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The European Commission’s Tobacco Products Directive 2014/40/EU (TPD)1 came into force in 2014 and lays out rules governing the manufacture, presentation and sale of tobacco and related products, including cigarettes, roll-your-own tobacco, cigars, cigarillos, smokeless tobacco, electronic cigarettes and herbal products for smoking. It strengthens the rules regarding the reporting on ingredients contained in tobacco products and regulates permissible additives (or levels thereof) to improve the functioning of the internal market while guaranteeing a high level of public health. Articles 6 and 7 specifically focus on additivesi to tobacco products. More in detail article 7 lists prohibition of specific tobacco products, among which 1. tobacco products with a characterising flavour (Art 7 (1)) 2. tobacco products containing the following additives2 (Art 7 (6)): 1. vitamins or other additives that create the impression that a tobacco product has a health benefit or presents reduced health risks; 2. caffeine or taurine or other additives and stimulant compounds that are associated with energy and vitality; 3. additives with colouring properties for emissions; 4. for tobacco products for smoking, additives that facilitate inhalation or nicotine uptake; 5. additives that have carcinogenic, mutagenic and reproductive toxicity (CMR) properties in unburnt form. 3. tobacco products containing additives in quantities that increase the toxic or addictive effect, or the CMR properties of a tobacco product at the stage of consumption to a significant or measurable degree (Art 7 (9)). In line with Article 6 of the TPD, more stringent reporting obligations, in the form of comprehensive studies, will apply for additives placed on a priority list to be adopted by the European Commission, taking into account the intended use of the products concerned and examining in particular the emissions resulting from the combustion process involving the additive concerned. The studies shall also examine the interaction of that additive with other ingredients contained in the …

The European Commission has established a priority list of 15 additives contained in cigarettes and roll-your-own tobacco subject to enhanced reporting obligations. The European Union (EU) Tobacco Products Directive (TPD) prescribes that Member States shall require manufacturers and importers of tobacco products to carry out comprehensive studies on these additives to assess their contribution to any of the properties listed in Article 6 of the TPD: toxicity or addictiveness, characterizing flavor, inhalation facilitation, nicotine uptake, and carcinogenic, mutagenic, or toxic for reproduction. The Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER) has provided guidance on the type and criteria for comprehensive studies, and on the most suitable methodologies to test these 15 tobacco additives as well as additives on future updated lists. The SCHEER proposes a stepwise strategy as the most pragmatic and efficient way to assess the effects of tobacco additives. In addition to proposing specific steps and tests to be considered by industry, some general criteria were also identified such as no comparative testing (testing cigarettes with and without the additive) and no animal studies. As tobacco additives have no benefits for health, but rather may promote use of and addiction to an extremely toxic product, a risk–benefit analysis is not the appropriate paradigm for assessing the additive. When comprehensive studies confirm that additives have any of the properties listed in Article 6 of the TPD, regulatory actions should be considered. If uncertainties cannot be solved by comprehensive studies, the SCHEER recommends that the assessors consider the worst-case evaluation.ImplicationsIn this article, the SCHEER proposes a stepwise strategy to assess (1) the toxic and addictive effects, (2) the characterizing flavor, and (3) facilitating inhalation properties of tobacco additives. The proposed steps and tests provide guidance to (1) Member State on which comprehensive studies should be requested and (2) tobacco industry on which strategy of testing should be applied to address the request and to prepare reports to be sent to the relevant authorities for the evaluation of tobacco additives “safety” to comply with the Tobacco Products Directive 2014/40/EU.

The burning of candles and incense is common in religious ceremonies worldwide. Analysis of incense smoke has shown the presence of particulate matter, volatile organic compounds, aldehydes and polycyclic aromatic hydrocarbons that are hazardous to health. Long-term exposure to smoke formed during combustion can cause airway dysfunction, allergic reactions and dermatological effects and is a risk factor implicated in the development of other serious diseases. In this paper the effect of these studies are reviewed and simple precautions suggested to avoid toxic effects of incense smoke.

The European Commission held a major conference from 11 to 13 November 2002 in the Palais du Heysel in Brussels to mark the launch of the European Union's Sixth Framework Programme (FP-6) for research, which covers the period 2002-2006.

Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTMI and GSTTI null genotypes (GSTM1 * 2 and GSTT1 * 2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1 * 1 (active) was present in 83% and GSTT1 * 1 (active) was present in 78% of all control subjects, while prevalence of GSTM1 * 2 and GSTT1 * 2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1 * 2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 10-47] and GSTT1 * 2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5-22). Combined null genotypes of GSTMI and GSTTI prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTMI and GSTTI increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population.

Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N(4)-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon5mdC) lesion in DNA in vitro. Our newly developed (32)P-postlabeling method was subsequently used to detect epsilon5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.

Exocyclic etheno-DNA adducts are formed by the reaction of lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE) with DNA bases to yield 1,N (6)-etheno-2'-deoxyadenosine (edA), 3,-N (4)-etheno-2'-deoxycytidine (edC), and etheno-2'-deoxyguanosine. These adducts act as a driving force for many human malignancies and are elevated in the organs of cancer-prone patients suffering from chronic inflammation and infections. Here, we describe the ultrasensitive and specific techniques for the detection of edA and edC in tissue and white blood cell (WBC) DNA. This approach is based on -combined immunopurification by monoclonal antibodies and (32)P-postlabeling analysis. The detection limit is about five adducts per 10(10) parent nucleotides, requiring 5-10 μg of DNA. In addition, we describe techniques for immunohistochemical detection of edA and edC in tissue biopsies, and the approaches for the -analysis of edA and edC excreted in urine. The utility of these detection methods for human studies is based on: (1) high sensitivity and specificity, (2) low amounts of DNA required, (3) capability to detect "background" levels of etheno-DNA adducts in biopsies, WBC, and urine samples of healthy subjects, and (4) reliable monitoring of the disease-related increase of these substances in patients.The described methods are useful in diagnosis and monitoring of chronic degenerative diseases, including cancer, atherosclerosis, and neurodegenerative disorders.

Mit dem inhalierten Rauch einer Zigarette gelangen rund 1 bis 2 mg Nikotin ins Blut. Das Nikotin erreicht innerhalb weniger Sekunden nach der Inhalation das Gehirn. Bei der Verwendung von Schnupf- und Kautabak sowie von Nikotinersatzprodukten wie Nikotinkaugummi gelangt das Nikotin deutlich langsamer ins Blut, erreicht aber letztlich vergleichbar hohe Werte wie beim Rauchen.

Das Einatmen von Tabakrauch aus der Raumluft wird als Passivrauchen bezeichnet. Der Tabakrauch, der beim Passivrauchen eingeatmet wird, enthalt die gleichen giftigen und krebserzeugenden Substanzen wie der vom Raucher inhalierte Rauch. Daher verursacht auch das Passivrauchen zahlreiche, zum Teil schwere Erkrankungen.

Fur Raucher entstehen durch ihren Tabakkonsum erhebliche finanzielle Aufwendungen. Raucher, die eine Packung Zigaretten am Tag rauchen, geben bei einem Packungspreis von 4 € im Monat etwa 120 € und im Jahr etwa 1.460 € fur Zigaretten aus.

Persistent oxidative stress and excess lipid peroxidation (LPO), induced by inflammatory processes, impaired metal storage, and/or dietary imbalance, cause accumulations and massive DNA damage. This massive DNA damage, along with deregulation of cell homeostasis, leads to malignant diseases. Reactive aldehydes produced by LPO, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein, and crotonaldehyde, react directly with DNA bases or generate bifunctional intermediates which form exocyclic DNA adducts. Modification of DNA bases by these electrophiles, yielding promutagenic exocyclic adducts, is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. Ultrasensitive detection methods have facilitated studies of the concentrations of promutagenic DNA adducts in human tissues, white blood cells, and urine, where they are excreted as modified nucleosides and bases. Thus, immunoaffinity-(32)P-postlabeling, high-performance liquid chromatography-electrochemical detection, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, immunoslotblot assay, and immunohistochemistry have made it possible to detect background concentrations of adducts arising from endogenous LPO products in vivo and studies of their role in carcinogenesis. These background adduct levels in asymptomatic human tissues occur in the order of 1 adduct/10(8) and in organs affected by cancer-prone inflammatory diseases these can be 1 or 2 orders of magnitude higher. In this review, we critically discuss the accuracy of the available methods and their validation and summarize studies in which measurement of exocyclic adducts suggested new mechanisms of cancer causation, providing potential biomarkers for cancer risk assessment in humans with cancer-prone diseases.

One-third of all cancers worldwide can be attributed to various tobacco habits. Both in tobacco smoke and smokeless tobacco, carcinogenic N-nitroso compounds (NOC) are implicated as DNA-damaging agents in cancers of the aerodigestive tract and the pancreas. The exposure from nitrosamines in certain types of tobacco use such as "toombak" in Sudan could be as high as a few milligrams per day. Using the N-nitrosoproline test, it has been shown that smoking contributes to endogenous nitrosation and likely increases NOC formation in vivo. Smokeless tobacco, most widely used in the form of chewing of betel quid (BQ) with tobacco, was shown to particularly enhance endogenous nitrosation in the oral cavity, a site where chewing habits are causally associated with cancer. Poor oral hygiene was found to contribute to the formation of nitrosamines in the oral cavity. The evidence so far accumulated demonstrates that tobacco habits increase endogenous NOC formation, thus adding to the burden of exposure by preformed carcinogenic NOC in tobacco products. In snuff dippers, the unexpected higher level of HPB released from hemoglobin, an exposure marker for carcinogenic tobacco-specific nitrosamines, has been attributed to the endogenous formation of these carcinogens. Recent studies have demonstrated that besides carcinogenic tobacco-specific nitrosamines, reactive oxygen species derived from BQ ingredients could also play a role in the etiology of oral cancer in chewers. Although the use of chemopreventive agents may block nitrosation reactions in vivo in tobacco users, cessation of tobacco habits is the only safe way for an efficient reduction of cancer risk, in view of the high exposure to other (preformed) tobacco-related carcinogens.