Society For Risk Analysis Annual Meeting 2017

Session Schedule & Abstracts

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Common abbreviations

Symposium: Risk Assessment in Tobacco Product Regulatory Decision Making

Room: Salon 1   3:30 pm–5:00 pm

Chair(s): Kristin Marano, P. Robinan Gentry

Sponsored by Risk Policy and Law Specialty Group

In 2009, the Family Smoking Prevention and Tobacco Control Act granted the US Food and Drug Administration (FDA) authority to regulate tobacco products, with the intention of protecting public health. Under the Act, there are various regulatory pathways including substantial equivalence, premarket tobacco product application, and modified risk tobacco product application, which, in turn, may require the applicant to demonstrate whether a product does not raise a different question of public health, is appropriate for the protection of public health, or is appropriate to promote public health, respectively. Quantitative risk assessment (QRA) provides a useful, practical, and efficient approach to address questions regarding human health risk and the potential effect on public health. The QRA process includes four steps: hazard identification, toxicity assessment, exposure assessment, and risk characterization. FDA has identified a list of chemicals in tobacco products and tobacco smoke as harmful and potentially harmful constituents (HPHC). Whereas these HPHC may be used to inform the QRA, an understanding of exposure is also needed to characterize the potential for risk, depending upon the regulatory pathway. In addition, it is critical to understand the current state of the science of risk assessment practice, as it is applied in a QRA framework, to evaluate tobacco products and to make regulatory decisions. Given that tobacco products and tobacco smoke are complex mixtures, it is also important to consider the state of the science in the risk assessment of mixtures. This session will provide a discussion of available data and methods appropriate for use in QRA of tobacco products, as well as how this process applies to the current state of the science to characterize exposures and health risks in support of different tobacco product regulatory pathways and regulatory decision making.

W4-J.1  3:30 pm  The State of the Science of QRA in Support of Different Tobacco Product Submission Types. Gentry PR*; Ramboll Environ

Abstract: Quantitative risk assessment (QRA) is an important tool used by multiple regulatory agencies. QRA informs decision-making by using the available scientific evidence to describe the potential impact to public health of exposures to individual chemicals and to mixtures. QRA techniques can be applied to tobacco products to address questions regarding human health risk and the potential influence on public health of different products. Specifically, QRA can be informative in substantial equivalence evaluations, premarket tobacco product applications, and modified risk tobacco product applications, the regulatory pathways for tobacco products in the US. When developing a QRA approach for tobacco products, it is important to understand both the available data for addressing public health questions, as well as the state of the science of QRA. Current regulatory approaches applied by, for example, the US EPA, incorporate decades of research, consider the available data that can be used to understand the potential for health effects, as well as consider the potential variability and uncertainty in the process and how this may impact decision making. This presentation will focus on a description of the data and methods available for conducting each step of the QRA process for tobacco products and the potential uncertainties/challenges with each step, considering the current state of the science and the use of QRA for other applications (e.g., environmental).

W4-J.2  3:50 pm  Characterization of Inhalation Exposure to Cigarette Smoke. LIU C*, MARANO K; RAI Services Company

Abstract: Quantitative risk assessment (QRA) may inform regulatory decisions regarding tobacco products. In general, QRA is a five-step process that includes problem formulation, hazard identification, dose-response assessment, exposure assessment, and risk characterization. Evaluation of human health risks from cigarette smoking requires an adequate assessment of the exposure, which is a challenging task in part because the concentration of chemicals in the respiratory tract and exposure duration are not constant. No regulatory guidance currently exists for exposure assessment of tobacco products, although examples exist in the peer-reviewed literature. The U.S. Environmental Protection Agency (EPA) provides guidance that addresses methods for quantitative evaluation of exposure and risk, which is useful and can be applied to tobacco products. Two different methods were developed to quantify inhalation exposure with machine-generated smoke yields from a market survey of U.S. cigarettes. The first method treats exposure to a chemical in smoke as a continuous process and estimates an exposure concentration by averaging the yields of the chemical from cigarettes consumed over the average daily volume of air inhaled by a user. The second method treats exposure to the chemical as discrete smoking sessions and estimates a respiratory concentration of the chemical via summation of discrete smoking sessions over the course of a day. Both methods incorporate standard exposure parameters to derive an upper-bound lifetime average exposure to the chemical. For simplicity and conservatism, both methods assume 100% retention of the chemical in the smoker’s body. The two methods provide risk estimates with relative percent differences within 30%; the first method was more conservative (i.e., risk-maximizing). Exposure assessment of tobacco products should be consistent with available evidence, guidance, and state of the science for risk assessment. These findings indicate that incremental modifications to exposure input assumptions do not materially affect the QRA results.

W4-J.3  4:10 pm  Chemical mixture human health risk assessment methods applicable to the evaluation of complex mixtures of tobacco smoke . Teuschler LK*; LK Teuschler & Associates

Abstract: Tobacco smoke is composed of thousands of components; 93 are named by the Food and Drug Administration as Harmful and Potentially Harmful Constituents and designated as causing carcinogenic, repro/developmental, cardiovascular, respiratory and/or addictive effects. Different effects may be caused by typically high dose exposure pathways/routes to chemicals and particles, e.g., inhalation (direct, side stream, second hand), oral smokeless tobacco. Sensitive populations (e.g., asthmatics, those with genetic susceptibility to cancer) need to be considered in quantitative risk assessment. Chemical mixture risk assessment approaches are historically divided into whole mixture and component-based methods. Whole mixture methods are more appropriate for evaluating complex tobacco smoke exposures, for which toxicology and epidemiologic data are available, but sufficient similarity procedures are needed to extrapolate results to other exposures or products. Component methods, based on additivity assumptions, generally use toxicology data on single chemicals. These may be unrepresentative of the whole mixture risk, but are useful, e.g., to make comparisons across product formulations. This presentation details the scientific principles that underpin the methods, describes applied approaches and discusses similarity of toxic action assumptions. Methods to be discussed include: whole mixture evaluation and sufficient similarity; response-addition, based on independent action, generally used for mixtures of carcinogens; dose-addition, based on similar action, typically used for noncancer endpoints (hazard index [HI], margin of exposure, relative potency factors); and methods to incorporate toxicological interactions (interaction-based HI, weight-of-evidence interaction profiles). Uncertainty in chemical mixtures risk assessments will be considered.

W4-J.4  4:30 pm  Regulatory Perspective on the Assessment of Tobacco Product Risk. Yeager RP*; US FDA

Abstract: Various centers of the FDA have used diverse risk assessment methods in executing their statutory authority. While a risk assessment is not required for a toxicological evaluation of tobacco products, when appropriate, a quantitative risk assessment (QRA) may be informative. The development of a QRA for tobacco products should consider the question to be answered by the risk model, within a given statutory framework. In general, evaluation of risks in any regulated consumer product requires consideration of the chemical exposure from product use, the route by which the product is consumed, the strength of evidence for adverse effects relevant to non-cancer or cancer endpoints, and how chemicals in a mixture may combine to result in adverse health effects. Thus, an evaluation of tobacco product associated risks could potentially be conducted by using an approach similar to traditional QRA. Generally, sound scientific justification is needed to support the selection of parameters, values, and their relationship in a predictive QRA model, including justification of explicit and implicit assumptions. There are a number of challenges in developing a QRA to estimate tobacco product risk but there are also opportunities to advance the use of QRA in tobacco science.

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