601‐D12‐001

EPA EXTERNAL REVIEW DRAFT

Framework for Human Health Risk Assessment  

to Inform Decision Making 

July 12, 2012

U.S. Environmental Protection Agency  

Office of the Science Advisor

Risk Assessment Forum

   
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Table of Contents

Disclaimer vi

Preface vii

List of Acronyms viii

List of Text Boxes ix

Executive Summary x

1 Introduction 1

1.1 Background and History 1

1.2 Overview of the Framework 3

1.2.1 Scope and Purpose 3

1.2.2 Description of the Framework 5

2 Planning 10

2.1 Planning and Scoping 10

2.1.1 Context, Purpose and Scope 14

2.1.2 Overarching Considerations 16

2.1.3 Responsibilities and Resources 21

2.1.4 Decision Points and Scientific Peer Review 22

2.1.5 Public, Stakeholder and Community Involvement 24

2.1.6 Past Experiences and Assessments 25

2.2 Problem Formulation 26

2.2.1 Conceptual Model 27

2.2.2 Analysis Plan 31

2.3 Fit for Purpose 38

3 Risk Assessment 40

3.1 Exposure Assessment 41
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3.2 Effects Assessment 42

3.2.1 Hazard Identification 43

3.2.2 Dose‐Response Assessment 45

3.3 Risk Characterization 46

4 Public, Stakeholder and Community Involvement 50

4.1.1 Stakeholders 52

4.1.2 Community 53

4.2 Communication 54

5 Informing Decisions 56

5.1 Characterizing the Risks for Risk Management Options 56

5.2 Risk Management Factors Beyond the Risk Assessment and Characterization 57

6 Summary 59

References 61

Appendix I. Examples of EPA Program‐Specific Resources and Guidance on Risk Assessment

Activities 73

   
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Risk Assessment Forum Technical Panel

Rita Schoeny (Co‐Chair) Office of Water (on Detail to Office of Research and

Development)

Kathryn Gallagher (Co‐Chair)     Office of Water  

Julie Fitzpatrick (Science Coordinator) Office of the Science Advisor/Risk Assessment

Forum

Kacee Deener         Office of Research and Development

Chris Dockins         Office of Policy

Michael Firestone         Office of Children’s Health Protection

William Jordan     Office of Chemical Safety and Pollution Prevention

Margaret McDonough    Region 1

Deirdre Murphy       Office of Air and Radiation

Marian Olsen         Region 2

Kathleen Raffaele    Office of Solid Waste and Emergency Response

   
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Disclaimer

This document is a draft for peer review. It has not been adopted by the U.S.

Environmental Protection Agency and should not be construed to represent agency policy. It is

being circulated for comments on its technical merit and policy implications. Any mention of

trade names or commercial products does not constitute endorsement or recommendation for

use.  

  
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Preface

The purpose of this document is to describe a Framework for conducting human health

risk assessments that are responsive to the needs of decision‐making processes in the U.S.

Environmental Protection Agency (EPA). This document does not present either a checklist or

compendium of requirements. Rather it includes issues to consider, provides suggested

questions to ask during risk assessment planning and execution, and identifies some useful

practices. The intended audience for this document includes those who assess risk, those who

use the information within and outside the EPA (e.g., risk managers), and those interested in

the process by which EPA conducts risk assessments. This document was produced by a

Technical Panel of the EPA Risk Assessment Forum.  

   
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List of Acronyms  

AIEO    American Indian Environmental Office

CAA    Clean Air Act

CASAC   Clean Air Scientific Advisory Committee

CERCLA Comprehensive Environmental Response, Compensation and Liability Act

CWA    Clean Water Act

EJ    Environmental Justice

EPA    U.S. Environmental Protection Agency

FQPA    Food Quality Protection Act

HPV    High Production Volume

IRIS    Integrated Risk Information System

IRP    Integrated Review Plan

ISA    Integrated Science Assessment

MOA    Mode of Action

NAAQS  National Ambient Air Quality Standards

NAS    National Academy of Science

NRC    National Research Council

OAQPS   Office of Air Quality Planning and Standards

OMB    Office of Management and Budget

OPPT    Office of Pollution Prevention and Toxics  

ORD    Office of Research and Development

PA    Policy Assessment

PCCRARM Presidential/Congressional Commission on Risk Assessment and Risk

Management

PMN    Premanufacture Notice

REA    Risk and Exposure Assessment

SAB    Science Advisory Board

SDWA    Safe Drinking Water Act  

TCCR    Transparency, Clarity, Consistency and Reasonableness

TSCA    Toxic Substances Control Act
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List of Text Boxes  

Text Box 1‐1: Examples of EPA Actions Informed by Risk Assessments......................................... 1

Text Box 1‐2: Examples of Key EPA Documents Describing Risk Assessment Frameworks........... 3

Text Box 1‐3: General Principles of Framework for Human Health Risk Assessment.................... 4

Text Box 2‐1: Key EPA References on Planning and Scoping........................................................ 10

Text Box 2‐2: Examples of Risk Assessment Planning and Scoping at EPA .................................. 12

Text Box 2‐3: The Silver Book Statements on Utility .................................................................... 13

Text Box 2‐4: Risk Assessment for Economic Benefits Analysis ................................................... 17

Text Box 2‐5: Key EPA Children’s Health Guidance Documents................................................... 19

Text Box 2‐6: Resources on Sustainability and Life Cycle Assessment......................................... 21

Text Box 2‐7: Definitions of “Public,” “Stakeholder” and “Community”...................................... 24

Text Box 2‐8: EPA Resources on Conceptual Models................................................................... 29

Text Box 2‐9: Examples of Conceptual Models in EPA Risk Assessments.................................... 31

Text Box 2‐10: Data Quality Resources......................................................................................... 33

Text Box 2‐11: EPA Exposure Assessment Resources for Human Health..................................... 33

Text Box 2‐12: EPA Resources on Hazard Identification and Dose‐Response Assessment.......... 35

Text Box 2‐13: Other Risk Analyses Resources............................................................................. 36

Text Box 2‐14: Definitions of Uncertainty and Variability ............................................................ 37

Text Box 2‐15: More Silver Book Statements on Utility ............................................................... 39

Text Box 3‐1: Key Elements of an Exposure Characterization...................................................... 43

Text Box 3‐2: Example of a Consideration for Effects Characterization: Mode of Action............ 44

Text Box 3‐3: Transparency—Clarity—Consistency—Reasonableness in the Risk Characterization

Handbook (U.S. EPA 2000b).......................................................................................................... 46

Text Box 3‐4: Characterizing Cancer Risk from Early Life Exposure ............................................. 47

Text Box 3‐5: Considerations for Risk Characterization: Cumulative Risk Assessment................ 49

Text Box 4‐1: EPA Resources for Public Involvement Efforts, Tools and Policies......................... 52

Text Box 6‐1: The Silver Book Recommendations for a Human Health Risk Assessment

Framework .................................................................................................................................... 59
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Executive Summary

The Framework for Human Health Risk Assessment to Inform Decision Making

(Framework) is intended to facilitate implementation of existing U.S. Environmental Protection

Agency (EPA) guidance for conducting human health risk assessments and to improve the utility

of risk assessment in the decision‐making process. The Framework takes into account

recommendations on risk assessment processes described in the National Research Council’s

(NRC) 2009 report, Science and Decisions: Advancing Risk Assessment (NRC 2009). Particular

emphasis is given to recommendations on the design of risk assessment and on improving the

utility of risk assessment. This Framework highlights the important roles of planning and

scoping as well as problem formulation in designing a risk assessment that will serve a specific

and documented purpose. In accordance with longstanding agency policy, it also emphasizes

the importance of scientific review and public, stakeholder and community involvement. The

Framework will strengthen the EPA’s emphasis on the importance of transparency of its human

health risk assessment and decision‐making processes. This document is not intended to

supersede existing EPA guidance; rather, by citing and discussing existing guidance in the

context of the full framework, this document is intended to foster increased implementation of

agency guidance.

The key elements of the process for conducting a risk assessment are as follows:

• Planning and scoping: This step ensures that the risk assessment is sound and serves its

intended purpose. It also allows those interested in the risk assessment process to

determine the context of the risk assessment and the intended use of its results. A

broad range of technical experts working as a team may be involved in this stage.

• Problem formulation: This analytical phase identifies the major factors that must be

considered in a specific assessment, thus informing the technical approach. An

important outcome of problem formulation is a conceptual model that identifies the

stressor(s), the exposed population(s) and the endpoint(s) that will be addressed in the

risk assessment as well as the relationships among them.

• Exposure and effects assessment: Exposure assessment, a primary component of a risk

assessment, will reflect the considerations identified in problem formulation. Effects

assessment includes hazard identification and dose‐response assessment.  Susceptible

or more highly exposed populations may also be identified in these assessments.
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• Risk characterization: This final, integrative step provides risk managers with a useful,

synthesized, set of conclusions about the risk that has been assessed. It is judged by four

principles: transparency, clarity, consistency and reasonableness.

• Public, stakeholder and community involvement: Input from the public is sought and

considered.  Such input is essential to the agency in fulfilling its mission to protect

human health and the environment.

• Informing decisions: The final step in the risk assessment process is connecting the

previously defined purpose and scope with the conclusions and strengths/limitations of

the risk assessment.

The Framework also reflects the NRC (2009) recommendations on assuring that risk

assessments are well tailored to the problems and decisions at hand, so that they can most

meaningfully inform the decision‐making process. In describing these recommendations, the

NRC (2009) report uses the terms “fit for purpose” and “utility of risk assessment,” among

others. The NRC (1983) four‐step risk assessment paradigm is maintained in the current

Framework, but there is increased emphasis on assuring the utility of each risk assessment. The

utility of risk assessment is not something that is evaluated as a separate step in the process or

as a final check that occurs once the risk assessment is completed. Rather, an emphasis on

utility of the risk assessment for informing risk management decisions begins with planning and

scoping and continues throughout the process. The Framework stresses the practical nature of

risk assessment; it highlights the need for analysis in support of decision making and prompts

the risk assessor to consider areas of overarching concern to the agency, including children’s

environmental health and environmental justice. The Framework encourages the consideration

of innovative technology and the still‐developing area of sustainability concepts in

environmental decision making. This Framework supports enhanced dialogue between risk

assessors and risk managers while recognizing the distinction in their roles.  
1 Introduction

1.1 Background and History

Since the agency’s inception, risk assessment has informed actions taken to protect

public health and the environment from a range of threats. Over time, the science, approaches

and methods employed for these

analyses have evolved. Risk

assessments performed by the agency

inform a broad range of regulatory

decisions (see Text Box 1‐1). Thus, the

design, objectives and specific outputs

of risk assessments vary depending on

the purpose and governing statute.

Agency economic analyses also draw

on risk assessments to estimate the

value of health benefits associated

with regulatory options and actio

Text Box 1‐1: Examples of EPA Actions Informed

by Risk Assessments

• Pesticide usage restrictions.  

• Hazardous waste site remediation goals and

approaches.

• Regulation of hazardous materials usage.

• Ambient air quality standards.

• Emissions standards for hazardous air

pollutants.  

ns.

   This document provides a Framework for Human Health Risk Assessment to Inform

Decision Making (Framework) that draws on agency experience and takes into account the

recommendations on risk assessment process from the ’NRC’s 2009 report, Science and

Decisions: Advancing Risk Assessment (NRC 2009)—also known as the “Silver Book.” In

particular, this Framework seeks to address Silver Book recommendations on the design of and

improving the utility of risk assessments. This Framework also draws on a considerable body of

additional expert advice, beginning with the National Academy of Sciences’ (NAS) NRC 1983

report, Risk Assessment in the Federal Government: Managing the Process (commonly referred

to as the “Red Book”), followed by the NRC’s 1994 Report, Science and Judgment in Risk

Assessment (commonly referred to as the “Blue Book”) , and incorporates principles from the

agency’s extensive human health risk assessment guidance. Following publication of the Red

Book, the agency issued Risk Assessment and Management: Framework for Decision Making

(U.S. EPA 1984), which first articulated the EPA’s risk assessment framework. In 1984, the

agency established what is now called the Risk Assessment Forum and in 1986 added the Risk

Assessment Council; in 1993, the Science Policy Council (now called the Science and Technology

Policy Council) replaced the Risk Assessment Council. Shortly after publication of the Red Book,

the EPA began issuing a series of guidelines for conducting risk assessments in a number of

areas (e.g., cancer, chemical mixtures, developmental toxicity, exposure assessment,

mutagenicity, neurotoxicity, and reproductive toxicity) (U.S. EPA 1986b, 1987, 2005a, 1986a,

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2000a, 1991b, 1992a, 1986c, 1998b, 1996, respectively). Many of these original agency‐wide

risk assessment guidelines include frameworks that have been updated over time.

In its emphasis on the planning aspects of conducting risk assessments, this Framework

builds on principles found in the EPA’s 1997 Guidance on Cumulative Risk Assessment. Part 1.

Planning and Scoping, which described an approach for integrated risk assessment and

management (U.S. EPA 1997a). The 1997 guidance was designed to help risk managers and risk

assessors plan and document the scope of risk assessments and consider appropriate

participants (that is, technical, advisory or stakeholder) and information sources to enrich the

risk assessment. Additionally, the 1997 guidance augmented the agency’s February 1995

Guidance for Risk Characterization (U.S. EPA 1995d) by emphasizing the need for providing a

transparent, clear, consistent and reasonable basis for any assessment, and strongly

encouraged the undertaking of a formal problem formulation exercise for all risk assessments.  

Prior to the 1997 Guidance on Cumulative Risk Assessment. Part 1. Planning and

Scoping, the agency published the Framework for Ecological Risk Assessment (U.S. EPA 1992b)

and subsequently released the Guidelines for Ecological Risk Assessment (U.S. EPA 1998a),

which incorporated planning and scoping into the ecological risk assessment process. In 2003,

the Framework for Cumulative Risk Assessment (U.S. EPA 2003a) further built on these

documents in formulating a flexible structure for conducting and evaluating cumulative risk

assessment (for human health or ecological risk). In 2006, the agency published A Framework

for Assessing Health Risk of Environmental Exposures to Children, which applied this general

structure (including problem formulation, analysis and risk characterization, the three critical

phases in the risk assessment process) in describing risk assessments focused on evaluating

potential risks arising as a result of early life exposure (U.S. EPA 2006a). In addition to these

more general agency documents, individual programs and offices have implemented risk

assessment frameworks specific to their missions. Examples of documents with risk assessment

frameworks are provided in Text Box 1‐2. Finally, the agency has developed a Risk Assessment

Portal (U.S. EPA, 2012i) that provides basic information about environmental risk assessments

and offers a comprehensive set of links to key EPA tools, guidance and guidelines.

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Text Box 1‐2: Examples of Key EPA Documents Describing Risk Assessment Frameworks

• Risk Assessment Guidance for Superfund Part A (U.S. EPA 1989, 1991, 1998a, 1999a,

2001d, 2004a, 2009)

• Framework for Ecological Risk Assessment (U.S. EPA 1992b)

• Guidance on Cumulative Risk Assessment:. Part 1. Planning and Scoping (U.S. EPA 1997a)

• Guidelines for Ecological Risk Assessment (U.S. EPA 1998a)

• Risk Characterization Handbook (U.S. EPA 2000b)

• Framework for Cumulative Risk Assessment (U.S. EPA 2003a)  

• Office of Air Quality Planning and Standards Air Toxics Risk Assessment Library – General

Framework for Residual Risk Assessment (U.S. EPA 2004e)

• A Framework for Assessing Health Risk of Environmental Exposures to Children (U.S. EPA

2006a)

• Office of Pollution Prevention and Toxics  Requirements for Submitting Electronic Pre‐

manufacture Notices (PMNs) (U.S. EPA 2010d)

1.2 Overview of the Framework  

1.2.1 Scope and Purpose

The purpose of this document is to describe a process for conducting human health risk

assessments that are responsive to the decision‐making needs of the EPA. It provides an

organizing structure for implementing existing EPA guidance on human health risk assessment.

This Framework highlights the important role of planning and scoping in designing a risk

assessment so that it serves its intended purpose, as well as the importance of scientific review

and public, stakeholder and community involvement. This Framework is expected to promote

and increase the transparency of the human health risk assessment process at the agency. It is

consistent with the EPA Scientific Integrity Policy (U.S. EPA 2012b) and follows the general

principles laid out in Text Box 1‐3.

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Text Box 1‐3: General Principles of Framework for

Human Health Risk Assessment

• Each risk assessment should be fit for its intended

purpose.

• Each risk assessment should state the purpose,

context and scope clearly.

• Risk assessment should be based on exposure

scenarios, consistent with the purpose and context.

As appropriate, it should include consideration of

susceptible population groups and lifestages.

• The risk assessment should follow an acceptable,

overtly logical path employing common sense and

sound judgment in applying relevant guidance.

• All steps, key assumptions, limitations and

decisions, along with associated rationale, should

be clearly conveyed.

• There should be consideration of the role of

scientific peer and public consultation and review.

• The risk assessment should be presented in a

readily understandable and useful form.

In building on the basic

components identified in the Red

Book (NRC 1983) and on

processes currently employed

across the agency, this

Framework takes into account

key recommendations from the

Silver Book (NRC 2009), which

called for more interaction among

risk assessors and risk managers

during the course of a risk

assessment while recognizing and

keeping separate their different

roles (NRC 2009). Thus, this

Framework emphasizes the

importance of early identification

of risk management options so

that risk assessment can most

efficiently inform choices among

such options. Risk management

decisions are beyond the scope of the risk assessment proper; a risk assessment is one of the

sources of information that informs the particular decision at hand. As discussed in Section 5 of

this document, the risk assessment should not “make” the decision; it should characterize the

risk, including specifying who, what or how much is at risk. The Framework describes planning

to maximize the utility of the risk assessment for informing risk management decisions.  

The Framework reflects the often iterative nature of risk assessment; that is, as some

scientific questions are answered, new ones may develop that require the generation of

additional data and/or analyses that better define the distribution of risk and/or address

uncertainty. Throughout the process, additional knowledge may result in further refinement of

the conceptual model and analysis plan.  

Finally, this Framework incorporates areas of overarching agency interest, such as the

evaluation of risks to children (U.S. EPA 1995c) and environmental justice (EJ) (U.S. EPA 2012a),

and promotes the consideration of the concepts of sustainability and technology innovation in

risk management decision making. Executive orders that apply to these areas are Executive

Order 13045 (protection of children) and Executive Order 12898 (environmental justice).

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In summary, this Framework describes approaches for organizing and conducting

human health risk assessments; it complements but does not replace any existing guidance or

guidelines. Building from the agency’s experience and NRC recommendations, the Framework is

intended to identify the critical aspects of the risk assessment process within a formal albeit

flexible structure. The Framework is not intended to be an exhaustive reference on all relevant

guidance; rather, the Framework is intended to clearly describe the overall process, with

attention to critical aspects of each component, giving relatively more attention to the

description of less technical (more process‐associated) components of the process, while

identifying relevant references for the more technical components. It describes and discusses a

series of steps and considerations important to formulating and performing a risk assessment

to inform decisions. A major objective of the Framework is to improve the consistency and

transparency of risk assessments while enhancing harmonization of approaches across the

agency. The Framework aims to maximize the utility of the risk assessment for informing risk

management decisions as well as ensuring the most efficient use of resources by aligning the

nature and/or scope of the risk assessment with the decision to be made.  

1.2.2 Description of the Framework

The Framework for Human Health Risk Assessment to Inform Decision Making, at its

most basic form, is illustrated in Figure 1‐1. This figure reflects the main elements of the

Framework and their roles in the risk assessment process in a form that encompasses the broad

range of EPA risk assessment contexts. The figure conveys a path from planning and scoping to

informing decisions and illustrates that the process provides opportunities for feedback along

this path, which may vary among applications.  

The main elements of the Framework are discussed in the subsequent four sections of

this document. The concept of “fit for purpose” is discussed in multiple sections in keeping with

the need for its consideration from planning through execution, to ensure that assessments

most meaningfully inform the decision‐making process. Sections focused on the other elements

are as shown below.  

• Planning and scoping and problem formulation are detailed in Section 2 (Planning).

• Exposure and effects assessment and risk characterization are discussed in Section 3

(Risk Assessment).

• Public, stakeholder and community involvement are addressed in Section 4 (Public,

Stakeholder and Community Involvement).

• Informing decisions is discussed in Section 5 (Informing Decisions).

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Figure 1‐1. Framework for Human Health Risk Assessment to Inform Decision Making.

As described in the Silver Book (NRC 2009), the process begins with a decision to

conduct a risk assessment after what is described as a “signal” of potential harm is brought to

the EPA’s attention. Generally, this would involve a set of existing or potential environmental

conditions that appear to pose a threat to human or environmental health. The process

outlined in the Framework initiates activities on the assessment of the risk potential of the

environmental conditions; that is, after the signal is received.  

The initial stage in conducting any EPA risk assessment focuses on carefully

characterizing the task to be completed; it includes planning and scoping and problem

formulation components. The planning and scoping phase involves understanding the specific

environmental issue to be addressed; the legal framework under which any action will be

taken; the risk management options; and the public‐, stakeholder‐ or community‐specific

issues. Specific regulatory or programmatic requirements are considered throughout the

planning process. An essential question in this phase is what level of complexity is required

(e.g., screening, deterministic, or probabilistic risk assessment) to inform the necessary

decision; this consideration is termed here as “fit for purpose.” Planning and scoping also

includes the identification of resources available to complete the assessment and the formation

of a risk assessment team capable of performing the technical analyses that may be needed.

The team members may include a project manager, risk assessor, and other staff with the

appropriate expertise necessary to address the specific question. Based on the information

developed during planning and scoping, the problem formulation is then conducted to develop

a conceptual model and incorporate the information into an analysis plan. The analysis plan

outlines how the exposure; hazard and dose‐response; and risk characterization components of

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the risk assessment will be conducted, with consideration of data quality; uncertainty and

variability; and public, stakeholder and community involvement for each component as

appropriate.

The core risk assessment then is conducted based on the analysis plan developed during

problem formulation. The risk assessment phase includes developing the exposure and effects

characterizations and integrating those results for presentation as part of the risk

characterization. A key aspect of the Framework, “fit for purpose,” is consideration of the

usefulness of the assessment for its intended purpose, to ensure that the assessment produced

is suitable and useful for informing the needed decisions. Attention to this concept is intended

to assure, through focused planning and problem formulation and periodic reconfirmation

during the process, that the informational needs of the risk managers will be met by the

information being generated by the assessment. Rather than a separate step or final check in

the process once the risk assessment is completed, an emphasis on the utility of the risk

assessment occurs throughout the process. This begins with planning and scoping and includes

evaluating the applicability of the risk assessment for informing risk management decisions;

these evaluations may take place in several points of the iterative risk assessment process. Thus

focus is maintained on the information needs for the risk management decisions by considering

such questions as: “Is the assessment achieving its objectives for informing risk management

decisions?” If the answer is negative, then the risk assessment team can make adjustments,

revisit steps or develop additional information as needed.

The risk assessment may be assessed via independent peer review and/or receiving

input from public, stakeholder and community involvement, recognizing that approaches for

addressing these different audiences will vary among assessments. Independent peer review

helps to ensure the integrity and quality of the scientific and technical aspects of the risk

assessment. Where there is a need for such review, it may involve internal or external technical

reviewers. Input from the public, internal and external stakeholders, and the affected

community(ies) can provide insights that may not otherwise be available to risk managers but

should in no way compromise the integrity or quality of the scientific and technical aspects of

the risk assessment.  

In the risk management phase, risk managers will use the information in the assessment

report to evaluate the management options that are identified, thereby Informing Decisions as

to the selection of actions appropriate under statutory authority, relevant Executive Orders

(e.g., 12898, 13045) and Homeland Security Presidential Directives. Considerations in this phase

of the Framework include the risk assessment results for the various options, in light of all

appropriate factors. An outcome of this phase may be recognition of the need for additional

assessment, leading to iteration of previous steps. This phase also may include development of

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a strategy for communicating conclusions with the public, internal and external stakeholders,

and affected community(ies). In addition, plans may be made for evaluation of the outcome of

any actions taken.  

The following case example describes the current process for conducting reviews of the

National Ambient Air Quality Standards (NAAQS) (U.S. EPA 2012f). This process includes explicit

phases for planning, assessment of currently available scientific evidence (including that on

hazard and dose response), risk and/or exposure assessment, and policy assessment and

rulemaking. In each phase there is consideration of the need for external peer review and/or

public comment. Although each component or step in this example may not rely on precisely

the same terms as those used in this Framework document, it illustrates one manner by which

the EPA implements the key aspects of this Framework for a program in which risk assessment

plays a role in informing regulatory decisions.

   

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Case Example: Reviews of National Ambient Air Quality Standards

EPA’s current process for reviewing the National Ambient Air Quality Standards (NAAQS) has four major phases:  

(1) planning, (2) science assessment, (3) risk/exposure assessment and (4) policy assessment and rulemaking. The

planning phase of the NAAQS review process begins with a science policy workshop to identify issues and questions to

frame the review. A draft Integrated Review Plan (IRP) for the review is prepared jointly by the EPA’s National Center

for Environmental Assessment and the EPA’s Office of Air Quality Planning and Standards (OAQPS). The draft IRP is

made available for consultation with the Clean Air Scientific Advisory Committee (CASAC) and for public comment. The

final IRP is prepared in consideration of CASAC and public comments, and it presents the current plan and specifies the

schedule for the entire review, the process for conducting the review and the key policy‐relevant science issues that

will guide the review.  

The second phase of the review, science assessment, involves the preparation of an Integrated Science Assessment

(ISA), which provides a concise review, synthesis and evaluation of the most policy‐relevant science, including key

science judgments that are important to the design and scope of exposure and risk assessments. The ISA provides a

comprehensive assessment of the current scientific literature pertaining to known and anticipated effects on public

health and welfare associated with the presence of the pollutant in the ambient air, emphasizing information that has

become available since the last air quality criteria review to reflect the current state of knowledge. The ISA forms the

scientific foundation for the NAAQS review and is intended to provide information useful in forming judgments about

air quality indicator(s), form(s), averaging time(s) and level(s).  

In the third phase, risk/exposure assessment, staff prepares planning documents that consider the extent to which

newly available scientific evidence and tools/methodologies warrant the conduct of quantitative risk and exposure

assessments. If warranted, these documents outline a general plan, including scope and methods, for conducting the

assessments. When an assessment is performed, one or more drafts of each risk and exposure assessment (REA)

document undergoes CASAC and public review prior to completion of final REA(s). The REA provides concise

presentations of methods, key results, observations, and related uncertainties.  

The review process ends with a policy assessment and rulemaking phase. The Policy Assessment (PA) is a document

that provides a transparent OAQPS staff analysis and staff conclusions on the adequacy of the current standards and

potential alternatives that are appropriate to consider prior to the issuance of proposed and final rules. The PA

integrates and interprets the information from the ISA and REA(s) to frame policy options for consideration by the

Administrator. Such an evaluation of policy implications is intended to help ‘‘bridge the gap’’ between the agency’s

scientific assessments, presented in the ISA and REA(s), and the judgments required of the EPA Administrator in

determining whether it is appropriate to retain or revise the NAAQS. The PA also is intended to facilitate the CASAC’s

advice to the agency and recommendations to the Administrator on the adequacy of the existing standards or revisions

that may be appropriate to consider, as provided for in the Clean Air Act. In evaluating the adequacy of the current

standards and (as appropriate) a range of alternative standards, the PA considers the available scientific evidence and,

as available, quantitative risk‐based analyses, together with related limitations and uncertainties. The PA focuses on

the information that is most pertinent to evaluating the basic elements of NAAQS: indicator, averaging time, form and

level. One or more drafts of a PA are released for CASAC review and public comment prior to completion of the final

PA. Following issuance of the final PA and consideration of conclusions presented therein, the agency develops and

publishes a notice of proposed rulemaking that communicates the Administrator’s proposed decisions regarding the

standards review. A draft notice undergoes interagency review involving other federal agencies prior to publication.

Materials on which this decision is based, including the documents described above, are made available to the public in

the regulatory docket for the review. A public comment period, during which public hearings generally are held,

follows publication of the notice of proposed rulemaking. Taking into account comments received on the proposed

rule, the agency develops a final rule that undergoes interagency review prior to publication to complete the

rulemaking process. (Technology Transfer Network NAAQS, U.S. EPA 2012p)

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2 Planning  

There are multiple challenges and requirements that may arise in conducting a risk

assessment. For example, an assessment conducted as part of a regulatory action may have

various legal considerations, including the statute under which it is being conducted (e.g., CAA,

Clean Water Act [CWA]) and the regulatory program of which it is a part (e.g., 6‐Year Review of

Drinking Water Contaminants under SDWA, Pesticide Registration Review, Risk and Technology

Review program). Such legal considerations may result in the selection of specific aspects of the

assessment.  

There may also be technical challenges. For example, there may be a need to develop

appropriate analytical techniques or to use fate and transport models to estimate the range of

contaminant concentrations (and hence, potential exposure). An assessor also may be faced

with a lack of toxicity data for specific chemicals or routes of exposure. Information on sensitive

populations may be unavailable. Information on the likelihood or timing of combined exposures

to multiple chemicals may be difficult to obtain or estimate. Other challenges or considerations

may be related to resources, such as the need for access to specific expertise (e.g., modeling).

Time constraints associated with decision making and funding—or lack thereof—also may be an

issue and should be noted in the analysis plan.    

2.1 Planning and Scoping

The planning and scoping phase

is an element of the EPA’s data quality

objectives process and is critical to

producing a sound risk assessment that

serves its intended purpose (U.S. EPA

1997a, 1998a, 2000b, 2002a, 2003a,

2006f; Presidential/ Congressional

Commission on Risk Assessment and

Risk Management [PCCRARM] 1997a,

1997b; NRC 2009). EPA’s guidance

related to the 2001 Data Quality Act

emphasizes the important role of

systematic planning and attention to

data quality objectives (U.S. EPA 2006f).

Text Box 2‐1 provides a list of EPA

references on planning and scoping.

This phase may involve a team of

Text Box 2‐1: Key EPA References on Planning

and Scoping

• Guidance on Cumulative Risk Assessment.

Part 1. Planning and Scoping (U.S. EPA

1997a)

• Guidelines for Ecological Risk Assessment

(U.S. EPA 1998a)

• Science Policy Council Handbook: Risk

Characterization (U.S. EPA 2000b)

• Lessons Learned on Planning and Scoping of

Environmental Risk Assessment (U.S. EPA

2002a)

• Framework for Cumulative Risk Assessment

(U.S. EPA 2003a)

• Guidance on Systematic Planning Using the

Data Quality Objectives Process (U.S. EPA

2006f)

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technical experts, such as toxicologists, economists and engineers, as well as risk assessors and

risk managers. In some cases, other subject matter experts may include attorneys and

community outreach specialists. It also may be informed by external scientific or stakeholder

input.  Questions addressed in the Planning and Scoping step (derived from U.S. EPA 1997a),

are as follows:

• What are the overall purposes and general scope of the risk assessment? Are there legal

limitations or other legal considerations? If so, what are they?

• What risk assessment products are needed by management for informed decision‐ 

making? What is needed for other analyses (e.g., economic analysis)?

• What resources are required, available or pending? Resources could include data or

models, funding, personnel, expertise and/or coordination with other organizations.

• Who will be involved in conducting the risk assessment, and what are their roles (e.g.,

technical, legal or stakeholder advisors)?  

• What schedule will be followed? This will include provision for timely and adequate

internal and independent external peer review where appropriate.

In general, planning and scoping provides the opportunity for the risk manager(s), risk

assessor(s) and others interested in the process to consider the context in which the risk

assessment is being conducted and the purpose(s) for which the results will be used. The risk

assessment team, in collaboration with the risk managers, also defines what is expected to be

covered, considering limitations or constraints (e.g., tools, resources or timing). Planning and

scoping is an important first step to ensure that each risk assessment has a clear purpose and

well‐defined vision. Products from planning and scoping (e.g., the conceptual model and

analysis plan) reflect a common understanding and agreement on boundaries and conduct of

the assessment by those involved. Several examples of planning and scoping for EPA risk

assessments are summarized in Text Box‐2‐2.

EPA and external advisors have repeatedly recognized that an important part of

ensuring the usefulness of each risk assessment is the dialogue between the risk manager and

the risk assessment team on the nature of the decision to be informed by the risk assessment

(PCCRARM 1997a and b; NRC 2009; U.S. EPA 1998a, 2000b, 2002a, 2003a). This dialogue may

include discussion of many topics, for example:

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• Basis for the risk assessment (e.g., regulatory requirements, public concern, scientific

findings).

• How the information will be used.

• Risk management options.

• Areas of interest and applicable policies.

• Overarching considerations (e.g., environmental justice, children’s health, cumulative

risk assessment and sustainability as presented in Section 2.1.2).

• Economics.

• Current knowledge.

• Level of effort.

• Plans for use and communication of the information.  

Text Box 2‐2: Examples of Risk Assessment Planning and Scoping at EPA

• In EPA’s review of pesticide registrations, planning and scoping occurs for a series of risk

assessments, which although focused on different pesticides are designed to address a

common overarching regulatory purpose and assessment scope (Registration Review

Update, U.S. EPA 2004g).

• In the planning phase for reviews of NAAQS, an integrated review plan is developed that

describes all phases of the review, including the risk/exposure assessment. Additionally, a

risk and exposure (REA) planning document is developed as the first step in the REA phase

(for an example, planning documents for the particulate matter NAAQS review are

available at: Particulate Matter Standards—Documents From Current Review—Planning

Documents [U.S. EPA 2011n]).

• Planning and scoping are key components of human health risk assessments conducted

under the Comprehensive Environmental Response, Compensation and Liability Act

(CERCLA; also known as Superfund), and arediscussed in the following guidance

documents:

3⁄4 Guidance for Conducting Remedial Investigations and Feasibility Studies Under

CERCLA (U.S. EPA 1988)  

3⁄4 Human Health: Planning and Scoping (U.S. EPA 2011o)

3⁄4 Ecological: Planning and Scoping (U.S. EPA 2011p)

• In EPA’s residual risk review of National Emissions Standards for Hazardous Air Pollutants,

the planning and scoping step encompasses a set of emissions source categories for which

risk assessments are of generally similar scope and basic design while differing in specific

aspects of the sources and the chemicals emitted. A general project is described at: Risk

and Technology Review (U.S. EPA 2011q), at which a case study risk assessment plan for

several source categories also is available.

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Figure 2‐1 calls out the key elements of planning and scoping in the Framework, each of

which are discussed in further detail in subsequent sections. Text Box 2‐3 provides context on

risk assessment from the Silver Book (NRC 2009).

Figure 2‐1. Framework for Human Health Risk Assessment to Inform Decision Making: Key

considerations for Planning and Scoping.  

Text Box 2‐3: The Silver Book Statements on Utility

“Risk assessments should not be conducted unless it is clear that they are designed to answer specific

questions, and that the level of technical detail and uncertainty and variability analysis is appropriate

to the decision context” (NRC 2009, 247).

“The technical framework for risk assessment presented in the Red Book should remain intact but

should be embedded in a broader framework in which risk assessment is used principally to help to

discriminate among risk‐management options” (NRC 2009, 256).  

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• Section 2.1.1 focuses on the need to consider the purpose and context for the risk

assessment, noting that different processes may be employed depending on this

context and purpose.  

• Section 2.1.2 describes important overarching considerations that may affect risk

management options.  

• Section 2.1.3 discusses consideration of responsibilities, resources, participants and

timeline.  

• Section 2.1.4 addresses planning for scientific review.  

• Section 2.1.5 details public involvement.  

• Section 2.1.6 discusses the incorporation of lessons learned from review of previous

assessments.

2.1.1 Context, Purpose and Scope  

Each human health risk assessment is conducted within a particular context, which may

be specific to regulatory or programmatic needs or which may be responsive to environmental

events or newly identified circumstances of potential public health concern. Many EPA risk

assessments are performed to inform specific decisions that guide the development of

regulatory actions. For example, risk assessments commonly inform federal regulations

governing the establishment and review of NAAQS; the provision of public drinking water; and

the registration of pesticides for U.S. distribution, sale and use. For such risk assessments that

are routine and in which the type and level of effort needed is well‐established, the degree of

additional planning and scoping that is warranted for each individual assessment may not be

intensive. In other cases, such as a response to a newly identified environmental concern,

careful planning and scoping is essential to the development of a risk assessment that provides

information needed to address the concern.  

For risk assessments performed within a regulatory context, statutory language or

legislative history may impose requirements or restrictions that will need to be considered in

scoping the risk assessment; for example, the Food Quality Protection Act (FQPA) includes

directives on assessing risk that apply to pesticides in foods and water. In some regulatory

contexts, a risk assessment (or some quantitative aspect of it) may be a key input into benefit‐

cost analyses of alternative regulatory options; these analyses may impose different or

additional requirements by comparison to regulatory contexts wherein costs are not

considered.

As stressed earlier, risk assessments are most useful when they are designed to answer

specific questions with a level of technical evaluation that is appropriate for the decision

context (“fit for purpose”). In situations that are perceived to be particularly complex, clear

articulation of the overall purpose or end use of an assessment may involve extensive

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interaction among the assessment team and the range of stakeholders to establish a common

understanding. Explicit consideration of the purpose and decision context in the planning phase

will help to ensure the most efficient use of resources in the development of a risk assessment

that fulfills its purpose. That is, the utility of and risk assessment is a function of how well it

informs the decision for which it is designed.

The planning phase includes explicit consideration of the nature of the assessment

question or the hypothesis that the assessment seeks to address, with the goal of developing or

clarifying the broad dimensions and elements of the assessment. In this step, the assessment

and management objectives are defined clearly.  

The particular purpose for which an assessment will be used (e.g., site‐specific versus

regional or national) often will have significant implications for the scope, level of detail and

approach of an assessment. The risk assessment scope can be defined, in a general sense, by

the scale of the environmental problem being considered (e.g., local scale vs. national scale)

and the regulatory context. One example is a risk assessment intended to investigate the health

risks associated with a hazardous waste site that falls under the CERCLA statute, while the

scope for this risk assessment may be site‐specific, considering multiple receptors, multiple

chemicals and multiple pathways of exposure for on‐ and off‐site receptors (depending on the

nature of the site). This will differ from the scope for a risk assessment on uses or exposure to a

particular chemical, which is conducted to inform a national regulation (such as a National

Primary Drinking Water Rule).

Scoping provides a foundation for the problem formulation step. Scope, in this context,

refers to the proposed boundaries of the assessment (e.g., what chemical[s] and exposure

pathway[s]). The scope is considered with other items (e.g., context, purpose, participants,

timeline, resources) in developing the detailed plan for the assessment. At this step, most EPA

assessment projects focus on identifying and considering information available in these areas:  

• Sources of contaminants.  

• Stressors, associated effects, susceptible populations and life stages.

• Routes and pathways.  

• Stakeholder concerns.

• Any spatial or temporal aspects of exposure (U.S. EPA 1997a, 2001b).  

Consideration of these elements during scoping helps to identify missing information

and potential assessment endpoints for the analysis plan. It also provides the basis for an early

conceptualization of the problem being assessed and the approaches for assessment. The

scoping discussion also should include regulatory context and any additional management or

programmatic needs or limitations. At this stage, consideration of the needs of related,

quantitative analyses (e.g., cost/benefit analysis or environmental impacts of associated policy

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decisions) can contribute to improved efficiency. It also will help to ensure the compatibility of

the quantitative analyses considered in the decision‐making step described in Section 5. For

example, Text Box 2‐4 notes considerations pertaining to risk assessment for economic benefits

analysis. Information considered and decisions made during the scoping step also shape the

development of the conceptual model and the analysis plan (as described in Section 2.2).  

In the planning and scoping phase, it also is important to identify any subprocesses that

will feed into the risk assessment (e.g., Integrated Risk Information System [IRIS]). It also is

important to identify larger processes (e.g., rulemaking that occurs within the agency’s Action

Development Process) (U.S. EPA 2011r). Furthermore, individual regulatory programs have a

formalized process detailing the risk assessment process (e.g., Superfund). These processes may

have specific information requirements and timelines, and these may impose additional

requirements on the risk assessment process. Depending on the nature of the risk assessment

and the importance of the decisions, it may be important to identify how the risk assessment

team will interact with other program offices affected by the ultimate decision. Interagency

coordination also may be needed.

2.1.2 Overarching Considerations

The purpose and scope of the assessment also should be considered in the context of

broad EPA priorities. The extent to which these affect any given risk assessment will depend on

many factors, including the risk assessment purpose, scope and regulatory context. These

overarching considerations, described below, may not affect all analyses; however, early

consideration and discussion of these issues can enhance the utility of the risk assessment.

Further, such considerations may receive particular attention in the risk management arena,

depending on the decision context. Several current examples of agency priorities that may be

important overarching considerations in human health risk assessments are described below.

Analysis of the following overarching considerations should involve consultation with experts

and offices that focus on them.  

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Text Box 2‐4: Risk Assessment for Economic Benefits Analysis

Although risk assessment and economic analysis often are considered very separate exercises, estimates

from or inputs to risk assessment sometimes may serve as inputs into models economists use for the

benefits side of benefit‐cost analysis. Therefore, when benefit‐cost analysis is needed to inform

decisions, early communication between the risk assessment and benefits analysis teams, including

consideration of the needs of both analyses, can contribute to efficiencies in the assessment designs.

Key considerations in economic benefits analyses include:  

  

• Identifying a set of human health endpoints that are economically meaningful; that is,

endpoints that can be linked to human well‐being and for which the risks can be monetized

using economic valuation methods. This may require the risk assessment to model additional

outcomes or different outcomes than it would otherwise. For example, benefits analysis

incorporates changes in all health effects across the relevant range of exposure, not just the

most sensitive. In this case, specific human health endpoints measured in laboratory or

epidemiological studies may need to be converted in the risk assessment to additional metrics

or normalized in such a manner that the effects can be valued in the economic analysis

• Estimating changes in the probabilities of human health outcomes rather than measures such

as reference doses and reference concentrations that do not estimate potential risk (as noted in

Chapter 5 of the Silver Book [NRC 2009]).  

• Producing expected or central estimates of risk for a given population rather than conservative

estimates. The Science Advisory Board (SAB) Advisory on EPA’s Superfund Benefits Analysis

highlights the issue of using conservative risk assessments in benefits analysis (U.S. EPA 2006b).

• Attempting to estimate the “cessation lag” associated with reductions in exposure. That is, the

analysis should characterize the time profile of changes in exposures and resulting changes in

risks. This concept is more fully described in the Arsenic Rule Benefits Analysis: An EPA SAB

Review (U.S. EPA 2001a).

• Attempting to characterize the full uncertainty distribution associated with risk estimates. Not

only does this contribute to a better understanding of potential outcomes, it also enables

economists to incorporate risk assessment uncertainty into a broader analysis of uncertainty.

Formal probabilistic assessment of uncertainty in benefits and costs is required by the Office of

Management and Budget for some regulations.  

Early communication between the teams can help to improve the analyses performed for both

purposes. For example, risk assessment estimates may be informative for benefit‐cost analysis and also

can contribute information and insights into how behavioral changes may affect exposure and, thus,

change the risk. Even in cases in which the economists’ contribution to the risk characterization is not

direct, communication between the teams will improve compatibility of the risk assessment and

economic analysis.  

Additional information on economic analysis at can be found in Guidelines for Preparing Economic

Analyses (US EPA, 2010a). 2010a).

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• Environmental Justice

EPA defines Environmental Justice (EJ) as the fair treatment and meaningful

involvement of all people regardless of race, color, national origin or income with

respect to the development, implementation and enforcement of environmental laws,

regulations and policies (U.S. EPA 2012q). Achieving EJ is an agency priority that is

factored into every decision (U.S. EPA 2010b). In the risk assessment process, the

potential for disproportionate environmental and public health impacts to minority or

low‐income populations is an important consideration during the problem formulation

and planning and scoping stages. There has been discussion on addressing EJ concerns

in existing environmental and civil rights laws, their implementing regulations, Executive

Order 12898 and the EPA’s EJ policies. More information can be found at EPA’s EJ

website (U.S. EPA 2012a) and in the Interim Guidance on Considering Environmental

Justice During the Development of an Action (U.S. EPA 2010b). For example, EPA

priorities in this area include development of technical guidance and implementation

plans. EPA has established the American Indian Environmental Office (AIEO) to

coordinate the agency‐wide effort to strengthen public health and environmental

protection in tribal lands, with a special emphasis on helping tribes administer their own

environmental programs. Information on the AIEO and related activities is available at

the American Indian Environmental Office website (U.S. EPA 2012g).  

• Children’s Health Protection

Protecting children’s health from environmental pollutants has long been part of

the EPA’s mission. Children may be proportionately more heavily exposed to some

environmental contaminants than adults based on their smaller size and  increased

consumption per body weight of certain foods. Furthermore, their behavior patterns,

such as playing close to the ground and hand‐to‐mouth activity, also may increase their

exposure to contaminants. In addition, they may be more vulnerable to environmental

hazards because their organ systems still are developing and undergoing processes that

are specifically sensitive to certain chemicals, leading to potential windows of

susceptibility. Children also may be less able than adults to metabolize, detoxify and

excrete some chemicals.

In 1995, the EPA established its Policy on Evaluating Health Risk to Children to

ensure that environmental health risks to children explicitly and consistently are

evaluated as part of the EPA’s risk assessments and that all standards set by the EPA are

protective of any heightened risks faced by children (U.S. EPA 1995c). In 1997, Executive

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Order 13045 on the Protection of Children from Environmental Health Risks and Safety

Risks was issued. This executive order requires all federal agencies to assign a high

priority to addressing health and safety risks to children, coordinate research priorities

on children’s health, and ensure that their standards take into account special risks to

children (EO 13045).  

Some public health statutes provide for the protection of sensitive populations,

population groups or subpopulations. For example, the 1996 Safe Drinking Water Act

(SDWA) amendments utilize the term “subpopulation” to describe groups with unique

attributes, including those defined by age or life stage. The EPA recognizes that these

terms, as used in such statutes, describe groups of people with common attributes,

including life stage, which may make them more sensitive or susceptible to the

stressor(s) being assessed. The EPA emphasizes the importance of recognizing that

childhood encompasses a sequence of life stages through which all members of a

population pass. A life stage approach to risk assessment considers the relevant periods

of exposure in developmental life stages and subsequent outcomes that may not be

expressed until later life stages (U.S. EPA 2005a). Accordingly, EPA’s risk assessments

consider and take into account, using a variety of approaches, the potential for

differences across life stages that may affect risk. This encompasses a statute’s use of

the term “subpopulation” and instead uses the term “life stage.” Text Box 2‐5 highlights

several guidance documents available to assist in considering of children’s health.

Text Box 2‐5: Key EPA Children’s Health Guidance Documents

• Policy on Evaluating Health Risk to Children (U.S. EPA 1995c)

• Supplemental Guidance for Assessing Susceptibility from Early‐Life Exposure to

Carcinogens (U.S. EPA 2005b)

• Guidance on Selecting Age Groups for Monitoring and Assessing Childhood

Exposures to Environmental Contaminants (U.S. EPA 2005c)

• A Framework for Assessing Health Risk of Environmental Exposures to Children

(U.S. EPA 2006a)

• Guide to Considering Children's Health When Developing EPA Actions:

Implementing Executive Order 13045 and EPA's Policy on Evaluating Health Risks

to Children (U.S. EPA 2006e)

• Child‐Specific Exposures Factors Handbook (U.S. EPA 2008a)

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• Cumulative Risk Assessment

In the EPA’s 2003 Framework for Cumulative Risk Assessment (U.S. EPA 2003a),

cumulative risk is defined as the combined risks from aggregate exposures to multiple

agents or stressors. Several key points are made in this definition. First, cumulative risk

explicitly involves multiple agents or stressors. Second, the “agents or stressors” are not

limited to chemicals; stressors may, in some cases, also include biological or physical

agents as well as activities that, directly or indirectly, alter or cause the loss of a

necessity (such as habitat) or adversely influence health or increase susceptibility to

other stressors. Third, this definition requires that the risks from multiple agents or

stressors be combined.  

This does not necessarily mean that the risks should be added; rather the term

“combining” may mean that some analysis is conducted to determine how the risks

from the various agents or stressors interact. An assessment that covers a number of

chemicals or other stressors but merely lists each chemical with a corresponding risk

without consideration of the other chemicals possibly present is not an assessment of

cumulative. Further, cumulative risk assessment is an analysis, characterization and

possible quantification of the combined risks to health or the environment from

multiple agents or stressors. One key aspect is that the specific characteristics of a given

cumulative risk assessment will vary depending on scientific and regulatory needs. For

example, a cumulative risk assessment need not necessarily be quantitative and is

frequently used in place‐based assessments. The Office of Pesticide Programs’

cumulative assessments under the FQPA and those used by the Office of Water for

pesticides are legally defined in the Guidance on Cumulative Risk Assessment of

Pesticide Chemicals That Have a Common Mechanism of Toxicity as applying only to

chemicals with a common mechanism of action (U.S. EPA 2002d). Other environmental

statutes, such as the National Environmental Policy Act and Clean Air Act (CAA) (e.g.,

hazardous air pollutant aspects), also include various requirements for cumulative and

multiple pollutant analyses.

• Sustainability

Sustainability is defined in Executive Order 13514 as a process “to create and

maintain conditions, under which humans and nature can exist in productive harmony,

that permit fulfilling the social, economic, and other requirements of present and future

generations” (Executive Order 13514, 74 Federal Register 52126 [October 8, 2009]).

Sustainability is based on the simple principle that everything humans need for survival

and well‐being depends, either directly or indirectly, on the natural environment. The

concept entails consideration of how we meet society’s needs of today while ensuring

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future generations can meet their own. Sustainability is important to ensure that

humans have, and will continue to have, the water, materials and resources to protect

human health and the environment. EPA efforts in the area of sustainability practices

include approaches such as labeling green products, promoting green chemistry, and

engineering and managing materials rather than creating waste. Text Box 2‐6 includes

EPA resources related to sustainability.

The planned risk assessment may

provide the risk manager with information

relevant to the sustainability of proposed

risk management options. Issues to

consider include the full life cycle impacts

of the agent, stressor or remedy under

review, as well as the potential unintended

consequences of decisions. Sustainability

and the U.S. EPA (NRC 2011) contains a

detailed discussion of how a framework

for sustainability relates to risk assessme

and risk management.

nt

   

Thorough analysis of the above overarching considerations involves consultation with

experts and offices that focus on them. As appropriate, the risk assessment team should be

expanded to include individuals with the expertise needed for their full consideration.

Text Box 2‐6: Resources on

Sustainability and Life Cycle Assessment

• EPA/Office of Research and

Development (ORD) Sustainability

Program (U.S. EPA 2011e)

• EPA/ORD National Risk Management

Research Laboratory Life Cycle

Assessment Website (U.S. EPA 2011f)

• Sustainability and the U.S. EPA (NRC

2011)

2.1.3 Responsibilities and Resources

The planning process includes the initial allocation of responsibilities for members for

the assessment team as well as clarification of the interactions of the risk assessment team with

the risk managers and stakeholders. It is important that planning be a transparent effort so that

the basis for the final environmental decision (and the alternative options, limitations and

approaches considered but not selected) is clearly understood early in the process by the public

and regulated community. A team approach to planning risk assessments is essential (NRC

2009, U.S. EPA 2002a).  

The composition of the risk assessment team is dependent on the nature of the

problem. At a minimum, the team comprises individuals with the necessary scientific expertise,

as well as risk managers and other personnel as appropriate. Depending on the level of

complexity of a risk assessment and the context for its conduct, a multidisciplinary approach is

often necessary. Some disciplines that may be pertinent include: toxicology; epidemiology;

hydrogeology; fate and transport modeling (e.g., indoor and outdoor air, surface and drinking

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water); computer science (including geographic information systems [GIS], data management);

chemistry; biology; various engineering fields (e.g., chemical, environmental, mechanical,

industrial, civil); economics; sociology; statistics and communications. Lawyers and policy

makers also may be called on to contribute to risk assessment planning. Depending on the

context and process in which the risk assessment is conducted, specific expertise may be

needed to develop particular tools, data or analyses. Coordination with other federal, tribal and

state agencies and with other stakeholders also may be appropriate, depending on the type of

assessment being conducted.

Different members of the assessment team will provide expertise for specific elements

of the planning discussion. For example, the risk manager may identify the regulatory needs of

the assessment, time frames and quantity of funds available for the assessment. The site

assessment team would focus on evaluation of the current and future concentrations of the

contaminants in various media. An exposure assessor may help the team consider the nature,

fate and transport of the contaminants; sources, routes, timing and pathways; the extent of

contamination; and the availability of data, either at the national or local level. Other specialists

may provide information on topics such as funding levels and sources, contractor requirements

and relevant interagency agreements.  

It also is important to describe or establish the resources in terms of staffing, budget

and time for the assessment as part of the planning phase. These aspects need to be

considered in the development of the analysis plan, as they can affect the scope and approach

for the assessment. The timeline for the assessment is developed, taking into account critical

legal and management time frames, as well as any need to meet external deadlines or

coordinate with the schedules of other organizations (including critical stakeholders or external

review bodies). When there is extensive stakeholder involvement, it is especially important that

this be reflected in the budget and schedule and understood by all participants (U.S. EPA

2003c). When evaluating the need for human data, bioethics should be considered (see the EPA

Office of the Science Advisor website on Ethics, Regulations, and Policies; U.S. EPA 2012h).

2.1.4 Decision Points and Scientific Peer Review

Various stages in the assessment process can provide decision points and opportunities

for scientific review and stakeholder involvement. For example, completion of a draft

conceptual model and analysis plan, or an iteration of the risk assessment, may be useful points

for focused discussion between the risk assessor and risk manager and/or for scientific review

and public, stakeholder and community involvement.  

At such decision points, internal review and checks for quality of the assessment are

important. Other types of review also may be necessary, depending on the scope and purpose

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of the assessment. For example, an independent external peer review may be an important

element. Also some assessments (e.g., those developed for NAAQS, pesticide registration

decisions, or through the IRIS program) include a public review step, often coincident with the

scientific review step.  

Scientific peer review is a process used to provide a critical evaluation of a specific

agency scientific and/or technical work product. The EPA has published a Peer Review

Handbook that describes the types and extent of reviews as well as the documentation needed

to fulfill EPA requirements (U.S. EPA 2006c). (The Peer Review Handbook incorporates the

guidance provided in the Office of Management and Budget’s [OMB] 2004 Final Information

Quality Bulletin for Peer Review, [OMB 2004]). The Peer Review Handbook makes distinctions

among peer involvement, peer consultation and peer review. Peer review is a documented

process conducted to ensure that activities are technically supportable, competently

performed, properly documented and consistent with established quality criteria. Peer review

may be internal (to the EPA) or external. It is conducted by qualified individuals or organizations

that are independent of those who performed the work and who are collectively equivalent in

technical expertise (i.e., peers) to those who performed the original work. Peer review usually

involves a one‐time interaction, or limited number of interactions, by the independent peer

reviewers with the authors of the work product. An assessment also may benefit from other

types of input (such as peer involvement and public comment) that differ from peer review

(U.S. EPA 2006c). Planning for the assessment includes discussion of whether and what types of

reviews will be included, in light of the context and constraints for the assessment, including

schedule and resources.  

Consideration of the need for and timing of peer review steps is encouraged in the early

stages of the project or methods selection and/or as part of the culmination of the work

product, as appropriate (U.S. EPA 2006c). During the assessment planning and scoping process,

the team will need to determine whether any of the analyses or products of the assessment

need peer review and if so what level of peer review may be required and at what stage in the

process. Evaluating peer review requirements early will help ensure that adequate resources

are allocated. In addition, peer review considerations are an integral part of setting assessment

milestones and schedules. EPA’s Peer Review Handbook (U.S. EPA 2006c) provides detailed

guidance for determining when peer review is required and how to plan and implement a peer

review. The principle underlying the agency’s peer review policy is that “all influential scientific

and technical work products used in decision‐making will be peer reviewed” (U.S. EPA 2006c,

30). The Peer Review Handbook stresses transparency in all parts of the peer review process,

and EPA supports systems (e.g., Science Inventory) for documentation and disclosure of peer

review plans and products (U.S. EPA 2012c).  

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2.1.5 Public, Stakeholder and Community Involvement

The planning phase also includes consideration of opportunities for involvement and/or

review by the public and by specific stakeholders. EPA’s public involvement policy (U.S. EPA

2003c), a framework for implementing it (U.S. EPA 2003d) and other references are available at

the EPA’s Public Involvement Policy and Related Documents website (U.S. EPA 2012d); public,

stakeholder and community involvement are described at greater length in Section 4 of this

Framework document. Depending on the context for the risk assessment and overarching

process governing its conduct, risk assessment products also may be made available for public

comment, as required or practical under specific regulatory programs. Public, stakeholder and

community involvement may be initiated through a formal notice of availability of the risk

assessment and opportunity for public comment, and/or there may be a formal period for

public comment associated with a regulatory decision that was informed by the risk

assessment. Public commenters generally include a wide range of interested parties, both

experts and nonexperts, but they are not expected to provide the kind of independent, expert

information and in‐depth analyses obtained from the peer‐review process (U.S. EPA 2006c). The

involvement of public, stakeholders and communities (defined in Text Box 2‐7) can help ensure

that the assessment process is transparent and that risk‐informed decision‐making proceeds

effectively, efficiently and credibly (NRC 2009). Such involvement also may facilitate

development of sustainable

solutions (NRC 2011).  

The roles for

stakeholders are considered

during the planning step.

Deciding how and when to

involve stakeholders will

depend on the context for

and nature of an assessment.

Depending on the project, a

list of critical points for

stakeholder input, such as

discussions on purpose,

scope and approach, may be

defined (U.S. EPA 2003b).  

Stakeholders may be

from programs within EPA;

other federal agencies; state,

Text Box 2‐7: Definitions of “Public,” “Stakeholder” and

“Community”

• Public Involvement refers to the full range of activities

that the EPA uses to engage the American people in the

agency's decision‐making process (U.S. EPA 2011g).  

• Stakeholders are individuals or representatives from

organizations or interest groups that have a strong

interest in the agency's work and policies (U.S. EPA

2011g).  

3⁄4 Internal Stakeholders include EPA program offices or

regions (U.S. EPA 2007d).

3⁄4 External Stakeholders include the public, affected

industries, public health or environmental

organizations, other federal agencies, states, and

local and tribal governments (U.S. EPA 2007d).

• Community Involvement is the process of engaging in

dialogue and collaboration with community members

(U.S. EPA 2011h).  

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local and tribal governments; regulated industries; the regulated community; community

members affected by an environmental release; and members of the general public. PCCRARM

(1997a and b) suggests the following questions to identify potential stakeholders:

• Who might be affected by the assessment?

• Who has information and expertise that might be helpful?

• Who has been involved in similar risk situations before?

• Who has expressed interest in being involved in similar decisions before?

• Who might reasonably think that they should be included?

Assessments that require short‐term, low‐budget efforts or preliminary screening

assessments may not have the scope, time or resources for extensive public, stakeholder and

community involvement. Community involvement, however, is important to many community‐

based or site‐specific assessments; for a highly controversial location‐specific assessment, early

and extensive public, stakeholder and/or community involvement can be essential to the

success of the risk assessment and the risk management options informed by the assessment.

The Framework for Implementing EPA’s Public Involvement Policy (U.S. EPA 2003d)

provides general guidance for scoping a public involvement process and identifies the following

seven basic steps for conducting effective public involvement:

1.   Plan and budget for public involvement activities.

2.   Identify the interested and affected public.

3.   Consider providing technical or financial assistance to the public to facilitate

involvement.

4.   Provide information and outreach to the public.

5.   Conduct public consultation and involvement activities.

6.   Review and use input and provide feedback to the public.

7.   Evaluate public involvement activities.

2.1.6 Past Experiences and Assessments

Review of past experiences and assessments is an important part of planning and can

contribute to the development of a more robust analysis plan and improve the usefulness of

the assessment. For example, in the review of existing national standards, consideration of

previous assessments and aspects of them where newly available information or tools may

impact risk estimates can inform the planning stages for a new risk assessment, including

conclusions regarding what new insights it might be able to provide. Further, such explicit

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consideration of the potential value added of a new assessment may improve the efficiency of

the associated risk‐based decision making. Additionally, valuable lessons can be learned or

information obtained from assessments performed for conceptually similar situations (e.g.,

previous analyses for a similar industry, analog or chemical). Assessments by other agencies

(federal, state and international) also may be useful to study. Understanding past risk

assessment decisions and associated risk assumptions within a specific regulatory program is

important to assuring the usefulness of a given risk assessment in the decision making process.

Further, notable distinctions of the current assessment from previous assessments (e.g., new

health effects evidence or technical approaches) may be important to describe in the analysis

plan for the current assessment, as well as in the risk characterization.

2.2 Problem Formulation

Problem formulation is the part of the risk assessment planning process that

systematically identifies the major factors to be considered in a particular assessment. It draws

from the regulatory, decision‐making and policy context of the assessment and informs the

technical approach of the assessment. EPA’s Guidelines on Ecological Risk Assessment defines

problem formulation as the analytical phase of the assessment wherein “the purpose for the

assessment is articulated, the problem is defined, and a plan for analyzing and characterizing

risk is determined” (U.S. EPA 1998a, 2). The formalization of problem formulation in the current

Framework is a significant step in improving risk assessment processes.  

An important outcome of the problem formulation step is a conceptual model that

identifies the stressor(s), the exposed population(s) and the endpoint(s) that will be addressed

in the risk assessment as well as the relationships among them. Assessment endpoints, as well

as the exposed population(s), are more limited in variety in human health risk assessment than

is the case in ecological risk assessment (U.S. EPA 1998a). Many agency regulatory programs

have established specific human health risk assessment endpoints, often linked to statutory

requirements. For example, risk assessments for the Superfund and Hazardous Air Pollutant

programs, among others, include among their assessment endpoints estimates of lifetime

individual cancer risk associated with the particular sources or sites assessed (U.S. EPA 1991a,

1999c). Alternatively, risk assessments performed for reviews of the NAAQS often focus on

population risk metrics particular to the health effects evidence for the air pollutant being

assessed. The analysis plan, the final product of problem formulation, is developed in light of

the conceptual model, any programmatically established assessment endpoints and other

planning considerations described in Section 2.1. Figure 2‐2 highlights the problem formulation

steps within the Framework.

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Figure 2‐2. Framework for Human Health Risk Assessment to Inform Decision Making: Key

Questions and Considerations for Problem Formulation.

2.2.1 Conceptual Model

A conceptual model includes both a written description and a visual representation of

actual or predicted relationships between humans (populations or population segments) and

the chemicals or other stressors to which they may be exposed. The complexity of the

conceptual model depends on the complexity of the problem; this may be related to the

number of stressors, exposure pathways or assessment endpoints; the nature of effects; and/or

the characteristics of the exposed population(s) or life stage(s). Generally, the conceptual

model identifies factors and endpoints that will be analyzed in the risk assessment. It also

addresses those items that may not be analyzed in the risk assessment, the recognition of

which may be important in the overall decision‐making process. For example, although a risk

assessment for a particular stressor may focus on exposure pathways or media relevant to the

regulatory decision being faced (e.g., ingestion of drinking water), the conceptual model also

will describe the role of other pathways (e.g., consumption of fish), ensuring appropriate

characterization of and context for the assessment results.

The visual representation of the conceptual model and the associated narrative describe

the basic rationale for pursuing a particular course of action in the assessment. It can provide

documentation of decisions for future reference during risk assessment and can be useful in

characterization and communication of the risk management decision. The conceptual model

also is valuable as a risk communication tool both within the agency and in interactions with the

public. The conceptual model is a scientific or technical work product that can include the

following:  

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• The rationale for selecting the sources, stressors, exposure pathways, receptors,

exposed populations, endpoints or risk metrics including effects.  

• The basis for the model development.  

• The scientific implications of additional data gathering.

A general conceptual model (visually represented in Figure 2‐3) defines the key

elements for the problem to be assessed and shows pathways and routes of exposure between

the stressors and effects (endpoints) for human receptors. The visual representation of the

conceptual model is a diagram that may include the following types of elements:

• Source(s) of stressors of interest in the environment (e.g., releases from a leaking

storage tank, waste material poured on the ground).  

• Types of stressor(s) that may be physical, chemical and/or biological.  

• Exposure pathways, including fate and transport processes by which stressors may

move from the original point of release through the environment (e.g., a chemical in soil

might penetrate down into groundwater or might volatilize into air) and the interaction

by which populations or individuals are exposed (e.g., ingestion of contaminated water,

inhalation of chemicals in air, dermal contact with contaminated soil).

• Receptors, which may be groups of individuals or populations identified by common

characteristics, including life stage (e.g., general population, infants, local residents near

site of concern, adult workers, recreational visitors, populations/life stages with unique

exposures and/or susceptibilities to stressors).  

• Types of endpoints to be considered (e.g., cancer, asthma, IQ decrement or

developmental effects).

• Risk metrics (e.g., cases of disease or disease incidence, hazard quotient, magnitude of

effect or margin of exposure).  

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Figure 2‐3. Example of a Generalized Conceptual Model With Examples of Possible Dimensions

and Linkages (adapted from U.S. EPA 2002a, 2003a).

Conceptual models are used to plan the risk assessment and associated data collection

activities, and they may be periodically revised as data become available. Conceptual models

consist of two principal components: (1) a set of risk hypotheses that describe predicted

relationships among stressor, exposure and health endpoint/response, along with the rationale

for their selection; and (2) a diagram that illustrates the relationships presented in the risk

hypotheses. Text Box 2‐8

identifies EPA guidance

documents with more

information about conceptual

models; references for

examples of conceptual

models from various EPA risk

assessments are in Text Box 2‐

9.  

Text Box 2‐8: EPA Resources on Conceptual Models  

• Ecological Risk Assessment Guidelines (U.S. EPA

1998a, 40–41)

• Lessons Learned on Planning and Scoping for

Environmental Risk Assessments (U.S. EPA 2002a,

5–6)

• Science Policy Council Handbook: Risk

Characterization (U.S. EPA 2000b, 29–30, B‐21, B‐

23).

• Cumulative Risk Assessment Framework (U.S. EPA

2003a, 25–27)

• Framework for Assessing Health Risk of

Environmental Exposures to Children (U.S. EPA

2006a, 3‐5 to 3‐9)

Figure 2‐4 presents a

diagram illustrating a detailed

conceptual model of multiple

exposure pathways and

receptors potentially affected

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by multiple sources of chemical stressors; this model was designed by EPA Region 8 (U.S. EPA

2012e) for the analysis of Superfund sites contaminated with PCBs.  

Figure 2‐4. Example Conceptual Model of Exposure Pathways for Multiple Receptors to

Multiple Stressors for Superfund Site Assessment (Region 8 Site Conceptual Model; U.S. EPA

2012e).  

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2.2.2 Analysis Plan

Text Box 2‐9: Examples of Conceptual Models in EPA Risk Assessments

• Conceptual model to inform lead NAAQS risk assessment (U.S. EPA 2007c, 2‐1 to 2‐19)

• Case Study on Concentrated Animal Feeding Operations (U.S. EPA 2002b, Appendix B)

• Re‐registration of Pentachlorophenol (U.S. EPA 2002c, Appendix C)

The analysis plan is the final stage of problem formulation (U.S. EPA 1989, 2000a, 2002a,

2003a). This is the implementation plan for performing the risk assessment and addressing the

agency’s needs. It describes agreements made during the planning and scoping process and

provides details on technical aspects of the risk assessment, as described below. In some cases,

the plan will specify a phased or tiered risk assessment approach to facilitate management

consideration; scientific review; and/or public, stakeholder and community involvement.  

During analysis planning, hypotheses about the relationships described in the

conceptual model are evaluated to determine how they will be assessed using available and

new data. Although the conceptual model may identify a larger set of pathways and

relationships, the analysis plan focuses on the pathways and relationships that will be pursued

during the analysis phase. The rationale for selecting or omitting pathways and relationships is

incorporated into the plan, as is acknowledgement of data gaps and uncertainties. The analysis

plan also may include a consideration of how the level of confidence (or precision) needed for

the management decision compares with that expected from available analytical approaches;

this is done to determine data needs and evaluate which analytic approach is best. When new

data are needed, the feasibility of obtaining them is evaluated. The analysis plan is most useful

when it contains explicit statements of how measures were selected, what the measures are

intended to evaluate, and which analyses they support.

The analysis plan may include these components:

• The assessment design and rationale for which relationships are addressed.  

• Description of the data and information, methods and models to be used in the analyses

(including uncertainty analyses).  

• The associated data gaps and limitations.  

Analysis plans may be brief or extensive depending on the assessment and its level of

complexity. For assessments performed for some purposes (e.g., the EPA’s new chemical

assessments under the Toxic Substances Control Act [TSCA]), a standard analysis plan is

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established for the set of assessments to be conducted for the same purpose and regulatory

context. The type or design of analyses to be conducted is influenced by statutory requirements

or programmatic objectives, data availability, resources and limitations, and the purpose and

scope of assessment. Thus, the risk assessment designs will vary, which will be reflected in the

development of the plan. For example, the EPA performs different types of risk assessments

that range from deterministic scenario‐based assessments to more complex probabilistic

population modeling analyses. Assessments may be screening‐level or more robust, depending

on various factors, including the specific resources available for the assessment. Further, the

organization of the analysis plan may vary with the purpose and context for the assessment. In

all cases, the plan addresses the quality of data to be used; assessments of exposure, hazard

and dose‐response; and risk analyses, including analyses of uncertainty and variability. These

areas are described in the subsections below.

2.2.2.1 Data Quality  

In developing and implementing the analysis plan, several aspects of the data and

information to be used in the assessment are evaluated, including the following (U.S. EPA

2003a):

• Soundness. The extent to which the scientific and technical procedures, measures,

methods or models employed to generate the information are reasonable and

consistent with the intended application.

• Applicability and utility. The extent to which the information is relevant for the

intended use.

• Clarity and completeness. The degree of clarity and completeness with which the data,

assumptions, methods, quality assurance, sponsoring organizations and analyses

employed to generate the information are documented.

• Uncertainty and variability. The extent to which the variability and uncertainty

(quantitative and qualitative) in the information or in the procedures, measures,

methods or models are evaluated and characterized.

• Evaluation and review. The extent of independent verification, validation, and peer

review of the information or of the procedures, measures, methods or models.

Evaluation of data quality requires context. Depending on how and for what purpose

the data will be used, the same data may be acceptable in one situation and unacceptable in

another. EPA has established a Quality System (U.S. EPA 2011i) to ensure that environmental

programs and decisions are supported by data of the type and quality needed and expected for

their intended use. A critical aspect of this system involves the use of data quality objectives for

the development of new data and evaluation of existing data. Aspects of a risk assessment for

which data quality may be important to consider in the analysis plan include:  

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• The collection, evaluation and use of environmental data, including distributions of

contaminants, considerations of information on sources of variability, tolerance for

potential decision errors and/or precision requirements (U.S. EPA 2011i).  

• Development, evaluation and use of

computer or mathematical models

including evaluation of uncertainty and

variability.

Text Box 2‐10: Data Quality Resources

• EPA Requirements for Quality

Assurance Project Plans (U.S. EPA

2001c)

• EPA’s Quality System for

Environmental Data and

Technology (U.S. EPA 2011i)

• Superfund Quality

Assurance/Quality Control (U.S.

EPA 2011j)

• Resources for Planning New Data

Collections (U.S. EPA 2011k)

• Use of secondary data collected for

purposes other than the planned

assessment.

Analysis plans also consider data quality guidance

specific to the program for which the assessment

is being conducted. Data quality resources are

given in Text Box 2‐10.  

2.2.2.2 Exposure Assessment  

The analysis plan describes the approach (quantitative or qualitative) to be employed

for characterizing exposure in the risk assessment. See Text Box 2‐11 for EPA resources on

exposure assessment. This exposure assessment plan is developed by drawing on the

information, considerations and decisions represented by the conceptual model for human

health (as described in Section 2.2.1 above). Accordingly, the plan describes the exposure

assessment elements specified in the conceptual model, including the relevant routes and

pathways, frequency and

duration of exposures,

populations and life stages,

and assessment metrics. The

plan also defines the

methods, models and

information or data that will

be used, as well as the

environmental conditions or

scenarios (e.g., conditions

associated with alternative

standards or clean‐up levels

for environmental

contaminants or different

Text Box 2‐11: EPA Exposure Assessment Resources for

Human Health

• Guidelines for Exposure Assessment (U.S. EPA 1992a)  

• Guidance on Selecting Age Groups for Monitoring and

Assessing Childhood Exposures to Environmental

Contaminants (U.S. EPA 2005c)

• A Framework for Assessing Health Risk of

Environmental Exposures to Children (U.S. EPA 2006a)

• Highlights of the Child‐Specific Exposure Factors

Handbook (U.S. EPA 2009)

• Exposure Factors Handbook (U.S. EPA 2011a)

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uses for a pesticide). Key limitations, assumptions and uncertainties associated with the tools

and approaches are recognized in the analysis plan.  

The plan also identifies the approach for describing exposure variability. For example,

the approach might specify a deterministic scenario‐based assessment to provide point

estimates for a particular population (e.g., long‐term residents or high‐end consumers of a

particular food such as fish) or life stage (e.g., very young children). In contrast, a more complex

probabilistic population modeling assessment might provide a distribution of estimates for the

specific population assessed; an example would be children living in three specific urban areas

under environmental conditions associated with a current standard or food consumption

patterns for specific age groups based on dietary survey information. The rationale for the

selected approach is described in the plan as well as the extent to which estimates will be

developed for the central and upper percentiles of the population being assessed. Further, the

plan generally delineates the approaches for assessing uncertainty and variability in the

exposure estimates.  

2.2.2.3 Hazard Identification and Dose­Response  

The analysis plan specifies the strategy for characterizing hazard and dose‐response

relationships for the stressors being assessed. For example, the strategy may include use of

publicly available hazard identification and dose‐response assessments that already have been

prepared (in accordance with agency guidance and methods), such as those in the EPA’s IRIS

database. Alternatively, the strategy may specify a different approach for characterizing the

hazard of the identified stressors and describing the dose‐ or concentration‐response

relationship that will be used in the risk assessment.  

The EPA has established a variety of guidance documents for all components of risk

assessment (see Text Box 2‐12). These documents address evaluation of particular types of

toxicity, dose‐response assessment and endpoint selection; the consideration of information on

mode of action (MOA) or pathways of toxicity; the role of toxicokinetic information; and factors

influencing sensitivity and susceptibility (e.g., nutrition, life stage, exposure characteristics and

disease state). Rather than describing in detail the steps in effects assessment, the analysis plan

may refer to these or other published documents.

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Text Box 2‐12: EPA Resources on Hazard Identification and Dose‐Response Assessment

• Guidelines for the Health Risk Assessment of Chemical Mixtures and Supplementary

Guidance for Conducting Health Risk Assessment of Chemical Mixtures (U.S. EPA 1986a,

2000a)

• Guidelines for Developmental Toxicity Risk Assessment (U.S. EPA 1991)

• Methods for Derivation of Inhalation Reference Concentrations (RfCs) and Application of

Inhalation Dosimetry (U.S. EPA 1994)

• Guidelines for Reproductive Toxicity Risk Assessment (U.S. EPA 1996)  

• Guidelines for Neurotoxicity Risk Assessment (U.S. EPA 1998b)

• A Review of the Reference Dose and Reference Concentration Processes (U.S. EPA 2002e)

• Guidelines for Carcinogen Risk Assessment (U.S. EPA 2005a)

• Supplemental Guidance for Assessing Susceptibility from Early‐Life Exposure to Carcinogens

(U.S. EPA 2005b)

• A Framework for Assessing Health Risk of Environmental Exposures to Children (U.S. EPA

2006a)

   

2.2.2.4 Risk Characterization

The analysis plan identifies and describes the strategy or approach for combining

exposure information with hazard and dose‐response information to generate risk estimates or

other measures for characterizing health risk. The approaches may vary widely, depending on

other considerations (described above for the planning phase), in the following manners:

purpose and context for the assessment, the available information, and resources and timeline

for the assessment. Risk analyses might range from deterministic scenario‐based assessment to

a probabilistic population modeling assessment. Either of these approaches may yield estimates

for general population risk or for specific, defined groups within the general population. For

estimates of individual risk, calculations can consider central tendency and the upper end of

distribution. The upper end of the distribution used for risk characterization may vary

depending on the needs of the assessment (e.g., the 90th, 95th or 99th percentiles) (U.S. EPA

1992a).

Assessments may be screening‐level or more robust depending on the purpose and

availability of data. Decisions on the type or design of the assessment are influenced by

statutory requirements or programmatic objectives, data or resource availability and

limitations, and purpose/scope of the assessment. Types of risk assessment metrics that might

be considered for the assessment include:

• Incidence of specific health outcomes.

• Risk of specific health outcomes.

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• Occurrences of exposures above health‐based benchmarks or comparison points.  

• Potential for occurrence of exposure above health‐based benchmarks.  

• Margins of exposure between a point of departure for an effect and a measured or

estimated environmental level.

• Hazard quotients for specific exposure scenarios (hazard quotients are measured or

estimated exposure levels divided by a reference value).

In defining the analyses to be performed, the plan also describes the associated limitations,

assumptions and plans for assessment of uncertainty and variability. Other EPA resources for

risk analysis are described in Text Box 2‐13.

Text Box 2‐13: Other Risk Analyses Resources

• Guidelines for the Health Risk Assessment of Chemical Mixtures and Supplementary

Guidance for Conducting Health Risk Assessment of Chemical Mixtures (U.S. EPA 1986a,

2000a)

• Risk Assessment Guidance for Superfund (U.S. EPA 1989, 1991, 1998a, 1999a, 2001d,

2004a, 2009)  

• Science Policy Council Handbook: Risk Characterization (U.S. EPA 2000b)

• Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human

Health (U.S. EPA 2000d)

• Framework for Cumulative Risk Assessment (U.S. EPA 2003a)

• Air Toxics Risk Assessment Reference Library (U.S. EPA 2004b, 2004c, 2006d)

• A Framework for Assessing Health Risk of Environmental Exposures to Children (U.S. EPA

2006a)

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2.2.2.5 Uncertainty and Variability

Drawing from EPA guidance and experience, the analysis plan describes how uncertainty

and variability will be characterized in the risk assessment. The complexity of the approaches

will be influenced by considerations identified earlier in the planning phase, including purpose

and context for the assessment, as well as timeline and resources. Planning for this stage of the

assessment also will consider how elements of an uncertainty/variability evaluation can inform

different parts of the assessment approach, improving the overall plan as well as the utility of

the final product. The plan may consider the value of obtaining additional data or information

to reduce areas of uncertainty. More information about uncertainty and variability can be

found in Text Box 2‐14.

Text Box 2‐14: Definitions of Uncertainty and Variability

Uncertainty refers to imperfect knowledge or lack of precise knowledge of the real world, either for

specific values of interest or in the description of the system. Although numerous schemes for classifying

uncertainty have been proposed, most focus on two broad categories: parameter uncertainty and model

uncertainty. Descriptions of both areas are found in Risk Assessment Principles and Practices (U.S. EPA

2004d).

Variability refers to the inherent natural variation, diversity and heterogeneity across time and/or space

or individuals within a population. Although we can better describe and understand variability in the

world, or a particular system, it is unavoidable and cannot be reduced (U.S. EPA 2010c).

Resources for Characterizing Uncertainty/Variability

• Guiding Principles for Monte Carlo Analysis (U.S. EPA 1997c)  

• Science Policy Council Handbook: Risk Characterization (U.S. EPA 2000b)  

• Risk Assessment Guidance for Superfund Volume III—Part A: Process for Conducting Probabilistic

Risk Assessment ( U.S. EPA 2001d)  

• Risk Assessment Principles and Practices (U.S. EPA 2004d)  

• A Framework for Assessing Health Risk of Environmental Exposures to Children (U.S. EPA 2006a)

• Guidance Document on Characterizing and Communicating Uncertainty in Exposure Assessment

(World Health Organization, 2008)  

• Using Probabilistic Methods to Enhance the Role of Risk Analysis in Decision‐Making With Case

Study Examples (U.S. EPA 2010c)

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2.3 Fit for Purpose

Risk assessments at the EPA are performed to inform risk management decisions.

Accordingly, throughout the process of planning and performing the analyses it is important to

confirm that the assessment will address the information needs of risk managers. Periodic

confirmations may be part of the decision points or review steps described above or may be

done as they otherwise fit within the process of the assessment. In the Silver Book (NRC 2009),

the NRC recommended use of a framework that “maximizes the utility of risk assessment,” with

a focus on assuring that risk assessments are well‐tailored to the problems and decisions at

hand so that they can most meaningfully inform the decision‐making process. In describing this

concept, the NRC (2009) report uses the terms “fit for purpose” and “utility of risk assessment,”

among others. Consistent with its usage as a key principle in quality assurance programs, “fit for

purpose” in this framework refers to the development of risk assessments and associated

products that are suitable and useful for their intended purpose(s) particularly that of informing

risk management decisions.  

In the EPA’s Framework described here, the utility of risk assessment is not an element

that is evaluated as a separate step in the process or a final check that occurs once the risk

assessment is completed. Rather, consistent with the NRC’s emphasis on consideration of risk

management needs early in the process, the agency’s Framework emphasizes attention to

utility throughout the process, beginning with planning and scoping, and including a specific

focus on the applicability of the risk assessment for informing risk management decisions.

Attention is given to this concept through focused planning and problem formulation and

confirmation during the process to ensure that the informational needs for the assessment are

being met by the information being generated by the assessment. Questions to consider in

evaluating the usefulness of the assessment design and its implementation include those listed

below:  

• Does the assessment design meet the objectives and have the attributes identified in

the problem formulation step?  

• Does the assessment, as implemented, meet the initial objectives? Or, if the initial

objectives have been modified (e.g., as a result of changed risk management options or

issues), does the assessment meet the modified objectives?  

• Does the assessment have the attributes identified in planning?

• If the assessment requires peer review, has this been done appropriately and have the

issues raised during the peer review been adequately addressed?  

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• How will the results of the risk assessment be communicated to the risk managers and

stakeholders?

• Does the assessment inform choices among risk management options? Are there any

additional risk assessment needs for discriminating between or implementing risk

management options?

Additional or revised analyses may be considered in the assessment, depending on the

answers to these and other questions that may reflect the specific risk management decision

being addressed.

The utility of the risk assessment is defined by the degree to which the assessment

informs choices among risk management options. Related to this, it is critical that there be

transparent dialogue between risk assessors and risk managers throughout the assessment

process, beginning with the planning stage. It is important to note, however, that the EPA

maintains the conceptual distinction between risk assessment and risk management, as

described in the Red Book (NRC 1983); the Framework does not allow for the manipulation of

the risk assessment to support predetermined policy choices. As articulated by the NRC in the

Silver Book, “the conduct of risk

assessments used to evaluate the risk‐

management options [is] in no way to

be influenced by the preferences of

risk managers” (NRC 2009, 244). For

more information from the Silver Book

see Text Box 2‐15.

Text Box 2‐15: More Silver Book Statements on

Utility

• “Risk assessment in EPA is not an end in itself but a

means to develop policies that make the best use of

resources to protect the health of the public and of

ecosystems“(NRC 2009, 240).

• “By focusing on early and careful problem

formulation and on the options for managing the

problem, implementation of the framework can do

much to improve the utility of risk assessment.

Indeed, without such a framework, risk assessments

may be addressing the wrong questions and yielding

results that fail to address the needs of risk

managers“(NRC 2009, 244).

It is important to note that the

uses of any risk assessment will vary

with the environmental problem being

assessed; statutory mandates; and the

limitations of data, methods, time and

resources. Further, as recognized in

Section 5, risk assessments often are

just one of a variety of factors that are

considered in making a decision.  

   

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3 Risk Assessment

Risk assessments conducted for the EPA range from relatively simple to complex

depending on needs of the risk management decision being made and the availability of

relevant data. The analyses that contribute to a risk assessment may range from those based on

default assumptions to more refined analyses that include site‐specific information and

quantitative uncertainty assessment consistent with agency policies and guidances (U.S. EPA

1992a, 2005a, 2011a). Planning and scoping identifies the level of assessment appropriate for

the needs of the risk manager and the role that risk information plays in the decision. Problem

formulation uses this information to develop the conceptual model and analysis plan. The

assessment step builds on the conceptual model and implements the analysis plan. The steps in

risk assessment often are performed together, in an integrative fashion, rather than as a linear,

sequential process. As information is developed and preliminary conclusions drawn, it is not

uncommon to revisit data needs or to revise the conceptual model and analysis plan.

Communication among all members of the risk assessment team (and perhaps with

stakeholders) is needed to ensure that the purpose of the assessment remains the major

impetus for these revisions to plans and expectations.

The EPA has issued guidance on all four steps of the risk assessment paradigm (exposure

assessment, hazard identification, dose response and risk characterization); note that these

publications are highlighted in Section 2. This Framework document focuses on context, utility

and planning for the risk assessment itself, so it does not provide detail on the conduct of the

steps.

EPA risk assessments may focus on individual risk metrics or may include population‐

level and/or life stage‐specific assessments to inform characterization of risk. Different

categories of assessments may be conducted by the agency related to the specific types of

regulatory or programmatic decisions they are developed to inform. The agency’s Risk

Assessment Portal (U.S. EPA 2012i) provides basic information about environmental risk

assessments and offers a comprehensive set of links to key EPA tools, guidance and guidelines.  

Figure 3‐1 highlights the assessment phase in the Framework detailing several cross‐

cutting areas for consideration in exposure or effects characterization. The risk assessor might

consider available data on metabolism; modeling; mode of action; toxicity; cumulative risk

(exposure and/or effects); the susceptibility of individuals based on factors such as life stage,

genetics and gender; specific population group factors including socio‐economic considerations,

uncertainty and variability; and other factors relevant to characterization of risk (see Text Boxes

3‐2 and 3‐3 ). The landscape of risk assessment is changing with new advances in molecular

biology, computational toxicology and risk assessment methodology. The areas of consideration

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noted in Figure 3‐1 are meant to be illustrative of today’s practices, rather than definitive or

comprehensive, and they are likely to change as the science of risk assessment advances.  

3.1 Exposure Assessment

Exposure characterization is one of the primary components of risk assessment. The

approaches employed for this component may vary across different risk assessments and will

reflect considerations described in the conceptual model and analysis plan.  

Exposure is characterized, quantitatively or qualitatively, for several key aspects of the

assessment: relevant routes and pathways, frequency and duration, and populations and life

stages. The specific type of exposure estimation needed and the level of complexity employed

for this component of the assessment will vary depending on the assessment purpose, legal

authority and other factors considered in the planning and scoping step. For example, this step

may involve new data collection, implementation of simple or complex fate/

transport/exposure models and/or other data analysis. A key aspect of all exposure

characterizations is consideration of the potential for susceptible or more highly exposed

populations, life stages or groups. Based on considerations and decisions in the conceptual

model, quantitative exposure assessments may include the development of estimates specific

to these populations or life stages. The available toxicokinetic information may also be

characterized and internal doses calculated.  The EPA’s Exposure Factors Handbooks provide a

compendium of exposure factors for a number of parameters for adults and children, including

such metrics as ingestion of soil, time spent in residence, surveys of fish ingestion, ingestion of

homegrown products and inhalation rates (U.S. EPA 1997b, 2008a, 2011a). Available

toxicokinetic information also may be characterized and internal doses calculated. Some key

elements of exposure characterizations are listed in the Text Box 3‐1.

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Figure 3‐1. Framework for Human Health Risk Assessment to Inform Decision Making: Key

Questions and Considerations for Assessment.  

3.2 Effects Assessment

In human health risk assessment, the characterization of effects includes hazard

identification and dose‐response assessment. The approaches employed for these components,

including, for example, the level of detail and complexity of quantitative aspects, may vary

across different risk assessments and will reflect considerations described in the conceptual

model and analysis plan.

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3.2.1 Hazard Identification

Text Box 3‐1: Key Elements of an Exposure Characterization

• Assess sources, pathways and routes of exposure and determine approach for consideration

of multiple pathways, as relevant.

• Investigate patterns of exposure (e.g., frequency and duration).

• Assess populations and life stages (e.g., the general population, highly exposed/vulnerable

groups, highly susceptible groups) and determine basis for inclusion.

• Consider the rationale for the analysis approach, including any monitoring, modeling or other

analyses of exposure distributions such as Monte‐Carlo or krieging.  

• Establish descriptors of exposure, generally including estimates for “average” and “high‐end”

exposures and susceptible populations or life stages.  

• Determine data and methods used in developing the exposure estimates.  

Drawn from EPA’s Guidance for Risk Characterization (U.S. EPA 1995d) and Guidelines for Exposure

Assessment (U.S. EPA 1992a).  

Hazard Identification is the process of identifying the type of hazard to human health

(e.g., cancer, birth defects) posed by the exposure of interest for a given risk assessment. In the

case of chemical stressors, the process examines the available scientific data for a given

chemical (or group of chemicals) and often develops a “weight of evidence” characterization of

hazard. This step requires identification, evaluation and synthesis of information to describe the

health effects of individual chemicals (or chemical mixtures). Studies evaluated may include

human clinical or epidemiological studies, in vivo or in vitro laboratory animal studies, or

mechanistic or kinetic studies in a variety of test systems. In recent years, risk assessors have

begun to consider additional types of data during hazard identification including those from

computational toxicology (quantitative structure‐activity relationship, high‐throughput assays)

and transcriptional or “omic” responses. Other data types may be identified in the future. Key

aspects of hazard identification include consideration of available information on toxicokinetics

(how the body absorbs, distributes, metabolizes and eliminates chemicals) and toxicodynamics

(effects that chemicals have on the body) as well as potential MOAs (or toxicity pathways)

related to the health effects identified. Text Box 3‐2 describes some contexts in which MOA of

the adverse outcome pathway is considered.  

In hazard identification, the strengths and limitations of the data and information used

to support the weight of evidence are described, including areas for which data may be

unavailable (data gaps). In situations where a quantitative risk assessment is to be performed, a

particular study or group of studies may be identified for use in dose‐response assessment.  

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Text Box 3‐2: Example of a Consideration for Effects Characterization: Mode of Action

The Guidelines for Carcinogen Risk Assessment (U.S. EPA 2005a) emphasizes the important contribution that

understanding a chemical’s MOA makes to informed risk assessment decisions. These can include:  

• Relevance of data (e.g., animal, in vitro, in silico) for human health risk assessment.

• Harmonization of risk assessments for various health endpoints.

• Conditions under which an agent is likely to cause cancer (or some other health endpoint).

• Choice of low dose extrapolation (e.g., linear or nonlinear).

• In cancer assessments, applicability of default age‐dependent adjustment factors for early life stage

exposure.  

The carcinogen guidelines and supplemental guidance (U.S. EPA 2005a, 2005b) include a framework for assessing

available data to determine whether a hypothesized MOA is likely to be involved in induction of a specific tumor

type. This framework also is useful for assessment of other health endpoints. For an example of application of the

MOA framework to reproductive effects see the Office of Pesticide Program’s work on the pesticide cacodylic acid

(U.S. EPA 2012l).  

Although the scientific community historically has been invested in understanding how chemicals cause biological

effects, the use of detailed information on MOA in human health risk assessment has been increasing as methods

are refined and more reliable information is generated. Recognizing the critical role in risk‐based decision making

of understanding how a chemical causes effects, Toxicity Testing in the 21st Century (NRC 2007) proposed that

the next generation of toxicology studies be designed to focus on “toxicity pathways.” These are normal

biological pathways that respond to chemicals or other stressors depending on the magnitude of the insult (dose,

timing, duration and frequency of perturbation). At low exposures, some systems will remain within their

homeostatic limits. At higher levels of stress, other adaptive biologic responses may occur, the adversity of which

may depend on physiological characteristics of those exposed; that is, groups of sensitive individuals may respond

adversely, whereas others may not. At greater magnitude of stress, the adaptive capacity may be overwhelmed

for all groups, increasing the likelihood of adverse effects. These and similar concepts may provide approaches for

applying greater scientific understanding of what a chemical does in causing an effect. This knowledge in turn will

support improved human health risk assessments.

The availability of data for these types of detailed assessments varies widely across chemicals. Accordingly the

EPA and the NRC continue to support the use of default methods and procedures to complete a risk assessment

when data are lacking.

Adverse Outcome Pathway: A description of plausible causal linkages that illustrates how a chemical interaction

with a biological system at the molecular level causes biological effects at the subcellular, cellular, tissue, organ

and whole animal levels of observation (Ankley et al. 2010).

Adverse Outcome Pathway: A description of plausible causal linkages that illustrates how a chemical interaction

with a biological system at the molecular level causes biological effects at the subcellular, cellular, tissue, organ

and whole animal levels of observation (Ankley et al. 2010).

Toxicity Pathways: Cellular response pathways that, when sufficiently perturbed, are expected to result in

adverse health effects (NRC 2007).

Toxicity Pathways: Cellular response pathways that, when sufficiently perturbed, are expected to result in

adverse health effects (NRC 2007).

Mode of Action: The sequence of key events and cellular and biochemical events (measurable parameters),

starting with the interaction of an agent with the target cell or tissue, through functional and anatomical changes,

resulting in cancer or other adverse health effects (U.S. EPA 2005a, Boobis et al. 2008). Mode of action differs

from mechanism in that the latter implies a more detailed understanding of the molecular basis of

the toxic effect (Seed et al. 2005).

Mode of Action: The sequence of key events and cellular and biochemical events (measurable parameters),

starting with the interaction of an agent with the target cell or tissue, through functional and anatomical changes,

resulting in cancer or other adverse health effects (U.S. EPA 2005a, Boobis et al. 2008). Mode of action differs

from mechanism in that the latter implies a more detailed understanding of the molecular basis of

the toxic effect (Seed et al. 2005).

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Hazard identification may be focused on health risks of exposure to specific individual

chemicals or identification of groups of chemicals with common MOAs (e.g., pesticides). In

some cases, the specific chemicals for such focus are identified by statute (e.g., the CAA

hazardous air pollutants). Thus the chemical exposures to be evaluated in the risk assessment

may vary across programs depending on the legal authorities under which the assessment is

conducted. In all cases the conceptual model and analysis plan will specify the extent, content

and limits of the hazard identification.  

3.2.2 Dose­Response Assessment  

In this component of effects characterization, the relationship between exposure or

dose of a contaminant and the occurrence of particular health effects or outcomes is assessed.

Drawing from the conceptual model and analysis plan, the dose‐response assessment (U.S. EPA

2012j) may be developed using a combination of data, science policy decisions and models. For

example, the response assessed may be incidence of some endpoint or health outcome (e.g.,

cancer incidence, incidence of a critical effect, hospital admission for a specific outcome or

death) or it may describe magnitude of response (e.g., magnitude of IQ loss). The assessment

also may include the derivation of an established metric such as EPA’s reference doses and

reference concentrations (U.S. EPA 2002e).  

In documentation of the dose‐response assessment, aspects of the full database,

particularly the key studies, are described along with their strengths and weaknesses, including

the potential impact of those weaknesses on the reliability of the overall assessment.

Toxicokinetic information also is described; in data‐rich situations, measured or modeled target

tissue dose may be used in the dose‐response calculations. In some cases, multiple chemicals

may be included in a single dose‐response assessment, with decisions made about the grouping

of chemicals, as well as the means by which the chemicals will be combined (e.g., common

MOA, common toxic effect, estimation of cancer potency factors, specific data for chemical

mixtures or likelihood of simultaneous exposure). Decisions on these issues are specific to the

individual risk assessment and may be influenced by the information gathered during problem

formulation. Details of the EPA practices and policies related to dose‐response assessment can

be found in the various guidance documents noted in Section 2 of this document and at EPA’s

Risk Assessment Guidance and Tools webpage (U.S. EPA 2012k).

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3.3 Risk Characterization

Risk characterization is the final, integrative step of risk assessment. The agency’s

Science Policy Council Handbook: Risk Characterization (U.S. EPA 2000b) describes risk

characterization as the step that “integrates information from the preceding components of the

risk assessment and synthesizes an overall conclusion about the risk that is complete,

informative, and useful for decision makers” (U.S. EPA 2000b, 10). The handbook further notes

that a risk characterization is judged by the extent to which it achieves principles of

transparency, clarity, consistency and reasonableness (TCCR). (See Text Box 3‐3 for descriptions

of TCCR.) The handbook recommends that these TCCR principles be applied in all stages of the

risk assessment, from planning and scoping through the conduct of the risk assessment, and in

all communication and documentation of the assessment.

Text Box 3‐3: Transparency—Clarity—Consistency—Reasonableness in the Risk

Characterization Handbook (U.S. EPA 2000b)

• Transparency “provides explicitness in the risk assessment process. It ensures that any

reader understands all the steps, logic, key assumptions, limitations, and decisions in the

risk assessment, and comprehends the supporting rationale that led to the outcome.”  

• Clarity “refers to the risk assessment product(s). Making the product clear makes the

assessment free from obscurity and easy to understand by all readers inside and outside of

the risk assessment process.”  

• Consistency “provides a context for the reader and refers to the presentation of the

material in the risk assessment. For example, are the conclusions of the risk assessment

characterized in harmony with relevant policy, procedural guidance, and scientific

rationales and if not, why the conclusions differ. Also, does the assessment follow

precedent with other EPA actions or why not. Consistency, however, should not encourage

blindly following the guidance for risk assessment and characterization at the expense of

stifling innovation.”  

• Reasonableness “refers to the findings of the risk assessment in the context of the state‐of‐

the science, the default assumptions and the science policy choices made in the risk

assessment. It demonstrates that the risk assessment process followed an acceptable,

overt logic path and retained common sense in applying relevant guidance. The

assessment is based on sound judgment.”  

Risks can be expressed qualitatively or quantitatively for the exposure pathways of

interest. A risk characterization conveys the nature and presence or absence of risks in

qualitative or quantitative terms. In addition, it describes information on how the risks were

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assessed, where assumptions and uncertainties still exist and where policy choices will need to

be made.  

In describing the nature and magnitude of risk for the assessed condition, the risk

characterization describes the universe of people who may be affected, including sensitive

and/or susceptible life stages or populations. These life stages and/or populations (e.g.,

potentially at‐risk groups) are first considered in the planning and scoping phases and may be

explicitly evaluated in the risk assessment. Text Box 3‐4 presents details on characterizing

cancer risk from early life exposures. Additionally, in consideration of highly exposed or

susceptible life stages and/or populations, risk characterizations generally present multiple risk

descriptors (e.g., high end and central tendency) and may include risk descriptors (e.g.,

maximum exposed individual, reasonable maximum exposure and central tendency) specific to

underlying legislative requirements (e.g., CERCLA, CAA, CWA) (U.S. EPA 1995d).  

Text Box 3‐4: Characterizing Cancer Risk from Early

Life Exposure

When assessing cancer risk resulting from early‐life

exposures, the risk assessor considers life stage

differences in both exposure and dose‐response. The

Guidelines for Carcinogen Risk Assessment (U.S. EPA

2005a) and EPA’s Supplemental Guidance for Assessing

Susceptibility from Early‐Life Exposure to Carcinogens

(U.S. EPA 2005b), provide guidance in this regard. The

preferred approach is the calculation of life‐stage

specific slope factors and use of life‐stage specific

exposure information when this is supported by data.

In the absence of sufficient data, age‐dependent

adjustment factors (ADAFs) in dose response (i.e.,

slope factors) are combined with age‐specific exposure

estimates when assessing cancer risks for chemicals

determined to act through a mutagenic MOA. This

integrative approach is used to assess total lifetime risk

resulting from lifetime or less‐than‐lifetime exposure

during a specific portion of a lifetime.

In risk characterization, information about uncertainty and variability (defined in Text

Box 2‐14) from each step of the risk assessment (e.g., use of default parameters, choice of

models and data used for quantitative analysis) is integrated into an overall discussion/analysis

of the impact of the uncertainty

and variability on estimated risks.

The EPA endeavors to ensure that

risk is not underestimated when

data are missing by using several

techniques. The EPA may

characterize uncertainty using a

qualitative assessment of the

overall strength and limitations of

the data used in the assessment.

To estimate the effect of data

uncertainty on modeled pollutant

impacts, various modeling tools

may be employed. It should be

noted that even the

quantification of uncertainty and

variability in probabilistic risk

assessments itself includes an

element of additional

uncertainty. It is important that

the level and type of uncertainty

analysis be commensurate with

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the decision to be made, in the context of the resources needed to refine such estimations. For

example, highly detailed quantitative uncertainty analyses may not be warranted for some

decisions while they might be useful for others.  

Communicating the results of probabilistic risk assessment requires particular attention.

Probabilistic risk assessments provide range and likelihood estimates for one or more aspects of

hazard, exposure or risk, rather than a single point estimate (U.S. EPA 2005e, 2010c). A goal of

probabilistic risk assessment is the quantitative characterization of the uncertainty and

variability in estimates of hazard, exposure, or risk (U.S. EPA 1997c). Risk assessors are

responsible for sharing information on probabilistic results so that risk managers have a clear

understanding of quantitative assessments of uncertainty and variability and how this

information will affect the risk management decision. A good dialogue between the risk

assessor and risk manager is key in aiding the risk manager’s understanding and use of the

results from the probabilistic risk assessment.

Areas of uncertainty that may make a difference in the outcome of the assessment (and

thus on informing choices among risk management options) are highlighted in the risk

characterization. For example, the risk characterization document includes a discussion of any

issues associated with the data quality (e.g., reliability and availability) that may impact the

calculated risks or other metrics. This may include explicit discussions of the evaluation process

and description of issues that may impact the reliability or utility of the endpoints identified for

use. A key question addressed in the risk characterization is whether the risk assessment

outcome would change significantly if data were interpreted differently or if different models

were used. This kind of uncertainty is difficult or impossible to characterize probabilistically. It is

essential, however, to describe uncertainty and variability so that the impact will not be

overlooked or misinterpreted. It may be useful to revisit the analysis plan if it is concluded that

gathering additional information will have a substantive impact on reducing uncertainty in the

assessment.  

The risk characterization step maintains and emphasizes the distinction between

scientific conclusions and policy judgments, which may include science policy choices such as

assumptions, default procedures and default values. In risk characterization, the assessor also

can usefully describe other policy considerations, such as calculating monetizable health

benefits under certain statutes or the lack of relevance of such calculations under other

statutes. Additional details on key information is presented in the agency’s Science Policy

Council Handbook: Risk Characterization (U.S. EPA 2000b) and the Policy for Risk

Characterization (U.S. EPA 1995a). Figure 3‐1 highlights the details of risk characterization in the

Framework.

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Text Box 3‐5 describes cumulative risk assessment (an overarching EPA interest) as a

consideration for risk characterization.  

   

Text Box 3‐5: Considerations for Risk Characterization: Cumulative Risk Assessment

Cumulative risk assessments may differ in design and associated results. Examples of Cumulative risk

assessment at the EPA include:  

Office of Pesticide Programs’ evaluation of cumulative risk (U.S. EPA 2012m) according to the Food

Quality Protection Act of 1996. Some texts include:  

• Guidance for Performing Aggregate Exposure and Risk Assessments (U.S. EPA 1999b)

• General Principles for Performing Aggregate Exposure and Risk Assessments. (U.S. EPA 2001b)

• Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common

Mechanism of Toxicity (U.S. EPA 2002d)

The Office of Air and Radiation’s assessment of hazardous air pollutant risks remaining after

implementation of technology‐based emissions standards (U.S. EPA 2011l)

The Office of Environmental Justice’s Ensuring Risk Reduction in Communities with Multiple Stressors:

Environmental Justice and Cumulative Risks/Impacts (U.S. EPA 2004f)

Region 3’s “Multi‐criteria Integrated Resource Assessment (MIRA)” (U.S. EPA 2011m)

Additionally, two NRC publications, Science and Decisions: Advancing Risk Assessment (NRC 2009) and

Phthalates and Cumulative Risk Assessment: The Tasks Ahead (NRC 2008), describe approaches to

consider in the practice of cumulative risk assessment. For example, Phthalates and Cumulative Risk

Assessment discusses the advantages of focusing on physiologic consequences rather than structural or

mechanistic similarity in conducting cumulative risk assessment as this is more directly relevant to

relating chemical exposures to human diseases and disorders. Science and Decisions discusses the

importance of considering nonchemical stressors and background processes in cumulative risk

assessment.

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4 Public, Stakeholder and Community Involvement

As discussed in Planning and Scoping (Section 2.1), public, stakeholder and community

involvement are key elements of the Framework throughout all phases of the risk assessment.

Figure 4‐1 highlights key questions and considerations for stakeholder involvement. As

indicated in the figure, public, stakeholder and community involvement are considered early

and often in the risk assessment and decision making process. Although the single term

“public” could be used to include the full range of external stakeholders, including community

members, this document specifically includes all three terms in recognition of differences in

what they each may convey to different readers and also in recognition of roles played by

internal stakeholders (see Text Box 2‐7 for definitions).  

Figure 4‐1. Framework for Human Health Risk Assessment to Inform Decision Making: Key

Questions and Considerations for Public, Stakeholder and Community Involvement.  

Public participation is an essential aspect of the EPA’s process for making decisions to

achieve the agency’s mission of protecting human health and the environment. This provides

the EPA with the opportunity to obtain and consider a range of views on the issue being

assessed as well as on management options. Effective public involvement (including key

stakeholders and/or communities) can enhance the deliberative process and improve the

content of the agency’s decisions (U.S. EPA 2003c), which is consistent with sustainability

principles. A critical feature of the Framework is the involvement of the public, stakeholders

and communities at key points in the process. The timing/frequency and level of community

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involvement will depend on a number of factors, including regulatory requirements, the nature

of the decision and community interest.

As discussed in Section 2.1.5, public involvement may begin when individuals and

organizations seek information from the EPA about a topic or issue or when the public receives

information from the EPA because the agency identifies them as a potentially affected party.

The EPA’s outreach activities serve and engage these individuals and organizations (U.S. EPA

2003c).  

Each decision or action by the agency may call for a different level of public

involvement, and certain members of the public, stakeholders or communities may need to be

involved at different steps in the risk assessment process. The EPA’s Public Involvement Policy

(U.S. EPA 2003c, 1) states that, “EPA staff and managers should seek input reflecting all points

of view and should carefully consider this input when making decisions.” In addition, the policy

(U.S. EPA 2003c, 1) states that, “EPA should not accept any recommendation or proposal

without careful, critical examination.”

The overall goal of public involvement is to provide opportunities for people to

contribute at every point along the progression of the decision making process. Individuals and

groups decide for themselves whether, when and how to participate. It is recognized that not

everyone who is interested in the situation being assessed chooses to be an active participant

in providing input (e.g., facts, data and opinions) to policy or regulatory decisions of the agency.

The information provided through the public involvement process is considered by the agency’s

officials in the decision making process.  

4.1 Audiences for the Risk Assessment  

If properly planned and executed, the technical risk characterization itself will be

consistent with the level of detail and complexity of the assessment conducted. The

information presented may vary by regulatory and audience needs, however. Co‐regulators

such as states and tribal nations also are audiences for the risk assessments; these groups may

prefer a high level of technical detail in communication of an assessment. Several statutes and

executive orders affect the development of regulatory rules and other EPA decisions and may

define specific activities for public, stakeholder and community involvement. In addition,

several programs have developed specific guidance on public involvement (Dalton and Harter

2009) (variously termed public, stakeholder and community involvement), and these guidance

documents are listed in Text Box 4‐1.

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4.1.1 Stakeholders

Text Box 4‐1: EPA Resources for Public Involvement Efforts, Tools and Policies

Public Involvement

• The Model Plan for Public Participation (U.S. EPA 2000c)  

• EPA’s Public Involvement Webpage (U.S. EPA 2011b)

• Pesticide Program Dialogue Committee: This Committee provides a forum for a

diverse group of stakeholders to provide feedback to the pesticide program on

various pesticide regulatory, policy and program implementation issues. (U.S. EPA

2011c)

Community Involvement

• EPA’s Superfund Community Involvement Plans (U.S. EPA 2002f)

• EPA’s Superfund Community Involvement Handbook (U.S. EPA 2005d)

• EPA’s Superfund Community Involvement Publications Webpage (U.S. EPA 2011d)

Risk Communication

• EPA’s Guidance for Assessing Chemical Contaminant Data for Use in Fish

Advisories, Volume IV: Risk Communication (U.S. EPA 1995b)

• Lessons Learned About Designing, Developing and Disseminating Environmental

Information Products (U.S. EPA 2000e)

• EPA’s Risk Communication In Action: The Risk Communication Workbook (U.S. EPA

2007a)

• EPA’s Risk Communication in Action: The Tools of Message Mapping (U.S. EPA

2007b)

• Sustainability and the U.S. EPA (NRC 2011)

The appropriate stakeholder involvement process will depend on the specifics of the

situation. Stakeholder involvement processes are highly adaptive and can be modified to take

changing circumstances into account. Additional details are found in Better Decisions Through

Consultation and Collaboration (Dalton and Harter 2009).  

Staff and management of EPA offices are important internal stakeholders in the process

of drafting rules, policies, permits or plans. The planning process considers inclusion of internal

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stakeholders in establishing the project. Three key considerations include involving

stakeholders early, obtaining “buy‐in” along the way and keeping stakeholders engaged.  

Communication with stakeholders outside the agency may vary depending on

regulatory requirements. For example, regulatory and non‐regulatory activities in the Office of

Chemical Safety and Pollution Prevention provide mechanisms to interact with stakeholders

while the EPA is developing the assessments. During the review of premanufacture notices

(PMNs) for new substances, the EPA Program Manager or other EPA personnel may contact the

submitter for additional information if the EPA identifies concerns or needs clarification of

technical information provided in the PMN. Rules issued under TSCA §5 (i.e., Significant New

Use Rules) and §6 (e.g., formaldehyde) provide a notice and comment period in the Federal

Register allowing public involvement in the Office of Pollution Prevention and Toxics’ (OPPT)

rulemaking actions (e.g., Proposed Significant New Use Rule for Multiwalled Carbon Nanotubes

[U.S. EPA 2010e] and Formaldehyde Emissions From Pressed Wood Products [U.S. EPA 2008b).

Public meetings are scheduled in different parts of the United States to increase public

involvement in the rulemaking process. Under the High Production Volume (HPV) Challenge

Program, OPPT posts notice of and links to data summaries and test plans for HPV chemicals

(U.S. EPA 2012n) and provides a 120‐day public comment period. The Office of Pesticide

Programs provides multiple opportunities for public comment and involvement in its

registration review program—at the opening of the process for a chemical on the Preliminary

Work Plan, on the draft risk assessment and on proposed regulatory actions.

Another example of stakeholder involvement is the IRIS process (U.S. EPA 2012o), which

provides multiple opportunities for stakeholder involvement. The process includes a call for

nominations that allows stakeholders to nominate chemicals for assessment through the IRIS

Program that includes a description why the chemical(s) should be considered for assessment.

Multiple opportunities for review and comment occur during the development of the health

hazard assessments. For example, the IRIS process includes a step that provides for review by

other offices within the EPA (agency review) and two opportunities for interagency science

consultation and discussion, which enable other federal agencies to comment on the

assessment. Finally, during the period of public review and comment, any interested member

of the public may comment on the assessment; there also is a public listening session in which

any stakeholder or member of the public has the opportunity to speak about the assessment.  

4.1.2 Community

Community involvement may be a component of the stakeholder involvement process,

particularly in cases in which the issue assessed relates to a specific location  

(e.g., decisions regarding contaminated waste sites or facilities with environmental releases).

Community involvement is the process of engaging in dialogue and collaboration with

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community members who may be directly impacted by the risk assessment. For example, in the

Superfund Program (U.S. EPA 2011h), the goal of community involvement is to advocate and

strengthen early and meaningful community participation during the investigation, while

conducting the risk assessment and during the decision making process (see EPA’s Public

Involvement Webpage; U.S. EPA 2011b).

4.2 Communication

Successful communication begins early in the risk assessment process during planning

and scoping and problem formulation (see Section 2.1.5) and has a pivotal role throughout the

process. As the Silver Book (NRC 2009, 250) points out, “communication among those involved

in the policy and technical evaluations are [sic] difficult to achieve, but they are necessary for

success.” Communication of risk may be challenging as a result of the complexity of the

information being conveyed, the inherent uncertainty in risk estimates and the varying needs of

the audiences (e.g., scientists, risk managers, various stakeholders, the media and the general

public). The Silver Book (NRC 2009, 66) recognized this issue, stating “... the critical final process

in risk assessment is ultimately communication.”  

Risk communication begins with understanding the risk characterization portion of the

risk assessment. Risk characterization is an integral part of a risk assessment and summarizes the

key findings and the strengths and weaknesses of the assessment for risk managers and others.

Although it provides information that may be useful for communicating with the public, risk

characterization is not synonymous with risk communication.

Risk communication emphasizes the process of providing information to the public,

including individuals, groups and other institutions, about levels of health or environmental risks.

Risk communication is used for such things as information and education, behavior change and

protective action, disaster warnings and emergency information, and joint problem solving.

Although the final risk assessment documentation (including the risk characterization) can be used

to communicate with the public, the risk communication process is probably better served by a

separate set of documents designed for particular audiences.

Risk communication tools are written, verbal or visual statements containing

information about risk. These tools put a particular risk in context, possibly adding comparisons

with other risks, often including advice about risk reduction behavior. Risk communications also

can encourage a dialogue between the sender and receiver of the message (U.S. EPA 2007a). In

general, the communication tools should be concise and provide adequate information for the

user but not at the level of detail provided in the risk characterization. In addition, care is

required to assure that the risk information is consistent with the data provided in the risk

characterization and includes risk assessment results, the strengths and limitations of the

analysis, and how they will be used by risk mangers.

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Risk communication documents need to consider the audience for the information. For

example, risk managers generally prefer not to receive the depth of detail found in the

technical risk characterization. The usual products prepared from the risk characterization for

risk managers often provide a summary and can take various forms depending on specific

needs (e.g., executive summary, bulleted list of key issues and conclusions, briefing packages)

(U.S. EPA 2000b). Risk characterization products prepared for the public, stakeholders and

communities can come in many forms. Generally, these communication pieces carry forward

the key issues and describe conclusions in a lay person’s context rather than a technical one

written for a scientific presentation or paper; this can include plain language definitions,

translations into appropriate languages, use of graphics as appropriate to convey information

and so on. Communication products are developed to meet the needs of the intended audience

and may include products such as fact sheets for interested public, press releases, slide shows,

public relations notices, decision documents, and speeches and talks (U.S. EPA 2000b). Text Box

4‐1 identifies resources helpful in developing a risk communication plan for various audiences.

   

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5 Informing Decisions

The final step in the risk assessment process is connecting the previously defined

purpose and scope with the conclusions and strengths/limitations of the risk assessment. The

assessments are conducted to provide a scientific characterization of risks based on analysis of

available information and knowledge that meets appropriate quality criteria. A description of

the human health risks, and characterization of the confidence in the information available to

describe the risks, supports risk management decisions. As discussed in Section 3.3, effective

risk characterization is based on transparency in conducting and explaining the risk assessment

combined with clarity, consistency and reasonableness in the preparation of the risk description

(U.S. EPA 2000b).The science supporting the risk assessment conclusions, as well as

consideration of important uncertainties, informs decisions among the risk management

options. As noted in Section 2.3, well planned, focused and conducted risk assessments will be

most useful and informative for decision making. Key questions and considerations for the

informing decisions step are shown in Figure 5‐1.

5.1 Characterizing the Risks for Risk Management Options

It is the role of the risk assessor to provide a transparent description of all aspects of the

risk assessment (e.g., default assumptions, data selected and policy choices) to make clear the

range of plausible risk associated with each risk management option. Clear communication

between the risk assessors and risk managers is vital to assuring that risk information is

conveyed appropriately.

Whatever approach is used to estimate risk, it is important to be clear in describing the

range of possible risks (e.g., risks to highly exposed individuals, average exposed individuals or

groups). For example, the extent to which the assessment may underestimate or overestimate

risk for some populations should be highlighted to inform the decision making appropriately. As

discussed in Section 3.3, these uncertainties may be characterized quantitatively (e.g., using

probabilistic methods) or qualitatively (e.g., describing how the results would change if the data

were interpreted differently). The risk assessment characterizes the nature and magnitude of

risk and who is at risk under different risk management options (including a “status quo”

option). The EPA’s policy is to describe the range of the risk and highlight susceptible

populations (U.S. EPA 1995a, 2000b).
Figure 5‐1. Framework for Human Health Risk Assessment to Inform Decision Making: Key

Questions and Considerations for Informing Decisions.  

The communication of the risk characterization will take different written and oral forms

to meet the needs of the intended audiences, including the risk managers. The level and

amount of detail in each product will vary according to the level and amount of detail of the risk

assessment that is being characterized by the product; thus, being fit for purpose. In addition, it

often will vary in format or detail for effective communication with the intended audience.

Summaries of the risk characterization may be provided to the risk managers depending on

their information needs. Key issues considered by risk managers include:

• Strengths of an assessment including the overall weight of evidence and the quality and

quantity of data supporting the hazard and/or exposure.

• Level of confidence or uncertainty in the assessment and the data underlying it.

• What are the life stages and/or populations at greatest risk?

• Information that would yield changes in the risk estimates under various candidate risk

management alternatives.

• Precedents that may inform the decision.

5.2 Risk Management Factors Beyond the Risk Assessment and

Characterization  

EPA uses risk assessment as a key source of scientific information for making sound

decisions about managing risks to human health and the environment. Risk management

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decisions, however, may be informed by a range of factors, evidence and policy choices, such as

the following:  

• Laws and Regulatory Requirements—legal mandates, flexibility and constraints.

• Economic Factors—costs, benefits and impacts of potential actions.

• Sustainability—life cycle, multimedia and long‐term impacts.

• Technological Factors—feasibility, impact and range of risk management options.

• Political Factors—interactions with different branches and levels of government and the

citizens that they represent.

• Public and Social Factors—susceptible population groups, nonchemical stressors and

cumulative risk assessment considerations.

Statutory or regulatory requirements and restrictions, including those established by

states and tribal nations, may limit decision options as the discretionary power afforded to

agencies in making regulatory decisions varies greatly. The EPA faces regulatory, licensing and

other decisions covering a wide range of environmental issues and pollutants. These decisions

are made within a number of EPA program offices, each responding to a unique mixture of

statutes, precedents and stakeholders. In statutes, Congress establishes legal requirements that

generally describe the level of protectiveness that EPA regulations must achieve, and the

statute may impose specific risk assessment requirements. In addition, court precedents can

affect how the EPA considers assessments of risk. The statutory or regulatory requirements

often also specify other kinds of factors for consideration in the risk management decision.  

   

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6 Summary

   The Framework for Human Health Risk Assessment to Inform Decision Making is

intended to foster increased implementation of existing EPA guidance for conducting human

health risk assessments and to improve the utility of risk assessment in the decision making

process. This document lays out a Framework for conducting human health risk assessments in

support of decision making at the EPA. It draws on current EPA experience in applying both the

planning and scoping and problem formulation steps as well as on the advice of the NRC (2009)

and other advisory groups. For example, the Framework addresses recommendations in the

Silver Book (NRC 2009) on assuring the utility of risk assessment or the assessments fit for

purpose (Text Box 6‐1). As indicated in the Framework diagram, Figure 6‐1, the NRC 1983 four‐

step risk assessment paradigm is maintained, but there is increased emphasis on interaction

between risk assessors and risk managers in planning the assessment to maximize utility.

Emphasis on utility is maintained throughout the process, beginning with planning and scoping

and during evaluation of the applicability of the risk assessment in informing risk management

choices. The Framework

highlights the practical

nature of risk

assessment.  For

example, although the

agency is committed to

advancing risk

assessment science,

assessments are not

academic exercises.

Rather, they are

intended to support

decision making for the

protection of human

health. Application of

the Framework, with its

emphasis on problem

formulation and utility

of the risk assessment,

ultimately will result in

better, more

transparent choices

among risk

Text Box 6‐1: The Silver Book Recommendations for a Human

Health Risk Assessment Framework  

• The technical framework for risk assessment presented in the

Red Book should remain intact but should be embedded in a

broader framework in which risk assessment is used

principally to help to discriminate among risk‐management

options (NRC 2009, 256).  

• The framework for risk‐based decision making (Figure 6‐1)

should have as its core elements a problem‐formulation and

scoping phase in which the available risk‐management

options are identified, a planning and assessment phase in

which risk‐assessment tools are used to determine risks under

existing conditions and with proposed options, and a

management phase in which risk and nonrisk information is

integrated to inform choices among options (NRC 2009, 256).  

• EPA should phase in the use of the framework with a series of

demonstration projects that apply the framework and that

determine the degree to which the approach meets the needs

of the agency risk managers, and how risk‐management

conclusions differ as a result of the revised orientation (NRC

2009, 256).

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management options. This Framework includes a foundation quite similar to that in Framework

for Ecological Risk Assessment (U.S. EPA 1992b), thus illustrating conceptual similarity between

the two types of risk assessment; however, it is not always advantageous to integrate human

health and ecological risk assessments. This Framework builds on agency policies and guidance,

and is directed at improving risk assessment products, but does not overturn or in any way

change existing science policy decisions.  

Figure 6‐1. Framework for Human Health Risk Assessment to Inform Decision Making  

EPA programs routinely apply components of this Framework for Human Health Risk

Assessment to Inform Decision Making as evidenced by the examples cited in the preceding

sections. It is expected, however, that this document will facilitate the formal recognition of

these components in agency risk assessment activities. The Framework’s explicit recognition of

the roles for planning, public, stakeholder and community involvement and consideration of

utility will assist in the development of risk assessments focused on informing risk management

decisions. Further, “institutionalization” of this Framework for Human Health Risk Assessment

to Inform Decision Making will contribute transparency to the agency’s risk assessment process

and a level of consistency across assessments, across media and programs as well as between

human health and ecological outcomes.  

The Framework is intended to be flexible. The structure will accommodate advances in

the technology and science; for example, development of life cycle analyses and use of data

from high throughput assays (those that generate data much more rapidly and for many more

chemicals than the standard toxicological assays of the 20th century). The Framework structure

is sufficiently adaptable to encompass needed changes in agency direction, developing needs

and new or revised legislative mandates.  

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References

Ankley, Gerald T., Richard S. Bennett, Russell J. Erickson, Dale J. Hoff, Michael W. Hornung,

Rodney D. Johnson, David R. Mount, John W. Nichols, Christine L. Russom, Patricia K.

Schmieder, Jose A. Serrano, Joseph E. Tietge, and Daniel L. Villeneuve 2010. “Adverse

Outcome Pathways: A Conceptual Framework to Support Ecotoxicology Research and

Risk Assessment.” Environmental Toxicology and Chemistry 29 (3): 730–741.  

Boobis, Alan R., John E. Doe, Barbara Heinrich‐Hirsch, M. E. (Bette) Meek, Sharon Munn,

Mathuros Ruchirawat, Josef Schlatter, Jennifer Seed, and Carolyn Vickers 2008. “IPCS

Framework for Analyzing the Relevance of a Noncancer Mode of Action for Humans.”

Critical Reviews in Toxicology 38 (2): 87–96.

Clay, Donald 1991. Memorandum from Donald R. Clay, Assistant Administrator. Subject: Role of

the Baseline Risk Assessment in Superfund Remedy Selection Decisions. April 22.

http://www.epa.gov/oswer/riskassessment/pdf/baseline.pdf  

Dalton, Deborah, and Philip J. Harter 2009. Better Decisions Through Consultation and

Collaboration. Prepared for the U.S. Environmental Protection Agency.

http://www.epa.gov/publicinvolvement/pdf/betterdecisions.pdf

Exec. Order No. 12898, 59 Fed. Reg. 7629 (Feb. 16, 1994).

http://www.epa.gov/lawsregs/laws/eo12898.html

Exec. Order No. 13045, 62 Fed. Reg. 19885 (Apr. 23, 1997).

http://www.epa.gov/lawsregs/laws/eo13045.html

Exec. Order No. 13514, 74 Fed. Reg. 52117 (Oct. 8, 2009).

http://www.epa.gov/oaintrnt/practices/eo13514.htm

National Research Council (NRC) 1983. Risk Assessment in the Federal Government: Managing

the Process. (The “Red Book”). National Academy of Sciences, National Research

Council, Committee on the Institutional Means for Assessments of Risk to Public Health,

Commission on Life Sciences. Washington, DC: National Academy Press.

http://www.nap.edu/openbook.php?isbn=0309033497

NRC 1994. Science and Judgment in Risk Assessment (The “Blue Book”). National Academy of

Sciences, National Research Council, Committee on Risk Assessment of Hazardous Air

Pollutants, Board on Environmental Sciences and Technology, Commission on Life

Sciences. Washington, DC: National Academy Press.

http://www.nap.edu/catalog.php?record_id=2125
EPA RISK ASSESSMENT FORUM EXTERNAL REVIEW DRAFT

62

NRC 2007. Toxicity Testing in the 21st Century: A Vision and a Strategy. Committee on Toxicity

Testing and Assessment of Environmental Agents. Washington, DC: National Academy

Press. http://www.nap.edu/catalog.php?record_id=11970

NRC 2008. Phthalates and Cumulative Risk Assessment: The Tasks Ahead. Committee on the

Health Risks of Phthalates. Washington, DC: National Academy press.

http://www.nap.edu/catalog.php?record_id=12528  

NRC 2009. Science and Decisions: Advancing Risk Assessment (The “Silver Book”). National

Academy of Sciences. Washington, DC: National Academy Press.

http://www.nap.edu/catalog.php?record_id=12209  

NRC 2011. Sustainability and the U.S. EPA. National Research Council, Committee on

Incorporating Sustainability in the U.S. Environmental Protection Agency. Washington,

DC: National Academy Press.

http://sites.nationalacademies.org/PGA/sustainability/EPA/index.htm

Office of Management and Budget 2004. Final Information Quality Bulletin for Peer Review.

Washington, DC. December 16.

http://www.whitehouse.gov/sites/default/files/omb/memoranda/fy2005/m05‐03.pdf

Presidential/Congressional Commission on Risk Assessment and Risk Management (PCCRARM)

1997a. Framework for Environmental Health Risk Management. Final Report, Volume 1.

Washington, DC: The Presidential/Congressional Commission on Risk Assessment and

Risk Management. http://www.riskworld.com/riskcommission/default.html

PCCRARM 1997b. Risk Assessment and Risk Management in Regulatory Decision‐Making. Final

Report, Volume 2. Washington, DC: The Presidential/Congressional Commission on Risk

Assessment and Risk Management.

http://www.riskworld.com/riskcommission/default.html

Seed, Jennifer, Edward W. Carney, Richard A. Corley, Kevin M. Crofton, John M. DeSesso, Paul

M. D. Foster, Robert Kavlock, Gary Kimmel, James Klaunig, M. E. Meek, R. Julian Preston,

William Slikker, Jr., Sonia Tabacova, Gary M. Williams, Jeanette Wiltse, R. Thomas

Zoeller, Penelope Fenner‐Crisp, and Dorothy E. Patton 2005. “Overview: Using Mode of

Action and Life Stage Information to Evaluate the Human Relevance of Animal Toxicity

Data.” Critical Reviews in Toxicology. 35 (8–9): 663–672.

U.S. Environmental Protection Agency (U.S. EPA) 1984. Risk Assessment and Management:

Framework for Decision Making. Washington, DC: Office of Policy, Planning and

Evaluation. EPA/600/985/002.

http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=20008KTF.txt
EPA RISK ASSESSMENT FORUM EXTERNAL REVIEW DRAFT

63

U.S. EPA 1986a. Guidelines for the Health Risk Assessment of Chemical Mixtures. Washington,

DC: Office of Research and Development. September. EPA/630/R‐98/002.

http://www.epa.gov/raf/publications/pdfs/CHEMMIX_1986.PDF

U.S. EPA 1986b. Guidelines for Carcinogen Risk Assessment. Washington, DC: Risk Assessment

Forum. September. EPA/630/R‐00/004.  

http://www.epa.gov/raf/publications/pdfs/CA%20GUIDELINES_1986.PDF

U.S. EPA 1986c. Guidelines for Mutagenicity Risk Assessment. Washington, DC: Risk Assessment

Forum. September. EPA/630/R‐98/003.

http://www.epa.gov/raf/publications/pdfs/MUTAGEN2.PDF  

U.S. EPA 1987. The Risk Assessment Guidelines of 1986. Washington, DC: Office of Health and

Environmental Assessment. August. EPA/600/8‐87/045.

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=29777#Download  

U.S. EPA 1988. Guidance for Conducting Remedial Investigations and Feasibility Studies Under

CERCLA. Washington, DC: Office of Solid Waste and Emergency Response, Office of

Emergency and Remedial Response. October. EPA/540/G‐89/004.

http://www.epa.gov/superfund/policy/remedy/pdfs/540g‐89004‐s.pdf

U.S. EPA 1989. Risk Assessment Guidance for Superfund: Volume 1, Human Health Evaluation

Manual (Part A). Washington, DC: Office of Emergency and Remedial Response.

December. EPA/540/1‐89/002.

http://www.epa.gov/oswer/riskassessment/ragsa/pdf/rags_a.pdf (Also see Parts B–D.)

U.S. EPA 1991a. Role of the Baseline Risk Assessment in Superfund Remedy Selection Decisions.

Memorandum from Agency Assistant Administrator for Solid Waste and Emergecny

Response, Donald R. Clay, Washington, DC. April 22.

U.S. EPA 1991b. Guidelines for Developmental Toxicity Risk Assessment. Washington, DC: Risk

Assessment Forum. EPA/600/Federal Register‐91/001.  

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=23162  

U.S. EPA 1992a. Guidelines for Exposure Assessment. Washington, DC: Risk Assessment Forum.

EPA/600/Z‐92/001. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=15263  

U.S. EPA 1992b. Framework for Ecological Risk Assessment. Washington, DC: Risk Assessment

Forum. EPA/630/R‐92/001. http://www.epa.gov/raf/publications/framework‐eco‐risk‐

assessment.htm

U.S. EPA 1994. Methods for Derivation of Inhalation Reference Concentrations (RfCs) and

Application of Inhalation Dosimetry. Washington, DC: Office of Research and
EPA RISK ASSESSMENT FORUM EXTERNAL REVIEW DRAFT

64

Development, Office of Health and Environmental Assessment. EPA/600/8‐90/066F.

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=71993  

U.S. EPA 1995a. Policy for Risk Characterization. Memorandum from Agency Administrator

Carol M. Browner, Washington, DC. March 21.

http://www.epa.gov/spc/pdfs/rccover.pdf

U.S. EPA 1995b. Guidance for Assessing Chemical Contaminant Data for Use in Fish Advisories,

Volume IV: Risk Communication. Washington, DC: Office of Water. March. EPA/823/R‐

95/001.

http://water.epa.gov/scitech/swguidance/fishshellfish/techguidance/guidance.cfm

U.S. EPA 1995c. Policy on Evaluating Health Risks to Children. Memorandum from Agency

Administrator Carol M. Browner, Washington, DC. October 20.

http://www.epa.gov/spc/2poleval.htm

U.S. EPA 1995d. Guidance for Risk Characterization. Washington, DC: Science Policy Council.

http://www.epa.gov/spc/pdfs/rcguide.pdf  

U.S. EPA 1996. Guidelines for Reproductive Toxicity Risk Assessment. Washington, DC: Risk

Assessment Forum. EPA/630/R‐96/009.

http://www.epa.gov/raf/publications/guidelines‐reproductive‐tox‐risk‐assessment.htm  

U.S. EPA 1997a. Guidance on Cumulative Risk Assessment, Part 1. Planning and Scoping.

Washington, DC: Science Policy Council. Attachment to memo dated July 3, 1997 from

the Administrator, Carol Browner, and Deputy Administrator, Fred Hansen, titled

“Cumulative Risk Assessment Guidance—Phase I Planning and Scoping.”

http://www.epa.gov/OSA/spc/2cumrisk.htm

U.S. EPA 1997b. Exposure Factors Handbook (Final Report). Washington, DC: Office of Research

and Development, National Center for Environmental Assessment. August. EPA/600/P‐

95/002Fa. http://www.epa.gov/ncea/pdfs/efh/front.pdf

U.S. EPA 1997c. Guiding Principles for Monte Carlo Analysis. Washington, DC: Risk Assessment

Forum. EPA/630/R‐97/001. http://www.epa.gov/ncea/pdfs/montcarl.pdf

U.S. EPA 1998a. Guidelines for Ecological Risk Assessment. Washington, DC: Risk Assessment

Forum. EPA/630/R‐95/002F. http://www.epa.gov/raf/publications/pdfs/ECOTXTBX.PDF

U.S. EPA 1998b. Guidelines for Neurotoxicity Risk Assessment. Washington, DC: Risk Assessment

Forum. EPA/630/R‐95/001F. http://www.epa.gov/raf/publications/pdfs/NEUROTOX.PDF

U.S. EPA 1999a. Risk Assessment Guidance for Superfund (RAGS) Volume 3—Part A: Process for

Conducting Probabilistic Risk Assessment). Draft. Washington, DC: Office of Solid Waste
EPA RISK ASSESSMENT FORUM EXTERNAL REVIEW DRAFT

65

and Emergency Response. December.

http://www.epa.gov/oswer/riskassessment/rags3adt/

U.S. EPA 1999b. Guidance for Performing Aggregate Exposure and Risk Assessments.

Washington, DC: Office of Pesticide Programs. November.

http://www.epa.gov/scipoly/sap/meetings/1999/february/guidance.pdf

U.S. EPA 1999c. Residual Risk Report to Congress. Research Triangle Park, NC: Office of Air

Quality Planning and Standards. March. EPA/453/R‐99/001.

http://www.epa.gov/ttncaaa1/t3/reports/risk_rep.pdf

U.S. EPA 2000a. Supplementary Guidance for Conducting Health Risk Assessment of Chemical

Mixtures. Washington, DC: Risk Assessment Forum. August. EPA/630/R‐00/002.

http://www.epa.gov/ncea/pdfs/chem_mix/chem_mix_08_2001.pdf

U.S. EPA 2000b. Science Policy Council Handbook: Risk Characterization. Washington, DC:

Science Policy Council. EPA/100/B‐00/002. http://www.epa.gov/spc/pdfs/rchandbk.pdf

U.S. EPA 2000c. The Model Plan for Public Participation. Washington, DC: Office of Enforcement

and Compliance. February. EPA/300/K‐00/001.

http://www.epa.gov/compliance/ej/resources/publications/nejac/model‐public‐part‐

plan.pdf

U.S. EPA 2000d. Methodology for Deriving Ambient Water Quality Criteria for the Protection of

Human Health. Washington, DC: Office of Water. EPA/822/B‐00/004.

http://water.epa.gov/scitech/swguidance/standards/criteria/health/methodology/inde

x.cfm  

U.S. EPA 2000e. Lessons Learned About Designing, Developing, and Disseminating

Environmental Information Products. Washington, DC: Office of Environmental

Information. November. EPA/260/R‐00/001.

http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1005LPL.txt

U.S. EPA 2001a. Arsenic Rule Benefits Analysis: An SAB Review. EPA/SAB/EC‐01/008.

http://www.epa.gov/ogwdw000/arsenic/pdfs/ec01008.pdf  

U.S. EPA 2001b. General Principles for Performing Aggregate Exposure and Risk Assessments.

Washington, DC: Office of Pesticide Programs. Fax‐On‐Demand. Fax no. (202) 401‐0527. Item

no. 6043. http://www.epa.gov/oppfead1/trac/science/aggregate.pdf

U.S. EPA 2001c. EPA Requirements for Quality Assurance Project Plans. Washington, DC: Office

of Environmental Information. March. EPA/240/B‐00/003.

http://www.epa.gov/quality/qs‐docs/r5‐final.pdf
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66

U.S. EPA 2001d. Risk Assessment Guidance for Superfund (RAGS) Volume III—Part A: Process for

Conducting Probabilistic Risk Assessment. Washington, DC: Office of Solid Waste and

Emergency Response. December. EPA/540/R‐02/002.

http://www.epa.gov/oswer/riskassessment/rags3adt/pdf/rags3adt_complete.pdf  

U.S. EPA 2002a. Lessons Learned on Planning and Scoping of Environmental Risk Assessment.

Memorandum from the Science Policy Council. January.

http://www.epa.gov/spc/pdfs/llmemo.pdf

U.S. EPA 2002b. “Appendix B: Case Study on Concentrated Animal Feeding Operations.” B. In

Lessons Learned on Planning and Scoping for Environmental Risk Assessments.

Washington, DC: Science Policy Council. http://www.epa.gov/spc/pdfs/handbook.pdf  

U.S. EPA 2002c. “Appendix C: Re‐registration of Pentachlorophenol.” In Lessons Learned on

Planning and Scoping for Environmental Risk Assessments. Washington, DC: Science

Policy Council. http://www.epa.gov/spc/pdfs/handbook.pdf  

U.S. EPA 2002d. Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a

Common Mechanism of Toxicity. Washington, DC: Office of Pesticide Programs. January.

http://www.epa.gov/oppfead1/trac/science/cumulative_guidance.pdf

U.S. EPA 2002e. A Review of the Reference Dose and Reference Concentration Processes.

External review draft. Washington, DC: Risk Assessment Forum. May. EPA/630/P‐

02/002F. http://www.epa.gov/raf/publications/pdfs/rfdrfcextrevdrft.pdf

U.S. EPA 2002f. “Superfund Community Involvement Plans.” September.

http://www.epa.gov/superfund/community/pdfs/toolkit/7clplans.pdf

U.S. EPA 2002g. Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a

Common Mechanism of Toxicity. Washington, DC: Office of Pesticide Programs.

http://www.epa.gov/scipoly/sap/meetings/2003/december11/cumulativeguidance2002

.pdf  

U.S. EPA 2003a. Framework for Cumulative Risk Assessment. Washington, DC: Risk Assessment

Forum. May. EPA/630/P‐02/001F.

http://www.epa.gov/raf/publications/pdfs/frmwrk_cum_risk_assmnt.pdf

U.S. EPA 2003b. Considerations in Risk Communication: A Digest of Risk Communication as a

Risk Management Tool. Cincinnati, OH: Office of Research and Development, National

Risk Management Research Laboratory. March. EPA/625/R‐02/004.

http://www.epa.gov/nrmrl/pubs/625r02004.html  

U.S. EPA 2003c. Public Involvement Policy. May. EPA/233/B‐03/002.

http://www.epa.gov/publicinvolvement/pdf/policy2003.pdf  
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U.S. EPA 2003d. Framework for Implementing EPA’s Public Involvement Policy. May. EPA/233/F‐

03/001. http://www.epa.gov/publicinvolvement/policy2003/framework.pdf  

U.S. EPA 2004a. Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation

Manual (Part E, Supplemental Guidance for Dermal Risk Assessment). Washington, DC:

Office of Solid Waste and Emergency Response. EPA/540/R/99/005.

http://www.epa.gov/oswer/riskassessment/ragse/

U.S. EPA 2004b. Air Toxics Risk Assessment Reference Library, Volume 1. Technical Resource

Manual. Research Triangle Park, NC: Office of Air Quality Planning and Standards.

EPA/453/K‐04/001A. http://www.epa.gov/ttn/fera/risk_atra_vol1.html

U.S. EPA 2004c. Air Toxics Risk Assessment Reference Library, Volume 2. Facility‐Specific

Assessment. Research Triangle Park, NC: Office of Air Quality Planning and Standards.

EPA/453/K‐04/001B. http://www.epa.gov/ttn/fera/risk_atra_vol2.html

U.S. EPA 2004d. Risk Assessment Principles and Practices. Washington, DC: Office of the Science

Advisor, Risk Assessment Task Force. March. EPA/100/B‐04/001.

http://www.epa.gov/osa/pdfs/ratf‐final.pdf

U.S. EPA 2004e. Air Toxics Risk Assessment Library. Volume 1 Technical Resource Manual.

Washington, DC: Office of Air and Radiation. April. Residual Risk Framework described in

Part II—Human Health Risk Assessment: Inhalation.

http://www.epa.gov/ttn/fera/data/risk/vol_1/chapter_05.pdf. All volumes available at:

http://www.epa.gov/ttn/fera/risk_atra_main.html

U.S. EPA 2004f. Ensuring Risk Reduction in Communities With Multiple Stressors: Environmental

Justice and Cumulative Risks/Impacts. Washington, DC: National Environmental Justice

Advisory Council, Cumulative Risks/Impacts Work Group. December.

http://www.epa.gov/environmentaljustice/resources/publications/nejac/nejac‐cum‐

risk‐rpt‐122104.pdf

U.S. EPA 2004g. Registration Review Update. Washington, DC: Office of Pesticide Programs,

Pesticide Program Dialogue Committee. October.

http://www.epa.gov/oppfead1/cb/ppdc/regisreview/regreview‐update.pdf

U.S. EPA 2005a. Guidelines for Carcinogen Risk Assessment. Washington, DC: Risk Assessment

Forum. March. EPA/630/P‐03/001B.

http://www.epa.gov/raf/publications/pdfs/CANCER_GUIDELINES_FINAL_3‐25‐05.pdf  

U.S. EPA 2005b. Supplemental Guidance for Assessing Susceptibility from Early‐Life Exposure to

Carcinogens. Washington, DC: Risk Assessment Forum. March. EPA/630/R‐03/003F.

http://www.epa.gov/ttn/atw/childrens_supplement_final.pdf
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U.S. EPA 2005c. Guidance on Selecting Age Groups for Monitoring and Assessing Childhood

Exposures to Environmental Contaminants (Final). Washington, DC: Risk Assessment

Forum. EPA/630/P‐03/003F. http://www.epa.gov/raf/publications/guidance‐on‐

selecting‐age‐groups.htm

U.S. EPA 2005d. Superfund Community Involvement Handbook. Washington, DC: Office of Solid

Waste and Emergency Response. April. EPA/540/K‐05/003.

http://www.epa.gov/superfund/community/cag/pdfs/ci_handbook.pdf

U.S. EPA 2005e.  A Probabilistic Exposure Assessment for children who Contact CCA‐Treated

Playsets and Decks.  Washington DC: U.S. Environmental Protection Agency. February.

http://www.epa.gov/heasd/sheds/CCA_all.pdf  

U.S. EPA 2006a. A Framework for Assessing Health Risk of Environmental Exposures to Children

(Final). Washington, DC: U.S. Environmental Protection Agency. EPA/600/R‐05/093F.

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=158363

U.S. EPA 2006b. Advisory on EPA’s Superfund Benefits Analysis. January 9.

http://yosemite.epa.gov/sab/sabproduct.nsf/58ADDDF28999BAC18525710100554A0F/

$File/superfund_sab‐adv‐06‐002.pdf  

U.S. EPA 2006c. Peer Review Handbook, 3rd Edition. Washington, DC: Science Policy Council.

EPA/100/B‐06/002.

http://www.epa.gov/peerreview/pdfs/peer_review_handbook_2006.pdf  

U.S. EPA 2006d. Air Toxics Risk Assessment Reference Library, Volume 3. Community‐Scale

Assessment. Research Triangle Park, NC: Office of Air Quality Planning and Standards.

EPA/452/K‐06/001C. http://www.epa.gov/ttn/fera/risk_atra_vol3.html

U.S. EPA 2006e. EPA’s Action Development Process. Guide to Considering Children’s Health

When Developing EPA Actions: Implementing Executive Order 13045 and EPA’s Policy on

Evaluating Health Risks to Children.

http://yosemite.epa.gov/ochp/ochpweb.nsf/content/ADPguide.htm/$File/EPA_ADP_Gu

ide_508.pdf

U.S. EPA 2006f. Guidance on Systematic Planning Using the Data Quality Objectives Process.

Washington, DC: Office of Environmental Information. EPA/QA/G‐4.

http://www.epa.gov/quality/qs‐docs/g4‐final.pdf  

U.S. EPA 2007a. Risk Communication in Action: The Risk Communication Workbook. Cincinnati,

OH: Office of Research and Development, National Risk Management Research

Laboratory. August. EPA/625/R‐05/003.

http://nepis.epa.gov/Exe/ZyNET.exe/60000I2U.TXT?ZyActionD=ZyDocument&Client=EP

A&Index=2006+Thru+2010&Docs=&Query=&Time=&EndTime=&SearchMethod=1&Toc
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Restrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&IntQFi

eldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5Czyfiles%5CIndex%20Data%5C06th

ru10%5CTxt%5C00000001%5C60000I2U.txt&User=ANONYMOUS&Password=anonymou

s&SortMethod=h%7C‐

&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i4

25&Display=p%7Cf&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc

=Results%20page&MaximumPages=1&ZyEntry=1&SeekPage=x&ZyPURL

U.S. EPA 2007b. Risk Communication in Action: The Tools of Message Mapping. Cincinnati, OH:

Office of Research and Development, National Risk Management Research Laboratory.

August. EPA/625/R‐06/012. http://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=60000IOS.txt

U.S. EPA 2007c. Lead: Human Exposure and Health Risk Assessment for Selected Case Studies.

Volume 1. Human Exposure and Health Risk Assessments—Full‐Scale. Research Triangle

Park, NC: Office of Air Quality Planning and Standards. July. EPA/452/R‐07/014a.

http://www.epa.gov/ttn/naaqs/standards/pb/data/Pb‐RA‐Vol‐1‐073007.pdf

U.S. EPA 2007d.  Better Decisions through Consultation and Collaboration.  Washington, DC:

U.S. Environmental Protection Agency. Conflict Prevention and Resolution Center

http://www.epa.gov/adr/Better_Decisions.pdf

U.S. EPA 2008a. Child‐Specific Exposure Factors Handbook (Final Report) 2008. Washington, DC:

U.S. Environmental Protection Agency. EPA/600/R‐06/096F.

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=199243

U.S. EPA 2008b. “Formaldehyde Emissions From Pressed Wood Products.” Proposed

rulemaking. Federal Register 73 (233): 73620–43629. http://www.epa.gov/fedrgstr/EPA‐

TOX/2008/December/Day‐03/t28585.htm  

U.S. EPA 2009. Highlights of the Child‐Specific Exposure Factors Handbook (Final Report).

Washington, DC: Office of Research and Development, National Center for

Environmental Assessment. EPA/600/R‐08/135.

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=200445

U.S. EPA 2010a. Guidelines for Preparing Economic Analysis. December 17. EPA/240/R‐10/001.

http://yosemite.epa.gov/ee/epa/eerm.nsf/vwAN/EE‐0568‐50.pdf/$file/EE‐0568‐50.pdf  

U.S. EPA 2010b. EPA’s Action Development Process. Interim Guidance on Considering

Environmental Justice During the Development of an Action. Washington, DC. July.

http://www.epa.gov/environmentaljustice/resources/policy/considering‐ej‐in‐

rulemaking‐guide‐07‐2010.pdf  
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U.S. EPA 2010c. Quantitative Health Risk Assessment for Particulate Matter. Research Triangle

Park, NC: Office of Air Quality Planning and Standards. EPA/452/R‐10/005.

http://www.epa.gov/ttn/naaqs/standards/pm/data/PM_RA_FINAL_June_2010.pdf

U.S. EPA 2010d. Requirements for Submitting Electronic Pre‐manufacture Notices (PMNs).

Washington, DC: Office of Chemical Safety and Pollution Prevention, Office of Pollution,

Prevention and Toxics. January. http://www.epa.gov/ncea/efh/pdfs/efh‐complete.pdf

U.S. EPA 2010e. “Proposed Significant New Use Rule for Multi‐walled Carbon Nanotubes.”

Proposed rulemaking. Federal Register 75 (22): 5546–5551.

http://www.regulations.gov/#!documentDetail;D=EPA‐HQ‐OPPT‐2009‐0686‐0001  

U.S. EPA 2011a. Exposure Factors Handbook. Washington, DC: Office of Research and

Development. September. EPA/600/R‐090/052F.

http://www.epa.gov/ncea/efh/pdfs/efh‐complete.pdf

U.S. EPA 2011b. “EPA Public Involvement.” Accessed November 11.

http://www.epa.gov/publicinvolvement/

U.S. EPA 2011c. “Pesticide Program Dialogue Committee.” Accessed November 11.

http://www.epa.gov/oppfead1/cb/ppdc/

U.S. EPA 2011d. “Superfund Community Involvement Publications.” Accessed November 11.

http://www.epa.gov/superfund/community/publications.htm

U.S. EPA 2011e. “Sustainability.” Accessed November 11. http://www.epa.gov/sustainability/

U.S. EPA 2011f. “Life‐Cycle Assessment.” Accessed November 11.

http://www.epa.gov/nrmrl/std/lca/lca.html  

U.S. EPA 2011g. “Definitions of the Most Commonly Used Public Stakeholder Involvement

Terms.” Accessed November 11. http://www.epa.gov/stakeholders/definit.htm

U.S. EPA 2011h. “Superfund Community Involvement.” Accessed November 11.

http://www.epa.gov/superfund/community/

U.S. EPA 2011i. “EPA’s Quality System for Environmental Data and Technology.” Accessed

November 11. http://www.epa.gov/quality/

U.S. EPA 2011j. “Superfund Quality Assurance/Quality Control.” Accessed November 11.

http://www.epa.gov/superfund/programs/clp/qaqc.htm

U.S. EPA 2011k. “Resources for Planning New Data Collections.” Accessed November 11.

http://www.epa.gov/quality/rnewdata.html
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U.S. EPA 2011l. “Risk and Technology Review.” Accessed November 11.

http://www.epa.gov/ttn/atw/rrisk/rtrpg.html

U.S. EPA 2011m. “Multi‐criteria Integrated Resource Assessment (MIRA).” Accessed November

11. http://www.epa.gov/reg3esd1/data/mira.htm

U.S. EPA 2011n. “Particulate Matter Standards—Documents From Current Review—Planning

Documents.” Accessed November 11.

http://www.epa.gov/ttn/naaqs/standards/pm/s_pm_2007_pd.html

U.S. EPA 2011o. “Human Health: Planning and Scoping.” Accessed November 11.

http://www.epa.gov/oswer/riskassessment/human_health_plan.htm

U.S. EPA 2011p. “Ecological: Planning and Scoping.” Accessed November 11.

http://www.epa.gov/oswer/riskassessment/eco_plan.htm

U.S. EPA 2011q. “Risk and Technology Review.” Accessed November 11.

http://www.epa.gov/ttn/atw/rrisk/rtrpg.html

U.S. EPA 2011r. EPA’s Action Development Process. Guidance for EPA Staff on Developing Quality

Actions. Washington, DC. March.

http://yosemite.epa.gov/sab/SABPRODUCT.nsf/5088B3878A90053E8525788E005EC8D8/$File/a

dp03‐00‐11.pdf  

U.S. EPA 2012a. “Environmental Justice Policy and Guidance.” Accessed May 24.

http://www.epa.gov/environmentaljustice/resources/policy/  

U.S. EPA 2012b. “U.S. Environmental Protection Agency Scientific Integrity Policy.” January 15.

http://www.epa.gov/research/htm/scientific‐integrity.htm  

U.S. EPA 2012c. “Science Inventory.” Accessed May 24. http://cfpub.epa.gov/si/

U.S. EPA 2012d. “Public Involvement Policy and Related Documents.” Accessed May 24.

http://www.epa.gov/publicinvolvement/public/  

U.S. EPA 2012e. “Region 8 Site Conceptual Model.” Accessed May 24.

http://www.epa.gov/region8/r8risk/hh_scm.html

U.S. EPA 2012f. “Process of Reviewing the National Ambient Air Quality Standards.” Accessed May 24.

http://www.epa.gov/ttn/naaqs/review.html  

U.S. EPA 2012g. “American Indian Environmental Office (AIEO).” Accessed May 24.

http://www.epa.gov/tribalportal/aieo/index.html  
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U.S. EPA 2012h. “Office of the Science Advisor: Ethics, Regulations, and Policies.” Accessed May 24.

http://www.epa.gov/phre/policy.htm  

U.S. EPA 2012i. “Risk Assessment Portal.” Accessed May 28. http://www.epa.gov/risk/

U.S. EPA 2012j. “Dose‐Response Assessment.” Accessed May 28.

http://www.epa.gov/riskassessment/dose‐response.htm

U.S. EPA 2012k. “Guidance & Tools.” Accessed May 28.

http://www.epa.gov/risk_assessment/guidance.htm

U.S. EPA 20121. “Cacodylic Acid.” Accessed May 28.

http://www.epa.gov/opp00001/reregistration/cacodylic_acid/

U.S. EPA 2012m. “Cumulative Risk Assessment Methods and Tools.” Accessed May 28.

http://www.epa.gov/oppsrrd1/cumulative/methods_tools.htm

U.S. EPA 2012n. “High Production Volume (HPV) Challenge: Robust Summaries and Test Plans.”

Accessed May 28. http://www.epa.gov/hpv/pubs/summaries/viewsrch.htm

U.S. EPA 2012o. “IRIS Process.” Accessed May 28. http://www.epa.gov/iris/process.htm

U.S. EPA 2012p. “Technology Transfer Network National Ambient Air Quality Standards (NAAQS).”

Accessed May 30. http://www.epa.gov/ttn/naaqs/  

U.S. EPA 2012q. “Environmental Justice.” Accessed May 30. http://www.epa.gov/environmentaljustice/  

World Health Organization. 2008. Guidance Document on Characterizing and Communicating

Uncertainty in Exposure Assessment. Geneva, Switzerland.

http://www.who.int/ipcs/methods/harmonization/areas/uncertainty%20.pdf

   
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Appendix I. Examples of EPA Program­Specific Resources

and Guidance on Risk Assessment Activities

Air Toxics Program (Office of Air Quality Planning and Standards [OAQPS]) 

• Air Toxics Risk Assessment Reference Library for conducting air toxics analyses at the 

facility and community-scale. The library provides information on the fundamental 

principles of risk-based assessment for air toxics and how to apply those principles in 

different settings as well as strategies for reducing risk at the local level. 

o Volume 1: Technical Resource Manual 

(http://www.epa.gov/ttn/fera/risk_atra_vol1.html) 

o Volume 2: Facility-Specific Assessment 

(http://www.epa.gov/ttn/fera/risk_atra_vol2.html) 

o Volume 3: Community-Scale Assessment 

(http://www.epa.gov/ttn/fera/risk_atra_vol3.html) 

• Residual Risk Report to Congress (http://www.epa.gov/ttn/oarpg/t3/reports/risk_rep.pdf) 

Hazardous Waste Program (Office of Solid Waste and Emergency Response [OSWER]) 

• Resource Conservation and Recovery Act Public Participation Manual

http://www.epa.gov/wastes/hazard/tsd/permit/pubpart/manual.htm

National Ambient Air Quality Standards Program (NAAQS) (OAQPS) 

• Process for NAAQS reviews, including role of risk assessment 

(http://www.epa.gov/ttn/naaqs/review.html) 

• Recent NAAQS risk assessments (http://www.epa.gov/ttn/fera/risk_criteria.html) 

• Current documents for NAAQS reviews (http://www.epa.gov/ttn/naaqs/) 

Pesticides Program (Office of Pesticide Programs) 

• Science Policy Issues and Guidance Documents 

(http://www.epa.gov/oppfead1/trac/science/) 

• Public Participation in Registration Decisions. Washington, DC: Office of Pesticide 

Programs, U.S .Environmental Protection Agency. 31 March 2010. - 

http://www.epa.gov/pesticides/regulating/public-participation-process.html

• Models and Databases (http://www.epa.gov/pesticides/science/models_db.htm) 

• Public Participation Process for Registration Actions 

(http://www.epa.gov/pesticides/regulating/public-participation-process.html) 
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Safe Drinking Water Program (Office of Water) 

• Public Access Information for the Safe Drinking Water Act 

http://water.epa.gov/lawsregs/guidance/sdwa/upload/2009_08_28_sdwa_fs_30ann_public

involve_web.pdf

Superfund Program (OSWER) 

• Risk assessment resources and guidance 

(http://www.epa.gov/oswer/riskassessment/risk_superfund.htm) 

• Supplement to RAGS Part A: Community Involvement in Superfund Risk Assessments

(1999) 

(http://www.epa.gov/oswer/riskassessment/ragsa/pdf/ci_ra.pdf) 

• Superfund Community Involvement Guidance and Publications 

(http://www.epa.gov/superfund/community/involvement.htm)