood of EC users was not significantly lower than that in the smokers (Figure 1b). There may be a few reasons for this: smoking is not the only important source of Pb, and the effect may be overshadowed by another pathway of human exposure (eg, food ingestion, frequent hand-to-mouth contact); it is possible that Pb deposited in bone during previous smoking40 is slowly fluxed to the circulation, increasing the Pb level in the blood. Therefore, a lack of significant decrease in the blood Pb level in EC users is not related to EC use but rather indicates other considerable sources of exposure and detoxification processes. Notably, the differences between EC users and nonsmokers and even between dual smokers and nonsmokers were also not statistically significant in contrast to smokers, whose average level of blood Pb was still significantly higher in this case. In addition, due to low sample size there are possibilities that the analysis was underpowered to detect significant differences in Pb exposure. To the best of our knowledge, this is the first study indicating the lower risk of Cd exposure among individuals who switched from conventional cigarettes to ECs. Until now, the assessment of the exposure risk for both metals was based on the amount of metals in aerosol and comparing the obtained values with chronic permissible daily exposure from inhalational medication defined by US Pharmacopeia.18 The authors considered results obtained by Goniewicz et al.,7 and after calculation of the quantity of Cd contained in aerosol from 1200 puffs (twice more than the estimated amount of puffs for EC users) concluded that the mean level of exposure was 2.6 times lower than that of permissible daily exposure. Only for one sample exposure was 10% higher than value from permissible daily exposure. In the case of Pb, the mean exposure was seven times lower than the inhalational permissible daily exposure level in licensed medications. The study has several limitations. First, it was a cross-sectional study design without follow-up data due to the difficulty in participation among volunteers during the 6-month period of the examination. Therefore, we cannot evaluate absolutely the association between cause and effect. Second, the studied group was relatively small, and the e-liquids and EC devices tested were limited compared with their availability on the Polish market. The EC devices we tested were also largely outdated, and currently they are almost completely unavailable in the European Union market. Finally, according to other published data, puff duration used in the study was very short, because the longer the heating duration, the more metals could be released during the heating of coil. However, longer than 3-second puff durations are mostly reported by users of newer EC devices. In our study, we tested early second-generation devices with real-live measured puffing topography among users of first and second-generation ECs in 2012.41 Using longer puffs duration, which was reported by other authors,42,43 might likely increase amount of metals in aerosol. Thus our results for metal emissions should be interpreted with caution, especially related to different types of tank systems, where different puffing regimes would be more appropriate, because different conditions of aerosol generation and e-liquid components may influence the transfer of metals to aerosols, increasing their level and same-user exposure. Additional limitation is the possible presence of nanoparticles in EC emissions, which could make exposure assessment more complicated than analysis of the blood for metals level. Blood analysis may not show the entire picture because nanoparticles inhaled by the nose can be delivered to the brain directly via axons. However, monitoring of Cd and Pb concentration in blood is commonly used to assess environmental and occupational exposure and elevated levels of these metals in blood have been shown to be associated with increased risk of ample range of health outcomes primarily cardiovascular, neurotoxic, renal, and bone effects.44,45 Exposure to heavy metals because of EC use cannot be considered only regarding Cd and Pb. The latest reports indicate the possibility of Ni, Cu, and Sn occurrence at levels higher than those in tobacco smoke.16,20,34 Therefore, further studies are needed to estimate the degree of EC harmfulness for their users, also in the field of heavy metal exposure. In conclusion, the results obtained in our study indicate that aerosols generated by ECs are free from Cd, and in most cases, from Pb, although the tested EC devices were usually a source of Cd and Pb contamination of e-liquids. The results of blood analysis confirmed that completely switching from cigarettes to EC leads to a high reduction in the exposure to carcinogenic Cd. Considering other reports indicating the lowering of exposure to carcinogenic compounds contained in tobacco smoke in EC users46, it is plausible to conclude that quitting smoking with the use of ECs may decrease the risk for neoplasia attributed to Cd and Pb exposure in smokers who switched to EC. Therefore, our results, together with other data on reduced exposure to harmful constituents that are present in tobacco cigarettes and ECs, can aid in evaluating ECs as a potential harm-reduction device. Supplementary Material Supplementary data are available at Nicotine and Tobacco Research online Funding This work was supported by the Institute of Occupational Medicine and Environmental Health Sosnowiec, Poland (grant number ZSCHiTG–9/2015) and Medical University of Silesia (grant number KNW–1–054/K/7/0). Declaration of Interests We have read and understood the journal’s policy on the declaration of interests. AP, MS–C, PO, and AS are employees of the Institute of Occupational Medicine and Environmental Health. One of the institute’s objectives is outsourcing for the industrial sector, including manufacturers of e-cigarettes. However, this has no influence on the study design. AS accepted personal fees from the eSmoking Institute in Poznan, Poland, and nonfinancial support from Chic Group LTD, a manufacturer of electronic cigarettes in Poland, outside of the submitted work. 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Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Exposure to Cadmium and Lead in Cigarette Smokers Who Switched to Electronic Cigarettes
JF - Nicotine and Tobacco Research
DO - 10.1093/ntr/nty161
DA - 2019-08-19
UR - https://www.deepdyve.com/lp/oxford-university-press/exposure-to-cadmium-and-lead-in-cigarette-smokers-who-switched-to-4RYAQPmC34
SP - 1198
VL - 21
IS - 9
DP - DeepDyve
ER -