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Society For Risk Analysis Annual Meeting 2009

Risk Analysis: The Evolution of a Science

Session Schedule & Abstracts

* Disclaimer: All presentations represent the views of the authors, and not the organizations that support their research. Please apply the standard disclaimer that any opinions, findings, and conclusions or recommendations in abstracts, posters, and presentations at the meeting are those of the authors and do not necessarily reflect the views of any other organization or agency. Meeting attendees and authors should be aware that this disclaimer is intended to apply to all abstracts contained in this document. Authors who wish to emphasize this disclaimer should do so in their presentation or poster. In an effort to make the abstracts as concise as possible and easy for meeting participants to read, the abstracts have been formatted such that they exclude references to papers, affiliations, and/or funding sources. Authors who wish to provide attendees with this information should do so in their presentation or poster.

Common abbreviations

Symposium: Evolution Response to NRC

Room: Federal Hill   3:30-5:00 PM

Chair(s): Dale Hattis, Lauren Zeise

W4-E.1  15:30  Musings on Implementing the NRC Unified Framework in Dose Response Assessment. Zeise L*; California Office of Environmental Health Hazard Assessment

Abstract: The National Research Council (NRC, 2008) recommended a unified framework for dose response assessment that includes a general approach for model choice and low dose risk estimation. For both carcinogenic and non-carcinogenic endpoints, background exposures and underlying disease processes can contribute to population background risk. Environmental exposures can add incrementally to these processes and dose response relationships can consequently be linear at low doses. On the other hand, there are a variety of circumstances where background additivity may not be operative and low dose linearity may not be expected. The NRC approach involves evaluating whether or not dose response relationships for individuals are threshold-like or low dose linear, and whether in the presence of background the population’s dose response curve is linear. The selection of a conceptual model for individual and population dose response is based on a systematic evaluation of background exposures and disease processes, possible vulnerable populations and possible modes of action by which the environmental agent may cause effects. This presentation, by a member of the NRC committee, discusses the implementation of the approach to estimate risks from environmental contaminants.

W4-E.2  15:50  Case Study Comparison of Human Health Noncancer Risk Assessment Models for Use in Benefits Analyses. Greco SL*, Hattis D, Axelrad D; ABT ASSOCIATES INC., CLARK UNIVERSITY, US ENVIRONMENTAL PROTECTION AGENCY

Abstract: Traditional noncancer risk assessment methods (a point of departure determined from the NOAEL or LOAEL from a toxicological study, divided by a series of uncertainty factors) have been used to set threshold exposures (e.g., reference dose/concentration, RfD/RfC). Such approaches have limited application in benefits assessments since it is assumed that exposure to environmental chemicals below the reference level is likely to be “without an appreciable risk of deleterious effects”. Furthermore, there is no way to quantify the actual risk at, below, or above the reference levels. Other approaches have been used (e.g., BMDS and CatReg), with the animal dose-response curves applied to humans after human equivalent dose adjustments. Another approach, termed Straw Man, is probabilistic in nature, and derives recommendations for RfD’s and RfC’s as “risk specific doses”, or estimates of the dose at which expected incidence of adverse effects is below a specified level with a designated degree of confidence. This type of RfD/RfC definition was recently espoused in the NRC report, Science and Decisions: Advancing Risk Assessment (2008). The Straw Man approach explicitly considers human heterogeneity, characterizes the traditional uncertainty factors as distributions using available evidence, is based on a spectrum of human and animal evidence, and has been recently updated to account for background exposures and susceptibility (Hattis and Lynch, 2009). We demonstrate each noncancer risk assessment approach using two case studies (tetrachlorobenzene for ingestion and carbonyl sulfide for inhalation) and estimating an RfD or RfC and the risk around the RfD or RfC. Generally, the application of the Straw Man model to the case study compounds resulted in lower (more protective) recommended RfD/RfC levels and higher risks at low doses than the other models. We discuss the details associated with the analysis and implications for noncancer risk assessment.

W4-E.3  16:10  Science and Decisions recommendations for dose-response assessment: Challenges and opportunities. Chiu WA*; U.S. Environmental Protection Agency

Abstract: In its report Science and Decisions: Advancing Risk Assessment, a committee of the National Research Council (NRC) made far-reaching recommendations to the U.S. Environmental Protection Agency (U.S. EPA) on the analysis of dose-response relationships for use in chemical risk assessment. In particular, they recommend a unification of cancer and non-cancer dose-response assessment with the goals of (i) quantifying the degree of risk at a specific dose; (ii) incorporating relevant information on chemical mechanisms/modes-of-action, inter-individual variability/susceptibility, and background pathological processes; and (iii) addressing uncertainty (degree of confidence) quantitatively. While conceptually straight-forward, U.S. EPA has identified a number of key challenges to achieving these objectives in the arenas of fundamental science, science policy, and practical implementation. A step-wise approach towards meeting these challenges is necessary in order to (i) strengthen the scientific basis for dose-response assessment; (ii) develop the necessary science policy interfaces with applicable laws, regulations, and U.S. EPA’s mission to protect public health and the environment; and (iii) gain experience in the application of the new assessment methods and in how their results support risk management decisions. This presentation outlines these challenges and suggests some potentially fruitful steps towards achieving the goals set forth by the NRC. Disclaimer: The views expressed in this abstract represent those of the author and do not necessarily reflect the views or policies of the US EPA.

W4-E.4  16:30  Alternatives to Pollutant-by-Pollutant Dose-Response Estimation for Air Toxics. Hattis D*, Lynch M; Clark University

Abstract: Perceived needs for extensive chemical-specific toxicological information have impeded efforts to assess risks and evaluate likely public health protection benefits of possible standards for hazardous air pollutants (HAPs). This paper explores two approaches that regulatory toxicologists may use to analyze risks and associated uncertainties for noncancer effects of HAPs with limited toxicological databases. The first approach supplements available chemical-specific information by viewing specific HAPs as random draws from reference sets of putatively analogous chemicals that have been studied in the past, the “Straw Man” model. The variability among previously studied chemicals is used to create distributions that represent each of the concerns that are addressed by traditional “uncertainty factors” in the derivation of reference concentrations. Another path toward risk assessments for HAPs is a growing set of human biomarkers of early effect that allow assessors to “move upstream” from ultimate endpoints of concern. Using these biomarkers, projections of potential health risks are made in two steps: (1) assess relationships between exposure to the chemical of interest and the intermediate biomarker of effect using limited chemical-specific information, and (2) assess relationships between the biomarker of effect and ultimate endpoints of concern from general epidemiological data. Several candidate biomarkers are available for this approach, but on the basis of recent epidemiological findings, one that appears particularly promising for ambient air pollutants is fetal growth restriction that produces changes in distributions of birth weights. Birth weights are strongly associated with infant mortality, neurodevelopmental delays, and long term failures of homeostatic controls such as type 2 diabetes.

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