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The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered 'carcinogenic to humans' by the International Agency for Research on Cancer (IARC) and are believed to be important in the carcinogenic effects of both smokeless tobacco and combusted tobacco products. This short review focuses on the results of recent studies on the formation of NNN and NNK in tobacco, and their carcinogenicity and toxicity in laboratory animals. New mechanistic insights are presented regarding the role of dissimilatory nitrate reductases in certain microorganisms involved in the conversion of nitrate to nitrite that leads to the formation of NNN and NNK during curing and processing of tobacco. Carcinogenicity studies of the enantiomers of the major NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the enantiomers of NNN are reviewed. Recent toxicity studies of inhaled NNK and co-administration studies of NNK with formaldehyde, acetaldehyde, acrolein and CO2, all of which occur in high concentrations in cigarette smoke, are discussed.
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Carcinógenos , Nicotiana , Nitrosaminas , Nitrosaminas/toxicidade , Humanos , Animais , Carcinógenos/toxicidade , Nicotiana/químicaRESUMO
Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.
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Neoplasias , Nitrosaminas , Tabaco sem Fumaça , Humanos , Carcinógenos/toxicidade , Mutagênicos , Neoplasias/induzido quimicamente , Nitratos , Nitritos , Nitrosaminas/toxicidade , Nitrosaminas/química , Nitrosaminas/metabolismo , Tabaco sem Fumaça/toxicidadeRESUMO
BACKGROUND: Smokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products. METHODS: We quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay. RESULTS: Our findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.
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Microbiota , Nitrosaminas , Tabaco sem Fumaça , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Concentração de Íons de Hidrogênio , Microbiota/genética , Nicotina/análise , Nitrosaminas/análise , RNA Ribossômico 16S/genética , Espectrometria de Massas em Tandem , Nicotiana/química , Tabaco sem Fumaça/efeitos adversos , Tabaco sem Fumaça/análiseRESUMO
INTRODUCTION: Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers. METHODS: Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured. RESULTS: Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol. CONCLUSION: Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.
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Tabaco sem Fumaça/análise , Alcaloides/análise , Europa (Continente) , Aromatizantes/análise , Humanos , Concentração de Íons de Hidrogênio , Nicotina/análise , Nitrosaminas/análise , Estados UnidosRESUMO
OBJECTIVE: We examined differences between nicotine concentrations and pH in cigarette and cigar tobacco filler. METHODS: Nicotine and pH levels for 50 cigarette and 75 cigar brands were measured. Non-mentholated and mentholated cigarette products were included in the analysis along with several cigar types as identified by the manufacturer: large cigars, pipe tobacco cigars, cigarillos, mini cigarillos, and little cigars. RESULTS: There were significant differences found between pH and nicotine for cigarette and cigar tobacco products. Mean nicotine concentrations in cigarettes (19.2 mg/g) and large cigars (15.4 mg/g) were higher than the other cigars types, especially the pipe tobacco cigars (8.79 mg/g). The mean pH for cigarettes was pH 5.46. Large cigars had the highest mean pH value (pH 6.10) and pipe tobacco cigars had the lowest (pH 5.05). CONCLUSIONS: Although cigarettes are the most common combustible tobacco product used worldwide, cigar use remains popular. Our research provides a means to investigate the possibility of distinguishing the 2 tobacco product types and offers information on nicotine and pH across a wide range of cigarette and cigar varieties that may be beneficial to help establish tobacco policies and regulations across product types.
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The bacterial communities present in smokeless tobacco (ST) products have not previously reported. In this study, we used Next Generation Sequencing to study the bacteria present in U.S.-made dry snuff, moist snuff and Sudanese toombak. Sample diversity and taxonomic abundances were investigated in these products. A total of 33 bacterial families from four phyla, Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes, were identified. U.S.-produced dry snuff products contained a diverse distribution of all four phyla. Moist snuff products were dominated by Firmicutes. Toombak samples contained mainly Actinobacteria and Firmicutes (Aerococcaceae, Enterococcaceae, and Staphylococcaceae). The program PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to impute the prevalence of genes encoding selected bacterial toxins, antibiotic resistance genes and other pro-inflammatory molecules. PICRUSt also predicted the presence of specific nitrate reductase genes, whose products can contribute to the formation of carcinogenic nitrosamines. Characterization of microbial community abundances and their associated genomes gives us an indication of the presence or absence of pathways of interest and can be used as a foundation for further investigation into the unique microbiological and chemical environments of smokeless tobacco products.
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Bactérias/classificação , DNA Bacteriano/análise , DNA Ribossômico/análise , RNA Ribossômico 16S/análise , Tabaco sem Fumaça/microbiologia , Bactérias/genética , Toxinas Bacterianas/genética , Farmacorresistência Bacteriana , Sequenciamento de Nucleotídeos em Larga Escala , Metagenoma , Filogenia , Software , Tabaco sem Fumaça/classificação , Estados UnidosRESUMO
Verve, an oral nicotine delivery product (ONDP), was introduced by Nu Mark (Altria Client Group, Richmond VA) for smokers to use in places where smoking is prohibited. This study assessed the effect of this ONDP on plasma nicotine levels, heart rate, product satisfaction, and ability to suppress smoking urge and cigarette cravings. Thirteen daily cigarette smokers [8 men and 5 women; average age 33.4years] attended two laboratory sessions, one occurred after overnight tobacco abstinence. Plasma samples were collected before and after ONDP use and measured for nicotine. In non-abstinent smokers, mean plasma nicotine levels increased from 18.3 to 21.0ng/mL. In abstinent smokers, average nicotine levels increased from 3.1 to 4.5ng/mL. After overnight tobacco abstinence, ONDP use significantly (p<0.01) increased heart rate from 69beats per minute (bpm) to 75bpm; while urge to smoke decreased significantly (p<0.01) from a score of 8.6 to 4.9. Participants indicated moderate product satisfaction that was not changed by tobacco abstinence. Analysis of unused ONDP revealed total nicotine levels of 1.68±0.09mg/disc. Spent ONDP discs were also analyzed to determine % nicotine liberated during chewing; results were 80% in the non-abstinent and 82% in the abstinent conditions (ns). Our study results indicate that ONDP use can increase plasma nicotine levels and heart rate and reduce cigarette cravings in abstinent smokers.
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Pressão Sanguínea/efeitos dos fármacos , Fissura/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Nicotina/administração & dosagem , Nicotina/farmacologia , Administração Oral , Adulto , Comportamento do Consumidor , Liberação Controlada de Fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/sangue , Nicotina/farmacocinética , Adulto JovemRESUMO
Rapé, a diverse group of smokeless tobacco products indigenous to South America, is generally used as a nasal snuff and contains substantial amount of plant material with or without tobacco. Previously uncharacterized, rapé contains addictive and harmful chemicals that may have public health implications for users. Here we report % moisture, pH, and the levels of total nicotine, un-ionized nicotine, flavor-related compounds, tobacco-specific N-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for manufactured and hand-made rapé. Most rapé products were mildly acidic (pH 5.17-6.23) with total nicotine ranging from 6.32 to 47.6 milligram per gram of sample (mg/g). Calculated un-ionized nicotine ranged from 0.03 to 18.5 mg/g with the highest values associated with hand-made rapés (pH 9.75-10.2), which contain alkaline ashes. In tobacco-containing rapés, minor alkaloid levels and Fourier transform infrared spectra were used to confirm the presence of Nicotiana rustica, a high nicotine tobacco species. There was a wide concentration range of TSNAs and PAHs among the rapés analyzed. Several TSNAs and PAHs identified in the products are known or probable carcinogens according to the International Agency for Research on Cancer. Milligram quantities of some non-tobacco constituents, such as camphor, coumarin, and eugenol, warrant additional evaluation.
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Nicotina/análise , Nitrosaminas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Tabaco sem Fumaça/análise , Alcaloides/análise , Brasil , Cinnamomum zeylanicum/química , Eugenol/análise , Cromatografia Gasosa-Espectrometria de Massas , Concentração de Íons de Hidrogênio , Mentol/análise , Nicotina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem , Nicotiana/químicaRESUMO
INTRODUCTION: Electronic cigarette (e-cigarette) use is increasing dramatically in developed countries, but little is known about these rapidly evolving products. This study analyzed and evaluated the chemical composition including nicotine, tobacco alkaloids, pH, and flavors in 36 e-liquids brands from 4 manufacturers. METHODS: We determined the concentrations of nicotine, alkaloids, and select flavors and measured pH in solutions used in e-cigarettes. E-cigarette products were chosen based upon favorable consumer approval ratings from online review websites. Quantitative analyses were performed using strict quality assurance/quality control validated methods previously established by our lab for the measurement of nicotine, alkaloids, pH, and flavors. RESULTS: Three-quarters of the products contained lower measured nicotine levels than the stated label values (6%-42% by concentration). The pH for e-liquids ranged from 5.1-9.1. Minor tobacco alkaloids were found in all samples containing nicotine, and their relative concentrations varied widely among manufacturers. A number of common flavor compounds were analyzed in all e-liquids. CONCLUSIONS: Free nicotine levels calculated from the measurement of pH correlated with total nicotine content. The direct correlation between the total nicotine concentration and pH suggests that the alkalinity of nicotine drives the pH of e-cigarette solutions. A higher percentage of nicotine exists in the more absorbable free form as total nicotine concentration increases. A number of products contained tobacco alkaloids at concentrations that exceed U.S. pharmacopeia limits for impurities in nicotine used in pharmaceutical and food products.
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Alcaloides/análise , Sistemas Eletrônicos de Liberação de Nicotina , Aromatizantes/análise , Nicotina/análise , Humanos , Concentração de Íons de Hidrogênio , Soluções , Nicotiana/química , Estados UnidosRESUMO
Most research on unburned tobacco has focused on the harmful chemicals associated with the tobacco itself. However, certain flavor additives in tobacco products can pose additional health risks. Flavors like camphor, coumarin, pulegone, eugenol, methyl salicylate, menthol and diphenyl ether have exhibited biological activity and/or toxicity in both lab animals and humans. This publication presents a new GC/MS method for the quantitation of ten flavor compounds (eucalyptol, camphor, menthol, pulegone, ethyl salicylate, methyl salicylate, cinnamaldehyde, eugenol, diphenyl ether and coumarin) in a variety of tobacco products, including smokeless products and cigar filler. Excellent linearity (>0.997), accuracy (93.9% - 106.6%) and precision (C.V., 0.5% - 3.0%) were achieved for all flavor analytes measured. A summary of the concentrations of these flavors in selected international smokeless tobacco (SLT) products including zarda, quiwam, gutkha, and khaini varieties from Southeast Asia and snuff, clove cigarette filler and flavored cigar filler from the United States is reported. High concentrations of eugenol (2110 µg/g), coumarin (439 µg/g), camphor (1060 µg/g) and diphenyl ether (4840 µg/g) were found in selected products. Accurate identification and quantitation of potentially hazardous flavor compounds is important because they can exist in relatively high levels in some tobacco products, including international SLT products. We outline a versatile method which can be used to quantitate flavor compounds in multiple types of tobacco products.
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In the U.S. menthol remains the sole permitted characterizing cigarette flavor additive in part because efforts to link menthol cigarette use to increased tobacco-related disease risk have been inconclusive. To perform definitive studies, cigarettes that differ only in menthol content are required, yet these are not commercially available. We prepared research cigarettes differing only in menthol content by deposition of L-menthol vapor directly onto commercial nonmenthol cigarettes, and developed a method to measure a cigarette's menthol and nicotine content. With our custom-mentholation technique we achieved the desired moderately high menthol content (as compared to commercial brands) of 6.7 ± 1.0 mg/g (n = 25) without perturbing the cigarettes' nicotine content (17.7 ± 0.7 mg/g [n = 25]). We also characterized other pertinent attributes of our custom-mentholated cigarettes, including percent transmission of menthol and nicotine to mainstream smoke and the rate of loss of menthol over time during storage at room temperature. We are currently using this simple mentholation technique to investigate the differences in human exposure to selected chemicals in cigarette smoke due only to the presence of the added menthol. Our cigarettes will also aid in the elucidation of the effects of menthol on the toxicity of tobacco smoke.
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In the United States, moist snuff has been studied more widely than other distinct categories of oral tobacco. In this study, we measured pH, moisture, nicotine (total and unprotonated), and tobacco-specific N-nitrosamines (TSNAs) for other established (twist, loose leaf, plug, and dry snuff without pouch) and emerging oral tobacco products (dry snuff pouch, US-made snus, and dissolvable tobacco). Among the seven product categories, product pH ranged from 4.7 to 7.9, and total nicotine concentration spanned from 3.9 to 40.1 mg/g. The most readily absorbable form of nicotine (unprotonated nicotine) varied more than 350-fold, ranging from 0.01 to 3.7 mg/g. While the highest total nicotine concentrations were observed in twist products, snus and dissolvable tobacco had the highest unprotonated nicotine levels. Among all products, total TSNA concentrations ranged from 313 to 76,500 ng/g with dry snuff having the highest total TSNA concentrations. This study demonstrates the diversity among oral tobacco products and highlights the potential of these products to deliver a wide range of nicotine and carcinogenic TSNAs. Characterizing the chemical content of these products may be helpful in further understanding the risk of marketing these products to oral tobacco users and smokers as an alternative and discrete form of tobacco.
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Nicotina/análise , Nitrosaminas/análise , Tabaco sem Fumaça/análise , Concentração de Íons de Hidrogênio , Estados UnidosRESUMO
This publication reports the first known use of gas chromatography-tandem mass spectrometry for the quantitation of five minor tobacco alkaloids (nornicotine, myosmine, anabasine, anatabine, and isonicoteine) in various tobacco samples. A summary of the concentrations of these minor alkaloid levels in the filler from 50 popular cigarette brands were found to be 659-986 µg/g nornicotine, 8.64-17.3 µg/g myosmine, 127-185 µg/g anabasine, 927-1390 µg/g anatabine, and 23.4-45.5 µg/g isonicoteine. Levels of minor alkaloids found in reference cigarettes (1R5F, 2R4F, 3R4F, CM4, and CM6) as well as burley, flue-cured, oriental, reconstituted, and Nicotiana rustica and Nicotiana glauca tobacco types are also reported. Quantitation of the minor tobacco alkaloids is important because the alkaloids have been shown to be precursors of carcinogenic tobacco specific N'-nitrosamines.
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Alcaloides/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nicotiana/química , Nicotiana/genética , Espectrometria de Massas em Tandem/métodos , Produtos do Tabaco/análiseRESUMO
INTRODUCTION: Iq'mik, a form of smokeless tobacco (ST), is traditionally used by Cup'ik and Yup'ik Eskimo people of western Alaska. Iq'mik is sometimes incorrectly considered to be a healthier alternative to smoking because its ingredients are perceived as "natural." Our chemical characterization of iq'mik shows that iq'mik is not a safe alternative to smoking or other ST use. METHODS: We measured nicotine and pH levels of tobacco and ash used to prepare iq'mik. We also characterized levels of toxins which are known to be present in ST including tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) using chromatographic separations coupled with isotope dilution mass spectrometry. RESULTS: Nicotine content in the iq'mik tobacco was very high, ranging from 35 to 43 mg/g, with a mean of 39 mg/g. The pH of the iq'mik tobacco-ash mixture was 11, an extremely high level compared with most ST products. High levels of PAHs were seen in the fire-cured tobacco samples with a benzo[a]pyrene level of 87 ng/g. Average TSNA levels in the tobacco were 34, 2,700, and 340 ng/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. CONCLUSIONS: Iq'mik contains high levels of the more easily absorbed unionized nicotine as well as known carcinogenic TSNAs and PAHs. The perception that iq'mik is less hazardous than other tobacco products due to the use of "natural" ingredients is not warranted. This chemical characterization of iq'mik gives a better understanding of the risk of possible adverse health effects of its use.
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Nicotina/análise , Nitrosaminas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Tabaco sem Fumaça/análise , Alaska , Benzo(a)pireno/análise , Humanos , Concentração de Íons de Hidrogênio , InuíteRESUMO
OBJECTIVE: Oral tobacco products contain nicotine and carcinogenic tobacco-specific N-nitrosamines (TSNAs) that can be absorbed through the oral mucosa. The aim of this study was to determine typical pH ranges and concentrations of total nicotine, unionised nicotine (the most readily absorbed form) and five TSNAs in selected oral tobacco products distributed globally. METHODS: A total of 53 oral tobacco products from 5 World Health Organisation (WHO) regions were analysed for total nicotine and TSNAs, including 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), using gas chromatography or liquid chromatography with mass spectrometric detection. Unionised nicotine concentrations were calculated using product pH and total nicotine concentrations. Fourier transform infrared spectroscopy was used to help categorize or characterise some products. RESULTS: Total nicotine content varied from 0.16 to 34.1 mg/g product, whereas, the calculated unionised nicotine ranged from 0.05 to 31.0 mg/g product; a 620-fold range of variation. Products ranged from pH 5.2 to 10.1, which translates to 0.2% to 99.1% of nicotine being in the unionised form. Some products have very high pH and correspondingly high unionised nicotine (eg, gul powder, chimó, toombak) and/or high TSNA (eg, toombak, zarda, khaini) concentrations. The concentrations of TSNAs spanned five orders of magnitude with concentrations of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) ranging from 4.5 to 516,000 ng/g product. CONCLUSIONS: These data have important implications for risk assessment because they show that very different exposure risks may be posed through the use of these chemically diverse oral tobacco products. Because of the wide chemical variation, oral tobacco products should not be categorised together when considering the public health implications of their use.
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Carcinógenos/análise , Nicotina/análise , Nitrosaminas/análise , Tabaco sem Fumaça/química , Saúde Global , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: This study examines child poisonings resulting from ingestion of tobacco products throughout the nation and assesses the potential toxicity of novel smokeless tobacco products, which are of concern with their discreet form, candy-like appearance, and added flavorings that may be attractive to young children. METHODS: Data representing all single-substance, accidental poisonings resulting from ingestion of tobacco products by children <6 years of age, reported to poison control centers, were examined. Age association with ingestion of smokeless tobacco versus other tobacco products was tested through logistic regression. Total nicotine content, pH, and un-ionized nicotine level were determined, and the latter was compared with values for moist snuff and cigarettes. RESULTS: A total of 13,705 tobacco product ingestion cases were reported, >70% of which involved infants <1 year of age. Smokeless tobacco products were the second most common tobacco products ingested by children, after cigarettes, and represented an increasing proportion of tobacco ingestions with each year of age from 0 to 5 years (odds ratio: 1.94 [95% confidence interval: 1.86-2.03]). A novel, dissolvable, smokeless tobacco product with discreet form, candy-like appearance, and added flavorings was found to contain an average of 0.83 mg of nicotine per pellet, with an average pH of 7.9, which resulted in an average of 42% of the nicotine in the un-ionized form. CONCLUSION: In light of the novelty and potential harm of dissolvable nicotine products, public health authorities are advised to study these products to determine the appropriate regulatory approach.
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Acidentes/estatística & dados numéricos , Nicotiana/intoxicação , Intoxicação/epidemiologia , Intoxicação/etiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Política de Saúde , Humanos , Masculino , Nicotina/intoxicação , Centros de Controle de Intoxicações/estatística & dados numéricos , Intoxicação/prevenção & controle , Embalagem de Produtos , Tabaco sem Fumaça/intoxicação , Estados UnidosRESUMO
In recent years, there has been a rapid proliferation of smokeless products with a wide range of nicotine content and flavoring formulations that may appeal to new users and existing cigarette smokers. The CDC nicotine method, which employs gas chromatography-flame ionization detection (GC-FID), provides a robust means for measuring nicotine in smokeless tobacco. However, several compounds, identified in a few flavored smokeless products, interfere with nicotine quantification using GC-FID. In response, the standard nicotine method (26.7 min run time) was modified to use faster GC ramping (3.7 min run time) and detection with mass spectrometry (GC-MS) in selected ion-monitoring mode to reduce signal interferences that can bias nicotine values. Seven conventional smokeless samples (n = 12) and blank tobacco samples spiked at three nicotine concentration levels (n = 5) were analyzed using the GC-FID and GC-MS methods and found to be in excellent agreement. However, only the GC-MS method provided confirmation of chromatographic peak purity in certain highly flavored products. The GC-MS method is not intended to replace the GC-FID method but to provide a method versatile enough to analyze a wide range of nicotine values in domestic and international samples of varying complexity. Accurate nicotine quantification is important for determining total nicotine content in tobacco and in subsequent calculations of un-protonated nicotine content.
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Cromatografia Gasosa-Espectrometria de Massas/métodos , Nicotina/análise , Tabaco sem Fumaça/químicaRESUMO
Exposure to hydroxyl-substituted arenes, commonly referred to as phenols or phenolic compounds, can have serious health consequences. Select phenols present in tobacco smoke are cardiovascular toxins, act as tumor co-promoters and show genotoxic activity. To examine the mainstream smoke levels of these compounds, we developed and applied a method for quantitative analysis of seven phenols (phenol, o-cresol, m-cresol, p-cresol, catechol, resorcinol, and hydroquinone) in mainstream smoke. Total mainstream smoke particulate matter was collected on a Cambridge filter pad and spiked with an isotopically labeled internal standard solution. This pad underwent an automated phenol derivatization procedure to increase analyte volatility and enhance detection. Following the derivatization step, phenols from the particulate matter were sampled using solid-phase microextraction with subsequent gas chromatography/mass spectrometric detection. Sensitivity, selectivity, accuracy, and reproducibility were more than adequate for routine detection of phenols in mainstream smoke. Detection limits ranged from 0.04-0.57 microg, with a quantification range of 0.1-710 microg. Higher sensitivity and sample throughput were achieved compared with previously described methods. Mainstream smoke from 28 brands of domestic commercial cigarettes was evaluated to assess typical levels, and reference cigarettes containing single tobacco blends were examined to ascertain the phenolic profile from different types of tobaccos. As expected under machine smoking conditions using the Federal Trade Commission parameters, full-flavored cigarettes deliver more phenols than the light varieties, followed by the ultra light varieties. Differences were seen in relative levels of phenolic compounds in the mainstream smoke from unfiltered cigarettes made with a single type of tobacco.
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Aromatizantes/química , Nicotiana/química , Fenóis/análise , Fumaça/análise , Catecóis/análise , Cresóis/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Hidroquinonas/análise , Resorcinóis/análise , Indústria do Tabaco , Estados Unidos , United States Federal Trade CommissionRESUMO
Indonesian clove cigarettes (kreteks), typically have the appearance of a conventional domestic cigarette. The unique aspects of kreteks are that in addition to tobacco they contain dried clove buds (15-40%, by wt.), and are flavored with a proprietary "sauce". Whereas the clove buds contribute to generating high levels of eugenol in the smoke, the "sauce" may also contribute other potentially harmful constituents in addition to those associated with tobacco use. We measured levels of eugenol, trans-anethole (anethole), and coumarin in smoke from 33 brands of clove-flavored cigarettes (filtered and unfiltered) from five kretek manufacturers. In order to provide information for evaluating the delivery of these compounds under standard smoking conditions, a quantification method was developed for their measurement in mainstream cigarette smoke. The method allowed collection of mainstream cigarette smoke particulate matter on a Cambridge filter pad, extraction with methanol, sampling by automated headspace solid-phase microextraction, and subsequent analysis using gas chromatography/mass spectrometry. The presence of these compounds was confirmed in the smoke of kreteks using mass spectral library matching, high-resolution mass spectrometry (+/-0.0002 amu), and agreement with a relative retention time index, and native standards. We found that when kreteks were smoked according to standardized machine smoke parameters as specified by the International Standards Organization, all 33 clove brands contained levels of eugenol ranging from 2,490 to 37,900 microg/cigarette (microg/cig). Anethole was detected in smoke from 13 brands at levels of 22.8-1,030 microg/cig, and coumarin was detected in 19 brands at levels ranging from 9.2 to 215 microg/cig. These detected levels are significantly higher than the levels found in commercial cigarette brands available in the United States.