Science to Support Decisions on Environmental Issues of National Importance Peter W. Preuss, Ph.D., Director National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency 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

1 “…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. 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.

2 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: 1.Licensing processes; such as for drug and medicines 2.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 3.Large industry effort; pharmaceutical and drug companies 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……….. (EPA’s research program; proposed 2010 budget ~ $580 Million)

3 Workshop on policy relevant science PHASE I: PROBLEM FORMULATION AND SCOPING 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 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 Management Options and Rulemaking/ PHASE III: RISK MANAGEMENT Workshop on problem and policy options Stakeholder Involvement Stage 3: Confirmation of Utility PHASE II: PLANNING AND CONDUCT OF RISK ASSESSMENT Stage 2: Risk Assessment NRC/NAS Advice Risk Assessment/ Risk Management External peer review and public comment Risk Characterization: Nature and magnitude of risks, key results and uncertainties Problem formulation, Scoping, Planning ~ 6 months Risk Assessment ~ 2 yrs Risk Management ~ 2 yrs Timeline PHASE II: PLANNING AND CONDUCT OF RISK ASSESSMENT Stage 1: Planning Implementation of Risk Based Decision-Making Framework… From problem formulation to rulemaking Includes Risk Managers

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

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

Linked Citations 6

Assessment Development Evergreen Literature Searches Additional studies Study Evaluation Data Extraction HERO Database Continuous, comprehensive literature review of peer-reviewed journal articles in multiple disciplines Additional studies identified from peer review, public comment Informative studies Highly Informative studies Policy-relevant studies Assessment 7

Data Extraction and Analysis 8

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

10 Table Noncancer effects in animals repeatedly exposed to chemical x by the oral route Reference/species Exposure (mg/kg- day) NOAELLOAEL Effect (mg/kg-day) Burek et al., 1980 F344 rat, M&F 0, 0.05, 0.2, 1, 5, or days in DW Degenerative nerve changes Hindlimb foot splay Decreased body weight Atrophy of testes & skeletal muscle Johnson et al., 1986 F344 rat, M&F 0, 0.01, 0.1, 0.5, or years in DW ND 2 ND Degenerative nerve changes (L Hindlimb foot splay Decreased body weight Early mortality after 24 weeks Other nonneoplastic lesions Friedman et al., 1995 F344 rat, M&F 0, 0.1, 0.5, or 2.0 (M) 0, 1.0, or 3.0 (F) 2 years in DW 0.5(M) 1.0(F) 2.0(M) 3.0(F) 2.0(M) 3.0(F) ND degenerative nerve changes (L Decreased body weight (8 – 9%) Early mortality after 60 weeks Other nonneoplastic lesions 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 Current Approach

11 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 Future Approach

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

EU’s REACH Program REACH: European Community’s regulation on chemicals and their safe use. Deals with the R egistration, E valuation, A uthorization and Restriction of Ch emical Substances. 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 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 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 REACH: An Expected Avalanche of Data

14 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.