Title -- Copyright -- Contents -- 1. Introduction -- 1.1 Background -- References -- 2. Contents and design features of tobacco products: their relationship to dependence potential and consumer appeal -- 2.1 Background -- 2.2 Terminology -- 2.3 Relationship between dependence potential and harm -- 2.4 Effect of contents and designs on dependence potential -- 2.4.1 Nicotine dose level -- 2.4.2 Other contents -- 2.4.3 Modifying nicotine delivery speed and efficiency by pH and free nicotine control -- 2.5 Regulatory implications and challenges -- 2.5.1 Personal and local vendor-made products -- 2.5.2 Nicotine levels -- 2.5.3 Assessing and regulating dependence potential -- 2.6 Conclusions -- 2.7 Research needs -- 2.8 Regulatory recommendations -- References -- 3. Candy-flavoured tobacco products: research needs and regulatory recommendations -- 3.1 Introduction -- 3.2 Purpose of the recommendations -- 3.3 Background -- 3.4 Description of flavoured tobacco products -- 3.4.1 Flavoured brands -- 3.4.2 Flavour application -- 3.5 Regional and global patterns of flavoured tobacco product use -- 3.6 Impact on public health -- 3.7 Science base and conclusions -- 3.8 Research needs -- 3.9 Regulatory recommendations -- References -- 4. Biomarkers of tobacco exposure and of tobacco smoke-induced health effects -- 4.1 Introduction -- 4.2 Background -- 4.3 Biomarkers: definition and description -- 4.4 Measuring exposure -- 4.5 Measuring injury and disease -- 4.6 Existing evidence on biomarkers -- 4.7 Specific biomarkers -- 4.7.1 Tobacco alkaloids -- 4.7.2 Minor tobacco alkaloids -- 4.7.3 Other particulate phase components -- 4.7.4 Gas phase components -- 4.7.5 DNA and protein adducts -- 4.7.6 Mutagenic activity of the urine -- 4.8 Measuring biological changes -- 4.8.1 Assessing oxidative stress -- 4.8.2 Measures of inflammation.

4.8.3 Measures of endothelial dysfunction -- 4.8.4 Measures of clotting -- 4.8.5 Insulin resistance -- 4.8.6 Circulating endothelial precursor cells -- 4.8.7 Femoral and internal carotid artery intima-media thickness -- 4.8.8 Sister chromatid exchanges in peripheral lymphocytes -- 4.9 Summary of existing biomarkers -- 4.10 Recommended uses for biomarkers of exposure and effect -- 4.10.1 Improving the accuracy of the definition of current tobacco use status -- 4.10.2 Evaluating the intensity of exposure to specific constituents -- 4.10.3 Evaluating the intensity of exposure as a proxy for total tobacco exposure -- 4.10.4 Measuring reduced injury or harm -- 4.11 Summary of biomarker recommendations -- References -- 5. Setting maximum limits for toxic constituents in cigarette smoke -- 5.1 Introduction -- 5.2 Regulatory strategy -- 5.3 Selection of the machine-testing method -- 5.4 Criteria for selecting constituents for regulating maximum limits -- 5.5 Specific regulatory recommendations for TSNAs -- 5.6 Interpretation of the maximum limit values -- 5.7 Communication of the results of the testing to the public -- 5.8 Methods for measuring nitrosamines -- 5.9 Considerations for modified cigarettes and potential reduced exposure products -- 5.10 Future directions -- References -- 6. Overall recommendations -- 6.1 Contents and design features of tobacco products: their relationship to dependence potential and consumer appeal -- 6.2 Candy-flavoured tobacco products: research needs and regulatory recommendations -- 6.3 Biomarkers of tobacco exposure and of tobacco smoke-induced health effects -- 6.4 Setting maximum limits for toxic constituents in cigarette smoke -- Acknowledgements -- Annex 1: Reports and other documents arising from meetings of the WHO Scientific Advisory Committee on Tobacco Product Regulation (SACTob).

Statement of principles guiding the evaluation of new or modified tobacco products (2003) -- Recommendation on nicotine and its regulation in tobacco and nontobacco products (2002) -- Recommendation on tobacco product ingredients and emissions (2003) -- SACTob recommendations on health claims derived from ISO/FTC method to measure cigarette yield (2003) -- Recommendation on smokeless tobacco products (2003) -- Annex 2: Reports and other documents arising from meetings of the WHO Study Group on Tobacco Product Regulation (TobReg) -- Guiding principles for the development of tobacco product research and testing capacity and proposed protocols for the initiation of tobacco product testing: recommendation 1 (2004) -- Best practices in tobacco control: regulation of tobacco products: Canada report (2005) -- Advisory note: waterpipe tobacco smoking: health effects, research needs and recommended actions by regulators (2005).