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The effect of smoking on hypertensive disorders of pregnancy is a public concern. Recent evidence suggests that the risk of hypertensive disorders of pregnancy is influenced by the presence of uterine fibroids. We explored the association between maternal smoking exposure and the risk of hypertensive disorders of pregnancy in relation to the presence of uterine fibroids using data from Japan's largest birth cohort study. This study focused on first-time mothers, and the study population comprised 2752 and 35,294 first-time mothers with and without uterine fibroids, respectively. Hypertensive disorders of pregnancy was categorized as early-onset (before 34 weeks) and late-onset (after 34 weeks). Maternal smoking exposure was assessed by measuring the urinary cotinine concentration during the mid-trimester. Participants were classified into four quartiles based on their urinary cotinine levels as follows: Q1 (low concentration) to Q4 (high concentration). Multivariate analysis adjusted for potential confounders revealed that in women without uterine fibroids, the Q3 urinary cotinine level was associated with a modified risk of early-onset hypertensive disorders of pregnancy (adjusted odds ratio: 0.63, 95% confidence interval: 0.44-0.89). Conversely, for women with uterine fibroids, Q4 urinary cotinine level was associated with an increased risk of hypertensive disorders of pregnancy (adjusted odds ratio: 1.68, 95% confidence interval: 1.05-2.72). In conclusion, this study indicated that the impact of maternal smoking exposure varied based on the presence of uterine fibroids, underscoring the importance of personalized preconception care., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Previous studies indicated that exposure to VOCs was linked to increased systemic inflammation levels. However, the dose-response relationships between urine VOCs metabolites and systemic inflammation have not been established, and the key metabolite of the toxic compounds has not been identified., Methods: We used data in 7007 US adults in the NHANES cycles (2011-2018) across 8 years. Urinary VOC metabolites were measured using ultra-performance liquid chromatography and electrospray tandem mass spectrometry (UPLC-ESI/MSMS). VOC metabolites were adjusted by urinary creatinine level before analysis. Systemic inflammation was assessed by systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) indices. Generalized linear models, restricted cubic splines (RCS), and weighted quantile sum (WQS) regression were applied to evaluate the associations, exposure-response (E-R) curve and identify the key contributor compound, adjusting for gender, age, race, BMI, marital condition, education level, smoking level, alcohol consumption and physical activity. Smoking status was assessed as an effect modifier., Results: Significant and robust positive correlations were found between 8 VOC metabolites and both SII and SIRI. They were N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA), mandelic acid (MA), N-Acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MHBMA3), phenylglyoxylic acid (PGA), and N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA). The RCS curves showed J-shaped or exponential shaped E-R relationships for most VOC metabolites. WQS regression found that exposure to the mixture of VOC metabolites was related to increased systemic inflammation, and MA was the key VOC metabolite contributing most to systemic inflammation levels. Smokers exhibited higher levels of urinary VOCs and larger susceptibility to VOC-related increases in SII and SIRI compared to non-smokers., Conclusion: This study demonstrated a strong link between urinary VOC metabolites and increased systemic inflammation, and smokers were more susceptible. Our findings highlighted the significance of reducing VOC exposure to mitigate the inflammation levels, particularly for smokers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, the concentrations of heavy metals such as cadmium (Cd), chromium (Cr), and lead (Pb) in the two groups of cigarette smokers and non-smokers in five age range groups were measured. Heavy metal concentrations were collected in participants' urine samples and analyzed using atomic absorption spectrophotometry (AAS). The results showed that the concentrations of these metals in the urine of smokers were higher than in non-smoker subjects. The mean concentration of Cd, Cr, and Pb for smokers were 1.188 ± 0.931, 1.929 ± 0.940, and 0.069 ± 0.023, respectively, while the mean concentration of Cd, Cr, and Pb for non-smokers were 0.151 ± 0.165, 0.203 ± 0.218, and 0.037 ± 0.030, respectively. The results revealed statistically significant differences when comparing the samples of smokers to the control group in all heavy metals in the present study. Also, the results revealed statistically significant differences in Cd, Cr, and Pb when comparing the samples of smokers to age groups. The trend of metals in urine samples in two groups (smokers and non-smokers) is as follows: Cd > Cr > Pb. The concentration of Cd, Cr, and Pb in all samples of the present study was higher than the biological limit, according to ACGIH. Therefore, Cd, Cr, and Pb were the most critical metals accumulated in the urine of cigarette smokers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ToxiLaus study aims at evaluating the impact of environmental toxic species on health and diseases' onset and development. Specifically, the ubiquitous presence of trace elements (TEs) in the environment urges for a better characterization of their influence on human organism. In its primary phase, the ToxiLaus study focused on measuring the urinary concentrations of 23 TEs in the baseline samples from the CoLaus|PsyCoLaus population-based cohort, using inductively coupled plasma mass spectrometry (ICP-MS). Statistical analyses were carried out on 5866 participants, investigating links between TEs concentrations and smoking status, metabolic syndrome and body mass index (BMI). Smoking status was associated with Cd, Zn, Pb, Mo and Hg (respectively OR = 3.64, 1.42, 1.20, 0.69 and 0.58) while metabolic syndrome was associated with Zn and Cd (OR = 1.81 and 1.24 respectively). Concentrations of Zn, Hg, Co, Ni, Cu, Mo, As, Sn, Tl, Fe where significantly different (p < 0.0001) between BMI groups (Normal, Overweight, Obese). Finally, this study provides an overview of the distribution of trace elements in a cohort large sample of the general population, as well as their main associations with cardiovascular risk factors. Theses relations will be further analysed in subsequent phases of the study., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Hypothesis: Evidence on the role of smoking in the development of chronic kidney disease (CKD) has mostly relied on self-reported smoking status. We aimed to compare the associations of smoking status as assessed by self-reports and urine cotinine with CKD risk., Methods: Using the PREVEND prospective study, smoking status was assessed at baseline using self-reports and urine cotinine in 4333 participants (mean age, 52 years) without a history of CKD at baseline. Participants were classified as never, former, light current, and heavy current smokers according to self-reports and comparable cutoffs for urine cotinine. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for CKD., Results: The percentages of self-reported and cotinine-assessed current smokers were 27.5% and 24.0%, respectively. During a median follow-up of 7.0 years, 593 cases of CKD were recorded. In analyses adjusted for established risk factors, the HRs (95% CI) of CKD for self-reported former, light current, and heavy current smokers compared with never smokers were 1.17 (0.95-1.44), 1.48 (1.10-2.00), and 1.48 (1.14-1.93), respectively. On further adjustment for urinary albumin excretion (UAE), the HRs (95% CI) were 1.07 (0.87-1.32), 1.26 (0.93-1.70), and 1.20 (0.93-1.57), respectively. For urine cotinine-assessed smoking status, the corresponding HRs (95% CI) were 0.81 (0.52-1.25), 1.17 (0.92-1.49), and 1.32 (1.02-1.71), respectively, in analyses adjusted for established risk factors plus UAE., Conclusion: Self-reported current smoking is associated with increased CKD risk, but dependent on UAE. The association between urine cotinine-assessed current smoking and increased CKD risk is independent of UAE. Urine cotinine-assessed smoking status may be a more reliable risk indicator for CKD incidence than self-reported smoking status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N -glucuronidated NNAL (NNAL- N -gluc), O -glucuronidated NNAL (NNAL- O -gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT 2 B 10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

Purpose: Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT)., Experimental Design: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening., Results: Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts., Conclusions: Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers., (©2024 The Authors; Published by the American Association for Cancer Research.)

Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3'-hydroxycotinine, and (2'S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans -3'-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1'S,2'S)-nicotine 1'-oxide in the samples of individuals from various groups.

Stainless steel welders are exposed to heavy filler metals. We evaluated the concentration of these metals in whole blood and urine, and the relevant biochemical parameters in relation to the total chromosomal aberrations (CAs), chromatid-type (CTA-type, CTAs) and chromosome-type (CSA-type, CSAs), in 117 welders and control individuals. Statistically higher concentrations of the total Cr, Ni and Mn were observed in whole blood and urine of welders, and the concentrations were higher in welders who smoked. On the contrary, concentrations of urinary heavy metals Cr and Mn adjusted for creatinine were significantly higher in the control groups. A statistically higher frequency of total CAs was observed in the whole group of welders, and also in the non-smoking welders, as compared to controls. The frequency of total CAs significantly correlated with the concentration of Cr, Ni and Mn in whole blood (R=0.61, P˂0.0001, R=0.33, P˂0.0001 and R=0.66, P˂0.0001, respectively), with urinary concentrations of Ni and Mn (R=0.27, P=0.003 and R=0.28, P=0.003, respectively) and with urinary concentrations of Cr, Ni and Mn adjusted for creatinine (R=0.22, P=0.029, R=0.26, P=0.005 and R=0.20, P=0.030, respectively). Likewise, the frequency of CTA-types significantly correlated with the concentration of Cr and Mn in whole blood (R=0.31, P=0.0007 and R=0.34, P=0.0002). The frequency of CSA-types significantly correlated with concentrations of Cr, Ni and Mn in whole blood (R=0.43, P˂0.0001, R=0.38, P˂0.0001 and R=0.46, P˂0.0001, respectively). The statistically higher values of serum creatinine and total bilirubin were detected in all welders, as well as in smokers when compared to the corresponding controls. The exposure to heavy metals in welders increased the frequencies of CAs and altered the balance between urinary excretion of heavy metals and their possible accumulation., Competing Interests: Declaration of Competing Interest To our best knowledge neither of the co-authors has any actual or potential competing interests regarding this manuscript. The study was conducted in agreement with ethical principles on strictly coded samples and the identity of the participants was not disclosed., (Copyright © 2024. Published by Elsevier B.V.)

Background: Smoking is a major risk factor for type 2 diabetes (T2D), but the evidence has mostly relied on self-reports. We aimed to compare the associations of smoking exposure as assessed by self-reports and urine cotinine with T2D., Methods: Using the PREVEND prospective study, smoking status was assessed at baseline by self-reports and urine cotinine in 4708 participants (mean age, 53 years) without a history of diabetes. Participants were classified as never, former, light current and heavy current smokers according to self-reports and analogous cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for T2D., Results: During a median follow-up of 7.3 years, 259 participants developed T2D. Compared with self-reported never smokers, the multivariable adjusted HRs (95% CI) of T2D for former, light current, and heavy current smokers were 1.02 (0.75-1.4), 1.41 (0.89-2.22), and 1.30 (0.88-1.93), respectively. The corresponding adjusted HRs (95% CI) were 0.84 (0.43-1.67), 1.61 (1.12-2.31), and 1.58 (1.08-2.32), respectively, as assessed by urine cotinine. Urine cotinine-assessed but not self-reported smoking status improved T2D risk prediction beyond established risk factors., Conclusion: Urine cotinine assessed smoking status may be a stronger risk indicator and predictor of T2D compared to self-reported smoking status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Determining the effect of dietary factors on cancer is a crucial issue when accounting for the effect of other major risks, such as smoking and drinking., Method: A total of 15,563 adults from the Korean National Cancer Center Community Cohort were analyzed to determine and to compare the effect of dietary factors on stomach and colorectal cancer in overall and in the subgroup of non-smokers (or urinary cotinine concentrations <5 ng/mg) and non-drinkers with Cox proportional-hazard models., Results: During the mean follow-up (13.7 years), 469 and 299 cases of stomach and colorectal cancer were identified, respectively. The preventive effect of vegetable, fish, and soybean/tofu intake on colorectal cancer was found in women after adjustment for smoking, drinking, BMI, and sociodemographic factors. In the subgroup analysis of non-smokers and non-drinkers, the effect on colorectal cancer was increased in women (≥1 time/week vs. almost never, vegetables: hazard ratio (HR) 0.30, 95% confidence interval (CI) 0.13-0.69; fish: HR 0.46, 95% CI 0.26-0.83), and the fresh fish intake effect on stomach cancer was newly identified in men (HR 0.36, 95% CI 0.15-0.86). These effects were more pronounced and additionally shown in other dietary factors such as soybean or tofu in women and vegetables and fish in men, when subjects with <5 ng/mg urinary cotinine concentrations applied., Conclusion: The protective effect of healthy eating on the risk of stomach and colorectal cancer were different by smoking and drinking status. Rigorous control of smoking and drinking effects is necessary when measuring the effect of dietary factors on cancer, properly., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The concentration in urine of N -acetyl-hydroxy-propyl-cisteine (3HPMA), an acrolein metabolite, has been employed as a marker of the risk of illness of smokers and the relative concentration of creatinine has been evaluated to verify the effect of moving from the practice of burning tobacco to nicotine vaping. From the results concerning the urine samples of 38 subjects, collected from 2021 to 2023 and analyzed by LC-MS/MS, corresponding to 5 active smokers, 13 previously heavy smokers who replaced traditional tobacco by vaping, and 20 non-smokers, a dramatic reduction was found in 3HPMA/creatinine in urine. 3HPMA varied from values of 2150-3100 μg g creatinine -1 to levels of 225-625 μg g creatinine -1 found for non-smokers, with the time decay described by the equation y = 0.3661 x 2 - 94.359 x + 6246.4 ( R 2 : 0.757), providing a time of approximately 10 years for tobacco memory after the cessation of the consumption of burned tobacco.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants formed during the incomplete combustion of organic matter such as tobacco. Among these, benzo[a]pyrene (BaP) has been classified as a known carcinogen to humans. It unfolds its effect through metabolic activation to BaP-(7R,8S)-diol-(9S,10R)-epoxide (BPDE), the ultimate carcinogen of BaP. In this article, we describe a simple and highly sensitive GC-NICI-MS/MS method for the quantification of urinary BaP-(7R,8S,9R,10S)-tetrol (( +)-BPT I-1), the hydrolysis product of BPDE. The method was validated and showed excellent results in terms of accuracy, precision, and sensitivity (lower limit of quantification (LLOQ): 50 pg/L). In urine samples derived from users of tobacco/nicotine products and non-users, only consumption of combustible cigarettes was associated with a significant increase in BPT I-1 concentrations (0.023 ± 0.016 nmol/mol creatinine, p < 0.001). Levels of users of potentially reduced-risk products as well as non-users were all below the LLOQ. In addition, the urine levels of six occupationally exposed workers were analyzed and showed the highest overall concentrations of BPT I-1 (844.2 ± 336.7 pg/L). Moreover, comparison with concentrations of 3-hydroxybenzo[a]pyrene (3-OH-BaP), the major detoxification product of BaP oxidation, revealed higher levels of 3-OH-BaP than BPT I-1 in almost all study subjects. Despite the lower levels, BPT I-1 can provide more relevant information on an individual's cancers susceptibility since BPDE is generated by the metabolic activation of BaP. In conclusion, BPT I-1 is a suitable biomarker to distinguish not only cigarette smokers from non-smokers but also from users of potentially reduced-risk products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Cigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited., Aims and Methods: This study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other exclusive cigar subtypes (ie, non-premium large cigars, cigarillos, and filtered cigars), cigarettes, and non-tobacco users., Results: In comparison to non-tobacco users, exclusive premium cigar users had higher geometric mean concentrations of the nicotine metabolite cotinine (5.8 vs. 0.5ng/mg, p < .0001), tobacco-specific nitrosamine (TSNA) (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL): 7.8 vs. 1.3pg/mg, p < .0001), and volatile organic compound (VOC) (N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA, acrylonitrile): 4.7 vs. 1.6ng/mg, p < .0001). Exclusive premium cigar users were less likely to be daily users than other tobacco user groups and had comparable BOEs with exclusive non-premium large cigar users but generally lower BOEs than exclusive cigarillo, filtered cigar, and cigarette smokers. Daily exclusive premium cigar users had similar nicotine and TSNA exposure but lower exposure to polycyclic aromatic hydrocarbons and volatile organic compounds than exclusive cigarillo and filtered cigar users., Conclusions: Premium cigar use exhibits different exposure to toxicants from other cigar subtype users. Regulations of premium cigars need to formalize product definition and take the population's health effects into consideration., Implications: This population study provides important information on BOE and potential harm with premium cigar use and its potential health effects. At present, premium cigars appear to pose a relatively low overall population health risk due to low frequency of use. However, future regulation of other tobacco products might change the landscape of premium cigar use and alter the overall health impact., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since nicotine use can be from both tobacco and non-tobacco sources. This study aimed to provide an in-depth evaluation of the suitability of anabasine and anatabine as WBE biomarkers of tobacco and subsequently estimate their excretion factors for WBE applications. Pooled urine ( n = 64) and wastewater samples ( n = 277), collected between 2009 and 2019 in Queensland, Australia, were analyzed for nicotine and its metabolites (cotinine and hydroxycotinine), as well as anabasine and anatabine. Anabasine performed as the better biomarker, showing a similar per capita load in pooled urine (2.2 ± 0.3 μg/day/person) and wastewater samples (2.3 ± 0.3 μg/day/person), while the per capita load of anatabine in wastewater was 50% higher than its load in urine. It is estimated that 0.9 μg of anabasine was excreted per cigarette smoked. Triangulation of tobacco sales data and tobacco use estimated from either anabasine or cotinine showed that anabasine-based estimates were 5% higher than sales data, while cotinine-based estimates were between 2 and 28% higher. Our results provided concrete evidence to confirm the suitability of anabasine as a specific biomarker for monitoring tobacco use by WBE.

Background: The US FDA announced its commitment to prohibiting menthol as a characterizing flavor in tobacco. The relationship between cigarette menthol and exposure to toxic substances in mainstream tobacco smoke is not well characterized., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 special sample were used to study markers of 26 harmful and potentially harmful constituents (HPHC) in tobacco smoke. These include urine metabolites of polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), and heavy metals in exclusive menthol (n = 162) and nonmenthol (n = 189) cigarette smokers. Urine metabolites of 7 PAHs, 15 VOCs, and 4 heavy metal biomarkers were compared by menthol status. Multivariable analyses were conducted on creatinine-adjusted concentrations., Results: There were no significant differences in cotinine levels or in 22 of 26 HPHCs. Among the urine metabolites of PAHs, the levels of 1-hydroxyphenanthrene were about 16% lower in menthol smokers. Among the urine metabolites of VOCs, menthol cigarette smokers presented significantly lower concentrations of acrylamide, N,N-dimethylformamide, and acrylonitrile. Menthol and nonmenthol smokers presented similar levels of heavy metals. Menthol did not affect the levels of cotinine and the nicotine metabolite ratio in urine., Conclusions: Menthol and nonmenthol cigarettes deliver similar levels of most HPHCs., Impact: Findings on toxicity are similar for menthol and nonmenthol cigarettes., (©2022 American Association for Cancer Research.)

Background: Smoking intensity, which is generally based on self-reported average cigarettes per day (CPD), is a major behavioural risk factor and strongly related to socioeconomic status (SES). To assess the validity of the CPD measure, correlations with objective markers of tobacco smoke exposure - such as urinary nicotine metabolites - were examined. Yet, it remains unclear, whether this correlation is affected by SES, which may indicate imprecise or biased self-reports of smoking intensity., Methods: We investigated the role of SES in the association between CPD and nicotine metabolites in current smokers among the participants of the population-based, prospective Heinz Nixdorf Recall Study. We determined urinary cotinine and additionally trans-3'-hydroxy-cotinine. SES was assessed by the International Socio-Economic Index of occupational status, and education. We calculated correlations (Pearson's r) between logarithmised CPD and cotinine in subgroups of SES and analysed SES and further predictors of cotinine in multiple linear regression models separately by gender., Results: Median reported smoking intensity was 20 CPD in male and 19 CPD in female smokers. Men showed higher cotinine concentrations (median 3652 μg/L, interquartile range (IQR) 2279-5422 μg/L) than women (3127 μg/L, IQR 1692-4920 μg/L). Logarithmised CPD correlated moderately with cotinine in both, men and women (Pearson's r 0.4), but correlations were weaker in smokers with lower SES: Pearson's r for low, intermediate, and high occupational SES was 0.35, 0.39, and 0.48 in men, and 0.28, 0.43, and 0.47 in women, respectively. Logarithmised CPD and urinary creatinine were main predictors of cotinine in multiple regression models, whereas SES showed a weak negative association in women. Results were similar for trans-3'-hydroxy-cotinine., Conclusions: Decreasing precision of self-reported CPD was indicated for low SES in men and women. We found no strong evidence for biased self-reports of smoking intensity by SES., (© 2022. The Author(s).)

Introduction: Understanding interactions of smoking topography with biomarkers of exposure to tobacco is essential for accurate smoking risk assessments., Methods: In this study, the smoking topography and the levels of tobacco smoke exposure urinary biomarkers of a sample of active Korean smokers were quantified and measured. The results were used to investigate the effect of daily activities and smoking time on the smoking topography. Moreover, correlations between the smoking topography parameters and biomarkers were assessed., Results: No significant effect of either the daily activities or time on the smoking topography of the subjects were observed. Synchronic correlations of the cigarette consumption per day (CPD) and the average flow per puff with both urinary cotinine and trans-3'-hydroxycotinine were significant. For the urinary nicotine metabolites, the peak levels appeared when the CPD was over 19 cigarettes per day and the average puff velocity was between 35 and 45 ml/s. Nevertheless, when the average flow was over 60 ml/s, the levels of cotinine and trans-3'-hydroxycotinine significantly dropped., Conclusions: The findings of this study may be beneficial for further smoking risk assessments with contributions of both the smoking topography and biomarkers to provide current smokers with applicable cession programs.Clinical significanceSmoking habits and levels of urinary biomarkers of Korean smokers are investigated.People with a higher dependency on nicotine smoke cigarettes with slower puffs.Effects of daily activities or time on smoking topography were not significant.Correlations between smoking topography and urinary biomarkers were significant.Peak biomarker levels were observed under certain smoking topography conditions.

Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10 -5 ) and a significant exposure-response relationship with 5MC (p = 7 × 10 -4 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10 -3 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites., (© 2021 Environmental Mutagen Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Introduction: Environmental arsenic contamination is a major toxicological problem worldwide due to its carcinogenic and nephrotoxic potential., Aim: The purpose of this observational study was to determine the suspected association between urinary arsenic (uAs) and urinary leucine (or leucyl) aminopeptidase 3 (uLAP 3 ) to evaluate uLAP 3 as a candidate biomarker of exposure to airborne arsenic., Materials and Methods: A total of 918 adults occupationally and/or environmentally exposed to airborne arsenic were enrolled in the study. Baseline information (age; sex; history of smoking; alcohol, fish and seafood consumption) was gathered. Total uAs concentrations [μg/L] of 918 subjects, as well as the sum of arsenic species (ΣiAs) in 259 subjects, were obtained. Urinary LAP 3 was measured by an immune-enzymatic assay using an ELISA kit. Urinary creatinine concentration was assessed with the IB/lAB/1289 research protocol (version II, 2015-09-17). The values of uAs and uLAP 3 were recalculated per unit of creatinine. The association between uAs and uLAP 3 was assessed using a logistic regression model adjusted for confounders., Results: The study identified a positive correlation between the logarithm of uAs and the logarithm of uLAP 3 in the study population (r = 0.1737, p < 0.0000) and between urinary creatinine and uLAP 3 concentration not adjusted for creatinine level (r = 0.1871, p < 0.001). In the logistic regression model, there was also an association between increased (≥15 µg/L) uAs and decreased (below the 25th quartile) uLAP 3 [OR uLAP 3 = 1.22 (95% CI 1.03 to 1.44, p < 0.02)]., Conclusions: These data suggest that urinary LAP 3 may be a potential biomarker of arsenic exposure, which warrants further study.

Purpose: Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients., Materials and Methods: This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure., Results: The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure., Conclusions: Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.

Objectives: Although several self-reported questionnaire-based studies have found an association between smoking and moderately increased albuminuria, this result remains controversial. We investigated whether moderately increased albuminuria was associated with smoking status, verified by urinary cotinine (an objective biomarker of tobacco exposure), using population-based, nationally representative data., Methods: This study included 2059 participants aged ≥ 50 years from the 2014 Korean National Health and Nutrition Examination Survey. Individuals with a urinary cotinine level ≥ 50 ng/mL were identified as cotinine-verified smokers. Moderately increased albuminuria was defined as a urine albumin-to-creatinine ratio ranging between ≥ 30 mg/g and < 300 mg/g. Multivariable logistic regression was used to evaluate the association between cotinine-verified smoking status and moderately increased albuminuria., Results: Among the study participants, 16.9% were cotinine-verified smokers, 84.8% of whom were men. After adjustment for multiple covariates, cotinine-verified smokers showed a significant positive association with moderately increased albuminuria (adjusted odds ratio: 4.37, 95% confidence interval: 1.63-11.71) compared with cotinine-verified non-smokers. The association between urinary cotinine and moderately increased albuminuria did not differ with age, sex, obesity, or comorbidities (P-value for interaction > 0.05 in all cases)., Conclusion: This large-scale observational study showed that cotinine-verified smoking is associated with moderately increased albuminuria in the Korean middle-aged and older general population, suggesting that smoking must be strictly controlled to reduce the risk of moderately increased albuminuria., Competing Interests: The authors have declared that no competing interests exist.

Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.

The longitudinal relationship between smoking status and risk of developing visual impairment (VI) remains unclear. We examined the relationship of smoking status and urinary cotinine level, an objective measure of smoking, with incidence of VI. This cohort study included 279,069 individuals free of VI who were followed for up to 8.8 years (median 4.8 years). VI was defined as when bilateral visual acuity was worse than 0.5 (cutoffs of 0.3 Logarithm of the Minimum Angle of Resolution). During 1,324,429.8 person-years of follow-up, 7852 participants developed new-onset bilateral VI. Self-reported current smoking status was associated with increased risk of developing VI in both men and women, with a stronger association in women (P for interaction = 0.01). Multivariable adjusted hazard ratios (95% confidence intervals) for incident VI comparing current smokers to never-smokers were 1.14 (1.04-1.25) in men and 1.52 (1.28-1.80) in women. Urinary cotinine levels of ≥ 100 ng/ml were significantly associated with increased risk of incident VI, and these associations remained when introducing changes in urinary cotinine and other confounders during follow-up as time-varying covariates. Cigarette smoking assessed based on self-report and urinary cotinine level was associated with increased incidence of VI. Our findings identify smoking as an independent risk factor for VI.

Objectives: The aim of the study was to investigate the correlations within the levels of biomarkers in different biological matrices, along with smoking topography variables, among active male smokers in Korea. Accordingly, we defined a transformation factor to convert level of tobacco smoke exposure and impact biomarkers from different biometrics., Methods: We examined smoking topography of recruited volunteers using a self-reporting survey. The level of tobacco smoke exposure and impact biomarkers in subjects' urine and blood were analysed. Results were used to assess the correlations between the topography survey items with biomarkers in biological matrices. The relationship between the biomarkers in urine and blood was analysed. Accordingly, we defined a transformation factor as the ratio of different biomarkers in urine and blood matrices., Results: Significant correlations among smoking topography variables and biomarkers were found. Besides, a strong significant association was found among urine and blood cotinine ( ρ  = 0.817) and NMR ( ρ  = 0.905). Urine vs blood cotinine and NMR transformation factors were calculated to be 6.17 L-Blood/g-Creatinine and 10.2, respectively., Conclusions: The validated transformation factor connects epidemiological cohort studies with tobacco smoking exposure risk assessment. Hence, this study might be beneficial for further habit-based smoking risk assessments to obtain successful regional cession policies.

A novel method for the quantification of the sulfur-containing metabolites of formaldehyde (thiazolidine carboxylic acid (TCA) and thiazolidine carbonyl glycine (TCG)) and acetaldehyde (methyl thiazolidine carboxylic acid (MTCA) and methyl thiazolidine carbonyl glycine (MTCG)) was developed and validated for human urine and plasma samples. Targeting the sulfur-containing metabolites of formaldehyde and acetaldehyde in contrast to the commonly used biomarkers formate and acetate overcomes the high intra- and inter-individual variance. Due to their involvement in various endogenous processes, formate and acetate lack the required specificity for assessing the exposure to formaldehyde and acetaldehyde, respectively. Validation was successfully performed according to FDA's Guideline for Bioanalytical Method Validation (2018), showing excellent performance with regard to accuracy, precision, and limits of quantification (LLOQ). TCA, TCG, and MTCG proved to be stable under all investigated conditions, whereas MTCA showed a depletion after 21 months. The method was applied to a set of pilot samples derived from smokers who consumed unfiltered cigarettes spiked with 13 C-labeled propylene glycol and 13 C-labeled glycerol. These compounds were used as potential precursors for the formation of 13 C-formaldehyde and 13 C-acetaldehyde during combustion. Plasma concentrations were significantly lower as compared to urine, suggesting urine as suitable matrix for a biomonitoring. A smoking-related increase of unlabeled biomarker concentrations could not be shown due to the ubiquitous distribution in the environment. While the metabolites of 13 C-acetaldehyde were not detected, the described method allowed for the quantification of 13 C-formaldehyde uptake from cigarette smoking by targeting the biomarkers 13 C-TCA and 13 C-TCG in urine.Graphical abstract.

Objective: The inhalation of air-borne toxicants is associated with adverse health outcomes which can be somewhat mitigated by enhancing endogenous anti-oxidant capacity. Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine), present in high abundance in skeletal and cardiac muscle. This multi-functional dipeptide has anti-oxidant properties, can buffer intracellular pH, chelate metals, and sequester aldehydes such as acrolein. Due to these chemical properties, carnosine may be protective against inhaled pollutants which can contain metals and aldehydes and can stimulate the generation of electrophiles in exposed tissues. Thus, assessment of carnosine levels, or levels of its acrolein conjugates (carnosine-propanal and carnosine-propanol) may inform on level of exposure and risk assessment., Methods: We used established mass spectroscopy methods to measure levels of urinary carnosine ( n  = 605) and its conjugates with acrolein ( n  = 561) in a subset of participants in the Louisville Healthy Heart Study (mean age = 51 ± 10; 52% male). We then determined associations between these measures and air pollution exposure and smoking behavior using statistical modeling approaches., Results: We found that higher levels of non-conjugated carnosine, carnosine-propanal, and carnosine-propanol were significantly associated with males ( p  < 0.02) and those of Caucasian ethnicity ( p  < 0.02). Levels of carnosine-propanol were significantly higher in never-smokers ( p  = 0.001) but lower in current smokers ( p  = 0.037). This conjugate also demonstrated a negative association with mean-daily particulate air pollution (PM 2.5 ) levels ( p  = 0.01)., Conclusions: These findings suggest that urinary levels of carnosine-propanol may inform as to risk from inhaled pollutants.

Introduction: We illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine., Methods: In smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05., Results: Creatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns., Conclusions: Relationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses., Implications: Lack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed., (© The Author(s) 2020. 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.)

Objectives: Determine uptake of furan, a potential human carcinogen, in waterpipe tobacco (WPT) smokers in home settings., Methods: We analysed data from a US convenience sample of 50 exclusive WPT smokers, mean age 25.3 years, and 25 non-smokers, mean age 25.5 years. For WPT smokers, data were collected at a home visit by research assistants during which participants smoked one WPT head of one brand for a mean of 33.1 min in their homes. Research assistants provided and prepared a WP for participants by weighing and loading 10 g of WPT in the WP head. At the completion of the smoking session, research assistants measured the remaining WPT. Cotinine and six furan metabolites were quantified in first morning urine samples provided on 2 consecutive days for non-smokers, and on the morning of a WPT smoking session and on the following morning for smokers., Results: WPT smokers consumed a mean of 2.99 g WPT. In WPT smokers, urinary cotinine levels increased significantly 26.1 times the following morning; however, urinary metabolites of furan did not increase significantly. Compared to non-smokers, 2 furan metabolites, N-acetyl-S-[1-(5-acetylamino-5-carboxylpentyl)-1H-pyrrol-3-yl]-L-cysteine and N-acetyl-S-[1-(5-amino-5-carboxypentyl)-1H-pyrrol-3-yl]-L-cysteine sulfoxide, were significantly higher in WPT smokers in pre and in post WPT smoking levels., Conclusions: To enable a more rigorous assessment of furan exposure from WPT smoking, future research should determine furan concentrations in WPT smoke, quantify furan metabolites from users of various WPT brands; and extend the investigation to social settings where WPT smoking is habitually practiced., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background : measure the efficacy of exhaled carbon monoxide (CO) measurement plus brief advisory sessions to reduce smoking exposure and smoking behaviour in kidney transplant recipients. Methods : Randomized, controlled, open-label clinical trial at a Spanish hospital.Smoking kidney transplant recipients giving their consent to participate were randomized to control (brief advice, n=63) or intervention group (brief advisory session plus measuring exhaled CO, n=59). Measurements: Sociodemographic characteristics, cardiovascular risk factors, treatment, rejection episodes, infections, self-reported smoking, drug use, level of dependence and motivation to stop smoking (Fagerström's and Richmond's test) and stage of change (Prochaska and DiClemente's Stages). Efficacy was assessed at 3, 6, 9 and 12 months as: cotinine test, CO levels in exhaled air, nicotine dependence, motivational stages of change, motivation to stop smoking, pattern of tobacco use and smoking cessation rates. Logistic regression models were computed. Results : At 12 months of follow-up, differences were found in exhaled CO between the intervention and control group(6.1±6.8vs.10.2±9.7ppm;p=0.028). Carboxyhemoglobin levels were lower in the intervention group as well as the positive cotinine test (1.2±1.2%vs.2.0±2.4%;p=0.039),(53.4%vs.74.2%). At 12 months, intervention reduces the probability of a positive urine test by 28%. Conclusions : Co-oximetry is a clinically relevant intervention for reduction of tobacco exposure in kidney transplant recipients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

(1) Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on the perinatal outcome. Aim: to assess the changes occurring in dietary iodine intake, potassium iodide supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). (2) Methods: Between 2009-2011, an observational study included a cohort of women whose pregnancies were monitored in the public health system in the Central and North Metropolitan areas of Catalonia. Women received individual educational counseling, a dietary questionnaire was completed, and a urine sample was collected for iodine determination at each trimester visit. (3) Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150 μg/L) increased from the first to the second trimester and remained stable in the third (57.3%, 68.9%, 68%; p < 0.001). Analysis of the relationship between UIC≥150 μg/L and the women's dietary habits showed that the percentage with UIC ≥150 μg/L increased with greater consumption of milk in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. (4) Conclusion: During pregnancy, increased intake of milk, iodized salt, and iodine supplements were associated with an increase in the UIC.

Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related human disease. ROS can oxidize lipids, which subsequently undergo fragmentation to produce F2-isoprostanes (F2-IsoPs). Eight-isoprostane is one of the most extensively studied F2-IsoPs and the most commonly used biomarker for the assessment of oxidative stress in human studies. This urinary biomarker is quantified using either chemical or immunological techniques. A "physiological" range for 8-isoprostanes is needed to use this biomarker as a measure of excess oxidative stress originating from occupational exposures. However, ranges reported in the literature are inconsistent. We designed a standardized protocol of a systematic review and meta-analysis to assess baseline values for 8-isoprostane concentrations in urine of healthy adults and identify determinants of their inter- and intra-individual variability. We searched PubMed from journal inception and up to April 2019, and screened articles for studies containing F2-IsoPs concentrations in urine for healthy adult participants. We grouped studies in three biomarker groups: "8-isoprostane", "Isoprostanes" "15- F2t-Isoprostane". We computed geometric mean (GM) and geometric standard deviation (GSD) as the basis for the meta-analysis. Of the initial 1849 articles retrieved, 63 studies were included and 107 subgroups within these study populations were identified. We stratified the subgroups analyzed with the chemical methods by body mass index (BMI) reported. We provide pooled GM values for urinary 8-isoprostane concentrations in healthy adults, separately for chemical and immunological analysis in this review. The interquartile range (IQR) in subgroups with a mean BMI below 25 measured using chemical methods was 0.18 to 0.40 μg/g creatinine. We show that there is a significant positive association between BMI and urinary 8-isoprostane concentrations. We recommend adjusting urinary 8-isoprostane concentrations in spot urine with creatinine, quantifying 8-isoprostane with chemical analytical methods, and reporting results as median and quartiles. This will help in comparing results across studies., Competing Interests: Declaration of Competing Interest The authors report no declaration of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nicotine is the major pharmacologically active substance in tobacco. Several studies have examined genotypes related to nicotine metabolism, but few studies have been performed in the Mexican population. The objective was to identify associations between gene variants in metabolizing enzymes and the urinary levels of nicotine metabolites among Mexican smokers. The levels of nicotine and its metabolites were determined in the urine of 88 young smokers from Mexico, and 167 variants in 24 genes associated with nicotine metabolism were genotyped by next-generation sequencing (NGS). Trans-3'-hydroxy-cotinine (3HC) and 4-hydroxy-4-(3-pyridyl)-butanoic acid were the most abundant metabolites (35 and 17%, respectively). CYP2A6*12 was associated with 3HC (p = 0.014). The rs145014075 was associated with creatinine-adjusted levels of nicotine (p = 0.035), while the rs12471326 (UGT1A9) was associated to cotinine-N-glucuronide (p = 0.030). CYP2A6 and UGT1A9 variants are associated to nicotine metabolism. 4HPBA metabolite was an abundant urinary metabolite in young Mexican smokers.

Few studies have assessed the accuracy of self-reported questionnaires to determine smoking habits relative to urinary biomarkers. This study investigated urinary cotinine cut-off concentrations distinguishing active, passive and non-smokers among pregnant women who participated in the Japan Environment and Children's Study, a nationwide birth cohort study. Pregnant participants with measured urinary cotinine concentrations (UCCs) and who completed self-reported questionnaires on smoking status were included ( n = 89,895). The cut-off values (COVs) for active and passive smokers were calculated by fitting mixed normal distribution functions to UCCs. The sensitivity and specificity of the questionnaires were subsequently evaluated. The median (interquartile range) UCC was 0.24 (0.083-0.96) µg/g-creatinine, with the detection rate of 89%. The COV for distinguishing active smokers from passive and non-smokers was 36.8 µg/g-creatinine. When this COV was considered to represent the true condition, the questionnaire had a sensitivity of 0.523, a specificity of 0.998, a positive predictive value (PPV) of 0.967 and a negative predictive value (NPV) of 0.957. The COV for distinguishing passive smokers from non-smokers was 0.31 µg/g-creatinine, with the questionnaire having a sensitivity of 0.222, a specificity of 0.977, a PPV of 0.868 and an NPV of 0.644. As many as 78% of passive smokers might be misclassified as non-smokers.

Pteridine derivatives are intermediate metabolites of folic acid and its cofactors. Oxidized-form pteridines, but not reduced-form pteridines, are fluorescent substances. The purpose of this study was to clarify whether oxidized-form pteridine level in urine, estimated by spectrofluorometry, reflects oxidative stress in vivo. The subjects were healthy middle-aged men (n = 258). Urinary pteridine level was estimated by spectrofluorometry with an excitation wavelength of 360 nm and an emission wavelength of 450 nm. Relationships of urinary pteridines with oxidative stress markers (urinary DNA/RNA oxidation products and 15-isoprostane F 2t ) and with smoking were analyzed. Concentrations of pteridines, DNA/RNA oxidation products and 15-isoprostane F 2t were used after logarithmic transformation in linear analyses. Pteridine levels were significantly correlated with levels of DNA/RNA oxidation products (Pearson's correlation coefficient: 0.626, p < 0.01) and 15-isoprostane F 2t (Pearson's correlation coefficient: 0.695, p < 0.01). These correlations were not confounded by age, body mass index, history of smoking and estimated glomerular filtration rate in multivariate analysis. The mean urinary pteridine level was significantly higher in heavy smokers (16 cigarettes or more per day) than in nonsmokers and light smokers (less than 16 cigarettes per day) and was higher in light smokers than in nonsmokers. Thus, urinary fluorometric pteridine levels were shown to be associated with known biomarkers of oxidative stress as well as smoking, which causes oxidative stress in vivo. We propose spectrofluorometrical estimation of urinary pteridines as a simple and useful method for evaluation of oxidative stress in vivo.

Background: While tobacco smoke contains thousands of chemicals, some of which are carcinogenic to humans, the content of electronic cigarette smoke is less known. This work aimed to assess and compare the exposure associated with different smoking habits by profiling urinary mercapturic acids as biomarkers of toxic compounds., Methods: In this pilot study, sixty-seven healthy adults with different smoking habits were investigated: 38 non-smokers (NS), 7 electronic cigarette users (ECU), and 22 traditional tobacco smokers (TTS). Seventeen urinary mercapturic acids, metabolites of 1,3-butadiene (DHBMA, MHBMA), 4-chloronitrobenze (NANPC), acrolein (3-HPMA), acrylamide (AAMA, GAMA), acrylonitrile (CEMA), benzene (SPMA), crotonaldehyde (CMEMA, HMPMA), ethylating agents (EMA), methylating agents (MMA), ethylene oxide (HEMA), N,N-dimethylformamide (AMCC), propylene oxide (2-HPMA), styrene (PHEMA), and toluene (SBMA), were quantified, along with urinary nicotine and cotinine., Results: Median urinary cotinine was 0.4, 1530 and 1772 μg/L in NS, ECU and TTS, respectively. Most mercapturic acids were 2-165 fold-higher in TTS compared to NS, with CEMA, MHBMA, 3-HPMA and SPMA showing the most relevant increases. Furthermore, some mercapturic acids were higher in ECU than NS; CEMA and 3-HPMA, in particular, showed significant increases and were 1.8 and 4.9 fold-higher, respectively., Conclusions: This study confirms that tobacco smoking is a major source of carcinogenic chemicals such as benzene and 1,3-butadiene; electronic cigarette use is a minor source, mostly associated with exposure to chemicals with less carcinogenic potential such as acrylonitrile and acrolein., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed., Competing Interests: The authors declare no conflict of interest

Polycyclic aromatic hydrocarbons (PAH) are well-established environmental carcinogens likely to be causative agents for some human cancers. Bay-region diol epoxides are ultimate carcinogenic metabolites of multiple PAH. Dihydrodiols are the important intermediate products of this pathway and can be further oxidized to form diol epoxides. We quantified two dihydrodiol metabolites of phenanthrene (Phe), the simplest PAH with a bay-region, in the 6 h urine of smokers (N = 25) and non-smokers (N = 25) using a newly developed and validated analytical method. After hydrolysis by ß-glucuronidase and sulfatase, and solid phase extraction, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-tandem mass spectrometry (GC-NICI-MS/MS). Levels (nmol/6h urine) of Phe-1,2-dihydrodiol (Phe-1,2-D) and Phe-3,4-dihydrodiol (Phe-3,4-D) were 2.04 ± 1.52 and 0.51 ± 0.35 , respectively, in smokers, significantly higher than those in non-smokers (1.35 ± 1.11 of Phe-1,2-D, p < 0.05; 0.27 ± 0.25 of Phe-3,4-D, p < 0.005). Cigarette smoking also influenced the regioselective metabolism of Phe, presenting as a significant difference in the urinary distribution pattern of Phe-1,2-D and Phe-3,4-D between smokers and non-smokers: the ratio Phe-3,4-D: Phe-1,2-D increased from 0.20 in non-smokers to 0.28 in smokers (p < 0.01), which can be explained by the induction of the phenanthrene metabolizing enzymes CYP1A2 and CYP1B1 by cigarette smoke. The method described here is the first example of facile quantitation of an intact human dihydrodiol metabolite of any PAH with three or more aromatic rings and will be applicable in clinical and molecular epidemiology studies of PAH metabolism and cancer susceptibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: A majority of studies on tobacco smoke exposure and sleep quality have relied on self-reported smoking, resulting in potential exposure misclassification and biases related to self-report. The objective of this study was to investigate associations between urinary cotinine, a biological marker of tobacco smoke exposure, and sleep quality measures, including sleep duration, sleep continuity or efficiency, sleep satisfaction and alertness during normal waking hours., Methods: Using data on a national sample of 10 806 adults (aged 18-79 years) from the Canadian Health Measures Survey (2007-2013), we performed binary logistic regression analyses to estimate associations between urinary cotinine concentrations and sleep quality measures, while controlling for potential confounders. Additionally, we performed ordinal logistic regression to assess the association between urinary cotinine concentrations and increased number of sleep problems., Results: Overall, 28.7% of adult Canadian survey respondents had urinary cotinine concentrations above the limit of detection (LOD), nd the prevalence of each sleep problem ranged from 5.5% to 35.6%. Elevated urinary cotinine concentrations (quartile 4 vs.

1,3-Butadiene (BD) is a known human carcinogen found in cigarette smoke, automobile exhaust, and urban air. Workers occupationally exposed to BD in the workplace have an increased incidence of leukemia and lymphoma. BD undergoes cytochrome P450-mediated metabolic activation to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxybutane (DEB) and 1,2-dihydroxy-3,4-epoxybutane (EBD), which form covalent adducts with DNA. We have previously reported a quantitative nanoLC/ESI+-HRMS3 method for urinary N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts as a mechanism-based biomarker of BD exposure. In the present study, the method was updated to include high throughput 96-well solid phase extraction (SPE) and employed to establish urinary EB-GII biomarker stability and association with smoking. Urinary EB-GII levels were measured bimonthly for 1 year in 19 smokers to determine whether single adduct measurement provides reliable levels of EB-GII in an individual smoker. In addition, association of EB-GII with smoking was studied in 17 individuals participating in a smoking cessation program. EB-GII levels decreased 34% upon smoking cessation, indicating that it is associated with smoking status, but may also originate from sources other than exposure to cigarette smoke., (© The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary PG. Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, miRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL8, IL13, and TNFα), although the absolute magnitude of changes was small. There were no significant changes in mRNA or miRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers., (©2019 American Association for Cancer Research.)

Data (N = 10336) from National Health and Nutrition Examination Survey for 2003-2016 for US adults aged ≥ 20 years were analyzed to evaluate the concentrations of blood and urine cadmium across the various stages of glomerular function. Estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73 m 2 was defined to be glomerular function stage 1 (GF-1), eGFR between 60 and 90 mL/min/1.73 m 2 defined as GF-2, eGFR between 45 and 60 mL/min/1.73 m 2 as GF-3A, and eGFR between 15 and 45 mL/min/1.73 m 2 as GF-3B/4. Regression models stratified by GF-stages were fitted to estimate associations between the observed levels of blood and urine cadmium across stages of GF. Based on the results of stratified modes, there were consistent increases in adjusted geometric means (AGM SM ) for both blood and urine cadmium from GF-1 to GF-3A although increases were not uniform from one GF stage to another. For the total population, AGM SM for blood and urine cadmium were GF-1 (0.47, 0.24), GF-2 (0.60, 0.37), GF-3A (0.72, 0.45), and GF-3B/4 (0.73, 0.45) μg/L. respectively. Although females had higher AGM SM s than males for both blood and urine cadmium, the difference in blood cadmium narrowed as kidney function deteriorated. Smokers had the steepest increases in AGM SM s for blood and urine cadmium across the stages of glomerular function and smoker-nonsmoker differences for blood cadmium narrowed as kidney function deteriorated but smoker-nonsmoker differences for urine cadmium widened as kidney function deteriorated. The important physiologic messages are that both blood and urine cadmium cease to increase from GF-3A to GF-3B/4, suggesting a new steady state based on renal failure. And, the narrowed difference in blood cadmium in smokers vs. nonsmokers suggests why this happens. Incremental exposures to cadmium are offset by excretion as renal failure progresses., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background & Aims: Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure., Methods: We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017., Results: Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20)., Conclusions: In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Because 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy., Methods: In a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence., Results: At baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition., Conclusions: Although menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers., Implications: Results of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Menthol, which creates mint flavor and scent, is often added to tobacco in both menthol and nonmenthol cigarettes. A potent tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is extensively metabolized to its equally carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as ( R )- or ( S )-NNAL enantiomers. NNAL is detoxified by UDP-glucuronosyltransferase (UGT) enzymes, with glucuronidation occurring on either NNAL's pyridine ring nitrogen (NNAL- N -Gluc) or the chiral alcohol [( R )- or ( S )-NNAL- O -Gluc]. To characterize a potential effect by menthol on NNAL glucuronidation, in vitro menthol glucuronidation assays and menthol inhibition of NNAL-Gluc formation assays were performed. Additionally, NNAL and menthol glucuronides (MG) were measured in the urine of smokers ( n = 100) from the Southern Community Cohort Study. UGTs 1A9, 1A10, 2A1, 2A2, 2A3, 2B4, 2B7, and 2B17 all exhibited glucuronidating activity against both l- and d-menthol. In human liver microsomes, both l- and d-menthol inhibited the formation of each NNAL-Gluc, with a stereospecific difference observed between the formation of ( R )-NNAL- O -Gluc and ( S )-NNAL- O -Gluc in the presence of d-menthol but not l-menthol. With the exception of three nonmenthol cigarette smokers, urinary MG was detected in all menthol and nonmenthol smokers, with l-MG comprising >98% of total urinary MG. Levels of urinary NNAL- N -Gluc were significantly ( P < 0.05) lower among subjects with high levels of total urinary MG; no significant changes in free NNAL were observed. These data suggest that the presence of menthol could lead to increases in alternative, activating metabolic pathways of NNAL in tobacco target tissues, increasing the opportunity for NNAL to damage DNA and lead to the development of tobacco-related cancers. SIGNIFICANCE STATEMENT: High levels of the major menthol metabolite, menthol-glucuronide, was observed in the urine of smokers of either menthol or nonmenthol cigarettes. The fact that a significant inverse correlation was observed between the levels of urinary menthol-glucuronide and NNAL-N-glucuronide, a major detoxification metabolite of the tobacco carcinogen, NNK, suggests that menthol may inhibit clearance of this important tobacco carcinogen., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Introduction: Pregnancy-induced increases in nicotine metabolism may contribute to difficulties in quitting smoking during pregnancy. However, the time course of changes in nicotine metabolism during early and late pregnancy is unclear. This study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among nonpregnant smokers., Methods: Urinary NMR (trans-3'-hydroxycotinine [3HC]/cotinine [COT]) was assessed using total (free + glucuronide) and free compounds among women (N = 47) from a randomized controlled trial for smoking cessation who self-reported smoking and provided a urine sample during early pregnancy (M ± SD = 12.5 ± 4.5 weeks' gestation), late pregnancy (28.9 ± 2.0 weeks' gestation), and 6 months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using liquid chromatography-tandem mass spectrometry and NMR were calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT., Results: NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy as measured by Total 3HC/Free COT (0.76, 0.89, 0.60; all p's < .05) and Free 3HC/Free COT (0.68, 0.80, 0.51; all p's < .05). Total 3HC/Total COT did not vary over time (p = .81)., Conclusions: Total 3HC/Free COT and Free 3HC/Free COT increased in the first trimester and continued to increase throughout pregnancy, suggesting a considerable increase in nicotine metabolism over gestation. Future analyses are needed to interpret the changes in NMR in the context of nicotine pharmacokinetics, as well as its impact on changes in smoking behavior and cessation outcomes., Implications: We observed that the NMR was significantly higher as early as 12 weeks' gestation and increased further as a function of gestational age. Among nonpregnant smokers, elevated NMR is associated with smoking phenotypes such as smoking more cigarettes per day and poorer response to nicotine patch; therefore, pregnancy-induced increases in the NMR may contribute to smoking during the first trimester of pregnancy and reducing or quitting smoking may become more challenging as the rate of nicotine metabolism accelerates over the course of pregnancy., (© The Author(s) 2018. 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.)

Human beings are inevitably exposed to volatile organic compounds (VOCs) of anthropogenic emissions as they are ubiquitous atmospheric pollutants. Smoking is an important exposure route of VOCs for the general population. Health effects induced by VOC exposure raise more concerns as they are identified with carcinogenicity, genotoxicity, neurotoxicity, and reproductive toxicity. trans-3'-Hydroxycotinine (OH-Cot) is a urinary biomarker of smoking, and 8-hydroxy-2'-deoxyguanosine (8-OHDG) is a urinary biomarker of DNA oxidative damage. To develop a method for quantifying VOC exposure levels of the general population and assessing the health risks induced by VOCs from second-hand smoking, an effective, rapid, and high-throughput method for the simultaneous determination of 31 metabolites of VOCs, 8-OHDG, and OH-Cot using solid-phase extraction coupled with UPLC-MS/MS was developed and validated. Method precision and accuracy, extraction recoveries, matrix effects, and storage stabilities of most analytes met the criterion (80-120%). Extraction recoveries increased from 85.1 to 100% after adjustment by isotoped internal standards (ISs). Furthermore, 13 C- and 15 N-labeled ISs were more effective to reduce the influence of matrix effects on recoveries and precisions than the deuterated analogs (73.0-116% vs. 53.6-140%). This developed method was successfully applied to determine urine samples collected from children. Results showed that N-acetyl-S-(3,4-dihydrobutyl)-L-cysteine, 2,2'-thiodiacetic acid (TGA), and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA) were well correlated with 8-OHDG with coefficients higher than 0.82, indicating those VOCs might easily lead to DNA damage. In conclusion, our co-monitoring of metabolites of VOCs with 8-OHDG and OH-Cot in one method provides a robust analytical method, which not only suggests the potential adverse health effects induced by VOCs but also discriminates and evaluates the contribution of passive smoking in human VOC exposure. Graphical abstract.

Objective: The study objective was to identify biobehavioral variables associated with greater intake of nicotine and a tobacco carcinogen among Black light smokers who smoke 1 to 10 cigarettes per day (CPD)., Methods: We analyzed baseline data collected from 426 Black light smokers enrolled in Kick It at Swope III (KIS III), a smoking cessation trial for Black smokers. We examined differences in concentrations of tobacco biomarkers, including urinary total nicotine equivalents (TNE) and total 4-(methylnitrosamino)-1-(3)pyridyl-1-butanonol (NNAL; a human carcinogen), across gender, age, plasma nicotine metabolite ratio (NMR), CPD, and measures of tobacco dependence, including time to first cigarette (TFC), using ANOVA., Results: Tobacco biomarker levels were significantly higher among those who smoked more CPD (6-10 vs 1-5 CPD) and those with greater reported physical dependence on tobacco. Concurrently, those who smoked 1-5 CPD smoked each cigarette more intensely than those who smoked 6-10 CPD. While we found no gender differences overall, among those who smoked 1-5 CPD, women had higher NNAL levels compared to men. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, was not significantly related to TNE or NNAL levels., Conclusion: Among Black Light smokers, higher cigarette consumption and greater physical dependence-but not rate of nicotine metabolism, menthol use, or socioeconomic status-were associated with greater toxicant exposure and thus a likely increased risk of tobacco-related diseases. The lack of data on light smokers, and specifically on Blacks, make this observation important given the disproportionate burden of lung cancer in this population., (Copyright © 2019 National Medical Association. Published by Elsevier Inc. All rights reserved.)

We report on the development of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously measuring eight biomarkers of volatile organic compound (VOC) exposure, with potential application to e-cigarette aerosol biomonitoring. Phenylmercapturic acid (PMA) and trans, trans-muconic acid (tt-MA) are metabolites of benzene; 2-aminothiazoline-4-carboxylic acid (ATCA) is a metabolite of cyanide; N-2-furoylglycine (N2FG) is a metabolite of furfural and furfuryl alcohol; 5-hydroxymethylfuroic acid (HMFA), 5-hydroxymethyl-2-furoylglycine (HMFG), and 2,5-furandicarboxylic acid (FDCA) are metabolites of 5-hydroxymethylfurfural; and 5-hydroxy-N-methylpyrrolidone (5HMP) is a metabolite of N-methyl-2-pyrrolidone. A pentafluorophenyl-modified silica column was used for chromatographic separation. The overall run time for the method is about 6 min per sample injection. The method has low to sub-nanograms per milliliter sensitivity, linearity over 3 orders of magnitude, and precision and accuracy within 15%. The method was used to measure human urine samples. Results showed that people with known benzene exposure (daily cigarette smokers) had higher levels of tt-MA and PMA compared with non-smokers. The method is advantageous for high-throughput analysis of selected VOC metabolites in large-scale, population-based studies such as the National Health and Nutrition Examination Survey (NHANES). Quantifying these urinary biomarkers is important to public health efforts to understand human exposure to VOCs from various sources, including tobacco products and electronic nicotine delivery systems., (Published by Elsevier B.V.)

4-(Methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), two tobacco specific nitrosamine carcinogens, can form adducts with DNA and proteins via pyridyloxobutylation upon phase I enzyme-mediated bioactivation. Such DNA modifications have been proposed as the root cause to initiate carcinogenesis. Upon hydrolysis, both DNA and protein modifications would release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). The released HPB, being tobacco carcinogen specific, has the potential to serve as a surrogate biomarker for both tobacco exposure and carcinogen bioactivation. Because of its easy access, blood is a great source of such investigations with the potential in epidemiological application. HPB quantification from haemoglobin (Hb), however, has been demonstrated with limited success. To further explore this potentially paradigm-shift opportunity, we reported, for the first time, the detection and quantification of HPB from albumin (Alb) adducts formed by the tobacco-specific nitrosamines in mice and in human smokers. The time-course quantitative analysis of HPB from mouse Alb upon NNK exposure suggests that such an Alb adduct is stable. The amounts of HPB from Alb adducts in smoker plasma averaged 1.82 ± 0.19 pg/mg Alb (0.42 to 3.11 pg/mg Alb), which was 36 times the value in nonsmokers (0.05 ± 0.01 pg/mg Alb). Importantly, HPB level from Alb correlated positively with the level of human tobacco exposure estimated by urinary total nicotine equivalent (TNE) (R 2  = 0.6170). For comparison, HPB level from Alb was 16.5 times that of Hb (0.12 ± 0.02 pg/mg Hb) in the plasma and red blood cell (RBC) samples of the same smokers. In addition, there was no significant correlation between HPB levels from Hb and TNE (R 2  = 0.0719). These data overall suggest that HPB from Alb adducts can serve as a surrogate biomarker to monitor the level of tobacco exposure and carcinogenic nitrosamine bioactivation., (Copyright © 2019 Elsevier B.V. All rights reserved.)