一种无烟气烟草制品秀爽的吸入毒理学评价

  目的  对一种无烟气烟草制品秀爽进行吸入毒理学评价。  方法  120只SD大鼠根据体重分性别随机分4组:对照组（n=30）、低剂量组（n=30）、中剂量组（n=30）、高剂量组（n=30）。对照组为空气暴露组,实验组吸入暴露剂量分别相当于人吸入暴露量的10倍、30倍、100倍。每天暴露1次,连续暴露14 d,恢复4 W。暴露期及恢复期每天观察各组大鼠一般状况、精神状态,腺体分泌,皮肤和粘膜颜色,呼吸状态,粪便性状,生殖器等情况及其它非常态症状。  结果  暴露期及恢复期,各组大鼠一般状况良好、自主活动正常、皮肤被毛清洁,亦未见其它毒性反应;各组大鼠体重正常增长,对照组和暴露组雌、雄鼠体重增长趋势未见显著性差异;眼科检查与大体解剖均无异常。  结论  秀爽对大鼠生长发育、生长代谢、重要脏器未造成影响。      

Effect of smokeless tobacco (snus) on smoking and public health in Sweden

Method: Narrative review of published papers and other data sources (for example, conference abstracts and internet based information) on snus use, use of other tobacco products, and changes in health status in Sweden.

Results: Snus is manufactured and stored in a manner that causes it to deliver lower concentrations of some harmful chemicals than other tobacco products, although it can deliver high doses of nicotine. It is dependence forming, but does not appear to cause cancer or respiratory diseases. It may cause a slight increase in cardiovascular risks and is likely to be harmful to the unborn fetus, although these risks are lower than those caused by smoking. There has been a larger drop in male daily smoking (from 40% in 1976 to 15% in 2002) than female daily smoking (34% in 1976 to 20% in 2002) in Sweden, with a substantial proportion (around 30%) of male ex-smokers using snus when quitting smoking. Over the same time period, rates of lung cancer and myocardial infarction have dropped significantly faster among Swedish men than women and remain at low levels as compared with other developed countries with a long history of tobacco use.

Conclusions: Snus availability in Sweden appears to have contributed to the unusually low rates of smoking among Swedish men by helping them transfer to a notably less harmful form of nicotine dependence.

     

Validity of self reports in a cohort of Swedish adolescent smokers and smokeless tobacco (snus) users

Objective: To validate self reports of cigarette and smokeless tobacco (snus) use in a prospective cohort of adolescents. Design: A cross sectional analysis of a cohort sub-sample. Setting: County of Stockholm, Sweden. Subjects: 520 adolescents in the final grade of junior high school (mean age 15.0 years). Main outcome measure: Concordance between self reported tobacco use and saliva cotinine concentration. Results: Using a cut point of 5 ng/ml saliva cotinine to discriminate active tobacco use, there was a 98% concordance between self reported non-use in the past month and cotinine concentration. The sensitivity of the questionnaire compared to the saliva cotinine test, used as the gold standard, was 90% and the specificity 93%. One hundred and fifteen out of 520 subjects (22%) reported monthly tobacco use. Among these, 67% (46/69) of the exclusive cigarette smokers, 82% (23/28) of exclusive snus users, and 94% (15/16) of mixed users (cigarettes + snus) had cotinine concentrations above 5 ng/ml. Among subjects reporting daily use 96% (64/67) had saliva cotinine concentrations above the cut point. Exclusive current cigarette users were more likely to be classified discordantly by questionnaire and cotinine test compared to snus users (odds ratio 3.2, 95% confidence interval 1.2 to 8.6). Conclusion: This study confirms the reliability of adolescents'' self reported tobacco use. In a context of low exposure to environmental tobacco smoke a cut off for saliva cotinine of 5 ng/ml reliably discriminated tobacco users from non-users. Irregular use of tobacco in this age group probably explains the discrepancy between self reported use and cotinine concentrations.     

Non-dioxin like polychlorinated biphenyls in mackerel (Scomber scombrus) available on the Serbian market

Mackerel is rich in omega-3 fatty acids, but this fish may be contaminated with environmental pollutants. The aim of this study was to evaluate concentrations of non-dioxin like polychlorinated biphenyls (ndl-PCBs) in 160 samples of mackerel available on the Serbian market. Average and maximum ndl-PCB concentrations were 7.9 ng/g and 74 ng/g, respectively. A higher average level of ndl-PCBs was found in mackerel from Spain, but this was still three times lower than the permitted level. We conclude that levels of ndl-PCBs in mackerel available on the Serbian market are acceptable.     

Nicotine lozenges for the treatment of smokeless tobacco use.

Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. We conducted an open-label, one-arm, phase II clinical trial to evaluate the efficacy of the 4-mg nicotine lozenge for the treatment of withdrawal and craving associated with tobacco abstinence among ST users. Eligible subjects received 4-mg nicotine lozenges for 6 weeks followed by a 6-week taper. Subjects completed daily tobacco withdrawal diaries, and data on lozenge use, adverse events, and lozenge acceptability were collected. Urine anabasine was collected at 3 and 6 months for biochemical confirmation of self-reported tobacco abstinence. Participants were 30 ST users with a mean age of 35.4 years (SD=6.5) using an average of 4.2 cans or pouches (SD=3.2) of ST per week for a mean of 15.1 years (SD=6.5). Among subjects continuously tobacco abstinent for the first 2 weeks, no significant increases in composite withdrawal symptoms were observed, compared with baseline symptoms, whereas craving decreased significantly. Biochemically confirmed 7-day point-prevalence tobacco abstinence was 53% (95% CI=34%-72%) at 12 weeks (end of treatment) and 47% (95% CI=28%-66%) at 6 months. Few adverse events attributable to the nicotine lozenge occurred, and the lozenge was perceived as helpful in assisting subjects quit ST. The use of the 4-mg nicotine lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in ST users. Future phase III clinical trials investigating the efficacy of nicotine lozenges are warranted.     

Effect of high-dose nicotine patch therapy on tobacco withdrawal symptoms among smokeless tobacco users.

No pharmacotherapies have been shown to increase long-term (> or = 6-month) abstinence rates among smokeless tobacco (ST) users. Available evidence suggests that underdosing may occur with standard-dose nicotine replacement therapy (NRT) in ST users. We investigated the effect of high-dose nicotine therapy on tobacco withdrawal symptoms among ST users in a randomized, controlled clinical pilot study. A total of 42 ST users using at least 3 cans or pouches per week were randomized to nicotine patch doses of 63, 42, or 21 mg/day or placebo for 8 weeks. Multiple daily assessments of tobacco withdrawal and nicotine toxicity were obtained with an electronic diary. During the first week of nicotine patch therapy, we observed a dose-response relationship such that higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.87, p = .009), less negative affect (chi2 = 3.85, p = .05), and less restlessness (chi2 = 3.90, p = .048). During the second week, higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.77, p = .009). Overall, the frequency of nicotine toxicity symptoms did not differ by dose group. Of specific symptoms, nausea was observed to be more frequent in the 63 mg/day dose group compared with placebo (p = .035). In conclusion, high-dose nicotine patch therapy resulted in a greater reduction of tobacco withdrawal symptoms among ST users using at least 3 cans per week. High-dose nicotine patch therapy is safe and well tolerated in this population of tobacco users.     

Use of smokeless tobacco is a risk factor for cigarette smoking.

This study assessed the risk of smoking uptake over 2 years in adolescent boys (in grades 7 and 9) who had used smokeless tobacco (ST). We used logistic regression to determine whether the odds of adolescent boys taking up regular smoking over a period of 2 years were greater among initial nonsmokers who used ST, compared with nonusers of ST, after accounting for six well-established predictors of smoking. Initiation of weekly smoking 2 years after baseline was associated with ST use at baseline, even after including dichotomous measures of parent, sibling, or close friend smoking; low academic grades; 30-day alcohol use; and a scale measure of deviant behavior. With these other predictors included in the model, the odds ratio for the association of ST use with weekly smoking after 2 years was strong and significant (OR = 2.55, 95% CI 1.45-4.47, p<.001). The use of ST in the 7th and 9th grades is a significant risk factor for subsequent smoking even when controlling for other factors.     

Assessment of allergic potential of (novel) foods

In safety assessment of Novel Foods such as functional foods, allergy is a special issue on which particular emphasis has been placed. The reason for such concern is that incidence of food allergies is constantly and rapidly increasing. The severity of the reported incidents and the number of foods incriminated are also on the rise. The outstanding challenge is to understand what makes a common innocuous protein or peptide behave as an allergen for some groups of people, or why it may suddenly or progressively become a much more potent allergen than usual. It is therefore necessary to consider the risks of creating or unmasking new immunoreactive structures, or of overexposure to already reactive substances, as a result of new food-production and processing technologies. No test such as the use of animal models, the analysis of structure, function and physico-chemical properties is as yet available to evaluate or predict the allergenicity of a “novel” protein in a wholly reliable and objective manner. No indication has yet suggested that novel foods, and particularly recombinant proteins or genetically modified foods, would be more (or less) allergenic than the corresponding conventional foods. No particular structure can be described as being solely and intrinsically allergenic. The predictive approaches to determining the allergenic potential of NFs should therefore be subject to case-by-case critical appraisal allied to mandatory implementation of monitoring of the potential postmarketing impact of these new foodstuffs on public health.     

Sensitivity and specificity of a reagent-impregnated test strip in identifying smokeless tobacco users.

This study was designed to determine the sensitivity and specificity of a reagent-impregnated test strip in identifying habitual snuff users and tobacco chewers. Urine specimens were obtained from smokeless tobacco users and controls and blind tested on-site using a reagent-impregnated test strip. Samples also were sent to our university hospital lab for cotinine and nicotine analysis by gas chromatography (GC). The test strip results were compared with GC results and self-reported use of snuff and chewing tobacco. A total of 61 subjects enrolled in the study: 26 snuff users, 25 tobacco chewers, and 10 nonconsumers of nicotine. Using GC assessment of nicotine and cotinine (>or=200 ng/ml) as the standard, we found the sensitivity of the test strip to be 96% (25/26) for snuff users and 96% (24/25) for tobacco chewers. When compared with self-report, the sensitivity of the test strip was 92.3% (24/26) for snuff users and 84% (21/25) for tobacco chewers. The specificity for nonusers of nicotine was 100% (10/10) for both the self-report and GC conditions. These results suggest that a reagent-impregnated test strip is a rapid, valid, and user-friendly means of differentiating smokeless tobacco users from nonconsumers of tobacco. The intensity of the pink color on the test strip is proportional to the amount of nicotine or its metabolites present in urine and therefore offers a semiquantitative measure of nicotine consumption.     

Self-help cessation programs for smokeless tobacco users: long-term follow-up of a randomized trial.

This paper presents long-term outcomes of the largest clinical trial of smokeless tobacco (SLT) cessation reported to date. SLT users in five northwestern states were recruited to call a toll-free number, and 1,069 users were randomized to one of two self-help conditions: either a manual-only condition or an assisted self-help condition, which included the manual, a targeted video, and two support phone calls. Significant between-group differences were not found for either the 12- or 18-month point-prevalence measure of abstinence from either SLT only or all tobacco products using outcomes based on either the responder or intention-to-treat outcomes. However, using a repeated point-prevalence measure across all three assessment points, we found that significantly more assisted self-help participants reported abstinence, compared with manual-only participants. Compared with manual-only participants, those in the assisted self-help condition were significantly more likely to use recommended cessation techniques. Results demonstrate that low-cost, minimal interventions delivered by mail and phone can help a sizable proportion of individuals quit using SLT.     

基于恒定市场份额模型(CMS)的中国烟草制品出口影响因素研究

恒定市场份额模型（Constant Market Share Model）是用来反映一国出口增长影响因素作用方向和作用程度的模型。本文运用恒定市场份额模型分析了我国烟草产品近15年来的出口数据,通过计量经济学手段测度了我国烟草产品在国际市场的产品结构效应、市场结构效应和产品竞争力效应,研究了我国烟草制品出口的影响因素。研究表明,我国烟草出口主要产品是烟叶,我国烟草制品在主要市场的竞争力逐渐减弱,但在新兴市场的出口额有所增加。      

Review of the evidence that pH is a determinant of nicotine dosage from oral use of smokeless tobacco

OBJECTIVE: To determine whether manipulation of the pH of moist-snuff products by manufacturers could control the delivery of nicotine. DATA SOURCES: Medline database 1966-97 using the following subject headings and keywords: nicotine, absorption, mouth mucosa, skin, hydrogen-ion concentration, smokeless tobacco, biological transport, and membranes; computer database of the tobacco bibliography maintained by the US Centers for Disease Control and Prevention's Office on Smoking and Health; bibliographies of pertinent journal articles, books, and governmental reports; personal communications with experts in nicotine pharmacology and addiction; and Brown & Williamson Tobacco Corporation documents in the Tobacco Control Archives of the University of California, San Francisco. STUDY SELECTION: Included all relevant animal studies, in-vitro studies, nicotine replacement therapy trials, and human observational studies. DATA SYNTHESIS: We found that the effects of pH on drug absorption have been well established in animal models for nicotine and many other acidic or basic compounds. Increased alkalinity promotes the absorption of nicotine and increases its physiological effects. Human studies, which are more limited, confirm these processes. For example, nicotine absorption is directly related to the pH when nicotine is delivered in either tobacco smoke or nicotine polacrilex gum. CONCLUSIONS: Although other factors could influence the rate of nicotine absorption from oral tobacco, manipulating tobacco pH appears to be the primary means by which the speed of nicotine absorption is determined in moist-snuff products.


     

European Union policy on smokeless tobacco: a statement in favour of evidence based regulation for public health

Rationale: This statement is an updated version of one released by the same authors in February 2003. The statement was produced to follow up the Royal College of Physicians (RCP) Tobacco Advisory Group report "Protecting smokers, saving lives: the case for a tobacco and nicotine regulatory authority",¹ which argued for an evidence based regulatory approach to smokeless tobacco and harm reduction and posed a series of questions that regulators must address in relation to smokeless tobacco.

The purpose of this statement is to provide arguments of fact and principle to follow the RCP's report and to outline the public health case for changing existing European Union (EU) regulation in this area. A review of regulation in relation to harm reduction and regulation of tobacco products other than cigarettes is required in Article 11 of EU directive 2001/37/EC,² and this is a contribution towards forming a consensus in the European public health community about what policy the EU should adopt in the light of this review, or following ongoing legal action that may potentially strike out the existing regulation altogether.

Public health case: We believe that the partial ban applied to some forms of smokeless tobacco in the EU should be replaced by regulation of the toxicity of all smokeless tobacco. We hold this view for public health reasons: smokeless tobacco is substantially less harmful than smoking and evidence from Sweden suggests it is used as a substitute for smoking and for smoking cessation. To the extent there is a "gateway" it appears not to lead to smoking, but away from it and is an important reason why Sweden has the lowest rates of tobacco related disease in Europe. We think it is wrong to deny other Europeans this option for risk reduction and that the current ban violates rights of smokers to control their own risks. For smokers that are addicted to nicotine and cannot or will not stop, it is important that they can take advantage of much less hazardous forms of nicotine and tobacco—the alternative being to "quit or die"... and many die. While nicotine replacement therapies (NRT) may have a role in harm reduction, tobacco based harm reduction options may reach more smokers and in a different, market based, way. Chewing tobacco is not banned or regulated in the EU but is often highly toxic, and our proposal could remove more products from the market than it permitted.

Regulatory options: We believe that the EU policy on smokeless tobacco should adapt to new scientific knowledge and that the European Commission should bring forward proposals to amend or replace Article 8 of directive 2001/37/EC with a new regulatory framework. Canada has developed testing regimens for tobacco constituents and these could be readily adapted to the European situation. A review of EU policy in this area is required no later than December 2004, and we believe the Commission should expedite the part of its review that deals with harm reduction and regulation of tobacco products other than cigarettes so as to reconsider its policy on smokeless tobacco. We held this view before Swedish Match brought its legal proceedings to challenge EU legislation and we will continue to hold these views if its action fails.