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Society For Risk Analysis Annual Meeting 2007

Risk 007: Agents of Analysis

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

W3-E The Future of Toxicity Testing and Modeling Room: 205   2:00 - 3:30 PM

Chair(s): Gail Charnley

W3-E.1    Toxicity Testing in the 21st Century: A Vision and a Strategy. Anderson M*; The Hamner Institutes for Health Sciences   MAndersen@thehamner.org Abstract: Advances in molecular biology, bioinformatics, genomics, and computational toxicology are paving the way for substantive changes to our current approach to toxicity testing. Today, the strategy is primarily a patchwork of tests developed in the 1950s and 60s with newer protocols added as concerns have emerged over a wider variety of health outcomes, such as subtle neurotoxic effects or adverse immunologic changes. Recent scientific advances, however, have the potential for transforming the current system from one based on whole-animal studies to one based on in vitro methods using cells, cell lines, or cellular components, preferably of human origin. At the request of the US EPA, a National Research Council committee developed a long-range vision and strategic plan for toxicity testing. The core of the committee’s vision is a system based on the identification and use of toxicity pathways—cellular response pathways that, when sufficiently perturbed, are expected to result in adverse health effects—and dose-response characterizations of these pathways. The vision emphasizes the development of suites of predictive, high-throughput assays to evaluate biologically significant perturbations in key toxicity pathways. Targeted testing, which would involve some degree of whole-animal testing, would be used to complement the toxicity-pathway tests to ensure adequate evaluation. The committee emphasized that population-based and exposure information should be considered, as well as the question of what data are needed for decision-making. A long-term, large-scale effort will be needed to implement the vision proposed. A critical factor for success will be the transformative research to elucidate and identify toxicity pathways and to understand and apply the test results for risk assessment and decision-making. The committee concluded that a core research institute that fosters intramural and extramural research to address both knowledge and methods development is needed to achieve the vision.

W3-E.2    EPA’s ToxCast Program for Predicting Hazard and Prioritizing the Toxicity Testing of Environmental Chemicals. Dix DJ*; US Environmental Protection Agency   dix.david@epa.gov Abstract: Only a fraction of the 30,000 chemicals in U.S. commerce have been fully characterized for toxicity, and defining toxicity can take years and cost millions of dollars per chemical. An alternative is to perform a set of relatively inexpensive and rapid high throughput screening (HTS) assays, derive signatures predictive of effects or modes of chemical toxicity from the HTS data, then use these predictions to prioritize chemicals for more detailed analysis. The U.S. EPA has made a significant investment in this approach through its ToxCastTM program (www.epa.gov/comptox/toxcast), with the goal of building accurate predictive models for thousands of antimicrobials, pesticide inert ingredients, new and existing industrial chemicals, and drinking water candidate contaminants with limited toxicity data available for hazard and risk assessments. Phase I of ToxCast is a proof-of-concept utilizing 300 chemicals of known toxicity in over 400 HTS and genomic assays to generate a set of bioactivity profiles to develop and validate predictive toxicity signatures. Phase I chemicals are primarily pesticide active ingredients that have been extensively tested, with known properties relative to carcinogenicity, and developmental, reproductive and neural toxicity. Phase I data generation and analysis is expected to be complete in 2008. Phase II will focus on expansion of ToxCast predictive signatures, generating HTS data for additional chemicals and confirming the sensitivity and specificity of the signatures. Assuming success in the earlier phases, regulatory application of ToxCast in Phase III will measure ToxCast signatures for thousands of environmental chemicals of unknown toxicity, generating prioritization scores for more extensive testing and providing an affordable, science-based system for categorizing chemicals. This work was reviewed by U.S. EPA and approved for publication but does not necessarily reflect official Agency policy.

W3-E.3    Decision-making on toxicity testing – the Voluntary Children\\\'s Chemical Evaluation Program (VCCEP). Patterson J*, Dourson M; Toxicology Excellence for Risk Assessment   patterson@tera.org Abstract: The Voluntary Children’s Chemical Evaluation Program (VCCEP) pilot was designed to use both toxicity data and exposure information to estimate potential risks to children and to guide decision-making as to what, if any, additional toxicity tests would be needed to characterize risks to children. In the VCCEP, industry sponsors have prepared and submitted hazard and exposure assessments for review by an independent peer consultation panel of experts. Peer consultation reports have been issued (a summary of all opinions expressed) and the U.S. Environmental Protection Agency (EPA) then develops data needs decisions for each substance indicating what additional toxicity testing would be desired. By December 2007, 15 of the 20 sponsored chemicals will have completed the VCCEP Tier 1 peer consultation phase; over half already have final EPA decisions regarding data needs. The VCCEP risk assessments have provided a unique opportunity for risk assessment scientists to prepare and review a large number of comprehensive children’s risk assessments involving a variety of chemicals and exposure scenarios. This pilot has provided a significant body of experience in developing child-focused exposure assessments; characterizing risks to children, using hazard, exposure and risk characterization assessments to identify data gaps and data needs; and use of experts to discuss key issues, evaluate available data, and identify data needs. The talk will discuss the decision-making process about toxicity testing for children\\\'s risks as per the VCCEP pilot.

W3-E.4    Models in Environmental Regulatory Decision-Making . Whipple C*, Ryan L; ENVIRON International; Harvard School of Public Health   cwhipple@environcorp.com Abstract: Models have long played a critical role in environmental regulatory decision-making. Their use is fraught with difficulties and can be controversial. The National Research Council’s Committee on Models in the Regulatory Decision Process was tasked by the US EPA to assess the diverse applications and develop guidance for the development and use of environmental regulatory models. The committee’s report aims to provide an across-agency vision for applications of models in future environmental regulatory activities. The committee found that the agency has played a major role in advancing the science and use of environmental modeling. However, models will always be constrained by computational limitations, assumptions, and knowledge gaps. Scientific advances will never make it possible to build a perfect model that accounts for every aspect of reality or to prove that a given model is correct in all respects for a particular regulatory application. They can best be viewed as tools to inform decisions rather than as machines to generate truth or make decisions. This makes evaluation of a regulatory model more complex than solely a comparison of measurement data with model results. The committee recommended that model evaluation be viewed as an integral and ongoing part of the life cycle of a model, from problem formulation and model conceptualization to the development and application of a computational tool. Regulatory model evaluation must consider how accurately a particular model application represents the system of interest while being reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs may require different forms of peer review, uncertainty analysis, and extrapolation methods. The committee offers recommendations in three areas of the modeling process: (1) model evaluation; (2) principles for model development, selection, and application; and (3) model management.

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