14 results on '"Peyton Jacob"'
Search Results
2. Thirdhand smoke exposure promotes gastric tumor development in mouse and human
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Chengfei Jiang, Lingyan Chen, Chunping Ye, Suzaynn F. Schick, Peyton Jacob, III, Yingjia Zhuang, Jamie L. Inman, Changbin Chen, Lara A. Gundel, Hang Chang, Antoine M. Snijders, Xiaoping Zou, Jian-Hua Mao, Bo Hang, and Pin Wang
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Thirdhand smoke (THS) ,CC036 mice ,Gene expression signature ,Gastric cancer ,Tumor-free survival ,Epithelial-mesenchymal transition ,Environmental sciences ,GE1-350 - Abstract
The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.
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- 2024
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3. Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice
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Hui Yang, Xinzhi Wang, Pin Wang, Li He, Suzyann F. Schick, Peyton Jacob, III, Neal Benowitz, Lara A. Gundel, Chi Zhu, Yankai Xia, Jamie L. Inman, Hang Chang, Antoine M. Snijders, Jian-Hua Mao, and Bo Hang
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Thirdhand smoke (THS) ,Collaborative Cross (CC) mice ,Genetic susceptibility ,Tumorigenesis ,Pan-tumor incidence ,Tumor burden ,Environmental sciences ,GE1-350 - Abstract
Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.
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- 2023
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4. Minor Tobacco Alkaloids as Biomarkers to Distinguish Combusted Tobacco Use From Electronic Nicotine Delivery Systems Use. Two New Analytical Methods
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Peyton Jacob, Lawrence Chan, Polly Cheung, Kristina Bello, Lisa Yu, Gideon StHelen, and Neal L. Benowitz
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tobacco ,e-cigarettes ,biomarkers of exposure ,tobacco alkaloids ,liquid chromatography -tandem mass spectrometry ,Chemistry ,QD1-999 - Abstract
Biomarkers for the use of electronic nicotine delivery systems (ENDS) are desirable for studies of the health effects of electronic cigarettes and related devices. However, the aerosols inhaled from these devices do not contain substances that are unique to this class of products, i.e., substances that are not present in cigarette smoke or those that do not have common environmental or dietary sources. Consequently, identifying selective biomarkers for ENDS use remains a challenge. If co-use of conventional tobacco products can be definitively ruled out, then nicotine and its metabolites are suitable for assessing exposure. Self-reports from questionnaires are often used to obtain information on product use. But self-reports may not always be accurate, and are not amenable to obtaining quantitative information on exposure. An alternative approach is to use selective biomarkers for conventional tobacco products to definitively rule out their use. In this article, we describe two new LC-MS/MS methods for the minor tobacco alkaloids anabasine, anatabine, nicotelline, anatalline, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific nitrosamine metabolite, all biomarkers that are selective for the use of conventional tobacco products. Applications of these biomarkers in studies of ENDS use and dual use of ENDS and conventional tobacco products are also discussed.
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- 2022
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5. Determination of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) arising from tobacco smoke in airborne particulate matter
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Noel J. Aquilina, Christopher M. Havel, Roy M. Harrison, Kin-Fai Ho, Neal L. Benowitz, and Peyton Jacob III
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Tobacco Smoke ,Tobacco-Specific Nitrosamines ,NNK ,Particulate Matter ,Environmental sciences ,GE1-350 - Abstract
The most important tobacco-specific nitrosamine found in cigarette smoke and formed in ageing smoke after cigarettes are extinguished is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is formed from nitrosation of nicotine, under particular conditions both in indoor and outdoor environments. NNK has been classified as a potent lung carcinogen which is expected to be found primarily in the particle-phase and to be stable in particulate matter. In this study tests have been carried out to show that a bisulfate-treated filter is more efficient than an untreated filter to collect both nicotine and NNK, and that the latter is stable in outdoor particulate matter. To characterize NNK in the outdoor environment, airborne samples were collected from 11 cities in USA, UK, Hong Kong and Malta with characteristics varying from low to high population densities and from urban to suburban to rural, and with desert characteristics and distinct climates. It has been shown that airborne particle + gas phase nicotine and particle-phase NNK behave in a linearly correlated manner. A seasonal analysis was carried out on a subset of data available from five sites in California, where the load of NNK in PM10 is driven by long range transport of the air masses passing over densely populated cities. In the winter season, the load of NNK in PM is higher than in summer in a statistically significant manner. The contamination of PM with NNK shows variability, but is observed at all sites. This paper highlights the potential risk of chronic exposure to NNK in particulate matter by the inhalation pathway.
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- 2022
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6. Vaping THC-O Acetate: Potential for Another EVALI Epidemic
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Neal L. Benowitz, Christopher Havel, Peyton Jacob, Donal F. O’Shea, Dan Wu, and Jefferson Fowles
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Health, Toxicology and Mutagenesis ,Toxicology - Published
- 2022
7. PM2.5 Concentrations in the Smoking Lounge of a Cannabis Store
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Abel S. Huang, Morgan B. C. Murphy, Peyton Jacob, and Suzaynn F. Schick
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Ecology ,Health, Toxicology and Mutagenesis ,Environmental Chemistry ,Pollution ,Waste Management and Disposal ,Water Science and Technology - Published
- 2022
8. Nicotine Intake in Adult Pod E-cigarette Users: Impact of User and Device Characteristics
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Jeremy Giberson, Natalie Nardone, Newton Addo, Sameera Khan, Peyton Jacob, Neal Benowitz, and Gideon St.Helen
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Public Health, Environmental and Occupational Health - Abstract
Introduction This study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes. Aims and Methods In 2019–2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined. Results Of 100 participants (64% male, 71% in the 18–34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%–6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1–2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE. Conclusions Nicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes. Implications The study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.
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- 2023
9. Supplementary Methods, Tables 1 - 5, Figures 1 - 3 from Comparison of Nicotine and Carcinogen Exposure with Water Pipe and Cigarette Smoking
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Neal L. Benowitz, Lisa Yu, Margaret Peng, Christopher Havel, Delia Dempsey, Ahmad H. Abu Raddaha, and Peyton Jacob
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PDF file - 481K, Table S-1. SRM Transitions and Collision Energies Table S-2. Equations for Mercapturic Acid Calibration Curves Table S-3. Precision and Accuracy for Mercapturic Acids in Urine, Intra-day (N=6) Table S-4. Concentrations of Mercapturic Acids in Urine of Cigarette Smokers. Comparison with Literature Values. Table S-5. Concentrations of PAH Metabolites in Urine of Smokers. Comparison with Literature Values. Figure S-1A. Chromatograms of urine extracts containing mercapturic acids: Metabolites of acrylamide (AAMA), ethylene oxide (HEMA), and acrolein (3-HPMA). Figure S-1B. Chromatograms of urine extracts containing mercapturic acids: Metabolites of 1,3-butadiene (MHBMA), acrylonitrile (CNEMA), and benzene (PMA). Figure S-1C. Chromatograms of urine extracts containing mercapturic acids: Metabolite of propylene oxide (2-HPMA) and separation from the isomer 3-HPMA. Figure S-2. Butadiene metabolite (MHBMA) calibration curves. Figure S-3. Benzene metabolite (PMA) calibration curves.
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- 2023
10. Data from Comparison of Nicotine and Carcinogen Exposure with Water Pipe and Cigarette Smoking
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Neal L. Benowitz, Lisa Yu, Margaret Peng, Christopher Havel, Delia Dempsey, Ahmad H. Abu Raddaha, and Peyton Jacob
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Background: Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe. We investigated biomarkers of toxicant exposure with water pipe compared with cigarette smoking.Methods: We conducted a crossover study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products.Results: When smoking an average of 3 water pipe sessions compared with smoking 11 cigarettes per day (cpd), water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide (CO), and a different pattern of carcinogen exposure compared with cigarette smoking, with greater exposure to benzene, and high molecular weight polycyclic aromatic hydrocarbon (PAH), but less exposure to tobacco-specific nitrosamines, 1,3-butadiene, acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs.Conclusions: A different pattern of carcinogen exposure might result in a different cancer risk profile between cigarette and water pipe smoking. Of particular concern is the risk of leukemia related to high levels of benzene exposure with water pipe use.Impact: Smoking tobacco in water pipes has gained popularity in the United States and around the world. Many believe that water pipe smoking is not addictive and less harmful than cigarette smoking. We provide data on toxicant exposure that will help guide regulation and public education regarding water pipe health risk. Cancer Epidemiol Biomarkers Prev; 22(5); 765–72. ©2013 AACR.
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- 2023
11. Respiratory Exposure to Thirdhand Cigarette Smoke Increases Concentrations of Urinary Metabolites of Nicotine
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Kelly Pratt, Andrew Hilty, Peyton Jacob III, and Suzaynn F Schick
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Thirdhand Smoke ,Inhalation ,Smoke ,Air Pollution ,Tobacco ,Public Health, Environmental and Occupational Health - Abstract
Introduction The aims of this study were to characterize particle size in a thirdhand smoke (THS) aerosol and measure the effects of controlled inhalational exposure to THS on biomarkers of tobacco smoke exposure, inflammation, and oxidative stress in human subjects. Secondhand cigarette smoke changes physically and chemically after release into the environment. Some of the resulting chemicals persist indoors as thirdhand cigarette smoke. THS that is sorbed to surfaces can emit particles back into the air. Aims and Methods Smoke particle size was measured with a scanning mobility particle sizer and condensation particle counter. Using a crossover study design, 18 healthy nonsmokers received a 3-hour inhalational exposure to THS and to filtered, conditioned air. THS was generated with a smoking machine and aged overnight in a chamber. The chamber was flushed with clean air to create the THS aerosol. The tobacco smoke metabolites cotinine, 3-hydroxycotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were measured in urine. Vascular endothelial growth factor and interleukin-6 in plasma, and 8-isoprostane in urine, were measured using enzyme-linked immunosorbent assay kits. Results Mean smoke particle size increased with aging (171 to 265 nm). We found significant increases in urinary cotinine and 3-hydroxycotinine after 3 hours of exposure to THS and no significant increases in NNAL, interleukin-6, vascular endothelial growth factor or 8-isoprostane. Conclusions Acute inhalational exposure to 22-hour old tobacco smoke aerosol caused increases in the metabolites of nicotine but not the metabolites of the tobacco-specific nitrosamine NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone). This corroborates the utility of cotinine and NNAL for secondhand and THS exposure screening. Implications This study shows that a 3-hour inhalational exposure to the tobacco smoke aerosol that forms in a room that has been smoked in and left unventilated overnight causes increases in urinary metabolites of nicotine, but not of the tobacco-specific nitrosamine NNK. This suggests that cleaning personnel and others who live and work in rooms polluted with aged or thirdhand cigarette smoke regularly may have inhalational exposures and potential health effects related to their exposure to nicotine and other smoke toxicants.
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- 2023
12. Thirdhand Exposures to Tobacco-Specific Nitrosamines through Inhalation, Dust Ingestion, Dermal Uptake, and Epidermal Chemistry
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Xiaochen Tang, Neal Benowitz, Lara Gundel, Bo Hang, Christopher M. Havel, Eunha Hoh, Peyton Jacob III, Jian-Hua Mao, Manuela Martins-Green, Georg E. Matt, Penelope J. E. Quintana, Marion L. Russell, Altaf Sarker, Suzaynn F. Schick, Antoine M. Snijders, and Hugo Destaillats
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Nicotine ,HONO ,mice ,Nitrosamines ,Tobacco Smoke and Health ,Prevention ,Dust ,General Chemistry ,cancer risk ,C57BL ,Eating ,Mice ,Good Health and Well Being ,Tobacco ,Carcinogens ,2.2 Factors relating to the physical environment ,Environmental Chemistry ,Animals ,Humans ,Aetiology ,skin liquids ,C57BL/6 mice ,Environmental Sciences ,Cancer ,Skin - Abstract
Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day-1, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Here, we present additional evidence of genotoxicity of NNA, an assessment of TSNA dermal uptake, and predicted exposure risks through different pathways. Dermal uptake was investigated by evaluating the penetration of NNK and nicotine through mice skin. Comparable mouse urine metabolite profiles suggested that both compounds were absorbed and metabolized via similar mechanisms. We then investigated the effects of skin constituents on the reaction of adsorbed nicotine with nitrous acid (epidermal chemistry). Higher TSNA concentrations were formed on cellulose and cotton substrates that were precoated with human skin oils and sweat compared to clean substrates. These results were combined with reported air, dust, and surface concentrations to assess NNK intake. Five different exposure pathways exceeded the NSRL under realistic scenarios, including inhalation, dust ingestion, direct dermal contact, gas-to-skin deposition, and epidermal nitrosation of nicotine. These results illustrate potential long-term health risks for nonsmokers in homes contaminated with thirdhand tobacco smoke.
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- 2022
13. Corrigendum to 'Harmonization of acronyms for volatile organic compound metabolites using a standardized naming system' [Int. J. Hygiene Environ. Health 235 (2021) 113749]
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Denise S. Tevis, Sharon R. Flores, Brandon M. Kenwood, Deepak Bhandari, Peyton Jacob, Jia Liu, Pawel K. Lorkiewicz, Daniel J. Conklin, Stephen S. Hecht, Maciej L. Goniewicz, Benjamin C. Blount, and Víctor R. De Jesús
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Public Health, Environmental and Occupational Health - Published
- 2023
14. Secondhand smoke exposure in school children in Malta assessed through urinary biomarkers
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Stephen Montefort, Neal L. Benowitz, Noel J. Aquilina, Peyton Jacob, and Peter Fsadni
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NNAL ,Nitrosamines ,Urinary system ,Toxicology ,Biochemistry ,Article ,Third-hand smoke ,chemistry.chemical_compound ,Secondhand smoke ,Thirdhand smoke ,Tandem Mass Spectrometry ,School children ,Environmental health ,Tobacco ,Humans ,Potency ,Medicine ,trans-3 '-hydroxycotinine ,Child ,Cotinine ,Lung ,Cancer ,General Environmental Science ,Asthma ,Chromatography ,Liquid ,Tobacco Smoke and Health ,Malta ,business.industry ,Prevention ,trans-3′-hydroxycotinine ,Biological Sciences ,medicine.disease ,Urinary biomarkers ,Health Effects of Indoor Air Pollution ,chemistry ,Chemical Sciences ,Respiratory ,Carcinogens ,Female ,Tobacco Smoke Pollution ,Analysis of variance ,business ,Environmental Sciences ,Biomarkers ,Chromatography, Liquid - Abstract
School children may be exposed to secondhand smoke (SHS) either at home, in transit or in social gatherings permitting smoking in their presence. Questionnaires about SHS often underestimate prevalence and extent of exposure. A more accurate tool is the use of biomarkers such as cotinine (COT) and trans-3'-hydrocycotinine (3HC) as biomarkers of SHS exposure, alongside 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a reduction product in the body of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), both potent carcinogens. We measured urinary COT, 3HC and total NNAL using sensitive and specific high-performance LC-MS/MS methods. The limit of quantification (LOQ) for each assay were 0.05ng/mL, 0.1ng/mL and 0.25pg/mL respectively. The aim of this study was to evaluate the exposure to SHS of school children (9-11 years), from five public schools in the island of Malta, from questionnaire information about smoking at home and verify it by urinary biomarker data of COT, 3HC and NNAL. These biomarkers were measurable in 99.4%, 95.4% and 98.3% of the participating children respectively. From the children reporting smoking at home, 11% had a history of asthma and had COT, 3HC and NNAL geometric mean concentrations double compared to the non-asthmatic group. In has been confirmed that non-smokers exposed to SHS and THS have a higher NNAL/COT ratio than the group identified as smokers according to specific and defined COT threshold levels (despite the fact that a priori, the entire study group was composed of non-smokers). The implication of high measured levels of urinary NNAL in children should be of concern given its potency. A main effects multifactor ANOVA model was developed and the children's house and school locations and the smoking frequency were statistically significant to predict the levels of the three metabolites. For 3HC only, the status of the employment of the mother was also an important predictor.
- Published
- 2022
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