EXTERNAL REVIEW DRAFT EPA/63O/P-02/001A
April 23, 2002
Framework for Cumulative Risk Assessment
Risk Assessment Forum
U.S. Environmental Protection Agency
Washington, DC 20460
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DISCLAIMER
This document is in the process of being reviewed in accordance with U.S.
Environmental Protection Agency's peer and administrative review policy. It has had extensive
peer involvement in development (including other Federal, State, and public involvement), but it
has not yet completed the formal peer review process or administrative review process, so it
should not be quoted or cited. The mention of commercial products is for illustration only and in
no way implies EPA endorsement of these products.
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Table of Contents
List of Figures vi
List of Text Boxes vii
Acknowledgments ix
Foreword x
Preface xi
Authors, Contributors, and Reviewers xiii
List of Abbreviations and Acronyms xvi
Executive Summary xviii
1. INTRODUCTION 1
1.1. Purpose and Scope of the Framework Report 5
1.2. Intended Audience 6
1.3. Key Definitions in Cumulative Risk Assessment 6
1.4. The Cumulative Risk Assessment as a Tool for a Variety of Users and Purposes
10
1.5. The Broader Decision-Making Context for Cumulative Risk Assessment 11
1.6. Organization of this report 13
2. THE PLANNING, SCOPING, AND PROBLEM FORMULATION PHASE 14
2.1. Planning and Scoping 15
2.1.1. Defining the Purpose of the Assessment 16
2.1.2. Defining the Scope of Analysis and Products Needed 17
2.1.3. Agreeing on participants, roles and responsibilities 19
2.1.4. Agreeing on the Depth of the Assessment and the Analytical Approach
21
2.1.5. Agreement on the Resources Available and Schedule 21
2.1.6. Review of Lessons Learned in Similar Studies 22
2.2. Problem Formulation, Conceptual Model, and Analysis Plan 22
2.2.1. Problem Formulation 23
2.2.2. Developing the Conceptual Model 23
2.2.3. Constructing the Analysis Plan 26
2.3. The Final Step Before the Analysis Phase: Discussion of Possible Outcomes .... 27
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3. THE ANALYSIS PHASE 30
3.1. General Process 31
3.2. Available Methods and Approaches 32
3.2.1. Examples of Increased Complexity of Cumulative Risk Assessment ... 32
3.2.2. Approaches for Predicting Risk of Multiple Stressors 36
3.2.2.1. Single Stressor Information 37
3.2.2.2. Information on Stressor Interactions and Multiple Exposures
40
3.2.2.3. Decision Indices 42
3.2.2.4. Probabilistic Approaches 44
3.3. Areas of Complexity and Current Research 44
3.3.1. Interactions Between Stressors and Other Factors 45
3.3.2. The Promise of Biomarkers and Biomonitoring 46
3.3.3. A Single Metric for Multiple Types of Hazard 47
3.3.3.1. Creating a Common Metric 48
3.3.3.2. General Issues with a Single Metric 51
3.3.4. Qualitative approaches 51
4. THE RISK CHARACTERIZATION PHASE 53
4.1. Risk Description 54
4.2. Uncertainty Analysis 56
4.2.1. Assumptions in the Assessment 57
4.2.2. Uncertainty and Variability 58
4.2.3. Uncertainty and Risk Addition 58
4.3. The Information Provided by Cumulative Risk Assessment 59
4.3.1. Making Sense of Multiple Stressor Effects 59
4.3.2. Cumulative Risk Assessments in a Public Health Context 60
4.3.3. How Scope and Purpose of the Assessment Affect Results 61
4.4. Using the Results of the Assessment 62
5. GLOSSARY 64
6. REFERENCES 66
APPENDIX A: RESEARCH AND DEVELOPMENT NEEDS 82
APPENDIX B: SELECTED RESOURCES FOR EXPOSURE AND RISK ASSESSMENT . 85
B.I. Resources Relevant to Chemical Exposures 85
B.2. Resources Relevant to Exposures to Non-Chemical Slressors 86
APPENDIX C: SOME THOUGHTS ON BACKGROUND EXPOSURES 89
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APPENDIX D: EXAMPLES OF ANALYSE PLANS 91
D.I. Human Health Analysis Plan for Pesticides under FQPA 91
D.2. Ecological Analysis Plan 91
APPENDIX E: TOXICOLOGIC SIMILARITY: ORGANOPHOSPHORUS PESTICIDES ... 93
APPENDIX F: OTHER TYPES OF CUMULATIVE ASSESSMENTS 96
F.I. Quality-of-Life Assessments 96
F.2. Cumulative Impact Assessments 97
F.3. Empirically-Derived Medical Models 98
F.4. Risk Surrogates 99
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List of Figures
1-1. Chemical or stressor focused assessment 1
1-2. Population-based assessments 2
1-3. Framework for cumulative risk assessment 13
2-1. The planning, scoping, and problem formulation phase 14
2-2. Generic conceptual model 24
2-3. Specific conceptual model for a complex project, NATA 25
3-1. The analysis phase 30
4-1. The interpretation phase 52
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List of Text Boxes
Some Examples of Cumulative Risk Assessment Activities in EPA in Late 2001
EPA's Risk Assessment Guidelines 5
FQPA's Terminology Interpretations 8
Cumulative Risk Assessment Features 9
The Core Principles of Community-Based Environmental Protection 11
Possible Management Goals 17
Examples of Different Cumulative Risk Assessment Scopes 18
Examples of Possible Interested or Affected Parties (Stakeholders) 19
Guidelines for Stakeholder Involvement 20
Reed Holderman's Lessons Learned 22
Example: SAB's Desired Outputs for Problem Formulation 23
Example: Cumulative Risk Initiative (CRI) for Cook Co., IL, and Lake Co., IN 29
Example: Scope of EPA's National-scale Assessment for Hazardous Air Pollutants 31
Some Examples of Models which Consider Time Aspects 34
Example Using Toxicologic Independence: National-scale Air Toxics Assessment 40
Example Using Toxicologic Similarity: The Dioxin Reassessment 42
Example Decision Index: The Hazard Index 44
Risk Characterization Guiding Principles 54
Some Thoughts on Risk Characterization 56
Morgan and Henrion's "Ten Commandments" for Good Policy Analysis 57
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Uncertainty Analysis Example: The Cumulative Exposure Project 59
EEA's Twelve Late Lessons Learned 63
Vermont's Quality of Life Criteria 96
NEPA's "Cumulative Impact" Definition 97
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1 Acknowledgments
2
3 This U.S. Environmental Protection Agency (EPA) report has been developed under the
4 auspices of EPA's Risk Assessment Forum, a standing committee of EPA scientists charged with
5 developing risk assessment guidance for Agency-wide use. An interoffice technical panel
6 chaired by Michael Callahan (Region 6) was commissioned to write this report. Other members
7 of the panel are Edward S. Bender (Office of Science Policy), George L. Bollweg (Region 5),
8 Vicki L. Dellarco (Office of Pesticides Programs), Lynn A. Delpire (Office of Pollution
9 Prevention and Toxics), Martin P. Halper (Office of Environmental Justice), Richard C.
10 Hertzberg (National Center for Environmental Assessment), Elizabeth Lee Hofmann (Office of
11 Emergency and Remedial Response), R. Craig Matthiessen (Chemical Emergency Preparedness
12 and Prevention Staff), Alexander McBride (Office of Solid Waste), Deirdre L. Murphy (Office of
13 Air Quality Planning and Standards,), Henry C. Topper (Office of Pollution Prevention and
14 Toxics), and Winona Victery (Region 9). In addition, Carole Braverman (Region 5), Loren Hall
15 (Office of Civil Rights), and Denis R. Borum (Office of Water) participated for part of the
16 duration of the panel. Steven M. Knott of the Risk Assessment Forum staff coordinated the
17 project as well as participated as a member of the panel. The resulting document included peer
18 involvement and peer review by scientists from EPA, other federal agencies, state agencies,
19 academia, public interest groups, and the private sector.
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1 Foreword
2
3 Several reports have highlighted the importance of understanding the accumulation of
4 risks from multiple environmental stressors. These include the National Research Council's
5 1994 report Science and Judgment in Risk Assessment and the 1997 report by the
6 Presidential/Congressional Commission on Risk Assessment and Risk Management entitled Risk
1 Assessment and Risk Management in Regulatory Decision-Making. In addition, legislation such
8 as the Food Quality Protection Act of 1996, has directed the Environmental Protection Agency to
9 move beyond single chemical assessments and to focus, in part, on the cumulative effects of
10 chemical exposures occurring simultaneously. Further emphasizing the need for EPA to develop
11 methods to assist consideration of cumulative risks are some of the cases filed with EPA under
12 Title VI of the 1964 Civil Rights Act.
13
14 The Superfund program began doing cumulative risk assessments at hazardous waste
15 sites as early as the 1980s. More recently, in response to the increasing interest in cumulative
16 risk, several other EPA programs have begun to explore approaches to cumulative risk
17 assessment. In 1997, The EPA Science Policy Council issued a guidance on planning and
18 scoping for cumulative risk assessments. More recently, the Office of Pesticide Programs has
19 developed cumulative risk assessment guidance focused on implementing certain provisions of
20 FQPA. In addition, the Office of Air Quality Planning and Standards is performing a national-
21 scale cumulative assessment of human health risks posed by outdoor air exposures to a set of 33
22 priority urban air toxics.
23
24 The EPA Science Policy Council has asked the Risk Assessment Forum to begin
25 developing Agency-wide cumulative risk assessment guidance that builds from these ongoing
26 activities. As a first step, a technical panel convened under the Risk Assessment Forum has been
27 working to develop a Framework for Cumulative Risk Assessment. This document is the result
28 of that technical panel's efforts. Building from the Agency's growing experiences, this
29 Framework is intended to identify the basic elements of the cumulative risk assessment process.
30 It should provide a flexible structure for the technical issues and define key terms associated with
31 cumulative risk assessment. Further efforts and experience in the coming years should advance
32 our knowledge beyond the Framework stage to a future set of Agency guidelines for cumulative
33 risk assessment.
34
35
36 William P. Wood, Ph.D.
37 Executive Director
38 Risk Assessment Forum
39
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1 Preface
2
3 In the past several years, cumulative risk assessment, aggregate exposure assessment, and
4 research on chemical mixtures has taken on increased importance. This is underscored by reports
5 such as the National Research Council's 1993 report Pesticides in the Diets of Infants and
6 Children, (NRC, 1993) the 1994 NRC report Science and Judgment in Risk Assessment, (NRC,
7 1994), the 1995 National Academy of Public Administration report Setting Priorities, Getting
8 Results (NAPA, 1995), the 1997 report by the Presidential/Congressional Commission on Risk
9 Assessment and Risk Management titled Risk Assessment and Risk Management in Regulatory
10 Decision-Making (PCCRARM, 1997), and the EPA Science Advisory Board report Toward
11 Integrated Environmental Decision-Making (USEPA, 2000a). There also have been several
12 recent pieces of legislation that mandate the consideration of cumulative risk and variability
13 factors in the risk characterization process. Specifically, the Food Quality Protection Act of 1996
14 (FQPA) [PL 104-170, August 3, 1996] directs EPA in its assessments of pesticide safety to
15 focus, in part, on the cumulative effects of pesticides that have a common mechanism of toxicity,
16 considering aggregate dietary and non-occupational pathways of exposure.
17
18 Assessment of cumulative risk through complex exposures is one of the high priorities of
19 the Agency, especially in light of FQPA mandates, and is germane and of great interest to all
20 program and regional offices. This area of research is also directly applicable to children's risk
21 issues. This Framework is meant to layout broad areas where analysis might be conducted if
22 needed. It does not suggest that cumulative risk assessment is a tool that should be used with
23 every issue, nor does it suggest that when cumulative risk assessment is applied, that all areas of
24 analysis outlined or discussed here must or even should be conducted in every assessment. The
25 scope of the assessment will define the areas to be analyzed. In some areas discussed in this
26 Framework, the methodology for doing the risk analysis may not yet exist.
27
28 According to the expert panel report Safeguarding the Future: Credible Science, Credible
29 Decisions (USEPA 1992a), a key role of science at EPA is to reduce uncertainties in
30 environmental decision-making. The report points out that while many EPA programs have
31 historically focused on chemical-specific impacts, methods to assess or control the effects of
32 chemical mixtures and general stressors on human health and ecosystems remained to be
33 developed. In Pesticides in the Diets of Infants and Children, (NRC, 1993) the NRC
34 recommended that all exposures to pesticides - dietary and nondietary- need to be considered
35 when evaluating the potential risks to infants and children. Estimates of total dietary exposure
36 should be refined to consider intake of multiple pesticides with a common toxic effect. Further,
37 the report identifies important differences in susceptibility with age. NRC in Science and
38 Judgment in Risk Assessment (NRC, 1994) states that health risk assessments should generally
39 consider all possible routes by which people at risk might be exposed, and recommends this
40 approach universally in the assessment of hazardous air pollutants regulated by EPA under the
41 Clean Air Act Amendments of 1990 [P.L. 101-549, November 15, 1990]. Regarding variability,
42 the NRC Science and Judgment report recommended that EPA assess risks to infants and
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1 children whenever it appears that their risks might be greater than those of adults. Public
2 criticisms cited in this report include statements made by some experts that EPA does not appear
3 to recognize the possibility of synergistic interactions when multiple chemical exposures occur,
4 nor does it consider extreme variability among individuals in their responses to toxic substances.
5 A related issue is the problem of how risks associated with multiple chemicals are to be
6 combined. Finally, the FQPA [P.L.104-170, August 3, 1996], requires research on the influence
7 of complex exposures on non-cancer human health effects of pesticides and other toxic
8 substances.
9
10 The issue of cumulative risk is also an important issue with the general public. In public
11 meetings of Superfund stakeholders, held in late 1996 in San Francisco and Washington, DC,
12 and in early 1998 in Atlanta, the issue of cumulative risk was raised several times in each session
13 (USEPA 1996a, USEPA 1998a).
14
15 Cumulative risk assessments will identify the need for many different kinds of data -
16 some of them are not the data commonly used now for risk assessment - and often, cumulative
17 risk assessment will demand large quantities of such data. Until data bases and data generation
18 research can provide such data, for the near term, identification of critical data and research
19 needs may be the primary result of many cumulative risk assessment endeavors.
20
21 As of August 1, 2001, there were 19,533 pesticide products on the market (USEPA,
22 2001a), and 79,120 existing chemicals on the TSCA inventory (USEPA, 2001b). Each year, an
23 additional number of chemicals are added. Assessing the cumulative effect of these chemicals
24 will be a great challenge to the Agency and may become the primary issue in the risk assessment
25 field in the next ten years.
26
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1 Authors, Contributors, and Reviewers
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3 Authors:
4
5 EPA Risk Assessment Forum Cumulative Risk Technical Panel:
6
1 Edward S. Bender, Office of Science Policy, ORD
8 George L. Bollweg, Air and Radiation Division, Region 5
9 Michael A. Callahan, Office of the Regional Administrator, Region 6 (Chair)
10 Vicki L. Delkrco, Office of Pesticides Programs, OPPTS
11 Lynn A. Delpire, Office of Pollution Prevention and Toxics, OPPTS
12 Martin P. Halper, Office of Environmental Justice, OECA
13 Richard C. Hertzberg, National Center for Environmental Assessment, ORD
14 Elizabeth Lee Hofmann, Office of Emergency and Remedial Response, OSWER
15 Steven M. Knott, Risk Assessment Forum, ORD
16 R. Craig Matthiessen, Chemical Emergency Preparedness and Prevention Staff, OSWER
17 Alexander McBride, Office of Solid Waste, OSWER
18 Deirdre L. Murphy, Office of Air Quality Planning and Standards, OAR
19 Henry C. Topper, Office of Pollution Prevention and Toxics, OPPTS
20 Winona Victery, Policy and Management Division, Region 9
21
22 Contributors and Reviewers:
23
24 EPA Reviewers:
25
26 Donald G. Barnes, EPA Science Advisory Board
27 Michael Firestone, Office of Children's Health Protection
28 Debra L. Forman, Region 3
29 Mark Maddaloni, Region 2
30 Elizabeth H. Margosches, Office of Pollution Prevention and Toxics
31 Marian Olsen, Region 2
32 James Rowe, Office of Research and Development
33 Scott Schwenk, Office of Research and Development
34 Michael Shapiro, O ffice of Solid W aste
35 Sally Shaver, Office of Air and Radiation
36 Margaret Stasikowski, Office of Pesticide Programs
37 Jeannette Wiltse, Office of Water
38 Jeffrey Yurk, Region 6
39
40 The following persons participated in peer involvement workshops held during 2001 to discuss and comment on the
41 draft Framework.
42
43 Federal Scientists' Meeting, May 1, 2001:
44
45 Michael A. Babich, Health Sciences Division, U.S. Consumer Product Safety Commission
46 Michael Buchman, Office of Response and Restoration, National Oceanic and Atmospheric Administration
47 Stephen Channel, Department of the Air Force, U.S. Department of Defense
48 Christopher T. DeRosa, Division of Toxicology, Agency for Toxic Substances and Disease Registry
49 Dennis Druck, Army Center for Health Promotion and Preventive Medicine, U.S. Department of Defense
50 Frank Hearl, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health
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1 Keith Hoddinott, Army Center for Health Promotion and Preventive Medicine, U.S. Department of Defense
2 Steve Jones, Office of Regional Operations, Agency for Toxic Substances and Disease Registry
3 Brian Kaplan, Division of Health Assessment and Consultation, Agency for Toxic Substances and Disease Registry
4 Ralph Kodell, National Center for Toxicological Research, U.S. Food and Drug Administration
5 Dan Lewis, Health Effects Laboratory Division, National Institute for Occupational Safety and Health
6 Margaret MacDonell, Argonne National Laboratory, U.S. Department of Energy
7 Mark McClanahan, National Center for Environmental Health, Centers for Disease Control and Prevention
8 Anita K. Meyer, HTRW Center of Expertise, U.S. Army Corps of Engineers
9 Moiz G. Mumtaz, Division of Toxicology, Agency for Toxic Substances and Disease Registry
10 Leslie G. Rubin, Animal and Plant Health Inspection Service, U.S. Department of Agriculture
11 Antoinette Sebastian, Office of Community Planning and Development, Dept. of Housing and Urban Development
12 Scott D. Sudweeks, Div. of Health Assessment and Consultation, Agency for Toxic Substances and Disease Registry
13 Timothy Taylor, Army Center for Health Promotion and Preventive Medicine, U.S. Department of Defense
14 John Wheeler, Division of Toxicology, Agency for Toxic Substances and Disease Registry
15 Jody Wireman, Department of the Air Force, U.S. Department of Defense
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17 States'Meeting, May 3, 2001:
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19 Glen Andersen, National Conference of State Legislators
20 Ligia Mora-Applegate, Florida Department of Environmental Protection
21 Alex M. Barren, Virginia Department of Environmental Quality
22 Sharon B axter, Office o f Pollution Prevention, Virginia Dep artment of Environmental Quality
23 Joseph P. Brown, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency
24 Michele F. Burgess, Georgia Department of Natural Resources
25 Perry Cohn, Environmental Health Service, New Jersey Department of Health
26 Linda J. Cullen, New Jersey Department of Environmental Protection
27 Susan Dempsey, Nebraska Department of Health and Human Services
28 Michael J. DiBartolomeis, Office of Environmental Health Hazard Assessment, California Env. Protection Agency
29 Michael Ellenbecker, Toxics Use Reduction Institute, University of Massachusetts at Lowell
30 George Hagevik, National Conference of State Legislators
31 Joann Held, Office of Air Quality, New Jersey Department of Environmental Protection
32 Bruce Hope, Oregon Department o f Environm ental Quality
33 Tom Hornshaw, Toxicity Assessment Unit, Illinois Environmental Protection Agency
34 Paul B. Jiapizian, Maryland Department of the Environment
35 David R. Johnson, Bureau of Environmental Epidemiology, Florida Department of Health
36 Michael Juras, Community Right-to-Know, South Carolina Department of Health and Environmental Control
37 Kevin Kessler, Air and Waste Division, Wisconsin Department of Natural Resources
38 Rosanna Kroll, Health and Toxicology Section, Maryland Department of Environment
39 Charles Moore, Office of Environmental Management, South Carolina Department of Natural Resources
40 Rebecca Pottratz, Communication Specialist, Wisconsin Department of Natural Resources
41 John Ridgway, Environmental Justice Program, Washington State Department of Ecology
42 Kirpal S. Sidhu, Environmental Epidemiology Division, Michigan Department of Community Health
43 Lawrence P. Sirinek, Division of Emergency and Remedial Response, Ohio Environmental Protection Agency
44 Alan Stern, Bureau for Risk Analysis, New Jersey Department of Environmental Protection
45 Chuck Stroebel, Environmental Research Scientist, Minnesota Department of Health
46 Barbara S. Taylor, Department of Health and Human Services, West Virginia Bureau for Public Health
47 Mark W erner, W isconsin Div ision of Pub lie Health
48 Carol Rowan West, Office ofResearch and Standards, Massachusetts Department of Environmental Protection
49 Victor R. Wilford, Department of Health and Human Services, West Virginia Bureau for Public Health
50 Stephen L. Wust, Drinking Water Bureau, New Mexico Environment Department
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3 Public Meeting, August 22-23, 2001:
4
5 Elizabeth Boa, American Chemistry Council, Inc.
6 Kenneth T. Bogen, Health and Ecological Assessment Division, Lawrence Livermore National Laboratory
7 James P. Butler, Environmental Assessment Division, Argonne National Laboratory
8 Douglas J. Crawford-Brown, Dept of Environmental Sciences and Engineering, University of North Carolina
9 Amy D. Kyle, School of Public Health, University of California-Berkeley
10 Norris McDonald, Center for Environment, Commerce and Energy
11 Beth E. Mileson, Technology Sciences Group, Inc.
12 Stephen S. Olin, Risk Science Institute, International Life Sciences Institute
13 William R. Rhyne, H&R Technical Associates, Inc.
14 Jennifer Sass, Health Program, Natural Resources Defense Council
15 Margo Schwab, School of Public Health, Johns Hopkins University
16 Ken W. Sexton, Center for Environment and Health Policy, University of Minnesota (Chair)
17
18 Written Public Comments:
19
20 James M. Solyst, American Chemistry Council, Inc.
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List of Abbreviations and Acronyms
ACGIH - American Conference of Government Industrial Hygierrists
AFS - AIRS Facility Subsystem
AIChE - American Institute of Chemical Engineers
AIHA - American Industrial Hygiene Association
AIRS - Aerometric Information Retrieval System
AMTIC - Ambient Monitoring Technology Information Center
APCA - American Crop Protection Association
APEX - Air Pollution EXposure model
ARE - Acute Reference Exposure
ATSDR - Agency for Toxic Substances and Disease Registry
CARES - Cumulative and Aggregate Risk Evaluation System
CBEP - Community-Based Environmental Protection
CEQ - Council for Environmental Quality
CFR - Code of Federal Regulations
CHIEF - Clearinghouse for Inventories and Emissions Factors
COHb - Carboxyhemoglobin
CRIA - Cumulative Risk Index Analysis
DALY - Disability-Adjusted Life Year
DOT - United States Department of Transportation
EPA - United States Environmental Protection Agency
FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act
FQPA - Food Quality Protection Act
GAO - United States General Accounting Office
GIS - Geographical Information System
HAP - Hazardous Air Pollutant
HEC - Human Equivalent Concentration
HRS - Hazard Ranking System
HUD - United States Department of Housing and Urban Development
IED - Integrated Environmental Decision-making
ILSI - International Life Sciences Institute
LADD - Lifetime Average Daily Dose
LDP - Locational Data Policy
LLE - Loss of Life Expectancy
LOAEL - Lowest Observed Adverse Effect Level
MOE - Margin of Exposure
MSDS - Materials Safety Data Sheet
NAAQS - National Ambient Air Quality Standards
NAP A - National Academy of Public Administration
NATA - National Air Toxics Assessment
NEPA - National Environmental Policy Act
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List of Abbreviations and Acronyms (Continued)
NHEXAS - National Human Exposure Assessment Survey
NIOSH - National Institute for Occupational Safety and Health
NOAEL - No Observed Adverse Effect Level
NRC - National Research Council
OAR - Office of Air and Radiation (EPA)
OECA - Office of Enforcement and Compliance Assurance (EPA)
OP - Organophosphorous
OPP - Office of Pesticide Programs (EPA)
OPPTS - Office of Prevention, Pesticides, and Toxic Substances (EPA)
ORD - Office of Research and Development (EPA)
OSWER - Office of Solid Waste and Emergency Response (EPA)
P.L. - Public Law
PAH - Polycyclic Aromatic Hydrocarbon
PCB - Polychlorinated Biphenyl
PCS - Permit Compliance System
PM-10 - Particulate Matter with diameter of 10 micrometers or less
pNEM - Probabilistic NAAQS Exposure Model
QALY - Quality-Adjusted Life Year
RfC - Reference Concentration
RfD - Reference Dose
SAB - Science Advisory Board
SAP - Scientific Advisory Panel
SAR - Structure-Activity Relationship
SCRAM - Support Center for Regulatory Air Models
SHEDS - Stochastic Human Exposure and Dose Simulation model
SPC - Science Policy Council
TEAM - Total Exposure Assessment Methodology
TEMRAP - The European Multi-Hazard Risk Assessment Project
TIA - Transient Ischemic Attack
TRI - Toxic(s) Release Inventory
TRIM.Expo - Total Risk Integrated Methodology, Exposure Module
U.S.C. - United States Code
UF - Uncertainty Factor
USEPA - United States Environmental Protection Agency
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1 Executive Summary
2
3 This report, "Framework for Cumulative Risk Assessment," is the first step in a long-
4 term effort to develop cumulative risk assessment guidelines. Its primary purpose is to offer a
5 simple, flexible structure for conducting and evaluating cumulative risk assessment within EPA.
6 Although this Framework report will serve as a foundation for development of future guidelines,
7 it is neither a procedural guide nor a regulatory requirement within EPA and is expected to
8 evolve with experience. This Framework report is intended to foster consistent approaches to
9 cumulative risk assessment within EPA, identify key issues, and define terms used in these
10 assessments.
11
12 This Framework is meant to lay out broad areas where analysis might be conducted if
13 needed. It does not suggest that cumulative risk assessment is a tool that should be used with
14 every issue, nor does it suggest that when cumulative risk assessment is applied, that all areas of
15 analysis outlined or discussed here must or even should be conducted in every assessment. The
16 scope of the assessment will define the areas to be analyzed. In some areas discussed in this
17 Framework, the methodology for doing the risk analysis may not yet exist. Appendix A includes
18 a summary of areas where research is needed.
19
20 In this report, "cumulative risk' means "the combined risks from aggregate exposures to
21 multiple agents or stressors." There are several key points which come from this definition of
22 cumulative risk. First, cumulative risk involves multiple agents or stressors, which means that
23 assessments involving a single chemical or stressor are not "cumulative risk assessments" under
24 this definition. Second, there is no limitation that the "agents or stressors" be only chemicals.
25 "Agents or stressors" may be chemicals, but they may also be biological agents, or physical
26 agents, or even the absence of a necessity such as habitat. Third, this definition requires that the
27 risks from multiple agents or stressors be combined. This does not necessarily mean "added,"
28 but it means that some analysis needs to be conducted as to how the risks from the various agents
29 or stressors interact. It also means that an assessment which covers a number of chemicals or
30 other stressors, but which merely lists each chemical with a corresponding risk without
31 consideration of the other chemicals present, is not an assessment of cumulative risk under this
32 definition.
33
34 Likewise, "cumulative risk assessment" in this Framework report means "an analysis,
35 characterization, and possible quantification of the combined risks to health or the environment
36 from multiple agents or stressors." One key aspect of this definition is that a cumulative risk
37 assessment need not necessarily be quantitative, so long as it meets the other requirements.
38
39 The framework itself is conceptually similar to the approach used in both human health
40 and ecological assessments, but it is distinctive in several areas. First, its focus on the combined
41 effects of more than one agent or stressor makes it different from many assessments conducted
42 today (which, if multiple stressors are evaluated, are usually evaluated individually and presented
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1 as if the others were not present). Second, by the fact that multiple stressors are affecting the
2 same population, there is increased focus on the specific populations potentially affected, rather
3 than a focus on hypothetical receptors. Third, consideration of cumulative risk may generate
4 interest in a wider variety of non-chemical stressors than traditional risk assessments.
5
6 The framework describes three main phases to a cumulative risk assessment: (1)
7 planning, scoping and problem formulation, (2) analysis, and (3) interpretation. In the planning,
8 scoping and problem formulation phase, a team of risk managers, risk assessors, and other
9 stakeholders establishes the goals, breadth, depth, and focus of the assessment. The end products
10 of this phase are a conceptual model and an analysis plan. The conceptual model establishes the
11 stressors to be evaluated, the health or environmental effects to be evaluated, and the
12 relationships among various stressor exposures and potential effects. The analysis plan lays out
13 the data needed, the approach to be taken, and the types of results expected during the analysis
14 phase.
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16 The analysis phase includes developing profiles of exposure, considering interactions (if
17 any) among stressors, and predicting risks to the population or populations assessed. It is in this
18 phase that difficult technical issues are addressed and hopefully resolved, for example, issues
19 relating to toxicity of mixtures, vulnerability of populations, or the interactions among stressors
20 which may be chemical or non-chemical. The end product of this phase is an analysis of the risks
21 associated with the multiple stressors to which the study population or populations are exposed.
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23 The third phase, interpretation, includes what is usually termed the "risk characterization"
24 discussion in risk assessment, where the risk estimates are put into perspective in terms of their
25 significance, the reliability of the estimates, and the overall confidence in the assessment. It is
26 also in this phase that an evaluation is made of whether the assessment met the objectives and
27 goals set forth in phase one.
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29 The discussion of cumulative risk in this Framework report takes a broad view of the
30 topic, including many aspects of an assessment that might conceivably be conducted in the
31 future, even though techniques may not currently exist to examine every question. It also
32 includes aspects of cumulative risk which may be outside of EPA's current legislative mandates,
33 and where expertise outside of the Agency would be needed to address certain questions if they
34 should arise. These aspects of cumulative risk are discussed here for the sake of technical
35 completeness and not as a recommendation that EPA perform all possible aspects of a
36 cumulative risk assessment in all EPA risk assessments - even all EPA cumulative risk
37 assessments.
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39 EPA is currently engaged in activities which fall under various aspects of the cumulative
40 risk assessment umbrella. Some of these activities are listed as illustrations in the box on the next
41 page. The broad interpretation of cumulative risk in this Framework report allows these activities
42 to be put into perspective relative to one another, and can illustrate how they fit together under
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Some Example Cumulative Risk Assessment Activities within EPA in late 2001
The Superfund Program has updated its guidance on risk assessment to include planning and scoping for
cumulative risk assessment and problem formulation for ecological risk assessments. The plan for the Office of
Solid Waste's Surface Impoundment Study includes both aconceptual model and an analytical pkn, per the
agency guidance on planning and scoping for cumulative risk.
The Office of Water is planning a watershed scale risk assessment involving multiple stiessors in ecological risk.
This approach was developed through a collaboration with external scientists and is now being field evaluated.
Several Regional Offices are evaluating cumulative hazanis, exposures, and effects of toxic contaminants in
urban environments. In Chicago (Region 5), citizens are concerned about the contribution of environmental
stressors toward endpoints such as asthma and blood lead levels. In Baltimore (Region 3), a
regional/OPPTS/community partnership tried to address the long term environmental and economic concerns in
three neighborhoods that are adjacent to industrial facilities and tank farms. Region 6 (Dallas) is developing a
geographic information system approach for planning and scoping cumulative risks.
The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative effects to human
health that can result from exposure to pesticides and other substances that have a common mechanism of toxicity.
The Office of Pesticides Programs (OPP) has developed guidance for conducting cumulative risk assessments
for pesticides, and has prepared a preliminary cumulative risk assessment for Organophosphorous pesticides.
The Office of Air and Radiation's air toxics program has a cumulative risk focus. Under the Integrated Urban
Air Toxics Strategy (IUATS), OAR will be considering cumulative risks presented by exposures to air emissions
of hazardous air pollutants from sources in the aggregate. Assessments will be performed both at the national
scale - release of a national scale assessment for base year 1996 is planned for later this year - and at the urban or
neighborhood scale. In partnership with ORD/NERL, the Office of Air Quality, Planning & Standards is
developing the Total Risk Integrated Methodology (TRIM), a modular, modeling system for use in single or
multi-media, single or multi-pathway, human health and ecological risk assessments of hazardous and criteria air
pollutants at the neighborhood or city scale. The Agency's guidance for planning and scoping of cumulative risk
was used to develop a conceptual model and analysis plan for the national scale air toxics risk assessment.
The National Center for Environmental Assessment (ORD) has completed ecological risk assessment
guidelines which support the cumulative risk assessment guidance. Five watershed case studies are being assessed
to demonstrate the guidelines approach. Each of these cases deals with cumulative impacts of stressors (chemical,
biological, and in some cases physical). In addition, NCEA has done a draft reassessment of dioxin and related
compounds.
The Risk Assessment Forum has convened a technical panel to develop guidance for conducting cumulative risk
assessments, of which this Framework is a first step.
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the framework. Individual Program Offices and Regions may have to make decisions affecting
the scope, types of stressors, or methods used for their programs' cumulative risk assessments,
based on legislative mandates or other criteria. Nothing in this Framework report should be
interpreted to mandate that cumulative risk assessment must be conducted, or must be conducted
a certain way, for any specific case. Likewise, this Framework report is not an attempt to layout
protocols to address all the risks or considerations that are needed to adequately inform
community decisions. Rather, this Framework report is an information document, focused on
describing various aspects of cumulative risk, whether or not the methods or data currently exist
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1 to adequately analyze or evaluate those aspects of the assessment. Because of the limitations of
2 current science, cumulative risk assessments in the near future will not be able to adequately
3 answer all questions posed by stakeholders or interested parties. This does not mean, however,
4 that they can't answer some of the questions asked; in fact, cumulative risk assessment may be
5 the best tool available to address certain questions dealing with multiple stressor impacts.
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1. INTRODUCTION
During much of its early history, EPA focused its efforts on cleaning up the overt
pollution problems of the 1960s and 1970s. Until EPA was established in 1970, relatively
uncontrolled air emission, water effluents, and dumping of wastes had led to pollution of the
environment that was easily detected by the five senses. The most effective and efficient way to
approach these overt problems of the 1970s was to find the entry point of the pollution into the
environment, and to keep it from entering the environment by controlling it there. Looking back,
we see a strategy that moved to control stack emission, industrial and municipal effluents,
pesticide application, land applications, burial of chemical wastes, and other "sources" of
pollution. In addition, criteria and standards were established as goals for cleanup of the various
environmental media. By the 1980s, this "command and control" strategy was well established in
environmental laws and regulations, but was reaching the point of diminishing returns from a
cost-benefit viewpoint.
The development of risk assessment methodology during the 1970s and early 1980s
closely followed the Agency's strategy for control of pollution, since risk assessments were being
used as one of the factors in EPA's decision-making for regulations. The focus on sources led
naturally to analysis of what types of pollutants were in effluents, air emissions, and waste sites.
These were chemical, biological, and sometimes
radiological agents. By the 1970s, the links between
some chemicals and certain diseases such as cancer
had been established through a series of bioassays,
or in the cases of chemicals like vinyl chloride and
asbestos, through epidemiological studies. New
analytical techniques of the 1970s also made it
possible to detect very minute concentrations of
chemicals for the first time. The focus of the EPA
strategy to control pollution (and the risk
assessment methodology being used to partially
support decisions) gradually leaned toward
assessing and controlling the individual chemicals.
Congressional legislation tended to underwrite this
approach by focusing on controlling sources and
even including lists of individual chemicals to be
controlled.
The risk assessment methodology of the
1970s and early 1980s, for this reason, tended
towards single chemical assessments (see Figure 1-
1). The 1983 National Research Council report Risk
Figure 1-1. Chemical (or stressor)
focused assessment starts with a source
and evaluates how the chemical gets to
various populations or ecological targets.
Individual assessments may choose to
pursue some or all pathways, media, or
population segments.
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Assessment in the Federal Government (NRC, 1983) was largely focused on the single chemical
risk assessment approach when it spoke of the four parts of a risk assessment: hazard
identification, dose-response assessment, exposure assessment, and risk characterization. EPA's
1986 Risk Assessment Guidelines (USEPA 1986a), with the exception of the mixtures guidelines
(USEPA, 1986b), were also largely focused on single chemical assessment.
Research conducted or sponsored by EPA in
the early 1980s, however, was taking the first steps
toward investigating a different type of risk
assessment methodology, one that focused on the
persons exposed, investigating the chemicals or
stressors to which they were exposed, and
consequent risks (Figure 1-2). This is in contrast to a
focus on either a chemical, to investigate its
environmental fate, exposed populations, and risks
(Figure 1-1), or focus on a source to investigate its
environmental releases, exposed populations, and
risks. The goals of the population-focused approach1
were much more useful to decision-makers who
were dealing with public health or ecological health
questions, rather than controlling sources of
pollution.
Figure 1-2. Population-based assessments
start with the receptors, and determine
what chemicals, stressors, or other risk
factors are affecting them.
The challenges posed by the population-
based assessment can be daunting, even if only a few of the stressors affecting a population are
evaluated together (i.e., cumulatively). Taken to the extreme, Figure 1-2 represents a concept of
"total risk" for the population or population segment being evaluated, with each chemical,
biological, radiological, or other stressor2 adding some fraction of the total risk. Looking at the
problem from an individual stressor viewpoint, to do this type of assessment would require not
A chemical-focused assessment may look at several populations affected by exposure to the chemical, but not at other
chemicals. A population-focused assessment looks at one population for perhaps many stressors, but not at other populations.
Consequently, for traditional, chemical-focused assessments, we say we conduct a "risk assessments for a certain chemical." In
contrast, the essence of a cumulative risk assessment is that the assessment is conducted "for a certain population." This
difference is shown schematically by comparing figures 1-1 and 1-2. How the population is identified for a cumulative
assessment is not addressed here.
A stressor is a physical, chemical, biological, or other entity that can cause an adverse response in a human or other
organism or ecosystem. A stressor can be exposure to a chemical, biological, or physical agent (e.g., radon), or it may be the lack
of, or destruction of, some necessity such as a habitat. A socioeconomic stressor, for example, might be the lack of needed health
care, which could lead to adverse effects. Harmful events, such as automobile crashes, could also be termed stressors. Obviously,
calculating risks from different types of stressors can use widely different methods, including probabilistic estimates of disease
via dose-response relationships, looking up rates in statistical tables of historical events, and other methods.
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1 only evaluating each individual stressor, but also developing a way to add up all the risks among
2 stressors across a population of individuals with different exposures and susceptibilities. In the
3 early 1980s, the state of the science was unready for virtually any part of the methods fordoing
4 this type of assessment.
5
6 But progress was being made toward developing a population-based methodology.
7 Starting in the late 1970s, a group of EPA researchers and contractors began developing what
8 would become the Total Exposure Assessment Methodology (TEAM) study (USEPA 1987).
9 TEAM measured the concentrations of a number of chemicals simultaneously at the point of
10 exposure. This led to a larger study, the National Human Exposure Assessment Survey
11 (NHEXAS) in the 1990s (Sexton, et, al. 1995). Both TEAM and NHEXAS were population-
12 based exposure assessment approaches which developed analytical tools and methodologies to do
13 this type of exposure assessment
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15 Also in the early 1980s, some progress was being made toward the question of how to
16 cumulatively consider the risks from different chemicals or stressors. The 1986 Risk Assessment
17 Guidelines (USEPA, 1986a) included a guideline on chemical mixtures (USEPA, 1986b), which
18 discussed how the risks from multiple chemicals could be evaluated as a whole. The work on this
19 guidance has continued most recently with the Supplementary Guidance for Conducting Health
20 Risk Assessment of Chemical Mixtures (USEPA, 2000e) which expands and supplements the
21 1986 beginnings.
22
23 About the same time the Agency made some progress on single chemical and chemical
24 mixture risk assessment with the 1986 Guidelines, some different kinds of risk assessment
25 problems began to catch the Agency's attention. In 1986, eleven Chicago-area community
26 groups joined together to file a petition under Section 21 of the Toxic Substances Control Act
27 asking for a community assessment in Southeast Chicago. A series of community-based actions
28 which started in 1982 and grew throughout the 1980s focused on disparities of risk among
29 various population subgroups, calling specific attention to cumulative effects of pollution on
30 minority subgroups (GAO, 1983; United Church of Christ, 1987). This series ofcommunity-
31 based actions, chronicled in the 1990 book Dumping in Dixie: Race, Class and Environmental
32 Quality (Bullard, 1990) eventually became known as the Environmental Justice movement. The
33 issues raised by the Environmental Justice movement were the basis of a 1994 Presidential
34 Executive Order [Executive Order 12898, February 11, 1994] which told Agencies, among other
35 things, that "Environmental human health analyses, whenever practicable and appropriate, shall
36 identify multiple and cumulative exposures." In the 1990s, Environmental Justice cases,
37 including the cases which have been filed under Title VI of the 1964 Civil Rights Act, [P.L. 88-
38 352, July 2, 1964] have further emphasized the need for a cumulative human health risk
39 assessment methodology.
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41 Even before Executive Order 12898 was issued, it was apparent that population-focused
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1 assessments (like Figure 1-2) were going to be needed, in addition to the chemical- or stressor-
2 focused assessments (like Figure 1-1), if EPA was going to be able to answer the questions and
3 issues being raised by the public. Community spokespersons and other "stakeholders," as well as
4 scientific panels, were increasingly coming to the Agency with problems that demanded amulti-
5 stressor approach (e.g., NRC 1994). Ecological problems, especially, were demanding a "place-
6 based" context (such as the Chesapeake Bay watershed) in which the various populations within
7 the area were looked at from a "total system" viewpoint. This place-based focus was a part of the
8 1992 Framework for Ecological Risk Assessment (USEPA 1992b) and the 1998 Guidelines for
9 Ecological Risk Assessment (USEPA 1998b).
10
11 Although clearly addressing more than cumulative human health or ecological risk
12 assessment, the National Environmental Policy Act of 1969 (NEPA) [P.L. 91-190, 42 U.S.C.
13 4321-4347, January 1, 1970, as amended by P.L. 94-52, July 3, 1975, P.L. 94-83, August 9,
14 1975, and P.L. 97-258, §4(b), Sept. 13, 1982], which was passed at about the same time EPA
15 was established, requires assessments on the cumulative impacts of federal or federally-funded
16 projects (such as roads, dams, power lines, military projects, and infrastructure development) on
17 natural ecosystems, endangered species, habitats, and opportunities for public enjoyment and
18 natural resource use. A primary concern for NEPA is "cumulative effects analysis," defined as
19 "the incremental impact of the action when added to other past, present, and reasonably
20 foreseeable future actions . . . Cumulative impacts result from individually minor but
21 collectively significant actions taking place over a period of time" (CEQ, 1997). Much of the
22 NEPA cumulative effects analysis is qualitative, but risk assessments and cause-and-effect
23 relationships are key parts of the analysis process for controversial projects.
24
25 In 1997, the Agency issued a policy memo, Guidance on Cumulative Risk Assessment,
26 Part 1: Planning and Scoping (USEPA, 1997a), which took the first formal step towards
27 developing guidance and guidelines for cumulative risk assessment.
28
29 By the first decade of the twenty-first century, cumulative risk assessment applications
30 have become relatively common. These applications are not only for assessments of chemicals
31 which operate by the same mode of action, as is mandated for the USEPA Pesticides Program,
32 but also community based, population-based, assessments which may include more varied
33 stressors than just chemicals alone. Much like the "place-based" ecological assessments, which
34 may cover a wide variety of physical, chemical, and biological stressors, some communities have
35 added human health and perhaps "quality of life" to the endpoints of interest in their place-based
36 assessments. It is the demand for more sophisticated human health risk assessments that has
37 driven the need for research into cumulative risk assessment, population-focused assessments,
38 aggregate exposure assessment, and risk from chemical mixtures.
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1.1. Purpose and Scope of the Framework Report
An understanding of the finite purpose and scope of this Framework report is important.
EPA and other organizations need detailed, comprehensive guidance on methods for evaluating
cumulative risk. Before such detailed Agency-level guidance is developed on a relatively new
field of risk assessment, it has been the recent policy of the Agency to first develop a simple
framework as a foundation for later comprehensive guidance. This Framework for Cumulative
Risk Assessment will emphasize chemical risks to human health in its discussion, but will do so
in the context of the effects from a variety of stressors, including non-chemical stressors. Some
important topics that could be
characterized as "cumulative risk," such as
global climate change, are beyond the
scope of this Framework report.
With this background, the
Framework has two simple purposes, one
immediate and one longer term. As a
broad outline of the assessment process,
the Framework immediately offers a basic
structure and provides starting principles
for EPA's cumulative risk assessments.
The process described by the Framework
report provides wide latitude for planning
and conducting cumulative risk
assessments in many diverse situations,
each based on common principles
discussed in the Framework report. The
process also will help foster a consistent
EPA approach for conducting and
evaluating cumulative risk assessments, for
identifying key issues, and for providing
operational definitions for terms used in
cumulative risk assessments.
In the longer term, the Framework
report offers the basic principles around
which to organize a more definitive set of
Cumulative Risk Assessment Guidance.
With this in mind, this report does not
provide substantive guidance on certain
issues that are integral to the risk
EPA's Risk Assessment Guidelines
Chemical Mixtures (USEPA 1986b)
Mutagenicity Risk Assessment (USEPA 1986c)
Carcinogen Risk Assessment (USEPA 1986d)
Developmental Toxicity Risk Assessment (USEPA 199la)
Exposure Assessment (USEPA 1992c)
Reproductive Toxicity Risk Assessment (USEPA 1996b)
Proposed Carcinogen Risk Assessment (USEPA 1996c, 1999a,
1999b)
Ecological Risk Assessment (USEPA 1998b)
Neurotoxicity Risk Assessment (USEPA 1998c)
Selected Policy and Guidance Documents
Risk Assessment Guidance for Superfund (USEPA 1989a)
Locational Data Policy (USEPA 1991b)
Framework for Ecological Risk Assessment (USEPA 1992b)
Application of Refined Dispersion Models (USEPA 1993a)
Policy /Guidance for Risk Characterization (USEPA 1995ab)
Benchmark Dose (1995c, 2000b)
Cumulative Risk Planning and Scoping (USEPA 1997a)
Guiding Principles for Monte Carlo Analysis (USEPA 1997b)
Acute Inhalation Exposure (USEPA 1998d)
Chemical Emergency Risk Management (USEPA 1998e)
Draft Comparative Risk Framework (USEPA 1998f)
Aggregate Exposure and Risk (USEPA 1999g)
Community Involvement in Superfund RA (USEPA 1999c)
Guidance for Ofisite Consequence Analysis (USEPA 1999d)
Guideline on Air Quality Models (USEPA 1999e)
Framework for Community Based Env. Prot. (USEPA 1999f)
Handbook for Risk Characterization (USEPA 2000c)
Handbook for Peer Review (USEPA 2000d)
Supplementary Guidance for Conducting Health Risk
Assessment of Chemical Mixtures (USEPA 2000e)
Cumulative Risk Assessment of Pesticide . . . Common
Mechanism of Toxicity (USEPA, 2002a)
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1 assessment process (see box at right and Appendix B for a listing of useM resources). These
2 include specific analytical methods, techniques for analyzing and interpreting data, and guidance
3 on issues influencing policy. Rather, on the basis of EPA experience and recommendations of
4 peer reviewers, EPA has reserved discussion of these important aspects of cumulative risk
5 assessment for future Guidance, which will be based on the risk assessment process described in
6 this Framework report.
7
8 This Framework report is meant to lay out broad areas where analysis might be conducted
9 if needed. It does not suggest that cumulative risk assessment is a tool that should be used with
10 every issue, nor does it suggest that when cumulative risk assessment is applied, that all areas of
11 analysis outlined or discussed here must or even should be conducted in every assessment. The
12 scope of the assessment should be defined in the planning and scoping stage (see section 2.1),
13 and may include or exclude stressors or pathways as relevant to the particular context or
14 application. In some areas discussed in this Framework report, the methodology for doing the
15 risk analysis currently may not exist.
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17
18 1.2. Intended Audience
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20 This Framework report is primarily intended for EPA risk assessors, EPA risk managers,
21 and other persons who either perform work under EPA contract or sponsorship or are subject to
22 EPA regulations concerning risk assessments. The terminology and concepts described here also
23 may be of assistance to other Federal, State, and local agencies as well as to members of the
24 general public, including stakeholders, who are interested in cumulative risk assessment issues.
25 The style and language used in this Framework report are chosen to be understood by as wide a
26 variety of interested parties as possible, from the policymaker to the risk assessment scientist to
27 the concerned non-scientist member of the general public. It is hoped that this Framework report
28 will be the first step in developing abroad scientific consensus about cumulative risk assessment,
29 and that further guidelines and guidance will build upon this foundation.
30
31
32 1.3. Key Definitions in Cumulative Risk Assessment3
33
34 In this Framework report, "cumulative risk" and "cumulative risk assessment" are defined
35 as follows, assuming a defined population:
36
In this section, a few basic definitions related to cumulative risk assessment will be discussed. For a glossary of
terms, the reader is directed to Section 5.
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1 Cumulative Risk: The combined risks from aggregate exposures4 to multiple agents or
2 stressors.
3
4 Cumulative risk assessment: An analysis, characterization, and possible quantification
5 of the combined risks to health or the environment from multiple agents or stressors.
6
7 There are several key points which come from this definition of cumulative risk. First,
8 cumulative risk involves multiple agents or stressors, which means that assessments involving a
9 single chemical or stressor are not "cumulative risks" under this definition. Second, there is no
10 limitation that the "agents or stressors" be only chemicals. "Agents or stressors" may be
11 chemicals, of course, but they may also be biological agents, or physical agents, or even the
12 absence of a necessity such as habitat. Third, this definition requires that the risks from multiple
13 agents or stressors be combined. This does not necessarily mean "added," but it means that some
14 analysis needs to be conducted as to if, and how, the effects or risks from the various agents or
15 stressors interact. It also means that an assessment which covers a number of chemicals or other
16 stressors, but which merely lists each chemical with a corresponding risk without consideration
17 of the other chemicals present, is not an assessment of cumulative risk under this definition.
18
19 The definition of cumulative risk assessment follows from the definition of cumulative
20 risk, but again, there is a key point: cumulative risk assessments can be qualitative as well as
21 quantitative.
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23 Some examples of types of cumulative risk assessments, and some examples of
24 assessments we would not describe as "cumulative risk assessments," are listed below. Each of
25 these presupposes a defined individual or population5:
26
27 1. Single agent or stressor assessments. Risks can be added or accumulated over time
28 for a single agent or stressor across sources, environmental pathways, or exposure routes. This
29 is consistent with "aggregate risk" in the FQPA terminology in the box on the next page.
30 Although this might conceivably be termed a cumulative risk assessment by some scientists, for
31 clarity in this Framework report, such single-stressor assessments will be termed "aggregate risk
32 assessments," rather than "cumulative risk assessments." Examples of this type of assessment
33 might be a multi-source assessment of benzene risk in a community, or an assessment of
34 individual risk to a specific pesticide from all uses combined. This type of assessment is not
See the text box on the following page for a definition of aggregate exposure.
Populations can be defined by geophysical boundaries, such as awatershed, geopolitical boundaries, suchas city or
county limits, or by cultural, racial, economic, or other criteria within a certain geographic boundary such as a neighborhood. The
definition of a population needs to be clear enough so that it can be agreed upon whether any specific individual is included in or
excluded from Ihe population.
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FQPA's Terminology Interpretations
The Food Quality Protection Act of 1996 [P.L. 104-170]
discusses the addition of exposure for a single chemical
across sources, pathways, routes, and time as aggregate
exposure. To be consistent with that terminology, the
Agency has elected to speak of multiple source/pathway/
route single stressor exposures and risks as "aggregate
exposures" and "aggregate risks." The EPA Science
Policy Council's Cumulative Risk Subcommittee has
developed the following working definitions for single-
chemical or single-stressor situations:
Aggregate exposure: The combined exposure of
an individual (or defined population) to a specific agent or
stressor via relevant routes, pathways, and sources.
Aggregate risk: The risk resulting from aggregate
exposure to a single agent or stressor.
discussed in this Framework except to be
referred to occasionally for clarity and
contrast to cumulative risk assessments.
2. Multiple stressor assessments.
Exposures can be accumulated over time,
pathways, sources, or routes for a number of
agents or stressors. These stressors may cause
the same effects (e.g., a number of
carcinogenic chemicals or a number of
threats to habitat loss), or a variety of effects.
A risk assessment for multiple stressors may
evaluate the risks of the stressors associated
health effects or ecological impacts, one
effect or impact at a time, or it may evaluate
the combined risk from some or all the
effects or impacts together. In either case, we
will call these assessments cumulative risk
assessments.
A multiple stressor cumulative risk assessment is distinct from a series of aggregate risk
assessments as it includes consideration of any combined impact of the stressors including the
potential for interactions among stressors (e.g., synergism or antagonism). One example of a
multiple stressor, single effect cumulative risk assessment would be the combined risk to an
individual or population from a series of pesticides all acting by the same mode of action and
causing the same effect.
Another example would be a dioxin assessment, where toxic equivalency factors (TEFs)
are used to combine the toxicities of dozens of different congeners of chlorinated dibenzo-p-
dioxins and dibenzofurans, resulting in a single estimate of risk for a specific effect from the
combination of congeners.
Another example is a physician's use of a model, derived empirically from
epidemiological studies, to estimate the probability of a woman's developing breast cancer over
the next ten years. The "stressors" in the example of the breast cancer model are certain factors
known to be correlated with that form of cancer, such as the woman's age at first childbirth, age
at menarche, having a previous biopsy with atypical hyperplasia, and others. This example shows
that stressors may not necessarily be chemical stressors, nor do they all even need to be the same
types of stressors.
Another type of cumulative risk assessment that will be discussed in this report is the
multiple stressor, multiple effects assessment. Again, stressors need not be limited to chemicals,
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nor do they even have to be the same
types of stressors to be included in this
type of assessment. Nor do the effects
have to be similar. For example,
chemical, biological, radiological, other
physical, and even psychological stressors
can cause a variety of human health or
ecological health effects. Assessing the
risk for these situations is considerably
more complex methodologically and
computationally than the examples of
aggregate risk assessments or single-
effect cumulative risk assessments given
in the above paragraphs.
As complex as this may sound,
there are several examples of this type of
assessment. Although these analytical
approaches may start with the stressors
and predict the risk of effects, more
generally these types of assessments start
with a defined geographical area or
defined population and try to determine
what stressors are important.
For example, cumulative
ecological risk assessments such as those
that have been conducted in the Columbia
River Basin and the Chesapeake Bay
focus on a number of observed adverse
conditions, then attempt to determine, among all of the possible stressors, which particular
combination is responsible for the observed adverse conditions (Barnthouse, et al., 2000).
The National Research Council, in its 1994 book Science and Judgment in Risk
Assessment (NRC, 1994, appendix I), lays out the general mathematics fora quantitative
approach to multiple stressor, multiple effect assessments. Recently, Bogen (2001) used this
approach to quantify combined risk of cancer and noncancer endpoints induced by the chemical
trichloroethylene (TCE), including quantitative characterization of associated interindividual
variability and associated uncertainty (including uncertainty regarding mechanism of
carcinogenic action). Technical hurdles involved in implementing this approach become those of
defining the set of relevant (preferably independent) endpoints and of quantifying the likelihood
of inducing each adverse health or ecotoxic response considered unacceptable as a function of the
Cumulative Risk Assessment Features
While many different types of exposures, stressors and other
factors can be included, the definition of cumulative risk might
be better understood by contrasting the featured and optional
considerations. By the definition given above for this Framework
report, the following features are included:
• multiple stressors
• consideration of how the stressors act together, rather
than individually
• population focused assessment. Although this does not
mean that the assessment must start with a population
and work "backwards" toward the source, it does mean
that the population needs to be defined and multiple
stressors are assessed with regard to impact on that
population, although not every individual will see the
same (or all) effects.
Additional layers of complexity, such as those listed below, may
or may not be addressed:
• multiple durations, pathways, sources, or routes of
exposure.
• multiple effects or impacts.
• nonconventional stressors or risk factors (e.g., lifestyle,
access to health care). These in general need continued
research.
• quantification of risks.
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1 endpoints.
2
3 Another example of a type of multiple stressor, multiple effect assessment would be a
4 cumulative community health risk assessment.
5
6 We believe that the definition of cumulative risk used in Ihis Framework report is
7 consistent with the sense of most definitions of "cumulative" such as are included in NEPA or
8 FQPA. A summary of the features and options of a cumulative risk assessment, by the definition
9 used in this report, is given in the box on the previous page.
10
11
12 1.4. The Cumulative Risk Assessment as a Tool for a Variety of Users and Purposes
13
14 As discussed in the Introduction, the results of the assessment should reflect the purpose
15 for doing the assessment. Information from cumulative risk assessments can also serve a variety
16 of other purposes, however. Insights gained may also be used to partly meet regulatory
17 mandates, to help identify targets for enforcement actions, or be considered when shaping policy
18 and regulation. Assessments may also conceivably be used in the long term planning with regard
19 to siting new sources of potential pollution in specific areas. Assessments also may be used for
20 general educational purposes not directly related to an immediate decision on a course of action.
21 Assessment results can also help guide priorities for voluntary or regulatory action, or to
22 mobilize community efforts to address concerns. They can be done retrospectively (to determine
23 past or current risks), prospectively (to assess the risks of, say, proposed facilities), or even
24 creatively (to design a development plan for a community). As helpful as results may be in any of
25 these other uses, however, some consideration must be given to the appropriateness of using the
26 assessment for these purposes, given the objectives and scope of the assessment.
27
28 Risk assessment, including cumulative risk assessment, is conceptually an analytic-
29 deliberative process (NRC, 1996). It includes both analytic (i.e., rigorous, replicable methods,
30 evaluated under the agreed protocols of an expert community) and deliberative (i.e., stakeholder-
31 value-and-judgment based) parts. Much of what is discussed in Chapter 2, the Planning and
32 Problem Formulation Phase, is deliberative in nature, which means it depends on input from
33 experts other than those who know how to do risk assessments. These include persons who are
34 knowledgeable about a community and its values. Although much of Chapter 3, the Analysis
35 Phase, is given over to the analytic process where risk assessment experts apply science to a
36 problem, the deliberative aspect returns in Chapter 4, the Interpretation Phase, especially where
37 risks of different types are being evaluated and combined.
38
39 Cumulative risk assessment, because of this analytic-deliberative process, can be applied to a
40 variety of different problems where analysis of the overall impacts of multiple sources, stressors,
41 pathways, or routes is necessary. It can be used as a regulatory analysis tool, such as in reviewing
42 the overall impact of several different pesticides that all act by the same mode of action (ILSI,
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1 1999), or in NEPA analyses (CEQ, 1997).
2 It can be used to analyze the overall
3 impacts of permit decisions or the results
4 of compliance with permits in a given
5 community.
6
7 Cumulative risk assessment can
8 also be used in a community-based
9 assessment approach, such as is outlined
m • CTIA> r if ^ v. Source: USEPA, 1999f
10 in EPA s Frameworkfor Commumty-
The Core Principles of Community-Based
Environmental Protection (CBEP)
1. Focus on a definable geographic area
2. Work collaboratively with stakeholders.
3. Assess the quality of all resources in a place.
4. Integrate environmental, economic, and social objectives.
5. Use the most appropriate tools.
6. Monitor and redirect efforts through adaptive management.
11 Based Environmental Protection
12 (USEPA, 1999f). The CBEP approach
13 (see box) encompasses both ecological and human health assessments. Cumulative risk
14 assessment, being a population-based or place-based analytic-deliberative process, is ideal for
15 CBEP-type applications.
16
17 Cumulative risk assessment is also applied in ecological assessments. The definition of
18 cumulative ecological risk assessment, as given in the EPA's 1998 Guidelines for Ecological
19 Risk Assessment is: A process that involves consideration of the aggregate ecological risk to the
20 target entity caused by the accumulation of risk from multiple stressors (USEPA, 1998b). A
21 recent Society of Environmental Toxicology and Chemistry publication (Foran and Ferenc, 1999)
22 discusses multiple stressors in ecological risk assessment, and gives a good overview of the topic
23 of cumulative ecological risk assessment.
24
25 When should a cumulative risk assessment be done? Recognizing that the scope and
26 nature of a cumulative risk assessment may range from a very limited qualitative assessment of a
27 local situation, to a comprehensive assessment of the cumulative risk patterns for a large
28 community, to a national assessment conducted within one of EPA's programs, the simple
29 answer is that one should be conducted whenever the combined impact of multiple stressors
30 needs to be considered. Only experience with these assessments over a period of time will
31 provide the wisdom needed to develop practical guidelines on this question.
32
33
34 1.5. The Broader Decision-Making Context for Cumulative Risk Assessment
35
36 Cumulative risk assessments maybe used to form hypotheses that could be tested, but it
37 is more likely that these assessments will be used as decision-making tools. Decisions can be at
38 a wide variety of levels, from a neighborhood group evaluating ways to improve or safeguard
39 their health and environment, to a Federal official weighing options for action at a much broader
40 geographical level. Although the decision-making method is beyond the scope of this Framework
41 report, such decisions usually involve more than the basic science and analysis that make up the
42 "scientific" part of risk assessment. Robert T. Clemen, in his book Making Hard Decisions notes
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1 that in one type of decision-making approach (called decision analysis):
2
3 Managers and policy makers frequently complain that analytical procedures from
4 management science and operations research ignore subjective judgments. Such
5 procedures often purport to generate "optimal" actions on the basis of purely objective
6 inputs. But the decision-analysis approach allows the inclusion of subjective judgments.
7 In fact, decision analysis requires personal judgments: they are important ingredients for
8 making good decisions. (Clemen, 1996, page 5)
9
10 Regardless of the type of decision being made or the decision-making approach, a
11 cumulative risk assessment's analytic part is not the decision-making vehicle in itself. That is,
12 "cranking out the numbers" will not be the sole basis for a decision. Although in some cases, the
13 estimated risks can weigh heavily in the decision, understanding the risk estimate is but one
14 factor in a broader decision-making process including risk management components such as
15 technical feasibility, economic costs and benefits, political realities, and other factors. The U.S.
16 EPA's Science Advisory Board (SAB) in their August, 2000, publication Toward Integrated
17 Environmental Decision-Making (USEPA, 2000a), constructed a framework for what it termed
18 Integrated Environmental Decision-making (ED). The SAB noted that "The IED Framework
19 recognizes that risks often are experienced simultaneously and are cumulative. . .". It speaks of
20 risk assessments in a very broad way, including human health effects, ecological effects, and
21 quality-of-life effects. The first phase and part of the second phase of the IED, "Problem
22 Formulation" and "Analysis and Decision-making" essentially correspond to the three phases we
23 discuss in this Framework for Cumulative Risk Assessment. Decision-making, and the SAB's
24 third phase, "Implementation and Performance Evaluation," are beyond the scope of this
25 Framework report.
26
27 The SAB's report (USEPA, 2000a) gives a good insight into the broader context for
28 cumulative risk assessment, and some of the aspects of the analytic-deliberative parts of the
29 assessment. The analytical-deliberative process will be discussed more in Chapters 2 through 4,
30 as these phases of the cumulative risk assessment process are examined.
31
32 The 1996 book Understanding Risk (NRC, 1996) also provided much information on the
33 analytic-deliberative aspects of a risk assessment, and devoted a great deal of discussion to risk
34 characterization. Needless to say, it is very important to apply cumulative risk assessment in the
35 context of the decision or decisions to be made. This is most efficiently done by early and
36 continued attention to the "risk characterization" step in the risk assessment process (NRC, 1996;
37 USEPA, 2000c). The box in section 4.1 summarizes some of the points made in Understanding
38 Risk.
39
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Cumuls
itive Risk
Assessment
Planning, Scoping, and
Problem F onmilation
/
\
/
N
v /
/ \
Analysis
\ /
/ N
\
/
\
/
Interpretation and
Risk Characterization
1
2
3
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5
6
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Figure 1-3. Framework for Cumulative Risk Assessment
1.6. Organization of this report
Figure 1-3 shows the basic structure of this Framework for Cumulative Risk Assessment.
Each of the three general process steps are described in detail in later chapters. The Framework is
organized to follow the outline in Figure 1-3, namely (a) a planning, scoping, and problem
formulation phase (Chapter 2), (b) an analysis phase (Chapter 3), and (c) an interpretation phase,
where the risk characterization is completed (Chapter 4). Chapter 5 is a glossary of terms,
followed by References in Chapter 6. Additional information on selected resources and
cumulative risk related topics are provided in the appendices.
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Planning, Scoping, and
Problem Formulation
Analysis
Interpretation and
Risk Characterization
Figure 2-1. The Planning, Scoping, and Problem Formulation Phase.
2. THE PLANNING, SCOPING, AND PROBLEM FORMULATION PHASE
The first step in any risk assessment process is to define the problem to be assessed. This
step has been called "problem formulation" in the Framework for Ecological Risk Assessment
(USEPA, 1992b), the NRC book Understanding Risk {NRC, 1996), Toward Integrated
Environmental Decision-Making (USEPA, 2000a) and elsewhere (e.g., USEPA, 1997a). It is a
phase where, according to NRC, "public officials, scientists, and interested and affected parties
clarify the nature of the choices to be considered, the attendant hazards and risks, and the
knowledge needed to inform the choices" (NRC, 1996).
Planning and Scoping of the assessment are often thought of as being part of the Problem
Formulation phase, although the 1997 Planning and Scoping guidance treats Planning and
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1 Scoping as a separate activity before problem formulation begins (USEPA, 1997a). Whether it is
2 considered a separate phase or not, it takes place at the very start of the process of doing a
3 cumulative risk assessment. For convenience, this section incorporates both Planning and
4 Scoping and Problem Formulation into a single phase.
5
6
7 2.1. Planning and Scoping
8
9 Risk assessments are conducted within some context, that is, they are usually conducted
10 because of a regulatory requirement, a community need, a health crisis, or some other "driving
11 force." This context generates individuals or groups with interest in having the assessment done,
12 and there are several summary articles or books available about the challenges of successful
13 participation bythese interested parties (e.g., Chess and Purcell, 1999; Frewer, 1999; Thomas,
14 1995). Theymay be public officials, risk experts, community leaders, or anynumber of others.
15 Planning and scoping begins with a dialogue among these interested parties.
16
17 Among these interested parties, there will be a person or a group of people charged with
18 making decisions about how a risk may be mitigated, avoided, or reduced. For the sake of
19 simplicity, we will call this person or group the "decision maker," or "risk manager6," and for
20 ease of discussion, will discuss the risk manager as if it were a single person.
21
22 During planning and scoping, risk experts (including those involved in assessing risk
23 such as ecologists, toxicologists, chemists, along with other technical experts such as economists
24 and engineers) and decision makers work together as a team, informed by stakeholder input, to
25 develop the rationale and scope for the risk assessment and characterization.
26
27 As part of the initial discussions concerning the need for a risk assessment, other
28 "interested and affected parties" besides the risk manager and risk assessor may help define
29 purpose, scope, and approach. This "risk assessment planning team" seeks agreement through
30 extensive dialogue and discussion on what analytical and deliberative steps need to be taken, and
31 by whom, by when, and why (USEPA, 2000a). The SAB's report Toward Integrated
32 Environmental Decision-Making explains some of the roles of the various participants on the risk
33 assessment planning team during the Planning and Problem Formulation phase:
34
35 "Scientists play an important role in [this phase] by collecting, analyzing, and presenting
36 data in such a way that all parties can appreciate the type and magnitude of the problem(s)
37 under discussion. This activity will generally involve all four parts of risk assessment,
38 including assessment of exposures experienced by special populations and/or ecological
39 resources. Planning, scoping, and screening - including selection of endpoints of
We will use the term "risk managemenfto indude actions that the risk assessment team recommends or implements
that are not taken by the risk assessment team,/>er se. These include actions to address the problems taken by others outside the
process, who may not be identified until the analysis is underway or complete.
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1 concern — also requires explicit input of societal values and stakeholder participation.
2 For instance, while some of the ecological endpoints may be chosen because of their role
3 in a valued ecosystem, there may also be ecological endpoints chosen because of their
4 direct significance to society. Examples of the latter include both economically important
5 species and 'charismatic' species. Similarly, in integrated decision-making, judgments
6 may have to be made about diverse health endpoints, such as cancer risks in the general
7 population and the risk of reproductive/developmental risks in children. While scientists
8 can help characterize such risks, they are not uniquely qualified to set priorities among
9 them and broader deliberation is essential. Finally, decision-makers also play an
10 important role during problem formulation; in addition to bringing the scientific and other
11 resources of the Agency to bear on the problem, they also should help to identify the
12 range of potential decisions and viable management options, while examining economic,
13 political, or other constraints on those options. Decision-makers also serve as managers
14 of the overall process." (USEPA, 2000a)
15
16 Another role of the risk assessment planning team is documentation. The activities of the
17 following sections are important, and should be documented by the team for several reasons.
18 Written records can be referred to by assessors and people at public meetings. They can also help
19 prepare for responding to comments, and begin establishing a peer-review record for any later
20 decisions or plans that need to be peer reviewed (USEPA, 2000d). The risk assessment planning
21 team should consider whether or not the overall project is to be peer reviewed, and if so, what
22 type of peer review will be conducted. The team should plan and execute the peer review at the
23 appropriate time. A peer review by an independent review group will not only help establish the
24 validity of the science, but can also provide neutral comments on some of the interpretations of
25 the assessment.
26
27 In some cases, it may be useful for the stakeholders to appoint a "point person" to serve
28 as point of contact for communications. This is not to imply that stakeholders must speak with a
29 single voice (which is not likely in any case), but that they have at least one person to help
30 facilitate interactions and identify available technical resources and other sources of information.
31 The Agency or stakeholders may also consider a public web site for the project. A variety of
32 resources can be posted, including cumulative risk tools and databases, project-related news, list
33 of experts, glossary, reports, related links, etc. An online discussion forum could also be
34 included on the web site as a more interactive way of exchanging information with stakeholders.
35
36 Finally, while including stakeholders in the risk assessment process, a regulatory agency
37 like EPA needs to balance stakeholder participation with the Agency's need to retain the ability
38 to carry out its responsibility to protect public health and the environment. For this reason, EPA
39 will usually need to set some reasonable boundaries around the process to ensure that progress is
40 being made in a timely and efficient fashion.
41
42 2.1.1. Defining the Purpose of the Assessment
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As discussed in section 1.5 above, the risk assessment should be developed to inform the
risk management decision by constructing an appropriate, decision-relevant risk characterization.
After the risk assessment planning team is assembled, the dialogue between the decision maker
and risk experts begins with a discussion on risk management objectives and information needed
to manage risks in the particular situation. The manager and assessment planning team must
discuss any regulatory or legal basis for the risk assessment, and what kind of information is
needed to satisfy such requirements. If interested and affected parties are part of the risk
assessment planning team, it is especially important that the entire team agree on the purpose of
the assessment, since a differing sense of purpose among the team will lead to problems later.
The purpose and risk management objectives guide the risk assessment strategy (see box for
some possible management goals from which risk management objectives can be derived, e.g., in
terms of key participants, data sources, selection of assessment endpoints, approach, and the
schedule for developing the assessment).
The previous discussion follows the
typical situation where the risk manager is
presented as an independent decision-maker,
such as a senior official in a regulatory agency
who is responsible for establishing permit
conditions for a facility of some type. There
are situations, however, where the risk
manager maybe one of the interested parties,
such as a local citizens' board. For example,
the risk assessment may indicate that
mitigation of risks may not be significantly
affected by any permit decisions but will
depend instead on local zoning decisions or on
decisions which affect traffic patterns in a
community. This is one of the reasons why, in
the final step in the planning and problem
formulation phase, the discussion of possible
outcomes (discussed in section 2.3), is so
important.
Possible Management Goals
The goals of risk management are varied. They may be risk
related, aiming to:
• Reduce or eliminate risks from exposure to hazardous
substances.
• Reduce the incidence of an adverse effect.
• Reduce the rate of habitat loss.
They maybe economic, aiming to:
•Reduce the risk without causing job loss.
•Reduce the risk without reducing property values.
They mayinvolve public values, aiming to:
• Protect the most sensitive population.
• Protect children.
• Preserve a species from extinction.
Source: Presidential/Congressional Commission, 1997
2.1.2. Defining the Scope of Analysis and Products Needed
Scoping a cumulative risk assessment effort involves defining the elements that will or
will not be included in the risk assessment7 (USEPA, 1997a). These include the sfressors,
sources, pathways, routes, and populations to be evaluated. As illustrated by the examples in the
text box (next page), the scope of a cumulative risk assessment may be narrow or broad. Initially,
An assessment which looks at all stressors over a period of time for a specific population would be a "total risk"
assessment, which is difficult to perform given our current methods.
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Examples of Different
Cumulative Risk Assessment Scopes
• Health risks associated with the aggregate exposure (via
all pathways and routes) to insecticides acting by a
common mode of action.
• Human health risks associated with outdoor inhalation
exposures of the general population to 33 priority air
pollutants nationwide.
• Human health risks associated with exposure via all
routes to all pollutants present or being released from a
hazardous waste site.
• Human health risks, for a specific neighborhood,
associated with exposure via all routes to all pollutants
present or being released from a set of adjacent sources,
including several industries, two hazardous waste sites,
traffic, and a municipal landfill.
the risk assessment planning team needs to
select the kind of risk information, exposure
scenarios and assessment issues that need to
be covered. These should be directly linked
to the risk-related questions being asked
when establishing the purpose. Limitations in
scope can be geographical (such as political
or ecological boundaries), environmental
(such as assessing only certain media),
demographic (such as assessing only risks to
children or asthmatics), statutory, or by using
other criteria such as data limitations. The
issue of "background" exposures to stressors
should be discussed and agreements reached
(see Appendix C). An adequate assessment
scope should make it clear what's included
and what's excluded from the assessment.
Care must be taken to reconcile the
limitations of scope with the list of questions to be answered in the statement of purpose. If, for
example, data limitations preclude the addressing of certain of the questions outlined in the
purpose, the list of questions to be addressed should be modified and the risk assessment
planning team agree to the narrower scope of the assessment.
Reasons for choosing the particular scope of the assessment, and how it will address the
questions posed in the purpose statement, should be stated explicitly. Defining the scope of the
assessment should include details on the limitations of resources, limitations of data, the impact
of risk elements on the risk estimate (i.e., some pathways maybe seen as having negligible
impact on the risks related to the questions being addressed), and limitations of the methods
available. In cases where an element of risk is likely to be important, but no valid data are
available, the assessor must highlight this deficiency or use judgment or assumed values to
approximate the missing data. Such judgments and approximations should be clearly
documented, and explained to the manager in the risk characterization.
Once the elements (sources, stressors, populations, etc.) have been identified through
brainstorming with all participants, the participants should discuss the need for and availability of
technical information and how such information may affect the overall uncertainty of the
assessment. Using input from the risk assessor, the risk assessment planning team must
determine what elements will and will not (or, can and cannot) be included in the risk
assessment. Some of the stakeholder concerns may not be suitable for analysis by risk
assessment, so other expertise and evaluation maybe required to provide this additional analysis.
Information gathered at this stage is preliminary and may be modified during the analysis phase.
Identification of potential stressors, populations to be assessed, and potential effects are all part
of the scoping process, and help define the method of approach.
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As examples of some of these scoping elements, stressors can include physical (including
radiological) stressors or chemical or biological agents that may cause an adverse effect. The
sources of the stressors can be human activities in sectors of society (e.g., manufacturing,
transportation, agriculture, land development), personal human activities (e.g., smoking, diet, and
other "lifestyle activities") or natural phenomena (e.g., forest fires, floods). Stressors that are not
physical, chemical, or biological, such as economic or other quality-of-life stressors may also be
identified, but good techniques for including the effect these have on risk currently may not exist.
Possible population elements to be assessed usually focus on the entities that are at risk,
e.g., populations, communities, ecosystem functions, or vulnerable subpopulations such as
persons with certain diseases, or persons at vulnerable life stages, such as children. The more
specifically these can be defined, the more focused the analysis can be. This will be helpful in
interpreting the results of the assessment.
2.1.3. Agreeing on participants, roles and responsibilities
The risk assessment planning team will usually recommend others who should participate
in the assessment's planning, scoping, and risk analysis phase. Depending on the schedule,
approach, and level of effort envisioned for the risk assessment, there maybe no additional
participants, or there may be many. Assessments will usually require substantial technical
expertise in the analytic portions of the assessment. Some of the fields of science that maybe
necessary or helpful include toxicology, epidemiology, ecology, risk assessment, exposure
assessment, fate and transport modeling (e.g., indoor and outdoor air, surface and drinking
water), computer science (including geographical information systems [GIS]), chemistry,
biology, various engineering fields (e.g., chemical, mechanical, industrial, civil), economics,
sociology, and others.
For the deliberative portions of the
assessment, there can be a number of
stakeholders and other interested parties that
should be considered for participation. The
box at the right lists some examples to choose
from among interested or affected parties for
the deliberative portions of the assessment.
For community-based assessments, in
particular, it is important that community
involvement be sought and encouraged. The
Presidential/Congressional Commission on
Risk Assessment and Risk Management
[hereafter, the "Commission"] (1997) suggests
the following questions to identify potential
Examples of Possible Interested or
Affected Parties (Stakeholders)
(adapted from USEPA 1999b)
State governments
Tribal governments
Local governments
Community groups
Grassroots organizations
Environmental groups
Consumer rights groups
Religious groups
Civil rights groups
Affected industry
Civic organizations
Business owners
Trade associations
Labor unions
Public health groups
Academic institutions
Impacted citizens
Other federal agencies
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interested or affected parties (stakeholders):
• "Who might be affected by the risk management decision? (This includes not only
groups that already know or believe they are affected, but also groups that may be
affected but as yet do not know it.)
• "Who has information and expertise that might be helpM?
• "Who has been involved in similar risk situations before?
• "Who has expressed interest in being involved in similar decisions before?
• "Who might be reasonably angered
if not included?"
It has become increasingly recognized
as important that stakeholders be involved in
risk assessment (e.g., NRC 1996,
Presidential/Congressional Commission. . .
1997,USEPA 1996a, 1997a, 1998a, 1999c,
1999 f, 2000a). The Commission suggested
guidelines for stakeholder involvement (see
box at right).
There are several issues concerning
the stakeholders' capacity to participate that
should not be overlooked by the risk
assessment planning team. First, some
stakeholders may need training to be able to
participate in technical and risk management
discussions. Second, as noted in the box at
right, some stakeholders may require
incentives such as travel funds or lodging at
sites of meetings outside the area where they
live. The risk assessment planning team,
along with the potential source of funds for
such incentives, should decide to what extent,
if any, such incentives can be provided, based
on the scope, level of effort, and financial
constraints of the risk assessment project.
Guidelines for Stakeholder Involvement
• Regulatory agencies or other organizations considering
stakeholder involvement should be clear about the extent
to which they are willing or able to respond to stakeholder
involvement before they undertake such efforts. If a
decision is not negotiable, don't waste stakeholders' time.
• The goals of stakeholder involvement should be
clarified at the outset and stakeholders should be involved
early in the decision-making process. Don't make saving
money the sole criterion for success or expect stakeholder
involvement to end controversy.
• Stakeholder involvement efforts should attempt to
engage all potentially affected parties and solicit a diversity
of perspectives. It may be necessary to provide appropriate
incentives to encourage stakeholder participation.
• Stakeholders must be willing to negotiate and should be
flexible. Theymust be prepared to listen to and learn f om
diverse viewpoints. Where possible, empower
stakeholders to make decisions, including providing them
with the opportunity to obtain technical assistance.
• Stakeholders should be given credit for their roles in a
decision, and how stakeholder input was used should be
explained. If stakeholder suggestions were not used,
explain why.
• The nature, extent, and complexity of stakeholder
involvement should be appropriate to the scope and impact
of a decision and the potential of the decision to generate
controversy.
Source: Presidential/Congressional Commission on Risk
Assessment and Risk Management, 1997
Roles and responsibilities for technical and non-technical participants (i.e., ground rules
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1 for participants) should also be proposed by the planning team, depending upon the schedule,
2 approach, and level of effort that is envisioned for the risk assessment. There will be several key
3 points in the risk assessment process where stakeholder input will be critical. Some of these are
4 the agreements on purpose, scope, and approach Each project should define and agree upon a list
5 of critical points for stakeholder input. The team may even decide to break stakeholders out into
6 several subgroups, with specific tasks such as (1) to understand the technical information and
7 report back to the larger group; (2) to elevate and clarify stakeholder issues as needed; or (3) to
8 provide information and facts to their peers and the analysts.
9
10 Sometimes citizens choose not to participate because they feel they will not influence the
11 outcome, the issue is too complex or technical, the effort is too great, or because the decision
12 process is unclear (USEPA, 200 Ic). Moreover, despite increased emphasis on stakeholder
13 participation, there are instances where it may not be appropriate for large scale stakeholder
14 involvement. EPA (as the decision maker) must determine whether, and to what degree,
15 stakeholder involvement in a cumulative risk decision will be useful and what objectives it may
16 accomplish. There is a continuum of objectives that may apply to individual cases, from
17 exchanging information on one end, through obtaining stakeholder recommendations, to
18 developing agreements for joint activities at the other end (USEPA, 1998g).
19
20 Much of the activities and data needed for cumulative risk assessment overlap the
21 jurisdiction of EPA, other public health agencies, and academia. The most successful future
22 cumulative risk assessments are likely to be those where cooperation among organizations
23 (Federal, State, private, environmental, academic, etc.) leads to use of the best data and tools for
24 the various parts of the assessment
25
26 2.1.4. Agreeing on the Depth of the Assessment and the Analytical Approach
27
28 The analysis approach (discussed further in section 2.2.3 and chapter 3) may fall
29 anywhere on a continuum from relatively unsophisticated methods which rely heavily on default
30 (and often conservative) assumptions, and consequently have greater uncertainty, to increasingly
31 refined assessments in which data are substituted for assumptions and uncertainty is reduced.
32 Some of the factors that go into deciding on the approach include the level of uncertainty in the
33 risk estimates that is acceptable to the participants, the intended use and audience for the
34 assessment, the time and money resources available, and the amount, quality and accessibility of
35 data. In making the decision on approach, there will need to be an understanding of both the
36 level of effort necessary for conducting the assessment selected, with an insight to alternatives,
37 and the features and limitations of the selected approach, in comparison to other approaches.
38
39 2.1.5. Agreement on the Resources Available and Schedule
40
41 Schedule and resources are often interrelated. They may also affect whether the work is
42 performed in-house by the organization or team desiring the assessment, or by contractor or other
43 external source. The need to meet external deadlines or coordinate with schedules of other
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organizations may become an overriding factor in defining what will be prepared. Assessments
requiring short-term, low budget efforts, or preliminary screening assessments, may not have the
scope, time or resources where extensive stakeholder involvement is necessary or beneficial. For
assessments, especially those where there is extensive stakeholder involvement, a budget and
time schedule should be developed and known by all participants.
2.1.6. Review of Lessons Learned in
Similar Studies
Much time and effort can be saved by
taking the advice of those who have been
through this process - or similar processes -
before. Risk assessment reports will often have
a review chapter of "lessons learned" (or, "if I
had to do this over again, this time I would . .
."). We have tried to include some of the
discussion of recent Agency experiences as
examples to illustrate parts of this Framework
report. In addition, the reader is encouraged to
find similar advice in other reports (e.g., Lesson
Learned on Planning and Scoping for
Environmental Risk Assessments, USEPA,
2002b). EPA's Office of Water has conducted
several watershed studies over the past decade
and has compiled a web page with lessons
learned (USEPA, 200 Id). One of the lists from
that source is in the box at right, but there are
many others. Even though the studies were not
all cumulative risk studies, much of the wisdom
gained is relevant.
2.2. Problem Formulation, Conceptual
Model, and Analysis Plan
One outcome of the problem
formulation phase is a conceptual model that is
intended to identify relevant stressors, sources,
pathways, exposure routes, receptors, and
effects, and to identify relationships among
them. The conceptual model serves as a basis
for the analysis plan, which is used to focus the
analysis phase of the assessment. These three
components are discussed in the sections
Reed Holderman's Lessons Learned
(California Coastal Conservancy, Santa Ynez Wateished)
1. Be sure that [the project] is needed, and if it is, build
community support for it before proceeding.
2. Invite everyone into the process and ask political leaders
to select the steering committee. Otherwise, people will
ask, "Who appointed you?"
3. Don't b e presumptu ous. On th e Santa Yne z River, we
assumed everybody would appreciate a well thought out
scope of work, budget, and schedule. Wrong. They said it
only proved that the whole thing was a set-up. Next time,
let [the whole planning team] figure it out!
4. When the majority of stakeholders tell you that they
want to deal with their issue first, believe them. I remain
convinced that our failure to sustain interest in the Santa
Ynez River plan was primarily because we were not
willing to assist the County in carrying out its proposed
channel clearing activities in the Lompoc valley as a
separate and distinct project.
5. Do whatever you can to break down barriers and
perceptions people have of each other. Be creative.
Family BBQs, Softball games, and parties have done
wonders to improve relationships among stakeholders and
build trust.
6. Maintain constant communication among stakeholders
throughout the process - and especially in the beginning -
to pass information along, answer questions, or deal with
rumors. Whether it's through regular meetings,
newsletters, web sites, phone trees, or all four, good
communication is a must.
7. And finally, line up your money and in-kind services in
advance of starting your [assessment] project, or else two
bad things will happen: (a) your stakeholders will buy into
a process and scope of work only to find out they can't
afford it; and (b) you will spend more time looking for
cash than participating in the planning process. Either
way, you lose.
[Source: Lessons Learned Web page (USEPA, 2001d)]
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below.
The Science Advisory Board in their report Toward Integrated Environmental Decision-
Making (USEPA, 2000a) suggests a list of desired outputs from the Problem Formulation part of
an environmental decision-making exercise. Although this is not precisely the same as a risk
assessment, many of the points they list have applicability to risk assessment, also. The SAB
suggests these should not only be left to the visual presentation of the Conceptual Model
Diagram, but should also be explained in narrative form. Some of the SAB's recommended
outputs, included here as an example, are listed in the box below. Not all of these would
necessarily be applicable to a given risk assessment, depending on the scope.
Example: SAB's Desired Outputs for Problem Formulation
The initial goals for the decision-making exercise, including environmental goals to be achieved
Which environmental problems/stressors/systems will be included and which will not, and thereasons for these decisions
The health, ecological, and quality-of life effects of concern
The spatial, temporal, and organizational dimensions of the problem
Relevant data and models, and possible approaches to data analysis
Scoping of the uncertainties involved and research needed to significantly reduce critical uncertainties
Initial review of the range of options available to reduce risks, considering likely economic, political, or other constraints
The endpoints upon which the condition of the ecological, human health, or societal systems ultimately will be judged
The types of factors that will be considered when reaching a decision
From Toward Integrated Environmental Decision-Making (USEPA, 2000a)
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2.2.1. Problem Formulation.
Problem formulation is a systematic planning step that identifies the major factors to be
considered in a particular assessment. It is linked to the regulatory and policy context of the
assessment. Problem formulation is an iterative process within which the risk assessor develops
preliminary hypotheses about why adverse effects might occur or have occurred. It provides the
foundation for the technical approach of the assessment. The outcome of the problem
formulation process is a conceptual model that describes the relationship between the slressors,
the population exposed, and the assessment endpoints that will be addressed in Ihe risk
assessment.
2.2.2. Developing the Conceptual Model
A conceptual model includes both a written description and a visual representation of
actual or predicted relationships between humans (or populations, population segments) or
ecological entities and the chemicals or other stressors to which they maybe exposed.
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A Generalized Conceptual Model
with Examples of Possible Elements and Linkages
I Sirefftrf
Rcceptori
Aeliiitiejflul
gencroie ex
rcteue
rtr escort
-Manufacturing
-Rpssilfuel
combustion
(eg.,far
transp citation,
hearing,
electricity)
-Waste
process ing
-Mining
-Agricultural
activities
-Natural
processes
Chemical,
plwacal, ex
mule peal
^ igertfMiiith
c nee in
effect
Chemical
•* -Organic
-Inorganic
Biobgkal
-Pathogens
-Exotic spp.
Physical
- Thermal
-Erosion/
sedimentation
-Habitat
aleration
A iv^if {M o/ofte1
/ofJOTj (&.# ,
&aSft ifoTuj
i2rf«i to fsa&fi
ccsv) MOT import
individual or
populc&ion
susceptibility to
o&TVf sfressors
*
-
Surface Water, Air,
Indoor Ar ,
groundwater or soil
are prfhwiyf .
fbrindiviiiuik,
ingestion,
inhalation, or
dermal absorption
are the rcnitf cf
t5p*furt
BiDacctimilatiDn
fbrecobgical
emfties biotic and
abiotic mteractions
are fcejs to how
stressorsare
presents dto
receptors.
Duration (e.g.,
lifetime , a year, a
day) and rre qusncy
(eg.,contiraious or
periodk) de scribe
Eq» son Pattern* .
— *
Scoioeieal
Populations,
ecological
c omnmftilifi $
and
ecosystems
maybe
r ec eptcrf fur
some
stressccs.
Mas &i Hedi h
fcLiir.riiiiili
andgroT^sof
people are
also
recejrtorf
-fitf int£
- Sensitive pop
- Oc cupational
-Ijlinoriries
- Bus,'. Justice
Communities
Habitat structure ,
species distribution,
cfciersity
EC osystem c onditiins
• PopoMifltikvels
• envTonmentalproc e ss
rates
Status of critic al spec ies
or speciss of special
concern.
Endpoiib sre meannef cor
effect* of rtref j erf
Mat an I&alth Sj^ra'ras
^
McitiUy and Illness ,
such as:
Cancers
• leukemia, hmg, etc
Other adverse health
effects
• Asthma, respiratory
impacts
•Kidney dise ase
•CHS effects
•He.
Figure 2-2. An example of a generic conceptual model (adapted from USEPA, 2002a).
Conceptual models represent many relationships, and may describe primary, secondary,
or tertiary exposure pathways. The model is developed by the risk assessor and may include input
from other experts (including stakeholders). The model narrative needs to distinguish - to the
extent possible - between what is known or determined, and what is assumed. Also, it needs to
include a discussion of uncertainties in the formulation of the assessment and state how the
assessment is cumulative, i.e., for which sources, stressors/agents, pathways/exposure routes,
receptors/populations, and endpoints. In some cases, conceptual models will be submitted for
peer review. A general conceptual model is illustrated in Figure 2-2. The conceptual model
includes factors and endpoints which may not be analyzed in the risk assessment, but may be
evaluated in the overall decision-making process.
The conceptual model and the associated narrative show the basic rationale for the
decisions made in pursuing a particular course of action in a cumulative risk assessment. It
provides a record of decisions for future reference during risk analysis, characterization, and
communication of the risk management decision. It is also valuable as a risk communication tool
both internally within the Agency and externally in interactions with the public. The
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Heavy lines indicate dimensions/elements included in thleitial National Scale Assessment;
Light lines indicate dimensions/elementiiat may be included in future assessments
Sources
Siressors
Pathways/
Media
Routes
Subpopiifatioiis
Extrinsic
"background" in air
Extrinsic "background"
in other media
Other Air Toxics
[
Outdoor air
Indoo
rnicroenvir
Subset of PBTs
Ingestion
Hispanic
Endpoints
T
•hite
1
African
American
j
cers
ung, others)
1
I
i
^
i
General
Population
1
Asian American
j
Respiratory
i
Vn ii n n
Childre
T
1 j
1 I 1 I
Blood (including
marrow & spleen)
Adoles-
cents
1
! 1
CNS
1 1
Adults Elderly
i 1 '•
i 1 1
Li¥erS
kidney
Cardio- Other health
¥ascular effects
Measures
PQ/ltltti ^SJIZCiWC Bltf
g, fly
Cancers
(leukemia, lung, others)
1
Distribution of
high-end cancer po|
risk estimates
Respiratory
l_
1 1
1
Blood (including
marrow & spleen)
1
P«i Dte Carclioge if
P rotate Carcltogei:
K>owi Carcliogs is
Estimated percent of
julation within specifiei
cancer risk ranges
Estimated
number of
cancer cases
-
CardloBBCi Sr Hasrd lidex
Lteraid Mdiey Hazard lidei
CNSHaiardlidsit
Distribution of
estimated
index values
Estimated percent of
population within specifiei
ranges of index values
Figure 2-3. Specific conceptual model for a complex project, OAQPS' National Scale Air Toxics Assessment
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1 conceptual model provides a scientific or technical work product that includes: (1) the scientific
2 rationale for the selection of the stressors, sources, receptors, exposed populations, exposure or
3 environmental pathways, endpoints or effects, (2) the scientific, technical, economic, or
4 sociologic basis for the construction of the conceptual model; and (3) the scientific implications
5 of additional data gathering. Figure 2-3 is an example of a conceptual model from the National
6 Air Toxics Assessment8.
7
8 It is not inconceivable, given the deliberative nature of the process of developing a
9 conceptual model, that more than one model will be considered as alternatives. If the team
10 decides to ultimately use more than one model, and to evaluate each as part of hypothesis testing,
11 a careful consideration of time and monetary resources needs to be made, as well as a very
12 careful consideration of how the results will be interpreted (see section 2.3).
13
14 2.2.3. Constructing the Analysis Plan
15
16 The analysis plan is the final stage of planning and scoping before the risk assessment.
17 The analysis plan is discussed in the Ecological Risk Assessment Guidelines (USEPA, 1998b),
18 Section 3.5. The analysis plan describes how hypotheses about the relationships among the
19 sources, stressors, exposure conditions, populations, and adverse effects, presented in the
20 conceptual model and narrative, will be considered during the risk analysis phase of the
21 assessment. The plan includes the rationale for which relationships (referred to as "risk
22 hypotheses" in the Guidelines for Ecological Risk Assessment) are addressed, methods, models,
23 and a discussion of data gaps and uncertainties. It also may include a comparison between the
24 level of confidence needed for the management decision with that expected from alternative
25 analyses in order to determine data needs and evaluate which analytical approach is best. In
26 some cases, a phased, or tiered, risk assessment approach can facilitate management decisions,
27 particularly in cases involving minimal data sets.
28
29 The analysis plan provides a synopsis of measures that will be used to evaluate risk
30 hypotheses (as shown in Appendix D) . The plan is strongest when it contains explicit
31 statements for how measures were selected, what adverse effect (or assessment endpoint) they
32 are intended to evaluate, and which analyses they support. Uncertainties associated with selected
33 measures and analyses and plans for addressing them should be included in the plan when
34 possible. The analysis plan can be a brief summary of what the key components of the risk
35 assessment are and how each component will be measured or calculated.
36
37 As in the conceptual model, the economic or societal importance, complexity, data and
38 resources available will determine the degree of sophistication and detail needed in the analysis
39 plan. Key data gaps should be identified. It should also include thoughts about how to fill the
40 information needs in the near-term using existing information, in the mid-term by conducting
NATA is the technical support component of EPA's National Air Toxics Program [see 64FR38706-38740 ("National
Air Toxics Program: Integrated Urban Strategy") or USEPA, 2001e.
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1 tests with currently available test methods to provide data on the agent(s) of interest, and over the
2 long-term to develop better, more realistic understandings of exposure and effects and more
3 realistic test methods to evaluate agents of concern. The plan should explain how measures were
4 selected, what they are intended to evaluate, and which analyses they support. Uncertainties
5 associated with selected measures and analyses, and plans for addressing them, should also be
6 explicitly stated.
7
8 The analysis plan should include (where feasible) milestones for completion of the risk
9 assessment. The plan may be revisited and revised periodically. Such revisions may be
10 anticipated, if new information is acquired, to refine hypotheses of exposure andtoxicity, to
11 modify the risk hypotheses addressed, or to compare public concerns with the projected risk
12 management options.
13
14
15 2.3. The Final Step Before the Analysis Phase: Discussion of Possible Outcomes
16
17 It is useful for the entire team to hold some preliminary discussions, before the analytical
18 efforts of the assessment are started, about the various possibilities of the cumulative risk
19 assessment results and their implications. Given that statutory mandates, regulations, property
20 rights, or due process may constrain or define most or all acceptability criteria, what conclusions
21 of the team will be associated with various results or risk levels? For example, for a risk
22 assessment team with members from the community, industry, and the local and other
23 government entities, what would happen if the assessment shows risk levels to be "low"? Would
24 members accept this? Conversely, if "unacceptable" risks are determined, will all team members
25 accept the results and their possible responsibility to do something about that risk? Do team
26 members understand the limitations of the information to be generated?
27
28 Discussions like these will help determine if the assessment can really address the
29 questions of the team. If not, the assessment may not be worth doing as planned. If members of
30 the team will not accept the possibility of a range of results of the analysis, then it is important to
31 reopen the entire planning and scoping discussion before anything is done in the analysis phase,
32 since the planning and scoping phase has not been satisfactorily completed. Although it is not
33 necessary to have unanimity among stakeholders on the plan before proceeding, knowing where
34 some of the potential disagreements may occur after the Analysis and Interpretation phases are
35 started allows the stakeholders as a group to plan beforehand for how such disagreements will be
36 addressed, should they occur.
37
38 As an example, the Baltimore Community Environmental Partnership Air Committee
39 Technical Report (USEPA, 2000f) is a case study where the stakeholders thought they had
40 agreement on roles, responsibilities and approach, only to find that the group acrimoniously
41 splintered after the analysis results came back. The Baltimore report contains valuable lessons
42 learned in the area of stakeholder disagreements and agendas, and can provide some insight for
43 planning teams.
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1 Finally, discussions just prior to the analysis phase may lead to an assessment very
2 different from the one originally envisioned. The CRI case study (box, next page) is one where
3 the original plan was to do a quantitative cumulative risk assessment, but because of the lack of
4 some critical information, the scope was changed. This led to an assessment that, while not as
5 broad as originally planned - and not even directly calculating risk - had better stakeholder buy-
6 in with a better chance of success of providing useful information.
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Example: Cumulative Risk Initiative (CRI) for Cook Co., IL and Lake Co., IN
(formerly Chicago Cumulative Risk Initiative, CCRT)
CRI BACKGROUND AND OVERVIEW
In 1995 the Chicago Legal Clinic and 11 Chicago-area community advocacy groups filed a petition under the Toxic
Substances Control Act (TSCA) requesting that the USEPA Administrator prohibit or further regulate the emissions from
eight proposed or constructed incinerators in the Chicago metropolitan area and Northwest Indiana. The petitioners
believed that neither current statutes nor local siting laws adequately address cumulative impacts of multiple sources of
toxic pollutants in a geographic area. They requested that the Administrator restrict emissions of dioxins, furans, mercury,
lead and cadmium from these sources. In May 1996 the petition was withdrawn in response to a USEPA offer to
participate in an investigation of multimedia pollutant impacts in Cook County, Illinois and Lake County, Indiana. This
effort became CRI. CRI is an attempt to investigate cumulative loadings and hazards from pollutant sources, develop
community-based activities to help address these concerns, and use analytic results to help prioritize use of regulatory
agency resources. USEPA and the petitioners agreed to afour phase project: (1) Environmental Loadings Profile (EPA
747-R-1-002); (2) Petitioner Risk Workshop (completed); (3) Hazard Screening Assessment (peer review draft available
Jan. 2002); and (4) Risk-Hazard Management Response (pending).
HAZARD SCREENING ASSESSMENT
The CRI Hazard Screening Assessment was authored primarily byArgonne National Laboratory with input from local,
state and federal participants. Reflecting stakeholder deliberations, the Report focuses on cumulative hazard (not "risk" as
typically defined by USEPA) associated with noncriteria air pollutants ("air toxics") in the two county study area. It relies
on "off-the-shelf air pollutant information, including USEPA's Toxics Release Inventory, Cumulative Exposure Project,
Regional Air Pollutant Inventory Development System, and outdoor air monitoring data. Emission estimates are "toxicity
weighted", while modeled/monitored outdoor air pollutant concentrations are compared with reference values to develop
hazard index-like ratios. The ratios or toxicity weighted emission estimates are used to derive indicators of cumulative
hazard, then mapped over study area locations. To identify geographic areas where potentially elevated hazards and
individuals with potentially greater susceptibility are collocated, anotherpart of the study assembles pollutant hazard
information and data on existing human disease rates and indicators.
PRELIMINARY LESSONS LEARNED
1. A major planning/scoping/problem formulation effort by a broad group of stakeholders narrowed the scope of the CRI
Hazard Screening Assessment and seemed to increase stakeholder "buy-in" with the process. This was valuable given the
complexity, expense, effort, time requirement and difficulty encountered in addressing even the narrowed scope.
2. Large data gaps make risk and hazard assessment of environmentally-relevant chemical exposures highly uncertain, even
for single agents. Expanded assessments that address cumulative risk considerations (e.g. mixtures; developmental toxicity;
non-chemical agents) are a better match for real-world circumstances but require acknowledgment of even more
uncertainty.
3. Obtaining and managing input from a large group of technical stakeholders is cumbersome and time-consuming, but that
group's perspective and expertise greatly improved the CRI assessment.
4. Given that the NRC's 1983 four-step "framework" required several years for broad use and acceptance in the U.S., the
greater complexity of cumulative risk (for CRI, cumulative hazard) assessment suggests an equally long period maybe
needed for terminology standardization, refinement of approaches and development of consensus methods.
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Planning, Scoping, and
Problem Formulation
Analysis
Interpretation and
Risk Characterization
Figure 3.1. The Analysis Phase
3. THE ANALYSIS PHASE
The Analysis Phase is primarily an analytic process where risk experts apply risk
assessment approaches to evaluating the problem at hand9. The risk assessment paradigm most
widely used by risk assessors during the past two decades was first documented by the National
Research Council (NRC, 1983). It consists of four parts: hazard identification, dose-response
assessment, exposure assessment, and risk characterization. This paradigm was developed when
almost all risk assessments were being conducted on single chemicals. Nevertheless, it is a useful
place to start when considering cumulative risks. As a prerequisite, assessors considering
cumulative risk assessments should be familiar with the 1983 NRC risk paradigm, as well as the
various EPA risk assessment guidelines (see text box in section 1.1).
Although the Analysis Phase is primarily an analytic process with heavy emphasis on the role of the scientist, risk
assessor, or other technical expert, other stakeholders can be involved in various ways as agreed upon before the Analysis Phase
begins. Some roles stakeholders might have in the Analysis Phase include (1) suggesting sources of data, or providing data for
the assessment; (2) helping clarify issues identified during Problem Formulation; (3) working alongside the risk assessment
experts to see what data and assumptions are being used and why, and to better understand how the risk assessment process
works; and (4) suggesting alternate scenarios that may reflectmore realistic exposure conditions in the community. Avariety of
roles for stakeholders in the Analysis Phase can be proposed and adapted for the particular circumstances of the individual case,
assuming that the roles can be agreed upon by the team.
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In both single and multiple stressor risk assessments, the analyst will look at hazard and
dose response relevant to the stressor(s) of interest, and perform an analysis of exposure(s) to
those stressor(s). This chapter begins with a basic discussion of this general process and its basic
ingredients (section 3.1). The second part of this chapter (section 3.2) discusses some of the
situations arising in cumulative risk assessment, methods currently available for addressing them,
steps in the process, and some limitations to these methods. Finally, section 3.3 identifies areas
of ongoing work particularly relevant to cumulative risk assessment.
3.1. General Process
In developing the conceptual model and analysis plan (see section 2.2), the scope of the
assessment was specified (see example in box at right). Some of the aspects of scope include
stressors, sources, pathways and media, exposure routes, populations and subpopulations,
endpoints, and measures.
The analysis plan should specify how data, modeling or assumptions will be obtained,
performed or defined for all of the details
concerning the characterization of exposure
for the defined set of stressors, to the
defined population and subpopulations.
Additionally, the analysis plan specifies the
strategy for obtaining and considering
hazard and dose-response information for
these stressors. And, the plan will specify
the method for combining the exposure
information with the hazard and dose-
response information to generate risk
estimates or measures. As the risk analysis
is refined, it maybe appropriate to revisit
and refine the exposure, hazard and dose-
response information in an iterative
fashion.
Example: Scope of EPA's national scale assessment
for hazardous air pollutants (also see Figure 2-3):
stressors
sources
pathways/media
routes
subpopulations
endpoints
metrics
33 priority urban HAPs
major industrial, small "area",
mobile (on- and off-road), & extrinsic
"background" in air
outdoor air, indoor air
microenvironments
inhalation
general population only
cancers, developmental, CNS, kidney,
liver, respiratory effects
for cancer: distribution of high-end
cancer risk estimates, predicted
percent of population within predicted
cancer risk ranges, predicted number
of cancer cases, HAP-specific and
cumulative
for other effects: distribution of
estimated hazard index values and
estimated percent of population within
specified ranges of index values
In the integration of exposure,
hazard and dose-response information for a
cumulative risk assessment, several aspects
of the assessment may be particularly
important. These include multiple stressor
hazard, dose-response and exposure issues,
exposure time or duration related issues,
vulnerability or susceptibility of the study
population, along with the influencing factors, and subpopulations with special exposures. These
items are discussed in the following section, along with the currently recognized methods for
evaluating the toxicity or risk associated with mixtures.
The area of identifying and assessing risk to susceptible subpopulations has an increased
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1 profile in cumulative risk assessments. A variety of factors maybe influential in affecting
2 population susceptibility. The extent to which these can be considered will be heavily dependent
3 on existing knowledge and available information. Section 3.2 discusses available methods for
4 identifying and estimating risk or hazard to susceptible or vulnerable subpopulations. Section
5 3.3 discusses areas of complexity and on-going work.
6
7
8 3.2. Available Methods and Approaches
9
10 There are many aspects of traditional risk assessment methodology which apply to
11 cumulative risk assessment. Predicting cumulative risk of multiple stressors, however, has
12 required the development of additional specific methods or approaches. Additionally, there are
13 some aspects of risk assessment, while common to both single-stressor and multiple-stressor
14 assessments, that may increase in complexity or significance, in a cumulative risk assessment.
15 Together they frame the methodological issues pertinent to the discussion of cumulative risk
16 assessment.
17
18 While these aspects common to single-stressor assessment may be many (e.g., the added
19 dimension of multiple stressors influences consideration of stressor sources, routes of exposure,
20 environmental media/pathways, and other factors), several examples are raised here. As one
21 example, the assessment of the dose-response relationship and corresponding characterization of
22 exposures in terms of duration, timing relevant to life stage and exposure history gains an
23 additional dimension with the need to consider this in some way cumulatively. The
24 consideration of population susceptibility or vulnerability, as recommended in the Agency's
25 policy and guidance on Risk Characterization (USEPA 1995a, 1995b, 2000c), also increases in
26 complexity. A third example of a complicating aspect in cumulative risk assessment is the
27 consideration of subpopulations with particularly distinctive exposures. These examples are
28 further discussed in section 3.2.1.
29
30 Although it is beyond the scope of this Framework report to describe all risk methods in
31 detail, Appendix B lists a variety of resources relevant to various exposure assessment methods.
32 Relatively speaking, there is a great deal of information on assessing human and environmental
33 exposures to chemical stressors, some information on biological and radiological stressors, but
34 relatively little information on many other types of stressors.
35
36 The most prominent aspect of cumulative risk assessment is often the prediction of the
37 combined effects of multiple stressors. Past and current activities in the development of
38 approaches for predicting risk of multiple stressors include the Agency's Guidelines for the
39 Health Risk Assessment of Chemical Mixtures (USEPA, 1986b) and Supplementary Guidance for
40 Conducting Health Risk Assessment of Chemical Mixtures (USEPA, 2000e). Concepts,
41 approaches, or methods described in these documents or elsewhere are discussed in section 3.2.2,
42 with clarification of their applicability, limitations and notable points regarding interpretation of
43 the results they produce.
44
45 3.2.1. Examples of Increased Complexity of Cumulative Risk Assessment.
46
47 Three examples of the potential for increased complexity of cumulative risk assessment
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1 compared to single stressor risk assessment are described here, and related to: 1) time related
2 aspects, 2) vulnerability or susceptibility, and 3) subpopulations with special or particularly
3 distinctive exposures. All three of these aspects are relevant in single stressor assessments, but
4 have the potential to be more complicated in multiple stressor assessments.
5
6 Time related aspects. The issue of repeated exposures to a single stressor or exposures
7 to multiple stressors that may vary in time dimensions may have implications with regard to
8 susceptibility, which, consequently, has implications regarding the dose-response relationship.
9 Traditionally in dose-response assessment, for many stressors and effects there is an inherent
10 presumption that it is the cumulative exposure (combination of intensity and duration) to which
11 the organism responds. Thus dose-response assessments based on one pattern of exposure (e.g.,
12 6 hours per day, 5 days per week over a lifetime) are routinely applied to the assessment of risk
13 associated with a variety of patterns of exposure.
14
15 In the case of linear carcinogens, this cumulative exposure assumption has been carried as
16 an explicit assumption in the risk assessment step. Regardless of the details of the exposure
17 circumstances for the study on which the cancer potency was based, it is assumed that there is a
18 linear relationship between amounts of exposure and associated cancer risk. For non-linear
19 carcinogens10, and conceivably for linear carcinogens, if data indicate deviation from the
20 assumption that cancer risk is proportional to lifetime dose, the details and sequence of exposure
21 may be important, both in developing the dose-response relationship and in predicting risk
22 associated with exposures of interest.
23
24 As some chemicals may have the ability to affect an organism's response to other
25 chemicals, consideration of the time sequence of exposure may take on an additional layer of
26 complexity in multiple chemical cumulative risk assessments. For example, persons with
27 relevant past exposures might have increased susceptibility to the effects of a particular chemical
28 due to a previous exposure to the same - or a second - chemical.
29
30 These considerations suggest that for cumulative risk assessment, chemical exposures
31 need to be characterized in terms of which other chemicals are present, and when. As noted in the
32 ILSI Framework for Cumulative Risk Assessment (ILSI, 1999): "Data collected specifically to
33 support a cumulative exposure assessment should conserve the covariance and dependency
34 structures associated with the chemicals of concern." It is important to note, however, that the
35 detail to which exposures are characterized should be closely tied to the detail of information
36 available in the dose-response assessment, since a lack of corresponding detail in the dose-
37 response assessment can pose a limitation on the interpretation and usefulness of detailed
38 exposure estimates.
39
40 Cumulative risk assessment can present challenges in matching exposure estimates with
41 dose-response relationships. Ideally, the dose-response assessment will indicate if the time
42 sequence for the chemical(s) or stressors of interest in the assessment is important for risk
43 estimation. In cumulative assessments involving chemicals where time sequence of exposure is
44 important, it may be necessary to characterize the details and sequence of exposure to the
The draft cancer guidelines (USEPA, 19991) explicitly recognize the potential for non-linear dose response. It is
only in the case where non-linear response is modeled that time sequence of exposure can be considered in the risk assessment.
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exposed population (see text box, previous page), so there will be a match in not only the form,
but also the assumptions between the dose-response relationship and the exposure/dose estimate.
Some Examples of Exposure Models which Consider Time Aspects
Calendex (Novigen Sciences, Inc), integrates different pathways (e.g., dietary - food and water - and
residential) and routes (oral, dermal, inhalation) of exposure using a calendar-based probabilistic approach .
One of the important factors of this approach is it provides estimates of risk which reflect aggregate and
cumulative exposure to discrete individuals with exposure pathways and routes appropriately linked for the
scenarios being assessed. Calendex also allows one to estimate exposure pre- and post use of a chemical, as
well as during degradation periods. Calendar based assessments maintain the integrity of the individual by
capturing: the location of the exposed individual, the time of year in which he or she was exposed, and the
patterns of exposure. Calendex also allows for a variety of time-breakout options for the analysis of exposure.
APEX - The Air Pollution Exposure (APEX) model is based on the pNEM probabilistic National Ambient Air
Quality Standards model (pNEM) for carbon monoxide (Johnson, et al., 2000). This model mimics the basic
abilities of the pNEM/CO model; it calculates the distributions of human exposure to selected airborne
pollutants within a selected study area as a function of time. As a dose model (for CO), it calculates the
pollutant dose within the body, specifically summarized by the blood carboxyhemoglobin (COHb)
concentration. APEX is a cohort-m icroenviro nmen t exposure model in that it combines daily activity diaries to
form a composite year-long activity pattern, which represent specific population cohorts and are tracked as they
move from one microenvironment to another. A cohort consists of a subset of the population that is expected to
have somewhat similar activity (and hence exposure) patterns; they are formed by combining demographic
groups and geographic locations (districts). Once each cohort has been modeled and its relative size determined,
an exposure distribution for the entire population can be assembled. A microenvironment is a description of
the immediate surroundings of an individual that serves as an indicator of exposure (e.g., inside a residence,
school or car, outdoors, etc.). APEX has been developed as one of the inhalation exposure models accessible in
the Exposure Event Module of the Total Risk Integrated Methodology (TRIM.Expo) for assessment of
exposures to either criteria or hazardous air pollutants (USEPA, 1999J)
Other models include the LifeLine Model, developed under a cooperative agreement between EPA/OPP and
Hampshire Research Institute (Hampshire Research Institute, 1999, 2000); the Stochastic Human Exposure and
Dose Simulation Model (SHEDS), under development by EPA's Office of Research and Development
(Zartarian, et al., 2000), and the Cumulative and Aggregate Risk Evaluation System (CARES), under
development by member companies of the American Crop Protection Association (APCA, 1999) along with the
Residential Exposure Year (RExY) model being developed by Infoscientific.com.
4
5
6
7
8
9
10
11
12
13
14
15
16
Vulnerability. One of the concepts that can be used in risk assessments (both for human
health and ecological assessments) is that of vulnerability of the population or ecosystem.
Vulnerability has been a common topic in socioeconomic and environmental studies. The
European Commission's TEMRAP (The European Multi-Hazard Risk Assessment Project),
studying vulnerability to natural disasters such as floods, windstorms, fires, earthquakes, and
others, defines 'Vulnerability as "the intrinsic predisposition of an exposed element [organism,
population, or ecologically valuable entity] to be at risk of suffering losses (life, health, cultural
or economic) upon the occurrence of an event of [a specific] intensity" (European Commission,
2000, bracketed material added).
Vulnerability of a population places them at increased risk of adverse effect, and may be
an important factor in deciding which stressors are important in doing a cumulative risk
assessment. The Agency's risk characterization policy and guidance (USEPA, 2000c) touches on
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1 this concept by recommending that risk assessments "address or provide descriptions of [risk to]
2 ... important subgroups of the population, such as highly exposed or highly susceptible groups".
3 Further, the Agency's guidance on planning and scoping for cumulative risk assessments
4 (USEPA, 1995b) recognizes the importance of "defining the characteristics of the population at
5 risk, which include individuals or sensitive subgroups which may be highly susceptible to risks
6 from stressors or groups of stressors due to their age, gender, disease history, size or
7 developmental stage". That guidance also recognizes the potential importance of other social,
8 economic, behavioral or psychological stressors that may contribute to adverse health effects
9 (e-g-» existing health condition, anxiety, nutritional status, crime and congestion). These same
10 concepts may also be discussed as a group in terms of "population vulnerability." The various
11 ways in which a population maybe vulnerable are discussed below in four categories:
12 susceptibility, differential exposure, differential preparedness, and differential ability to recover.
13
14 The first of these is susceptibility. Susceptible individuals within a population have a
15 different or more pronounced dose-response relationship when confronted with a stressor.
16 Reasons for susceptibility may be related to any number of sensitivity factors, including life stage
17 (e-g-» children or the elderlymay be more susceptible), genetic polymorphisms (e.g., genetic
18 susceptibilities which occur in a small but significant percentage of the population), or existing
19 disease state (e.g., asthmatics). In addition, susceptibility maybe related to the conditions of
20 exposures (e.g., prior exposures leading to the development of sensitization reactions, or having
21 had exposures which compromise the immune system). Confronted with equal concentrations of
22 a chemical for equal durations, for example, a biologically susceptible individual may show
23 effects while the typical individual within the population would not. Although we generally do
24 not have a lot of data available on this topic, susceptibilities or sensitivities may also exist among
25 races or genders.
26
27 The second category of vulnerability is differential exposure. While it is obvious by
28 examining a dose-response curve that two individuals at different exposure levels may have a
29 different likelihood of effects, this also extends to differences in historical exposure, body
30 burden, and background exposure, which are sometimes overlooked in an assessment.
31
32 The third category of vulnerability is differential preparedness to withstand the insult of
33 the stressor, and the fourth is the differential ability to recover from the effects of the stressor.
34 These last two are linked to what kind of coping systems and resources an individual, population,
35 or community has. Preparedness or recovery is often a crucial factor in ecological assessments. In
36 human health assessments, lack of access to health care, income differences, unemployment, or
37 lack of insurance, for example, may affect acommunity's ability to prepare for or recover from a
38 stressor. One aspect of differential ability to recover is illustrated by differing survival rates for
39 the same disease (e.g., Lantz, et. al 1998).
40
41 Cumulative risk assessments maybe uniquely suited to addressing the issues related to
42 vulnerability. In order to do that, however, there needs to be some relationship between the
43 factors discussed above and changes in risk. At the current state of the science, many of these
44 factors have not been extensively developed beyond correlations between mortality rates and
45 several socioeconomic factors such as income (e.g., Lynch, et al. 1998). Susceptibility has had
46 much more development than the other factors, and current approaches implemented by EPA and
47 others to address risk of noncancer endpoints routinely employ a 10-fold factor to address
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1 heterogeneity in sensitivity. Variability with regard to susceptibility was discussed in detail by
2 NRC (1994), and the current state of knowledge concerning epidemiologically based (e.g.,
3 oncogene-specific) risk factors provides empirical data upon which at least crude estimates of the
4 magnitude of heterogeneity in susceptibility to toxic response can be based. Much research in
5 this area, however, remains to be done.
6
7 Subpopulations with Special Exposures. Certain subpopulations can be highly exposed
8 to stressors based on geographic proximity to sources of these stressors, coincident direct or
9 indirect occupational exposures, their activity patterns, or a combination of these factors. The
10 Agency's Risk Characterization policy and guidance (USEPA, 2000c) includes recognition of the
11 need for risk information to include as available, information on highly-exposed subgroups.
12 Accordingly, risk assessments, including those that are cumulative, may need to include special
13 emphasis on identifying and evaluating these subpopulations.
14
15 Subpopulations at risk of high exposure due to geographic proximity could include
16 workers at a facility which is a source of a slressor or residents near such sources. Specific
17 examples might be people living downwind from a coal burning power plant, those near and
18 using a polluted water b ody (for examp le, for fishing or recreation), or along roadways with high
19 levels of vehicular traffic. Occupational exposures may be either direct (occurring in the
20 workplace) or indirect (occurring at home). Indirect occupational exposures include those
21 experienced by family members of those occupationally exposed, who maybe exposed to
22 occupational chemicals brought into the house by the worker (e.g., on clothing). Thus, workers
23 or family members may be subject to greater exposures than others in the population without this
24 additional burden.
25
26 Examples of subpopulations at high exposure due to activity patterns may include people
27 who exercise heavily in polluted air, recreational or subsistence fishers or hunters who consume
28 large quantities offish or game, farmers or others who get a large percentage of their food from a
29 location near a source of pollution and live in areas with high pesticide use, individuals with long
30 commutes in automobiles, or children (because they consume a larger amount of food, drink, and
31 air relative to their body weight, and because of additional exposure routes such as incidental soil
32 ingestion). Additionally, some subpopulations may be affected by the combined impact of high
33 geographic exposure and high exposure activity patterns (e.g., runners who run along heavily
34 traveled roadways, and those who fish for food in heavily polluted urban rivers).
35
36 It is important to recognize that some heavily exposed populations may also be
37 particularly vulnerable or susceptible to the effects associated with the stressors of concern.
38 Examples of those who could be particularly vulnerable to certain stressors include children
39 during certain stages of development, people with chronic respiratory problems, the elderly, and
40 those economically disadvantaged without access to medical care. A cumulative risk assessment
41 may need to take into account potential combinations of high exposure and high vulnerability,
42 but few, if any, methods are available and accepted today to address the combined effects of
43 exposure and vulnerability. This is an important area for further research and methods
44 development.
45
46
47 3.2.2. Approaches for Predicting Risk of Multiple Stressors.
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1
2 Combination toxicology (Carpy, et al., 2000) is the study of the toxicity of mixtures. In
3 such studies, one may either measure the mixture toxicity directly (whole mixture toxicity), or
4 one may develop an estimate of the combined toxicity from information on the multiple
5 component stressors acting in concert with each other. If evaluated using its component
6 chemicals, the mixture toxicity data set should only be treated as a snapshot of a
7 multidimensional dose-response relationship, because the joint toxicity and interactions can
8 change with changes in exposure route, duration, relative proportions of the components, or the
9 effect being tracked. The application of such a data set to a specific situation then requires careful
10 matching of the test mixture composition and exposure conditions to those of the target situation.
11 In whole mixture toxicity, once the mixture toxicity is known, a risk evaluation can be done on
12 the mixture using the 1983 NRC risk assessment paradigm. On the other hand, component based
13 mixture assessments are rarely evaluated using the strict NRC paradigm, because the exposure
14 and toxicity information must be compatible, requiring some iteration to obtain toxicity
15 information that is relevant to the actual exposure estimates (USEPA, 2000e).
16
17 To address concerns over health risks from multi-chemical exposures, EPA issued
18 Guidelines for Health Risk from Exposure to Chemical Mixtures in 1986 (USEPA, 1986b).
19 Those Guidelines described broad concepts related to mixtures exposure and toxicity and
20 included few specific procedures. In 1989, EPA published guidance for the Superfund program
21 on hazardous waste that gave practical steps for conducting a mixtures risk assessment (USEPA,
22 1989a). Also in 1989, EPA published the revised document on the use of Toxicity Equivalence
23 Factors for characterizing health risks of the class of lexicologically similar chemicals that
24 included the dibenzodioxins and dibenzofurans (USEPA, 1989b). In 1990, EPA published a
25 Technical Support Document to provide more detailed information on toxicity of whole mixtures
26 and on toxicologic interactions (e.g., synergism) between chemicals in a two-chemical mixture
27 (USEPA, 1990a). Whole mixture assessments, toxicologic independence and similarity, and risk
28 methods using toxicologic interactions are discussed at length in the recent Supplementary
29 Guidance for Conducting Health Risk Assessment of Chemical Mixtures (USEPA, 2000e).
30
31 Risk assessment on mixtures usually involves substantial uncertainty. If the mixture is
32 treated as a single complex substance, these uncertainties range from inexact descriptions of
33 exposure to inadequate toxicity information. When viewed as a collection of a few component
34 chemicals, the uncertainties also include the generally poor understanding of the magnitude and
35 nature of toxicologic interactions, especially those interactions involving three or more
36 chemicals. Because of these uncertainties, the assessment of health risk from chemical mixtures
37 should include a thorough discussion of all assumptions and the identification when possible of
38 the major sources of uncertainty.
39
40 3.2.2.1. Single Stressor Information.
41
42 Assessments which evaluate the risk from a single stressor do not fall into the category of
43 cumulative risk assessments by the definition given in Section 1.3, whether these single-stressor
44 assessments address a single (dominant) endpoint or multiple endpoints, or whether the
45 exposures are simple or complex (e.g., multi-source, multi-pathway, multi-route exposure). Some
46 of them may be termed "aggregate risk assessments" by extension of the FQPA terminology.
47 They can, however, provide useful information for cumulative assessments.
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1 A cumulative risk assessment considers the joint impact of multiple stressors. Studies on
2 individual stressors can, however, provide informative qualitative information for multi-stressor
3 assessments, particularly regarding hazard identification The collection of single stressor effects
4 can indicate the variety of types of adverse effects likely to result from the stressor combination,
5 though perhaps not the magnitude or extent of the effects. Factors affecting population
6 susceptibility to the individual chemicals are also likely to be important with the combined
7 exposure. To go further in terms of quantitative risk assessment requires consideration of the
8 potential for joint toxicity. For most exposure situations, hazard and dose-response studies of all
9 of the joint effects from the multiple stressors will not be available, so that conclusions will have
10 to be based at least partly on the single stressor information.
11
12 Exposure assessments for single stressors also need further consideration before they can
13 be used to characterize long term cumulative exposure to all the stressors by all pathways.
14 Transport and environmental transformation of a chemical can be influenced by presence of other
15 chemicals. Consequently, both the exposure levels and the relative proportions of chemicals at
16 future times may not correspond well to present measurements of a combination of chemicals
17 unless these influences are taken into account. In addition, exposure to one stressor may
18 influence the uptake of a second stressor. For example, a nonchemical stressor that increases
19 ventilation rate will increase the inhalation uptake of airborne chemicals.
20
21 Toxicologic independence. Two situations allow plausible approximations of the joint
22 exposure-response relationship using only the single stressor information: toxicologic
23 independence and toxicologic similarity (USEPA 2000e). In the case of toxicologic
24 independence, if the toxicity modes of action are biologically independent, then as long as there
25 are no pre-toxicity interactions (e.g., metabolic inhibition, influence on uptake), the single
26 stressor information is sufficient to approximate the joint exposure-response relationship. When
27 the effects from two or more stressors are different, the cumulative response, if lexicologically
28 independent, is merely all the single stressor responses, as if the other stressors were not present.
29 For example, joint but low exposure to heat (causing minor elevated heart rate) and toluene
30 (causing minor hearing loss) would be expected to cause both the minor heart rate elevation and
31 minor hearing loss, but to the same extent as expected for each stressor alone. If each stressor is
32 below its toxicity threshold, then for stressors exhibiting toxicologic independence, there will be
33 no estimated cumulative response, because the set of individual responses is then a collection of
34 zeros.
35
36 When the single stressor and cumulative toxicities are each represented by a frequency or
37 probability for affected individuals, also termed a probabilistic risk, then independence means
38 that "response addition," as defined in the Agency's Supplementary Guidance for Conducting
39 Heath Risk Assessment of Chemical Mixtures (USEPA 2000e), can be applied for each adverse
40 effect that the stressors have in common. When all the single stressor risks are low, the joint risk
41 of a common effect under response addition can be approximated by the simple sum of the single
42 stressor risks. For example, if reproductive toxicity is the general effect common to the multiple
43 chemicals, the cumulative risk of reproductive effects (at low single chemical risk levels) is
44 approximately the sum of the single chemical reproductive risks. Risk addition under
45 independence places no constraints on the individual chemical dose-response curves.
46
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1 Toxicologic Similarity. In the second situation, the stressors are grouped according to
2 the common mode of action for each effect of concern determined in the planning and scoping
3 phase (USEPA, 2002a). For all effects caused by that mode of action, "dose addition" (USEPA,
4 2000e) can be applied to the stressor group. Thus far, this approach has only been used with
5 combinations of lexicologically similar chemicals, not with combinations of chemicals with
6 other kinds of stressors such as radiation, physical factors or health status. With similar
7 chemicals, each chemical exposure is converted into the equivalent exposure level of one of the
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An Example using lexicological Independence: National-Scale Air Toxics Assessment
The National-Scale Air Toxics Assessment, which is based on 1996 emissions data, provides results that are
useful in understanding the quality of air and its possible effect on human health nationwide. The assessment
includes 32 air toxics (a subset of EPA's list of 188 air toxics) and also diesel particulate matter (which is used
as a surrogate measure for diesel exhaust). Specifically, the assessment consists of 4 steps that will produce
nationwide estimates of: (1) the release of these pollutants into the air from various sources; (2) the
concentration of these compounds in the air; (3) the exposure of populations to this air; and (4) the risk of both
cancer and non-cancer health effects resulting from this exposure.
Purpose: The results of the national-scale assessment will provide important information to help EPA continue
to develop and implement various aspects of the national air toxics program. They will not be used directly to
regulate sources of air toxics emissions. While regulatory priority setting will be informed by this and future
national assessments, risk-based regulations will be based on more refined and source-specific data and
assessment tools. More specifically, the assessment results will help to: identify air toxics of greatest potential
concern; characterize the relative contributions to air toxics concentrations and population exposures of different
types of air toxics emissions sources (e.g., major, mobile) and set priorities for the collection of additional air
toxics data and research to improve estimates of air toxics concentrations and their potential public health
impacts. Important additional data collection activities will include upgraded emission inventory information,
ambient air toxics monitoring, and information on adverse effects to health and the environment; establish a
baseline for tracking trends over time in modeled ambient concentrations of air toxics; and establish a baseline
for measuring progress toward meeting goals for inhalation risk reduction from ambient air toxics.
The Four Steps: The national-scale assessment includes the following four major steps for assessing air toxics
across the contiguous United States (also Puerto Rico and the Virgin Islands).
(1) Compiling a 1996 national emissions inventory of air toxics emissions from outdoor sources. The types of
emissions sources in the inventory include major stationary sources (e.g., large waste incinerators and factories),
area and other sources (e.g.,dry cleaners, small manufacturers, wildfires), and both onroad and nonroad mobile
sources (e.g., cars, trucks, boats). EPA made some modifications to the 1 996 National Toxics Inventory to
prepare the emissions for computer modeling.
(2) Estimating 1996 ambient concentrations based on the 1996 emissions as input to an air dispersion model
(the ASPEN model). As part of this modeling exercise, EPA compared estimated ambient concentrations to
available ambient air toxics monitoring data to evaluate model performance.
(3) Estimating 1996 population exposures based on a screening-level inhalation exposure model (HAPEM4)
and the estimated ambient concentrations (from the ASPEN model) as input to the exposure model. Estimating
exposure is a key step in determining potential health risk. People move around from one location to another,
outside to inside, etc., so exposure isn't the same as concentration at a static site. People also breathe at different
rates depending on their activity levels, so the amount of air they take in varies. For these reasons, the average
concentration of a pollutant that people breathe (i.e., exposure concentration) may be significantly higher or
lower than the concentration at a fixed location (i.e., ambient concentration).
(4) Characterizing 1996 potential public health risks due to inhalation of air toxics. This includes both cancer
and noncancer effects, using available information on air toxics health effects, current EPA risk assessment and
risk characterization guidelines, and estimated population exposures. Using the toxicological independence
formula and the default assumption of additivity of risks (USEPA 1986b, 2000e), this assessment combines
cancer risk e stimates by summing them for certain weight of evidence groupings, and also across all group ings.
For non-cancer effects, the assessment assumes dose additivity, and aggregates or sums hazard quotients for
individual air toxics that affect the same organ or organ system (USEPA 2000e), in this case combining air
toxics that act as respiratory irritants.
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1 chemicals, called the index chemical. The joint toxicity or risk from the combined exposure is
2 then estimated by determining the effects or risk for that equivalent exposure level using the
3 dose-response information for the index chemical. For example, with the dioxins and furans (see
4 text box, next page), each congener exposure level is converted into its equivalent exposure as
5 the index chemical, 2,3,7,8-TCDD (USEPA, 1989b).
6
7 Although the assumption itself is not complicated, the decision to assume toxicologic
8 similarity can be complicated, depending on the level of assessment decided in the planning and
9 scoping phase and described in the analysis plan. The implementation used in Superfund
10 assessments (USEPA 1989a, Part D) is a rough approximation to dose addition where a Hazard
11 Index is determined whenever chemicals have a common target organ. The implementation by
12 the Office of Pesticide Programs in support of FQPA (USEPA, 2002a) is much more extensive
13 and requires knowledge of modes of action in order to calculate the Relative Potency Factors
14 (RPFs) for the effect of concern (see example in Appendix E). The Toxicity Equivalence Factor
15 (TEF) method used for the dioxins is a special case of the RPF method (see Appendix E); it
16 requires the most toxicologic similarity because the similarity applies to every toxic effect by any
17 type of exposure (USEPA, 2000e).
18
19 Single stressor information can also be used with dissimilar chemicals to gauge the
20 potential for toxicologic interaction. For example, chemicals with long whole body half lives, or
21 long tissue residence times, have the potential to be present in those tissues at the same time.
22 Such overlapping exposures can result in a higher effective tissue dose, altered tissue doses
23 caused by toxicokinetic interactions, or altered toxicity from interacting toxic mechanisms. When
24 a careful evaluation indicates no internal dose overlap, including metabolites, the single
25 exposures might be considered independently.
26
27 3.2.2.2. Information on Stressor Interactions and Multiple Exposures.
28
29 One important simplification that has been common in the assessment of single stressors
30 has been the separate evaluation of many of the key steps. That is, simplifying assumptions have
31 often been made regarding many characteristics of exposure (e.g., continuous vs. intermittent,
32 variations in magnitude) . For a given exposure route, for example, only one dose-response curve
33 may be used for the bounding case of setting a cleanup or action level of exposure, and also the
34 predictive case of estimating existing risk. These simplifying assumptions allow the dose-
35 response step to be performed in isolation from the exposure assessment step, with the two steps
36 executed in either order. For health-protective action levels, one may use bounds, such as the
37 upper bounds on toxic potency and exposure and lower bounds on the resulting acceptable
38 exposure level. Such bounds may be much easier to calculate, but maybe more difficult to
39 interpret in terms of the uncertainties, likelihood and closeness to the best or central estimate.
40
41 The incorporation of multiple chemicals, other stressors, and multiple exposure
42 conditions obviously complicates the assessment and the use of simplifying assumptions. In
43 cumulative assessments, performing the exposure and dose-response steps of the risk assessment
44 paradigm separately is an approximation that obviously invokes a simplifying assumption. If the
45 dose response data do not represent the same conditions as the exposure being assessed, an
46 extrapolation has to be made, which introduces additional uncertainty that must be clearly stated.
47 Joint or cumulative toxicity depends on the total dose or exposure, relative exposure levels,
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An Example using Toxicologic Similarity: The Dioxin Reassessment
Scientists from the Environmental Protection Agency (EPA), other Federal agencies and the general scientific
community have been involved in a comprehensive reassessment of dioxin expo sure and human health effects
since 199 1 (USE PA, 2002c). The final dioxin reassessment will consist of three parts. Part 1: Estimating
Exposure to Dioxin-Like Compounds will include four volumes that focus on sources, levels of dioxin-like
compounds in environmental media, and human exposures. Part 2: Human Health Assessment Document for
2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds will consist of two volumes that include
information on critical human health end points, mode of action, pharmacokinetics, dose-response, and TEFs.
Part 3: Integrated Summary and Risk Characterization for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and
Related Compounds will be a stand-alone document. In this summary and characterization, key findings
pertinent to understanding the potential hazards and risks of dioxins are described and integrated, including a
discussion of all important assumptions and uncertainties.
2,3,7,8-Tetrachlorodibenzo-/>-dioxin(dioxin) is highly toxic to many animal species producing a variety of
cancer and noncancer effects. Other 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans,
and coplanar polychlorinated biphenyls (PCBs), exhibit similar effects albeit at different doses and with different
degrees of confidence in the database. The similarities in toxicity between species and across different dioxin
congeners stem from a common mode of action via initial binding to the aryl hydrocarbon (Ah) receptor. This
common mode of action is supported by consistency in effects evident from data from multiple congeners. This
has led to an international scientific consensus that it is prudent science policy to use the concept of toxic
equivalency factors (TEFs) to sum the contributions of individual PCDD, PCDF, and coplanar PCB congeners
with dioxin-like activity (van den Berg, et al., 1998). The data supportive of dioxin-like toxicity, both cancer and
noncancer, are strongest for those congeners that are the major contributors to the risk to human populations. In
addressing receptor-mediated responses resulting from complex mixtures of dioxin-like congeners, this
assessment has provided a basis for the use of integrated measures of dose, such as average body burden, as more
appropriate default metrics than daily intake. The Agency recognizes, however, that the final choice of an
appropriate dose metric may depend on the endpoint under evaluation.
In this study, 2,3,7,8-tetrachlorodibenzo-p-dioxinwas chosen as the index chemical, and the other dibenzo-p-
dioxins and dibenzofurans, and coplanar polychlorinated biphenyl doses were adjusted to 2,3,7,8-TCDD
equivalent toxicities so the doses could be added.
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and the many characteristics of exposure (e.g., duration, continuous vs. intermittent presence,
route, co-occurrence with other chemicals), and in many cases the complexities introduced by
multiple stressors will not allow use of some of the common simplifying assumptions of single-
stressor assessments. For example, toxicologic interactions have been shown to change using the
same doses but with a reversal of the sequence of exposure (i.e., chemical B then A instead of A
then B), so that the exposure and dose-response steps must be compatible and performed
together.
Nonchemical stressors can also cause toxicologic interactions. Biological stressors, like
their chemical counterparts, can interact with chemical exposures and change the overall risk in
non-additive ways. Ototoxic chemicals, such as toluene, can damage the auditory system and
have been shown to potentiate the effects of a physical stressor, noise, on hearing loss (Morata, et
al., 1997; Morata, 2000).
Toxicity and interaction data for the exposure-response relationship for the mixture of
interest that covers the full range of exposures is usually impossible because of limits on cost and
other resources. More feasible approaches to cumulative risk characterization, beyond that with
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1 various simplifying assumptions, then require close matching of the exposure and dose-response
2 steps to minimize the data requirements. In many cases, screening level ranking may be the only
3 practical assessment. In some cases, there will be sufficient information for some quantitative
4 evaluation of cumulative health risks that reflect both the complex exposures and toxicologic
5 interactions. The issues for these cases are now presented along with their main research
6 implications, starting with the simplest case where only chemical interactions are considered.
7
8 "Joint chemical toxicity" means the outcome of exposure to multiple chemicals that
9 includes the single chemical effects along with any toxicologic interactions. Chemical
10 interactions can be divided into two major categories: those resulting from toxicokinetic and
11 those resulting from toxicodynamic modes of action (USEPA, 2000e). Toxicokinetic modes of
12 interaction involve alterations in metabolism or disposition of the toxic chemicals, for example,
13 by the induction or inhibition of enzymes involved in xenobiotic activation and detoxification.
14 Toxicodynamic modes of interaction include those processes that affect a tissue's response or
15 susceptibility to toxic injury. A simplifying observation is that most interactions seem to involve
16 pharmacokinetics. Unfortunately, most studies of toxicologic interaction to date have only
17 involved two chemicals, and few have quantified the magnitude of the interaction or its
18 dependence on exposure conditions.
19
20 Toxicologic interactions are commonly described with terms such as synergism and
21 antagonism. These terms are only marginally useful, in part because the underlying toxicological
22 concepts are only defined for two-chemical mixtures, while most environmental and
23 occupational exposures are to mixtures of many more chemicals. Further, the mathematical
24 characterizations of synergism and antagonism are inextricably linked to the prevailing definition
25 of "no interaction," instead of some intrinsic toxicological property (Hertzberg and MacDonell,
26 2002). The U.S. EPA has selected "dose addition" as the primary no-interaction definition for
27 mixture risk assessment, so that synergism would represent observed toxic effects that exceed
28 those predicted from dose addition (USEPA, 2000e). The EPA mixture risk guidance also
29 describes a modified Hazard Index that incorporates evidence of pairwise toxicologic interactions
30 but notes that the pairwise evidence may be specific to the exposure conditions of the study. The
31 guidance further encourages development of full biomathematical models for the joint toxicity,
32 such as those based on pharmacokinetics, so that qualitative interaction labels such as synergism
33 are replaced by quantitative estimates of mixture response that directly reflect the actual
34 environmental exposure levels.
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36
37 3.2.2.3. Decision Indices.
38
39 The complexities with cumulative risk assessment include the frequent need to combine
40 pieces of information that differ widely from each other. Exposure data for some stressors may
41 be only as time-weighted averages, while others reflect daily human activity patterns. Toxicity
42 data for some chemicals may allow estimation of probabilistic risk for one endpoint, while only
43 providing qualitative descriptions of other endpoints. It is possible to develop the risk
44 characterization using the original information in a high dimensional matrix, but such a summary
45 will be difficult to evaluate and communicate. One approach to diverse multivariate data used
46 successfully for weather forecasting is the decision index, with examples such as the smog index,
47 the pollen count, and the mold index commonly used to assist in public and personal decisions
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about environmental exposure. A similar approach can be taken for cumulative risk assessment
(Hertzberg, 2000).
Example Decision Index: The Hazard Index
The Hazard Index for oral exposure is implemented by
Superfund assessors by the formula:
HI = sum[ HQj ] = sum[ E/RfDj ]
where E, and RfDj are the daily exposure and Reference
Dose of chemical j.
The RfD is itself a kind of decision index in that it reflects
a dose that is selected to be sufficiently low that any toxic
effects are judged highly unlikely. All available dose-
response data, on all effects, are considered in determining
each RfD. Uncertainties in the RfD will differ across the
chemicals, making the uncertainty in HI difficult to
characterize.
The advantage of a decision index is
the simplicity in converting highly
multivariate technical information into a
single number. The most common example
used for cumulative health risk is the Hazard
Index (HI) for mixture risk (see box at right).
Although specific for a single affected target
organ, each HI reflects multiple studies of
multiple chemicals, often involving multiple
test animal species and test exposures, and
highly varied measures of toxicity.
The main disadvantage of a simple
index is that the uncertainties in its
calculation are largely hidden. Another key
disadvantage is in quantifying what are often
scientific judgments. For example, the Hazard Index implemented under Superfund (USEPA,
1989a) is a number whose decision threshold is usually given as 1.0, so that when the HI is
greater than 1, additional action is indicated. The actual value of HI is not that informative; HI=6
is not necessarily twice as bad as HI=3.
One alternative for addressing multiple effects is to recast these qualitative judgments in
terms of severity categories or levels of concern, and then use statistical methods such as
categorical regression that use only the ordering of the severity scores, but not their actual values.
The result is not a risk of a particular toxic effect, but rather a risk of exceeding a certain
minimum toxic severity level, or level of minimal concern (Hertzberg, 1989; Guth, et al., 1993).
In the best situations, such as the EPA interaction-based Hazard Index (USEPA, 2000e), the
decision index formula is modular so that component pieces can be evaluated separately for
accuracy, and so that improvements in one area can be easily incorporated to give an improved
index.
Another example of a decision index with more overt display of its diverse parts is the
Hazard Ranking System (HRS), a formula developed for characterizing the relative hazards of a
particular waste site. These hazards were highly diverse, including corrosivity, explosivity,
toxicity and soil conditions. As with the HI, different uncertainties in the components make the
uncertainty of the HRS index difficult to describe. Instead of merely presenting the index as a
number, a high dimensional graphical presentation could be used such as the star plots of
multivariate data (Chambers, et al., 1983; Hertzberg, 2000), where each arm of the star represents
one of the sub-indices. While this approach shows the relative contribution of each factor, it
again hides the uncertainties of the factors as well as of the HRS index itself.
Hybrid methods also have been used for complex risk assessments that combine
judgment with numerical descriptions of risk or dose-response. The EPA interaction-based
Hazard Index (USEPA, 2000e) and the mixture risk approaches of the Agency for Toxic
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1 Substances and Disease Registry (Hansen, et al., 1998) both include a judgmental weight of
2 evidence (WOE) score to reflect the strength of evidence for toxicologic interactions and
3 relevance to human health risk. The ATSDR WOE is used in communicating risks and
4 intervention options, while the EPA WOE is used to calculate a modified Hazard Index. A
5 slightly different approach is the Integral Search System data base program for combinations of
6 carcinogens (Woo et al., 1994) by which available studies on pairwise interactions of
7 carcinogenicity are used to modify the risk range of the combination from that predicted by
8 response addition (USEPA, 2000e). In all these cases, scientific judgment is used to alter the risk
9 description or quantitative estimate, but only in terms of an approximate risk interval or a
10 decision threshold.
11
12 3.2.2.4. Probabilistic Approaches.
13
14 The recent report by Bogen (2001) illustrates an alternative probabilistic approach to
15 noncancer endpoints, in which methods used for integrated quantitative treatment of uncertainty
16 and variability are made consistent with those used for probabilistic assessment of cancer risk.
17 This report addresses many issues concerning the implementation of probabilistic methods for
18 noncancer endpoints, and cites a number of related references (e.g., Lewis, 1993; Dourson et al.,
19 1994; Slob and Pieters, 1998).
20
21 Any approach to cumulative risk assessment needs to carefully define the set of relevant
22 endpoints. Precisely how this is done has important logical and practical implications for how
23 the cumulative risk may be calculated and interpreted. For example, the risk of inducing a given
24 endpoint may differ among different people in a population at risk for some endpoints, (e.g.,
25 cancer conditional on all carcinogen exposures), but may be unaffected by interindividual
26 variability (e.g., in exposure or susceptibility) for other endpoints (such as ecological or aesthetic
27 effects). Defining the latter risks in terms of individual riskper se will thus complicate
28 calculating cumulative risk if a probabilistic approach to cumulative risk assessment is used, and
29 perhaps if other approaches are used as well.
30
31 In contrast, the probabilistic approach to cumulative risk assessment maybe facilitated by
32 defining the risk of a given endpoint in terms of population risk, i.e., in terms of the predicted
33 number of cases of that endpoint. Alternatively (or additionally), similar simplification can be
34 achieved for all heterogeneous endpoints by defining the risk of that endpoint only with respect
35 to those persons in the population at risk who are reasonably maximally exposed (e.g.,
36 individuals adjacent to a proposed source), or to those persons who will incur the greatest
37 increased risk (e.g., children or other members of a sensitive subpopulation who might be located
38 adjacent to a proposed source).
39
40 3.3. Areas of Complexity and Current Research
41
42 One reason for the somewhat limited availability of cumulative risk assessments maybe
43 the accompanying complexity that arises in various aspects of the assessment. Some of this is
44 discussed in the previous section, along with currently available methods specific to human
45 health risk assessment. In this section, some areas where research is ongoing are discussed, and
46 some existing methods for quantitatively assessing multiple types of risk or hazard using a single
47 metric are described.
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1 3.3.1. Interactions Between Stressors and Other Factors.
2
3 In identifying and characterizing susceptible subpopulations, it may be important to
4 consider a variety of factors such as current physical and mental health status and past exposure
5 histories, which may exacerbate the effects of the stressors of interest. Economic considerations
6 such as economic status, community property values, source of income, level of income, and
7 standard of living may also affect susceptibility and exposure of subpopulations to certain other
8 stressors. Risks associated with chemical or biological stressors may be significantly affected by
9 "vulnerability factors" such as lack of health care or genetic predisposition to some diseases and
10 effects. Community traditions and beliefs may affect activity patterns and behaviors and therefore
11 affect exposure to stressors as well as the risk management options deemed acceptable.
12 Depending on the scope of the assessment and the stressors included, "lifestyle factors" such as
13 smoking habits, nutritional habits and others may be important to susceptibility.
14
15 In what could be characterized as an exploration of how somewhat abstract factors may
16 affect susceptibility, the Agency for Toxic Substances and Disease Registry (ATSDR) held an
17 expert panel workshop in 1995 on the subject of psychological responses to hazardous substances
18 (ATSDR, 1995). In this report, the panel noted that there is "a significant lack of information"
19 about how often communities near hazardous waste sites or spills suffer chronic stress reactions,
20 but that psychological stress causes both psychological changes that can be measured by self-
21 reports and objective tests, as well as physical changes such as increased blood pressure, heart
22 rate, and biochemical parameters such as changes in stress hormones. Assessing the levels of
23 stress, and their potential contribution to risk, is difficult for a variety of reasons. The report notes
24 that "unlike the damage and injuries caused by a natural disaster, many toxic substances are
25 invisible to the senses.... In the face of no external cues and uncertain circumstances, each person
26 affected by a hazardous exposure develops their own beliefs about the nature of the resultant
27 harm. These beliefs are based on the facts available to them, pre-existing opinions, cultural
28 factors, sensory cues, and the beliefs of leaders and others in the community. . . . Unlike a natural
29 disaster, which hits and has a low point after which recovery can begin, the response to a
30 hazardous waste site can take 12 to 20 years."
31
32 Although the ATSDR report indicates that stress related to hazardous chemicals in the
33 community can show measurable physical effects, they stopped short of saying that long-term
34 health effects from this stress can be converted to risk estimates at this time. One of the questions
35 the panel was asked to address was, "Given what is known regarding the psychology of stress,
36 are there interactions between chronic stress and exposure to neurotoxicants that could shift the
37 dose-response curve for neuro toxins?" The panel concluded:
38
39
40 "A methodology does not exist that would allow for discrimination between stress or
41 neurotoxicant-mediated effects in community-based studies. . . . Experimental animal
42 data exist to suggest that stress levels can modulate a toxic response; however, the
43 question of specificity remains. Given that stress can induce or unmask a latent effect of
44 a toxicant, there is the possibility that chronic stress could alter basal levels of
45 neuro functioning and shift the threshold for neurotoxicity. Indeed, one may find a shift in
46 the dose response to a neurotoxicant; however, a specific effect of the neurotoxicant
47 needs to be examined in greater detail than the generalized non-specific endpoints.
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1 Detecting such a shift would require the knowledge of toxicant-specific biological
2 mechanisms of actions, which most often are not known." (ATSDR, 1995, page 30)
3
4 The ATSDR report made many suggestions for research to fill data gaps in this area, and
5 scientists may make significant progress in this area in the coming years.
6
7 Another group of factors which may influence the risk to health or the environment,
8 whose evaluation may require a different approach from the traditional NRC risk paradigm, is the
9 group of "quality-of-life" issues. Although a cumulative human health or ecological health risk
10 assessment is not a cumulative impact analysis such as is conducted under NEPA, changes in
11 quality-of-life factors may affect the vulnerability of a population to health or ecological risks,
12 and consequently may be part of the considerations in a cumulative risk assessment. Since few, if
13 any, established and accepted relationships are currently available quantitatively linking quality-
14 of-life factors and health or ecological risk, this is an area in which further research may prove
15 valuable.
16
17 To evaluate the effects on human or ecological health from these types of stressors, a
18 more deliberative approach (in the analytical-deliberative process) is needed than is used in, say,
19 cancer risk analysis. EPA's Guidebook to Comparing Risks and Setting Environmental Priorities
20 (USEPA, 1993b) suggests a six-step process that may help characterize quality-of-life factors,
21 some of which may be relevant to the assessment (e.g., in considering population susceptibility).
22 An example of a set of quality-of-life criteria, and their descriptions, developed by the State of
23 Vermont's Agency of Natural Resources (State of Vermont, 1991) is provided in Appendix F.
24
25 Quality-of-life issues can encompass much more than the criteria mentioned in Appendix
26 F as an example. Some human health or ecological cumulative risk assessments may consider
27 quality-of-life factors as having a role in susceptibility to the stressors being assessed.
28
29 3.3.2. The Promise of Biomarkers and Biomonitaring.
30
31 There are a variety of measures that are inherently cumulative. These include biomarkers
32 (they give the full effect or full exposure, regardless of source) and measures of the incidence and
33 prevalence of disease in a community. The latter give an indication of the total effect of multiple
34 sources of exposure. In light of our understanding of the multifactorial basis of disease, a public
35 health approach that says "regardless of the cause, a community has x level of disease" can be
36 informative. Such statistics can be compared across geographical areas that have different
37 sources or different groups that have different levels of vulnerability. The approach is based
38 strongly in the field of epidemiology. Indeed, the most often heard critique of epidemiology -
39 that it is the prevalence or incidence of disease documented as a function of the combined effect
40 of many exposures (over time and/or space), is exactly what makes it so well suited for
41 cumulative risk assessment. It is likely that epidemiological concepts will figure prominently in
42 cumulative risk assessment, both in identifying the underlying vulnerability of a population and
43 by generating hypotheses regarding the determination of relative contributions of multiple
44 stressors.
45
46 Sources of data include cross sectional analyses that determine prevalence levels, as well
47 as basic surveillance techniques. With respect to the latter, The Pew Environmental Health
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1 Commission (http://pewenvirohealth.jhsph.edu/html/home/home.html then click on "reports")
2 has recently completed a series of reports that document the extent of national and state level
3 resources for chronic disease surveillance. Reports focus on the type of surveillance systems
4 needed, as well as the status of registries for birth defects and asthma. Health Track
5 (http://health-track.org/ and http://healthyamericans.org/) is the outgrowth of that research, and is
6 devoted to tracking and monitoring of chronic disease that would help communities begin to
7 identify patterns of health problems.
8
9 Biomarkers are inherently cumulative risk measures. Using biological measurements -
10 biomarkers - to determine prior exposures (biomarkers of exposure) or the current health status
11 of individuals (biomarkers of effect) holds some promise for cumulative risk assessments of the
12 future. Use of biomarkers for a group of chemicals or stressors which act upon individuals in the
13 same way can give the assessor a picture of where an individual currently falls on the continuum
14 from exposure to effects, making it much easier to predict risks if additional exposure occurs.
15
16 A few biomarkers (or even a single one) can possibly represent exposure to a suite of
17 chemicals. Although this reduces the analytical burden and simplifies the process of estimating
18 cumulative risk, the approach loses some of the advantages of single-chemical assessment
19 (especially being able to quickly discern the importance of different pathways and routes of
20 exposure contributing to the risk).
21
22 Biomarkers may be the approach of choice in the fUture, but the state-of-the-science is not
23 developed enough to make this practicable today in an assessment with large numbers of diverse
24 stressors (although it may be possible to do this for more simple cases). Currently, biomarker
25 development is not at the stage where they can be widely applied. For example, information on
26 the cumulative risks in a local population of a group of chemicals that are toxic to the liver might
27 be provided by selective liver function tests, but causal inferences would have to take account of
28 many other factors that may affect liver function. Likewise, body burden data for chlorinated
29 dioxins and related compounds may show that exposure has occurred, but assumptions would
30 need to be made as to the pathways, route, and timing of exposures, as well as scenarios
31 developed for future exposures if risks are to be estimated.
32
33 One of the benefits of this approach, the development of data which show the actual
34 current exposure and risk status of a population, is also its major impediment: it can require
35 extensive (or for humans, possibly invasive) monitoring. This can be not only costly, but
36 difficult to obtain. This approach uses primarily measurement methods, and also can develop
37 statements of probability of adverse effects of additional incremental exposures. This approach
38 holds great promise for simplification of a cumulative risk assessment, but few methods exist at
39 this time for applying this approach in a cumulative assessment. The main drawback of the
40 biomarker approach, at least for a regulatory agency like EPA, is that a decision to act to reduce
41 risk is often dependent on separation of contributions from exposure pathways so that effective
42 policies can be determined.
43
44 3.3.3. A Single Metric for Multiple Types of Hazard.
45
46 The most complex cumulative risk assessments will evaluate both multiple exposures
47 (potentially, multiple sources, stressors, pathways and durations) and multiple effects. Ideally
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1 this evaluation would provide projections regarding the potential for a particular complex
2 exposure to cause particular effects to different physiological systems, and also provide an
3 integration of these projections into a qualitative characterization of overall potential impact to
4 human health. Some applications have attempted this via approaches which range from treating
5 the assessment as a number of multi-stressor, single effect assessments, where the risks from the
6 various effects are combined or characterized at the final step, to those that are more integrated
7 throughout.
8
9 For example, cumulative ecological risk assessments such as those that have been
10 conducted in the Columbia River Basin and the Chesapeake Bay focused on a number of
11 observed adverse conditions, then determined, among all of the possible stressors, which
12 particular combination was most influential in creating the observed adverse conditions.
13 Stressors such as overharvesting of natural resources, modification of natural hydrology, land use
14 change, point-source and non-point-source pollution, including toxic chemicals, and presence of
15 exotic species are analyzed, with the goal of the assessment being to design effective restoration
16 strategies to eliminate or ameliorate the conditions (Barnthouse, et al., 2000).
17
18 If it is considered desirable to the assessment, an important cumulative risk assessment
19 activity may be determining how (if at all possible) to combine risks from different effects - or
20 the even more problematic disparate measures of risk - and present them in an integrated
21 manner. Depending on the purpose and risk management objectives (see section 2.1.1), some
22 cumulative risk assessments may employ some sort of single, common metric to describe overall
23 risk.
24
25 One, but certainly not the only, approach to simplifying this problem is to collapse this
26 "n-dimensional matrix" of hazards and risks into a few or even a single measure (Murray, 1994).
27 However, this requires converting the various measures of risk to a common metric or otherwise
28 translating them into a common scale or index. Some methods for combining disparate measures
29 of risk are briefly described below.
30
31 3.3.3.1. Creating a Common Metric.
32
33 As discussed earlier in this chapter, there are several different theoretical approaches to
34 cumulative risk assessment. Some of these require synthesizing a risk estimate (or risk
35 indication) by "adding up" risks for different parts of the risk picture. Actual mathematical
36 addition, of course, requires a "common denominator," or a common metric. Frequently used
37 common metrics are risk, money, time, and effort. Finding a common metric for dissimilar risks
38 (cancer vs. non-cancer, human vs. ecological, etc.) is not strictly an analytic process, since some
39 judgments must be made as to how to link two or more separate scales of risks. These judgments
40 often involve subjective values, and because of this, it is a deliberative process.
41
42 As an example of combining different effects into a common metric and the consequent
43 judgment needed to achieve a common metric, the EPA Office of Pollution Prevention and
44 Toxics in 1999 released its CD-ROM called "Risk-Screening Environmental Indicators Model,
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1 Version 1.0" (USEPA, 19991)11. In this model, emissions for both carcinogens and non-
2 carcinogens are weighted by atoxicity factor so that they can be combined in a risk-based
3 screening "score" for a particular geographic area. The scale for this weight for carcinogens is
4 related to the unit risk factor, and the weight for the non-carcinogens is based on the RfD.
5 According to the authors, it is possible to relate these two scales by making a judgment as to how
6 they relate. They note that in their case, "when combining cancer and noncancer endpoints, it is
7 assumed that exposure at the RfD is equivalent to a 2.5 x 10~4 cancer risk" (Bouwes and Hassur,
8 1998; USEPA, 1998h).
9
10 Obviously, as Bouwes and Hassur acknowledge, equating an HQ value of 1.0 (i.e.,
11 exposure is at the RfD) with a cancer risk of 2.5 x 10"4 is a judgment that is outside the strictly
12 analytic part of an assessment; the equating of the two points in the respective scales represents a
13 value judgment and as such can be debated. Therefore, this particular part of the assessment is
14 deliberative in nature. In most cases, construction of a single scale for different types of
15 endpoints will involve comparative risk, a field where different types of risks or endpoints are
16 ranked, compared, or converted to a scale based on the judgments and values of the persons
17 doing the assessments (USEPA, 1993b, 1998f, 1999J).
18
19 There have been some attempts to allow for transparent and quantitative incorporation of
20 values into a common metric. One example flows from the suggestion that "time is the unit of
21 measure for the burden of disease"; whether the disease results in disability or premature
22 mortality (Murray, 1994). Based on this premise, economic analyses of the costs and benefits of
23 disease intervention strategies have used Quality Adjusted Life Years (QALYs) and Disability
24 Adjusted Life Years (DALYs) as the metrics for the adverse effects of disease. These metrics are
25 intended to reflect the years of life spent in disease states (considering the variation in severity of
26 effects) and the years of life lost due to premature mortality resulting from disease as a surrogate
27 measure for risk from a variety of different types of effect. Even if this conversion of effects into
28 QALYs or DALYs were successful, for diseases that result in periods of morbidity and disability
29 (but not death), weighting factors (based on judgments) are used to equate time spent in various
30 disease states with years lost to mortality. In this way, dissimilar adverse effects can be
31 combined to provide a single measure of disease burden. However, it should be noted that
32 aggregation of effects in this manner obscures the meaning of the final measure. QALYs and
33 DALYs do not represent an actual shortening of the lifespan but are indicators of the overall
34 degradation of well-being that results from various disease states. Therefore, QALYs and
35 DALYs maybe best suited for ranking and comparative analyses.
36
37 Experience with applying such measures as QALYs and DALYs to environmental risk
38 problems is extremely limited. Some very early methods development work has been initiated
39 which explores the use of QALYs for combining microbial and disinfection by-product risks
40 (USEPA, 1998f). However, some concerns have been raised about the adequacy of such
41 measures, especially when integrated with economic information for decision making USEPA,
42 2000g). Further methods development work is needed to improve the utility of QALYs and
43 DALYs for environmental risk assessments; especially with respect to the incorporation of
44 uncertainty (USEPA, 1999J).
As of this writing, EPA has RSEI version 2.0 in beta test. Details are at www.epa.go v/oppt/env_ind/beta_test.htm.
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1 Categorical regression may provide another tool for combining disparate effects using a
2 common metric. In this approach, adverse effects are assigned to severity categories (again, a
3 judgment making the process deliberative) and the ordered categories are regressed against
4 increasing dose (Teuschler et al., 1999). The use of categorical regression as a tool for
5 combining disparate effects has definite limits on interpretation of the results. Since the toxicities
6 are only represented by categories, and judgment is used to place the observed response into a
7 severity category, the results are rather coarse. But because the analysis is almost totally
8 empirical, that is, no low-dose extrapolation is required, the results can still be quite useful.
9 EPA has also used decision indices (see section 3.2.2.3) based on dissimilar measures,
10 and while they do not produce risk estimates, the indices can still prove useful. The approach
11 involves developing a composite score - or index - from measures of various risk dimensions .
12 Various environmental risk indices have been developed and applied to ranking and comparative
13 analyses. Often, these indices employ surrogate measures for risk rather than using actual
14 calculations of the probability of adverse effects. One such index is the Hazard Ranking System
15 (MRS) [47 Fed. Reg. 31219, dated July 16, 1982, and amended 55 Fed. Reg. 51532, dated
16 December 14, 1990], used to place uncontrolled waste sites on the National Priorities List (NPL)
17 for Superfund. This index is based on the likelihood of off-site movement of waste, the toxicity
18 of the waste, and the people and sensitive environments that may be affected. It also uses
19 corrosivity, toxicity, fire hazard and other factors, all scored and combined into one numerical
20 indicator of overall hazard potential. Such an approach for a composite index has been suggested
21 for communication of cumulative risk (Hertzberg, 2000).
22
23 Fischhoff et al. (1984) provided an example of this approach as applied to the evaluation
24 of energy technologies. In this case, disparate risks are assigned a score from a fixed scale (e.g.,
25 from 0, representing no risk, to 100, representing the worst risk for that dimension). The scores
26 are then weighted to reflect value judgments about the importance of the various risk dimensions
27 and the composite score is calculated by summing the individual weighted scores. Again, the
28 aggregation of dissimilar adverse effects obscures the meaning of the final score making it more
29 appropriate for ranking and comparative analyses.
30
31 Recently, EPA has been working on several index-based approaches to dealing with
32 cumulative risk issues. EPA Region III and the Office of Research and Development have been
33 jointly working to develop a Potential Risk Indexing System (USEPA, 1993c, 1995d, 1997c).
34 This index also uses a vulnerability index, and gauges the overall well-being of a locale and
35 various subpopulations. Again, the volume and toxicity of released stressors serve as surrogate
36 measures of risk in developing this index.
37
38 Combining diverse effects and risk using either common metrics or indices each have
39 pros and cons. A weakness of the index approach is that information is "lost," and the meaning
40 of the final score can be obscured, by aggregating dissimilar information. One strength, however,
41 is common to both approaches. Both techniques have the ability to incorporate social values in
42 an explicit and quantitative manner in the risk assessment. For example, in the derivation of
43 DALYs, weights can be used to reflect the different social roles people play as they age (Murray,
44 1994). In the composite scores developed by Fischhoff (1984), public concern was incorporated
45 as an adverse effect. This is an important feature for methods that will be applied to cumulative
46 risk assessments, especially for communities. Given that cumulative assessments have a
47 community/population focus, the ability to incorporate social values in an overall assessment of
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1 well-being will be critical.
2
3
4 3.3.3.2. General Issues with a Single Metric.
5
6 As described above, each approach to portraying the results of a cumulative risk
7 assessment has desirable and undesirable features. While common metrics and indices can
8 incorporate social values in an explicit and quantitative manner, the meaning of the final measure
9 can be obscured by aggregation of dissimilar effects. The abstract meaning of the final measure
10 could lead to difficulties when communicating the results of the cumulative risk assessment to
11 the public. Graphical and mapping techniques do not necessarily overcome such problems with
12 communication. While these techniques may avoid some of the problems associated with the
13 mathematical aggregation of dissimilar effects, it can be difficult to accurately describe the
14 information that a graphic is intended to convey.
15
16 Because we have relatively little experience in combining different types of risk, a key
17 issue is the need for methods development in this area. The approaches described above indicate
18 a beginning. Additional exploratory work is needed, however, to further develop existing
19 methods and to find additional methods that are flexible, can incorporate social values, are easy
20 to communicate, and provide an integrated portrayal of the overall well-being of a community
21 and its various subpopulations.
22
23 3.3.4. Qualitative approaches.
24
25 There will be cases where cumulative risk cannot be quantified in any meaningful or
26 reliable way. Qualitative approaches can be valuable for cumulative risk assessment and, in the
27 near-term, may be the only practical way to address many of the complexities involved.
28 Qualitative approaches may be used as a way to overcome the complexity and data deficiencies
29 that hinder quantitative approaches. In many assessments, risk may not be a quantifiable
30 variable.
31
32 For these cases, there may be qualitative approaches that provide some insight. Broad
33 indicators related to exposure in complex ways (e.g., production volumes, emissions inventories,
34 environmental concentrations, etc.) and indicators of toxicity can be communicated using
35 geographic information systems. Displaying complex multi-dimensional matrices in a map can
36 help visualize locations of areas with multiple stressors. Furthermore, geographically based
37 measures of hazard are potentially useful cumulative measures - although they do not provide
38 information on the risks, the locations of hazards can be used as an indicator of cumulative
39 exposures, thus risks from all of the potential chemicals associated with that site. The
40 environmental justice literature has used this approach.
41
42 Quantitative results might eventually be reduced to a more qualitative scale (High,
43 Medium or Low), or the qualitative results could provide "comments" tacked to the quantitative
44 results. The assessment might simply raise "red flags" associated with specific issues (e.g.
45 density of emitters in a community; presence of minority populations; special exposure
46 pathways; etc); a high number of such flags would indicate unacceptable cumulative risk, even if
47 this isn't quantified. This approach has been used in the European Union, and their experience
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[ref needed] in using qualitative methods for permitting suggests that "qualitative" is not
"irrational". Other relevant tools include expert judgment techniques, focus groups, opinion
surveys, citizen juries, alternative dispute resolution, and others.
Planning, Scoping, and
Problem Formulation
Analysis
Interpretation and
Risk Characterization
Figure 4.1. The Interpretation and Risk Characterization Phase.
4. THE RISK CHARACTERIZATION PHASE
The last phase of cumulative risk assessment, Risk Characterization, integrates and
interprets the results of the Analysis phase and addresses the problem(s) formulated in the
Planning and Scoping phase. It should describe the qualitative and/or quantitative risk
assessment results; list the important assumptions, limitations and uncertainties associated with
those results; and discuss the ultimate use of the analytic-deliberative outcomes. Given the
complexity of cumulative risk issues and the need for clarity and transparency in risk
characterization, such 'full disclosure' presents a major communication challenge.
As in the Analysis Phase, there is a substantial analytical component of the Interpretation
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Phase, but there is also a considerable need for deliberation. At a minimum, stakeholders in this
phase should (1) understand the outcome of the cumulative risk assessment; (2) ask questions
about how best to frame the interpretation; (3) confirm that the cumulative risk assessment met
the goals set in the Problem Formulation, or if not, why not. As in the previous phase, the
stakeholders' role is only limited by what is proposed and agreed upon in the individual case
being assessed.
Risk estimation in a cumulative risk assessment will involve some combination of risks,
either risks from various stressors causing similar effects, or risks from various stressors causing
different types of effects. The stressors maybe similar or widely different. Combinations of many
types of stressors with different endpoints in a single assessment will quickly cause the risk
estimation step to become very complex and difficult.
Because of its potential complexity, and because in some cases cumulative risk
assessments will be dealing with "uncharted territory" methodologically, it is very important that
the planning, conduct, analysis, and characterization of a cumulative risk assessment be
transparent. As stated by OMB (OMB,
2002), the "benefit of transparency is that
the public will be able to assess how much
an agency's analytic result hinges on the
specific analytic choices made by the
agency." The process, methodology, data,
assumptions, and selection among alternate
interpretations must be very carefully
documented and very clearly stated. This is
noted again in the next section.
4.1. Risk Description
The ultimate product in the risk
assessment process is the risk
characterization, in which the information
from all the steps is integrated and an
overall conclusion about risk is synthesized
that is complete, informative, and useful for
decision-makers. The nature of the risk
characterization will depend on the
information available, the regulatory
application of the risk information, and the
resources (including time) available. It is
important to identify and discuss all major
issues associated with determining the
nature and extent of the risk. Further, the
EPA Administrator's March 1995 Policy for
Risk Characterization (U.S. EPA, 1995a)
specifies that a risk characterization "be
prepared in a manner that is clear,
Risk Characterization Guiding Principles
Regarding information content and uncertainty aspects:
> The risk characterization integrates the information from the
exposure and dose-response assessments, using a combination
of qualitative information, quantitative information, and
information regarding uncertainties.
> The risk characterization includes a discussion of uncertainty
and variability.
>• Well-balanced risk characterizations present risk conclusions
and information regarding the strengths and limitations of the
assessmentfor otherrisk assessors, EPA decision-makers, and
the public.
Regarding risk descriptors:
<• Information about the distribution of individual exposures is
important to communicating the results of a risk assessment.
> Information about population exposure leads to another
important way to describe risk.
> Information about the distribution of exposure an d risk for
different subgroups of the population are important components
of a risk assessment.
> Situation-specific information adds perspective on possible
future events or regulatory options.
> An evaluation of the uncertaintyin the risk descriptors is an
important component of the uncertainty discussion in the
assessment.
Source: USEPA, 1995b.
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1 transparent, reasonable, and consistent with other risk characterizations of similar scope prepared
2 across programs in the Agency." In short, estimates of health risk are to be presented in the
3 context of uncertainties and limitations in the data and methodology.
4
5 The 1995 Guidance for Risk Characterization (USEPA, 1995b) lists several guiding
6 principles for defining risk characterization in the context of risk assessment (see text box), both
7 with respect to information content and uncertainty aspects and with respect to descriptions of
8 risk. EPA has recently published a handbook on risk characterization (USEPA, 2000c).
9
10 Risk assessments are intended to address or provide descriptions of risk to one or more of
11 the following: (1) individuals exposed at average levels and those in the high-end portions of
12 the risk distribution; (2) the exposed population as a whole; and (3) important subgroups of the
13 population such as highly susceptible groups or individuals (e.g., children), if known. Risk
14 predictions for sensitive subpopulations are a subset of population risks. Sensitive
15 subpopulations consist of a specific set of individuals who are particularly susceptible to adverse
16 health effects because of physiological (e.g., age, gender, pre-existing conditions),
17 socioeconomic (e.g., nutrition), or demographic variables, or significantly greater levels of
18 exposure (USEPA, 1992a). Subpopulations can be defined using age, race, gender, and other
19 factors. If enough information is available, a quantitative risk estimate for a subpopulation can
20 be developed. If not, then any qualitative information about subpopulations gathered during
21 hazard identification should be summarized as part of the risk characterization.
22
23 The 1996 book Understanding Risk(NRC, 1996) devoted a great deal of discussion to risk
24 characterization. Risk characterization is most efficiently conducted by early and continued
25 attention to the "risk characterization" step in the risk assessment process (NRC, 1996; USEPA,
26 2000c). The box on the following page summarizes some of the points made in Understanding
27 Risk.
28
29
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Some Thoughts on Risk Characterization
The NRC book Understanding Risk (NRC, 1996) has
risk characterization as its primary focus. In their
conclusions, NRC states:
1. Risk characterization should be a decision-driven
activity, directed towards informing choices and solving
problems. The view of risk characterization as a
translation or summary is seriously deficient. . .. Risk
characterization should not be an activity added at the
end of risk analysis; rather, its needs should largely
determine the scope and nature of risk analysis.
2. Coping with a risk situation requires a broad
understanding of the relevant bsses, harms, or
consequences to the interested and affected parties. A
risk characterization must address what the interested
and affected parties believe to be at risk in the particular
situation, and it must incorporate their perspectives and
specialized knowledge.
3. Risk characterization is the outcome of an analytic-
deliberative process. . . . Analysis and deliberation can
be thought of as two complementary approaches to
gaining knowledge about the world, forming
understandings on the basis of knowledge, and reaching
agreement among people.
4. The analytic-deliberative process leading to a risk
characterization should include early and explicit
attention to problem formulation.
5. The analytic-deliberative process should be mutual
and recursive. ... A recurring criticism of risk
characterization is that the underlying analysis failed to
pay adequate attention to questions of central concern to
some of the interested and affected parties. This is not
so much a failure of analysis as a failure to integrate it
with broadly based deliberation: the analysis was not
framed by adequate understanding about what should be
analyzed. . . . Structuring an effective analytic-
deliberative process for informing a risk decision is not a
matter for a recipe. Every step involves judgment, and
the right choices are situation dependent. Still, it is
possible to identify objectives that also serve as criteria
for judging success:
Getting the science right. The underlying analysis meets
high scientific standards in terms of measurement,
analytic methods, data bases used, plausibility of
assumptions, and respectfulness of both the magnitude
and character of uncertainty. . .
Getting the right science. The analysis has addressed
the significant risk-related concerns of public officials
and the spectrum of interested and affected parties, such
as risks to health, economic well-being, and ecological
and social values, with analytic priorities having been
set so as to emphasize the issues most relevant to the
decision.
Getting the right participation. The analytic-deliberative
process has had sufficiently broad participation to
ensure that the important, decision-relevant information
enters the process, that all important perspectives are
considered, and that the parties' legitimate concerns
about inclusiveness and openness are met.
Getting the participation right. The analytic-
deliberative process satisfies Ihe decision makers and
interested and affected parties that it is responsive to
their needs: that their information, viewpoints, and
concerns have been adequately represented and taken
into account; that they have been adequately consulted;
and that their participation has been able to aflect the
way risk problems are defined and understood.
Developing an accurate, balanced, and informative
synthesis. The risk characterization presents the state of
knowledge, uncertainty, and disagreement about the risk
situation to reflect the range of relevant knowledge and
perspectives and satisfies the parties to a decision that
they have been adequately informed within the limits of
available knowledge.
6. Those responsible for a risk characterization should
begin by developing a diagnosis of the decision
situation so that they can better match the analytic-
deliberative process leading to the characterization to
the needs of the decision, particularly in terms of level
and intensity of effort and presentation of parties. . . .
Diagnosis of risk decision situations should follow eight
steps: (1) diagnose the kinds of risk and the state of
knowledge, (2) describe the legal mandate, (3) describe
the purpose of the risk decision, (4) describe the affected
parties and anticipate public reactions, (5) estimate
resource needs and timetable, (6) plan for organizational
needs, (7) develop a preliminary process design, and (8)
summarize and discuss the diagnosis with the
responsible organization.
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4.2. Uncertainty Analysis
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In their 1990 book Uncertainty: A Guide to Dealing with Uncertainty in Quantitative
Risk and Policy Analysis, Morgan and Henrion (1990) note that historically, the most common
approach to uncertainty in policy analysis (including in risk assessment) has been to ignore it. In
a section titled "Why Consider Uncertainty?" they advance three primary reasons, all of which
are especially relevant to an analytic-deliberative process such as cumulative risk assessment.
They suggest that it is important to worry about uncertainty:
• "when one is performing an analysis in which people's attitude toward risk is likely to be
important, for example, when people display significant risk aversion;
• "when one is performing an analysis in which uncertain information from different
sources must be combined. The precision of each source should help determine its
weighting in the combination; and
• "when a decision must be made about whether to expend resources to acquire additional
information. In general, the greater the uncertainty, the greater the expected value of
additional information."
Morgan & Henrion's "Ten Commandments"
for Good Policy Analysis
Do your homework with literature, experts, and users.
Let the problem drive the analysis.
Make the analysis as simple as possible, but no simpler.
Identify all significant assumptions.
Be explicit about decision criteria and policy strategies.
Be explicit about uncertainties.
Perform systematic sensitivity and uncertainty analysis.
Iteratively refine the problem statement and the analysis.
Document clearly and completely.
10. Expo se the work to peer review.
Source: Morgan and Henrion, 1990.
Morgan and Henrion provide
"ten commandments" for good policy
analysis, and although all are
commendable, and several have been
discussed elsewhere in this Framework
report, we should look more closely at
numbers 6-8 in the box at right for
some insight into uncertainty analysis.
There are many resources available
which talk in detail about how to
perform uncertainty analysis (e.g.,
USEPA, 1997b, Morgan and Henrion,
1990). While detailed instruction on
how to perform uncertainty analysis is
beyond the scope of this Framework
report, we believe that a discussion of some general principles is in order.
4.2.1. Assumptions in the Assessment
Cumulative risk assessment will typically be used in a decision-making process to help
inform the decision-maker(s). For this reason, it is important that the decision makers be made
explicitly aware of any assumptions that may significantly affect the conclusions of the analysis
(item #6 in the box above). Morgan and Henrion suggest that these assumptions include:
• the main policy concerns, issues, or decisions that prompted the assessment;
• the evaluation criteria to be used to define issues of concern or options;
• the scope and boundaries of the assessment, and ways in which alternate selections might
influence the conclusions reached;
• soft or intangible issues that are ignored or inadequately dealt with in the quantitative
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1 analysis (e.g., intrinsic value of wilderness, equity of distribution of risks and benefits);
2 • approximations introduced by the level of aggregation or by level of detail in models;
3 • value judgments and tradeoffs; and
4 • the objective function used, including methods of combining ratings on multiple criteria
5 (or combining risk scales), [adapted from Morgan and Henrion, 1990]
6
7 Identifying significant assumptions can often highlight "soft" uncertainties that are not
8 easily quantified, and are therefore often left out of a quantitative uncertainty analysis.
9 Nevertheless, these "soft" assumptions can often contribute more to the overall uncertainty of the
10 assessment than the factors more easily quantified.
11
12 In item #7 in Morgan and Henrion's "ten commandments," they list three types of
13 uncertainty that analysts should explicitly include:
14
15 • uncertainty about technical, scientific, economic, and political quantities (e.g., quantities
16 like rate constants often lend themselves to quantitative uncertainty estimates relatively
17 easily);
18 • uncertainty about the appropriate functional form of technical, scientific, economic, and
19 political models (e.g., are the models used, such as dose-response models, biologically
20 sound?);
21 • disagreements among experts about the values of quantities or the functional form of
22 models (e.g., different health scientists using different forms of dose-response models).
23
24 In Item #8 in the box on the previous page, Morgan and Henrion suggest that an assessor
25 needs to find out which assumptions and uncertainties may significantly alter the conclusions,
26 and that process can be conducted using sensitivity and uncertainty analysis. Techniques for these
27 include:
28
29 • deterministic, one-at-a-time analysis of each factor, holding all others constant at nominal
30 values;
31 • deterministic joint analysis, changing the values of more than one factor at a time;
32 • parametric analysis, moving one or a few inputs across reasonably selected ranges to
33 observe the shape of the response; and
34 • probabilistic analysis, using correlation, rank correlation, regression, or other means to
35 examine how much of the uncertainty in the conclusions is attributable to which inputs.
36
37 Finally, Morgan and Henrion answer the question of why we should consider uncertainty
38 analysis with the following point. "Policy analysts have a professional and ethical responsibility
39 to present not just "answers" but also a clear and explicit statement of the implications and
40 limitations of their work. Attempts to fully characterize and deal with important associated
41 uncertainties help them to execute this responsibility better." (Morgan and Henrion, 1990)
42
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46 4.2.2. Uncertainty and Variability
47
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In their 1994 report Science and Judgment in Risk Assessment (NRC, 1994), the National
Research Council noted a clear difference between uncertainty and variability, and recommended
that the distinction between these two be maintained:
"A distinction between uncertainty (i.e., degree of potential error) and inter-individual
variability (i.e., population heterogeneity) is generally required if the resulting
quantitative risk characterization is to be optimally useful for regulatory purposes,
particularly insofar as risk characterizations are treated quantitatively. The distinction
between uncertainty and individual variability ought to be maintained rigorously at the
level of separate risk-assessment components (e.g., ambient concentration, uptake, and
potency) as well as at the level of an integrated risk characterization." (NRC, 1994, page
242)
Variability and uncertainty have been treated separately and distinctly in single-chemical
assessments such as the assessment of trichloroethylene in ground water at Beale Air Force Base
in California (Bogen, 2001). The treatment of variability and uncertainty will be an important
issue in cumulative risk assessments, also, although at the time of this writing there are no good
examples available of an elegant treatment of this issue for cumulative risk.
4.2.3. Uncertainty and Risk Addition
Calculating individual stressor risks,
and then combining them, presents largely the
same challenges as combination toxicology,
but also adds some statistical stumbling
blocks. Toxicity addition, independence,
synergism, or antagonism still need to be
evaluated, but since risk estimates for various
stressors are often presented as values on the
same numeric scale (e.g., as cancer
probabilities), cancer risks are often just
added together.
Since most cancer slope factors are
not "most probable estimates," but 95% upper
confidence levels, adding traditional risk
levels can cause the resulting sum to
overestimate a 95% upper confidence level
risk for a mixture. There have been several
recent papers discussing this problem and
how it may effect the resulting estimates. Kodell and Chen (1994) looked at several binary
mixtures and calculated that the summation of individual upper 95% confidence intervals for
chlorobenzene and hexachlorobenzene would overestimate the upper-bound risk of a binary
mixture of these compounds by 2-6%, while for chlorobenzene and trichloroethylene, the
overestimate would be in the range of 12-15%. Seed, et al. (1994) noted that, "in most cases, the
magnitude of the difference in cancer risk estimates calculated by [Kodell and Chen's] various
Uncertainty Analysis Example:
The Cumulative Exposure Project
EPA's Cumulative Exposure Project (CEP), completed in
1998, modeled 1990 outdoor concentrations of hazardous
air pollutants (HAPs) across the United States, which were
combined with unit risk estimates to estimate the potential
increase in excess cancer risk fom multiple HAPs. The
cancer risks of different HAP s were assumed to be additive
and were summed across pollutants in each census tract to
estimate a total cancer risk in each census tract.
Consideration of some specific uncertainties, including
underestimation of ambient concentrations, combining
upper 95% confidence bound potency estimates, and
changes to potency estimates, found that cancer risk may
be underestimated by 15% or overestimated by 40-50%.
Other unanalyzed uncertainties could make these under- or
overestimates larger.
Source: Woodruff, et al., 2000
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1 methods will be greatest for mixtures of eqipotent compounds. However, even for mixtures of
2 equipotent compounds, the differences in joint risk estimated by summing the upper 95%
3 confidence levels. . .are not great." After analyzing four cases, Cogliano (1997) concluded that
4 "as the number of risk estimates increases, their sum becomes increasingly improbable, but not
5 misleading." For example, in adding 20 different cancer risk estimates based on a 95% upper
6 bound, the resulting sum of the upper bounds was no more than 2.2 times the true upper bound.
7 Cogliano goes on to suggest that, for certain cases not involving synergistic or antagonistic
8 interactions, "depending on the number of carcinogens and the shape of the underlying risk
9 distributions, division by a factor of 2 can be sufficient to convert a sum of upper bounds into a
10 plausible upper bound for the overall risk" (Cogliano, 1997).
11
12 The assumption of toxicologic independence (see section 3.2.2) may not be a bad
13 assumption if other evidence supports it, but it should be addressed in the assessment if used
14 (i.e., if risks are added). Although there are some scientists who believe that toxicologic
15 interactions are of minor consequence at concentrations observed in the environment (see
16 discussion in USEPA, 2000e), the scientific evidence for such an assumption has not been firmly
17 established.
18
19 Notwithstanding the statistical limitations of adding traditional risk estimates, and the
20 implicit assumption that the toxicities will be additive12 (i.e., no interactions such as synergism or
21 antagonism occur), the numerical ease for combining risks in this way may make it the most
22 popular method for approximating cumulative risks in the short term, at least at a screening level
23 of assessment.
24
25 4.3. The Information Provided by Cumulative Risk Assessment
26
27 It is important to clarify how cumulative risk assessment and this Framework report relate
28 to community assessments and community decision making. Certainly, the Agency'sRisk
29 Characterization Handbook (USEPA, 2000c) emphasizes that whatever information is imparted,
30 it be transparent, clear, consistent, and reasonable. For example, if it is known that the results of a
31 particular cumulative risk assessment will be severely limited because of a lack of data or
32 available methods, it may be advisable to start with a screening analysis to set priorities for a
33 subsequent more detailed, focused study. In simple terms, what can a cumulative risk assessment
34 tell us, and what can't it tell us?
35
36 4.3.1. Making Sense of Multiple Stressor Effects
37
38 The information provided by cumulative risk assessment is only a portion of the
39 information that communities and governments need to make informed decisions about risks.
40 There are almost always a multitude of factors that affect health in a community (e.g., crime,
41 drugs, health care access, vehicle safety, climate, infectious disease, diet. . .), some of which may
42 not have been considered within the scope of any given cumulative risk assessment. Community
43 decision-making will typically take risks to the environment into account, as well as
12
At risk levels often seen with pollutant concentrations observed in the environment, the combined risks calculated assuming
"response additivity" (that is, each component acts as if the other were not present) are approximately the same as with dose additivity (USEPA,
2000e).
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1 consideration about historical and cultural values, and questions of fairness and distribution of
2 risks. The methodology is not currently available to understand how these factors (or stressors)
3 may affect cumulative health risk.
4
5 Additionally, benefits that may be associated with chemical or other stressor exposures -
6 benefits such as jobs and useful products or services - may be important contexts for decisions
7 on the risks considered in cumulative risk assessments.
8
9 This Framework report is not an attempt to lay out protocols to address all the risks or
10 considerations that are needed to adequately inform community decisions. Rather, it is focused
11 on describing various aspects of cumulative risk, whether or not the methods or data currently
12 exist to adequately analyze or evaluate those aspects of the assessment. The Framework report
13 devotes considerable time to a discussion of improving the methods for a single part of the
14 broader picture — characterizing health risks associated with exposures to multiple chemicals via
15 multiple routes. Because of the limitations of the current state of the science, cumulative risk
16 assessments in the near future will not be able to adequately answer all questions posed by
17 stakeholders or interested parties. This does not mean, however, that they can't be useful in
18 providing insights to some of the questions asked; in fact, cumulative risk assessment may be the
19 best tool available to address certain questions dealing with multiple stressor impacts.
20
21 4.3.2. Cumulative Risk Assessments in a Public Health Context
22
23 The public, in a variety of forms, continually draws attention to health statistics, asking
24 for clarification of the relationship between environmental pollution (and risk assessments
25 concerning it) and public health. It is important to clarify that to draw relationships between
26 environmental pollutant exposures and disease incidence, a body of epidemiological study is
27 necessary, and trying to "work backwards" from health statistics to risk factors requires full
28 knowledge of the risk factors associated with the relevant disease(s).
29
30 Health statistics, including death rates and incidence of various diseases, illustrate the
31 impact of a variety of risk factors (e.g., smoking as well as environmental pollutants) and risk
32 reduction factors (e.g., exercise and good nutrition, as well as pollution control measures).
33 Indeed, population health statistics are reflective of all risk and risk reduction factors in a
34 population's history-to-date. Even the best cumulative risk assessment given today's state of the
35 science would fall short of being able to include an evaluation of the magnitude and interactions
36 of all stressors and effects. At best, the risk estimates of a cumulative risk assessment will reflect
37 some of the risks which may be reflected in community health statistics. With rare exceptions13,
38 cumulative risk assessment estimates would not be expected to match exactly with community
39 health statistics, even for specific health endpoints such as specific cancers.
40
41
42
43 4.3.3. How Scope and Purpose of the Assessment Affect Results
It is conceivable lhat high risks to rare specific effects could be comparable between arisk assessment and
community health statistics given current state of the art. To be sure this is not coincidental, a substantial effort to match risk
assessment scenarios with actual histories or exposures would have to be made.
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1 Historically, the Agency's risk assessments have focused on assessing the risks from
2 environmental pollutants to public health or the environment, usually for the purposes of
3 prioritizing risk management activities or triggering regulatory action. Given the need for pub lie
4 health protective decisions, traditional risk assessment tools usually focus on predicting high
5 ends of the risk distribution. Also, the traditional tools are not designed to predict risk of diseases
6 other than cancer. Additionally, the many environmental pollutants comprise only some of the
7 categories of risks to public health. While quite adequate for their original purpose, when the
8 results of these types of assessments are viewed from another perspective, such as a community
9 concerned about the cumulative health impacts of five industrial and commercial facilities within
10 a two block area, they may not be useful.
11
12 The Agency is doing more place-based human health and ecological assessments (i.e.,
13 compared to source- or media-specific assessments) than in the past, but it will be some time
14 before place-based assessments become commonplace. Consistent with good practices for
15 planning and scoping, these often may be driven by specific risk management needs. To the
16 extent there are parties that were outside the process, their desired objectives and purpose may
17 differ from those for which the assessment was designed. For this reason, users of cumulative
18 risk assessments are advised to carefully study the scope and purpose of the assessment at hand,
19 as well as the analysis plan and resulting characterization, in order to determine whether it is
20 suitable (or partly suitable) to answer questions outside its stated objectives and purpose.
21
22
23 4.4. Using the Results of the Assessment
24
25 Once the results of an assessment are in hand, the assessment participants will usually
26 focus primarily on the use of those results. The intended use of the assessment was considered at
27 the beginning, in the Problem Formulation Phase, both to plan the assessment work and to set the
28 stage for what possible actions might be taken at this point.. A detailed discussion of the use of
29 the results of a cumulative risk assessment is beyond the scope of this document, but in deciding
30 on a course of action, other considerations will need to be taken into account along with the
31 results of the cumulative risk assessment.
32
33 If the goals of a cumulative risk analysis are to estimate the risk from multi-chemical and
34 multi pathway exposure to individuals living within a geographical area of concern, then an
35 important objective in presenting the results is to identify the major risk contributors in order to
36 understand the sources, pathways, and stressors which contribute most to that overall risk. The
37 results of a cumulative risk assessment provide an additional tool for the risk manager, one that
38 permits a more complete accounting and more explicit analysis to target follow-up risk
39 mitigation strategies toward those stressors which most contribute to the population's risk.
40
41 If action to mitigate or prevent risk is the goal of the stakeholders, then options for action
42 discussed in the planning of the assessment can be re-evaluated in light of the results of the
43 assessment. Some of the issues after re-evaluating the action alternatives might include: "Is
44 regulatory authority available to address concerns or are voluntary actions better suited to address
45 the risks?" or "Can the concerns be addressed by the stakeholders involved in the assessment or
46 are the options for mitigation and prevention beyond the scope of their control?" In the latter
47 case, for example, siting issues are usually decided locally and may be within the authority of the
62
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
participants of a local assessment. In contrast,
risk from mobile sources or acid rain are likely
to require action beyond the scope of a single
local community. In that case, taking action
will require working with other communities
and is likely to take more time. Discussion of
the options available for addressing results of
a risk assessment will help to keep
expectations in line with possibilities.
In taking action - or not taking action -
after a cumulative risk assessment has been
interpreted, the team may benefit from lessons
learned by others, just as in the planning,
scoping, and problem formulation phase. The
European Environment Agency (EEA) in early
2002 released an extensive study of twelve
classic case studies in human and
environmental health protection, and the
lessons learned from them (EEA, 2001). The
report is available on the internet and should
be "food for thought" for any group
contemplating protective actions, but
particularly for community assessments.
Twelve of the EEA's "late lessons learned" are
reproduced in the box at right.
EEA's 12 Late Lessons Learned
- Acknowledge and respond to ignorance, as well as
uncertainty and risk, in technology appraisal and public
policy-making.
- Provide adequate long-term environmental and health
monitoring and research into early warnings.
- Identify and work to reduce blind spots and gaps in
scientific knowledge.
- Identify and reduce interdisciplinary obstacles to
learning.
- Ensure that real world conditions are adequately
accounted for in regulatory appraisal
- Systematically scrutinize the claimed justifications and
benefits alongside the potential risks.
- Evaluate a range of alternative options for meeting needs
alongside the option under appraisal, and promote more
robust, diverse and adaptable technologies so as to
minimize the costs of surprises and maximize Ihe benefits
of innovation.
- Ensure use of "lay" and local knowledge, as well as
relevant specialist expertise in the appraisal.
- Take full account of the assumptions and values of
different social groups.
- Maintain regulatory independence from interested parties
while retaining an inclusive approach to information and
opinion gathering.
- Identify and reduce institutional obstacles to learning and
action.
- Avoid "paralysis by analysis" by acting to reduce
potential harm when there are reasonable grounds for
Source: EEA, 2001
Finally, it is important to keep in mind
that the results of the risk assessment will be
only one of the factors that will need to be considered in making a decision on action to address
the risk. Risk information can make an important and valued contribution to the decision-
making process, but risk information, by itself, can not determine the decision. Factors such as
the availability of resources for change, fairness and other community values, politics, business
and employment considerations, quality of life issues, or concern for future generations will also
influence any decision made. In the siting example mentioned above, the assessment may
determine that the new facility does not significantly increase risk to the community and a
decision not to site the facility might still be made on the basis of a quality of life issue unrelated
to risk. Or, in contrast, a community may decide that the economic and employment benefits
outweigh the risks associated with the siting. Other risk factors not considered in the assessment
may also enter into the decision-making process. This can include both the environmental risks
not covered in the cumulative risk assessment as well as the non-environmental risks that may
affect a community. With limited resources, a community may use all available risk information
to most effectively target its resources.
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1 5. GLOSSARY
2
3 Adverse effect - A biochemical change, functional impairment, or pathological lesion that either
4 singly or in combination adversely affects the performance of the whole organism or reduces an
5 organism's ability to respond to an additional environmental challenge.
6
7 Agent - a chemical, radiological, mineralogical, or biological entity that may cause deleterious
8 effects in an organism after the organism is exposed to it.
9
10 Aggregate exposure - The combined exposure of an individual (or defined population) to a
11 specific agent or stressor via relevant routes, pathways, and sources.
12
13 Aggregate risk - The risk resulting from aggregate exposure to a single agent or stressor.
14
15 Benchmark dose (BMD) - The dose producing a predetermined, altered response for an effect.
16 A BMD10, for example, would be calculated based on a benchmark response of 10%.
17
18 Benchmark response (BMR) - A predetermined level of altered response or risk at which the
19 benchmark dose is calculated. Typically, the BMRs used are 1%, 5%, or 10%.
20
21 Conceptual model - Both a written description and a visual representation of actual or predicted
22 relationships between humans or ecological entities and the chemicals or other stressors to which
23 they may be exposed.
24
25 Cumulative risk - The combined risks from aggregate exposures to multiple agents or stressors.
26
27 Cumulative risk assessment - An analysis, characterization, and possible quantification of the
28 combined risks to health or the environment from multiple agents or stressors.
29
30 Dose additivity - In a mixture, when each chemical behaves as a concentration or dilution of
31 every other chemical. The response of the combination of chemicals is the response expected
32 from the equivalent dose of an index chemical (the chemical selected as a basis for
33 standardization of toxicity of components in a mixture). The equivalent dose is the sum of
34 component doses scaled by their toxic potency relative to the index chemical. For example, for
35 chlorinated dibenzodioxins (CDDs), 2,3,7,8-TCDD is selected as the index chemical, and other
36 CDD concentrations are adjusted for their potency relative to 2,3,7,8-TCDD, then treated as if
37 they were 2,3,7,8-TCDD "equivalents."
38
39 Dose-response relationship - A relationship between (1) the dose, either "administered dose" or
40 absorbed dose, and (2) the extent of toxic injury produced by that chemical or agent. Response
41 can be expressed either as the severity of injury or proportion of exposed subjects affected.
42
43 Endpoint - An observable or measurable biological or chemical event used as an index of the
44 effect of a stressor on a cell, tissue, organ, organism, etc.
45
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1 Lowest observed adverse effect level (LOAEL) - The lowest dose or exposure level in a study
2 which there is a statistically or biologically significant increase in the frequency or severity of an
3 adverse effect in the exposed population as compared with an appropriate, unexposed control
4 group.
5
6 Model - A mathematical representation of a natural system intended to mimic the behavior of the
7 real system, allowing description of empirical data and predictions about untested states of the
8 system. Use of models is usually facilitated by computer programming of the mathematics and
9 construction of a convenient input and output format.
10
11 No observed adverse effect level (NOAEL) - An exposure level at which there are no
12 statistically or biologically significant increases in the frequency or severity of adverse effects
13 between the exposed population and its appropriate control; some effects may be produced at this
14 level, but they are not considered to be adverse or precursors to adverse effects. In an experiment
15 with several NOAELs, the common usage of the term NOAEL is the highest exposure without
16 adverse effects.
17
18 Ototoxic stressor - A stressor which causes damage to the ear or the sense of hearing.
19
20 Reference Concentration (RfC) - An estimate (with uncertainty spanning perhaps an order of
21 magnitude) of a continuous inhalation exposure to the human population (including sensitive
22 subgroups) that is likely to be without an appreciable risk of deleterious noncancer effects during
23 a lifetime.
24
25 Reference Dose (RfD) - An estimate (with uncertainty spanning perhaps an order of magnitude)
26 of a daily exposure to the human population (including sensitive subgroups) that is likely to be
27 without an appreciable risk of deleterious noncancer effects during a lifetime.
28
29 Response additivity - In a mixture, when the toxic response (rate, incidence, risk, or probability
30 of effects) from the combination is equal to the conditional sum of component responses as
31 defined by the formula for the sum of independent event probabilities. For two chemical
32 mixtures, for example, the body's response to the first chemical is the same whether or not the
33 second chemical is present.
34
35 Risk - Absolute risk: The probability of injury, disease, or death under specific circumstances. In
36 quantitative terms, risk is expressed in values ranging from zero (representing the certainty that
37 there is no chance of harm), to one (representing the certainty that harm will occur). Incremental
38 risk: The probability of injury, disease, or death under specific circumstances, relative to the
39 background probability. In quantitative terms, risk is expressed in values ranging from zero
40 (representing the certainty that the probability of harm is no greater than the background
41 probability), to one (representing the certainty that harm will occur).
42
43 Stakeholder - An interested or affected party in an ongoing or contemplated project (usually
44 involving a group or team planning the project, analyzing one or more problems, and making
45 decisions for possible actions based on the interpretation of that analysis).
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1 Stressor - Any physical, chemical, or biological entity that can induce an adverse response.
2 Stressors may also be the lack of an essential entity, such as a habitat.
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1 6. REFERENCES
2
3 ACGIH, 1998. Threshold Limit Values for Chemical Substances and Physical Agents.
4 American Conference of Government Industrial Hygienists, Cincinnati, OH.
5
6 AIChE, 1992. Guidelines for Hazard Evaluation Procedures, 2nd Edition with Worked
1 Examples. Center for Chemical Process Safety, American Institute of Chemical Engineers, New
8 York, NY.
9
10 AIChE, 1996. Guidelines for Use of Vapor Cloud Dispersion Models, 2nd Ed. Center for
11 Chemical Process Safety, American Institute of Chemical Engineers, New York, NY.
12
13 AIHA, 2000. Emergency Response Planning Guidelines Series. Emergency Response Planning
14 Guidelines Committee, American Industrial Hygiene Association, Fairfax, VA.
15
16 Albert, Roy E., 1999. Unifying the standard setting process for carcinogens and non-carcinogens.
17 Applied Occupational and Environmental Hygiene 14:742-747
18
19 Albert, Roy E., Joellen Lewtas, Stephen C. Nesnow, Todd W. Thorslund, and Elizabeth L.
20 Anderson, 1983. Comparative potency method for cancer risk assessment application to diesel
21 particulate emissions. Risk Analysis 3:101-117
22
23 American Heart Association, 2000. Stroke Risk Factors. Internet: www.americanheart.org.
24
25 Andersen, MelvinE., M. Elizabeth Meeks, Gary A. Boorman, David J. Brusick, Samuel M.
26 Cohen, Yvonne P. Dragan, Clay B. Frederick, Jay I. Goodman, Gordon C. Hard, Ellen J.
27 O'Flaherty, and Denise E. Robinson, 2000. Lessons learned in applying the U.S. EPA proposed
28 cancer guidelines to specific compounds. Toxicological Sciences 53:159-172
29
30 APCA, 1999. "Cumulative & Aggregate Risk Evaluation System: CARES. Conceptual Model."
31 American Crop Protection Association. Washington, DC. Internet: www.alphacares.org/
32
33 ATSDR, 1995. Report of the Expert Panel Workshop on the Psychological Responses to
34 Hazardous Substances. Agency for Toxic Substances and Disease Registry, U.S. Department of
35 Health and Human Services. Atlanta, Georgia. Internet: www.atsdr.cdc.gov/HEC/PRHS/
36
37 Barnes, Donald G., Ann Alford-Stevens, Linda Birnbaum, Frederick W. Kutz, William Wood,
38 and Dorothy Patton, 1991. Toxic equivalency factors for PCBs? Quality Assurance 1:70-81.
39
40 Barnes, Donald G. and Michael L. Dourson, 1988. Reference dose (RfD): description and use in
41 health risk assessments. Regulatory Toxicology and Pharmacology 8:471-486.
42
43 Barnthouse, Lawrence W., David R. Marmorek, and Calvin N. Peters, 2000. Assessment of
44 multiple stresses at regional scales. In: Multiple Stressors in Ecological Risk and Impact
45 Assessment: Approaches to Risk Estimation. (Ferenc and Foran, Eds.) Society of Environmental
67
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Toxicology and Chemistry, SET AC Press, Pensacola, Florida. ISBN 1-880611-40-6
2 Beck, B.D., R.B. Connolly, M.L. Dourson, D. Guth, D. Hattis, C. Kimmel, S.C. Lewis, eds.
3 Fundam. Appl. Toxicol. 20:9-12.
4
5 Berenblum, Isaac, and Philippe Shubik, 1947. A new quantitative approach to the study of stages
6 of chemical carcinogenesis in the mouse's skin. British Journal of Cancer 1:384-391
7
8 Bogen, K T., 2001. "Methods for Addressing Uncertainty and Variability to Characterize
9 Potential Health Risk from Trichloroethylene-Contaminated Ground Water at Beale Air Force
10 Base in California: Integration of Uncertainty and Variability in Pharmacokinetics and Dose-
11 Response." Lawrence Livermore National Laboratory, U.S. Department of Energy, Livermore,
12 CA. UCRL-ID-135978 Rev 1
13
14 Bouwes, Nicolaas W. and Steven M. Hassur, 1998. "OPPT's Risk-Screening Environmental
15 Indicators: Toxic Weights for Toxic Release Inventory (TRI) Chemicals and Chemical
16 Categories." Office of Pollution Prevention and Toxic Substances, Office of Prevention,
17 Pesticides, and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC.
18 April 28, 1998
19
20 Bullard, Robert D., 1990. Dumping in Dixie: Race, Class, and Environmental Quality.
21 Westview Press, Boulder, CO. ISBN: 0-8133-7954-7
22
23 Carpy, Serge A, Werner Kobel, and John Doe, 2000. Health risk of low-dose pesticides mixtures:
24 A review of the 1985-1998 literature on combination toxicology and health risk assessment.
25 Journal of Toxicology and Environmental Health Part B, 3:1 -25
26
27 CEQ, 1997. "Considering Cumulative Effects Under the National Environmental Policy Act."
28 Council on Environmental Quality, Executive Office of the President, Washington, DC.
29
30 Chambers, JM, WS Cleveland, B Kleiner, PA Tukey. 1983. Graphical methods for data analysis.
31 Wadsworth International Group, Belmont, CA, 145-171.
32
33 Chess, C. and K. Purcell (1999). Public Participation and the Environment: Do We Know What
34 Works? Environmental Science & Technology 33(16): 2685-2692.
35
36 Clemen, Robert T., 1996. Making Hard Decisions: An Introduction to Decision Analysis. 2nd Ed.
37 Duxbury Press, Wadsworth Publishing Co., Belmont, CA. ISBN 0-534-26034-9
38
39 Cogliano, Vincent James, 1997. Plausible upper bounds: Are their sums plausible? Risk Analysis
40 17:77-84
41
42 Cohen, Bernard L., 1991. Catalog of risks extended and updated. Health Physics 61:317-335.
43
44 DOT, 1998. "High-Speed Ground Transportation Noise and Vibration Impact Assessment." Final
45 Draft. Office of Railroad Development, Federal Railroad Administration, U.S. Department of
68
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Transportation. Washington, DC. Report No. 293630-1 Internet:
2 http://projectl .parsons. com/ptgnechsr/noise_manual.htm
3
4 Dourson, M.L., S.P. Felter, andD. Robinson. 1996. Evolution of science-based uncertainty
5 factors in noncancer risk assessment. Regulatory Toxicol. Pharmacol. 24, 108-120.
6
7 Dourson, Michael L., Linda K. Teuschler, Patrick R. Durkin, and William M. Stiteler, 1997.
8 Categorical regression of toxicity data: A case study using aldicarb. Regulatory Toxicology and
9 Pharmacology 25:121-129.
10
11 Eadon, George A., Laurence S. Kaminsky, Jay Silkworth, K. Aldous, D. Hilker, P. O'Keefe, R.
12 Smith, J. Gierthy, J. Hawley, N. Kim, et al, 1986. Calculation of 2,3,7,8-TCDD equivalent
13 concentrations of complex environmental contaminant mixtures. Environmental Health
14 Perspectives 70:221 -227
15
16 EEA, 2001. "Late Lessons from Early Warnings: The Precautionary Principle 1896-2000."
17 European Environment Agency, Copenhagen. Environmental Issue Report No. 22 (Released 10
18 January 2002) Internet: http://reports.eea.eu.int/environmental_issue_report_2001_22/en
19
20 Environmental Defense, 2001. "Scorecard." Internet: http://www.scorecard.org
21
22 European Commission, 2000. "The European Multi-Hazard Risk Assessment Project
23 (T.E.M.R.A.P.)" Directorate General XII for Science Research and Development, Environment
24 and Climate - 1994/1998 - Climatology and Natural Hazard, European Commission. Brussels,
25 Belgium. Internet: http://phypc9.geo.ulg.ac.be/nouveau/temrap/MainWebPage.htm
26
27 Ferenc, Susan A. and Jeffrey A. Foran (Eds.), 2000. Multiple Stressors in Ecological Risk and
28 Impact Assessment: Approaches to Risk Estimation. Society of Environmental Toxicology and
29 Chemistry, SET AC Press, Pensacola, Florida. ISBN 1-880611-40-6
30
31 FIFRA SAP, 2000. "Cumulative Risk Assessment Methodology Issues of Pesticide Substances
32 that Have a Common Mechanism of Toxicity." Report from Session II of the FIFRA Scientific
33 Advisory Panel Meeting of December 9, 1999 (Report dated February 4, 2000). FIFRA
34 Scientific Advisory Panel, Office of Science Coordination and Policy, Office of Prevention,
35 Pesticides and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. SAP
36 Report 99-06B
37
38 Fischhoff, Baruch, Watson, S., and Hope, C., 1984. Defining risk. Policy Sciences 17:123-139
39
40 Foran, Jeffrey A. and Susan A. Ferenc (Eds.), 1999. Multiple Stressors in Ecological Risk and
41 Impact Assessment. Society of Environmental Toxicology and Chemistry, SETAC Press,
42 Pensacola, Florida. ISBN 1-880611-32-5
43
44 Frewer, L. (1999). Risk Perception, Social Trust, and Public Participation in Strategic Decision
45 Making: Implications for Emerging Technologies. Ambio 28(6): 569-574
69
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Gandolfi, A.J., I.K. Brendel, R.L. Fisher, and J-P Michaud, 1995. Use of tissue slices in chemical
2 mixtures toxicology and interspecies investigations. Toxicology 105:285-290
3
4 GAO, 1983. "Siting of Hazardous Waste Landfills and Their Correlation with Racial and
5 Economic Status of Surrounding Communities." U.S. General Accounting Office. Washington,
6 DC. GAO/RCED 83-168
7
8 Guth, D. J., R. C. Hertzberg , and A. M. Jarabek. 1993. Exposure-response analysis: modeling
9 severity against concentration and duration. In: "Improvements in Quantitative Noncancer Risk
10 Assessment: Symposium Overview," Society of Toxicology meeting; February 1992; Seattle,
11 WA.
12
13 Haber, F., 1924. Zur Geschichte des Gaskrieges [On the History of Gas Warfare], in: Funf
14 Vortrage aus den Jahren 1920-1923 (Five Lectures from the years 1920-1923), Springer, Berlin,
15 76-92.
16
17 Hampshire Research Institute, 1999. "Review of an Aggregate Exposure Assessment Tool."
18 Presentation to the U.S. EPA FIFRA Scientific Advisory Panel, September, 1999. Hampshire
19 Research Institute, Alexandria, VA. Internet:
20 www.epa.gov/scipoly/sap/l 999/september/aggbkgd.pdf
21
22 Hampshire Research Institute, 2000. "Overview of the Fundamentals of Version 1.0 of LifeLine
23 Software for Modeling Aggregate and Cumulative Exposures to Pesticides." Hampshire
24 Research Institute, Alexandria, VA. Internet:
25 www.epa.gov/scipoly/sap/2000/september/final_fundamentals.pdf
26
27 Hansen, Hugh, Christopher T. De Rosa, Hana Pohl, Michael Fay, and Moiz M. Mumtaz, 1998.
28 Public health challenges posed by chemical mixtures. Environ Health Perspect 106:1271-1280.
29
30 Hertzberg, Richard C. 1989. Fitting a model to categorical response data with application to
31 species extrapolation. Health Physics, 57(Supplement 1):405-409.
32
33 Hertzberg, Richard C., 2000. "Communicating cumulative risk: sound bites from chaos."
34 Luncheon address, presented at the conference, Toxicology and Risk Assessment Approaches for
35 the 21st Century, April 10-13, 2000, Kings Island, OH.
36
37 Hertzberg, Richard C, and M.M. MacDonell, 2002. Synergy and other ineffective mixture risk
38 definitions. The Science of the Total Environment 288:31-42.
39
40 Hertzberg, Richard C., Glenn Rice, and Linda K. Teuschler, 1999. "Methods for health risk
41 assessment of combustion mixtures." In: Hazardous Waste Incineration: Evaluating the Human
42 Health and Environmental Risks. S. Roberts, C. Teaf and J. Bean, eds. CRC Press LLC, Boca
43 Raton. Pages 105-148
44
45 Hertzberg, Richard C. and Linda K. Teuschler, 2001. "Ideas for Evaluating Quantitative
70
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Formulas for Dose-Response Assessment of Chemical Mixtures," presented at the Application of
2 Technology to Chemical Mixture Research Conference, January 9-11, 2001, Fort Collins, CO.
3
4
5 HUD, 1991. "The Noise Guidebook." Office of Community Planning and Development, U.S.
6 Department of Housing and Urban Development. Washington, DC. HUD-953-CPD(l)
7
8 ILSI, 1998. Aggregate Exposure Assessment. International Life Sciences Institute, Washington,
9 DC. ISBN 1-57881-040-X
10
11 ILSI, 1999. A Framework for Cumulative Risk Assessment. International Life Sciences Institute,
12 Washington, DC. ISBN 1-57881-055-8
13
14 ILSI, 2000. Revised Framework for Microbial Risk Assessment. International Life Sciences
15 Institute, Washington, DC. ISBN: 1-57881-081-7
16
17 ILSI, 2001. Aggregate Exposure Assessment: Model Evaluation and Refinement Workshop
18 Report. International Life Sciences Institute, Washington, DC. ISBN 1-57881-120-1
19
20 Johnson, Ted, GaryMihlan, JackyLaPointe, Kris Fletcher, Jim Capel, Arlene Rosenbaum,
21 Jonathan Cohen, and Pat Stiefer, 2000. "Estimation of Carbon Monoxide Exposures and
22 Associated Carboxyhemoglobin Levels for Residents of Denver and Los Angeles using
23 pNEM/CO (version 2.1)." Draft report prepared for Office of Air Quality Planning and
24 Standards, Office of Air and Radiation, U.S. Environmental Protection Agency. Research
25 Triangle Park, NC. Contract No. 68-D6-0064.
26
27 Kodell, Ralph L., and James J. Chen, 1994. Reducing conservatism in risk estimation for
28 mixtures of carcinogens. Risk Analysis 14:327-332
29
30 Kroschwitz, Jacqueline I. and Mary Howe-Grant (Eds.), 1994. Kirk-Othmer Encyclopedia of
31 Chemical Technology. 4th Edn. John Wiley and Sons, New York. ISBN 0-47152-677-0
32
33 Lantz, Paula M, James S. House, James M. Lepkowski, David R. Williams, Richard P. Mero and
34 Jieming Chen, 1998. Socioeconomic factors, health behaviors, and mortality: Results from a
35 nationally representative prospective studyof US adults. Jour. Amer. Medical Assoc. 279:1703-
36 1709.
37
38 Lewis, S.C. 1993. Reducing uncertainty with adjustment factors: Improvements in quantitative
39 noncancer risk assessment. Fund. Appl. Toxicol. 20, 2-4.
40
41 Lewtas, Joellen, 1985. Development of a comparative potency method for cancer risk
42 assessment of complex mixtures using short-term in vivo and in vitro bioassays. Toxicol. Ind.
43 Health 1:193-203
44
45 Lewtas, Joellen, 1988. Genotoxicity of complex mixtures: Strategies for the identification and
71
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 comparative assessment of airborne mutagens and carcinogens from combustion sources.
2 Fundamentals of Applied Toxicology 10:571-589
3
4
5
6 Lynch, John W., George A. Kaplan, Elsie R. Pamuk, Richard D. Cohen, Katherine E. Heck,
7 Jennifer L. Balfour, and Irene H. Yen, 1998. Income inequality and mortality in metropolitan
8 areas of the United States. Am. J. Public Health 88:1074-1080
9
10 Morata, Thais C., 2000. "Suggested Guidelines to Studying the Combined Effects of
11 Occupational Exposure to Noise and Chemicals on Hearing." National Institute for Occupational
12 Safety and Health. Cincinnati, OH. Dated February, 2000. Internet:
13 http://www.ucl.ac.uk/noiseandhealth/WP3%20draft%20protocol%20-%20Morata.doc
14
15 Morata, T.C., A.C. Fiorini, P.M. Fischer, S. Colacioppo, K.M. Wallingford, E.F. Kreig, D.E.
16 Dunn, L. Gozzoli, M.A. Padrao, and C.L.G. Cesar, 1997. Toluene-induced hearing loss among
17 rotogravure printing workers. Scandanavian Journal of Work, Environment & Health 23:289-298
18
19 Morgan, M. Granger, and Max Henrion, 1990. Uncertainty: A Guide to Dealing with Uncertainty
20 in Quantitative Risk and Policy Analysis. Cambridge University Press, New York, NY. ISBN 0-
21 521-36542-2
22
23 Mottram, J.C., 1944. A developing factor in experimental blastogenesis. J. Pathol. Bacteriol.
24 56:181-187
25
26 Murray, C., 1994. Quantifying the burden of disease: the technical basis for disability-adjusted
27 life years. Bull. World Health Org. 72 (3):429-445
28
29 NAP A, 1995. Setting Priorities, Getting Results: A New Direction for EPA. National Academy
30 of Public Administration. Washington, DC. LCCN: 95-68048
31
32 NOAA, 1999. "An Assessment of Lower Snake River Hydrosystem Alternatives on Survival and
33 Recovery of Snake River Salmonids." National Marine Fisheries Service, National Oceanic and
34 Atmospheric Administration. Seattle, WA. Dated April 14, 1999
35
36 NRC, 1983. Risk Assessment in the Federal Government: Managing the Process. Committee on
37 the Institutional Means for Assessments of Risk to Public Health, Commission on Life Sciences,
38 National Research Council. National Academy Press, Washington, DC. ISBN 0-309-03349-7
39
40 NRC, 1993. Pesticides in the Diets of Infants and Children. National Academy Press,
41 Washington DC.
42
43 NRC, 1994. Science and Judgment in Risk Assessment. Committee on Risk Assessment of
44 Hazardous Air Pollutants, Board on Environmental Sciences and Technology, Commission on
45 Life Sciences, National Research Council. National Academy Press, Washington, DC. ISBN 0-
72
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 309-04894-X
2
3 NRC, 1996. Understanding Risk: Informing Decisions in a Democratic Society. Committee on
4 Risk Characterization, Commission on Behavioral and Social Sciences and Education, National
5 Research Council. National Academy Press, Washington, DC. ISBN 0-309-05396-X
6
7 OMB, 2002. "Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and
8 Integrity of Information Disseminated by Federal Agencies " Federal Register 67:369-378
9
10 Osowski, Sharon L., Joseph D. Swick, Jr., Gerald R. Carney, Hector B. Pena, Jeffrey E.
11 Danielson, and David A. Parrish, 2001. A watershed-based cumulative risk impact analysis:
12 Environmental vulnerability and impact criteria. Environmental Monitoring and Assessment
13 66:159-185
14
15 Perry, Robert H., Don W. Green, and James O. Maloney, Eds., 1997. Perry's Chemical
16 Engineers' Handbook. 7th Edn. McGraw Hill Professional Publishing, New York. ISBN 0-
17 07049-841-5
18
19 Portier, Christopher J., 2001. "Virtual Human Concept and its Application to Chemical Mixture
20 Research," presented at Application of Technology to Chemical Mixture Research Conference,
21 January 9-11, 2001, Fort Collins, CO.
22
23 Presidential/Congressional Commission on Risk Assessment and Risk Management, 1997. Risk
24 Assessment and Risk Management in Regulatory Decision-Making. Washington, DC.
25
26 Rouse, P. and J.G. Kidd, 1941. Conditional neoplasms and sub-threshold neoplastic states: A
27 study of the tar tumors of rabbits. J. Exp. Med. 73:369-390
28
29 Seed, Jennifer, Ronald P. Brown, Stephen S. Olin, and Jeffery A. Foran, 1995. Chemical
30 mixtures: Current risk assessment methodologies and future directions. Regulatory Toxicology
31 and Pharmacology 22:76-94
32
33 Sexton, Ken, David E. Kleffman & Michael A. Callahan, 1995. An introduction to the National
34 Human Exposure Assessment Survey (NHEXAS) and related phase I field studies. J. Expos.
35 Anal. Environ. Epidem. 5, 229-232. Related papers are in the same issue of J. Expos. Anal.
36 Environ. Epidem. 5, 233-444.
37
38 Slob, W., and M.N. Pieters. 1998. A probabilistic approach for deriving acceptable human intake
39 limits and human health risks from toxicological studies: General framework. Risk Anal. 18, 787-
40 798.
41
42 State of Vermont, 1991. "Environment 1991: Risks to Vermont and Vermonters." Agency of
43 Natural Resources, State of Vermont. Waterbury, VT.
44
45 Teuschler, Linda K., Michael L. Dourson, William M. Stiteler, Peter McClure, and Heather
73
-------
DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Tully, 1999. Health risks above the reference dose for multiple chemicals. Regulatory
2 Toxicology and Pharmacology 30: S19-S26.
3
4 Thomas, J. (1995). Public Participation in Public Decisions: New Skills and Strategies for
5 Public Managers. Jossey-Bass, San Francisco
6
7
8 United Church of Christ, 1987. Toxic Waste and Race in the United States: A National Report on
9 the Racial and Socro-Economic Characteristics of Communities with Hazardous Waste Sites.
10 United Church of Christ Commission for Racial Justice. New York, NY.
11
12 USEPA, 1986a. "The Risk Assessment Guidelines of 1986." Risk Assessment Forum, Office of
13 Research and Development, U.S. Environmental Protection Agency. Washington, DC.
14 EPA/600/8-87/045
15
16 USEPA, 1986b. "Guidelines for the Health Risk Assessment of Chemical Mixtures." Risk
17 Assessment Forum, Office of Research and Development, Environmental Protection Agency.
18 Washington, DC. EPA/630/R-98/002
19
20 USEPA, 1986c. "Guidelines for Mutagenicity Risk Assessment." Risk Assessment Forum,
21 Office of Research and Development, Environmental Protection Agency. Washington, DC.
22 EPA/630/R-98/003
23
24 USEPA, 1986d. "Guidelines for Carcinogen Risk Assessment." Risk Assessment Forum, Office
25 of Research and Development, Environmental Protection Agency. Washington, DC. EPA/630/R-
26 98/001
27
28 USEPA, 1987. "The Total Exposure Assessment Methodology (TEAM) Study." Office of Acid
29 Deposition, Environmental Monitoring and Quality Assurance, Office of Research and
30 Development, U.S. Environmental Protection Agency. Washington, DC. EPA/600/6-87/002
31
32 USEPA, 1988. "Federal Guidance Report No. 11: Limiting Values of Radionuclide Intake and
33 Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion."
34 Office of Radiation Programs, U.S. Environmental Protection Agency. Washington, DC. EPA-
35 520/1-88-020
36
37 USEPA, 1989a. "Risk Assessment Guidance for Superfund, Volume 1: Human Health
38 Evaluation Manual. Office of Emergency and Remedial Response, Office of Solid Waste and
39 Emergency Response, U.S. Environmental Protection Agency. Washington, DC. EPA/540/1-
40 89/002
41
42 USEPA, 1989b. "Interim Procedures for Estimating Risks Associated with Exposure to
43 Chlorinated dibenzo-p-dioxins and -dibenzofurans (CDDs and CDFs) and 1989 update. Risk
44 Assessment Forum, Office of Research and Development, U.S. Environmental Protection
45 Agency. Washington, DC. EPA 625/3-89/016
74
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 USEPA, 1990a. "Technical Support Document on Health Assessment of Chemical Mixtures."
2 Office of Research and Development, U.S. Environmental Protection Agency. Washington, DC.
3 EPA/600/8-90/064
4
5 USEPA, 1990b. "Reducing Risk: Setting Priorities and Strategies for Environmental Protection."
6 Science Advisory Board, U.S. Environmental Protection Agency. Washington, DC. SAB-EC-90-
7 021
8
9 USEPA, 199la. "Guidelines for Developmental Toxicity Risk Assessment." Risk Assessment
10 Forum, Office of Research and Development, U.S. Environmental Protection Agency.
11 Washington, DC. EPA/600/FR-91/001
12
13 USEPA, 1991b. "Locational Data Policy." U.S. Environmental Protection Agency. Washington,
14 DC. IRM Policy Manual 2100-CGH2, dated April 8, 1991
15
16 USEPA, 1992a. "Safeguarding the Future: Credible Science, Credible Decisions. A Report of the
17 Expert Panel on the Role of Science at EPA." Washington, DC. EPA/600/9-91/050
18
19 USEPA, 1992b. "Framework for Ecological Risk Assessment." Risk Assessment Forum, Office
20 of Research and Development, U.S. Environmental Protection Agency. Washington, DC.
21 EPA/630/R-92/001
22
23 USEPA, 1992c. "Guidelines for Exposure Assessment." Risk Assessment Forum, Office of
24 Research and Development, U.S. Environmental Protection Agency. Washington, DC.
25 EPA/600/Z-92/001
26
27 USEPA, 1993a. "Guidance on the Application of Refined Dispersion Models for
28 Hazardous/Toxic Air Release." Office of Air Quality Planning and Standards, Office of Air and
29 Radiation, U.S. Environmental Protection Agency, Research Triangle Park, NC. EPA 454/R-93-
30 002
31
32 USEPA, 1993b. "A Guidebook to Comparing Risks and Setting Environmental Priorities."
33 Office of Policy, Planning and Evaluation, U.S. Environmental Protection Agency. Washington,
34 DC. EPA 230-B-93-003
35
36 USEPA, 1993c. "Chemical Indexing System for the Toxic Chemical Release Inventory, Part I:
37 Chronic Index." Air, Radiation and Toxics Division, EPA Region III, U.S. Environmental
38 Protection Agency. Philadelphia, PA. EPA/903/R-93/002
39
40 USEPA, 1993d. "Federal Guidance Report No. 12: External Exposure to Radionuclides in Air,
41 Water, and Soil." Office of Air and Radiation, U.S. Environmental Protection Agency.
42 Washington, DC. EPA-402-R-93-081
43
44 USEPA, 1994. "Methods for Derivation of Inhalation Reference Concentrations and Application
45 of Inhalation Dosimetry." Office of Health and Environmental Assessment, Office of Research
75
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC.
2 EPA/600/8-90/066F
3
4 USEPA, 1995a. "Policy for Risk Characterization." Memorandum from U.S. Environmental
5 Protection Agency Administrator Carol M. Browner, dated March 21, 1995. Washington, DC.
6
7 USEPA, 1995b. "Guidance for Risk Characterization." Policy paper dated February, 1995.
8 Science Policy Council, U.S. Environmental Protection Agency. Washington, DC.
9
10 USEPA, 1995c. "The Use of the Benchmark Dose Approach in Health Risk Assessment." Risk
11 Assessment Forum, Office of Research and Development, U.S. Environmental Protection
12 Agency. Washington, DC. EPA/630/R-94/007
13
14 USEPA, 1995d. "Chemical Indexing System for the Toxic Chemical Release Inventory, Part I:
15 Chronic Index; Addendum." Air, Radiation and Toxics Division, EPA Region III, U.S.
16 Environmental Protection Agency. Philadelphia, PA. EPA/903/R-93/002a (August, 1995)
17
18 USEPA, 1995e. "Compilation of Air Pollutant Emission Factors, Volume I: Stationary Point and
19 Area Sources." Fifth Edition. Office of Air Quality Planning and Standards, Office of Air and
20 Radiation, U.S. Environmental Protection Agency. Research Triangle Park, NC. EPA AP-42
21
22 USEPA, 1996a. "RAGS Reform Stakeholder Forums: Synopsis of Participants' Comments. San
23 Francisco, California, October 30-November, 1, 1996, and Washington, DC, November 6-
24 November 8, 1996." Office of Emergency and Remedial Response, U.S. Environmental
25 Protection Agency, Washington, DC.
26
27 USEPA, 1996b. "Guidelines for Reproductive Toxicity Risk Assessment." Risk Assessment
28 Forum, Office of Research and Development, U. S. Environmental Protection Agency.
29 Washington, DC. EPA/63O/R-96/009
30
31 USEPA, 1996c. "Proposed Guidelines for Carcinogen Risk Assessment." Risk Assessment
32 Forum, Office of Research and Development, U. S. Environmental Protection Agency.
33 Washington, DC. EPA/600/P-92/003C
34
35 USEPA, 1996d. "Compilation of Air Pollutant Emission Factors, Volume I: Stationary Point and
36 Area Sources." Fifth Edition, Supplements A & B. Office of Air Quality Planning and Standards,
37 Office of Air and Radiation, U.S. Environmental Protection Agency. Research Triangle Park,
38 NC. EPA AP-42
39
40 USEPA, 1996e. "Radiation Exposure and Risk Assessment Manual (RERAM)." Office of Air
41 and Radiation, U.S. Environmental Protection Agency. Washington, DC. EPA 402-R-96-016
42
43 USEPA, 1997a. "Guidance on Cumulative Risk Assessment, Part 1. Planning and Scoping."
44 Science Policy Council, U.S. Environmental Protection Agency, Washington, DC. Attachment to
45 memo dated July 3, 1997 from the Administrator, Carol Browner, and Deputy Administrator,
76
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Fred Hansen, titled "Cumulative Risk Assessment Guidance-Phase I Planning and Scoping."
2
3 USEPA, 1997b. "Guiding Principles for Monte Carlo Analysis." Risk Assessment Forum,
4 Office of Research and Development, Washington, DC. EPA/63O/R-97/001
5
6 USEPA, 1997c. "Chemical Indexing System, Part II: Vulnerability Index." Waste and Chemicals
7 Management Division, EPA Region III, U.S. Environmental Protection Agency. Philadelphia,
8 PA. EPA/903/R-97/021
9
10
11
12 USEPA, 1997d. "Compilation of Air Pollutant Emission Factors, Volume I: Stationary Point and
13 Area Sources." Fifth Edition, Supplement C. Office of Air Quality Planning and Standards,
14 Office of Air and Radiation, U.S. Environmental Protection Agency. Research Triangle Park,
15 NC. EPAAP-42
16
17 USEPA, 1998a. "Risk Assessment Guidance for Superfund (RAGS) Stakeholder Forum:
18 Synopsis of Participants' Comments. Atlanta, Georgia, March 2-4, 1998." Office of Emergency
19 and Remedial Response, U.S. Environmental Protection Agency, Washington, DC.
20
21 USEPA, 1998b. "Guidelines for Ecological Risk Assessment." Risk Assessment Forum, Office
22 of Research and Development, Washington, DC. EPA/630/R-95/002F
23
24 USEPA, 1998c. "Guidelines for Neurotoxicity Risk Assessment." Risk Assessment Forum,
25 Office of Research and Development, U.S. Environmental Protection Agency. Washington, DC.
26 EPA/630/R-95/001F
27
28 USEPA, 1998d. "Methods for Exposure-Response Analysis for Acute Inhalation Exposure to
29 Chemicals: Development of the Acute Reference Exposure." Review Draft. Office of Research
30 and Development, U.S. Environmental Protection Agency. Washington, DC. EPA/600/R-98/051
31
32 USEPA, 1998e. "General Guidance for Risk Management Programs (40 CFR Part 68)."
33 Chemical Emergency Preparedness and Prevention Office, Office of Solid Waste and Emergency
34 Response, U.S. Environmental Protection Agency, Washington, DC. EPA 550-B-98-003
35
36 USEPA, 1998f. "Comparative Risk Framework: Methodology and Case Study." SAB Review
37 Draft dated November 9, 1998. National Center for Environmental Assessment, Office of
38 Research and Development, U.S. Environmental Protection Agency. Cincinnati, OH.
39
40 USEPA, 1998g. "Report of the Common Sense Initiative Council's Stakeholder Involvement
41 Work Group." Common Sense Initiative Council, U.S. Environmental Protection Agency.
42 Washington, DC.
43
44 USEPA, 1998h. "An SAB Report: Review of Disproportionate Impact Methodologies." Science
45 Advisory Board, U.S. Environmental Protection Agency. Washington, DC. EPA-SAB-IHEC-99-
77
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 007
2
3 USEPA, 19981. "Handbook for Air Toxics Emission Inventory Development, Volume I:
4 Stationary Sources." Office of Air Quality Planning and Standards, Office of Air and Radiation,
5 U.S. Environmental Protection Agency. Research Triangle Park, NC. EPA-454/B-98-002
6
7 USEPA, 1998J. "Human Health Risk Assessment Protocol for Hazardous Waste Combustion
8 Facilities." Peer Review Draft. Office of Solid Waste and Emergency Response, U.S.
9 Environmental Protection Agency. Washington, DC. EPA530-D-98-001 Internet:
10 www.epa.gov/epaoswer/hazwaste/combust/riskvolJitm
11
12
13 USEPA, 1998k. "A Common Mechanism of Action: The Organophosphate Pesticides."
14 Scientific Advisory Panel, United States Environmental Protection Agency. Washington, DC.
15 Internet: http://www.epa.gov/scipoly/sap/1998/march/comec.htm
16
17 USEPA, 1999a. "Guidelines for Carcinogen Risk Assessment." Review draft dated July, 1999.
18 Risk Assessment Forum, Office of Research and Development, U.S. Environmental Protection
19 Agency. Washington, DC. NCEA-F-0644
20
21 USEPA, 1999b. "Review of Revised Sections of the Proposed Guidelines for Carcinogen Risk
22 Assessment." Science Advisory Board, U.S. Environmental Protection Agency. Washington, DC.
23 EPA-SAB-EC-99-015
24
25 USEPA, 1999c. "Risk Assessment Guidance for Superfund: Volume 1 - Human Health
26 Evaluation Manual. Supplement to Part A: Community Involvement in Superfund Risk
27 Assessments." Office of Solid Waste and Emergency Response, United States Environmental
28 Protection Agency. Washington, DC. EPA 540-R-98-042/PB99-963303
29
30 USEPA, 1999d. "Risk Management Program Guidance for Offsite Consequence Analysis."
31 Chemical Emergency Preparedness and Prevention Office, Office of Solid Waste and Emergency
32 Response, U.S. Environmental Protection Agency, Washington, DC. EPA 550-B-99-009
33
34 USEPA, 1999e. "Guideline on Air Quality Models." Office of Air Quality Planning and
35 Standards, Office of Air and Radiation, U.S. Environmental Protection Agency. Research
36 Triangle Park, NC. 40CFR Ch. I (7-1 -99 Edition), Appendix W to Part 51, Pages 390-481
37
38 USEPA, 1999f. "EPA's Framework for Community-Based Environmental Protection." Office of
39 Policy/Office of Reinvention, U.S. Environmental Protection Agency, Washington, DC. EPA
40 237-K-00-001
41
42 USEPA, 1999g. "Guidance for Performing Aggregate Exposure and Risk Assessments." Office
43 of Pollution Prevention and Toxic Substances, Office of Pesticide Programs, U.S. Environmental
44 Protection Agency. Washington, DC. Item 6043, dated October 29, 1999. Available on the
45 internet at: http://www.epa.gov/fedrgstr/EPA-PEST/1999/November/Day-10/6043.pdf
78
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1
2 USEPA, 1999h. "Total Risk Integrated Methodology, TRM.Expo.: Technical Support
3 Document." External Review Draft. Office of Air Quality Planning and Standards, Office of Air
4 and Radiation, U.S. Environmental Protection Agency. Research Triangle Park, NC. EPA-
5 453/D-99-001
6
7 USEPA, 19991. "Risk-Screening Environmental Indicators: 1988-1997 TRI Data 'Air-Only'
8 Model." Office of Pollution Prevention and Toxic Substances, Office of Prevention, Pesticides,
9 and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. CD-ROM
10 Version 1.0, dated July 6, 1999. (Version 2.0 is now in beta-testing.)
11
12
13
14 USEPA, 1999J. "An SAB Report on the National Center for Environmental Assessment's
15 Comparative Risk Framework Methodology." Science Advisory Board, U.S. Environmental
16 Protection Agency. Washington, DC. EPA-SAB-DWC-99-016
17
18 USEPA, 1999k. "Handbook for Criteria Pollutant Inventory Development: A Beginner's Guide
19 for Point and Area Sources." Office of Air Quality Planning and Standards, Office of Air and
20 Radiation, U.S. Environmental Protection Agency. Research Triangle Park, NC. EPA-454/R-99-
21 037
22
23 USEPA, 19991. "Federal Guidance Report No. 13: Cancer Risk Coefficients for Environmental
24 Exposure to Radionuclides." Office of Air and Radiation, U.S. Environmental Protection
25 Agency. Washington, DC. EPA-402-R-99-001
26
27 USEPA, 1999m. "Guidance for Identifying Pesticide Chemicals and Other Substances that Have
28 a Common Mechanism of Toxicity;" Office of Pesticide Programs, Office of Prevention,
29 Pesticides, and Toxic Substances, United States Environmental Protection Agency. Washington,
30 D.C. Internet: http://www.epa.gov/fedrgstr/EPA_PEST/1999/February/Day_05/
31
32 USEPA, 2000a. "Toward Integrated Environmental Decision-Making." Science Advisory Board,
33 U.S. Environmental Protection Agency. Washington, DC. EPA-SAB-EC-00-011
34
35 USEPA, 2000b. "Benchmark Dose Technical Guidance Document" Draft report. Risk
36 Assessment Forum, Office of Research and Development, U.S. Environmental Protection
37 Agency. Washington, DC. EPA/630/R-00/001
38
39 USEPA, 2000c. "Science Policy Council Handbook: Risk Characterization." Science Policy
40 Council, U.S. Environmental Protection Agency. Washington, DC. EPA 100-B-00-002
41
42 USEPA, 2000d. "Science Policy Council Handbook: Peer Review." 2nd Edition. Science Policy
43 Council, U.S. Environmental Protection Agency. Washington, DC. EPA 100-B-OO-OOl
44
45 USEPA, 2000e. "Supplementary Guidance for Conducting Health Risk Assessment of Chemical
79
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 Mixtures." Risk Assessment Forum, Office of Research and Development, U.S. Environmental
2 Protection Agency. Washington, DC. EPA/630/R-00/002
3
4 USEPA, 2000f. "Baltimore Community Environmental Partnership Air Committee Technical
5 Report. Community Risk-Based Air Screening: A Case Study in Baltimore, MD." Office of
6 Pollution Prevention and Toxics, Office of Prevention, Pesticides, and Toxic Substances, U.S.
7 Environmental Protection Agency. Washington, DC. EPA 744-R-00-005
8
9 USEPA, 2000g. "Handbook for Non-Cancer Health Effects Valuation." Non-Cancer Health
10 Effects Valuation Subcommittee of the EPA Social Science Discussion Group, Science Policy
11 Council, U.S. Environmental Protection Agency. Washington, DC. Dated November, 2000.
12
13
14
15 USEPA, 2000h. "AP-42: Compilation of Air Pollutant Emission Factors, Volume II: Mobile
16 Sources." Office of Transportation and Air Quality, Office of Air and Radiation. Washington,
17 DC. EPA AP-42, Volume II Internet: www.epa.gov/otaq/ap42.htm
18
19 USEPA, 20001. "Catalog of Hazardous and Solid Waste Publications." 13th Edition. Office of
20 Solid Waste and Emergency Response, U.S. Environmental Protection Agency. Washington, DC.
21 EPA530-B-00-001 Internet: www.epa.gov/epaoswer/osw/catalog.htm
22
23 USEPA, 2000J. "Guide to Field Storage of Biosolids, Appendix A: Odor Characterization,
24 Assessment and Sampling." Office of Wastewater Management, Office of Water, U.S.
25 Environmental Protection Agency. Washington, DC. EPA/832-B-00-007 Internet:
26 www.epa.gov/owm/bio/fsguide/
27
28 USEPA, 200la. Personal communication Debby Sisco,. Biological and Economic Analysis
29 Division, Office of Pesticide Programs, Office of Prevention, Pesticides, and Toxic Substances,
30 U.S. Environmental Protection Agency. Washington, DC. August 1, 2001
31
32 USEPA, 200 Ib. Personal communication. Anna Koutlakis, Office of Prevention, Pesticides, and
33 Toxic Substances, U.S. Environmental Protection Agency. Washington, DC. August 1, 2001
34
35 USEPA, 200Ic. "Stakeholder Involvement & Public Participation at the U.S. EPA: Lessons
36 Learned, Barriers, & Innovative Approaches." Office of Policy, Economics and Innovation, U.S.
37 Environmental Protection Agency. Washington, DC. EPA-100-R-00-040.
38
39 USEPA, 2001 d. "Top 10 Watershed Lessons Learned." Office of Wetlands, Oceans and
40 Watersheds, Office of Water, U.S. Environmental Protection Agency. Washington, DC. Internet:
41 http://www.epa.gov/owow/watersheds/lessons/index.html
42
43 USEPA, 200le. "National-Scale Air Toxics Assessment for 1996." SAB Review Draft. Office of
44 Air Quality, Planning and Standards, Office of Air and Radiation, U.S. Environmental Protection
45 Agency. Washington, DC. EPA-453-R-01-003
80
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 USEPA, 2002a. "Guidance on Cumulative Risk Assessment of Pesticide Chemicals that Have a
2 Common Mechanism of Toxicity." Office of Pesticide Programs, Office of Prevention,
3 Pesticides, and Toxic Substances, U.S. Environmental Protection Agency. Washington, DC.
4 January 14, 2002. Internet: http://www.epa.gov/pesticides/trac/science/cumulative_guidance.pdf
5
6 USEPA, 2002b. "Lesson Learned on Planning and Scoping for Environmental Risk
7 Assessments." Science Policy Council, U.S. Environmental Protection Agency. Washington,
8 DC. January, 2002. Internet: http://www.epa.gov/ORD/spc/2cumrisk.htm.
9
10 USEPA, 2002c. "Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo
11 -p-Dioxin (TCDD) and Related Compounds." National Center for Environmental Assessment,
12 Office of Research and Development, U.S. Environmental Protection Agency. Washington, DC.
13 [to be published]
14
15 van den Berg, Martin, Linda Birnbaum, Albertus T.C. Bosveld, Bjorn Brunstrom, Philip Cook,
16 Mark Feeley, John P. Giesy, Annika Hanberg, Ryuichi Hasegawa, Sean W. Kennedy, Timothy
17 Kubiak,John Christian Larsen, F.X. Rolaf van Leeuwen, A.K. Djien Liem, Cynthia Nolt, Richard
18 E. Peterson, Lorenz Poellinger, Stephen Safe, Dieter Schrenk, Donald Tillitt, Mats Tysklind,
19 Maged Younes, Fredrik Wsern, and Tim Zacharewski, 1998. Toxic equivalency factors (TEFs)
20 for PCBs, PCDDs, PCDFs for humans and wildlife. Environmental Health Perspectives
21 106:775-792
22
23 WHO, 1983. "Guidelines on Studies in Environmental Epidemiology." Environmental Health
24 Criteria 27. International Programme on Chemical Safety. World Health Organization. Geneva.
25 EHC 27
26
27 Woodruff, Tracey J., Jane Caldwell, Vincent J. Cogliano, and Daniel A. Axelrad, 2000.
28 Estimating cancer risk from outdoor concentrations of hazardous air pollutants in 1990.
29 Environmental Research Section A 82:194-206
30
31 Yang, Raymond S.H., 2001. "Application of Computer Modeling to Simple or Complex
32 Mixtures," presented at Application of Technology to Chemical Mixture Research Conference,
33 January 9-11, 2001, Fort Collins, CO.
34
35 Zartarian, Valerie G., Haluk Ozkaynak, Janet M. Burke, Maria J. Zufall, Marc L. Rigas, and
36 Edwin J. Furtaw, Jr, 2000. "A Modeling Framework for Estimating Children's Residential
37 Exposure and Dose to Chlorpyrifos via Dermal Residue Contact and Non-Dietary Ingestion."
38 Environmental Health Perspectives 108:505-514
81
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DRAFT - External Review Draft - April 23,2002- Do Not Quote or Cite
1 APPENDIX A: RESEARCH AND DEVELOPMENT NEEDS
2
3 The Framework for Cumulative Risk Assessment is intended to provide a basic structure
4 for the issues and define key terms and concepts. In some cases, the concepts introduced in the
5 Framework report require the application of knowledge and methods that are not currently
6 available. The following is a discussion of the needed areas of research and methods
7 development, highlighted within the Framework report, that may be most important to an
8 evaluation of cumulative risks. This is not intended to be a comprehensive listing of cumulative
9 risk assessment research needs.
10
11 EPA and other scientists are currently investigating the use of similar approaches for
12 cancer and noncancer assessments. Although we will not discuss this research need here, it
13 would be useful to cumulative risk assessment to have similar approaches, and it is a topic of
14 current discussion within scientific circles (e.g., Albert, 1999).
15
16 Understanding the Timing of Exposure and its Relationship to Effects
17
18 A key concept in the definition of cumulative risk is that it represents an accumulation of
19 risk over time. However, unlike the traditional approach to risk assessment where exposure
20 events are summed and averaged over a period of time, cumulative risk assessment will involve
21 developing an understanding of how the sequence and timing of exposures influence the ultimate
22 risk of effects. For example, for multiple stressors, it is important to understand how prior
23 exposures to one or several stressors influence the risks from subsequent exposures to the same
24 or different stressors. In addition, it is important to understand the implications of these
25 exposures occurring during critical periods of an individual's life (e.g., important periods of
26 development or periods of disease). Several exposure models are under development which
27 recognize the need to understand the timing of various exposure events (e.g., Calendex, APEX,
28 Lifeline, SHEDS, and CARES/RExY).
29
30 In addition to gaining a better understanding of the sequence and timing of exposures and
31 their relationship to effects, it is important to understand how acute, non-lethal exposures from
32 accidents contribute to chronic or long-term effects.
33
34 Understanding the Composition and Toxicity of Mixtures
35
36 Chemical mixtures can change or degrade over time and space making the assessment of
37 exposure a particular challenge. For cumulative risk assessment, the composition of the mixture
38 at the point of contact with the receptor needs to be well characterized. Both measurement
39 techniques (at the receptor) and predictive models are applicable in this characterization.
40
41 EPA's Guidance for the Health Risk Assessment of Chemical Mixtures (USEPA, 2000e)
42 presents approaches for combining the toxicities of multiple chemical stressors. These
43 approaches necessarily involve a number of simplifying assumptions when the mixtures are
44 complex. Although the current methods provide a valuable resource for assessing cumulative
45 risks, future cumulative risk assessment will need a more complete understanding of the
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1 interactions among chemicals in complex mixtures. Some current research efforts are seeking to
2 identify toxicologic principles of joint action that are applicable to mixtures involving many
3 chemicals.
4
5 Applying the Risk Factor Approach to Environmental Health Risks
6
7 The risk factor approach has been used in the medical profession to predict the chances of
8 individuals developing various diseases. It has proved to be a useM approach not only in
9 assessing certain cumulative risks, but also in communicating with patients. In this approach,
10 characteristics of a population (e.g., age, ethnicity, personal habits, genetic polymorphisms, prior
11 diseases, etc.) are correlated with the incidence of disease. For some diseases (e.g., breast cancer,
12 coronary artery disease, stroke) these correlations are well established. However, there are
13 substantial data gaps in terms of the role played by exposures to environmental stressors in the
14 development of human disease, and correlations of environmental exposures with disease
15 outcomes are generally not available.
16
17 Using Biomarkers and Biomonitoring
18
19 The use of biomarkers of exposure or effect holds a great deal of promise for cumulative
20 risk assessment. This approach can provide a method to assess stressors in groups. Currently,
21 however, this approach is not practicable when considering a large number of diverse stressors,
22 since appropriate biomarkers for many types of stressors have not yet been developed.
23
24 Considering Hazards Presented by Non-Chemical Stressors
25
26 Cumulative risk assessment could encompass the interactions of chemical stressors with
27 biological stressors, radiological stressors, other physical stressors, socioeconomic stressors and
28 lifestyle conditions. In trying to assess all these different types of stressors, it is helpful to
29 determine what types of effects the stressors produce, and then to try to group stressors by like
30 effects. Ideally, one would like to know the mechanism or mode of action by which various
31 stressors cause effects to allow a more refined grouping. Currently, however, there are few
32 methods to understand how these disparate stressors interact to result in risk.
33
34 Considering Psychological Stress as Part of Cumulative Risk
35
36 Psychological stress causes both psychological and physiological changes that can be
37 measured. Assessing levels of stress and their potential contribution to risk, however, is difficult
38 for a variety of reasons. The Agency for Toxic Substances and Disease Registry (ATSDR) began
39 the process of identifying research needs in this area through an expert panel workshop held in
40 1995.
41
42 Considering All Aspects of Vulnerability
43
44 The issue of the vulnerability of a population can be thought of as having four
45 components: susceptibility of individuals, differential exposures, differential preparedness to
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1 withstand the insult, and differential ability to recover from effects. Traditional risk assessment
2 may consider one or more of these categories but rarely are all considered. The overall
3 consideration of all four categories may be more important in cumulative risk assessment than in
4 traditional one-chemical assessments. A cumulative risk assessment, for example, may need to
5 consider potential combinations of high exposure and high vulnerability across stressors.
6 Methods development work is needed in this area.
7
8 Methods for Combining Different Types of Risk
9
10 Another key concept in the definition of cumulative risk assessment is that it represents
11 the combined risk from multiple stressors. This implies that, in some cases, it may be necessary
12 to combine disparate measures of risk (i.e., different types of effects) to simplify the expression
13 of cumulative risks. There have been some attempts to collapse complex arrays of risk into a few
14 or even a single measure. These approaches have involved the use of common metrics (e.g.,
15 Quality Adjusted Life Years, Disability Adjusted Life Years, Loss of Life Expectancy, etc.),
16 indices (e.g., Hazard Ranking System, etc.), and the categorization of effects (e.g., as for
17 categorical regression). Alternatively, Geographic Information Systems (GIS) and mapping
18 techniques can be used to graphically portray integrated information on risks without
19 mathematically combining disparate measures. Much methods development work remains to be
20 completed in each of these areas.
21
22 Development of Default Values for Cumulative Risk Assessments
23
24 Just as conventional risk assessments use a series of default values for screening or other
25 applications, it may be necessary to investigate whether certain defaults need to be established
26 specifically for cumulative risk assessments.
27
28 Development of Case Studies and Issue Papers on Specific Cumulative Risk Topics
29
30 The more detailed technical issues and methodologies should be developed as a series of
31 issues papers that would augment the Framework report. The level of detail would, of course,
32 vary depending on the topic, and may include the generic material from other guidance
33 documents. The issues papers (or white papers) should also include details on additional
34 approaches to cumulative risk assessment that are currently being explored (including screening-
35 level analyses, place-based assessments, comparative risk assessments, NEPA cumulative effects
36 analyses, and hazard assessments). In addition, the issues papers could include summaries of
37 case studies of cumulative risk projects that would extend the Framework from theoretical to
38 practical approaches and applications.
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1 APPENDIX B: SELECTED RESOURCES FOR EXPOSURE AND RISK ASSESSMENT
2
3 B.I. Resources Relevant to Chemical Exposures
4
5 EPA Guidelines:
6
7 Most of EPA's general guidelines are listed in the text box in section 1.1, page 5.
8
9 Air-related sources and activities:
10
11 EPA's Clearinghouse for Inventories and Emission Factors (CHIEF) website
12 (www.epa. gov/ttn/chief/) is an excellent starting place that has many of the relevant
13 documents on methods and data for constructing emissions inventories available for
14 download. These include Handbook for Criteria Pollutant Inventory Development: A
15 Beginner's Guide for Point and Area Sources (USEPA, 1999k), Handbook for Air Toxics
16 Emission Inventory Development, Volume I: Stationary Sources (USEPA, 1998i),and
17 Compilation of Air Pollutant Emission Factors (for both stationary and mobile sources)
18 (USEPA, 1995e, 1996d, 1997d, 2000h), as well as many other documents and software.
19
20 EPA's Support Center for Regulatory Air Models (SCRAM) website
21 (www.epa.gov/ttn/scram/) provides extensive information on the models discussed in
22 Guideline on Air Quality Models (USEPA, 1999e), including downloadable software and
23 users guides for many of the models.
24
25 The Ambient Monitoring Technology Information Center (AMTIC) website
26 (www. epa. gov/ttn/amtic/) contains information on monitoring programs, monitoring
27 methods, and other monitoring-related information.
28
29 The umbrella website for all three of the above is the Technology Transfer Network
30 (www.epa.gov/ttn/). which also has other useful information and links in addition to those
31 noted above.
32
33 Sources to land, and waste-related activities:
34
35 The EPA Office of Solid Waste and Emergency Response has published an extensive
36 catalog summarizing their publications (USEPA, 2000i). They have also published a
37 "peer review draft" document called Human Health Risk Assessment Protocol for
38 Hazardous Waste Combustion Facilities (USEPA, 1998J) which deals with how to assess
39 risks from hazardous waste incinerators. These reports are available on-line.
40
41 Chemical accidents, transportation-related spills:
42
43 There are several steps in assessing an accidental chemical release exposure. The typical
44 analytical steps in an overall accidental chemical release risk assessment are process
45 analysis, likelihood or frequency of accidents, source term modeling, dispersion or
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1 consequence modeling, and the exposure assessment
2
3 *• The process analysis is a formal, systematic analysis of the process where a
4 chemical is handled to determine the probabilities and consequences of acute,
5 catastrophic failures of engineered systems leading to an accidental release of the
6 chemical. This analysis is often called a Process Hazards Analysis (PHA).
7 Several formal PHA evaluation techniques are available including "What-If,"
8 "Failure Mode and Effect Analysis," "Event-Tree", and "Fault-Tree" analysis
9 (USEPA 1998e, AIChE, 1992).
10
11 * The likelihood or frequency of accidents step is an evaluation of each of the
12 scenarios uncovered in the process analysis step for likelihood or frequency of
13 occurrence.
14
15 *• Source term modeling, which estimates the amount or rate of release in case of
16 accident, is performed once the failure scenarios are determined. A wide variety of
17 published calculation methods or models are available (USEPA 1998e, USEPA
18 1999d) to determine the source terms for an accidental chemical release.
19
20 *• Dispersion or consequence modeling is performed once the source terms (rate and
21 duration of the release) are known. A wide variety of dispersion and consequence
22 modeling tools, ranging from simple screening models to sophisticated and
23 complex computer applications, are available for this step (USEPA 1999d, AIChE
24 1996, USEPA 1993a). In addition to the source terms generated above, several
25 other data elements are needed, such as physical/chemical properties (e.g.,
26 whether the vapor cloud is heavier than air or water reactive), meteorological
27 conditions (e.g., wind speed and direction, temperature, humidity), and terrain
28 surrounding the facility (e.g., buildings or valleys that may channel or disperse a
29 vapor cloud). Physical/chemical properties can be found in chemical reference
30 texts such as Kirk-Othmer's Encyclopedia of Chemical Technology (Kroschwitz
31 and Howe-Grant, 1994), Perry's Chemical Engineers' Handbook (Perry, et al.,
32 1997), on Material Safety Data Sheets (MSDS)14, or in the Guidance for Offsite
33 Consequence Analysis (USEPA 1999d). Meteorological conditions are often
34 collected on-site or at local airports. Information about terrain can be collected
35 from topological maps or by visual inspection. Guidance on all these parameters is
36 available in USEPA 1999d.
37
38 The final step in a chemical accident exposure analysis is the exposure assessment. The
39 exposure assessment is related to, and builds from, the dispersion or consequence
40 modeling step. The dispersion or consequence modeling depends on a health endpoint
41 and the exposure level related to that endpoint. Besides lethality, concentrations for
42 certain health effects (e.g., odor thresholds, eye irritation) are available for several
There are many searchable MSDS data bases on-line that can be located with most search engines.
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1 common toxic substances (NIOSH 1997, ACGIH 1998, AIHA 2000).
2
3
4 B.2. Resources Relevant to Exposures to Non-Chemical Stressors
5
6 Biological stressors:
1
8 The ILSI Risk Science Institute recently published a workshop report entitled "Revised
9 Framework for Microbial Risk Assessment" (ILSI, 2000), which looks at methods for
10 assessing risks to microorganisms such as Cryptosporidium, which has caused disease
11 outbreaks when it contaminates drinking water. The methodology is superficially similar
12 to a risk assessment conducted for a chemical pollutant, but only at the most general
13 level. How exposure is characterized, for example, includes many differences from
14 environmental chemical exposure assessment. Under "characterization of exposure," for
15 example, the framework includes (1) pathogen characterization, (2) pathogen occurrence,
16 (3) exposure analysis, and finally developing (4) an exposure profile.
17
18 Radiological stressors:
19
20 EPA's Office of Air and Radiation maintains a web page at
21 http://www.epa.gov/radiation/assessment/. This page provides (or cites) much of the
22 needed documentation for performing risk assessments for radionuclides. This includes
23 the Radiation Exposure and Risk Assessment Manual (RERAM) (USEPA, 1996e) and
24 several Federal Guidance Reports (USEPA, 1988, 1993d, 19991).
25
26 Noise, vibration, and congestion:
27
28 The U.S. Department of Housing and Urban Development has issued The Noise
29 Guidebook (HUD, 1991), which implements the existing noise regulations [24 CFR 51-
30 B] and includes the HUD Noise Assessment Guidelines. (The Guidebook is available in
31 hard copy only.)
32
33 The Federal Railroad Administration has developed a manual called High-Speed Ground
34 Transportation Noise and Vibration Impact Assessment (DOT, 1998) which provides the
35 theory, equations, and applications of noise and vibration analysis for high-speed
36 railroads. Much of the theory and information is also applicable to other noise and
37 vibration problems. Appendix A of the DOT Guide is a general discussion of noise
38 concepts, with references. The Guide is available on-line.
39
40 The National Institute of Occupational Health and Safety has done much research on the
41 interaction of noise with chemical exposures (Morata, 2000).
42
43 Odor:
44
45 EPA's Office of Wastewater Management has issued a report called Guide to Field
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1 Storage ofBiosolids (USEPA, 2000J) which contains an appendix on "Odor
2 Characterization, Assessment, and Sampling." Odor assessment is an analytic-
3 deliberative process, involving both science-based analytical methods and more
4 subjective analysis. The appendix of the Guide discusses sensory characterization of
5 odors (character, intensity, pervasiveness, quantity), some practical options for assessing
6 odors in a community, and the chemistry of odors (including range of odor thresholds). It
7 also discusses odor sample collection and analysis, and has several dozen references for
8 further information. This report is available on-line.
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1 APPENDIX C: SOME THOUGHTS ON BACKGROUND EXPOSURES
2
3 When looking at aggregate exposures or cumulative risks of citizens, "background
4 exposures" to specific chemicals are no less "real" exposures than the pollution usually studied
5 for regulatory purposes. Whereas in historical single-chemical assessments conducted for
6 limiting pollution, background sources of the chemical were often irrelevant to the questions
7 being asked of the assessment (or ignored as having negligible effect on risk), background
8 sources are rarely irrelevant with cumulative risk assessments15.
9
10 Background concentrations can be categorized as either naturally-occurring, that is,
11 chemicals which are naturally present in the environment before it was influenced by humans, or
12 anthropogenic, that is, present in the environment due to historical human-made sources.
13 Naturally-occurring background chemicals may be either localized or ubiquitous. Anthropogenic
14 background sources can be either localized from a point source, or generalized from unidentified
15 sources or non-point sources.
16
17 Assessments of morbidity incidence and death rates, market basket surveys, and pesticide
18 residue surveys also provide information which can be reflective of background chemical
19 concentrations as well as overt pollution. Background issues extend across all media, beyond
20 regulated sources, and beyond direct exposure. Many chemicals are naturally present in the
21 environment (e.g., soils, water, vegetation and other biota) and are consequently part of dietary,
22 dermal and inhalation exposures. In some cases, naturally-occurring substances may occur at
23 levels that exceed health-based or risk-based regulatory standards (e.g., drinking water
24 standards), or other levels established to protect human health and the environment. Since
25 cumulative risk assessments are population based, exposures due to naturally-occurring
26 background concentrations should typically be considered to be of importance.
27
28 There are several important issues related to natural or anthropogenic background
29 concentrations in cumulative risk assessment. First, if the risks posed by "background"
30 concentrations of certain chemicals are significant (and some may approach or exceed health
31 reference levels), their exclusion from the cumulative risk estimates and characterization may
32 seriously distort the portion of the total estimated risk thought to be posed to the population by a
33 specific evaluated source. A second issue is the problem of whether background chemical
34 exposures can be clearly distinguished from specific source-related chemicals, and how to
35 quantify these exposures. It may be important in a cumulative risk assessment to estimate
36 background exposures separately from specific source-related exposures, so that the risk assessor
The word "background" is often used to describe exposures to chemicals or other stressors that derive from sources
other than the sources being assessed. For example, in the Agency's assessment of residual risk associated with hazardous air
pollutant emissions from particular categories of sources that remain after the implementation of technology-based controls,
"background" is defined as all hazardous air pollutant exposures (via inhalation or other routes) not associated with the source(s)
being assessed. At a Superfund site, "background contamination" refers to contamination that is not related to the site release of
chemicals, as denned by Comprehensive, Environmental Response, Compensation and Liability Act (CERCLA).[P.L. 96-510,
December 11, 1980, as amended by P.L. 98-802, August 23, 1983, and P.L. 99-499, October 17, 1986] Such focusing or
segregation in a risk assessment can be useful to decisions involving pollution sources covered by particular statutory authorities,
but it is typical of a chemically-focused assessment rather than a population-focused assessment such as a cumulative risk
assessment.
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1 can provide the community with a more complete picture of both total and known source-related
2 risks. This also provides a clearer, more complete picture for making risk management
3 decisions. Finally, there may be problems in identifying representative geographic areas for
4 determining "background levels" for comparison.
5
6 Finally, background exposures for a community or population may also include both
7 voluntary and involuntary exposures, and subsequent risks. Involuntary exposures are associated
8 with the naturally-occurring or anthropogenic background concentrations described above.
9 Voluntary exposures, such as are associated with lifestyle decisions, are exposures due to
10 activities such as smoking, consuming char-grilled meats with PAHs, or other choice-based
11 exposures, and may also sometimes be defined in the assessment as "background" exposures if
12 they are not assessed directly in the cumulative risk assessment.
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1 APPENDIX D: EXAMPLES OF ANALYSIS PLANS
2
3 D.I. Human Health Analysis Plan for Pesticides under FQPA
4
5 Risk management/regulatory goal: Protection of the general human population and susceptible
6 subpopulations to adverse effects from exposure to pesticide "X" under the 1996 Food Quality
7 Protection Act (FQPA)
8
9 Assessment endpoints:
10 - human or animal health status of exposed versus unexposed populations/cohorts/dose
11 groups
12
13 Measures of Effects:
14 - general types of toxicological effects grouped according to acute, subchronic, and
15 chronic exposure durations
16 - organ-specific toxicity such as reproductive effects, developmental effects,
17 neurotoxicity, developmental n euro toxicity, immunotoxicity, hepatotoxicity,
18 pulmonary effects, cardiovascular effects, etc.
19 - general classes of toxic effects such as carcinogenicity, mutagenicity
20
21 Measures of Exposure:
22 - monitoring of food, water, residential, occupational exposures, etc. (direct or surrogate)
23 - monitoring of biological fluids or biomarkers (blood, urine, DNA or other
24 macromolecules)
25
26 What Can and Cannot be Done Based on Planning and Scoping
27 - pathways and relationships to be evaluated
28 - resource restraints
29 - milestones for completion of risk assessment
30
31 Methods for Conducting Risk Analysis
32 -RfD
33 - Margin of Exposure (MOE)
34 - probabilistic risk assessment based on dose-response or exposure parameters
35 - quotients (e.g., ratio of exposure level to toxicity threshold)
36 - narrative discussions
37 - other considerations (e.g., mechanisms of action, toxicokinetic models, timing of dose,
38 sensitive population characteristics)
39
40 Data Needs and Uncertainties
41
42 D.2. Ecological Analysis Plan
43
44 Risk management/regulatory goal: Viable, self-sustaining coho salmon population that supports
45 a subsistence and sport fishery.
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1 Assessment endpoints: Coho salmon breeding success, fry survival, and adult return rates.
2
3 Measures of Effects:
4 - egg and fry response to low dissolved oxygen
5 - adult behavior in response to obstacles
6 - spawning behavior and egg survival with changes in sedimentation
7 - population data over time in relation to fish passage
8
9 Measures of Ecosystem and Receptor Characteristics:
10 - water temperature, water velocity, and physical obstructions
11 - abundance and distributions of suitable breeding substrate
12 - abundance and distribution of suitable food sources for fry
13 - feeding, resting, and breeding behavior
14 - natural reproduction, growth, and mortality rates
15
16 Measures of Exposure:
17 - number of hydroelectric dams and associated ease offish passage
18 - toxic chemical concentrations in water, sediment, and fish tissue
19 - nutrient and dissolved oxygen levels in ambient waters
20 - riparian cover, sediment loading, and water temperature
21
22 What Can and Cannot be Done Based on Planning and Scoping
23 - pathways and relationships to be evaluated
24 - resource restraints
25 - milestones for completion of risk assessment
26
27 Methods for Conducting Risk Analysis
28 - quotients
29 - narrative discussions
30 - stressor-response curves with probabilities
31
32 Data Needs and Uncertainties
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1 APPENDIX E: TOXICOLOGIC SIMILARITY: ORGANOPHOSPHORUS PESTICIDES
2
3 The Food Quality Protection Act of 1996 (FQPA) requires that EPA reassess pesticide tolerances
4 (legal limits for residues in food) that were in effect as of August 1996. As part of the
5 reassessment, EPA must consider available information concerning the cumulative effects on
6 human health resulting from exposure to multiple chemicals that have a common mechanism of
7 toxicity. In this context, pesticides are determined to have a common mechanism of toxicity if
8 they produce the same toxic effect, in the same organ or tissue, and by essentially the same
9 sequence of major biochemical events (USEPA, 1999m).
10
11 Shortly after enactment of FQPA, EPA began developing new methods and tools that would
12 allow the consideration of combined risks from exposure to several pesticides via several
13 pathways and routes of exposure. Actual data sets for organophosphorous pesticides were used
14 in pilot analyses to test these methods. The methods and pilot analyses were subjected to peer
15 review through the FIFRA Scientific Advisory Panel (SAP) to ensure the use of sound science.
16 As part of this ongoing effort, on December 28, 2001 EPA's Office of Pesticide Programs (OPP)
17 announced the availability of the Preliminary Organophosphorus Cumulative Risk Assessment
18 [66FR67249-67250]. The risk assessment is available electronically at:
19 http://www.epa. gov/pesticides/cumulative. In preparing the cumulative risk assessment for the
20 organophosphorous (OP) pesticides, OPP followed 5 major steps.
21
22 1. Selection of the specific pesticides, pesticide uses, pathways and routes of exposure to include
23 in the quantitative analysis.
24
25 The selection of the specific OP pesticides began with identifying a "common mechanism
26 group." This was accomplished following the Guidance For Identifying Pesticide
27 Chemicals And Other Substances That Have A Common Mechanism Of Toxicity
28 (available at http://www.epa.gov/pesticides/trac/science). All 39 registered OP pesticides
29 share inhibition of acetylcholinesterase as a common mechanism for causing adverse
30 effects (USEPA, 1998k).
31
32 The common mechanism group was further refined to reflect current use patterns and
33 information on the detection of residues from USDA's Pesticide Data Program. This
34 resulted in the following recommendations for quantitative analysis: include 22 OP
35 pesticides for the food pathway of exposure; 24 OPs for the water pathway and 10 OPs
36 for residential exposures were identified based on use patterns and their individual
37 assessments.
38
39 2. Dose-response analysis for toxic potencies, relative contribution from each OP, and selection
40 of an index chemical to use as the point of reference in the dose-response analysis.
41
42 To determine the combined risk from multiple OP pesticides, EPA used the Relative
43 Potency Factor (RPF) approach [for additional examples of comparative potency
44 approaches, also see Albert, et al., 1983; Lewtas, 1985, Lewtas, 1988]. The index
45 chemical was selected based on the quality of the dose-response data. Then the relative
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1 potency of each OP pesticide was estimated by taking the ratio of its toxic potency to that
2 of the index chemical.
3
4 In selecting studies for evaluating toxic potencies, EPA used relative potency factors and
5 points of departure developed from cholinesterase inhibition in rats exposed to pesticides
6 for 21 days or more. This practice was adopted to reflect cholinesterase inhibition at a
7 point in the treatment schedule at which a steady state had been achieved. OPP elected to
8 use data reflecting a steady state in the interest of producing relative potency factors that
9 are reproducible and reflect less uncertainty due to rapidly changing time-sensitive
10 measures of cholinesterase.
11
12 Also, EPA considered that people generally have had some level of prior exposure to OP
13 pesticides. Further, the effects of exposure can persist for several days to weeks.
14 Therefore, people may be more vulnerable to subsequent exposures to OP pesticides than
15 might be predicted by not considering these prior exposures.
16
17 3. Estimation of the risk associated with all pertinent pathways of exposure in a manner that is
18 both realistic and reflective of variability due to differences in location, time, and demographic
19 characteristics of exposed groups.
20
21 Evaluation of the OP pesticide use profiles allowed for the identification of exposure
22 scenarios that may overlap, co-occur, or vary between chemicals. In addition, the use
23 profiles allowed for the identification of populations of potential concern. Based on this
24 analysis, EPA considered exposure to OP pesticides in food to be uniform across the
25 nation (i.e., there are no significant differences in food exposure due to time of year or
26 geographic location). For the residential and drinking water pathways of exposure, EPA
27 divided the nation into 12 regions for assessment. This allowed for the consideration of
28 such factors as the location of vulnerable surface watersheds and region specific pest
29 pressures. To estimate risks, EPA used a calendar based computer model titled Calendex.
30 This model integrates the various pathways of exposure while simultaneously
31 incorporating the time dimensions of the data. The model produces a detailed profile of
32 the potential exposure to individuals across a calendar year.
33
34 4. Identification of the significant contributors to risk.
35
36 Although interpretation of the preliminary organophosphorous cumulative risk
37 assessment is ongoing, there are some early indications concerning contribution to risk.
38 The drinking water pathway for exposure does not appear to be a major contributor to the
39 total cumulative risk. Residential exposure appears to be a contributor to risk,
40 particularly inhalation exposures from certain no-pest strips and crack and crevice
41 treatments. Childhood exposure from mouthing hands also appears to be a contributor
42 but there is a great deal of uncertainty associated with the estimates.
43
44 5. Characterization of the confidence in the results and the uncertainties encountered.
45
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1 In addition to some uncertainties noted above, EPA identified many areas for additional
2 analysis including: sensitivity analyses on input parameters, verification of residential
3 use patterns, closer examination of the tails of the food consumption distribution, and
4 evaluation of the effect of assumptions about residue concentrations in baby foods.
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APPENDIX F: OTHER TYPES OF CUMULATIVE ASSESSMENTS
There are several other types of cumulative assessments that are related to the types of
human health and ecological cumulative assessments done by the Agency. It is beyond the scope
of this Framework to discuss these in detail, but a short explanation of several other types of
cumulative assessments are given in this appendix.
F.I. Quality-of-Life Assessments
One type of assessment which
resembles a cumulative risk assessment, but
whose evaluation may require a different
approach from the traditional NRC risk
paradigm, is the quality-of-life assessment
These assessments define "harm" to an
individual or community broadly, then
evaluate the importance of the various threats
of harm to a set of "quality-of-life" criteria
(see box at right). These assessments do not
usually attempt to predict probability that the
harm will occur (as would a cumulative risk
assessment), but rather aim to apply the
community's values to deal with the most
important perceived threats.
Although a quality-of-life assessment
is not a risk assessment in most cases, changes
in quality-of-life factors may affect the
vulnerability of a population to health or
ecological risks, and consequently maybe part
of the considerations in a cumulative risk
assessment. Since few, if any, established and
accepted relationships are currently available
quantitatively linking quality-of-life factors
and health or ecological risk, this is an area in
which further research may prove valuable.
To evaluate the effects on human or
ecological health from these types of impacts,
a more deliberative approach (in the
analytical-deliberative process) is needed than
is used in, say, cancer risk analysis. To help
better characterize these impacts, EPA's Guidebook to Comparing Risks and Setting
Environmental Priorities (USEPA, 1993b) suggests a six-step process in Quality-of-Life
Analysis:
Vermont's Quality of Life Criteria
Impacts on Aesthetics: Reduced visibility, noise, odors,
dust and other unpleasant sensations, and visual impact
from degradation of natural or agricultural landscapes.
Economic Weil-Being: Higher out-of-pocket expenses to
fix, replace, or buy items or services (e.g., higher waste
disposal fees, cost of replacing a well, higher housing
costs), lower income or higher taxes paid because of
environmental problems, and health-care costs and lost
productivity caused by environmental problems.
Fairness: Unequal distribution of costs and benefits (e.g.,
costs and benefits may be economic, health, aesthetic).
Future Generations: Shifting the costs (e.g., economic,
health risks, environmental damage) of today's activities to
people not yet able to vote or not born yet.
Peace of Mind: Feeling threatened by possible hazards in
air or drinking water, or potentially risky structures of
facilities (e.g, waste sites, power lines, nuclear plants), and
heightened stress caused by urbanization, traffic, etc.
Recreation: Loss of access to recreational lands (public
and private), and degraded quality of recreation experience
(e.g., spoiled wilderness, fished-out streams).
Sense of Community: Rapid growth in population or
number of structures, or development that changes the
appearance and feel of a town; loss of mutual respect,
cooperation, ability, or willingness to solve problems
together; individual liberty exercised at the expense of the
individual; the loss of Vermont's landscape and the
connection between the people and the land.
Source: State of Vermont, 1991
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1 1. Identify impacts and determine the values of the community.
2 2. Identify and define evaluative criteria.
3 3. Collect and analyze data on impacts.
4 4. Characterize impacts for all problem areas.
5 5. Present findings and rank problem areas for quality-of-life impacts.
6 6. Analyze future environmental conditions and risk management considerations.
7
8 Quality-of-Life impacts are determined by analyzing a set of criteria developed for each
9 community, depending on what they value. Stressors are those things that threaten to degrade the
10 quality-of-life criteria for that community. An example of a set of quality-of-life criteria, and
11 their descriptions, is in the box on the previous page. These criteria were developed by the State
12 of Vermont's Agency of Natural Resources (State of Vermont, 1991). Vermont's experience in
13 evaluating these criteria was described as a qualitative description of harm, or in their terms,
14 "risk:"
15
16 "Because most of these seven criteria are intangible, they are extremely difficult to
17 measure or quantify. The Quality-of-Life Work Group described how each problem area
18 affects each criterion and how widespread or intense the effects are. Although these non-
19 quantitative descriptions of risk often lack precision and scientific objectivity, they focus
20 attention on specific critical issues and thus are useful tools for comparing the problems
21 systematically and consistently." (State of Vermont, 1991)
22
23 Quality-of-life issues can encompass much more than the criteria used here as an
24 example. Ultimately, such an analysis may introduce much additional complexity into the
25 analysis. There may, for instance, be feedback loops not easily evaluated (e.g., loss of property
26 value, aesthetics, etc., tend to negatively affect the socioeconomic system, which in turn tends to
27 increase rates of crime, traffic accidents, and communicable-pathogen transmission, all
28 ultimately reflecting on overall community
29 health or ecological risk). Some cumulative
30 risk assessments may consequently include
31 quality-of-life impacts as indirect measures of
32 health effects if sufficient links can be
33 established between the two.
34
36 F.2. Cumulative Impact Assessments
37
38 The National Environmental Policy
39 Act (NEPA) has certain requirements for
40 "cumulative impacts" assessment (see box at
/ii • t^\ t,- t, t i * Source: CEQ, 1997
41 right), which looks at various stressors
NEPA's "Cumulative Impact" Definition
CEQ Regulation 1508 for Implementing the National
Environmental Policy Act of 1969 [P.L. 91-190, 42 U.S.C.
4321-4347, January 1, 1970, as amended by P.L. 94-52,
July 3, 1975, P.L. 94-83, August 9, 1975, and P.L. 97-258,
§4(b), Sept. 13, 1982] defines "cumulative impact" as "the
impact on the environment which results from the
incremental impact of the action when added to other past,
present, and reasonably foreseeable future actions
regardless of what agency (Federal or non-Federal) or
person undertakes such other actions. Cumulative impacts
can result from individually minor but collectively
significant actions taking place over a period of time."
42 leading to a variety of impacts or effects on
43 the environment. Although the Council on
44 Environmental Quality's guidelines for cumulative impact analysis (CEQ, 1997) take a primarily
45 qualitative approach to the analysis, this is a multiple stressor, multiple effect assessment.
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1 The projects or actions that NEPA addresses can be viewed as sources of stressors.
2 Environmental impact assessment under NEPA contains a description of the affected
3 environment that contains four types of information; (1) data on the status of important natural,
4 cultural, social, or economic resources and systems; (2) data that characterize important
5 environmental or social stress factors; (3) a description of pertinent regulations, administrative
6 standards, and development plans; and (4) data on environmental and socioeconomic trends.
7 Health effects on populations and susceptible individuals are part of the affected environment as
8 considered by the NEPA cumulative effects analysis, but the NEPA analysis may also consider
9 effects on historic and archaeological resources, socioeconomic factors like employment, human
10 community structure, and quality of life changes. Although there is not always a clear
11 relationship between these NEPA cumulative impacts and effects relevant to human health, the
12 NEPA methods and tools for cumulative impact analysis may be useful for cumulative risk
13 assessments. For example, cumulative impact analysis begins with an extensive scoping process
14 and relies on conceptual models to plan the analysis. NEPA effects data may help risk assessors
15 identify susceptible subpopulations, environmental pathways, or exposure patterns.
16
17 EPA's Region VI has developed a system called the Cumulative Risk Index Analysis
18 (CRIA), primarily for NEPA-type assessments (Osowski, et al., 2001). The CRIA contains some
19 90 criteria to evaluate the health of an area and its ecosystem/human populations. These criteria
20 help evaluate factors as diverse as human health, ecosystem health, and environmental justice
21 considerations. Each criterion, which leads to an indexing of 1-5, has been through the
22 deliberative process, peer review, and is well documented.
23
24 We also acknowledge that other Federal Agencies have been preparing "cumulative risk
25 analyses" for various purposes related to their own mission as part of environmental impact
26 statements (e.g., NOAA, 1999).
27
28 F.3. Empirically-Derived Medical Models
29
30 The medical profession has long used empirically-derived models to predict the chances
31 of particular health effects in individual patients. In this approach, the characteristics of
32 individuals within the population are correlated with the incidence of specific diseases or effects.
33 For example, the risk factors for stroke are: increasing age, heredity (family history) and race,
34 prior stroke, high blood pressure, cigarette smoking, diabetes mellitus, carotid and other artery
35 disease, heart disease, transient ischemic attacks (TIAs), high red blood cell count, sickle cell
36 anemia, socioeconomic factors, excessive alcohol consumption, and certain types of drug abuse
37 (American Heart Association, 2000). Each of these risk factors can be correlated with stroke
38 incidence, and then the risk of stroke from various combinations of these factors can be explored.
39 In this way, the analysis is "cumulative,"but "risk factors" are not always synonymous with
40 "stressors."
41
42 Physicians use models containing effect-specific risk factors to advise patients of the
43 probabilities of future effects (e.g., stroke, breast cancer) based on their medical history.
44 Although the medical data upon which these factors are based have been well developed for
45 many effects in humans, there are substantial data gaps remaining in terms of the role played by
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1 exposures to many chemicals in the environment in the development of human disease. This
2 approach may be built on links between risk factors and effects for better studied stressors, but
3 may be limited or nonexistent for less robust health effects data bases. Although this approach
4 may some day be applicable to human health and environmental risk assessment such as EPA
5 conducts, at present the data and methods are not available.
6
7
8 F.4. Risk Surrogates
9
10 Geographic Information Systems (GIS) and related mapping techniques (e.g.,
11 Environmental Defense, 2001) appear to hold some promise as tools for presenting integrated
12 information concerning cumulative risks without mathematically combining disparate measures.
13 Considerable methods development work remains to be completed.
14
15 Not all statements of probability of harm are expressed as probabilities of specific health
16 effects. Bernard Cohen, in his Catalog of Risks Extended and Updated (Cohen, 1991), uses
17 mortality ratios to derive "loss of life expectancy" (LLE) estimates for a wide variety of risk-
18 related activities. For example, workers in all occupations have a 60 day LLE as a result of
19 working, but workers in agriculture have a 320 day LLE, construction workers a 227 day LLE,
20 etc., as a result of their particular occupation. These types of statements are empirically derived,
21 probability-based statements of harm that do not use "probability of adverse health effect" as the
22 basis for the risk statement. For estimates such as LLEs, one could theoretically add up the
23 various activities and the corresponding LLEs in days to estimate a cumulative risk in terms of
24 loss of life expectancy. These "other" types of risk-surrogate probability statements could
25 conceivably be used in cumulative risk assessment, although there is apparently no methodology
26 currently being used to do so.
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