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

2. National Center for Environmental Assessment 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 Dose-Response Assessment Risk Characterization Exposure Assessment Hazard Identification Risk Management Decisions Political Considerations Economic Factors Social Factors Statutory and Legal Considerations Public Health Considerations Risk Management Options

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

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

6. Office of Research and Development National Center for Environmental Assessment 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 NCEA’s Human Health Assessment work focuses on:

7. Office of Research and Development National Center for Environmental Assessment 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 NCEA: Human Health Assessment (continued)

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. Office of Research and Development National Center for Environmental Assessment 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 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 www.epa.gov/iris

10. Office of Research and Development National Center for Environmental Assessment Preparing for Change NAS/NRC Consultations 2007Toxicity Testing in the 21 st Century: A Vision and a Strategy 2007Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment 2008Phthalates and Cumulative Risk Assessment 2008 Science and Decisions-Advancing Risk Assessment 2009Toxicity Pathway-Based Risk Assessment: Preparing for Paradigm Change, May 11-13, 2009

11. Office of Research and Development National Center for Environmental Assessment 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.