Cumulative Risk Assessment at the U.S. Environmental Protection Agency: The Past, The Present and The Future

Transcription

1 Cumulative Risk Assessment at the U.S. Environmental Protection Agency: The Past, The Present and The Future Nhan Nguyen and Cathy Fehrenbacher Office of Chemical Safety and Pollution Prevention (OCSPP) Office of Pollution Prevention and Toxics (OPPT) United States Environmental Protection Agency (EPA) The views expressed in this presentation are those of the author and do not necessarily reflect the views or policies of the US EPA.

2 Acknowledgments For technical discussions, slides and general review: Glenn Rice - ORD Linda Teuschler - ORD Lawrence Martin - OSA, RAF Anjali Lamba - OCSPP Louis (Gino) Scarano - OCSPP Todd Stedeford - OCSPP Jennifer Seed - OCSPP September 2014 Combined Exp to Multiple Chem - Japanese Symposium 2

3 Outline Definition of Cumulative Risk Assessment (CRA) Introduction The United States Environmental Protection Agency (EPA, or the Agency ) Part 1: The Past Part 2: The Present Part 3: The Future September 2014 Combined Exp to Multiple Chem - Japanese Symposium 3

4 EPA s 2003 Definition of CRA (1 of 2) Cumulative risk is the combined risks from aggregate exposures to multiple agents or stressors, which may include chemicals, biological or physical agents Cumulative risk assessment is an analysis, characterization, and possible quantification of the combined risks to human health or the environment from multiple agents or stressors September 2014 Source: U.S. EPA Framework for Cumulative Risk Assessment. U.S. EPA/ORD/RAF, Washington, DC. EPA/600/P-02/001F. Available at: Combined Exp to Multiple Chem - Japanese Symposium 4

5 EPA s 2003 Definition of CRA (2 of 2) CRA is population-based with stakeholder emphasis and consideration of Vulnerability Factors: - Susceptibility/sensitivity (e.g., genetics, lifestages, disease states) - Differential exposure (e.g., homes close to pollutant sources, diet of locally caught fish or game) - Differential preparedness (e.g., lack of access to health care) - Differential ability to recover (e.g., poor nutrition) September 2014 Source: U.S. EPA Framework for Cumulative Risk Assessment. U.S. EPA/ORD/RAF, Washington, DC. EPA/600/P-02/001F. Available at: Combined Exp to Multiple Chem - Japanese Symposium 5

6 Introduction This is going to be a simple, overview presentation of cumulative risk assessment in EPA with other related details provided in extra slides Many references and links are also provided September 2014 Combined Exp to Multiple Chem - Japanese Symposium 6

7 The US EPA Our Mission is to protect human health and the environment. September 2014 Combined Exp to Multiple Chem - Japanese Symposium 7

8 Where Pesticides and Industrial Chemicals are Located OCSPP (1,078 People) OSWER (529 People) The US EPA: 16,205 People Office of Administrator (415 People) OAR (1,177 People) ORD (1,802 People) Yellow Program Red Research Green - Regions Where the Administrative Part of the Risk Assessment Forum is Located OW (590 People) Regional Offices 10 of them (7,702 People) Where the Superfund Program is Administered Where all of EPA s national laws are carried out; including the Superfund Program is Implemented September 2014 Combined Exp to Multiple Chem - Japanese Symposium 8

9 Other Agencies Also Dept. of Health and Human Services (DHHS) Food and Drug Administration (FDA) National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP) Centers for Disease Control and Prevention (CDC) Agency for Toxic Substances Disease Registry (ATSDR) National Health and Nutrition Exposure Survey (NHANES) National Institute for Occupational Safety and Health (NIOSH) Occupational Safety and Health Administration (OSHA) Consumer Product Safety Commission (CPSC) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 9

10 Government Agencies and CRA Individual Groups and Laws Within EPA (air, water, solid waste, pesticides) Across government (pharmaceuticals, chemicals, consumer products, occupational exposures) Difficult to have a single, focused approach for something as complicated as CRA September 2014 Combined Exp to Multiple Chem - Japanese Symposium 10

11 The Reasons to Perform a CRA ( Initiating Factors ) 1 of 2 Federal Laws Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), 1980 (also known as Superfund ) Chemical-centric site evaluations including mixtures Safe Drinking Water Act Amendments, 1996 Mixtures of contaminants (chemicals, microbes) in drinking water Clean Air Act, 1990 Air toxic mixtures, sensitive/differentially exposed populations Food Quality Protection Act (FQPA), 1996 CRA of pesticides mixtures with common toxicity Consumer Product Safety Improvement Act, 2008 CRA of phthalate mixtures for children s products September 2014 Combined Exp to Multiple Chem - Japanese Symposium 11

12 The Reasons to Perform a CRA (2 of 2) Executive Order (February 11, 1994) (Directive from the President of the US, does not require Congressional approval) Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations At-risk, differentially impacted communities Vulnerable populations (e.g., children, native Americans) Other reasons: The existence of sources/releases of pollutants to the environment Disease or illness occurrence/cluster (either human health or eco) Concentration of chemicals in environmental media September 2014 Combined Exp to Multiple Chem - Japanese Symposium 12

13 Part 1: The (Recent) Past Important Reports EPA Outside of EPA October 2010 Internal EPA Meeting September 2014 Combined Exp to Multiple Chem - Japanese Symposium 13

14 U.S. EPA Reports on CRA Theory and Practice Risk Assessment Guidance for Superfund ( ) Methodology for Multipathway Exposures to Combustor Emissions (1998) Five CRA s & Guidance on Cumulative Risk of Pesticides (2002b;2006a,b,c;2007a; 2011) Office of Solid Waste and Emergency Response Used by Regions Air Program Concepts, Methods and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document (2007b) Pesticides Published by Office of Research and Development Toolbox September 2014 Combined Exp to Multiple Chem - Japanese Symposium 14

15 U.S. EPA Reports on CRA Theory and Practice: Risk Assessment Forum Planning & Scoping for Cumulative Risk Assessment (1997) Planning & Scoping Lessons Learned (2002a) Five White Papers on CRA Published in Open Literature: Directions for CRA, Vulnerability, Combined Effects of Multiple Stressors, Environmental Mixtures, Biomarkers (2007c) Guidance for Assessing Health Risks of Chemical Mixtures (1986, 2000) Framework for Cumulative Risk Assessment (2003) Continuing: Workshops in 2011, 2012, 2014 Expert Panel in 2013 September 2014 And more to come. Combined Exp to Multiple Chem - Japanese Symposium 15

16 Other Reports (non-epa) NAS and NRC multiple reports from Including Science and Decisions (2009) and Phthalates and Cumulative Risk Assessment (2008) Presidential/Congressional Commission on Risk Assessment /Risk Management DHHS, ATSDR 2004 International World Health Organization (WHO 2007) European Union (EU) 2009 Mixtures Report September 2014 Combined Exp to Multiple Chem - Japanese Symposium 16

17 US EPA Internal Meeting in October, 2010: Convened to Address Recent NAS Reports (1 of 2) Science & Decisions (2009) Recommendations EPA should draw on other approaches to incorporate interactions between chemical and nonchemical stressors Ecological Risk Assessment Social Epidemiology Increase role of biomonitoring, epidemiologic, and surveillance data Develop guidelines and methods for simpler analytical tools Feb 18, 2014 Combined Exp to Multiple Chem - Japanese Symposium 17

18 US EPA Internal Meeting in October, 2010: Convened to Address Recent NAS Reports (2 of 2) Phthalates & CRA (2008) Recommendations Focus on common health outcomes Group chemicals by common adverse outcomes Feb 18, 2014 Combined Exp to Multiple Chem - Japanese Symposium 18

19 Part 2: The Present The EPA Risk Assessment Forum Other EPA Activities Program offices, Regions and research September 2014 Combined Exp to Multiple Chem - Japanese Symposium 19

20 What is the Risk Assessment Forum (RAF)? The Office of the Science Advisor (OSA), provides leadership for cross-agency science and technology policy and facilitates its integration into the Agency s programs and decisions. The RAF in the OSA is an appointed committee of senior EPA scientists who develop Agency-wide consensus on risk assessment issues and risk assessment guidance. The RAF establishes technical panels to undertake substantive initiatives, such as the Cumulative Risk Assessment Technical Panel. The CRA Technical Panel is charged with development of the CRA Guidelines. September 2014 Combined Exp to Multiple Chem - Japanese Symposium 20

21 The RAF CRA Technical Panel Established in 1997 Current membership is at end of presentation Over 30 scientists from across the agency Important to recognize it is separate from their daily work We will talk more about the RAF under The Future September 2014 Combined Exp to Multiple Chem - Japanese Symposium 21

22 But let s look at the rest of EPA for now National, overarching CRA efforts: Pesticides Water Air More local (place-based or geographic boundaries) Superfund Regional Office of Research and Development ORD Office of Chemical Safety and Pollution Prevention - OCSPP September 2014 Combined Exp to Multiple Chem - Japanese Symposium 22

23 Example Program Office Applications of CRA Concepts (1 of 2) Office of Solid Waste and Emergency Response (OSWER) Planning and scoping phase (typically done for site-specific risk assessments) Stakeholder involvement Potentially vulnerable receptors evaluated (e.g., young children, workers) (generally done for site-specific risk assessments) Multiple chemicals/multiple exposure pathways (e.g., soil, water, air) Office of Chemical Safety and Pollution Prevention (OCSPP) Multiple pesticides, all pathways of dietary and nondietary exposures Toxicity adjustments (e.g., of relative potency factors) for exposures to children Exposure assessments incorporate behavioral and environmental factors Develop approaches for CRA of adverse outcomes (e.g., CRA of phthalates) Begin identifying and compiling case studies and applications of CRA incorporating occupational scenarios September 2014 Combined Exp to Multiple Chem - Japanese Symposium 23

24 Example Program Office Applications of CRA Concepts (1 of 2) Office of Air and Radiation (OAR) Chemical mixture risk assessment methods used to assess health risks from multiple air toxics under National Air Toxics Assessment (NATA), Petroleum Refinery Sector Risk and Technology Review (RTR) rules Exposure estimates consider inhalation, and where data permit, ingestion Office of Water (OW) Regulates some chemical groups as mixtures (e.g., trihalomethanes, haloacetic acids) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 24

25 Office of Research and Development (ORD) Research and Publications Annual Course at Society of Risk Analysis (SRA) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 25

26 Objectives: CRA Toolbox (Appendix A of U.S. EPA, 2007) Consolidate resources for cumulative risk assessors Include notes to help facilitate application Provide coverage for key elements of the assessment process Organized into 5 main topic areas: Planning, scoping and problem formulation Environmental fate and transport analyses Exposure analysis Toxicity analysis Risk/uncertainty characterization, presentation of results Reflects >70 resources; updates are planned (MacDonell et al. 2013) Example resources from the CRA Toolbox are shown at the end Online at: September 2014 Combined Exp to Multiple Chem - Japanese Symposium 26

27 Office of Pesticide Programs (1 of 2) FQPA of 1996 requires EPA to do CRA Methods based on common mechanism of action (guidance document (US EPA 2002) - Five common groups have been formed so far - htm#op : Organophosphates (2001, 2002, 2006) acetylcholinesterase inhibition (via phsophorylation) 50 pesticides Triazines (2006) disruption of hypothalamic-pituitary-gonadal (HPG) axis in neuroendocrine development- Three pesticides (plus metabolites) Chloroacetanilides (2006) formation of nasal turbinate tumors via common tissue reactive metabolites - Three pesticides (plus metabolites) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 27

28 Office of Pesticide Programs (2 of 2) N-methyl carbamates (2007) acetylcholinesterase inhibition (via carbamylation) Ten pesticides Pyrethrins/pyrethroids (2011) shared structural characteristics, disruption of voltage-gated sodium channels leading to alteration of neuronal membranes and ultimately neurotoxicity 33 pesticides Because pesticide CRA is based on common mechanism, assumed dose addition (used relative potency factor, or RPF approach) and because pesticide registration requires much information no data gaps. September 2014 Combined Exp to Multiple Chem - Japanese Symposium 28

29 Office of Air National Air Toxics Assessment (NATA) (1 of 2) Latest report (2005) evaluates human health endpoints for 187 air pollutants Is a screening approach Looked at cancer and non-cancer separately Combined cancer effects by summing unit risk estimates (regardless of cancer type or mode of action) Combined non-cancer effects using hazard index method (i.e., the summing of hazard quotients) Did for two endpoints (neuroxicity and respiratory effects) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 29

30 Air/NATA 2 of 2 When no data on cancer/non-cancer were available, a value of zero was used for summation purposes (and no individual chemical evaluation was reported) (an overview of the methods published in 2011) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 30

31 Other Activities in US NAS Emerging Science meeting on CRA (July, 2011) - NIEHS Workshop (September, 2011) - Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects International Toxicology of Mixtures Conference (October, 2011) soon to be special issue of Toxicology (Elsevier) Toxicology and Risk Assessment Conference TRAC (May, 2012) course on: Cumulative Risk Assessment: Grouping and Analyzing Combined Chemical, Biological, Physical and Socio-Economic Stressors - EPA Progress review on external grants on CRA May, Alliance for Risk Assessment (ARA) May, 2012 non-profit effort to advance methods in risk assessment science post as response to NAS reports - September 2014 Combined Exp to Multiple Chem - Japanese Symposium 31

32 Part III: The Future The EPA RAF CRA Panel September 2014 Combined Exp to Multiple Chem - Japanese Symposium 32

33 EPA Risk Assessment Forum (RAF) Cumulative Risk Assessment (CRA) Technical Panel Charge to Panel: Write Agency Guidelines for CRA Panel History Established in 1997 Developed Framework Document in 2003 Developed case studies via seminar series/workshops in (end product still being developed) Re-invigorated in July 2010 Developed outline for Agency Guidelines for CRA in 2011 Writing teams established in September 2014 Combined Exp to Multiple Chem - Japanese Symposium 33

34 EPA s RAF CRA Guidelines Effort Current CRA Technical Panel in place since Efforts include: Draft CRA Guidelines outline Cross-EPA writing teams Draft workshop report on integrating chemical and nonchemical stressors Defining CRA terms (e.g., vulnerability, sensitivity) Draft report on EPA s use of dose addition in risk assessments Developing CRA tools and approaches for planning, scoping, problem formulation, risk communication, risk analysis, risk characterization Public webinar series on CRA science issues [jointly sponsored with EPA s National Center for Environmental Research (NCER)] Need for Collaborative Efforts Coordinate across EPA program and other offices and regions Address aspects of CRA under the purview of other Federal/State agencies Cultivate partnerships with academia, private industry, tribes, environmental groups, etc. September 2014 Combined Exp to Multiple Chem - Japanese Symposium 34

35 CRA Guidelines Science Challenges and Research Issues (1 of 2) Chemical and nonchemical stressors and vulnerability factors Identify and determine relative importance Grouping and analysis strategies for diverse stressors Analysis tiers graded by data availability/quality, resources, need e.g., higher tier analyses may require multiple-route internal doses of chemicals or emergency room visit incidence for a specific disease endpoint Joint exposure distributions for stressor combinations Identify local at-risk populations and geographic areas Address problems combining national database information (e.g., NHANES, Census, Toxic Release Inventory) September 2014 Combined Exp to Multiple Chem - Japanese Symposium 35

36 CRA Guidelines Science Challenges and Research Issues (2 of 2) Need methods and data to inform health impacts of stressor combinations Epidemiology studies/methods Traditional / high throughput toxicology Extend chemical mixture risk assessment methods to analyze diverse stressors Develop cumulative risk communication strategies for stakeholders and risk managers Consider data and resource limitations, statutory requirement constraints September 2014 Combined Exp to Multiple Chem - Japanese Symposium 36

37 Conclusions on CRA Readiness (1 of 2) CRA focus is important for getting environmental health risk assessment right Evaluate real world exposures and recognize population vulnerabilities Accurate and complete CRAs should result in improved environmental decision-making and risk management Vulnerable populations (e.g., children, differentially exposed populations) should benefit from the conduct of CRAs Scientific challenges limit EPA s current ability to implement CRA EPA research plans and efforts are in place to fill gaps in available data and methods, but some science is immature Primary focus to identify, measure and determine the importance of combinations of chemical and nonchemical stressors, including population vulnerabilities and buffers September 2014 Combined Exp to Multiple Chem - Japanese Symposium 37

38 Conclusions on CRA Readiness (2 of 2) CRA Guidelines are needed to span program office and regional responsibilities while keeping EPA activities within legal mandates Some aspects of CRA are already practiced by many organizations within EPA; multi-route/pathways exposures to chemical mixtures are commonly evaluated; vulnerable populations are often considered September 2014 Combined Exp to Multiple Chem - Japanese Symposium 38

39 References (EPA 1 of 3) U.S. EPA Guidelines for the Health Risk Assessment of Chemical Mixtures. U.S. EPA/ORD, Washington, DC. September. EPA/630/R-98/002. U.S. EPA Guidance on Cumulative Risk Assessment, Part 1. Planning and Scoping. U.S. EPA/SPC, Washington, DC. Attachment to memo dated July 3, 1997 from the Administrator, Carol Browner, and Deputy Administrator, Fred Hansen, titled Cumulative Risk Assessment Guidance- Phase I Planning and Scoping. Available at: U.S. EPA Risk Assessment Guidance for Superfund: Volume 1, Human Health Evaluation Manual (Part A). U.S. EPA/OERR, Washington, DC. EPA/540/1-89/002. (Also see Parts B-D.) U.S. EPA Guidance on Cumulative Risk Assessment, Part 1. Planning and Scoping. U.S. EPA/SPC, Washington, DC. Attachment to memo dated July 3, 1997 from the Administrator, Carol Browner, and Deputy Administrator, Fred Hansen, titled Cumulative Risk Assessment Guidance- Phase I Planning and Scoping. Available at: U.S. EPA Methodology for Assessing Health Risks Associated with Multiple Pathways of Exposure to Combustor Emissions. U.S. EPA/ORD/NCEA, Cincinnati, OH. December. EPA/600/R- 98/137. U.S. EPA Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures. U.S. EPA/RAF, Washington, DC. EPA/630/R-00/002. Available at: U.S. EPA. 2002a. Lessons Learned on Planning and Scoping of Environmental Risk Assessment. Memorandum from Science Policy Council. January. Available at: U.S. EPA Framework for Cumulative Risk Assessment. U.S. EPA/ORD/NCEA, Washington, DC. EPA/600/P-02/001F. Available at: September 2014 Combined Exp to Multiple Chem - Japanese Symposium 39

40 References (EPA - 2 of 3) PESTICIDES: U.S. EPA. 2002b. Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity. U.S.EPA/OPP, Washington, DC. Available at: U.S. EPA Framework for Cumulative Risk Assessment. U.S. EPA/ORD/NCEA, Washington, DC. EPA/600/P-02/001F. Available at: U.S. EPA. 2006a. Organophosphorus Cumulative Risk Assessment 2006 Update. U.S. EPA/OPP, Washington, DC. Available at: op/op_cra_main.pdf U.S. EPA. 2006b. Cumulative Risk from Triazine Pesticides. U.S. EPA/OPP, Washington, DC. Available at: U.S. EPA. 2006c. Cumulative Risk from Chloroacetanalide Pesticides. U.S. EPA/OPP, Washington, DC. Available at: U.S. EPA. 2007a. Revised N-Methyl Carbamate Cumulative Risk Assessment. U.S. EPA/OPP, Washington, DC. Available at: U.S. EPA. 2011, Pyrethroids/Pyrethrins Cumulative Risk Assessment. U.S. EPA/OPP, Washington, DC. Available at September 2014 Combined Exp to Multiple Chem - Japanese Symposium 40

41 References (EPA - 3 of 3) U.S. EPA Concepts, Methods and Data Sources for Health Risk Assessment of Multiple Chemicals, Exposures and Effects. U.S. EPA/NCEA, Cincinnati, OH. EPA/600/R-06/013A. Available at: U.S. EPA. 2007c. U.S. EPA. Risk Assessment Forum White Papers on Cumulative Risk: Callahan, M.A. and K. Sexton If cumulative risk assessment is the answer, what is the question? Environ Health Perspect 115(5): ; defur, P.L. et al Vulnerability as a function of individual and group resources in cumulative risk assessment. Environ Health Perspect 115(5): ; Menzie, C.A. et al A phased approach for assessing combined effects from multiple stressors. Environ Health Perspect 115(5): ; Ryan, P.B. et al Using biomarkers to inform cumulative risk assessment. Environ Health Perspect 115(5): ; Sexton, K. and D. Hattis Assessing cumulative health risks from exposure to environmental mixtures Three fundamental questions. Environ Health Perspect 115(5): EPA-funded research for (through NCER): cords_per_page/all September 2014 Combined Exp to Multiple Chem - Japanese Symposium 41

42 Other References Agency for Toxic Substances and Disease Registry (ATSDR) Guidance manual for the assessment of joint toxic actions of chemical mixtures. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.: European Commission Mixtures report (2009): NRC Understanding Risk Informing Decisions in a Democratic Society. NRC Phthalates and Cumulative Risk Assessment: The Tasks Ahead. NRC Science and Decisions: Advancing Risk Assessment. Presidential/Congressional Commission on Risk Assessment and Risk Management, (PCCRARM) vols Teuschler, LK, GE Rice, CR Wilkes, JC Lipscomb, FW Power A Feasibility Study of Cumulative risk Assessment Methods for Drinking Water Disinfection By- Product Mixtures, Journal of Tox Env. Health (Part A), (67): September 2014 Combined Exp to Multiple Chem - Japanese Symposium 42