Society For Risk Analysis Annual Meeting 2013

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: Integrating Diverse Streams of Evidence for Chemical Assessments: Getting from Association to Causation, Part I

Room: Key Ballroom 2   10:30 AM- 12:00 PM

Chair(s): Kimberly Wise

Sponsored by DRSG

M2-B.1  10:30  Evolution of Weight of Evidence Assessment in Mode of Action Analysis. Meek ME*; University of Ottawa

Abstract: The World Health Organization (WHO)/International Programme on Chemical Safety (IPCS) mode of action/human relevance (MOA/HR) framework has been updated to reflect evolving experience in its application and to incorporate recent developments in toxicity testing and non-testing methods. The modified framework is incorporated within an iterative roadmap, encouraging continuous refinement of problem formulation, mode of action based testing strategies and risk assessment. It can be used as originally intended, where the outcome of chemical exposure is known, or in hypothesizing potential effects resulting from exposure, based on information on putative key events in established modes of action from appropriate in vitro or in silico systems and other evidence. It clarifies the conceptually synonymous terms of MOA and adverse outcome pathways (AOPs) and builds on experience in ever increasing numbers of case studies to additionally inform weight of evidence analysis for hypothesized modes of action. The modified Bradford Hill (BH) considerations have been additionally articulated to simplify application and a template for comparative assessment of weight of evidence and associated uncertainty for various modes of action developed. The contribution of these developments to weight of evidence considerations in related initiatives will be addressed.

M2-B.2  10:50  Judging the Quality of Evidence for REACH. Lewis RJ*, Money C, Boogaard PJ; ExxonMobil Biomedical Sciences, Inc.

Abstract: An approach has been developed for how the quality of human data can be systematically assessed and categorized. The approach mirrors that applied for animal data quality considerations (Klimisch scores), in order that human data can be addressed in a complementary manner to help facilitate transparent (and repeatable) weight of evidence comparisons. The definition of quality proposed accounts for both absolute quality and interpretability, thereby enabling consistent and trasparent incorporation of data into human health risk assessments. Using examples, the presentation will illustrate how the scheme can be applied for weight of evidence comparisons, building from a systematic assessment of available data quality and adequacy. The utility of the scheme for describing data reliability, especially when contributing entries to the IUCLID database, will also be shown.

M2-B.3  11:10  On the utility of criteria-based methods of causal inference. Weed DL*; DLW Consulting Services, LLC

Abstract: Criteria-based methods have been discussed in the epidemiologic literature since the late 1950’s and continue to be used today, with recent extension into the assessment of toxicologic evidence. This paper will discuss the theoretical and practical utility of criteria-based methods of causal inference, including but not limited to Hill’s criteria (i.e. strength, consistency, dose-response, specificity, temporality, biological plausibility, experimentation, coherence, and analogy). Included will be a discussion of how these methods fit within a broader methodology for assessing causation. Assessing the utility of criteria-based methods involves: (1) a historical assessment of the use of these criteria, (2) the use of these criteria in organizational settings and by toxicology, and (3) the relationship between these criteria and the scientific method. Criteria for causation have been continuously used in scientific practice for 50 years. These criteria represent key concerns of the scientific method. Examples follow. The criterion of consistency reflects the scientific principles of replicability and testability. The criterion of strength (of association) reflects the basic scientific concept of critically testing alternative explanations. Experimentation reflects the need to test and control for alternative hypotheses. Temporality is a key feature of any causal hypothesis. Specificity reflects the need to test the hypothesis of interest and not some different hypothesis. Biological plausibility incorporates biological explanations with those explanations at the level of human populations by examining the extent to which the basic causal hypothesis has been tested in cellular systems and in animal models. Dose response reflects a basic toxicological principle: the greater the exposure to a causal agent, the greater the effect. The criteria and the general scientific method are not only compatible but inseparable. Challenges to the use of the criteria will

M2-B.4  11:30  Integrating evidence: The importance of exposure and framing the question. Shirley SH*, Grant RL, Honeycutt M; Texas Commission on Environmental Quality

Abstract: In 2009 the National Academies (NAS) emphasized the importance of problem formulation and exposure assessment, among other best practices. Robust problem formulation is helpful when incorporating biological relevance and chemical specific knowledge to meaningfully guide risk management options. As a first step, it is important to clarify the potential for exposure to chemicals of concern (COC) in order to develop the most reasonable and useful risk assessments. Once a potential COC has been identified, it is crucial to characterize sources, pathways, receptors and temporal patterns of exposure. For evaluation of inhalation exposures, ambient air monitoring data becomes increasingly important, although uncertainty around how air monitoring data correspond to personal exposures and specific health endpoints often remains. Initial stages of an exposure assessment may identify discrepancies between concentrations of COCs described in epidemiological or toxicological studies and concentrations to which the general population may be exposed. For example, design values from centrally-located monitors may be used in observational epidemiology studies to identify statistical correlations between concentrations and health endpoints of interest. However, when exposures are characterized for populations of interest, it may become apparent that it is unlikely individuals were routinely exposed to these levels, and therefore it is improbable that a particular health effect is due to the concentrations described in the study (i.e., an association is shown, but not causation). In conclusion, regulatory agencies often utilize problem formulation and exposure characterization along with weight of evidence criteria (such as the Hill criteria) to derive useful and robust risk assessments that can inform risk management determinations. Exposure assessments and problem formulation play major roles in these decisions.

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