Science to Support Decisions on Environmental Issues of National Importance

1. Science to Support Decisions on Environmental Issues of National Importance Presentation for the National Academy of Sciences Board of Research Data and Information Public Symposium: Scientific Data and Evidence Based Policy and Decision Making September 24, 2009 Peter W. Preuss, Ph.D., Director National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency

2. “…ensure that federal policies are based on the best and most unbiased scientific information.” Barack Obama National Academy of Sciences annual meeting April 27, 2009 • EPA leads the nation's environmental science, research, education and assessment efforts. • The mission of the Environmental Protection Agency is to protect human health and the environment. • Since 1970, EPA has been working for a cleaner, healthier environment for the American people. • http://www.epa.gov/epahome/aboutepa.htm However, in all but one or two program areas, EPA is asked to accomplish this weighty mission without a clear mandate or method to obtain the relevant scientific data and evidence on which to base a policy or regulatory decision.

3. Avenues for Scientific Data and Evidence Collection…other than EPA • In some areas, such as drug development and certain human diseases, there are established pathways to obtain relevant scientific information on potential effects: • Licensing processes; such as for drug and medicines • Large government research programs, such as the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Diseases (NIAID) • NIAID Proposed 2010 Budget ~$4.8 Billion • NCI Proposed 2010 budget ~$5 Billion • Large industry effort; pharmaceutical and drug companies (EPA’s research program; proposed 2010 budget ~ $580 Million) • All these pathways for data collection, except in the case of pesticides, do not really exist when it comes to environmental science for either human health issues or ecological issues. • The situation is worse for scientific data and evidence for ecological decision making (e.g., wetlands, fresh and marine water quality) • But in the absence of adequate data, EPA must still act………..

4. Implementation of Risk Based Decision-Making Framework… From problem formulation to rulemaking PHASE II: PLANNING AND CONDUCT OF RISK ASSESSMENT Stage 1: Planning PHASE II: PLANNING AND CONDUCT OF RISK ASSESSMENT Stage 2: Risk Assessment PHASE I: PROBLEM FORMULATION AND SCOPING Stage 3: Confirmation of Utility NRC/NAS Advice PHASE III: RISK MANAGEMENT Effects Assessment: concise evaluation and synthesis of most policy-relevant studies for hazard identification and dose-response Exposure Assessment: concise, quantitative assessment of nature and magnitude exposures Risk Characterization: Nature and magnitude of risks, key results and uncertainties Synopsis of views on the problem, a range of policy options and rationales Integrated Plan: timeline, key policy-relevant scientific questions and level of uncertainty and variability analyses Risk Management Options and Rulemaking/ RiskAssessment/ Risk Management Includes Risk Managers Includes Risk Managers Workshop on problem and policy options Workshop on policy relevant science External peer review and public comment External peer review and public comment Stakeholder Involvement Problem formulation, Scoping, Planning ~ 6 months Timeline Risk Assessment ~ 2 yrs Risk Management ~ 2 yrs

5. Health & Environmental Research Online EPA’s comprehensive system to identify, compile, characterize, analyze, synthesize and prioritize scientific studies. • Facilitates complete, sustainable and effective assessment development • Houses citations and study data from scientific literature • Includes studies in EPA’s priority areas • Efficient and intelligent information extraction and synthesis • Assures the highest scientific integrity in data quality. • Employs advanced searching and screening techniques using advanced algorithms • Utilizes rapid and comprehensive information retrieval • Provides transparency to stakeholders and the public 4

6. Literature Search and Screening Appealing design, relevancy ranking, faceted navigation Simultaneous search of multiple databases Vast repository of underlying content. Citations Visualization Clustering Theme Mapping Classification HERO Database Metadata: scientific discipline, agents, outcomes, etc. 5

7. Linked Citations 6

8. Assessment Development Assessment Informative studies are well-designed, properly implemented, with methods and results thoroughly described. Continuous, comprehensive literature review of peer-reviewed journal articles in multiple disciplines Highly Informative studies provide evidence on mode of action or potential susceptibility to effects, reduce uncertainty or exposure error, or offer innovative methods or designs. Informative studies HighlyInformativestudies Policy-relevantstudies Policy-relevant studies may include those conducted at or near relevant concentrations. Additional studies identified from peer review, public comment Citations from allstudies are included in the database for transparency and accessibility. HERO Database 7

9. Data Extraction and Analysis Scientists extract data from policy-relevant studies to use for cross-study analysis. Figures such as this ForestPlot show results at a glance. Links in the online PDF bring the reader to the full extracted data in the HERO Database. This easy-to-understand graphic distills complicated scientific data for use by policy-makers – including the EPA Administrator – and the public. 8

10. Decision Support Tools for High-Throughput Risk Assessment PURPOSE: To integrate modern computing and information technology with molecular biology to improve prioritization of data requirements and risk assessment of chemicals.

11. Current Approach • Large number of animals • Low throughput • Expensive • Time consuming • Pathology endpoints • Dose response extrapolations over a wide range • Application of uncertainty factors • Little focus on mode of action and biology • Few epidemiology studies

12. Future Approach • In vitro assays anchored by historic in vivo bioassays • Less expensive • Less time consuming • At exposure levels of interest hence, limited dose response extrapolations • Predictive tools of human health outcomes rather than uncertainty factors • Primary focus on modes of action and molecular biology • Molecular epidemiology studies

13. ToxCast in vitro data (467 assays) Cell Free HTS Multiplexed TF Human BioMap HCS qNPAs XMEs Impedance Genotoxicity Chemicals >200,000 dose response experiments 12

14. One million chemicals may eventually be evaluated. • Approximately 200,000 chemicals already have been preregistered for consideration. • Dossiers on 40,000 chemicals are anticipated by 2012. • REACH also emphasizes replacing in vivo with in vitro testing. • Under TSCA Section 8(e), new data from REACH will come to EPA. • Additionally, the proposed U.S. Kid’s Safe Chemicals Act may model REACH EU’s REACH Program REACH: An Expected Avalanche of Data REACH: European Community’s regulation on chemicals and their safe use. Deals with the Registration, Evaluation, Authorization and Restriction of Chemical Substances. • Government’s are ill prepared to utilize the volume and complexity of information coming our way. • Work is underway at U.S. EPA to prepare for the volume and type of REACH data. 13

15. The Changing Landscape of Human Health Risk Assessment • There are tens of thousands of chemicals that are untested and lack assessment of potential for human toxicity. • Current toxicology testing methods are too expensive, too slow, and can cope with too few chemicals. • Recent advances in biology and computer sciences are enabling research that could not have been anticipated even 10 years ago. • Toxicology approaches are evolving away from reliance on in vivo testing of laboratory animals • Current approaches to risk analysis need to be significantly modified to deal with more chemicals; innovative approaches (e.g. Screening application, Human health endpoint approach) • Next Generation (NexGen) risk assessment approaches are being discussed that can use the new data types and arrays (“omics”); case study approach • NexGen risk assessments -- Developing a proposed strategy to position EPA for the future and contribute to meaningful change within the larger risk assessment/risk management community.