Reeder Sams, Ph.D., Chief HPAG National Center for Environmental Assessment

1. Reeder Sams, Ph.D., Chief HPAG National Center for Environmental Assessment Office of Research and Development Human Health Risk Assessment and Information for SRP July 28, 2009

2. Basic Principles of Risk Assessment at EPA • The starting point for risk assessment is a critical analysis of available scientific information. • Quantitative estimates of risk are, to the extent possible, • Biologically-motivated, • Data-driven. • When there is insufficient data, default methods are used that • Protect public health, • Ensure scientific validity (i.e., scientifically plausible and extensively peer reviewed), and • Create an orderly and predictable process. • Implementation of these principles involves extensive peer review.

3. Risk Assessment / Risk Management Statutory and Legal Considerations Social Factors Public Health Considerations Risk Management Decisions Risk Management Options Economic Factors Political Considerations Dose-Response Assessment Hazard Identification Risk Characterization Exposure Assessment

4. Research Assessment Application Risk Assessments and Management Regulatory Programs, Regions Application Dose-Response Assessments (IRIS,Criteria Docs); Communication, support Assessments Methods, Models, Data NCEA Needs Risk Assessment Methods, Models for Extrapolation Guidelines for Interpretation NCEA/ RAF, NCER Data Synthesis And Modeling Toxicity Testing Research on Mode of Action (TK/TD), dose-response, etc Research on Exposure EPA Labs NCER Others (e.g., NTP, NCI) Data Generation 5

5. Human Health Assessment at EPA • NCEA occupies a critical position in EPA’s Office of Research and Development between: • the researchers in ORD labs who are generating new findings and data on human health • AND • the risk managers in the EPA program offices and regions who must make regulatory, enforcement, and remedial action decisions Statutory and Legal Considerations Dose-response Assessment Social Factors Public Health Considerations Hazard Identification Risk Management Decisions Risk Characterization Risk Management Options Exposure Assessment Economic Factors Political Considerations

6. NCEA’s Human Health Assessment work focuses on: • Conducting human health risk assessments and management of the Agency’s Integrated Risk Information System (IRIS) (e.g., tetrachloroethylene [perc], methyl tertiary butyl ether [MTBE], methanol, trichloroethylene [TCE], acrylamide, inorganic arsenic and 72 others underway) • Producing Integrated Science Assessments for air contaminants under Clean Air Act • Ozone – completed March 2006 • Lead – completed September 2006 • Particulate Matter -- underway • Nitrogen Oxides -- completed July 2008 • Sulfur dioxide -- completed September 2008 • Carbon Monoxide -- underway

7. NCEA: Human Health Assessment (continued) • Providing risk assessment research, methods, guidelines, training materials, and technical and regulatory support to EPA’s Program Offices and Regional Offices and the public • Uncertainty analysis • Identification of possible modes of action • Physiologically-Based Pharmacokinetics (PBPK) Modeling • Approaches to quantification • Approaches for Assessing Risk of Environmental Exposures to Age-Susceptible Populations (children, elderly) • Less than Lifetime Assessments • Approaches for cumulative risk assessment

8. EPA’s Human Health Risk Assessment Tools • Integrated Risk Information System (IRIS) • Exposure Factors Handbook • Child-Specific Exposure Factors Handbook • A Framework for Assessing Health Risk of Environmental Exposures to Children • Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (Final Report) • EPA’s Benchmark Dose Software (BMDS) www.epa.gov/ncea

9. EPA’s Integrated Risk Information System • IRIS provides qualitative and quantitative health effects information on over 540 substances • Addresses chronic exposures • Many high-profile, first applications of risk assessment guidelines and science policy • Reference Dose (RfD)/Reference Concentration (RfC) for non-cancer effects • Cancer risk: Hazard characterization, oral slope factors, and oral and inhalation unit risks • Improvements in transparency, public participation, and consistency • The new IRIS process was established on May 21, 2009 www.epa.gov/iris

10. Preparing for Change NAS/NRC Consultations

11. Conclusions • Human health risk assessment approaches are evolving in the presence of better understanding of biological mechanisms. • Significant uncertainties remain and are being addressed. • Questions remain about the direction of risk assessment. • Challenges for risk assessors: • Evaluate when additional data are important for decision-making • Consider the scale of assessment • Integrate information from various paradigms • Concepts of risk are changing, and continue to evolve.