EPA External Review Draft December 16, 2005 

 i 
External Review Draft December 16, 2005 

 

 

 
Preface

The Office of Research and Development (ORD) multi-year plans (MYPs) present ORD’s 

proposed research and development activities in a variety of areas over the next 5-8 years, 

assuming constant funding. The MYPs serve to plan the direction of ORD’s activities and to 

communicate this program within ORD and with others. Multi-year planning permits ORD to 

consider the strategic directions of the Agency and how research and development activities can 

evolve to best contribute to the Agency’s mission of protecting human health and the 

environment. MYPs are considered to be “living documents.” ORD intends to update the MYPs 

on a regular basis to reflect the current state of the science, resource availability, and Agency 

priorities. ORD will update or modify future performance information contained within this 

planning document as needed. 

The draft Human Health Risk Assessment Multi-Year Plan (RA MYP) has been prepared 

following the “ORD Multi-Year Planning Guidance Update” (2002). Planning input was sought 

from ORD-National Center for Environmental Assessment (NCEA) and Risk Assessment Forum 

staff, and from EPA Programs, Regions, and other ORD laboratories and centers through the 

Human Health Research Coordination Team (RCT). Internal Agency review was conducted 

through the RCT process and managed independently by the ORD Office of Science Policy. Peer 

review comments were also sought from the ORD Science Council through a process managed by 

designated Science Council members. Additional meetings were held to solicit input from 

managers and directors in EPA Program Offices, including the Office of Water, Office of Air and 

Radiation, Office of Prevention, Pesticides and Toxic Substances, and Office of Solid Waste and 

Emergency Response. Comments received have been reviewed in detail and incorporated as 

appropriate in this revised internal draft RA MYP, accompanied by a disposition of these internal 

review comments. The revised draft RA MYP and disposition of comments will be reviewed by 

the ORD Science Council, followed by the ORD Executive Council. On approval, the draft RA 

MYP will be submitted for external peer review. Appreciation is extended to all the EPA staff 

who have contributed to the preparation and review of this draft RA MYP. 

 

 
Table of Contents 

Introduction.....................................................................................................................................1

Background .....................................................................................................................................5

Antecedents of the RA MYP ..............................................................................................5

Logic Model .........................................................................................................................6

Relevance and the Planning Process .................................................................................7

Quality and Peer Review.................................................................................................... 8

Technical Support...............................................................................................................8

Performance ........................................................................................................................9

Progress to Date/Changes...............................................................................................................9

Overview of the Long Term Goals ..............................................................................................12

LTG1: Integrated Risk Information System (IRIS) and other priority health hazard 

assessments ........................................................................................................................13

LTG 2: State-of-the-science risk assessment models, methods, and guidance........................17

ORD-NCEA Activities...................................................................................................... 17

Risk Assessment Forum Activities ..................................................................................18

LTG 3: Air Quality Criteria Documents ....................................................................................22

Potential Additional Work...........................................................................................................23

Classification of External Annual Performance Goals and Measures.....................................24

Appendix A: Long Term Goals and Associated Annual Performance Goals (APG) and 

Annual Performance Measures (APM) ..........................................................................25

Appendix B: RA LTG 2 Annual Performance Measures (APMs) and Support Activities in 

an Annual Operating Plan Format ................................................................................. 34

References......................................................................................................................................35

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EPA External Review Draft December 16, 2005 

Human Health Risk Assessment (RA) Multi-Year Plan

 

Introduction

 

 Human health risk assessment is a process in which information is analyzed to determine if 

an environmental hazard might cause harm to exposed persons. It is the essential intermediary 

means by which primary data and published literature are compiled, analyzed and summarized for 

application to decision-making in real world situations. Risk assessment in the federal government 

is based on the tenets outlined by the National Academy of Sciences (NAS 1983, 1994), namely 

hazard identification, dose-response assessment, exposure assessment, and risk characterization, as 

a foundation for subsequent risk management decisions. This science-based framework for 

decision-making is central to EPA’s implementation of its statutory responsibilities and to its 

mission to protect human health and the environment. The Human Health Risk Assessment MultiYear Plan (RA MYP) serves as a primary EPA mechanism to implement this process, linking 

laboratory and field science with the use of this information by EPA programs, regions and the 

broader community. To achieve this goal, the RA MYP directs efforts toward: 

< Providing qualitative and quantitative health hazard assessments of priority environmental 

contaminants for incorporation in applied risk assessments, exemplified by the Integrated 

Risk Information System (IRIS) Toxicological Reviews and Summaries, reference doses 

(RfDs), reference concentrations (RfCs), oral cancer slope factors and cancer inhalation 

unit risks; 

 

< Preparing Air Quality Criteria Documents (AQCDs) for criteria air pollutants as a 

mandated pre-requisite to EPA’s review of National Ambient Air Quality Standards 

(NAAQS); 

< Conducting environmental risk assessments of national importance, such as potential health 

impacts in the aftermath of the attack on the World Trade Center and the reassessment of 

the health risks posed by dioxin; 

< Developing models, methods and guidance to incorporate the latest scientific advances into 

EPA risk assessment practice, thereby maintaining the scientific quality and objectivity of 

EPA assessments consistent with the state-of-the-science; 

< Identifying, evaluating and conveying to the scientific community key uncertainties and 

research needed to improve health risk assessments through laboratory, field and methods 

research; and, 

< Supporting the Risk Assessment Forum (Forum), through which risk assessors across the 

Agency can communicate and harmonize risk assessment practices to facilitate a consistent 

and predictable framework for EPA activities. 

 

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EPA External Review Draft December 16, 2005 

 The principal purposes of ORD’s multi-year plans are planning and communication – 

communication among ORD laboratories and centers, and communication between ORD and the 

EPA programs, regions, and broader science community. The risk assessment MYP differs from 

other ORD MYPs in that it does not describe plans for conducting or funding primary research. 

Rather, the RA MYP draws on data and primary methods development science generated under 

other ORD multi-year plans. Activities under the RA MYP also receive substantial information 

from the published literature and other federal, private, and international organizations. This 

information is then analyzed and prepared for use by EPA programs and regions to respond to their 

regulatory and decision-making needs in a timely manner. 

 The flow of information from research, through risk assessment, to risk management is 

displayed in figure 1 (NAS 1983; revised 1994). Primary data generation refers to laboratory and 

field observations and measurements, along with information on extrapolation methods. This 

information is used by risk assessors to evaluate the hazardous properties of environmental agents 

and the extent of human exposure to these agents. As noted by the NAS (1994), although the 

conduct of a risk assessment involves research of a kind, it is primarily a process of gathering and 

evaluating extant data and imposing science-policy choices. The product of this evaluation is a 

characterization statement regarding the probability that exposed populations might be harmed and 

to what degree, expressed quantitatively or in relatively qualitative ways. Because risk assessment 

provides an organized profile of the current state of knowledge on a substance and systematically 

elucidates scientific uncertainties, it can provide valuable guidance to research scientists regarding 

the types of data that can most effectively improve understanding. Risk management is maintained 

as a distinct process where additional considerations regarding public health, economic, social and 

political consequences are factored into agency decisions and actions. 

Figure 1: NAS/NRC Risk Assessment/Management Paradigm (NAS, 1994) 

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EPA External Review Draft December 16, 2005 

 The NAS paradigm is applied in the ORD context through the separation of laboratory and 

field research from the risk assessment activities planned in the RA MYP. Primary data generation 

and model development are conducted in the ORD laboratories on hazard identification and doseresponse parameters, exposure variables, and risk management options. This information is used by 

risk assessors in NCEA and directly in program offices to prepare a scientific foundation for 

subsequent decision-making. Research needs identified through the risk assessment process are 

conveyed to the research laboratories through the ORD planning process and in collaboration with 

National Program and Laboratory Directors. The principal purpose of RA MYP development 

activities is to provide direct support to risk assessment needs, such as guidance on model validation 

procedures, secondary data analysis in the context of a specific risk assessment, or collation of 

information on exposure factors, but not to generate new data. In this way, the RA MYP is a client 

of the ORD laboratories, both receiving data and helping to prioritize research needs in conjunction 

with the EPA programs. 

 The principal customers for risk assessment information are the EPA programs and regions 

under many of EPA’s implementing statutes. For example: 

 

< The Clean Air Act (CAA, Section 103) mandates that EPA conduct a national research and 

development program for the prevention and control of air pollution. This program is to 

include assessment of risks, development of methods and tools for analysis of data, and 

development of AQCDs to serve as the basis for review of the NAAQS on a five year cycle. 

The 1990 CAA Amendments further mandate determination of risks from mobile, area, and 

major sources of air toxics. 

< The Safe Drinking Water Act (1996) authorizes research and assessments focusing on 

Cryptosporidium, disinfection byproducts, arsenic, sulfate and radon, including effects on 

sensitive subpopulations. Other research provisions address risks associated with waterborne 

disease, complex mixtures, and unregulated contaminants. 

< The Food Quality Protection Act (1996) mandates research and assessment of risk from 

exposures to pesticides, including aggregate exposures and cumulative risk, and risk to 

sensitive subpopulations. 

< The Comprehensive Environmental Response, Compensation and Liability Act

(CERCLA; Superfund, 1980) requires research, development and training to improve EPA’s 

scientific capability to assess and evaluate effects on, and risk to, human health from 

hazardous substances. 

 The RA MYP plays a unique role in serving the needs of the EPA programs and regions 

through incorporating, integrating and coordinating the use of scientific information as a foundation 

for regulatory decision-making. The core IRIS, AQCD and other assessments are directly 

responsive to program needs and are primary considerations in Agency actions to protect human 

health and the environment. In partnership with the ORD laboratories, the RA MYP is at the 

forefront of applying quantitative methods advances to risk assessment, such as the use of PBPK 

models to reduce uncertainty in risk extrapolations and to replace default uncertainty factors. The 

RA MYP also maintains a leadership role in incorporating mode of action (MoA) evaluations to 

support EPA decision-making, as emphasized in the Carcinogen Risk Assessment Guidelines and 

used in recent assessments to evaluate the relevance of animal tumors to humans and the associated 

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EPA External Review Draft December 16, 2005 

dose-response relationships. In conducting these cancer assessments, the RA MYP is uniquely 

responsive to program needs by developing and applying quantitative methods and guidance to 

estimate cancer risks and associated uncertainty parameters. RA MYP activities are characterized by 

their ability to integrate information within and across scientific disciplines to solve risk assessment 

questions, whether substance-specific or novel methods development work. These activities are 

coordinated across EPA research and program offices, through formal means under the RA MYP, 

such as the IRIS consensus review and Risk Assessment Forum processes, or more informally 

through leadership in interpreting and applying risk assessment science to inform environmental 

decision-making. 

 Beyond EPA, RA MYP products are widely recognized as the principal environmental health 

risk assessment benchmarks in the United States, exemplified by the IRIS outputs, AQCDs, and Risk 

Assessment Forum guidance documents. Although non-regulatory and non-binding in nature, these 

health risk assessment products and the scientific analyses therein are referenced in many federal, 

state, local, and stakeholder environmental decisions. 

 The RA MYP encourages close relationships with these partner federal, state and 

international organizations, both in accessing sources of toxicological and epidemiological data and 

through collaborative risk assessment development activities. Access to data is facilitated through 

staff contacts with other federal agencies conducting primary environmental health research, 

particularly the NIH-NIEHS National Toxicology Program and the CDC-National Center for 

Environmental Health. Assessment activities are coordinated through interagency working groups 

and collaborative relationships. Of particular note is the Memorandum of Understanding between 

EPA-IRIS and the Agency for Toxic Substances and Disease Registry (ATSDR). ATSDR prepares 

Toxicological Profiles for hazardous substances found at National Priorities List (NPL; “superfund”) 

sites, including quantitative Minimal Risk Levels (MRLs) for non-cancer effects. The EPA-ATSDR 

MOU emphasizes coordination and sharing of information on substances under evaluation by both 

organizations. An EPA-ATSDR joint pilot assessment has commenced for 1,1,2,2-

tetrachloroethane, where contract resources are leveraged to prepare toxicological materials and 

summaries for both organizations. Close relationships are also maintained with international 

organizations dealing with environmental health risks, including the World Health Organization 

through its International Programme on Chemical Safety (IPCS), the International Agency for 

Research on Cancer (IARC), and the United Nations Environment Programme (UNEP). 

 

 Resources currently allocated to the RA MYP were consolidated in fiscal year 2004 under 

EPA Government Performance Results Act (GPRA) Goal 4, Healthy Communities and Ecosystems. 

The FY’07 President’s Budget requests 122 full time equivalent (FTE) work years and $13.6 million 

dollars of extramural funds for the RA MYP. Approximately three quarters of these resources are 

assigned to the preparation of assessments (e.g., IRIS and other major health hazard assessments 

~60% and AQCDs ~15%), with the remainder to methods and guidance development (~25%). At 

any one time, approximately 80 IRIS assessments are underway, plus additional major health hazard 

assessments, AQCDs, and between 25 and 50 Provisional Peer Reviewed Toxicity Values (PPRTVs) 

for substances prioritized by the Office of Solid Waste and Emergency Response (OSWER). The 

RA MYP does not plan ecological risk assessment activities, which are addressed under other ORD 

plans, although a number of RA MYP activities explore aspects of integrated human health and 

ecological risk assessment. 

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EPA External Review Draft December 16, 2005 

Background

Antecedents of the RA MYP: Modern efforts at quantifying presumptively safe levels of 

environmental exposures began in the 1940s through the development of threshold limit values 

(TLVs) in occupational settings. The concept of acceptable levels was extended to food 

contaminants in the 1950s (Lehman and Fitzhugh, 1954). Passage of the “Delaney Clause” to the 

Food Additive Amendments in 1958 focused attention on potential cancer risks by stipulating that no 

substance found carcinogenic in animals could be added to food. Further impetus toward 

quantitative risk assessment came from the 1980 Supreme Court decision on occupational standards 

for benzene. In this decision, several judges opined that OSHA could regulate only if it found that 

benzene posed a “significant risk of harm,” signaling that some form of quantitative risk assessment 

was necessary as a prelude to regulatory decision-making. These developments led to the now 

landmark NAS (1983) publication “Risk Assessment in the Federal Government.” In this 

publication, the NAS proposed the four step paradigm of hazard identification, dose-response 

assessment, exposure assessment, and risk characterization, separate from, but linked to, risk 

management decisions. Additional independent reviews of risk assessment in the federal 

government (NAS, 1994; Presidential/Congressional Commission, 1997) have confirmed the role of 

quantitative risk assessment as an essential foundation for decision-making. 

 The risk assessment/risk management paradigm is EPA’s organizing principle for generating 

and using scientific information (EPA Strategic Plan, Cross-Goal Strategy Science; U.S. EPA, 

2003). EPA has implemented risk assessment practices through creating specific risk assessment 

organizations and as a fundamental component of its decision-making processes. Specific 

organizations include ORD-NCEA, the Risk Assessment Forum, and program offices such as the 

Risk Assessment Division of OPPTS. The risk assessment paradigm of effects, exposure, 

assessment and management has also been extended to the structuring of the ORD laboratories and 

centers. As a fundamental component in decision-making processes, EPA’s Strategic Plan (GPRA 

Goal 4, Healthy Communities and Ecosystems) directs the Agency to “identify and synthesize the 

best available scientific information, models, methods and analyses to support Agency guidance and 

policy decisions related to the health of people, communities and ecosystems.” With regard to 

chemical, organism, and pesticide risks, EPA Strategic Objective 4.1 seeks to “Prevent and reduce 

pesticide, chemical, and genetically engineered biological organism risks to humans, communities, 

and ecosystems.” ORD’s Strategic Plan (U.S. EPA, 2001) further commits to pursuing “science for 

a purpose,” noting that ORD is part of a regulatory Agency and that its scientific products and 

expertise are critical to supporting Agency decision-making. 

 To better achieve these risk assessment objectives, the Administration directed in 2003 that 

ORD consolidate planning for risk assessment to foster a more integrated approach to resource 

allocation, prioritization and accountability. This consolidation was necessary because: 

< Many NCEA assessments supported more than one program office and covered several 

existing multi-year plans. Prior to consolidation, NCEA had human health risk assessment 

resources in 25 long-term goals under 14 multi-year plans; 

 

 Many chemical assessments, such as the perchlorate, trichloroethylene, formaldehyde and 

 dioxin assessments, did not appear or were inadequately funded in existing MYPs; and, 

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EPA External Review Draft December 16, 2005 

< Research coordination teams had provided funding only for small, incremental risk 

assessment methods development activities, with the result that there was no coherent, 

integrated process for improving methods. 

 The objectives of the consolidation to the risk assessment MYP were to: improve the 

quality and timeliness of assessments; focus development and incorporation of scientific advances 

into risk assessment methods and products; improve the alignment of ORD laboratory and center 

research and programs; and increase technical support to program offices and regions. 

 Some confusion arose initially because of the functional ties and similarity in titles and 

acronyms between the consolidated Human Health Risk Assessment plan (initial acronym 

HHRA, now RA) and the similarly titled Human Health Research Plan (HHRP). As noted, these 

two plans are distinct in that the RA MYP receives data and methods development science 

produced under the HHRP and other MYPs from the ORD laboratories, as well as from the 

published literature. The RA MYP helps prioritize research in the ORD laboratories by 

identifying critical data gaps and scientific needs, but does not conduct or fund this work itself. In 

contrast, the HHRP plans and coordinates the performance of primary laboratory work on the 

health effects of environmental pollutants, emphasizing core research to produce a fundamental 

understanding of the key biological, chemical and physical processes that underlie environmental 

systems. 

Logic Model: The primary objective of the RA MYP is to provide EPA programs and regions 

with health hazard assessment information on priority substances included in planned Agency 

decisions and actions. This objective is achieved through the preparation of hazard identification 

and dose-response assessments under the IRIS program, other major assessments, air quality 

criteria documents, and provisional peer reviewed toxicity values. Methods development and 

guidance functions are conducted to support this primary objective, thereby ensuring that EPA 

risk assessment products are consistent with the state-of-the-science and information quality 

objectives, and are considered quality products after undergoing scientific peer review. 

 Figure 2 displays the logic model for the RA MYP. The intermediate and long-term 

outcomes on the far right of figure 2 respond to the Agency's strategic plan to synthesize the best 

available scientific information to prevent and reduce risks to humans and communities. Through 

sound science and risk-based decision-making, public health protection can be achieved while 

facilitating the efficient use of economic resources. The RA MYP supports this Agency strategy 

through providing health hazard, quantitative risk and exposure information in the format most 

appropriate to support decision-making actions. The assessments are based on scientific models, 

methods and guidance developed through this and other ORD MYPs and the published literature. 

Outreach and transfer of RA MYP products occurs through the IRIS database, NCEA and Forum 

websites, peer reviewed agency and journal publications, and ongoing communication, training 

and technical support to EPA program and regional offices and at scientific conferences. 

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EPA External Review Draft December 16, 2005 

Outreach and Effective Transfer

Outputvia the IRIS database, NCEA and Forum 

websites, peer reviewed agency and journal 

publications, and participation at scientific 

society and regional risk assessment meetings.

Inputthrough Congressional mandate, annual 

programmatic reviews, Federal Register 

solicitation, public meetings and external peer 

consultation.

Environmental Indicators

Impact Matrix: measuring incorporation of 

RA outputs into agency risk assessment 

practices and decisions, including use in 

agency site assessments, RODsand 

regulations, and the benefits resulting from 

this use of sound science, evaluated through 

independent external scientific review, such 

as the EPA BOSC and CASAC.

Resources

We apply our 

human resources 

and expertise in 

the diverse 

scientific fields 

contributing to risk 

assessment 

practice, 

supplemented 

through extramural 

funding and 

contractor support, 

and incorporating 

stakeholder, public 

and peer review 

input ...

Research Activities

... to compile, analyze 

and summarize the 

state of the science on 

environmental health 

hazards posed to 

humans by 

substances of priority 

concern to agency 

decision-makers, 

along with the models, 

methods, guidance 

and technical support 

necessary to enhance 

the quality of these 

analyses ...

Clients

... to risk 

assessors and 

managers in 

EPA client 

Offices and 

Regions 

dealing with air, 

water, land, and 

enforcement, in 

addition to 

other state and 

local risk 

assessors, the 

public and 

international 

organizations...

Short-term

Outcomes

... so that they 

have high quality 

health hazard 

information under 

the Integrated 

Risk Information 

System (IRIS) 

and Air Quality 

Criteria 

Documents 

(AQCD), based 

on sound 

scientific models, 

methods, and 

guidance ...

Immediate 

Outcomes

... leading to 

enhanced riskbased decisionmaking and levels 

of environmental 

agents in the air, 

water, land and 

food without 

appreciable risk to 

the public ...

Outputs

... to provide 

human health 

hazard 

assessments and 

quantitative risk 

information in a 

form most 

appropriate for 

decision-making, 

supported by peer 

reviewed agency 

reports, journal 

articles, and 

technical 

presentations ...

Long Term 

Outcomes

... resulting in 

improved 

health, wellbeing and 

prosperity of 

communities 

through 

science-based 

environmental 

decision 

making. 

Figure 2:Logic Model for the Human Health Risk Assessment Multi-Year Plan

Outreach and Effective Transfer

Outputvia the IRIS database, NCEA and Forum 

websites, peer reviewed agency and journal 

publications, and participation at scientific 

society and regional risk assessment meetings.

Inputthrough Congressional mandate, annual 

programmatic reviews, Federal Register 

solicitation, public meetings and external peer 

consultation.

Environmental Indicators

Impact Matrix: measuring incorporation of 

RA outputs into agency risk assessment 

practices and decisions, including use in 

agency site assessments, RODsand 

regulations, and the benefits resulting from 

this use of sound science, evaluated through 

independent external scientific review, such 

as the EPA BOSC and CASAC.

Resources

We apply our 

human resources 

and expertise in 

the diverse 

scientific fields 

contributing to risk 

assessment 

practice, 

supplemented 

through extramural 

funding and 

contractor support, 

and incorporating 

stakeholder, public 

and peer review 

input ...

Research Activities

... to compile, analyze 

and summarize the 

state of the science on 

environmental health 

hazards posed to 

humans by 

substances of priority 

concern to agency 

decision-makers, 

along with the models, 

methods, guidance 

and technical support 

necessary to enhance 

the quality of these 

analyses ...

Clients

... to risk 

assessors and 

managers in 

EPA client 

Offices and 

Regions 

dealing with air, 

water, land, and 

enforcement, in 

addition to 

other state and 

local risk 

assessors, the 

public and 

international 

organizations...

Short-term

Outcomes

... so that they 

have high quality 

health hazard 

information under 

the Integrated 

Risk Information 

System (IRIS) 

and Air Quality 

Criteria 

Documents 

(AQCD), based 

on sound 

scientific models, 

methods, and 

guidance ...

Immediate 

Outcomes

... leading to 

enhanced riskbased decisionmaking and levels 

of environmental 

agents in the air, 

water, land and 

food without 

appreciable risk to 

the public ...

Outputs

... to provide 

human health 

hazard 

assessments and 

quantitative risk 

information in a 

form most 

appropriate for 

decision-making, 

supported by peer 

reviewed agency 

reports, journal 

articles, and 

technical 

presentations ...

Long Term 

Outcomes

... resulting in 

improved 

health, wellbeing and 

prosperity of 

communities 

through 

science-based 

environmental 

decision 

making. 

Figure 2:Logic Model for the Human Health Risk Assessment Multi-Year Plan

Relevance and the Planning Process: The planning process for the RA MYP is closely linked to 

the needs of program and regional offices. Planning is conducted on a broad scale through 

preparation of the RA MYP, and on a more focused and iterative scale specific to each of the long 

term goals, particularly the selection and prioritization of IRIS assessments and PPRTVs, and the 

timing of AQCDs. On a broad scale, RA MYP development is conducted through a formal 

process that involves participation of EPA programs, regions and ORD laboratories in the human 

health research coordination team (RCT). RCT members are designated by their respective 

offices to represent their organizational needs and resources. The RCT planning process is 

supplemented by briefings to senior program managers on proposed MYP activities and outputs. 

The results of the planning process include revision or prioritization of planned ORD activities 

over the 5 - 8 year cycle of the MYP, including potential restructuring of the MYP long term 

goals. Draft MYPs prepared through this process are subject to internal EPA peer review by the 

RCT members and delegated program, regional or laboratory representatives. Internal peer 

review is also undertaken by the ORD Science Council, with approval by the ORD Executive 

Council prior to independent external peer review. RCT planning is an ongoing activity, 

recognizing that the MYPs are living documents subject to revision as programmatic needs and 

scientific developments alter priorities. 

 On a more focused scale, ongoing planning processes exist for a number of specific 

activities under the RA MYP. Formal planning of the IRIS assessment agenda occurs annually 

through a call to EPA programs and regions for nominations of priority substances for 

assessment. This is supplemented by an IRIS screening process that has been instituted to 

determine if newly published literature might impact existing, older IRIS assessments, and hence 

warrant consideration for revision. Provisional Peer Reviewed Toxicity Values (PPRTVs) are 

prepared on an ongoing basis at the request of the Office of Solid Waste and Emergency 

Response (OSWER) for those substances found at clean-up sites and for which no IRIS value is 

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EPA External Review Draft December 16, 2005 

available. Revisions to the AQCDs are planned every 5 years subject to the requirements of the 

Clean Air Act, taking into consideration resource constraints, OAQPS priorities, and court 

deadlines. 

 Due to the extent of this planning and programmatic input on priority needs, the RA MYP 

has a very close linkage between its outputs and programmatic use in hazardous site assessments 

and regulatory considerations. IRIS quantitative cancer and non-cancer risk values are accorded 

priority consideration in OSWER and regional site clean-up evaluations and are a prerequisite 

consideration in many regulatory determinations. AQCDs constitute the scientific basis for 

OAQPS staff papers relating to decisions on the National Ambient Air Quality Standards 

(NAAQS) for criteria air pollutants. RA MYP models, methods and guidance outputs generally 

serve as the standard for Agency health hazard assessment practice and are influential on a 

national and international scale. 

Quality and Peer Review: All RA MYP products are subject to internal and independent external 

peer review to assure their quality and objectivity. Peer reviews are conducted consistent with the 

policies detailed in EPA’s Peer Review Guidelines (U.S. EPA, 1998) and the OMB (2004) peer 

review guidance. These policies include categorization of all RA MYP products regarding their 

potential scientific, policy, and economic implications as a determinant of the level of peer review 

required. Many RA MYP products are considered influential or highly influential documents 

under these guidelines, and hence are subject to the most stringent peer review requirements, 

including independent external peer panels or review by EPA’s Science Advisory Board or the 

National Academy of Sciences. Other documents, such as journal manuscript submissions, 

undergo internal peer review prior to submission through normal publication peer review 

mechanisms. All EPA external peer reviewers are independently selected by peer review 

contractors, and are required to submit conflict of interest declarations. The conduct of the 

external peer review is organized and managed by an independent contractor or science 

organization. Public comment is solicited on major products undergoing peer review. 

 

 RA MYP products are also subject to the OMB and EPA Information Quality Guidelines 

(IQGs). These guidelines emphasize the importance of quality and objectivity in information 

disseminated by the federal government, and the benefits of independent peer review. A process 

is established under the IQGs whereby members of the public can submit a Request for 

Correction (RFC) should they believe that information disseminated by the federal government is 

erroneous. RA MYP activities are consistent with the IQGs through the emphasis on quality 

science and pre-dissemination reviews, implementation of the relevant ORD peer review 

guidelines and policies, and NCEA’s responsiveness to Requests for Correction submitted 

through the Office of Environmental Information (OEI). 

 

Technical Support: Technical support to customer programs and regions is a key component of all 

RA MYP activities, whether assessment production, methods development, guidance or other 

outputs. This support is provided through both formal and informal channels. Formal technical 

support is provided through the IRIS Help Desk and the Superfund Health Risk Technical 

Support Center. Where necessary, these support centers can access additional expertise from 

NCEA and other EPA scientists. Direct technical assistance is also provided by NCEA scientists 

to programs and regions that request regulatory or site specific support. These efforts are tracked 

internally through the Programmatic and Regulatory Support Tracking System. More informal 

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EPA External Review Draft December 16, 2005 

9 

channels are also widely used to expedite assistance on less complex issues, testifying to the 

widespread use of risk assessment products across the Agency and beyond. 

 Within the purview of the RA program, technical expertise is often transferred between 

projects in order to achieve program objectives. For example, Forum projects prepared under this 

MYP represent major Agency consensus documents requiring considerable technical and 

managerial input. To achieve the Forum objectives, technical support functions allocated to the 

Forum staff may be supplemented by experts from NCEA Divisions, who may chair or co-chair 

the Forum work groups alongside representatives of other EPA programs. Transfer of technical 

expertise also occurs between RA MYP long term goals, such as certain IRIS assessments serving 

as vehicles for informing the development of new models and methods. The RA MYP proposes 

continuing and emphasizing the existing formal technical support arrangements, and also 

recognizes the extent and importance of the ad hoc expert assistance provided to customers across 

EPA. 

Performance: RA MYP performance is tracked through a variety of Agency management 

systems. Within ORD-NCEA, IRIS outputs and production schedules are tracked through the 

internet accessible IRIS Track System (www.epa.gov/iristrac). As part of the ORD management 

system, RA MYP activities are tracked through the Annual Performance Goal (APG) and Annual 

Performance Measure (APM) system. Annex 1 provides the APG/M performance measures for 

this MYP, including products, output goals and completion dates. These deliverables are tracked 

by the ORD Office of Resource Management and Administration (ORMA) in the Integrated 

Resource Management System (IRMS) on a quarterly basis, with annual reporting. Major 

deliverables are reported to the White House Office of Management and Budget (OMB) and 

Congress. 

 

 OMB has also instituted the Performance Appraisal Rating Tool (PART), whereby all 

federal programs are rated on their performance in achieving identifiable public benefit outcomes. 

PART evaluation of the RA MYP is anticipated in FY’07. The proposed outcome measures for 

the RA MYP are outlined in Figure 2, under the subtitle Environmental Indicators. The RA MYP 

outcomes will be based on an impact matrix measuring the incorporation of RA MYP products 

into Agency risk assessment practice and decisions, including their use in site assessments, 

records of decision (RODs), and regulations, and the benefits to the public from this use of sound 

science. The impact of risk assessment models, methods and guidance development under the 

RA MYP will be evaluated through independent external scientific review, such as the ORD 

Board of Scientific Counselors (BOSC) and the Clean Air Scientific Advisory Committee 

(CASAC). 

Progress to Date/Changes 

 Although the RA MYP represents the first consolidated risk assessment planning 

instrument in ORD, assessment activities have been conducted in ORD-NCEA and its 

predecessor organizations (e.g., Office of Health and Environmental Assessment, OHEA; 

Carcinogen Assessment Group, CAG, etc.) for many years. These activities continue to be at the 

forefront of risk assessment science and remain central to EPA actions to protect human health 

and the environment. 
EPA External Review Draft December 16, 2005 

10 

 IRIS began two decades ago as an internal EPA activity to facilitate communication 

among ORD, programs and regions to harmonize the otherwise disparate reference values 

prepared for hazardous substances in different parts of the Agency. IRIS has since expanded to 

become the premier federal database for qualitative and quantitative environmental health hazard 

assessments. These assessments are widely regarded by regulators and stakeholders as providing 

a transparent and well documented resource on substances of central importance to environmental 

issues. IRIS values are now the primary toxicity values used in preliminary remediation 

evaluations (OSWER Directive 9285.7-53; 12/5/2003) and in many regulatory reviews conducted 

by EPA programs, such as the Office of Water and the Office of Air and Radiation. OSWER 

records of decision (RODs) for superfund sites and EPA regulatory proposals that reference IRIS 

values are then subject to additional public comment and peer review under the relevant 

adjudicatory procedures and Administrative Procedures Act (APA). IRIS has also been in the 

forefront of applying scientific advances to substance-specific assessments, such as PBPK 

modeling and data-derived uncertainty factors for intraspecies and interspecies extrapolation (e.g., 

boron), and to advancing mode of action considerations in cancer hazard characterization (e.g., 

perchlorate). 

 AQCDs have been prepared by NCEA or its predecessors since the creation of the EPA in 

early 1970s. AQCDs and the resulting NAAQS have been pivotal in achieving the air quality 

standards experienced today in the United States and they have influenced regulatory actions 

worldwide. The latest particulate matter AQCD was finalized in 2004, and the Ozone AQCD is 

scheduled for finalization in early 2006. Through the preparation of AQCDs, public health 

protection has been furthered by the ongoing, close, collaborative relationships between risk 

assessors, OAQPS regulators, and research scientists studying criteria air pollutants under other 

ORD research MYPs. 

 ORD-NCEA has also been responsive to urgent agency priorities, whether emergency risk 

assessment needs in the aftermath of the World Trade Center attack and Hurricane Katrina, or in 

response to immediate program office needs. Following the WTC attacks, NCEA was called on 

to assemble and assess the various data sources on air and dust concentrations of pollutants at 

ground zero and in the surrounding buildings. Experience gained from the WTC assessment has 

proven valuable in providing expeditious risk assessment support and advice to EPA’s 

remediation and re-entry evaluations in New Orleans following Hurricane Katrina. Urgent 

program needs have also been assisted through expedited re-assignment of staff resources. 

Platinum and cerium provisional reference concentration assessments were prepared in response 

to a special request from the OAR-Office of Transportation and Air Quality (OTAQ) regarding 

their evaluation of a proposed diesel fuel additive containing both of these metals. Independent 

reviews of the scientific validity of intentional dosing human pesticide studies were prepared by 

NCEA scientists to assist the Office of Pesticide Programs (OPP) in their re-registration 

evaluation of the scientific and ethical attributes of these studies, under intense public and 

Congressional scrutiny. Assistance was also provided to the Office of Pollution Prevention and 

Toxics (OPPT) in preparing the science background for a consent agreement on air toxics. 

 The models, methods and guidance development work in NCEA have been at the 

forefront of risk assessment science. Model development and application of the integrated 

exposure and uptake biokinetic model (IEUBK) for lead and other metals has become a standard 
EPA External Review Draft December 16, 2005 

11 

exposure assessment tool in site evaluations. Collaborative work continues between ORD 

laboratories and centers (NHEERL, NCEA, NCCT) on PBPK modeling and its application to risk 

assessment. Internet accessible statistical software packages have been well received by the risk 

assessment community, including the benchmark dose software and categorical regression 

software. NCEA environmental exposure products are considered a primary reference source in 

risk assessment practice, including ongoing work collating the Exposure Factors Handbook and 

the Children’s Exposure Factors Handbook. NCEA collaborative work with OPPTS on the 

Dioxin Exposure Initiative (DEI) set national and international quality standards through products 

such as the dioxin source inventory, coupled with the National Dioxin Air Monitoring Network 

(NDAMN). The DEI work provides a data framework to link dioxin source emissions to 

exposure pathways to human dose, informing program office considerations on dioxin risks and 

potential intervention strategies. Methods guidance work in NCEA on the derivation of 

inhalation reference concentrations and the application of inhalation dosimetry, and more recently 

on less than lifetime reference values, have been directly responsive to expressed program needs. 

 Risk Assessment Forum outputs have included the recent publication of EPA’s 

Carcinogen Risk Assessment Guidelines and the related Supplemental Guidance for Assessing 

Cancer Susceptibility Resulting from Early-Life Exposure to Carcinogens. Informed by extensive 

scientific peer review, these Guidelines advance cancer risk assessment methods by moving 

beyond alphanumeric cancer classifications to a narrative format with standard descriptors. This 

facilitates consideration of routes and nature of exposure, and a mode of action evaluation of the 

relevance to humans of tumors seen in animals. The early-life supplement sets the standard for 

quantitative evaluations of increased cancer risks from early-life exposure to carcinogens that 

have a mutagenic mode of action. The Forum has also recently published a Review of the RfD/C 

Processes, recommending modifications and enhancements to Agency practices dealing with noncarcinogenic risks. These activities complement the various Agency risk assessment guidance 

documents prepared by the Forum, including guidelines on reproductive toxicity, developmental 

toxicity, neurotoxicity, cumulative risk assessment, mutagenicity assessment, and exposure 

assessment, to name the most recent (www.epa.gov/ncea/raf). 

 The above-noted activities were conducted under a variety of program and media-specific 

plans in EPA’s GPRA goal structure. The newly consolidated RA MYP proposes continuing the 

broad themes apparent above, focusing on enhancing IRIS, AQCD and risk assessment guidance 

outputs through better aligning budget resources with planning priorities. In the interim between 

the consolidation of ORD’s risk assessment budget in 2004 and the finalization of this RA MYP, 

health risk assessment planning has been conducted on an annual basis during the President’s 

Budget submission cycle. As such, annual performance goals (APGs) and measures (APMs) have 

been updated in each successive annual planning cycle, accompanied by the deletion of redundant 

APG/Ms under other MYPs for that budget period. Through the preparation of this multi-year 

plan, all current year and out-year NCEA and Forum health risk assessment APG/Ms are 

consolidated into the RA MYP, or deleted. The objectives of many of the APMs have been 

retained, such as the movement of AQCDs from the ozone and particulate matter plans to the RA 

MYP. These actions have been coordinated with the relevant National Program Directors and 

ORD Laboratory and Center Directors. 
EPA External Review Draft December 16, 2005 

12 

Overview of the Long Term Goals

 

 As noted, the overarching objective of the RA MYP is the production of state-of-thescience health hazard assessments to respond to program and regional needs on a timely basis, 

along with the models, methods and guidance necessary to maintain the quality of these risk 

assessment products. To achieve this, there are three long term goals (LTGs) under the RA MYP: 

 LTG 1: Integrated Risk Information System (IRIS) and other priority health hazard 

assessments: Agency, state and local risk assessors use the state-of-thescience health hazard assessment information provided on priority 

substances in their decisions and actions to protect human health from risks 

posed by environmental pollutants. 

 LTG 2: State-of-the-science risk assessment models, methods, and guidance: EPA 

programs, states and other risk assessors use the risk assessment models, 

methods, and guidance provided to enhance, through the incorporation of 

contemporary scientific advances, the quality and objectivity of their 

assessments and decision-making on environmental health risks. 

LTG 3: Air Quality Criteria Documents: As mandated in the Clean Air Act, the 

ambient air criteria pollutants are reviewed and AQCDs revised to reflect 

the best available scientific information on identifiable effects on public 

health and the environment from exposure to the pollutant, and this 

information is used by the EPA Office of Air and Radiation in their review 

and promulgation of the National Ambient Air Quality Standards 

(NAAQSs) to protect public health with an adequate margin of safety. 

 Because the LTG 2 work is an essential support to LTG 1 and 3 assessment activities, the 

level of effort between these goals is maintained at a ratio of approximately 25 percent LTG 2 

development work to 75 percent assessment effort. With this guidance, table 1 summarizes the 

level of effort devoted to the LTGs: 

Table 1: Area Emphasis in MYP Planning Window

LTG 1: IRIS and other priority assessments Level, increasing subject to initiative request 

LTG 2: Models, methods and guidance Level, decreasing if RA budget reductions 

LTG 3: Air quality criteria documents Level 
EPA External Review Draft December 16, 2005 

13 

LTG1: Integrated Risk Information System (IRIS) and other priority health hazard 

assessments

 

 The core of the RA MYP activities is the Integrated Risk Information System (IRIS). 

IRIS is an Agency-wide program managed by NCEA with active participation by program offices 

and regions, who nominate chemicals for the annual IRIS agenda and, through designated 

reviewers, participate in the Agency consensus review of assessments. A typical IRIS output 

includes a Toxicological Review and Summary of the environmental health hazards posed by a 

substance to humans. The Toxicological Review provides a hazard characterization of available 

toxicological information, in addition to quantitative estimates of human risk. Quantitative risk 

values include the IRIS reference dose (RfD; and reference concentration, RfC), which is: 

“An estimate of a daily oral exposure for a given duration to the human population 

(including susceptible subgroups) that is likely to be without an appreciable risk of 

adverse health effects over a lifetime. It is derived from a BMDL, a NOAEL, a LOAEL, 

or another suitable point of departure, with uncertainty/variability factors applied to reflect 

limitations of the data used.” 

 

 The cancer slope factor is an upper bound estimate of the increased cancer risk from a 

lifetime of exposure to an agent, expressed as the proportional increase in cancer risk per 

mg/kg/day dose. These qualitative and quantitative assessments are summarized and 

disseminated through the internet at www.epa.gov/IRIS. Other types of assessment values, such 

as acute and less-than-lifetime toxicity values, are currently in a pilot development phase and will 

be incorporated into IRIS documents as they become available. Tools and guidance for 

conducting the new assessments are being developed under LTG 2 of the RA MYP. 

 Although non-regulatory, quantitative IRIS values influence many environmental 

decisions and may serve as a basis for additional regulatory consideration. The hazard 

characterization and dose-response assessments provided by IRIS constitute the first two steps in 

the NAS (1983) risk assessment paradigm, the other steps being exposure assessment and risk 

characterization. In the Agency context, IRIS toxicity values resulting from the dose-response 

assessment (e.g., RfD, CSF) can be combined with site-specific exposure estimates (e.g., 

exposure to the chemical in food, in drinking water, in soil at a waste site, in air near an 

incinerator) to provide a risk estimate for the situation of interest. In doing so, the “health hazard 

assessment” information provided by IRIS contributes to a fuller “risk assessment” as defined 

under the NAS paradigm and applied in programmatic and regional actions. 

 In addition to standard IRIS assessments, the RA MYP also conducts more resource 

intensive assessments of major chemicals. Designation as a major assessment takes into 

consideration such factors as the regulatory scope and priority of the substance, its production 

volume, potential economic impact, scientific complexity, precedent setting nature, and/or 

national importance. These highly complex assessments often lead EPA to identify new research 

needs, apply new methodologies, or conduct multiple high level external scientific peer reviews to 

ensure the application of sound science. These requirements are generally associated with 

additional external scrutiny and increased time for completion, potentially impacting NCEA’s 

ability to accurately estimate finalization dates beyond those under its direct control. A number 

of major assessments also go beyond hazard and dose-response information by providing 
EPA External Review Draft December 16, 2005 

exposure and risk characterization conclusions, such as the World Trade Center assessment and 

dioxin reassessment. Due to their importance, major assessments are identified on a substancespecific basis in this MYP. 

 It should not be construed from the previous summary that IRIS assessments are 

boilerplate in nature, beyond the standardized outputs for ease of use by risk assessors and 

managers (e.g., RfD, RfC, CSF). Each IRIS assessment presents its own unique database, 

scientific questions, and science-policy judgments. These substance-specific factors highlight the 

importance of the transparent, Agency-wide consensus process undertaken to develop IRIS values 

and to maintain this contemporary repository of information. The individual nature of each IRIS 

assessment is the product of a number of factors, commencing with the quantity, quality and 

relevance of available toxicological data. Individual IRIS assessments may also vary due to 

different opportunities to apply new advances in risk assessment science, such as improved 

models, methods, and updated Agency guidance. Specific program requests may also be 

responded to through a combination of risk assessment guidance development followed by 

implementation of this guidance in IRIS and AQCD assessments. Examples of this progression 

include methods development for, and calculation of, acute and less-than-lifetime reference doses, 

and application of the supplemental guidance for children’s cancer risk in IRIS assessments. In 

this way, IRIS serves as a dynamic system where substance-specific scientific needs can be 

identified for research and development, and, conversely, as a vehicle where the results of such 

scientific advances can be applied for use in decision-making. 

 The process for developing an IRIS assessment commences with the solicitation of 

chemical nominations from EPA programs and regions, and, in some years, from other 

government agencies and the public. EPA uses four general criteria to set priorities: 1) EPA 

statutory, regulatory, or program-specific implementation needs; 2) availability of new scientific 

information or methods that might significantly change the current IRIS information; 3) interest to 

other levels of government or the public; and 4) availability of other scientific assessment 

documents such that only a modest additional effort would be needed to complete the review and 

documentation for IRIS. IRIS also screens the published literature to determine if new 

information has become available that might alter an existing IRIS toxicity value. The results of 

this screening are factored into setting priorities. 

 Upon selection of a substance for review, the process for developing assessments is 

detailed in the IRIS standard operating procedures and consists of 1) an annual Federal Register 

announcement of EPA’s IRIS agenda and call for scientific information from the public on 

selected chemical substances; 2) a search of the scientific literature; 3) development of IRIS 

summaries and support documents; 4) Agency review; 5) external peer review and public 

comment; 6) management review and approval; and 7) entry of IRIS summaries and support 

documents into the IRIS database. Modifications to this process to incorporate additional 

interagency and National Academy of Sciences (NAS) review are under consideration. 

 As outlined in the standard operating procedures, the development of an IRIS summary 

and toxicological review commences with agreement on the scope of the assessment, a proposed 

timeline, and major projected milestones. Broad Agency expertise is solicited early on through 

holding a scoping or problem formulation meeting, including invitations to interested NCEA staff 

and coordination with scientists from the ORD effects laboratory (NHEERL). Invitations are also 

14 
EPA External Review Draft December 16, 2005 

extended to representatives from EPA Offices and Regions, and may include staff from ATSDR 

or other government agencies and the chemical manager's assessment development contractor. 

The scoping meeting seeks early identification of critical science issues pertinent to the 

assessment, as well as to facilitate communication of forthcoming laboratory results relevant to 

the proposed assessment schedule. Additional internal peer consultation is sought in the 

development phase of the assessment on such matters as advice on the location or interpretation 

of studies, modeling approaches, interpretation of risk assessment guidelines, identification of 

issues for Agency review, and other facets of assessment preparation. This is followed by more 

formal internal peer review and then Agency-wide review, in advance of the external review 

phase. 

 All IRIS assessments undergo independent external peer review, accompanied by a federal 

register announcement of the public meeting and a request for comments to be submitted 

approximately two weeks beforehand for consideration by the peer reviewers. Each 

Toxicological Review contains a summary and disposition of these peer review and major public 

comments. The progression of individual chemical assessments through this process, along with 

estimated future completion dates, are tracked through the publicly available IRIS Track database 

(http://cfpub.epa.gov/iristrac/index.cfm). 

 

 Complementing these major assessments are the provisional peer-reviewed toxicity values 

(PPRTVs) for substances of potential concern but where no IRIS value is available. PPRTVs are 

developed and peer reviewed on an expeditious basis at the request of the Office of Solid Waste 

and Emergency Response (OSWER), which uses PPRTVs in its evaluation of Superfund sites. 

 Figure 3 conveys the APG diagram for RA LTG 1. Major risk assessments are identified 

and contribute to an annual IRIS output total of 16 or more hazard/dose-response assessments. 

This number is based on estimated completion dates of assessments commenced since the 

expansion of IRIS resources in the period 2001 to 2005. It represents a rapid increase in output 

maintained at a projected annual rate of completion, assuming constant resource allocations while 

projecting additional review and finalization requirements. To this total are added an annual 

output of 25 new and 25 revised PPRTVs for OSWER, following the initial completion of 150 

PPRTVs. These annual performance goals and measures are listed in Appendix 1. 

 The APG output for major assessments is defined as “Agency completion for interAgency 

review or external peer review.” This is the process stage at which the Agency relinquishes direct 

control of production dates. The interagency process consists of review by the Executive Office 

of the President, coordinated as needed with other federal agencies. Experience has demonstrated 

that finalization and public dissemination dates for major assessments depend heavily on the path 

chosen for finalization of the external review phase. Delays in finalization are likely to compound 

due to the ongoing advancement of science in the interim, necessitating additional revisions to the 

assessments and further peer review. 

 

 Decisions on the type and extent of external peer review and finalization procedures are 

often made late in the assessment process as the science unfolds and areas of controversy become 

apparent. These late decisions are not amenable to advance planning on a chemical-specific basis 

in the Agency multi-year planning process. Recognizing, however, the importance of these 

15 
EPA External Review Draft December 16, 2005 

individual, major assessments, the RA MYP has sought to maximize information on individual 

substances without compromising its ability to define ambitious, yet realistic, future APG targets. 

This balance is achieved through providing chemical-specific completion dates up to the step of 

interagency or external peer review. Because of the central importance of finalization and 

external dissemination of RA assessments, additional APMs are anticipated to track assessment 

finalization and public dissemination dates as sufficient advance information becomes available. 

In the interim, estimated completion dates are publicly available in IRIS Track. RA MYP 

resources have also been retained in out-years for the completion of these priority assessments 

and, coupled with anticipated new starts, constitute an ambitious out-year plan of increasing 

output of external review and finalized assessments on a fixed resource base. 

LTG 1: Integrated Risk Information System (IRIS) and other priority health hazard assessments: 

Agency, state and local risk assessors use the state-of-the-science health hazard assessment 

information provided on priority substances in their decisions and actions to protect human health 

from risks posed by environmental pollutants. 

06 07 08 09 10 11 12

Provisional 

Toxicity 

Values

IRIS 

assessments

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylamide

MTBE 

naphthalene (ca)

perchloroethylene

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (nonCa) 

ethanol

styrene

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (ca), 

polycyclic 

aromatic 

hydrocarbons

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed, 

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylonitrile

formaldehyde

methanol

methylene Cl

trichloroethylene 

dioxin

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Major 

Assessments

Figure 3: Human Health Risk Assessment LTG 1 Annual Performance Goals

LTG 1: Integrated Risk Information System (IRIS) and other priority health hazard assessments: 

Agency, state and local risk assessors use the state-of-the-science health hazard assessment 

information provided on priority substances in their decisions and actions to protect human health 

from risks posed by environmental pollutants. 

06 07 08 09 10 11 12

Provisional 

Toxicity 

Values

IRIS 

assessments

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylamide

MTBE 

naphthalene (ca)

perchloroethylene

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (nonCa) 

ethanol

styrene

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (ca), 

polycyclic 

aromatic 

hydrocarbons

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed, 

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylonitrile

formaldehyde

methanol

methylene Cl

trichloroethylene 

dioxin

16 IRIS 

hazard/DR 

assessments

+

25 new & 

25 revised 

PPRTVs

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylamide

MTBE 

naphthalene (ca)

perchloroethylene

16 IRIS 

hazard/DR 

assessments

+

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed,

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

Major 

Assessments

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

acrylonitrile

formaldehyde

methanol

methylene Cl

trichloroethylene 

dioxin

16 IRIS 

hazard/DR 

assessments

+

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (nonCa) 

ethanol

styrene

16 IRIS 

hazard/DR 

assessments

+

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

to be developed, 

ongoing 

finalization & 

new starts

16 IRIS 

hazard/DR 

assessments

+

Complete 

health hazard 

assessments 

for interagency 

review or 

external peer 

review for:

asbestos (ca), 

polycyclic 

aromatic 

hydrocarbons

16 IRIS 

hazard/DR 

assessments

+

Major 

Assessments

Figure 3: Human Health Risk Assessment LTG 1 Annual Performance Goals

IRIS 

assessments

Provisional 

Toxicity 

Values

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

25 new & 

25 revised 

PPRTVs

16 
EPA External Review Draft December 16, 2005 

LTG 2: State-of-the-science risk assessment models, methods, and guidance

 Risk assessment models, methods and guidance development under the RA MYP is 

directed toward incorporating scientific advances into risk assessment practice, similar to 

equipment upgrades to maintain standards of practice. The LTG 2 outputs support the applied 

decision-making needs of the EPA programs and regions, either directly or through RA LTG 1 

(IRIS) and 3 (AQCD) outputs. These program needs vary from estimating risk levels in exposed 

people and determining safe levels of environmental pollutants in media such as air and water, to 

supporting regulatory actions on specific substances and developing clean-up standards for 

restoring the environment. In making these decisions, risk managers seek information on best 

estimates of risk, the uncertainty in these estimates, and whether their decisions will be 

sufficiently protective of potentially sensitive populations, such as children. 

 Of central importance to these environmental decisions is the need to better quantify risks 

and characterize uncertainty at the low environmental exposure levels generally experienced in 

real world situations by large numbers of people, including susceptible populations. This public 

health protection objective cannot be achieved through direct research testing of people due to 

ethical, logistical and statistical constraints. Decisions can be informed, however, through 

extrapolation from available in vitro, in vivo, epidemiological and other data. These 

extrapolations include between animals and humans, from high to low dose, between routes of 

exposure, and among individual humans, including susceptible populations. Research to inform 

risk decisions can be broken down along these extrapolation components and the numerous 

factors that contribute to the variability and uncertainty in each component. For instance, high to 

low dose extrapolation can be informed by understanding such factors as dose-response model 

shape and the relevance of the high dose mode of action to low doses. Primary research on these 

components is undertaken by the ORD laboratories under various MYPs, and is a primary 

consideration of the ORD Human Health Research Program. RA MYP LTG 2 acts to 

incorporate these data and analyses, along with other published literature, into EPA risk 

assessment practices and risk assessment outputs. 

 Two distinct, yet inter-related, organizational units are supported under RA MYP LTG 2. 

The first is the models, methods and guidance development work conducted by ORD-NCEA. 

The second is the Risk Assessment Forum, which is administratively housed in NCEA with 

support staff and extramural funding under LTG 2, but which is functionally an Agency-wide 

organization. As an Agency-wide organization, Forum activities are supplemented through 

additional ORD, program and regional resources provided through committee staffing and 

extramural funding. Details on these two organizational units are as follows: 

ORD-NCEA Activities under LTG 2: Risk assessment development activities in NCEA respond 

to the diverse array of scientific disciplines informing risk assessment practice and the expanding 

science base in these fields. Failure to stay current with scientific advances can impact the 

quality of assessments when evaluated against external peer review standards. This could 

potentially impugn Agency products and the ability of programs to make appropriate and timely 

risk management decisions. Given this breadth of science, the NCEA LTG 2 planning process 

commenced with the identification of risk assessment activity foci by ORD-NCEA science staff 

and management. The selection of foci took into consideration programmatic priorities, applied 

 17 
EPA External Review Draft December 16, 2005 

risk assessment needs, the impact of ongoing scientific developments, and the expertise available 

to incorporate these advances into Agency practice. The resulting risk assessment foci serve to 

facilitate resource allocation and strategic hiring in NCEA, in addition to conveying priorities for 

laboratory research elsewhere in ORD. The LTG 2 foci are: 

< Physiologically-based pharmacokinetic (PBPK) modeling, using measured biological 

parameters, such as blood flow and diffusion rates, to mathematically model differences 

and improve extrapolation between and within animal species, humans, and their 

lifestages to better estimate dose-response functions in toxicology. Whereas primary 

physiological data and PBPK models are principally developed in the laboratories, the 

RA MYP activities are focused on the applicability of these models, their uncertainty 

parameters, and guidance for use in risk assessment. 

< Mode of action (MoA), applying available data to increase understanding of the way in 

which toxicity occurs in order to inform decisions on the relevance of high dose effects to 

low level environmental exposures, within and between species, and the quantitative 

impacts of these factors on dose-response functions used in risk assessment. 

< Quantitative methods to incorporate state-of-the-science mathematical, probabilistic and 

statistical advances into EPA risk assessment practice, particularly dealing with 

uncertainty and variability analysis in dose-response assessment for low environmental 

exposures. 

< Inhalation toxicology to apply risk assessment and pulmonary toxicology advances to 

EPA inhalation methods for interspecies extrapolation and dose-response assessment. 

< Exposure assessment, to maintain the quality and utility of the exposure factors 

handbooks for use Agency-wide, and the application and refinement of exposure methods 

to risk assessment. 

< Mixtures assessment, moving beyond single chemical assessments to develop and apply 

novel methods for quantitative health risk assessment of chemical mixtures, accompanied 

by guidance on chemical mixtures exposure assessment for use in complex, real world, 

environmental situations. 

< Microbial risk assessment, to extend and apply risk assessment methods, particularly 

probabilistic approaches and dynamic system analyses, to priority pathogens hitherto 

inadequately addressed on a quantitative basis, thereby facilitating the assessment of 

pathogen risks necessary for informed decision-making. 

Risk Assessment Forum Activities under LTG 2: The Risk Assessment Forum was established 

in 1983 to promote consensus on risk assessment issues and to ensure that this consensus is 

incorporated into appropriate Agency risk assessment documents. The Forum focuses on generic 

issues fundamental to the risk assessment process and related science-policy issues. Forum 

activities include reports of Agency colloquia on specific risk assessment topics to inform and 

communicate among Agency programs, and the development of Agency-wide guidelines, issue 

18 
EPA External Review Draft December 16, 2005 

papers, and training on complex risk assessment topics, such as the cancer guidelines, children’s 

risk, cumulative risk, and harmonization of cancer and non-cancer risk assessments. These 

documents set Agency science-policy for the conduct of risk assessment activities, and provide 

leadership to other national and international actions. Major Forum guidance documents are 

developed in accordance with the Agency’s regulatory and policy development process, and 

become Agency policy upon approval by the Administrator or the EPA Science Policy Council. 

 The Chairperson for the Forum is appointed by the EPA Deputy Administrator. Forum 

committee members are assembled from throughout the Agency in a formal process to provide 

scientific and programmatic expertise to study and report on risk assessment issues from an 

agency-wide perspective. Direct staff, logistical and extramural funding support for the Forum 

are tracked under RA MYP LTG 2. 

 Forum activities may be proposed at any time by regions and program offices, and are 

evaluated by the Forum steering committee. Criteria for choosing projects include: Agency-wide 

applicability, new or emerging risk assessment issues, opportunity for developing Agency-wide 

consensus, current project work loads and the availability of scientific staff to serve as panel 

members. Ongoing and planned Forum activities are listed in Table 2: 

Table 2: Planned Activities and Publications of the Risk Assessment Forum

Integrating economics and risk assessment.

Data derived uncertainty factors. 

Metals assessment framework. 

Benchmark dose technical guidance. 

Children’s exposure age-groups. 

Harmonization of uncertainty factors. 

Body weight to the three-quarter power. 

Exposure assessment guidelines update. 

Mutagenic mode of action guidance. 

Peroxisome proliferation (PPAR) mode of action. 

Immunosuppression risk assessment guidance. 

Guidance on bladder tumors. 

Cumulative risk assessment issue papers. 

Cumulative risk assessment guidance. 

Microbial risk assessment guidance. 

 There is a close relationship between the NCEA risk assessment foci and the planned 

Forum activities. Contemporary Forum documents contribute a science-policy foundation for 

ongoing risk assessment development work in NCEA. Future Forum documents serve as a locus 

for the synthesis and output of NCEA foci development activities. Because of this interrelationship, NCEA and Forum products are included together in the following APG structure 

and wiring diagrams, with the Agency-wide Forum products labeled in the APG/Ms (appendix 

A) and distinguished by italics and broken perimeter lines in Figure 5 and Appendix B. 

 Figure 4 illustrates the linkage provided in the RA MYP between primary research and the 

application of this information to risk assessment and, ultimately, risk management decisions. 

The ORD research MYPs (e.g., human health, computational toxicology, drinking water) are 

depicted as examples of focused contributors to the broad body of scientific information that 

informs risk assessment practice. While the research from specific ORD MYPs is incorporated as 

it becomes available, example linkage times are illustrated where ORD laboratory research will 

particularly influence the flow of risk assessment methods development activities planned under 

LTG 2 and depicted across the center of this figure. The LTG 2 products then inform risk 

19 
EPA External Review Draft December 16, 2005 

assessment practices under LTG 1 (IRIS) and LTG 3 (AQCD). The primary research and LTG 2 

products may also be directly incorporated into program and regional assessments. Experience 

from conducting risk assessments feeds back into the identification of priority research needs, 

and, hence, the iterative development and transfer of new scientific information into risk 

assessment practice. 

LTG 2: State-of-the-science risk assessment models, methods and guidance: EPA programs, states and 

other risk assessors use the risk assessment models, methods, and guidance provided to enhance, through 

the incorporation of contemporary scientific advances, the quality and objectivity of their assessments and 

decision-making on environmental health risks. 

06 07 08 09 10 11 12

Quantitative 

RA models 

& tools

Integrating 

RA advances 

into 

quantitative 

frameworks 

Integrating & 

synthesizing 

progress in 

RA models 

and methods

Quantitative 

RA advances, 

including 

central 

tendency & 

uncertainty

Risk 

assessment 

guidance

HH Research 

LTG4 –

Evaluating 

Risk 

Management 

Decisions

ORD HH 

Research 

LTG3 –

Populations 

at Risk 

ORD HH 

Research 

LTG2 –

Cumulative

/Aggregate

ORD 

Drinking 

Water 

Research

ORD HH 

Research 

LTG1 –

Mode of 

Action

Agency Risk Assessment Practice

Risk Assessment LTG3 – Air Quality Criteria Documents

Risk Assessment LTG1 – IRIS and Other Health Hazard Assessments

Mode of Action 

to refine RA & 

extend beyond 

the range of 

data

Guidance on 

RA models & 

uncertainty 

analysis

Expanding 

single 

substance RA 

to complex 

environmental 

mixtures

ORD 

Comp. Tox. 

Research

Scientific Advances, Publications and other Data Informing Human Health Risk Assessment

Figure 4: RA LTG 2 Flow Chart and APG Relationships

ORD 

Air 

Toxics

Research

ORD

Ozone

Research

ORD 

Particulate 

Matter 

Research

LTG 2: State-of-the-science risk assessment models, methods and guidance: EPA programs, states and 

other risk assessors use the risk assessment models, methods, and guidance provided to enhance, through 

the incorporation of contemporary scientific advances, the quality and objectivity of their assessments and 

decision-making on environmental health risks. 

06 07 08 09 10 11 12

Quantitative 

RA models 

& tools

Integrating 

RA advances 

into 

quantitative 

frameworks 

Integrating & 

synthesizing 

progress in 

RA models 

and methods

Quantitative 

RA advances, 

including 

central 

tendency & 

uncertainty

Risk 

assessment 

guidance

HH Research 

LTG4 –

Evaluating 

Risk 

Management 

Decisions

ORD HH 

Research 

LTG3 –

Populations 

at Risk 

ORD HH 

Research 

LTG2 –

Cumulative

/Aggregate

ORD 

Drinking 

Water 

Research

ORD HH 

Research 

LTG1 –

Mode of 

Action

Agency Risk Assessment Practice

Risk Assessment LTG3 – Air Quality Criteria Documents

Risk Assessment LTG1 – IRIS and Other Health Hazard Assessments

Mode of Action 

to refine RA & 

extend beyond 

the range of 

data

Guidance on 

RA models & 

uncertainty 

analysis

Expanding 

single 

substance RA 

to complex 

environmental 

mixtures

ORD 

Comp. Tox. 

Research

Scientific Advances, Publications and other Data Informing Human Health Risk Assessment

Figure 4: RA LTG 2 Flow Chart and APG Relationships

ORD 

Air 

Toxics

Research

ORD

Ozone

Research

ORD 

Particulate 

Matter 

Research

 Figure 5 provides details on the LTG 2 annual performance goals. The objective of the LTG 2 

APGs is to advance risk assessment science along themes most relevant to EPA’s mission needs. In 

doing so, the APGs serve to maintain the quality and objectivity of RA MYP and other Agency risk 

assessment products when evaluated against contemporary peer review science standards. Each APG 

represents the cumulative result of the individual contributing ORD-NCEA and Forum APMs (listed by 

year in Appendix A) and support activities. Each APG also builds on previous APG outputs, 

demonstrating a progression of risk assessment advances that culminate in synthesis and guidance 

outputs to support Agency activities and provide a common basis for decision-making. This progression 

of risk assessment themes occurs in parallel with the incorporation of the individual development 

activities, as they occur, into substance-specific assessments. Appendix B provides additional detail on 

the LTG 2 development activities in an annual operating plan structure, grouped and color coded by the 

risk assessment foci discussed previously. 

 The progression of planned risk assessment advances commences in FY’06 and ’07 with 

improved quantitative modeling methods, particularly measures of central tendency and uncertainty 

analysis which are of central importance to concerns expressed by EPA programs, stakeholders and the 

20 
EPA External Review Draft December 16, 2005 

scientific community. Rather than providing single point estimates of upper bound risks, the FY’07 

APG tracks scientific advances toward estimating risk distributions and providing a fuller 

characterization of uncertainty and variability. As these quantitative models are developed and 

experienced is gained with their use, opportunities exist to broaden their applicability and integrate these 

methods into other quantitative assessment frameworks. This is achieved in the FY’08 APG through 

integrating quantitative advances into PBPK modeling procedures, interspecies scaling defaults, 

exposure assessment and microbial risk assessment models. 

06 07 08 09 10 11 12

Quantitative 

RA models & 

tools:

Provide models 

and tools for 

improving 

quantitative 

dose-response 

relationships, 

characterizing 

human 

exposures and 

reducing 

uncertainty in 

risk assessments

Integrating RA 

advances into 

quantitative 

frameworks:

Integrate PBPK, 

exposure, microbial 

and biological 

modeling advances 

into quantitative risk 

frameworks, thereby 

applying 

mathematical 

modeling and data 

advances to 

biological systems, 

including: 

application of 

uncertainty analysis 

to PBPK modeling, 

exposure factors 

parameters, and 

microbial RA 

models; and

Forum activities on

the quantitative 

basis for 

interspecies scaling;

dermal exposure 

methods; and 

exposure assessment 

guidelines.

Mode of Action to 

refine RA & 

extend beyond the 

range of data:

Incorporate mode of 

action advances to 

improve approaches 

for cancer and noncancer RA, 

facilitating 

quantitative 

estimates of risk 

within the range of 

data and at 

environmental 

exposure levels, 

including a 

framework for 

applying MoA in 

RA and linking this 

to dose-response 

analysis; and 

Forum activities on

the implications of 

MoA in peroxisome

proliferation, 

bladder tumors, 

mutagenesis, and

immunosuppression.

Guidance on RA 

models & 

uncertainty 

analysis:

Apply uncertainty 

analyses in 

biologically-based 

risk assessment 

models, 

accompanied by the 

development of risk 

assessment 

guidance to 

disseminate 

information, 

including tools to 

characterize 

uncertainty and 

variability in PBPK 

models; lifestage

data and its 

application to 

children’s RA; and 

RfC methods 

guidance, less than 

lifetime RA 

guidance, and 

Forum guidance on

microbial RA . 

Expanding single 

substance RA to 

complex 

environmental 

mixtures:

Develop models, 

methods and 

guidance to move 

beyond single 

chemical 

assessments to 

incorporate 

methods and 

modeling advances 

for 

environmentallyrelevant mixtures of 

chemicals, through 

mixtures exposure 

assessment 

guidance; 

cumulative risk 

case studies for 

community 

assessment; and a 

Forum guidance on

cumulative risk 

assessment.

Integrating & 

synthesizing 

progress in RA 

models & 

methods:

Integrate and 

synthesize 

improvements in 

dose-response 

methods and 

models in risk 

assessment, 

including synthesis 

of the application 

of distributional 

data and 

uncertainty in RA 

quantitation and 

models; and 

methods for 

judgment-based 

probabilistic 

analysis and 

decision-making.

Quantitative RA 

advances, including 

central tendency & 

uncertainty:

Develop mathematical 

models to address an 

expanded range of data 

sets, including measures 

of central tendency and 

uncertainty analysis, 

accompanied by 

dissemination for use in 

quantitative risk 

assessment, including: 

categorical regression, 2-

stage clonal, and acute 

models to incorporate 

current standards of RA 

science into EPA 

practice; methods for 

central tendency and 

uncertainty in RA 

modeling; BMD 

software development; 

and Forum activities on

BMD guidance; data 

derivation and harmonization of uncertainty 

factors; and age groups 

for children’s exposure 

assessment.

RA guidance: 

Development of 

guidance, 

methods and 

technical support 

for conducting 

risk assessments 

and benefits 

analysis for 

Agency-wide 

use in risk 

management 

decisions.

Figure 5: Human Health Risk Assessment LTG 2 Annual Performance Goals

* Forum activities in italics

06 07 08 09 10 11 12

Quantitative 

RA models & 

tools:

Provide models 

and tools for 

improving 

quantitative 

dose-response 

relationships, 

characterizing 

human 

exposures and 

reducing 

uncertainty in 

risk assessments

Integrating RA 

advances into 

quantitative 

frameworks:

Integrate PBPK, 

exposure, microbial 

and biological 

modeling advances 

into quantitative risk 

frameworks, thereby 

applying 

mathematical 

modeling and data 

advances to 

biological systems, 

including: 

application of 

uncertainty analysis 

to PBPK modeling, 

exposure factors 

parameters, and 

microbial RA 

models; and

Forum activities on

the quantitative 

basis for 

interspecies scaling;

dermal exposure 

methods; and 

exposure assessment 

guidelines.

Mode of Action to 

refine RA & 

extend beyond the 

range of data:

Incorporate mode of 

action advances to 

improve approaches 

for cancer and noncancer RA, 

facilitating 

quantitative 

estimates of risk 

within the range of 

data and at 

environmental 

exposure levels, 

including a 

framework for 

applying MoA in 

RA and linking this 

to dose-response 

analysis; and 

Forum activities on

the implications of 

MoA in peroxisome

proliferation, 

bladder tumors, 

mutagenesis, and

immunosuppression.

Guidance on RA 

models & 

uncertainty 

analysis:

Apply uncertainty 

analyses in 

biologically-based 

risk assessment 

models, 

accompanied by the 

development of risk 

assessment 

guidance to 

disseminate 

information, 

including tools to 

characterize 

uncertainty and 

variability in PBPK 

models; lifestage

data and its 

application to 

children’s RA; and 

RfC methods 

guidance, less than 

lifetime RA 

guidance, and 

Forum guidance on

microbial RA . 

Expanding single 

substance RA to 

complex 

environmental 

mixtures:

Develop models, 

methods and 

guidance to move 

beyond single 

chemical 

assessments to 

incorporate 

methods and 

modeling advances 

for 

environmentallyrelevant mixtures of 

chemicals, through 

mixtures exposure 

assessment 

guidance; 

cumulative risk 

case studies for 

community 

assessment; and a 

Forum guidance on

cumulative risk 

assessment.

Integrating & 

synthesizing 

progress in RA 

models & 

methods:

Integrate and 

synthesize 

improvements in 

dose-response 

methods and 

models in risk 

assessment, 

including synthesis 

of the application 

of distributional 

data and 

uncertainty in RA 

quantitation and 

models; and 

methods for 

judgment-based 

probabilistic 

analysis and 

decision-making.

Quantitative RA 

advances, including 

central tendency & 

uncertainty:

Develop mathematical 

models to address an 

expanded range of data 

sets, including measures 

of central tendency and 

uncertainty analysis, 

accompanied by 

dissemination for use in 

quantitative risk 

assessment, including: 

categorical regression, 2-

stage clonal, and acute 

models to incorporate 

current standards of RA 

science into EPA 

practice; methods for 

central tendency and 

uncertainty in RA 

modeling; BMD 

software development; 

and Forum activities on

BMD guidance; data 

derivation and harmonization of uncertainty 

factors; and age groups 

for children’s exposure 

assessment.

RA guidance: 

Development of 

guidance, 

methods and 

technical support 

for conducting 

risk assessments 

and benefits 

analysis for 

Agency-wide 

use in risk 

management 

decisions.

Figure 5: Human Health Risk Assessment LTG 2 Annual Performance Goals

* Forum activities in italics

06 07 08 09 10 11 12

Quantitative 

RA models & 

tools:

Provide models 

and tools for 

improving 

quantitative 

dose-response 

relationships, 

characterizing 

human 

exposures and 

reducing 

uncertainty in 

risk assessments

Integrating RA 

advances into 

quantitative 

frameworks:

Integrate PBPK, 

exposure, microbial 

and biological 

modeling advances 

into quantitative risk 

frameworks, thereby 

applying 

mathematical 

modeling and data 

advances to 

biological systems, 

including: 

application of 

uncertainty analysis 

to PBPK modeling, 

exposure factors 

parameters, and 

microbial RA 

models; and

Forum activities on

the quantitative 

basis for 

interspecies scaling;

dermal exposure 

methods; and 

exposure assessment 

guidelines.

Mode of Action to 

refine RA & 

extend beyond the 

range of data:

Incorporate mode of 

action advances to 

improve approaches 

for cancer and noncancer RA, 

facilitating 

quantitative 

estimates of risk 

within the range of 

data and at 

environmental 

exposure levels, 

including a 

framework for 

applying MoA in 

RA and linking this 

to dose-response 

analysis; and 

Forum activities on

the implications of 

MoA in peroxisome

proliferation, 

bladder tumors, 

mutagenesis, and

immunosuppression.

Guidance on RA 

models & 

uncertainty 

analysis:

Apply uncertainty 

analyses in 

biologically-based 

risk assessment 

models, 

accompanied by the 

development of risk 

assessment 

guidance to 

disseminate 

information, 

including tools to 

characterize 

uncertainty and 

variability in PBPK 

models; lifestage

data and its 

application to 

children’s RA; and 

RfC methods 

guidance, less than 

lifetime RA 

guidance, and 

Forum guidance on

microbial RA . 

Expanding single 

substance RA to 

complex 

environmental 

mixtures:

Develop models, 

methods and 

guidance to move 

beyond single 

chemical 

assessments to 

incorporate 

methods and 

modeling advances 

for 

environmentallyrelevant mixtures of 

chemicals, through 

mixtures exposure 

assessment 

guidance; 

cumulative risk 

case studies for 

community 

assessment; and a 

Forum guidance on

cumulative risk 

assessment.

Integrating & 

synthesizing 

progress in RA 

models & 

methods:

Integrate and 

synthesize 

improvements in 

dose-response 

methods and 

models in risk 

assessment, 

including synthesis 

of the application 

of distributional 

data and 

uncertainty in RA 

quantitation and 

models; and 

methods for 

judgment-based 

probabilistic 

analysis and 

decision-making.

Quantitative RA 

advances, including 

central tendency & 

uncertainty:

Develop mathematical 

models to address an 

expanded range of data 

sets, including measures 

of central tendency and 

uncertainty analysis, 

accompanied by 

dissemination for use in 

quantitative risk 

assessment, including: 

categorical regression, 2-

stage clonal, and acute 

models to incorporate 

current standards of RA 

science into EPA 

practice; methods for 

central tendency and 

uncertainty in RA 

modeling; BMD 

software development; 

and Forum activities on

BMD guidance; data 

derivation and harmonization of uncertainty 

factors; and age groups 

for children’s exposure 

assessment.

RA guidance: 

Development of 

guidance, 

methods and 

technical support 

for conducting 

risk assessments 

and benefits 

analysis for 

Agency-wide 

use in risk 

management 

decisions.

Figure 5: Human Health Risk Assessment LTG 2 Annual Performance Goals

* Forum activities in italics

 The FY’09 APG reports on actions undertaken to incorporate biological and mode-of-action 

considerations to refine risk assessment practice and to extend the analysis beyond the range of data. 

Mode of action information is critical to determining the relevance of animal data to humans, and to 

informing quantitative estimates of risk within the range of data and at environmental levels. Early 

deliverables include Forum products on mutagenic mode of action and peroxisome proliferation 

guidance. The APGs in fiscal years 10 to 12 of this plan are directed toward developing guidance and 

synthesizing the risk assessment advances accomplished under this MYP and from the scientific 

literature. In doing so, these goals consolidate the science, generate a common basis for Agency risk 

assessment practice, and provide a foundation for future planning activities. 

21
EPA External Review Draft December 16, 2005 

 

22

LTG 3: Air Quality Criteria Documents

 Sections 103, 108, and 109 of the Clean Air Act govern the establishment, review, and 

revision of the National Ambient Air Quality Standards (NAAQS) and direct the Agency to issue 

air quality criteria for identified ubiquitous pollutants that may reasonably be anticipated to 

endanger public health or welfare. RA MYP LTG 3 produces the mandated ambient Air Quality 

Criteria Documents (AQCD) which evaluate the latest relevant available scientific information 

addressing the nature and extent of health and welfare effects associated with exposure to 

ambient concentrations of the particular pollutant. ORD laboratory research is also conducted 

pursuant to the CAA under the particulate matter, ozone and other MYPs. 

 For the AQCDs, NCEA scientists and external authors develop chapters on atmospheric 

chemistry, ecology, toxicology, epidemiology, and exposure sources, ambient concentrations and 

measurement methods. A close collaboration is maintained in the planning and execution of 

AQCD preparation between NCEA and the recipient OAR-Office of Air Quality Planning and 

Standards (OAQPS). Draft AQCDs are reviewed internally and through workshops covering 

specific areas of the assessment. External review drafts undergo public comment and detailed 

scrutiny by the Clean Air Scientific Advisory Committee (CASAC). With closure on the final 

AQCD, NCEA consults with OAR-OAQPS in the development of their Staff Paper risk 

assessment, which serves as the basis for regulatory review of the NAAQS. EPA has set 

NAAQS for six pollutants: carbon monoxide (CO), lead (Pb), nitrogen dioxide (NO2), 

tropospheric ozone (O3), particulate matter (PM10 and PM2.5), and sulfur dioxide (SO2). The 

AQCDs are reviewed and revised on a regular cycle in response to statutory requirements. 

 Specific APGs for LTG 3 are illustrated in Figure 7, with all the AQCDs scheduled for 

revision during this multi-year planning period. Figure 8 demonstrates the annual operating plan 

requirements to fulfil these APGs, with each AQCD being preceded by a project plan, multiple 

external review drafts, public comment and CASAC review, prior to finalization for delivery to 

OAQPS. The individual AQCD requirements overlap to form a staggered matrix of ongoing 

activities under RA LTG 2. 

LTG 3: Air Quality Criteria Documents: As mandated in the Clean Air Act, the ambient air criteria 

pollutants are reviewed and AQCDs revised to reflect the best available scientific information on 

identifiable effects on public health and the environment from exposure to the pollutant, and this 

information is used by the EPA Office of Air and Radiation in their review and promulgation of the 

National Ambient Air Quality Standards (NAAQSs) to protect public health with an adequate 

margin of safety. 

 2005 2006 2007 2008 2009 2010 2011 2012 

Final PM 

AQCD - 

completed 

Final PM 

AQCD

Final O3

AQCD 

Final SO2

AQCD

Final NOx

AQCD

Final Pb 

AQCD 

Final O3

AQCD

Final CO 

AQCD

Figure 6: Human Health Risk Assessment LTG 3 Annual Performance Goals 
EPA External Review Draft December 16, 2005 

 

23

 

 2005 2006 2007 2008 2009 2010 2011 2012 

Figure 7: RA LTG 3 Annual Operating Plan APMs and Support Activities 

Final PM 

AQCD - 

completed 

Final PM 

AQCD

Final O3

AQCD 

Final Pb 

AQCD 

Final O3

AQCD

Project Plan 

PM 

1st ERD 

PM 

1st ERD 

O3 

1st ERD Pb 

2nd ERD 

PM 

2nd ERD O3 

2nd ERD Pb 

Project Plan 

O3

1st ERD 

O3

2nd ERD 

O3 

Project Plan 

Pb 

1st ERD 

Pb 

2nd ERD 

Pb 

Final SO2

AQCD

Final NOx 

AQCD

Project Plan 

NOx 

1st ERD 

SO2 

1st ERD NOx 2nd ERD NOx

Project Plan 

SO2 

2nd ERD SO2

Final CO 

1 AQCD st Project Plan ERD CO 2nd ERD 

Potential Additional Work

 Health hazard assessments conducted under the RA MYP have become increasingly 

controversial due to their public health and cost implications and the variety of scientific 

conclusions that can be drawn from toxicity studies. Because these assessments provide the key 

scientific analyses supporting many critical Agency decisions, the Administrator has directed 

that ORD institute enhanced review and consultation procedures to ensure the highest scientific 

quality and transparency. To this end, ORD has proposed new steps in the assessment 

development process that complement and expand existing review procedures. These steps 

require additional extramural resources to integrate review and consultation by the National 

Academy of Sciences (NAS) into the assessment development process. NAS involvement will 

contribute to the identification and resolution of scientific issues and increased confidence and 

wide acceptance of EPA assessments. The availability of additional resources would be used by 

ORD to establish contracts with the NAS for approximately 3 -5 high priority peer consultations 

on major issues and peer reviews of major assessments. These reviews are much more costly 

than current peer reviews and consultations, and existing RA MYP resources are insufficient to 

support these activities. Additional resources will also be used to support early involvement of 

federal agencies and the public in assessment development, including formal notice of assessment development and the opportunity for input by interested federal agencies and the public. 
EPA External Review Draft December 16, 2005 

 

24

 Beyond extramural funding for NAS peer reviews, additional resource allocations to the 

RA MYP would be used to support additional assessments of priority chemicals. To do so, 

however, requires a balance between RA staff FTE increases and extramural funding for contract 

and peer review support. 

 Additional work is also anticipated to incorporate rapidly developing fields of science as 

tools in risk assessment practice and products. These developing risk assessment tools will be 

applied directly into IRIS and AQCD assessments as available and appropriate under existing 

LTG 1 and 3 resources. For instance, additional information from the rapidly growing field of 

“omics” research (genomics, proteomics, metabolomics) will be incorporated into specific risk 

assessments based on information from the published literature and developed by the EPA 

National Center for Computational Toxicology. The experience gained from the applied use of 

“omics” tools will then contribute to evaluating their broad implications for risk assessment 

practice under the LTG 2 mode of action and quantitative methods development foci. Bayesian 

statistics and other decision analysis methods are also increasingly used in risk assessments, and 

will contribute to methods development case studies under the LTG 2 quantitative risk 

assessment focus. 

 Re-prioritization of work under a fixed budget is also likely in response to emerging 

concerns, changed agency priorities, and research developments that may expedite or raise new 

opportunities for risk assessment. This flexibility is tempered by the need to remain focused on 

those activities most conducive to serving the agency mission and to avoid diluting efforts below 

a critical level given the finite budget and staff resources available. Timing and coordination are 

also necessary to ensure that adequate research information is available prior to conducting an 

assessment, and that time lags be considered when adding or re-scheduling assessment work, 

such as the planning, document preparation and peer review requirements necessary over several 

years for IRIS and AQCD assessments. Recruitment planning may also be necessary to adjust 

staff expertise to changing circumstances. 

Classification of External Annual Performance Goals and Measures 

 

 All RA MYP LTG 1 and LTG 3 APGs are recommended for classification as external 

APGs. 
EPA External Review Draft December 16, 2005 

 

Appendix A: Long Term Goals and Associated Annual Performance Goals (APG) and 

 Annual Performance Measures (APM) 

 

GPRA Goal 4: Healthy Communities and Ecosystems 

Program Project: 84, Human Health Risk Assessment 

LTG 1: Integrated Risk Information System (IRIS) and other priority health hazard 

assessments: Agency, state and local risk assessors use the state-of-the-science health 

hazard assessment information provided on priority substances in their decisions and 

actions to protect human health from risks posed by environmental pollutants.

LAB/ 

CENTER

ANNUAL PERFORMANCE GOALS AND MEASURES YEAR

APG 6: IRIS and other priority health hazard assessments: Complete 16 2006 ORD 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review 

2006 NCEA 

APM Complete 25 new and 25 revised provisional peer reviewed 

toxicity values to support OSWER decision-making 

2006 NCEA 

APG 7: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2007 ORD 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including acrylonitrile, methanol, methylene chloride, 

trichoroethylene and dioxin 

2007 NCEA 

APM Complete 25 new and 25 revised provisional peer reviewed 

toxicity values to support OSWER decision-making 

2007 NCEA 

APG 8: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2008 ORD 

25
EPA External Review Draft December 16, 2005 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including asbestos (nonCa), ethanol and styrene 

2008 NCEA 

APM 25 new and 25 revised provisional peer reviewed toxicity values 

to support OSWER decision-making 

2008 NCEA 

APG 9: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2009 ORD 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including asbestos (cancer) and polycyclic aromatic 

hydrocarbons 

2009 NCEA 

APM 25 new and 25 revised provisional peer reviewed toxicity values 

to support OSWER decision-making 

2009 NCEA 

APG 10: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2010 ORD 

APM Complete16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including additional nominated priority substances and 

finalization of assessments for internet dissemination 

2010 NCEA 

APM 25 new and 25 revised provisional peer reviewed toxicity values 

to support OSWER decision-making 

2010 

APG 11: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2011 ORD 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including additional nominated priority substances and 

finalization of assessments for internet dissemination. 

2011 NCEA 

26
EPA External Review Draft December 16, 2005 

APM 25 new and 25 revised provisional peer reviewed toxicity values 

to support OSWER decision-making 

2011 NCEA 

APG 12: IRIS and other priority health hazard assessments: Complete 16 

health hazard assessments of high-priority chemicals for interagency review 

or external peer review and 25 new and 25 revised provisional peer reviewed 

toxicity values so that EPA program offices, regions, state and local risk 

assessors have state-of-the-science health hazard assessment information on 

priority substances included in planned Agency decisions and actions. 

2012 ORD 

APM Complete 16 health hazard assessments of high priority 

chemicals for interagency review or external peer review, 

including additional nominated priority substances and 

finalization of assessments for internet dissemination. 

2012 NCEA 

APM 25 new and 25 revised provisional peer reviewed toxicity values 

to support OSWER decision-making 

2012 NCEA 

 

27
EPA External Review Draft December 16, 2005 

LTG 2: State-of-the-science risk assessment models, methods and guidance: EPA programs, 

states and other risk assessors use the risk assessment models, methods, and guidance provided 

to enhance, through the incorporation of contemporary scientific advances, the quality and 

objectivity of their assessments and decision-making on environmental health risks.

LAB/ 

CENTER

ANNUAL PERFORMANCE GOALS AND MEASURES YEAR

APG 263: Quantitative risk assessment models and tools: Provide models 

and tools for improving quantitative dose-response relationships, 

characterizing human exposures and reducing uncertainty in risk assessments 

so that by 2010 the Agency will have improved information for estimating 

human health exposures and risks 

2006 ORD 

APM 53 Models for saturable effects using dichotomous data 

incorporated in BMD software in support of IRIS dose-response 

assessment development 

2006 NCEA 

5 final acute reference dose exposure (ARE) assessments of key 

HAP chemicals to support the residual risk program 

APM 55 2006 NCEA 

External Review Draft of updated Exposure Factors Handbook 

for Children to reduce uncertainty in exposure assessments 

APM 498 2006 NCEA 

External Review Draft of model for estimating human exposure 

to multiple metal contaminants using biokinetic modeling 

techniques to reduce uncertainty in exposure assessments 

APM 230 2006 NCEA 

2 final reports on dose-response models and population exposure 

methods for assessing microbial risks and defining microbial 

research needs for OW 

APM 357 2006 NCEA 

APG 264: Risk Assessment Guidance: Development of guidance, methods, 

and technical support for conducting risk assessments and benefits analysis 

for Agency-wide use in risk management decisions 

2006 ORD 

APM 424 2 draft case studies to demonstrate the potential for quantifying 

health benefits and risks by integrating methods from toxicology, 

statistics, epidemiology and economics 

2006 NCEA/ 

RAF 

APM 462 Final report supporting development of methodology to guide 

the replacement of inter/intraspecies default uncertainty factors 

with factors based on data 

2006 NCEA/ 

RAF 

APM Complete and deliver to the Agency’s Science Policy Council a 

cross-Agency framework for the assessment of metals (moved 

from 2005 APG129, APM 547) 

2006 NCEA/ 

RAF 

28
EPA External Review Draft December 16, 2005 

APG 7: Quantitative risk assessment advances, including central 

tendency & uncertainty: Develop mathematical models to address an expanded 

range of data sets, including measures of central tendency and uncertainty analysis, 

accompanied by dissemination for use in quantitative risk assessment, including .... 

2007 ORD 

APM Benchmark dose technical guidance. 2006 NCEA/ 

RAF 

APM Report on selecting age groups for evaluating children’s 

exposure to environmental contaminants. 

2006 NCEA/ 

RAF 

APM Approaches to harmonization of uncertainty factors for cancer 

and non-cancer risk assessment (moved from 06 APG264, APM 

458) 

2007 NCEA/ 

RAF 

APM External review draft guidance on replacing default values for 

uncertainty factors with those based on data. 

2007 NCEA/ 

RAF 

Development of three to four additional low dose linear and nonlinear models for application in acute and chronic dose-response 

assessments, incorporating biological and statistical 

considerations in selection and decision-making 

recommendations 

APM 2007 NCEA 

Report on methods for developing central estimates and 

uncertainty bounds in dose-response analysis – current 

techniques, alternatives and decision parameters for application 

to risk assessment. External Review Draft 

APM 2007 NCEA 

APG 8: Integrating risk assessment advances into quantitative 

frameworks: Integrate PBPK, exposure, microbial and biological modeling 

advances into quantitative risk frameworks, thereby applying mathematical modeling 

and data advances to biological systems, including ... 

2008 ORD 

APM Use of body weight to the three-quarter power (BW3/4) as a 

default for interspecies extrapolation 

2006 NCEA/ 

RAF 

APM Final report on Approaches for the Application of 

Physiologically-Based Pharmacokinetic (PBPK) Models and 

Supporting Data in Risk Assessment 

2006 NCEA 

Final report on a Framework for Assessing Health Risks to 

Children from Environmental Exposures 

APM 2006 NCEA 

Technical summary of methods for estimating exposure through 

dermal absorption of contaminants 

APM 2007 NCEA 

Exposure factors handbook revision for use by programs and 

regions in modeling exposures - External Review Draft 

APM 2008 NCEA 

APM Report on analysis (with workshop input) of uncertainty in 

PBPK models and application to risk assessment 

2008 NCEA 

29 
EPA External Review Draft December 16, 2005 

Microbial risk assessment models of exposure, dose response, 

and population susceptibility 

APM 2008 NCEA 

APM Exposure assessment guidelines update 2008 NCEA/ 

RAF 

APG 9: Mode of Action to refine RA & extend beyond the range of data:

Incorporate mode of action advances to improve approaches for cancer and noncancer risk assessment, facilitating quantitative estimates of risk within the range of 

data and at environmental exposure levels, including ... 

2009 ORD 

APM Mutagenic mode of action guidance 2006 NCEA/ 

RAF 

APM Guidance on peroxisome proliferation (PPAR) mode of action 2007 NCEA/ 

RAF 

APM Immunosuppression risk assessment guidance 2007 NCEA/ 

RAF 

APM Guidance on bladder tumors 2007 NCEA/ 

RAF 

APM Develop a mode of action framework for application in chemical 

risk assessments 

2008 NCEA 

External review draft report on linking mode of action 

information in dose-response analysis 

APM 2009 NCEA 

APG 10: Guidance on risk assessment models & uncertainty analysis:

Apply uncertainty analyses in biologically-based risk assessment models, 

accompanied by the development of risk assessment guidance to disseminate 

information, including... 

2010 ORD 

APM Cumulative risk assessment technical issue papers, case studies, 

and research on methods and priorities 

2006 NCEA/ 

RAF 

APM Revised reference concentration (RfC) methodology for use by 

the IRIS program to develop dose-response assessments for 

chronic exposure, external review draft 

2008 NCEA 

Case studies on the application of the lifestage approach to 

children’s risk assessment for selected chemicals 

APM 2008 NCEA 

Methods and guidance for use by IRIS in developing less-thanlifetime dose-response assessments for program offices, regions 

and states, using acute exposure methods and case studies of 

specific duration 

APM 2009 NCEA 

APM Microbial risk assessment guidelines 2009 NCEA/ 

RAF 

30 
EPA External Review Draft December 16, 2005 

APM Report on incorporation of variability and lifestage data for 

PBPK modeling 

2009 NCEA 

APM Microbial risk assessment case studies 2010 NCEA 

Final revised reference concentration (RfC) methodology for use 

by the IRIS Program to develop dose-response assessments for 

chronic exposure 

APM 2010 NCEA 

Modeling tools to characterize uncertainty and population 

variability in PBPK models 

APM 2010 NCEA 

APM Guidance on lifestage based risk assessment 2010 NCEA 

APG 11: Expanding single substance risk assessment to complex 

environmental mixtures: Develop models, methods, and guidance to move 

beyond single chemical assessments to incorporate methods and modeling advances 

for environmentally-relevant mixtures of chemicals, through ...

2011 ORD 

APM Cumulative risk assessment guidance 2009 NCEA/ 

RAF 

APM Mixtures exposure assessment guidance 2011 NCEA 

Cumulative risk dose response case studies for community risk 

assessment 

APM 2011 NCEA 

APG 12: Integration and synthesis of progress in risk assessment 

methods & models: Integrate and synthesize improvements in dose-response 

methods and models in risk assessment, including... 

2012 ORD 

APM Synthesis of methods and technical guidance for judgment-based 

probabilistic analysis and decision-making 

2011 NCEA 

APM Synthesis of application of distributional data and uncertainty in 

risk assessment quantitation and models 

2012 NCEA 

31 
EPA External Review Draft December 16, 2005 

LTG 3: Air Quality Criteria Documents: As mandated in the Clean Air Act, the ambient air 

criteria pollutants are reviewed and AQCDs revised to reflect the best available scientific 

information on identifiable effects on public health and the environment from exposure to the 

pollutant, and this information is used by the EPA Office of Air and Radiation in their review and 

promulgation of the National Ambient Air Quality Standards (NAAQSs) to protect public health 

with an adequate margin of safety.

ANNUAL PERFORMANCE GOALS AND MEASURES YEAR LAB/ 

CENTER

APG 6: Complete the Air Quality Criteria Document (AQCD) for Ozone in 

support of the EPA/OAQPS review and promulgation of the National 

Ambient Air Quality Standard (NAAQS) 

2006 ORD 

APM External Review Draft AQCD for Ozone which serves as the 

basis for the EPA/OAQPS staff paper for the National Ambient 

Air Quality Standard (NAAQS) 

2005 NCEA 

Final AQCD for Ozone which serves as the basis for the 

EPA/OAQPS staff paper for the National Ambient Air Quality 

Standard (NAAQS) 

APM 2006 NCEA 

APG 7: Complete the Air Quality Criteria Document (AQCD) for Lead in 

support of the EPA/OAQPS review and promulgation of the National 

Ambient Air Quality Standard (NAAQS) 

2007 ORD 

APM External Review Draft AQCD for Lead which serves as the basis 

for the EPA/OAQPS staff paper for the National Ambient Air 

Quality Standard (NAAQS) 

2006 NCEA 

Final AQCD for Lead which serves as the basis for the 

EPA/OAQPS staff paper for the National Ambient Air Quality 

Standard (NAAQS) 

APM 2007 NCEA 

APG 8: Complete the Air Quality Criteria Document (AQCD) for Nitrogen 

Oxides in support of the EPA/OAQPS review and promulgation of the 

National Ambient Air Quality Standard (NAAQS) 

2008 ORD 

APM External Review Draft AQCD for Nitrogen Oxides which serves 

as the basis for the EPA/OAQPS staff paper for the National 

Ambient Air Quality Standard (NAAQS) 

2007 NCEA 

Final AQCD for Nitrogen Oxides which serves as the basis for 

the EPA/OAQPS staff paper for the National Ambient Air 

Quality Standard (NAAQS) 

APM 2008 NCEA 

APG 9: Complete the Air Quality Criteria Document (AQCD) for Sulfur 

Dioxide in support of the EPA/OAQPS review and promulgation of the 

National Ambient Air Quality Standard (NAAQS) 

2008 ORD 

32 
EPA External Review Draft December 16, 2005 

33 

APM External Review Draft AQCD for Sulfur Dioxide which serves 

as the basis for the EPA/OAQPS staff paper for the National 

Ambient Air Quality Standard (NAAQS) 

2007 NCEA 

APM Final AQCD for Sulfur Dioxide which serves as the basis for the 

EPA/OAQPS staff paper for the National Ambient Air Quality 

Standard (NAAQS) 

2008 NCEA 

APG 10: Complete the Air Quality Criteria Document (AQCD) for Carbon 

Monoxide in support of the EPA/OAQPS review and promulgation of the 

National Ambient Air Quality Standard (NAAQS) 

2010 ORD 

APM External Review Draft AQCD for Carbon Monoxide which 

serves as the basis for the EPA/OAQPS staff paper for the 

National Ambient Air Quality Standard (NAAQS) 

2008 NCEA 

APM Final AQCD for Carbon Monoxide which serves as the basis for 

the EPA/OAQPS staff paper for the National Ambient Air 

Quality Standard (NAAQS) 

2010 NCEA 

APG 10: Complete the Air Quality Criteria Document (AQCD) for 

Particulate Matter in support of the EPA/OAQPS review and promulgation of 

the National Ambient Air Quality Standard (NAAQS) 

2010 ORD 

APM External Review Draft AQCD for Particulate Matter which 

serves as the basis for the EPA/OAQPS staff paper for the 

National Ambient Air Quality Standard (NAAQS) 

2008 NCEA 

APM Final AQCD for Particulate Matter which serves as the basis for 

the EPA/OAQPS staff paper for the National Ambient Air 

Quality Standard (NAAQS) 

2010 NCEA 

APG 12: Complete the Air Quality Criteria Document (AQCD) for Ozone in 

support of the EPA/OAQPS review and promulgation of the National 

Ambient Air Quality Standard (NAAQS) 

2012 ORD 

APM External Review Draft AQCD for Ozone which serves as the 

basis for the EPA/OAQPS staff paper for the National Ambient 

Air Quality Standard (NAAQS) 

2010 NCEA 

APM Final AQCD for Ozone which serves as the basis for the 

EPA/OAQPS staff paper for the National Ambient Air Quality 

Standard (NAAQS) 

2012 NCEA 
Review Draft December 16, 2005 

34 

Appendix B: RA LTG 2 Annual Performance Measures (APMs) and Support Activities in an Annual Operating P

06 07 08 09 10 11 

Microbial

Microbial RA WkshpsExp, DR, Pop..Dyn.;Thesaurus & framwk

Microbial RAcase studies

Microbial model dev Exp, DR, Pop. Dyn

Microbial RA Guidelines

L’stage physiolparameter d’basefor PBPK models

Sensit. subpop

Burden water borne disease

Children’s framew’k

Guidance on l’stage based RA

Exposure

Exp. factors hd’bk

Age groups for exposure Exp. assm’t gd’ln

Cumulative; Mixtures

DBP cumulative RA using RPFs DBP aggregate exposure linked 

to PBPK model

DBP MoA models

Mixtures Exposure Assessment Guidelines

DBP & THM PBPK models; exp.assess

Cum. risk DR case studies of community risk

Cumulative RA papers Cumulative RA guid

DBP mixtures Risk Assess

SadduR

Central estim. & & uncertainty

Dichot; cat reg; biokinetic models

PBPKMode of Action

Quantitative Methods

Acute models and tools Pilot Acute Case Studs 

& synthesis HAP acute 

info. database

Guidance/methods for <lifetime RA

RfC revised methods IRD

RfC revised methods ERD

RfC guidance methods revision

Inhalation

BMD web upgrade

Low dose model; 2-stage clonal model

Enz. polymorph variability dbase for PBPK mods

Lifestage differences in kinetics & biology

Data deriv. UF

Analysis of uncertainty in PBPK models

Simplif Route-Route, PBPK

3-4 DR models for RA, inc.Ac

Non-proprietary tools for quantit. modeling & uncertainty

Synthesis of judgement-based prob. anal. & decision making

Decision case studies

Linking MoAto DR analysis

Modeling tools to characterize uncertainty & pop. variability in PK models

BMD tech. guidance

3⁄4 intersp. scaling 

Bladder, ImmunoS, PPAR MoA guid

Case studies acute

Mutagenic

Toxaphene deg/tox; Organotin MoA, tox

Intro to PBPK in RA

Organotinmixture RA

Toxapheneorganotin mixtfeasibility

3-5 case stds. on precursor biomarkers

Child exp. factors hd’bk

MoA framework

DR mutagen MoA

DR early life nonmutagenic

Genomics in RA

ERD benefits analysis model

Dermal exp. meth

Children’s case studies

H’book on var. & l’stage data for PBPK modeling

Wkshp uncert. in PBPK

Data deriv. UF; Harmoniz UFs

06 07 08 09 10 11 

Microbial

Microbial RA WkshpsExp, DR, Pop..Dyn.;Thesaurus & framwk

Microbial RAcase studies

Microbial model dev Exp, DR, Pop. Dyn

Microbial RA Guidelines

L’stage physiolparameter d’basefor PBPK models

Sensit. subpop

Burden water borne disease

Children’s framew’k

Guidance on l’stage based RA

Exposure

Exp. factors hd’bk

Age groups for exposure Exp. assm’t gd’ln

Cumulative; Mixtures

DBP cumulative RA using RPFs DBP aggregate exposure linked 

to PBPK model

DBP MoA models

Mixtures Exposure Assessment Guidelines

DBP & THM PBPK models; exp.assess

Cum. risk DR case studies of community risk

Cumulative RA papers Cumulative RA guid

DBP mixtures Risk Assess

SadduR

Central estim. & & uncertainty

Dichot; cat reg; biokinetic models

PBPKMode of Action

Quantitative Methods

Acute models and tools Pilot Acute Case Studs 

& synthesis HAP acute 

info. database

Guidance/methods for <lifetime RA

RfC revised methods IRD

RfC revised methods ERD

RfC guidance methods revision

Inhalation

BMD web upgrade

Low dose model; 2-stage clonal model

Enz. polymorph variability dbase for PBPK mods

Lifestage differences in kinetics & biology

Data deriv. UF

Analysis of uncertainty in PBPK models

Simplif Route-Route, PBPK

3-4 DR models for RA, inc.Ac

Synthesis of judgement-based prob. anal. & decision making

Non-proprietary tools for quantit. modeling & uncertainty

EPA External 

Decision case studies

Linking MoAto DR analysis

Modeling tools to characterize uncertainty & pop. variability in PK models

BMD tech. guidance

3⁄4 intersp. scaling 

Bladder, ImmunoS, PPAR MoA guid

Case studies acute

Mutagenic

Toxaphene deg/tox; Organotin MoA, tox

Intro to PBPK in RA

Organotinmixture RA

Toxapheneorganotin mixtfeasibility

3-5 case stds. on precursor biomarkers

Child exp. factors hd’bk

MoA framework

DR mutagen MoA

DR early life nonmutagenic

Children’s case studies

H’book on var. & l’stage data for PBPK modeling

Wkshp uncert. in PBPK

Data deriv. UF; Harmoniz UFs

Genomics in RA

ERD benefits analysis model

Dermal exp. meth
EPA External Review Draft December 16, 2005 

References

Lehman, A.J. and Fitzhugh, O.G. 1954. Ten-fold safety factor studies. Assoc Food Drug Officials of 

the US Quarterly Bulletin XVIII(1): 33-35. 

NAS. 1983. Risk Assessment in the Federal Government: Managing the Process. Committee on the 

Institutional Means for Assessment of Risks to Public Health. Commission on Life Sciences. National 

Research Council. National Academy Press. Washington, D.C. 

NAS. 1994. Science and Judgement in Risk Assessment. Committee on Risk Assessment of 

Hazardous Air Pollutants. Board on Environmental Studies and Toxicology. Commission on Life 

Sciences. National Research Council. National Academy Press. Washington, D.C. 

OMB. 2004. Final Information Quality Bulletin for Peer Review. Office of Management and Budget. 

M-05-03. December 16. http://www.whitehouse.gov/omb/memoranda/fy2005/m05-03.pdf 

Presidential/Congressional Commission. 1997. Risk Assessment and Risk Management in Regulatory 

Decision-Making. Final Report, Volume 2. Presidential/Congressional Commission on Risk 

Assessment and Risk Management. http://www.riskworld.com/Nreports/1997/riskrpt/volume2/pdf/v2epa.PDF 

U.S. EPA. 2003. EPA Strategic Plan. Direction for the Future. 2003 - 2008. Office of the Chief 

Financial Officer. Office of Planning, Analysis, and Accountability. EPA-190-R-03-003. 

U.S. EPA. 2001. Office of Research and Development Strategic Plan. Office of Research and 

Development. EPA/600/R-01/003. http://www.epa.gov/osp/stplan.htm 

U.S. EPA. 1998. Peer Review Handbook. Office of Science Policy, Office of Research and 

Development. EPA 100-B-98-001. Washington, D.C. 

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