• measure exposure to tobacco product and smoke constituents
• analyze reduced exposure to tobacco products and smoke constituents
• assess product use behaviors by individuals and product characteristics that impact individual exposure reduction, and
• identify characteristics of potential users of the tobacco product that have the potential to influence exposure (e.g., gender, ethnicity).

WORK PRODUCT
The results of this investigation will be presented in summary format to the Core Committee at their October 19-20, 2005 meeting, as a summary chapter in the RRRvw Core Committee report by April 2006, and as a formal report by late 2006.

AREAS OF INQUIRY

Estimates of External Exposure

    Tobacco Product and Tobacco Smoke Chemistry

• What are the currently available techniques for generating different types of tobacco smoke?
• What methods are currently being used for the chemical analysis of tobacco products and tobacco smoke?
• Methods for analyzing tobacco product and smoke chemistry will be evaluated, for example:
  • Have methods for measuring tobacco product and smoke constituents been validated and standardized?
  • How relevant are cigarette machine yields of mainstream tobacco smoke constituents to smokers' actual exposures?
  • How relevant are methods used to characterize environmental tobacco smoke to bystanders' actual exposure?
• What are the appropriate benchmarks to which potential reduced risk tobacco products should be compared (e.g., Kentucky reference cigarette(s), the leading product as assessed by market share, the lowest risk product currently available, each individual smoker's brand at the time of switching to the new product, each individual smoker's dominant brand of his or her smoking history)?
• What methods are in development for the chemical analysis of tobacco products and tobacco smoke?
• What and how much can the analysis of tobacco product and tobacco smoke chemistry contribute to an overall framework for assessing the potential for a tobacco product to lower the risk of adverse health effects as compared to smoking cigarettes?

    Smoking Behavior, Puffing Behavior/Smoking Topography

• What measures are used to assess cigarette puffing behavior/smoking topography?
• What other measures are used to assess smoking behavior (e.g., # cigarettes/day, amount of cigarette smoked)?
• What are the appropriate comparison products?
• What are the limitations of using smoking topography and other measures of smoking behavior to estimate tobacco smoke exposure?
• How do measures of cigarette puffing behavior/smoking topography relate to biomarkers of exposure?
• What and how much can cigarette puffing behavior/smoking topography and other smoking behavior measures contribute to an overall assessment of risk?
• What impact do product characteristics (e.g., elasticity) have on smoking behavior and topography?

    Exposure to Environmental Tobacco Smoke

• What approaches have been used to acquire information on exposure to environmental tobacco smoke?
• What are the limitations of this information for estimating exposure to environmental tobacco smoke?
• What is the relationship between biomarkers of exposure/internal dose and other information on exposure to environmental tobacco smoke?
• What can information about exposure to environmental tobacco smoke contribute to an overall assessment of the potential for reduced risk?

Characteristics of Potential Users of the Tobacco Product that are Associated with Smoking Behaviors that Affect the Degree of Exposure and Implications for Study Design

    Evidence from Previous Studies

• What user characteristics influence degree of exposure?
• What are the implications of this information on study design for assessing exposure in users of a potential reduced-risk tobacco product?

Estimates of Internal Exposure/Dose

    Biomarkers of Exposure/Internal Dose

• What are the currently available biomarkers of exposure/internal dose to tobacco product and tobacco smoke constituents?
• Have these biomarkers been validated? Have they been assessed in terms of specificity, sensitivity, replicability, inter-laboratory variability, intra-individual variation, and inter-individual variation?
• How will exposure to substances introduced through product design modifications (e.g., added ingredients, fiberglass) that potentially pose an additional hazard be assessed?
• Which factors have the potential to confound biomarkers of exposure/internal dose?
• Which factors can modify exposure to tobacco and tobacco smoke constituents (e.g., genetics)?
• How well do biomarkers of exposure/internal dose predict tobacco related diseases in humans?
• What clinical study designs have been used to assess exposure/internal dose of tobacco product and tobacco smoke constituents?
• Which clinical study designs are likely to be most useful for evaluating reduced risk claims (e.g., crossover studies)?
• What are the advantages and disadvantages of measuring biomarkers in various biological sample matrices?
• How does the sample population of a clinical study influence the applicability of results?
• What is the appropriate duration for conducting clinical studies on exposure?
• What are the appropriate benchmarks to which potential reduced tobacco products should be compared (e.g., Kentucky reference cigarette(s), the leading product as assessed by market share, each individual smoker's brand at the time of switching to the new product, each individual smoker's dominant brand of his or her smoking history)?
• Are there any tobacco product or smoke constituent ratios that are conserved in human measurements?
• How do current biomarkers of exposure/internal dose fall short and what is required of future biomarkers?
• What are the biomarkers of exposure/internal dose in development?
• What and how much will biomarkers of exposure/internal dose contribute to an overall assessment of the capacity for a tobacco product to reduce risk?
• How much emphasis should be placed on these kinds of measures?

    Other Methods

• What can microarrays contribute to an exposure assessment?
• What can breath analysis methods contribute to an individual exposure assessment?
• What can filter analysis contribute to an individual exposure assessment?
• Are there other methods that should be considered?

    Smokeless Tobaccco Product Use Characteristics

• What approaches have been used to acquire information about tobacco product use characteristics (e.g., amount used, amount of time held in the mouth)?
• What are the appropriate comparison products?
• What are the limitations of information about use characteristics for estimating tobacco product exposure?
• What is the relationship between tobacco product use history measures (e.g., amount used /day) and biomarkers of external exposure/internal dose?
• What can information about tobacco product use characteristics contribute to an overall assessment of the likelihood for reduced risk?

Research Needs

• What critical uncertainties are associated with the described methods for assessment of individual exposure to tobacco product and tobacco smoke?
• What are the future directions/requirements for assessing individual exposures?

Conclusions

• What is the relative value of the various approaches used to assess individual exposure for the evaluation of exposure reduction?
• How should the measures used to assess individual exposures to tobacco product and tobacco smoke constituents inform the overall process of evaluating the potential for reduced risk?