The effects of dosed tobacco in evidentiary breath testing using non-drinking subjects.

A total of seventeen subjects were administered breath tests with alcohol dosed tobacco to see if there was an interference with the evidentiary breath testing. Fourteen subjects provided one set of two breath samples without the dosed tobacco followed by a set of two breath samples with the dosed tobacco. The other three subjects provided one breath sample without the dosed tobacco and then one breath sample with the dosed tobacco within the same testing sequence. Eight subjects had breath test readings of 0.00g/210L with the dosed tobacco. Mouth alcohol was detected with the dosed tobacco in six of the subjects, and a reading of 0.01g/210L, 0.04g/210L, and 0.05g/210L were found in five of the subjects. If the officer follows the directive of checking the mouth for a foreign substance and following a 15-20min observation/deprivation period, a false positive result will likely be avoided. If the officer does not find tobacco when checking the mouth for a foreign substance, and dosed tobacco is present during the breath test, most likely there would not be a measurable amount of alcohol to report or there would be a mouth alcohol reading from the sample.

The in vitro toxicology of Swedish snus.

Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes.

E-cigarettes: promise or peril?

Electronic cigarettes (e-cigarettes) use a heating element to vaporize nicotine and other ingredients, simulating the visual, sensory, and behavioral aspects of smoking without the combustion of tobacco. An ever-growing number of companies around the world manufacture a wide variety of e-cigarette brands, despite scant information on the safety of the ingredients for human inhalation. This article provides an overview of the history, production, and marketing of e-cigarettes, the contents of e-cigarettes and vapor, how they are used, public health concerns, and implications for nursing practice, research, and policy development.

p53 Codon 72 polymorphism in oral exfoliated cells in a Sudanese population.

Earlier studies have investigated the tumor suppressor gene p53 as a co-factor in the development of oral squamous cell carcinoma (OSCC). Our previous studies have indicated that chronic use of Sudanese snuff (toombak) and the presence of human papilloma virus (HPV) may be involved in the high prevalence of OSCC in Sudan. This study investigated the prevalence of p53 codon 72 polymorphism in brush biopsies obtained from a Sudanese population. A total of 174 individuals were included in the study; chronic toombak users (n=152) and non-users (n=22). DNA was extracted from all the samples and genotyped for the codon 72 polymorphism by polymerase chain reaction/restriction fragment length polymorphism. The Arg/Pro genotype was found in 53% of the 174 study participants, compared to 21% found with Arg/Arg and 26% found with Pro/Pro. Stratifying by toombak use, 28 (18%), 45 (29%) and 79 (52%) of the 152 samples from toombak users had Arg/Arg, Pro/Pro and Arg/Pro respectively, compared to 9 (41%), 0 (0%) and 13 (59%) found in the 22 samples from non users. The differences between the samples from toombak users and non users in Arg/Arg and Pro/Pro codon 72 polymorphism and HPV infection were statistically significant (p<0.05). Our study indicated that a high prevalence of the genotype Arg/Pro at the p53 codon 72 may contribute to susceptibility to OSCC, especially in combination with the use of carcinogenic tobacco-specific nitrosamine (TSNA)-rich toombak. Our observations warrant an in-depth study for understanding the role of p53 polymorphism in human oral cancers.

Toxicological evaluation of smokeless tobacco: 90-day rodent feeding studies.

This manuscript presents data from 90-day toxicology studies designed to characterize the subchronic effects of a smokeless tobacco blend and an aqueous extract of that blend when administered to rodents in NTP-2000 feed. Positive control (nicotine tartrate) and treatment groups were matched for a range of nicotine levels. The doses evaluated were 0.3, 3, and 6 mg nicotine/kg body weight/day in Wistar Hannover rats and 6, 60, and 120 mg nicotine/kg/day in CD-1 mice. Variables evaluated included plasma nicotine and cotinine, body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights), and histopathology. Plasma nicotine and cotinine levels were dose-responsive. Key effects such as body weight reductions and organ weight changes occurred in rats and mice predominantly at the highest doses of test articles and positive control in the absence of treatment-related gross or histopathological changes. Organ weight changes were attributed mainly to the lower body weights of treated vs. control groups. The blend- and extract-induced effects generally paralleled each other and the nicotine-induced effects. Based on these studies, the doses evaluated spanned the no observable adverse effect level, the lowest observable adverse effect level and the maximum tolerated dose.

[Smokeless tobacco and cardiovascular risk]. / Snus et risque cardiovasculaire.

The use of "snus" (smokeless tobacco) can be detrimental to health. Snus delivers rapidly high doses of nicotine which can lead to addiction. The use of snus increases the risk of myocardial infarction and stroke. Nicotine substitution therapy as well as bupropion and varenicline reduce withdrawal symptoms and tobacco craving during snus cessation. However, they have been shown not to assist in long-term abstinence. Information concerning potential cardiovascular hazards of snus must be incorporated into health educational programs in order to discourage its use. Snus is not a recommended product to help stop smoking.

[Smokeless tobacco]. / Le snus.

The use of snus (smokeless tobacco) can be detrimental to health. Containing carcinogenic nitrosamines (Swedish snus do not contain nitrosamine). Snus delivers rapidly high doses of nicotine which can lead to dependence. It do not induce bronchial carcinoma differently smoked tobacco. Lesions usually develop in the area of the mouth where the snus is placed. Non-malignant oral lesions include leukoedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. The most frequently occurring premalignant lesion is leukoplakia. Studies reveal conflicting evidence about the risk of oral and gastroesophageal cancer with regard to snus users. However, the use of snus has proved to be a risk factor in developing pancreatic cancer and increases the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, snus is associated with an increased risk of pre-eclampsia and premature delivery. Nicotine substitution therapy and bupropion and varenicline reduce withdrawal symptoms and tobacco craving during snus cessation. However, they have not been shown to assist in long-term abstinence. Information concerning potential hazards of using snus products must be incorporated into health educational programmes in order to discourage its use. Snus is not a recommended product to help in stopping to smoke.

Assessment of potential toxicity of a smokeless tobacco product (naswar) available on the Pakistani market.

BACKGROUND: 'Naswar' is a smokeless tobacco product (STP) widely used in Pakistan. It has been correlated with oral and oesophageal cancer in recent clinical studies. The toxic effects associated with STPs have been associated with trace level contaminants present in these products. The toxin levels of Pakistani naswar are reported for the first time in this study. METHODS: A total of 30 Pakistani brands of naswar were tested for a variety of toxic constituents and carcinogens such as cadmium, arsenic, lead and other carcinogenic metals, nitrite and nitrate, and nicotine and pH. RESULTS: The average values of all the toxins studied were well above their allowable limits, making the product a health risk for consumers. Calculated lifetime cancer risk from cadmium and lead was 1 lac (100,000) to 10 lac (1,000,000) times higher than the minimum 10E-4 (0.00001) to 10E-6 (0.000001), which is the 'target range' for potentially hazardous substances, according to the US Environmental Protection Agency. Similarly, the level of arsenic was in the range of 0.15 to 14.04 µg/g, the average being 1.25 µg/g. The estimated average bioavailable concentration of arsenic is 0.125-0.25 µg/g, which is higher than the allowable standard of 0.01 µg/g. Similarly, the average minimum daily intake of chromium and nickel was 126.97 µg and 122.01 µg, as compared to allowable 30-35 µg and 35 µg, respectively; a 4-5 times higher exposure. However, beryllium was not detected in any of the brands studied. The pH was highly basic, averaging 8.56, which favours the formation of tobacco specific amines thus making the product potentially toxic. This study validates clinical studies correlating incidence of cancer with naswar use in Pakistan. CONCLUSIONS: This study shows that the production, packaging, sale and consumption of naswar should be regulated so as to protect the public from the health hazards associated with its consumption.

Monitoring tobacco-specific N-nitrosamines and nicotine in novel Marlboro and Camel smokeless tobacco products: findings from Round 1 of the New Product Watch.

INTRODUCTION: Information on chemical composition of the new oral "spitless" smokeless tobacco products is scarce, and it is not clear whether there is some variability as a function of purchase place or time due to either unintended or intended manufacturing variations or other conditions. METHODS: We analyzed tobacco-specific N-nitrosamines (TSNA) and nicotine in Marlboro Snus, Camel Snus, and dissolvable Camel products Orbs, Sticks, and Strips that were purchased in various regions of the country during the summer of 2010. RESULTS: A total of 117 samples were received from different states representing six regions of the country. Levels of unprotonated nicotine in Marlboro Snus and Camel Snus varied significantly by regions, with the differences between the highest and the lowest average regional levels being relatively small in Marlboro Snus (∼1.3-fold) and large in Camel Snus (∼3-fold). Some regional variations in TSNA levels were also observed. Overall, Camel Snus had significantly higher TSNA levels than Marlboro Snus, and Camel Strips had the lowest TSNA levels among all novel products analyzed here. The amount of unprotonated nicotine in the dissolvable Camel products was comparable to the levels found in Marlboro Snus. CONCLUSIONS: Our study demonstrates some regional variations in the levels of nicotine and TSNA in Marlboro and Camel novel smokeless tobacco products. Continued monitoring of this category of products is needed as the existing products are being test marketed and modified, and new products are being introduced. This information is particularly important given its relevance to Food and Drug Administration regulation of tobacco products.

Dietary intake of cadmium from Bangladeshi foods.

UNLABELLED: Human exposure to cadmium (Cd) is associated with various diseases and high levels of Cd have been detected in Bangladeshi population warranting further research to identify the source of this exposure. In this study, Cd levels in 327 and 94 samples of Bangladeshi food and non-food samples, respectively, were determined using inductively coupled plasma mass spectrometry. This is the largest number of Bangladeshi food and nonfood samples investigated for their Cd content. High Cd levels were detected in leafy vegetables (mean 31 [SD 29]µg/kg). Of these vegetables, lal shak (Amaranthus tricolor) contained the highest Cd level (303 µg/kg [wet weight]; mean 100.5 [SD 95]µg/kg). Bangladeshi rice also showed significant concentration of Cd (mean 37.2 [SD 30]µg/kg). Of particular concern is the very high level of Cd detected in some puffed rice, which we attribute to the illegal practice of using urea for whitening the puffed rice. Tobacco leaves, which are commonly consumed during betel quid chewing by Bangladeshis, contain significant levels of Cd (mean 95 [SD 87]µg/kg). The total daily intake (TDI) of Cd from foods for Bangladeshis was estimated to be 34.55 µg/d. This is rather high when compared to the TDI of Cd for other populations. Our analysis reveals that this is mainly due to the very high intake of rice and vegetables, and lower consumption of animal products (which are low in Cd), by the Bangladeshis. We also determined the provisional maximum tolerable daily intake and target hazard quotients values for Cd. Clearly a more balanced diet is necessary to reduce the Cd intake in the Bangladeshi population, especially by reducing the very high intake of rice and certain leafy vegetables. Food manufacturing and agricultural practices needs to be altered to reduce the entry of Cd into the food chain. PRACTICAL APPLICATION: Exposure to high levels of Cd can be harmful to human health and this study provides a comprehensive analysis of Cd levels in a variety of food items from Bangladesh. The findings are of particular importance to consumers of Bangladeshi foods in both Bangladesh and in other countries. Data obtained will be valuable resources for food safety and regulatory bodies as our study suggests entry of Cd in foods through use of illegal chemicals in food manufacturing processes.

Sources of and technical approaches for the abatement of tobacco specific nitrosamine formation in moist smokeless tobacco products.

The presence of TSNA has been suggested as a potentially important cancer risk factor for moist smokeless tobacco (MST) products. We describe studies of the impact of tobacco agronomic and production practices which influence TSNA formation. TSNA were measured at points in the MST production chain from the farm to the finished product at the end of shelf life. Analyses were conducted to define points at which TSNA may occur, the factors related to the magnitude of occurrence, and actions which may be taken to mitigate such occurrence. Weather conditions during the curing season can have a dramatic impact on TSNA levels in tobacco, with wet seasons markedly increasing TSNA levels in cured tobacco. TSNA levels in MST do not increase beyond levels in cured tobacco when production practices limit the presence of nitrate reducing bacteria. Therefore, TSNA in such products are a function of the agronomic practices and conditions under which tobacco is produced at the farm level. Regional and annual variation in TSNA levels results from the stochastic nature of agronomic factors related to TSNA formation during tobacco growing and curing.

Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats.

RATIONALE: Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans. OBJECTIVE: To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models. METHODS: Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity. RESULTS: Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone. CONCLUSIONS: The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction.

[Smokeless tobacco]. / Tabac non fumé

Use of smokeless tobacco (ST) (chewing tobacco and snuff) can lead to a number of consequences detrimental to health. ST rapidly delivers high doses of nicotine, which can lead to dependence and is also a source of carcinogenic nitrosamines. Changes usually develop in the mouth area where the ST is most often placed. Non-malignant oral lesions include leuko-oedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. Oral premalignant lesions are leukoplakia, erythroplakia, submucosal fibrosis and lichen planus. Betel chewing, with or without tobacco, may increase the incidence of oral cancer. There is conflicting evidence with regard to snuff users about the risk of oral and gastro-oesophageal cancer. ST use is a risk factor for pancreatic cancer and may increase the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, ST is associated with an increase in pre-eclampsia, preterm delivery and stillbirth. Nicotine replacement therapy and bupropion reduce withdrawal symptoms and tobacco craving during ST cessation. However, they have not been shown to help long-term abstinence. Information concerning the potential hazards of ST products should be incorporated into educational programmes to discourage its use and to help users to quit. Smokeless tobacco is not recommended to help smoking cessation.

Toxic elements in tobacco and in cigarette smoke: inflammation and sensitization.

Biochemically and pathologically, there is strong evidence for both atopic and nonatopic airway sensitization, hyperresponsiveness, and inflammation as a consequence of exposure to tobacco mainstream or sidestream smoke particulate. There is growing evidence for the relation between exposure to mainstream and sidestream smoke and diseases resulting from reactive oxidant challenge and inflammation directly as a consequence of the combined activity of neutrophils, macrophages, dendritic cells, eosinophils, basophils, as a humoral immunological consequence of sensitization, and that the metal components of the particulate play a role in adjuvant effects. As an end consequence, carcinogenicity is a known outcome of chronic inflammation. Smokeless tobacco has been evaluated by the IARC as a group 1 carcinogen. Of the many harmful constituents in smokeless tobacco, oral tissue metallothionein gradients suggest that metals contribute to the toxicity from smokeless tobacco use and possibly sensitization. This work reviews and examines work on probable contributions of toxic metals from tobacco and smoke to pathology observed as a consequence of smoking and the use of smokeless tobacco.

The molecular basis for induction of human cancers by tobacco specific nitrosamines.

Cellular DNA damage that is misrepaired or not repaired, constitutes a necessary, although not sufficient prerequisite for induction of cancer. For carcinogenic oral snuffs with extremely high concentrations of tobacco specific nitrosamines (TSNA) the DNA adduct levels predicted from animal experiments exceed those found in "unexposed" individuals. On the other hand, and supported by extensive Swedish epidemiological data, no significant increase of TSNA-induced DNA damages can be anticipated in humans from the use of low-nitrosamine oral snuffs. The extrapolated adduct concentrations are orders of magnitude lower than those found in the corresponding human tissues, a discrepancy that is difficult to account for by species differences. Furthermore, in exposed subjects the observed increment in the background levels of pyridyloxobutyl(POB)-hemoglobin adducts - a relevant indicator for TSNA activation - lie in a range predicted by rodent data. When based on the same type of tissues this provides justification for extrapolating rates of TSNA induced adduct formation from animals to humans. A TSNA exposure that does not affect the background level of pro-mutagenic DNA lesions should be considered as "virtually safe". The high background concentrations of methylated and POB-DNA adducts in "unexposed" humans must be ascribed to other sources than tobacco.

The stereoisomers of menthol in selected tobacco products. A brief report.

INTRODUCTION: Menthol has long been an important flavorant in tobacco products, and both its historical and present uses are topics of increasing debate. Menthol can exist in eight different stereoisomeric forms (as four enantiomeric pairs) that possess different sensory properties. As regards use in tobacco products, the open scientific literature and available industry documents focus on the D-menthol and l-menthol enantiomeric pair, and in particular on l-menthol, but are ambiguous about the actual importance of D-menthol in tobacco products. This study provides the first openly available measurements regarding the stereoisomeric forms of menthol as found in selected United States sub-brands of smokeless tobacco (SLT), cigarettes, and cigarette smoke. METHODS: Gas chromatography/mass spectrometry (GC/MS) was applied using a "chiral" GC column to separate and determine the forms of menthol present in headspace air above various samples of United States sub-brands of SLT, cigarette filler material, and cigarette smoke particulate matter. Additional GC × GC/Time-of-flight mass spectrometry measurements were also made. RESULTS: The dominant form of menthol by far in any of the samples was l-menthol. CONCLUSIONS: For the selected cigarettes and SLT products tested from the U.S. market, the only form of menthol found was l-menthol. Other forms may be present in products that were not tested. No evidence was found of thermal racemization upon smoking of l-menthol to a d+l mixture.

Betel quid chewing elevates human exposure to arsenic, cadmium and lead.

Several studies have reported increased skin lesions in betel quid (a mixture of Piper betel leaves, areca nut, tobacco/flavoured tobacco, lime) chewers compared to non-chewers, exposed to arsenic (As) contaminated drinking water in Bangladesh and India. The current study has determined As, cadmium (Cd) and lead (Pb) levels of betel quids and its components using inductively coupled plasma mass spectrometry (ICP-MS). The highest concentrations of As were found in slaked lime (4.56 mg kg(-1)) followed by Piper betel leaves (0.406 mg kg(-1)) and flavoured tobacco (zarda) (0.285 mg kg(-1)), with a mean concentrations of As in betel quids of 0.035 mg kg(-1) (SD 0.02 mg kg(-1)). Mean concentrations of Cd and Pb in ordinary quids were 0.028 (SD 0.07 mg kg(-1)) and 0.423 (SD 1.4 mg kg(-1)), respectively. We estimated that a daily intake of 6 betel quids could contribute 1.2, 1.9 and 8.5% of the provisional maximum tolerable daily intake (PMDTI) for As, Cd and Pb, respectively. Since betel quid chewing is most prevalent among women, our finding raises concern that women chewers - especially pregnant chewers - may be harming their health and that of their unborn babies through increased exposure to a mixture of toxic elements (As, Cd and Pb).