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Science and Decisions: Advancing Risk Assessment
SCIENCE AND DECISIONS
Advancing Risk Assessment
Committee on Improving Risk Analysis Approaches Used by the U.S. EPA
Board on Environmental Studies and Toxicology
Division on Earth and Life Studies
NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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Science and Decisions: Advancing Risk Assessment
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This project was supported by Contract EP-C-06-056 between the National Academy of Sciences and the U.S. Environmental Protection Agency. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
Library of Congress Cataloging-in-Publication Data
National Research Council (U.S.). Committee on Improving Risk Analysis Approaches Used by the U.S. EPA.
Science and decisions : advancing risk assessment / Committee on Improving Risk Analysis
Approaches Used by the U.S. EPA, Board on Environmental Studies and Toxicology, Division on Earth and Life Studies.
p. cm.
Includes bibliographical references.
ISBN-13: 978-0-309-12046-3 (pbk.)
ISBN-10: 0-309-12046-2 (pbk.)
ISBN-13: 978-0-309-12047-0 (pdf)
ISBN-10: 0-309-12047-0 (pdf)
1. Environmental risk assessment—United States. 2. Technology—Risk assessment—United States. 3. Health risk assessment—United States. I. National Research Council (U.S.). Board on Environmental Studies and Toxicology. II. National Research Council (U.S.). Division on Earth and Life Studies. III. Title.
GE150.N37 2009
361.1—dc22
2008055771
Additional copies of this report are available from
The National Academies Press
500 Fifth Street, NW Box 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.edu
Copyright 2009 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
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Science and Decisions: Advancing Risk Assessment
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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Science and Decisions: Advancing Risk Assessment
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Science and Decisions: Advancing Risk Assessment
COMMITTEE ON IMPROVING RISK ANALYSIS APPROACHES USED BY THE U.S. ENVIRONMENTAL PROTECTION AGENCY
Members
THOMAS A. BURKE (Chair),
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
A. JOHN BAILER,
Miami University, Oxford, OH
JOHN M. BALBUS,
Environmental Defense, Washington, DC
JOSHUA T. COHEN,
Tufts Medical Center, Boston, MA
ADAM M. FINKEL,
University of Medicine and Dentistry of New Jersey, Piscataway, NJ
GARY GINSBERG,
Connecticut Department of Public Health, Hartford, CT
BRUCE K. HOPE,
Oregon Department of Environmental Quality, Portland, OR
JONATHAN I. LEVY,
Harvard School of Public Health, Boston, MA
THOMAS E. MCKONE,
University of California, Berkeley, CA
GREGORY M. PAOLI,
Risk Sciences International, Ottawa, ON, Canada
CHARLES POOLE,
University of North Carolina School of Public Health, Chapel Hill, NC
JOSEPH V. RODRICKS,
ENVIRON International Corporation, Arlington, VA
BAILUS WALKER, JR.,
Howard University Medical Center, Washington, DC
TERRY F. YOSIE,
World Environment Center, Washington, DC
LAUREN ZEISE,
California Environmental Protection Agency, Oakland, CA
Staff
EILEEN N. ABT, Project Director
JENNIFER SAUNDERS, Associate Program Officer (through December 2007)
NORMAN GROSSBLATT, Senior Editor
RUTH CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Manager,
Technical Information Center
RADIAH A. ROSE, Editorial Projects Manager
MORGAN R. MOTTO, Senior Program Assistant (through February 2008)
PANOLA GOLSON, Senior Program Assistant
Sponsor
U.S. ENVIRONMENTAL PROTECTION AGENCY
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Science and Decisions: Advancing Risk Assessment
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1
Members
JONATHAN M. SAMET (Chair),
University of Southern California, Los Angeles
RAMÓN ALVAREZ,
Environmental Defense Fund, Austin, TX
JOHN M. BALBUS,
Environmental Defense Fund, Washington, DC
DALLAS BURTRAW,
Resources for the Future, Washington, DC
JAMES S. BUS,
Dow Chemical Company, Midland, MI
RUTH DEFRIES,
Columbia University, New York, NY
COSTEL D. DENSON,
University of Delaware, Newark
E. DONALD ELLIOTT,
Willkie, Farr & Gallagher LLP, Washington, DC
MARY R. ENGLISH,
University of Tennessee, Knoxville
J. PAUL GILMAN,
Covanta Energy Corporation, Fairfield, NJ
JUDITH A. GRAHAM (Retired),
Pittsboro, NC
WILLIAM M. LEWIS, JR.,
University of Colorado, Boulder
JUDITH L. MEYER,
University of Georgia, Athens
DENNIS D. MURPHY,
University of Nevada, Reno
DANNY D. REIBLE,
University of Texas, Austin
JOSEPH V. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEAD G. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERT F. SAWYER,
University of California, Berkeley
KIMBERLY M. THOMPSON,
Harvard School of Public Health, Boston, MA
MARK J. UTELL,
University of Rochester Medical Center, Rochester, NY
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies
EILEEN N. ABT, Senior Program Officer for Risk Analysis
SUSAN N.J. MARTEL, Senior Program Officer for Toxicology
KULBIR BAKSHI, Senior Program Officer
ELLEN K. MANTUS, Senior Program Officer
RUTH E. CROSSGROVE, Senior Editor
1
This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.
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Science and Decisions: Advancing Risk Assessment
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)
Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008)
Respiratory Diseases Research at NIOSH (2008)
Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)
Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)
Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)
Models in Environmental Regulatory Decision Making (2007)
Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)
Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)
Environmental Impacts of Wind-Energy Projects (2007)
Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)
Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)
New Source Review for Stationary Sources of Air Pollution (2006)
Human Biomonitoring for Environmental Chemicals (2006)
Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)
Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)
State and Federal Standards for Mobile-Source Emissions (2006)
Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)
Health Implications of Perchlorate Ingestion (2005)
Air Quality Management in the United States (2004)
Endangered and Threatened Species of the Platte River (2004)
Atlantic Salmon in Maine (2004)
Endangered and Threatened Fishes in the Klamath River Basin (2004)
Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)
Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)
Biosolids Applied to Land: Advancing Standards and Practices (2002)
The Airliner Cabin Environment and Health of Passengers and Crew (2002)
Arsenic in Drinking Water: 2001 Update (2001)
Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)
Compensating for Wetland Losses Under the Clean Water Act (2001)
A Risk-Management Strategy for PCB-Contaminated Sediments (2001)
Acute Exposure Guideline Levels for Selected Airborne Chemicals (seven volumes, 2000-2008)
Toxicological Effects of Methylmercury (2000)
Strengthening Science at the U.S. Environmental Protection Agency (2000)
Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)
Ecological Indicators for the Nation (2000)
Waste Incineration and Public Health (2000)
Hormonally Active Agents in the Environment (1999)
Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)
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Science and Decisions: Advancing Risk Assessment
The National Research Council’s Committee on Toxicology: The First 50 Years (1997)
Carcinogens and Anticarcinogens in the Human Diet (1996)
Upstream: Salmon and Society in the Pacific Northwest (1996)
Science and the Endangered Species Act (1995)
Wetlands: Characteristics and Boundaries (1995)
Biologic Markers (five volumes, 1989-1995)
Science and Judgment in Risk Assessment (1994)
Pesticides in the Diets of Infants and Children (1993)
Dolphins and the Tuna Industry (1992)
Science and the National Parks (1992)
Human Exposure Assessment for Airborne Pollutants (1991)
Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)
Decline of the Sea Turtles (1990)
Copies of these reports may be ordered from the National Academies Press
(800) 624-6242 or (202) 334-3313
www.nap.edu
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Science and Decisions: Advancing Risk Assessment
Preface
Risk assessment has become a dominant public-policy tool for informing risk managers and the public about the different policy options for protecting public health and the environment. Risk assessment has been instrumental in fulfilling the missions of the U.S. Environmental Protection Agency (EPA) and other federal and state agencies in evaluating public-health concerns, informing regulatory and technologic decisions, setting priorities for research and funding, and developing approaches for cost-benefit analyses.
However, risk assessment is at a crossroads. Despite advances in the field, it faces a number of substantial challenges, including long delays in completing complex risk assessments, some of which take decades to complete; lack of data, which leads to important uncertainty in risk assessments; and the need for risk assessment of many unevaluated chemicals in the marketplace and emerging agents. To address those challenges, EPA asked the National Academies to develop recommendations for improving the agency’s risk-analysis approaches.
In this report, the Committee on Improving Risk Analysis Approaches Used by the U.S. EPA conducts a scientific and technical review of EPA’s current risk-analysis concepts and practices and offers recommendations for practical improvements that EPA could make in the near term (2-5 y) and in the longer term (10-20 y). The committee focused on human health risk assessment but considered the implications of its conclusions and recommendations for ecologic risk assessment.
This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of this report: Lawrence W. Barnthouse, LWB Environmental Services, Inc.; Roger G. Bea, University of California, Berkeley; Allison C. Cullen, University of Washington; William H. Farland, Colorado State University; J. Paul
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Science and Decisions: Advancing Risk Assessment
Gilman, Convanta Energy Corporation; Bernard D. Goldstein, University of Pittsburgh; Lynn R. Goldman, Johns Hopkins University; Dale B. Hattis, Clark University; Carol J. Henry, American Chemistry Council (retired); Daniel Krewski, University of Ottawa; Amy D. Kyle, University of California, Berkeley; Ronald L. Melnick, National Institute of Environmental Health Sciences; Gilbert S. Omenn, University of Michigan Medical School; Louise Ryan, Harvard School of Public Health; and Detlof von Winterfeldt, University of Southern California.
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by the review coordinator, William Glaze, Georgetown, TX and the review monitor, John Ahearne, Sigma Xi. Appointed by the National Research Council, they were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the committee and the institution.
The committee gratefully acknowledges the following for making presentations to the committee: Nicholas Ashford, Massachusetts Institute of Technology; Robert Brenner, Michael Callahan, George Gray, Jim Jones, Tina Levine, Robert Kavlock, Al McGartland, Peter Preuss, Michael Shapiro, Glenn Suter, and Harold Zenick, EPA; Douglas CrawfordBrown, University of North Carolina; Kenny Crump, ENVIRON International Corporation; Robert Donkers, Delegation of the European Commission to the United States; William Farland, Colorado State University; James A. Fava, Five Winds International; Penny FennerCrisp, International Life Sciences Institute Research Foundation; Dale Hattis, Clark University; Amy D. Kyle, University of California, Berkeley; Rebecca Parkin, George Washington University; Chris Portier, National Institute of Environmental Health Sciences; Lorenz Rhomberg, Gradient Corporation; Jennifer Sass, Natural Resources Defense Council; Jay Silkworth, General Electric Company; and Thomas Sinks, Centers for Disease Control and Prevention.
The committee is thankful for the useful input of Roger Cooke, Resources for the Future and Dorothy Patton, Environmental Protection Agency (retired) in the early deliberations of this study. The committee is also grateful for the assistance of the National Research Council staff in preparing this report. Staff members who contributed to this effort are Eileen Abt, project director; James Reisa, director of the Board on Environmental Studies and Toxicology; Jennifer Saunders, associate program officer; Norman Grossblatt and Ruth Crossgrove, senior editors; Mirsada Karalic-Loncarevic, manager of the Technical Information Center; Radiah Rose, editorial projects manager; and Morgan Motto and Panola Golson, senior program assistants.
I would especially like to thank the committee members for their efforts throughout the development of this report.
Thomas Burke, Chair
Committee on Improving Risk Analysis Approaches Used by the U.S. EPA
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Science and Decisions: Advancing Risk Assessment
Abbreviations
ARARs Applicable or Relevant and Appropriate Requirements
ATSDR Agency for Toxic Substances and Disease Registry
BMD benchmark dose
CARE Community Action for a Renewed Environment
CASAC Clean Air Scientific Advisory Committee
CBPR community-based participatory research
CERCLA Comprehensive Environmental Response Compensation and Liability Act
CTE central tendency exposure
DBP dibutyl phthalate
DBPs disinfection byproducts
EPA U.S. Environmental Protection Agency
EPHT Environmental Public Health Tracking Program
FIFRA Federal Insecticide, Fungicide and Rodenticide Act
FQPA Food Quality Protection Act
GAO Government Accountability Office
GIS geographic information systems
HAPs hazardous air pollutants
HI hazard index
IARC International Agency for Research on Cancer
IPCS International Program on Chemical Safety
IRIS Integrated Risk Information System
LNT linear, no-threshold
MACT maximum achievable control technology
MCL maximum contaminant level
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Science and Decisions: Advancing Risk Assessment
MCLG maximum contaminant level goal
MeCl2 methylene chloride
MEI maximally exposed individual
MOA mode of action
MOE margin of exposure
MTD maximum tolerated dose
NAAQS National Ambient Air Quality Standards
NCEA National Center for Environmental Assessment
NEJAC National Environmental Justice Advisory Council
NER National Exposure Registry
NHANES National Health and Nutrition Examination Survey
NOAEL no-observed-adverse-effect level
NPL National Priorities List
NRC National Research Council
NTP National Toxicology Program
OAR Office of Air and Radiation
OP organophosphate
OPPTS Office of Prevention, Pesticides and Toxic Substances
OSWER Office of Solid Waste and Emergency Response
OW Office of Water
PBPK physiologically based pharmacokinetic
PD pharmacodynamic
PDF probability density function
PK pharmacokinetic
POD point of departure
PPDG Pesticide Program Dialogue Group
RAGS Risk Assessment Guidance for Superfund
Red Book Risk Assessment in the Federal Government: Managing the Process
RfC reference concentration
RfD reference dose
RI/FS remedial investigation and feasibility study
RME reasonable maximum exposure
ROD record of decision
RR relative risk
RRM relative risk model
SDWA Safe Drinking Water Act
SEP socioeconomic position
TCA 1,1,1-trichloroethane
TCE trichloroethylene
TSCA Toxic Substances Control Act
UF uncertainty factor
VOI value-of-information
WHO World Health Organization
WOE weight-of-evidence
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Science and Decisions: Advancing Risk Assessment
Contents
SUMMARY
3
1
INTRODUCTION
15
Background,
16
Challenges,
17
Traditional and Emerging Views of the Roles of Risk Assessment,
18
Technical Impediments to Risk Assessment,
20
Improving Risk Analysis,
21
The National Research Council Committee,
22
Organization of the Report,
23
References,
24
2
EVOLUTION AND USE OF RISK ASSESSMENT IN THE ENVIRONMENTAL PROTECTION AGENCY: CURRENT PRACTICE AND FUTURE PROSPECTS
26
Overview,
26
Statutory Plan and Regulatory Structure,
27
The Pivotal Role of the Red Book,
29
Current Concepts and Practices,
36
Institutional Arrangements for Managing the Process,
47
Extramural Influences and Participants,
53
Conclusions and Recommendations,
57
References,
59
3
THE DESIGN OF RISK ASSESSMENTS
65
Risk Assessment As a Design Challenge,
65
Design Considerations: Objectives, Constraints, and Tradeoffs,
68
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Science and Decisions: Advancing Risk Assessment
Environmental Protection Agency’s Current Guidance Related to Risk-Assessment Design,
73
Incorporating Value-of-Information Principles in Formative and Iterative Design,
80
Conclusions,
89
Recommendations,
90
References,
90
4
UNCERTAINTY AND VARIABILITY: THE RECURRING AND RECALCITRANT ELEMENTS OF RISK ASSESSMENT
93
Introduction to the Issues and Terminology,
93
Uncertainty in Risk Assessment,
97
Variability and Vulnerability in Risk Assessment,
108
Uncertainty and Variability in Specific Components of Risk Assessment,
113
Principles for Addressing Uncertainty and Variability,
119
Recommendations,
121
References,
122
5
TOWARD A UNIFIED APPROACH TO DOSE-RESPONSE ASSESSMENT
127
The Need for an Improved Dose-Response Framework,
127
A Unified Framework and Approach for Dose-Response Assessment,
135
Case Studies and Possible Modeling Approaches,
151
Implementation,
173
Conclusions and Recommendations,
177
References,
182
6
SELECTION AND USE OF DEFAULTS
188
Current Environmental Protection Agency Policy on Defaults,
189
The Environmental Protection Agency’s System of Defaults,
193
Complications Introduced by Use of Defaults,
195
Enhancements of the Environmental Protection Agency’s Default Approach,
198
Performing Multiple Risk Characterizations for Alternative Models,
205
Conclusions and Recommendations,
207
References,
208
7
IMPLEMENTING CUMULATIVE RISK ASSESSMENT
213
Introduction and Definitions,
213
History of Cumulative Risk Assessment,
216
Approaches to Cumulative Risk Assessment,
219
Key Concerns and Proposed Modifications,
223
Recommendations,
235
References,
237
8
IMPROVING THE UTILITY OF RISK ASSESSMENT
240
Beyond the Red Book,
241
A Decision-Making Framework that Maximizes the Utility of Risk Assessment,
242
The Framework: An Overview,
245
Additional Improvements Offered by the Framework,
251
Potential Concerns Raised by the Framework,
253
Conclusions and Recommendations,
255
References,
256
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9
TOWARD IMPROVED RISK-BASED DECISION-MAKING
258
Transition to the Framework for Risk-Based Decision-Making,
259
Institutional Processes,
259
Leadership and Management,
262
Conclusions and Recommendations,
262
References,
271
APPENDIXES
A BIOGRAPHIC INFORMATION ON THE COMMITTEE ON IMPROVING RISK ANALYSIS APPROACHES USED BY THE ENVIRONMENTAL PROTECTION AGENCY
275
B STATEMENT OF TASK OF THE COMMITTEE ON IMPROVING RISK ANALYSIS APPROACHES USED BY THE ENVIRONMENTAL PROTECTION AGENCY
281
C TIMELINE OF SELECTED ENVIRONMENTAL PROTECTION AGENCY RISK-ASSESSMENT ACTIVITIES
283
D ENVIRONMENTAL PROTECTION AGENCY RESPONSE TO RECOMMENDATIONS FROM SELECTED NRC REPORTS: POLICY, ACTIVITY, AND PRACTICE
299
E ENVIRONMENTAL PROTECTION AGENCY PROGRAM AND REGION RESPONSES TO QUESTIONS FROM THE COMMITTEE
367
F CASE STUDIES OF THE FRAMEWORK FOR RISK-BASED DECISION-MAKING
399
BOXES, FIGURES, AND TABLES
Boxes
2-1
Agencywide Risk-Assessment Guidelines,
33
2-2
Science Policy and Defaults,
36
2-3
Agency Guidance on Risk Characterization: Attention to Uncertainty,
39
2-4
Commentary on Risk Characterization for the Dioxin Reassessment,
40
2-5
Guideline Implementation and Risk-Assessment Impacts,
42
2-6
Choices and a Reference Dose Value for Perchlorate,
44
2-7
Impact of New Studies,
47
2-8
Arsenic in Drinking Water: Uncertainties and Standard-Setting,
51
2-9
Risk Assessment Planning: Multiple Participants,
55
2-10
After Peer Review,
56
3-1
Selected Elements of Scope Considered During Planning and Scoping,
74
3-2
Selected Methodologic Considerations in Problem Formulation,
75
3-3
Planning and Scoping: An Example Summary Statement,
77
3-4
Major Elements of an Analysis Plan,
79
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Science and Decisions: Advancing Risk Assessment
4-1
Terminology Related to Uncertainty and Variability,
96
4-2
Some Reasons Why It Is Important to Quantify Uncertainty and Variability,
98
4-3
Cognitive Tendencies That Affect Expert Judgment,
102
4-4
Levels of Uncertainty Analysis,
103
4-5
Examples of Uncertainties for Comparisons of Discrete and Continuous Possibilities,
106
4-6
Expressing and Distinguishing Model and Parameter Uncertainty,
108
4-7
Recommended Principles for Uncertainty and Variability Analysis,
120
5-1
A Risk-Specific Reference Dose,
140
5-2
Conceptual Model 1: Default Linear Low-Dose Extrapolation for Phosgene,
159
5-3
Calculating a Risk-Specific Dose and Confidence Bound in Conceptual Model 2,
164
6-1
Boron: Use of Data-Derived Uncertainty Factors,
200
8-1
Key Definitions Used in the Framework for Risk-Based Decision-Making,
246
8-2
Phase I of the Framework for Risk-Based Decision-Making (Problem Formulation and Scoping),
247
8-3
Phase II of the Framework for Risk-Based Decision-Making (Planning and Conduct of Risk Assessment),
248
8-4
Other Technical Analyses Necessary for the Framework for Risk-Based Decision-Making,
249
8-5
Elements of Phase III of the Framework for Risk-Based Decision-Making (Risk Management),
250
Figures
S-1
A framework for risk-based decision-making that maximizes the utility of risk assessment,
11
2-1
The National Research Council risk-assessment–risk-management paradigm,
31
2-2
The World Health Organization’s framework for integrated health and ecologic risk assessment,
34
2-3
Timeline of major documentary milestones,
37
3-1
Schematic representation of the formative stages of risk-assessment design,
73
3-2
Illustration of the scope of a risk assessment, indicating both pathways considered (bold lines) and pathways not considered,
78
3-3
Schematic of the application of value-of-information analysis to assess the impacts of additional studies in a specific decision context,
83
3-4
Schematic of an analysis of the value of various methodologic opportunities (or “value of methods” analysis) to enhance the risk-assessment process and products,
87
4-1
Illustration of key components evaluated in human health risk assessment, tracking pollutants from environmental release to health effects,
95
4-2
Factors contributing to variability in risk in the population,
110
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Science and Decisions: Advancing Risk Assessment
5-1
Current approach to noncancer and cancer dose-response assessment,
130
5-2
Value of physiologic parameter for three hypothetical populations, illustrating that population responses depend on a milieu of endogenous and exogenous exposures and on vulnerability of population due to health status and other biologic factors,
131
5-3a
New conceptual framework for dose-response assessment,
136
5-3b
Risk estimation and description under the new conceptual framework for dose-response assessment,
137
5-4
Linear low-dose response in the population dose-response relationship resulting from background xenobiotic and endogenous exposures and variable susceptibility in the population,
141
5-5
Nonlinear or threshold low-dose response relationships for individuals and populations,
142
5-6
Linear lo w-dose response models for individuals and population,
142
5-7
Dose-response relationships involving a continuous effect variable,
143
5-8
New unified process for selecting approach and methods for dose-response assessment for cancer and noncancer end points involves evaluation of background exposure and population vulnerability to ascertain potential for linearity in dose-response relationship at low doses and to ascertain vulnerable populations for possible assessment,
144
5-9
Population vulnerability distribution,
147
5-10
Examples of conceptual models to describe individual and population dose-response relationships,
149
5-11
Widely differing sensitivity can create a bimodal distribution of risk,
151
5-12
Three example conceptual models lead to different descriptions of dose-response relationships at individual or population levels,
152
5-13
Baseline airway reactivity as vulnerability factor for allergen-induced respiratory effects expressed as relative risk,
155
5-14
Effect of asthma-related gene polymorphisms on human vulnerability to asthma,
156
5-15
Dose-response relationship for liver spongiosis in 1,4-dioxane-exposed rats,
157
5-16
Steps in derivation of risk estimates for low-dose nonlinear end points,
161
5-17
Steps to derive population and individual risk estimates, with uncertainty in estimates from animal data,
167
5-18
A, AUC for proximate carcinogen in bladder in units of nanograms-minutes simulated for 500 people. B, simulated fraction bound in bladder, presumed to indicate differences in susceptibility due to PK and physiologic parameters,
170
8-1
A framework for risk-based decision-making that maximizes the utility of risk assessment,
243
9-1
A framework for risk-based decision-making that maximizes the utility of risk assessment,
268
E-1
Community involvement activities at NPL sites,
377
E-2
The framework for ecological risk assessment,
388
E-3
Conditions for regulation under SDWA 1996,
389
OCR for page R18
Science and Decisions: Advancing Risk Assessment
Tables
3-1
Transition in EPA Human Health Risk-Assessment Characteristics According to EPA,
69
4-1
Examples of Factors Affecting Susceptibility to Effects of Environmental Toxicants,
109
5-1
Potential Approaches to Establish Defaults to Implement the Unified Framework for Dose-Response Assessment,
175
6-1
Examples of Explicit EPA Default Carcinogen Risk-Assessment Assumptions,
194
6-2
Examples of Explicit EPA Default Noncarcinogen Risk-Assessment Assumptions,
195
6-3
Examples of “Missing” Defaults in EPA “Default” Dose-Response Assessments,
196
7-1
Modified Version of Stressor-Based Cumulative-Risk-Assessment Approach from Menzie et al. (2007) Oriented Around Discriminating among Risk- Management Options,
222
C-1
Timeline of Selected EPA Risk-Assessment Activities,
284
D-1
Environmental Protection Agency Response to National Research Council Recommendations of 1983-2006: Policy, Activity, and Practice,
301
E-1
Nine Evaluation Criteria for Superfund Remedial Alternatives,
378
E-2
Examples of Default Exposure Values with Percentiles,
380
