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Recent evidence suggests that e-cigarette users tend to change their puffing behaviors when using e-liquids with reduced nicotine concentrations by taking longer and more frequent puffs. Using puffing regimens modelled on puffing topography data from 19 experienced e-cigarette users who switched between 18 and 6 mg/mL e-liquids with and without power adjustments, differences in daily exposure to carbonyl compounds and estimated changes in cancer risk were assessed by production of aerosols generated using a smoking machine and analyzed using gas and liquid chromatography. Significant differences across conditions were found for formaldehyde and acetaldehyde (p < 0.01). Switching from a higher to a lower nicotine concentration was associated with greater exposure regardless of whether power settings were fixed or adjustable which is likely due to increased liquid consumption under lower nicotine concentration settings. Daily exposure for formaldehyde and acetaldehyde was higher for 17/19 participants when using low (6 mg/mL) compared with high (18 mg/mL) nicotine e-liquid concentration when power was fixed. When power adjustments were permitted, formaldehyde and acetaldehyde levels were higher respectively for 16/19 and 14/19 participants with the use of 6 compared with 18 mg/mL nicotine e-liquid.

Background: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions., Materials and Methods: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions ® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry., Results: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O 2 /[s ⋅ 110 8 platelets]); bootstrap-boosted P 1α =0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O 2 /[s ⋅ mg of protein]); bootstrap-boosted P 1α =0.049., Conclusion: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples., Competing Interests: Disclosure The costs of this study were defrayed from regular finances of the Department of Pneumology and Allergy, The animal house of the Pharmaceutical Faculty, Department of Hemostasis and Hemostatic Disorders, of Medical University of Lodz, Poland, and of the Department of General and Inorganic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec of Medical University of Silesia, and Institute of Occupational Medicine and Environmental Health in Sosnowiec. AB is also supported by the fund for the young investigators of the Medical University of Lodz (502-03/1-151-03/502-14-364-18). KS received the Etiuda scholarship funded by the NCN (2016/20/T/NZ3/00505). LK is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA. LK works as an expert for the Polish National Committee for Standardization and for the European Committee for standardization of requirements and test methods for e-liquids and emissions. Additionally, JK is and LK was an employee 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 studies design. The other authors report no conflicts of interest in this work.

Introduction: Article 20 of the European Tobacco Products Directive (EU-TPD) specifies that e-liquids should not contain nicotine in excess of 20 mg/mL, thus many vapers may be compelled to switch to lower concentrations and in so doing, may engage in more intensive puffing. This study aimed to establish whether more intensive puffing produces higher levels of carbonyl compounds in e-cigarette aerosols., Methods: Using the HPLC-UV diode array method, four carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein) were measured in liquids and aerosols from nicotine solutions of 24 and 6 mg/mL. Aerosols were generated using a smoking machine configured to replicate puffing topography data previously obtained from 12 experienced e-cigarette users., Results: Carbonyl levels in aerosols from the puffing regimen of 6 mg/mL were significantly higher (p < .05 using independent samples t tests) compared with those of 24 mg/mL nicotine. For the 6 and 24 mg/mL nicotine aerosols respectively, means ± SD for formaldehyde levels were 3.41 ± 0.94, and 1.49 ± 0.30 µg per hour (µg/h) of e-cigarette use. Means ± SD for acetaldehyde levels were 2.17 ± 0.36 and 1.04 ± 0.13 µg/h. Means ± SD for acetone levels were 0.73 ± 0.20 and 0.28 ± 0.14 µg/h. Acrolein was not detected., Conclusions: Higher levels of carbonyls associated with more intensive puffing suggest that vapers switching to lower nicotine concentrations (either due to the EU-TPD implementation or personal choice), may increase their exposure to these compounds. Based on real human puffing topography data, this study suggests that limiting nicotine concentrations to 20 mg/mL may not result in the desired harm minimalization effect., Implications: More intensive puffing regimens associated with the use of low nicotine concentration e-liquids can lead to higher levels of carbonyl generation in the aerosol. Although in need of replication in a larger sample outside a laboratory, this study provides pragmatic empirical data on the potential risks of compensatory puffing behaviors in vapers, and can help to inform future regulatory decisions on nicotine e-liquid concentrations. The cap on nicotine concentration at 20 mg/mL set by the EU-TPD may therefore have the unintended consequence of encouraging use of lower nicotine concentration e-liquid, in turn increasing exposure to carbonyl compounds through compensatory puffing.

Objective: The cardiovascular effects of lead are caused primarily through an effect on blood pressure but are not just limited to an increased risk of hypertension. The aim of our study was to determine to what extent chronic exposure to lead affects new risk factors for cardiovascular disease (CVD) development, such as biomarkers of inflammation (C reactive protein (CRP) and fibrinogen) and biomarkers of endothelial dysfunction (homocysteine, asymmetric dimethylarginine (ADMA) and L-homoarginine)., Methods: A cross-sectional study was performed on a sample of 231 male volunteers, aged 20-60 years, working for at least 2 years in jobs with exposure to lead during the mining and processing of lead-zinc ores. The association between lead in blood and CVD biomarkers was evaluated using multiple linear regression, and the effects of exposure level were observed in workers divided into subgroups according to their blood lead concentration: <250, 250-400 and >400 µg/L., Results: Lead in the blood correlated with new risk factors for CVD except for ADMA. Multiple regression analysis revealed that predictive properties for lead in the blood increased for particular biomarkers in the following order: L-homoarginine, fibrinogen, CRP and homocysteine. Among the specified groups, significant differences were observed only between the groups with the most and least exposure to lead, which differed in concentrations by 54.3% for CRP, 19.3% for fibrinogen, 10.6% for homocysteine and -25.5% for L-homoarginine., Conclusions: These findings support the hypothesis that occupational exposure to lead can promote atherosclerosis, particularly in highly exposed individuals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: Glycerin (VG) and propylene glycol (PG) are the most common nicotine solvents used in e-cigarettes (ECs). It has been shown that at high temperatures both VG and PG undergo decomposition to low molecular carbonyl compounds, including the carcinogens formaldehyde and acetaldehyde. The aim of this study was to evaluate how various product characteristics, including nicotine solvent and battery output voltage, affect the levels of carbonyls in EC vapor., Methods: Twelve carbonyl compounds were measured in vapors from 10 commercially available nicotine solutions and from 3 control solutions composed of pure glycerin, pure propylene glycol, or a mixture of both solvents (50:50). EC battery output voltage was gradually modified from 3.2 to 4.8V. Carbonyl compounds were determined using the HPLC/DAD method., Results: Formaldehyde and acetaldehyde were found in 8 of 13 samples. The amounts of formaldehyde and acetaldehyde in vapors from lower voltage EC were on average 13- and 807-fold lower than in tobacco smoke, respectively. The highest levels of carbonyls were observed in vapors generated from PG-based solutions. Increasing voltage from 3.2 to 4.8V resulted in a 4 to more than 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage device were in the range of levels reported in tobacco smoke., Conclusions: Vapors from EC contain toxic and carcinogenic carbonyl compounds. Both solvent and battery output voltage significantly affect levels of carbonyl compounds in EC vapors. High-voltage EC may expose users to high levels of carbonyl compounds., (© The Author 2014. 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.)

Significance: Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals., Materials and Methods: Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods., Results: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product., Conclusions: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).

Background: Tobacco smoking is one of the most important risk factors for cardiovascular disease (CVD) and few biomarkers have been linked to the increased risk of CVD and tobacco smoking. Tobacco smoke has been shown to elevate the plasma levels of asymmetric dimethylarginine (ADMA), a metabolite of L-arginine and an endogenous inhibitor of endothelial nitric oxide synthase. The other potential biomarker that has not been studied to date is L-homoarginine, a homolog of L-arginine. The aim of this study was to evaluate the effects of cigarette smoking on L-homoarginine and other CVD biomarkers., Methods and Results: In a cross-sectional study of 231 healthy male volunteers, we measured plasma levels of L-homoarginine, L-arginine, and ADMA using the HPLC method. In smokers, we found that plasma L-homoarginine levels were 16.7% lower compared with nonsmokers after adjusting for age, body mass index, plasma creatinine, and metal blood levels (P<0.05). Plasma ADMA levels were only 6.0% higher in smokers when compared with the levels found in nonsmokers (P>0.05)., Conclusions: Our results suggest that, in contrast to ADMA, there is a strong association between exposure to tobacco smoke and plasma L-homoarginine levels. Further research in this field is needed to explain the mechanisms of the relationship of low L-homoarginine levels, smoking, and cardiovascular health.

Objectives: Changes in enzymatic antioxidant activity are frequently observed in workers occupationally exposed to lead. Few studies have investigated the influence of lead on the non-enzymatic antioxidant system. The aim of our study was to assess the influence of occupational exposure to lead on the plasma concentration of two hydrophobic forms of vitamin E: α-tocopherol and γ-tocopherol., Methods: A sample of 401 healthy men, aged 19-62, participated in the study. In total, 340 of these subjects were employed at the Mine and Metallurgical Plant in southern Poland. The workers who were occupationally exposed to lead were divided into quartiles (groups of 85 subjects). The lead concentrations in the blood of the subjects in the control group and in the lead exposure quartiles correspond to the following ranges: 10-72 μg/l (control group); 82-206 μg/l (Q1); 209-308 μg/l (Q2); 308-394 μg/l (Q3) and 395-644 μg/l (Q4), respectively., Results: Significant differences were observed only for the plasma concentration of γ-tocopherol, which differed between the control group and Q1 (by 24.1%, p=0.0368), between Q1 and Q3 (by -18.8%, p=0.0115) and between Q1 and Q4 (by -25.7%, p=0.0002). Multiple linear regression analysis showed that the statistically significant, predictive properties of the γ-tocopherol plasma concentration were as follows: triglycerides (β=0.440)> age (β=0.131)> whole cholesterol (β=0.117)> blood lead concentration (β=-0.108). For α-tocopherol, significant prognostic properties were triglycerides and total cholesterol (β=0.485 and β=0.399, respectively)., Conclusions: Occupational exposure to lead is strongly correlated with the concentration of γ-tocopherol but not α-tocopherol.