Office of Research and Development's (ORD)
Human Health Risk Assessment (HHRA) Program
Mid-Cycle Progress Report to the Board of Scientific Counselors (BOSC)
July 12, 2010
Submitted by:
Peter W. Preuss, PhD
Director, National Center for Environmental Assessment
Office of Research and Development
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Office of Research and Development's Human Health Risk Assessment Program's Mid-Cycle
Progress Report to the Board of Scientific Counselors
The U.S. Environmental Protection Agency's (EPA) Office of Research and Development
(ORD) relies on its Board of Scientific Counselors (BOSC) to conduct independent expert
reviews of its environmental research programs every four to five years. The Human Health Risk
Assessment (HHRA) Program Subcommittee of the BOSC met in Washington, DC on
November 14-16, 2007, and the BOSC Executive Committee provided a final report in May,
2008. The principal charge to the BOSC reviewers was to evaluate ORD's HHRA Program from
a program assessment framework relative to program relevance, structure, performance, quality,
leadership, communication, and outcomes. A second priority was to provide a summary
assessment and performance ranking for each of the three long-term goals identified with the
HHRA Program. A set of specific charge questions was used to guide the Subcommittee through
the review, producing a number of recommendations with regard to the program.
On May 27, 2008, ORD received the BOSC's Review of the Office of Research and
Development's Human Health Risk Assessment Program at the US Environmental Protection
Agency. In that report, the BOSC concluded that the Program's goals are fully consistent with
the Agency's strategic mission and with the Program's multi-year plan (MYP). The products
from LTG 1 and LTG 3 are critical to EPA's regulatory mission and form the foundation for
regulatory decisions and policies in a variety of program offices and regions. The BOSC also
found that: 1) Integrated Risk Information System (IRIS) assessments are critical to a number of
goals and objectives listed in EPA's 2006-2011 Strategic Plan; 2) IRIS serves as the
internationally recognized standard in chemical risk assessment for other federal, state, local and
international regulatory bodies and the private sector; 3) LTG 3 is aligned with the requirements
for assessment of criteria air pollutants as mandated by the Clean Air Act (CAA), and the
importance of the HHRA Program in meeting CAA requirements could not be overstated; 4) the
research conducted under LTG 2 focuses on critical needs and that good strategic choices have
been made to concentrate research in areas that are likely to result in marked improvements in
risk assessment; and 5) the HHRA Program has been highly responsive to the needs of the
program offices and regions who strongly value the work and expertise of the HHRA, both in
providing risk assessment products (IRIS assessments, provisional peer reviewed toxicity values-
PPRTVs, and integrated science assessments-ISAs) and in supporting emergency responses to
crises like the 9/11 terrorist attacks on the World Trade Center and Hurricane Katrina.
The BOSC, however, raised concerns regarding the rate of production of assessments, the 10-
year life span of IRIS assessments, the review cycle of IRIS assessments and the potential effects
of removing older IRIS assessments from the database. The BOSC report's recommendations
and HHRA Program's original response are outlined below, along with an update on progress
made in responding to the recommendations.
Recommendation 1: NCEA should assess what needs to be done to increase the Program's
ability to produce more IRIS and PPRTV assessments per year, not only to meet their own stated
objectives but also to satisfy the needs of their clients. This could either be in the form of a
recommendation to the Agency for more resources, or the development of a more streamlined
process.
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Original Response: The HHRA Program agrees that there is a need to provide more IRIS and
PPRTV assessments per year and that there are both process requirements and resource
limitations that affect productivity. For example, one prime limitation relates to the extensive
reviews required for IRIS assessments and the additional demands on staffing and resources to
conduct and respond to these reviews. On April 10, 2008, EPA Deputy Administrator, Marcus
Peacock announced an update to the IRIS process for development of new assessments and
reassessments and recommended the expeditious implementation of changes. The HHRA
Program is implementing the revised process to meet current commitments and is revising the
chemical prioritization and selection process to better reflect client office assessment priorities
and associated resource requirements.
In addition, an IRIS Update Process is being developed that will include an updated literature
search and re-evaluation of the qualitative and quantitative determinations in IRIS assessments
greater than ten years old. This new process is integrated with the current Literature Screening
Project which has identified existing chemical assessments where either no new data are
available or new data are available for updating values. Application of new analytical methods
(e.g., benchmark dose, PBPK modeling) will also be taken into consideration where appropriate
as part of the re-evaluation. In some cases, significant new data may warrant advancing
assessments into the queue as a new IRIS assessment. The update process will include peer
review by a Federal Standing Science Committee as well as a Standing External Peer Review
Panel. This IRIS Update Process will process 8-12 chemicals at a time to maximize throughput
of updated assessments.
The HHRA Program is addressing the concerns raised by the BOSC to assess what needs to be
done to increase the program's ability to produce more PPRTV assessments per year. The
program has recently undertaken improvements in the standardization of document development
and enhancements in the peer review and clearance processes. It is anticipated that these efforts
will decrease the time required for the production of PPRTV assessments and increase the
number of PPRTVs available to the program office.
Original Action/Timeline: The HHRA Program is implementing changes addressing
development of new IRIS assessments and reassessments, is revising the chemical prioritization
and selection process to address client office needs, has initiated development of a process for
updating older assessments on IRIS and begun efforts to enhance and streamline the PPRTV
process. The next update of the HHRA MYP will reflect any significant changes in these
programs and new metrics agreed upon with the Office of Management and Budget (OMB).
Progress regarding these efforts will be discussed at the mid-cycle review of the HHRA
Program.
Updated Response: No changes to the ORD action.
Current Progress: The HHRA Program has taken several steps to meet this recommendation.
The FY 2010 enacted budget includes additional resources for the IRIS program. Further, the
process used to develop IRIS assessments was revised in May 2009 (www.epa.gov/iris/process):
the new process allows for more rapid completion of assessments while retaining transparency
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and opportunity for Agency and Interagency comments, as well as vigorous independent external
peer review and public review and comment. The table below illustrates how the new process
has greatly improved the ability of the IRIS program to provide high quality human health risk
information to EPA's programs and regions in a timely fashion. After the announcement of the
new process, the fourth quarter of fiscal year 2009 began. More final assessments were posted
on IRIS in that single quarter of one year than in each of the previous three years. Thus, the
HHRA's IRIS program has quickly demonstrated progress under the new process and will
continue to show significant results in 2010 and beyond.
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FY2006
FY2007
FY2008
FY2009
May 21,2009
New IRIS Process
FY 2009 Total
FY2010
(Qu. 1-3)
FY2010
Projected
Draft Assessments
Start Interagency
Review/Consultation
11
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5
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2nd 4
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3rd „
qtr 2
4th
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10
5
Draft Assessments
Start Independent
External Peer Review
1
12
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7
10
7
1
I
Final Assessments
Posted on IRIS
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6
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3
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Additionally, we have developed an IRIS Logistics Team to coordinate all aspects of
administrative support for the IRIS program. The development of this team has created
efficiencies by centralizing logistical activities and relieving scientific staff of administrative
burdens. This is a matrix managed team that includes project officers of contracts for IRIS
document development, technical editing, and peer review; the NCEA Webmaster; the IRIS
coordinator, who maintains the public tracking system for IRIS assessments, organizes listening
sessions, and works with the chemical manager to develop project schedules; members of the
NCEA Technical Information Staff, who develop and coordinate Federal Register Notices (FRN)
and clearance for documents; the interagency point of contact, who handles all correspondence
with interagency reviewers; and the NCEA communications director, who coordinates all
communications dealing with IRIS draft and final assessments. Administrative support staff
schedule, organize and administer IRIS-related meetings and briefings and coordinate with the
EPA Science Advisory Board (SAB) and National Academy of Sciences (NAS) when these
bodies conduct peer reviews of IRIS assessments.
NCEA has met extensively with EPA's program and regional offices to better understand their
assessment needs. Additionally, NCEA is working with the California Environmental Protection
Agency's (Cal/EPA) Office of Environmental Health Hazard Assessment (OEHHA) and the
Agency for Toxic Substances and Disease Registry (ATSDR) under separate Memorandums of
Understanding (MOU). It is anticipated that these efforts will eventually increase efficiency and
assessment output. NCEA has also begun a project to update older IRIS assessments.
Additional details are described in our progress under Recommendation #2.
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We have taken steps to facilitate more efficient production of PPRTV assessments by: (1)
developing a PPRTV review team within NCEA; (2) streamlining the information included in a
PPRTV assessment to focus on pertinent data and decision-making sections; (3) educating EPA
contractors about expectations for PPRTV assessment documents; and (4) batching assessment
development and internal and external reviews. This has proven to be a successful effort. In FY
2009, NCEA produced 69 new PPRTV assessments. These 69 PPRTV assessments included a
total of 140 new individual toxicity values (e.g., Reference Dose-RfD, Reference Concentration-
RfC, Oral Cancer Slope Factor, etc.) that were added to the PPRTV database.
NCEA has also negotiated new program metrics with OMB. Specifically, NCEA's newly
negotiated performance metric indicates the HFIRA Program will complete health hazard and
dose response assessments of high priority chemicals as interagency science consultation drafts
or external peer review drafts with a program-defined value of 50 points applied to a 3-year
rolling average. Additionally, the HHRA Program will post on the IRIS Web page completed
health hazard assessments of high priority chemicals for public dissemination with a program
defined value of 20 points applied to a 3 year rolling average. To account for differences in the
level of complexity of assessments, the HHRA Program has also negotiated with OMB a tiering
system that provides three different levels of complexity and associated points for reaching
milestones for assessments. Tier 1 assessments are standard assessments that are expected to
require a typical level of effort from NCEA scientists and be limited in controversy and the
complexity of the science as well as the level of effort required for the assessment. Tier 1
assessments are assigned a point value of "1" for each major negotiated milestone met. Tier 2
assessments are more extensive in that they require more FTE effort, have a greater level of
controversy or visibility, and are more scientifically complex than Tier 1. Tier 2 assessments are
assigned a point value of "2" for each major negotiated milestone met. Tier 3 assessments are the
most complex. They require an exceptional level of FTE support, are highly controversial and/or
visible, and are exceptional in the complexity of the science involved in the assessment. Tier 3
assessments are assigned a point value of "5" for each major negotiated milestone met.
Additionally, the HHRA Program has begun a pilot project on advancing the next generation of
risk assessment (NexGen) that will explore the feasibility of using advances in molecular and
systems biology for developing health assessments. It is anticipated this pilot project will help
pave the way for using high throughput data to develop rapid health assessments. This is a
collaborative effort across ORD and with the National Institutes of Environmental Health
Sciences (NIEHS), the National Human Genome Research Institute (NHGRI), and Cal/EPA.
Recommendation 2: Mechanisms should be considered for retaining IRIS assessments older
than 10 years that have not been updated, rather than allowing these assessments to expire and be
removed from the IRIS database and Web site. One option is to simply annotate them as such.
Original Response: The HHRA Program appreciates the support of the BOSC to retain IRIS
assessments older than ten years that have not been updated on the Web site. The program has
considered this recommendation and discussed with the programs offices and other interested
partners the issue of whether to retain IRIS assessments older than ten years that have not been
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updated or to remove them from the IRIS database and Web site. Older assessments will remain
in the IRIS database and Web site and annotated as to the literature screening results until they
undergo updating by the new IRIS update process or the traditional IRIS process.
Original Action/Timeline: Implementation of the IRIS update process is underway and
progress regarding these efforts will be discussed at the mid-cycle review of the HHRA.
Updated Response: No change to the ORD action.
Current Progress: NCEA has decided that IRIS assessments older than 10 years will not be
removed from the IRIS database. Additionally, a process for updating old IRIS chemical
assessments has been developed and is nearing the implementation stages. The HHRA Program
issued a FRN in October 2009 announcing the establishment of this IRIS Update Project.
Additionally, the HHRA Program has developed a two-tiered peer review process consisting of a
Federal Standing Science Committee followed by a Standing External Review Panel of the SAB
under the Federal Advisory Committee Act (FACA). The SAB issued a FRN in March 2009
requesting the nomination of experts to serve on this committee. Committee members have since
been identified and the panel has been established.
The intent of the IRIS Update project is to revisit all dose-response assessment values (RfDs,
RfCs, Oral Cancer Slope Factors, and Inhalation Cancer Unit Risks) in IRIS with a posting date
more than 10 years old. The values under current assessment by the standard IRIS process (on
IRIS Track) and the values for pesticides not in active use are eliminated from the list of IRIS
values greater than 10 years old. The remaining values are then prioritized for being updated.
This prioritization takes into consideration several factors, including frequency of occurrence in
National Priority List (NPL) waste sites, occurrence as hazardous air pollutants used in residual
risk assessments, the presence of chemicals on the Contaminant Candidate List (CCL), and other
intra- and inter-agency interests. From this list, smaller batches of assessments (-10) are
selected for literature searches by a contractor. After the literature search, the path for
development of a revised dose-response assessment value is based on whether new data exists or
not and whether new values are proposed or not (binning).
Recommendation 3: The HHRA Program should continue to develop ties with NCCT, and
should provide formal input to that program on the aspects of its research that will be of value to
HHRA.
Original Response: The HHRA Program agrees with the BOSC's recommendation and is
continuing to enhance communication and collaboration with NCCT. A number of such
activities are underway including: 1) NCEA management and staff involvement in the
development of the ORD Strategy for Toxicity Testing for the 21st Century; 2) formation of an
NCEA-led cross-Agency workgroup on the analysis and application of physiologically based
pharmacokinetic (PBPK) models for perchlorate that includes principal scientists from NCCT;
and 3) NCEA scientists serving as internal Agency reviewers of DSSTox database. Examples of
more informal collaborations are: 1) NCCT scientists' participation in NCEA sponsored
workshops and conferences such as the State of the Science workshop on Issues and Approaches
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in Low Dose-Response Extrapolation for Environmental Health Risk Assessment and the annual
Toxicology and Risk Assessment Conference; 2) cross program sharing of information and
resources, e.g., access to NCCT models and databases for SAR/QSAR screening approaches; 3)
use of NCEA ARRAYTrack database and server by NCCT staff; 4) NCEA consultations with
NCCT staff on the exposure communities of practice workgroup; 5) consultation on benchmark
dose (BMD) methods and models development; and 6) cross-participation in program seminars
(e.g., NCCT seminar on the virtual fetus held August 2008). In addition, efforts to enhance
LTG1 assessment development include collaboration with NCCT on agenda-setting for the IRIS
program and sharing assessment needs and prioritization information provided by clients with
NCCT for consideration in prioritization of testing and evaluation in ToxCast. Future
collaborations on the use of mode of action information in the virtual liver modeling efforts are
also being discussed between scientists in both programs.
NCEA is continuing to build and strengthen expertise in the area of computational toxicology
with staff participation in the upcoming Computational Systems Biology and Dose Response
Workshop sponsored by the Hamner Institutes for Health Sciences. Dr. Rory B. Conolly of
EPA's NCCT is one of the course advisors and trainers.
Original Action/Timeline: The HHRA Program has initiated and will continue to seek
opportunities to further collaborate with NCCT to share data and information. In addition, NCEA
is continuing to build and strengthen expertise in the area of computational toxicology. Further
efforts will be discussed at the mid-cycle review of the HHRA Program.
Updated Response: No change to the ORD action.
Current Progress: NCEA has taken several steps to further develop ties between NCEA and
NCCT. For example, NCEA scientists participated in the NCCT ToxCast meeting in May 2009.
NCEA facilitated that participation by organizing a half-day seminar prior to the meeting to
provide an overview of ToxCast and computational toxicology tools in preparation for that
meeting.
Additionally, NCEA has developed a pilot project, which involves NCCT, to focus on the next
generation (NexGen) of risk assessment. This is driven by 1) new scientific advances,
particularly in understanding the gene environment; 2) challenges to current risk assessment
practices as articulated by the National Research Council (NRC) in their 2009 report Science and
Decisions: Advancing Risk Assessment; and 3) the European Union's Registration, Evaluation,
Authorization and restriction of Chemicals (REACH) legislation that will require new testing and
assessment of tens to hundreds of thousands of chemicals in commerce. In developing this
program, the HHRA Program has worked with NCCT, as well as ORD's other labs and centers
and EPA's program and regional offices. NexGen assessments will be developed at three levels
of complexity to be responsive to the risk context. Category 1 would use reliable high and
medium throughput assays and structure-activity analyses to conduct a screening assessment and
rank chemicals for further analysis. Depending on the priority established in Category 1, the risk
context and the available data, two levels of additional analyses could be conducted:
assessments prepared for data poor chemicals based upon a relatively narrow context of use and
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relying on standard practices (Category 2, e.g., PPRTV-like); or a broader, more complex
assessment relying on state-of-the-science practices (Category 3).
The HHRA Program has provided information on chemicals of key concern to the NCCT
program for inclusion in the ToxCast program. Included are those chemicals currently on the
IRIS agenda or under assessment in the PPRTV program. Additionally, NCEA has developed a
list of thousands of chemicals that appear on a variety of priority lists (Hazardous Air Pollutants-
HAP, CCL, etc.) and compiled public health information (both exposure and toxicity) about each
chemical. This information was also provided to the NCCT program. All of these chemicals will
be added to Phase 2 of the NCCT's ToxCast program, per NCEA's suggestion.
NCEA is also actively involved in an effort to expand the ToxRef database to include
developmental neurotoxicity data. In collaboration with NCCT, NCEA has provided funding for
data entry, and NCEA scientists are serving as advisors in developing the database structure and
in assuring accurate interpretation of the data for entry.
NCCT and NCEA share postdocs through the Cross-ORD Postdoctoral fellowship program. Dr.
Holly Mortensen works with both NCCT and NCEA. At NCCT, she has developed a toxicity
pathway database that will be used to assess ToxCast assay results. This approach is in line with
the NRC Toxicity Testing in the 21st Century's long range vision of moving toward a toxicity
pathway perturbation based risk assessment approach. At NCEA, she is working on the use of
genomics to inform intraspecies differences in response to toxic agents. She is currently co-
authoring a manuscript on the use of 'omics data to inform susceptibility.
On several occasions, the Center Directors for NCCT and NCEA have presented jointly on the
future of toxicology and risk assessment, including a briefing for the Senate Appropriations
Committee staff on June 9, 2009. Other events where the importance of the two centers working
together was presented include: The NAS' May 2009 symposium on toxicity-pathway-based risk
assessment (http://dels-old.nas.edu/best/risk_analysis/symposium.shtml) and the BOSC's
Computational Toxicology Subcommittee in September 2009.
NCEA and NCCT are collaborating through the EPA Risk Assessment Forum (RAF) to provide
training for scientists in ORD on the application of computational methods in risk assessment,
training for risk assessors on computational tools that are available for application in risk
assessment (hazard and dose response), and training for decision makers on the implications of
these new technologies.
Finally, several NCEA scientists have joined NCCT on detail assignments to the NCCT
fellowship program. This relationship has been beneficial to both NCEA and NCCT and has led
to additional collaborations between the two Centers and also between NCEA and other labs
within ORD. This work will develop assessment applications for high throughput and high
content data, methods and models. It will feed into and complement ORD's new integrated
transdisciplinary research program on Safe Products for a Sustainable World.
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STRUCTURE
The BOSC believes that the HHRA Program has a comprehensive and logical framework for
producing high-quality risk assessments and for managing internal and external review
processes. The consolidation of staff from multiple groups into a single core program under the
HHRA rubric has facilitated communication and the adoption of standard practices and
continuously improving processes. The interaction and cooperation between the HHRA Program
and other ORE) programs, program offices and regions is occurring at higher levels than previous
interactions. However, the BOSC pointed out that while HHRA staff members have provided
invaluable service to program offices, regions, states, etc. in responding to emergencies (e.g.. the
9/11 terrorist bombings, Hurricane Katrina) or assisting in difficult cleanup activities (e.g.
asbestos cleanup in Libby, Montana), these high-value activities are not captured in the overall
framework and HHRA MYP.
Recommendation 4: The BOSC considers the responsiveness of the staff members to national
emergencies and the HHRA Program's contributions to particularly difficult cleanup sites as
being of such high value that this should somehow be captured in the Annual Performance Goals
(APGs).
Original Response: The HHRA Program appreciates the BOSC's recognition of the high value
of the program's responsiveness and contributions to national emergencies or assisting in
difficult cleanup activities. We agree with the recommendation that these contributions should be
accounted for in a meaningful way within the overall framework of the HHRA Program. It is
clear that HHRA staff expertise will continue to an integral part of such responses. The program
also recognizes that one of the significant implications of responding to such events as national
emergencies may be the reallocation of staff from key assessments or projects within LTG1, 2,
and/or 3. As noted by the BOSC, it may not be plausible due to the unplanned nature of such
events to fully account for or plan the resources needed to respond to such events or requests
within an APG. The current APM/APG structure of ORD's MYPs is that APGs are major
outputs that represent significant and timely milestones along a critical path toward the
accomplishment of a LTG and that are planned over several years (three-five years). The
program will however, work more closely with EPA's Office of Emergency Management
(OEM) to be better prepared to respond to such events.
The HHRA Program has also started to implement procedures to better track these activities and
the resources expended internally. Under its regulatory and program support activities, NCEA
currently tracks monthly program office and regional requests for assistance and assignment of
HHRA staff to cross-Agency regulatory workgroups. This system is being expanded to include
emergency responses. In addition, NCEA is working with ORD's Labs and Centers and the
Office of Science Policy to develop measures for support activities across ORD.
Original Action/Timeline: The HHRA Program has started to better track these activities and
the resources expended both internally and across ORD. The program will also work more
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closely with OEM to be better prepared to respond to such events. The next update of the
HHRA MYP will include a section or description relating to these response efforts.
Updated Response: No change to the ORD action.
Current Progress: NCEA is tracking these emergency support activities and is holding
discussions internally about how this should be described in the next version of the HHRA MYP.
While it is impossible to predict the number and type of emergency response activities that may
arise, we expect this tracking will give us a better idea of what level of commitment we could
reasonably expect in the future for this type of support.
Over the past calendar year, NCEA has assisted with several high-profile support activities. In
the summer of 2009, NCEA scientists provided extensive support to the Agency as it dealt with
characterizing the risk of polychlorinated biphenyls (PCBs) in caulk in schools and other
buildings. HHRA scientists developed a PCB exposure estimation tool and developed advisory
limits for indoor school air concentrations. NCEA also provided support in 2009 to EPA's
Region 5 and Office of Solid Waste and Emergency Response (OSWER), completing an
evaluation of the University of Michigan Dioxin Exposure Study (UMDES). This evaluation
provided perspective on how the UMDES results could inform Agency decision-making
concerning dioxin in soils in Region 5. NCEA also provided rapid support to Region 7 as they
dealt with an emergency situation involving hexavalent chromium. NCEA coordinated a
conference call and presentation to provide information to Region 7 about the health effects of
hexavalent chromium. As a result of this request, NCEA convened a meeting with other EPA
programs and regions with an interest in hexavalent chromium to discuss accelerating an IRIS
assessment for the chemical. Because of these meetings, NCEA has rapidly developed a draft
health assessment document for hexavalent chromium that meets the identified needs of the
programs and regions; that assessment is moving through the IRIS process at an accelerated rate.
Also, NCEA served as a primary advisor to staff and scientists in the State of Hawaii, EPA's
Region 9, and the Office of Air Quality Planning and Standards (OAQPS) regarding health risks
associated with acute exposures to sulfur dioxide from volcanic activity, to support development
of public health advisory levels and recommendations.
NCEA has maintained a consistent level of support and visibility to EPA's programs and
regions. Through high profile, timely, and high quality support as identified above, as well as
through established programs like the Superfund Technical Support Center and the PPRTVs,
NCEA has become the "go to" organization for high quality and rapid scientific support.
NCEA has enhanced this visibility by conducting outreach to EPA's regional offices through one
or two day regional visits. These visits typically consist of both informal discussions and formal
presentations on a variety of topics. The goals of the meeting are to inform the regions of
NCEA's products and capabilities, better understand regional issues and concerns, and
strengthen ties at the management and staff levels. So far, NCEA has visited Regions 2, 3, 6, 8,
and 9 with very successful results. Additional visits are being planned.
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Finally, NCEA is currently helping the Agency respond to the Gulf oil spill emergency by
providing information on the potential toxicity of constituents in crude oil and the dispersants
used in cleaning up the spill.
Recommendation 5: The BOSC recommends that, in addition to the goals of 16 new IRIS and
50 new or revised PPRTV assessments per year, goals be established for increasing the number
of assessments. The BOSC recognizes that it may not be possible to do more, given current
staffing and budgetary limitations, but there is clearly a significant demand for these products.
Original Response: The HHRA Program agrees that there is a need to establish goals for
increasing the number of assessments beyond that of 16 new IRIS and 50 new or revised PPRTV
assessments per year. However, as noted in response to Recommendation # 1, there are both
process requirements and resources limitations that affect productivity. The HHRA Program is
implementing the revised process to meet current commitments and is revising the chemical
prioritization and selection process to better reflect client office assessment priorities and
associated resource requirements. Further, the HHRA Program is developing a process for the
update of IRIS assessments ten years and older.
The HHRA Program is also addressing the concerns raised by the BOSC to increase the
program's ability to produce more PPRTV assessments per year and has initiated significant
modifications to protocols for the development of draft documents. In addition, the HHRA
program has initiated a process for the evaluation of PPRTVs with sufficient data to develop into
IRIS assessments. Two PPRTV assessments (vanadium pentoxide and cobalt) are being
evaluated and modified for entry into the IRIS review process. PPRTV assessments are also
being evaluated for use in the IRIS Update Process.
Original Action/Timeline: The HHRA Program has begun a number of efforts to streamline
and increase the number of assessments produced per year such as: 1) the development of an
IRIS Update Process; 2) significant modifications to the PPRTVs development process; 3) the
modification of PPRTVs with sufficient data for entry into the IRIS process; and 4) PPRTV
assessments are being evaluated for use in IRIS Update Process. An assessment of the
programs' effectiveness, productivity and resource needs will be made as part of the
implementation of these efforts. Consultations are also ongoing with OMB on new measures
and metrics for the program.
Updated Response: See response to Recommendation #6 for updates on modifying PPRTV
assessments to IRIS assessments.
Current Progress: The HHRA Program has taken several steps to meet this recommendation.
The FY 2010 enacted budget includes additional resources for the IRIS program. Further, the
process used to develop IRIS assessments was revised in May 2009; the new process will allow
for more rapid completion of assessments while retaining transparency and opportunity for
Agency and Interagency comments, as well as vigorous independent external peer review and
public review and comment. The table provided in the response to Recommendation #1
illustrates how the new process has greatly improved the ability of EPA's IRIS program to
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provide high quality human health risk information to EPA's programs and regions in a timely
fashion. After the announcement of the new process, the fourth quarter of fiscal year 2009
began. More final assessments were posted on IRIS in that single quarter of one year than in
each of the previous three years. Thus, HHRA's IRIS program has quickly demonstrated
progress under the new process, and will continue to show significant results in 2010 and
beyond.
Additionally, we have developed an IRIS Logistics team that coordinates all IRIS-related
administrative support. Additional details are provided in the response to Recommendation #1.
We have met extensively with EPA's program and regional offices to better understand their
assessment needs. Additionally, we are working with Cal/EPA and ATSDR under separate
MOUs; we expect these efforts to eventually increase our efficiency and assessment output.
We have also begun a program to update older IRIS assessments. Additional details on this
program are described in our progress under Recommendation #2.
We have taken steps to facilitate more efficient production of PPRTV assessments by: (1)
developing a PPRTV review team within NCEA; (2) streamlining the information included in a
PPRTV assessment to focus on pertinent data and decision-making sections; (3) educating EPA
contractors about expectations for PPRTV assessment documents; and (4) batching assessment
development and internal and external reviews. This has proven to be a successful effort. In FY
2009, NCEA produced 69 new PPRTV assessments. These 69 PPRTV assessments included a
total of 140 new individual toxicity values (e.g., RfD, RfC, Oral Cancer Slope Factor, etc.) that
were added to the PPRTV database.
NCEA has also negotiated new program metrics with OMB. Specifically, NCEA's newly
negotiated performance metric indicates the HHRA Program will complete health hazard and
dose response assessments of high priority chemicals as interagency science consultation drafts
or external peer review drafts with a program-defined value of 50 points applied to a 3-year
rolling average. Additionally, the HHRA Program will post on the IRIS web page completed
health hazard assessments of high priority chemicals for public dissemination with a program
defined value of 20 points applied to a 3 year rolling average. To account for differences in the
level of complexity of assessments, the HHRA Program has also negotiated with OMB a tiering
system that provides three different levels of complexity and associated points for reaching
milestones for assessments. Tier 1 assessments are standard assessments that are expected to
require a typical level of effort from NCEA scientists and be limited in controversy and the
complexity of the science required for the assessment. Tier 1 assessments are assigned a point
value of "1" for each major negotiated milestone met. Tier 2 assessments are more extensive in
that they require more FTE effort, have a greater level of controversy or visibility, and are
scientifically more complex than Tier 1. Tier 2 assessments are assigned a point value of "2" for
each major negotiated milestone met. Tier 3 assessments are the most complex. They require an
exceptional level of FTE support, are highly controversial and/or visible, and are exceptional in
the complexity of the science involved in the assessment. Tier 3 assessments are assigned a
point value of "5" for each major negotiated milestone met.
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The following charts illustrate the HHRA Program's progress in meeting these program metrics.
100
Process Milestones (IRIS)
Planning
Estimate
Q2 Q3
Quarters (FY 2010)
Q4
Final Assessments Posted (IRIS)
-^-Planning
Estimate
-•-Actuals
Q2 Q3
Quarters (FY 2010)
Recommendation 6: The BOSC recommends that well-developed PPRTVs be considered as a
source of prioritization in the development of full IRIS documents. This should assist the HHRA
Program in meeting its goal of producing 16 IRIS assessments per year, but also should facilitate
the accomplishment of stretch goals for completing additional assessments.
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Original Response: The HHRA Program fully agrees with the BOSC recommendation that
well-developed PPRTVs be considered as a source for the possible development of IRIS
assessments. As noted in the response to Recommendation # 5 above, the HHRA Program has
initiated this effort and currently PPRTVs for vanadium pentoxide and cobalt have been selected
for modification and entry into the IRIS process.
Original Action/Timeline: HHRA management is routinely evaluating new and renewed
PPRTVs for potential development of new IRIS assessments or updating existing IRIS
assessments. Thus far PPRTVs for vanadium pentoxide and cobalt have been selected for
modification into IRIS assessments.
Updated Response: In late 2008, the program made a decision to focus resources on ongoing
assessments that were at or beyond the Agency review step of the assessment development
process in order to accelerate the agenda. The specific examples chosen from the PPRTV
program were in the earlier stages of assessment. The feasibility of using PPRTVs for
development of IRIS assessments continues to be explored.
Current Progress: NCEA has looked at the possibility of using the PPRTVs for cobalt and
vanadium pentoxide as sources for IRIS assessments. In 2008, NCEA decided to focus
assessment efforts on those chemicals on the IRIS agenda that were further along in the
assessment process. Those chemicals at the earlier stages of work, or for which work had not yet
begun, were temporarily put on hold so staff could focus their efforts on completing those
assessments that were further along in the process. Cobalt and vanadium pentoxide were in this
group, called "Table 2", in the earlier stages of assessment.
To better understand the Agency's needs, NCEA has proactively sought advice from EPA's
program and regional offices in an effort to identify the highest priority assessment needs across
the Agency for chemicals currently on the IRIS agenda. Those highest priority needs will be
addressed through the IRIS program. Where needs have been identified as a lower priority,
NCEA has consulted with the programs and regions to determine if a PPRTV would meet the
identified need. This would allow the assessment to be completed in a more rapid timeframe and
free up capability within the IRIS program for the highest priority needs. This exercise also
helped us to set priorities for those chemicals on "Table 2" so as staff time becomes available as
chemical assessments are completed, we can focus efforts on the highest priority chemicals first.
PROGRAM PERFORMANCE
The BOSC summarized HHRA's performance as making substantial and satisfactory progress on
each LTG based both on the clearly defined milestones (APGs and APMs) and on providing the
support requested in response to unscheduled emergency needs. The BOSC did note, however,
that with respect to LTG 1, the APGs for every year include the completion of 16 high priority
health hazard assessments and 50 new or renewed PPRTVs. This rate of completion will not
satisfy the stated goal to have no IRIS entries over ten years old because there are now over 540
IRIS chemicals, and a renewal rate alone of 54 per year would be needed to achieve that goal.
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Therefore, the BOSC reiterated their recommendation that NCEA should assess what needs to be
done to increase the rate of assessment completion.
Recommendation: NCEA should assess what needs to be done to increase the program's ability
to produce more IRIS and PPRTV assessments per year, not only to meet their own stated
objectives but also to satisfy the needs of their clients. This could either be in the form of a
recommendation to the Agency for more resources, or the development of a more streamlined
process.
Original Response: See response to recommendations #1, 2, 5 and 6 above.
Original Action/Timeline: See response to recommendations #1, 2, 5 and 6 above.
Updated Response: No change to the ORD action.
Current Progress: See responses to recommendations #1, 2, 5 and 6 above.
PROGRAM QUALITY
The quality of the products of the HHRA Program was judged primarily on the basis of the
global acceptance and use of the health assessments and the presentation of the research efforts
completed and currently being pursued by staff scientists. The BOSC stated, on both counts, the
very high quality of those products was evident. They also stated that IRIS assessments are
considered internationally to be of the highest quality and reliability. The research efforts
presented to the BOSC had a high degree of scientific relevance and merit. The review of criteria
air pollutants has an excellent record of past performance.
Recommendation 7: In order to maintain the high level of quality that is evident in the HHRA
work products, the BOSC strongly recommends that steps be taken to ensure the transparency of
decisions made in the process of performing IRIS and PPRTV assessments and IS As
Original Response: ORD appreciates the BOSC's recognition of the "very high quality" of its
products and noting of the international status of IRIS assessments as being "considered to be of
the highest quality and reliability" and agrees with the recommendation that steps be taken to
ensure the transparency of decisions. As part of the new IRIS process announced on April 10,
2008 by EPA Deputy Administrator, Marcus Peacock, the program has begun chemical specific
"listening sessions". Since the April announcement, the HHRA Program has conducted listening
sessions for the carbon tetrachloride, cerium, beryllium, and tetrachloroethylene IRIS
assessments. Protocols and standard operating procedures for the selection, prioritization and
development of IRIS assessments are available on the IRIS Web site and the program is
currently revising the chemical prioritization and selection process to better reflect client office
assessment priorities and associated resource requirements. All external peer review meetings
are announced in the Federal Registered and are open to the public.
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The IRIS Update Process is currently under development. In developing the draft process, the
HHRA Program has met with EPA's programs and regions, the EPA Science Policy Council and
the Toxic and Risk Subcommittee of the Committee on the Environment and Natural Resources
(CENR) for their input into the process. Agreements have been established to involve all
interested parties and agencies in the prioritization and peer-review of updated chemicals
assessments. The draft process includes both public notices through the Federal Register
announcing chemicals under consideration and a request for available data and announcement of
external peer review meetings. All external peer review meetings for the IRIS Update program
will be conducted through a FACA process and will be open to all interested parties.
For PPRTVs, OSWER works with the HHRA Program to identify and prioritize chemicals for
development. New contaminants are selected based on their frequency and level of
contamination at Superfund sites and whether or not toxicity values are available from other
entities like Cal/EPA or ATSDR. Existing PPRTVs are re-evaluated every five years and
updated as appropriate.
As noted in the BOSC report and discussed during the face-to-face meeting, the Agency has
developed a new NAAQS review process which includes the development of ISAs by the HHRA
Program. The new process was developed by an internal EPA workgroup in consultation with
the Clean Air Scientific Advisory Committee (CASAC), Congressional staff and interested
stakeholders. The new process also includes extensive collaboration and consultation between
ORD and OAR throughout the entire review. It incorporates additional steps for peer
consultation with outside experts and stakeholders and includes an integrated planning step that
guides the entire review. This integrated planning is achieved through workshops jointly
sponsored by ORD and OAR to receive input from experts including members of CASAC who
discuss key issues. The transition to the new process began in 2007 with the NOx and SOx
reviews.
Original Action/Timeline: The HHRA Program is developing and implementing a new IRIS
development process which includes extensive intra- and interagency and public involvement,
revised approaches to chemical prioritization and accountability, and a new Update Process
Also, as noted above, ISAs are being developed as part of the new NAAQS process which
includes extensive collaboration and consultation between ORD and OAR and public
involvement throughout the entire review. An update on the development of IRIS assessments,
PPRTVs, and ISAs will be provided at the mid-cycle review.
Updated Response: NCEA has also developed and is using the Health and Environmental
Research Online (HERO) system, which houses the scientific literature used to develop ISAs as
well as IRIS and PPRTV assessments. Additionally, several steps have been taken to further
increase transparency and communication.
Current Progress: In May 2009, the Administrator of the EPA announced a new IRIS process
that is more streamlined yet retains a strong commitment to transparency through multiple
opportunities for intra and inter-Agency review, external peer review, and public comment.
Additionally, in March 2010, EPA announced the availability of the Health and Environmental
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Research Online (HERO) database, which was praised by EPA as "a milestone in transparency"
and a part of EPA's "open government directive to conduct business with transparency,
participation, and collaboration." The publicly accessible HERO database (www.epa.gov/hero)
provides an easy way to review the scientific literature behind NCEA's science assessments.
The database includes more than 300,000 scientific articles including the authors, titles, dates,
and abstracts. In addition, through a simple keyword search, anyone can see information from
the articles that were used to develop specific risk assessments. HERO includes peer-reviewed
literature used by EPA to develop ISAs that support the NAAQS review. It also includes
references and data from IRIS, a database that supports critical agency policymaking for
chemical regulation, and from PPRTVs.
At the time of the BOSC review, EPA was in the process of implementing revisions to the
NAAQS review process, and NCEA was developing ISAs for reviews of the NAAQS for
nitrogen oxides and sulfur oxides. In the past three years, NCEA has completed the initial set of
ISAs for oxides of nitrogen and sulfur (NOx- health effects, SOx - health effects, and ecological
effects of NOx and SOx) along with ISAs for PM and CO, meeting several court-ordered
deadlines along the way. In the process, NCEA has restructured the ISA to place a concise
summary and integrative synthesis of the key findings at the beginning of the assessment,
focusing on the key policy-relevant findings with figures that present the findings from across
health studies relevant to pollutant concentrations to better inform decision makers. NCEA has
developed a causality framework that has been used in all five ISAs, and provides transparency
and consistency in the process of drawing conclusions and causal judgments. CASAC panels
have lauded the implementation of the causal framework, the process for developing the ISA and
the structure of the ISA; positive comments have been received during the peer reviews of draft
ISAs for both PM and CO.
Also, in the recent draft dioxin report entitled, EPA 's Reanalysis of Key Issues Related to Dioxin
Toxicity and Response to NAS Comments flittp ://www. epa. gov/dioxin), there is lengthy
discussion and accompanying schematics detailing the delineated study selection process for the
identification of appropriate studies for TCDD dose-response analysis. In addition, in February
2009, to assist NCEA in responding to the NAS, NCEA convened a scientific workshop to
identify and address issues related to the dose-response assessment of TCDD and to ensure that
EPA's response to the NAS focused on the key issues and reflected the most meaningful science.
This workshop was open to the public and included scientific experts from academia, industry,
non-profit organizations, and government. These experts discussed potential approaches to
TCDD dose-response assessment and considerations for EPA's response to NAS. As a result,
the process used by EPA to determine key scientific approaches and decisions in the
development of the recent draft dioxin report can be held up as a model for transparency and
public participation.
NCEA has also been providing listening sessions for the public and stakeholders for chemicals
on the IRIS agenda. Additionally, for high profile chemicals like formaldehyde, dioxin, and
arsenic, NCEA has provided briefings for other Agencies and stakeholders at key points in the
assessment process.
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Finally, NCEA has taken steps to standardize assessment practices within the Center. Standard
Operating Procedures for developing IRIS assessment documents have been written, and NCEA
has started to convene regular science policy discussion meetings with staff to make sure science
policy practices are consistent across assessments.
SCIENTIFIC LEADERSHIP
The BOSC found that: 1) there are important areas in which HHRA Program scientists have
played leadership roles at both the national and international levels; 2) the HHRA Program is
clearly recognized as an international leader in risk assessment in both methods development and
implementation; and 3) the areas of impressive leadership are related to IRIS and Air Quality
Health and Environmental Assessments. The report also states that, taken as a whole, the
evidence speaks to a community of highly trained and productive scientists, many of whom are
leaders in their field, who are providing leadership to the United States and international
governments as well as scientific communities and are engaged in risk assessment science and in
solving important risk assessment problems.
Recommendation 8: The HHRA Program should consider using available resources to recruit
one or two additional senior scientists, especially into the LTG 2 program where efforts are
underway to integrate emerging technologies into the risk assessment processes.
Original Response: The HHRA Program appreciates the feedback and recognition by the
BOSC of the quality and extent of its leadership both nationally and internationally. The HHRA
Program agrees with the recommendation to enhance that quality by recruiting senior scientists
throughout its program and will look for opportunities to fill positions with senior leaders from
both within the Agency and outside experts.
Original Action/Timeline: Recently, the HHRA Program recruited a senior scientist from
NHEERL, Dr. Linda Birnbaum. In addition, ORD has obtained authority to hire experts and
senior scientists under Title 42. The HHRA Program has initiated one recruitment action under
this program and will announce an additional recruitment in 2009.
Updated Response: Dr. Birnbaum has taken a new job. She is now the Director of the National
Institute of Environmental Health Sciences (NIEHS).
Current Progress: For the last three years NCEA has had the benefit of input from two senior
statisticians who participate in the Oak Ridge Institute for Science and Education (ORISE)
fellows program. Dr. Kenny Crump has been a leading investigator in the field of dose response
modeling over the past 30 years. His participation in the ORISE fellows program has allowed
him to contribute to important science issues faced by EPA in the area of quantitative risk
assessment. In particular he has delved deeply into issues regarding application of biologically
based dose response models for risk assessment needs. This effort has sharpened our
understanding of the strengths and limitations of such models in advancing understanding of
chemical risks. Dr. Crump is currently working on the quantitative application of genomics and
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other high-throughput data in chemical risk assessment. Dr. Bimal Sinha, Professor of Statistics
with University of Maryland Baltimore County, has worked with NCEA to advance statistical
methods for several areas of quantitative risk assessment. These areas have included application
of more robust statistical procedures in modeling data from pharmacokinetic studies, extension
of methods for incorporating experimental error estimates in benchmark dose modeling, and
analysis of exposure statistics data.
The HHRA Program has used the ORISE program to bring on board a few senior scientists to
help address some of the complex scientific issues discussed in the 2009 National Research
Council (NRC) Report, Science and Decisions: Advancing Risk Assessment. Additionally,
scientists from the HHRA Program are actively engaged with scientists in academia, state
governments, and industry, both across the U.S. and internationally, to discuss issues, conduct
research, and develop pertinent case studies that will be useful in addressing the NRC
recommendations. Complex scientific issues being discussed include probabilistic methods and
accounting for uncertainty and variability in quantitative dose-response; mode of action,
background exposures and disease processes, and vulnerable populations in low dose
extrapolation; and applying similar quantitative approaches for cancer and non-cancer health
assessment.
In particular, ORISE Faculty Fellow Dr. Gary Ginsberg (University of Connecticut) is working
with NCEA on developing new methods and models for incorporating information regarding
susceptible populations into EPA risk assessments. ORISE Faculty Fellow Dr. David Eastmond
is working with NCEA scientists to develop a database on the mutagenic mode of action of
certain chemicals of interest to the IRIS program. Drs. Ginsberg and Eastmond have made
several seminar presentations to NCEA staff on risk assessment issues.
NCEA has also recruited and hired a Title 42 Division Director to manage NCEA's Research
Triangle Park (RTF) Division. NCEA intends to recruit additional Title 42 and/or SL (senior
level) scientists to fill critical hiring needs in the organization.
Additionally, NCEA plans to add five ORISE post docs to the IRIS program to work on IRIS
assessments. Two scientists have been hired under this program so far and will start in the
summer 2010. Interviews for the remaining three positions are ongoing. In addition to the
ORISE program, NCEA has also increased capacity in key scientific areas through the American
Association for the Advancement of Science (AAAS) and Association of Schools of Public
Health (ASPH) Fellowship programs. Several postdocs and fellows have been added to LTG2 as
part of the HHRA's NexGen effort. Additionally, a collaborative NexGen effort among other
labs and centers has effectively expanded the LTG2 effort. See description of NexGen in
response to Recommendation #1.
COORDINATION AND COMMUNICATION
The BOSC stated that communication and coordination activities have been effectively
institutionalized within HHRA. These activities are well established and occur vertically and
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horizontally within NCEA and with other relevant EPA programs and regional offices. Well-
documented systems are in place and have operated for many years to provide a systematic,
structured prioritization and communication strategy to assure that EPA program and regional
office scientists and managers are effectively involved in setting priorities for assessment
development and that HHRA activities such as IRIS and PPRTV assessments reflect the client's
needs. The BOSC noted that with the exception of PPRTVs, HHRA products including
assessments (such as IRIS and ISAs), methods, guidelines, and reference documents such as the
Exposure Factors Handbooks, are all available to the public on the Internet and provide
information not available from any other source.
Recommendation 9: PPRTVs far outnumber IRIS assessments and are being developed at four
to five times the rate of IRIS assessments. They have been developed specifically to address the
site specific needs of EPA's Superfund program. Currently, PPRTVs and their supporting
documentation are only available on a Web site restricted to use by EPA staff or to those who
obtain special permission from EPA. The BOSC encourages EPA to make the PPRTVs publicly
available for use in hazardous waste site risk assessment and promote their use where
appropriate.
Original Response: The HHRA Program agrees that PPRTVs are extremely important to the
Superfund program and these assessments are important for assessing hazards at waste sites.
PPRTVs are available to the states and other partners involved in waste site assessments and they
are provided updates on a quarterly basis. PPRTVs are also being made available to other
program offices within EPA for screening and prioritization of research needs, e.g. use by Office
of Water to prioritize research needs for CCL3 decisions. PPRTVs are also being modified
where appropriate to support the development of IRIS assessments and new PPRTVs evaluated
for use in IRIS Update Process.
Please note there currently are over 547 chemical assessments on IRIS. PPRTVs have been
developed for 381 chemicals.
Original Action/Timeline: PPRTVs are available to the states and other partners involved in
waste site assessments and they are provided updates on a quarterly basis. Within EPA PPRTVs
are being made available to other program offices for screening and prioritization of research
needs.
Updated Response: No change to the ORD action.
Current Progress: PPRTVs are currently available to all EPA staff and by request to states and
other partners involved in waste site assessments. Updates are provided on a quarterly basis.
NCEA has been proactive about conducting more outreach to EPA's programs and regions,
including providing them with information about PPRTVs. As a result, the PPRTV Web site
(which is available to any EPA employee) has been shared with several EPA program offices
outside of the Superfund program. These programs have indicated this information will help
them address screening and prioritization needs as well as the need for toxicity numbers.
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At this time, NCEA does not think it is possible to make the PPRTV database publicly available.
We have explored the feasibility and think there are potential issues and complicating factors.
However, we have planned a follow-up conversation with OSWER to discuss this once again,
and we continue to explore the possibility of making the PPRTV database publicly available.
OUTCOMES
The BOSC concluded that outcome measures are extremely well defined for each LTG and that
annual measures are well described. The procedures for IRIS and PPRTVs appear to be well
considered and to work well, but how decisions are made is not immediately transparent. The
BOSC was particularly interested to know whether chemicals that had not reached a high enough
priority level to be reviewed in a given year were carried over for consideration in ensuing years,
and whether they were accorded a higher priority status by virtue of having been on the list for a
period of time. The BOSC also reiterated its recommendation (See Recommendation #4) to
consider capturing in the APGs the program's responsiveness to national emergencies and high
profile site clean-ups.
Recommendation 10: The HHRA Program needs to consider information on the potential
public health concern of various chemicals as it prioritizes them for IRIS or PPRTV review. It
appears that some of this information is being provided by the program and regional offices, but
it would be of value for the program to make transparent the basis for its prioritization decisions
for IRIS and PPRTVs.
Original Response: The HHRA Program agrees with the BOSC's recommendation to consider
information on the potential public health concern of various chemicals as it prioritizes them for
IRIS or PPRTV review and the need for transparency within the program. Criteria for the
selection and prioritization of chemicals for new IRIS assessments and reassessments have been
established and are available on the IRIS website (www.epa.gov/iris). The IRIS process
provides both opportunities for public comment as well as providing available data. Currently
NCEA is meeting with the program offices and regions to provide more explicit information on
the IRIS process and setting priorities. For the IRIS Update Process a draft process has been
developed which includes a detailed selection and prioritization process as well as public
notification. The selection of chemicals for development of new PPRTVs or updating
assessments is determined by OSWER in consultation with ORD. The selection criteria are
based on frequency and extent of contamination at Superfund sites, the availability of toxicity
values from other sources and the availability of qualitative and quantitative information.
Original Action/Timeline: NCEA is meeting with the program offices and regions to provide
more explicit information on the IRIS process and setting priorities. Progress regarding these
efforts will be discussed at the mid-cycle review of the HHRA Program.
Updated Response: NCEA has met extensively with EPA's programs and regions, and recently
completed a prioritization exercise using feedback from the programs and regions along with
public health information.
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Current Progress: NCEA has held extensive meetings with EPA's program and regional
offices to discuss the process that is used to prioritize nominated chemicals for assessment
through the IRIS program. After several conversations with and feedback from these offices, we
have developed a revised process for prioritizing how chemicals will be added to the IRIS
agenda. This process includes collecting information about the public health concerns of the
nominated chemicals. It also involves more transparency, as well as a "feed-back" loop to the
programs and regions. Additionally, NCEA recently conducted an exercise where we asked the
programs and regions for input on regulatory and other needs for assessments for chemicals
currently on the IRIS agenda for which work has not yet begun. The purpose of this exercise was
to help the HHRA Program set priorities for completing currently backlogged assessments.
The HHRA Program will soon issue a FRN requesting nominations for chemicals to be added to
the IRIS agenda. This notice will provide more detail than previous notices in an effort to
increase transparency about the IRIS program and how decisions are made to add chemicals to
the agenda.
NCEA has also developed a list of thousands of chemicals that appear on a variety of priority
lists (HAP, CCL3, etc.) and compiled public health information (both exposure and toxicity)
about each chemical. This information may be used in the future to help the HHRA Program
proactively identify chemicals that may be a concern for public health, which would then be
presented to EPA's program and regional offices for input.
NCEA meets regularly with OSWER to set priorities for chemicals to assess under the PPRTV
program. NCEA is quite flexible in adding chemicals and reprioritizing when a high priority
need is indentified by OSWER. Additionally, as part of NexGen efforts, the HHRA Program is
investigating the use of ToxCast and ExpoCast information to help set priorities for adding
chemicals to the list for PPRTV development.
The HHRA Program is also looking at options for incorporating public heath information into
the program's prioritization process for health assessments using value of information tools.
Examples of options that are being considered include consultation with the BOSC workgroup
on decision analysis and value of information and other mechanisms.
Additionally, NCEA is currently performing an IRIS human health assessment for six phthalates
and developing a cumulative risk assessment for these chemicals as recommended by the NRC in
its report Phthalates and Cumulative Risk: The Tasks Ahead. It is expected that this cumulative
assessment will serve as a framework for extension to other compounds that act by a similar
effect. Specifically, the assessment includes the following phthalates: dibutyl phthalate (DBF),
di(2-ethylhexyl)phthalate (DEHP), butyl benzyl phthalate (BBP), di-isobutyl phthalate (DffiP),
di-isononyl phthalate (DINP), and dipentyl phthalate (DPP). The IRIS Human Health Risk
Assessment for Selected Phthalates will include noncancer and cancer qualitative and
quantitative human health effects information and estimation of risk where the data are available
for each of the phthalates. Several of the phthalates included in this assessment were already on
the IRIS agenda. However, after release of the NRC report, the HHRA Program decided to add a
few phthalates, as recommended by the NRC, based on their impact on a common health
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endpoint. Considering this public health information facilitated the addition of a few new
chemicals to the IRIS agenda.
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Office of Research and Development's Human Health Risk Assessment Program's Mid-Cycle Progress Report to the Board of
Scientific Counselors
Human Health Risk Assessment Program - BOSC Mid-Cycle Progress Report Summary Table
Recommendation
ORD Action
Timeline for Action
Recommendation #1:
NCEA should assess what
needs to be done to increase
the Program's ability to
produce more IRIS and
PPRTV assessments per year,
not only to meet their own
stated objectives but also to
satisfy the needs of their
clients. This could either be
in the form of a
recommendation to the
Agency for more resources,
or the development of a more
streamlined process.
Original Response: The
HHRA Program is
implementing changes
addressing development of
new IRIS assessments and
reassessments, is revising
the chemical prioritization
and selection process to
address client office needs,
has initiated development of
a process for updating older
assessments on IRIS and
begun efforts to enhance
and streamline the PPRTV
process.
Updated Response: No
changes to the ORD action.
Original Timeline: The next update of the HHRA MYP will reflect any significant changes in
these programs and new metrics agreed upon with OMB. Progress regarding these efforts will
also be discussed at the mid-cycle review of the HHRA Program in 2010.
Current Progress: The HHRA program has taken several steps to meet this recommendation.
The FY 2010 enacted budget includes additional resources for the IRIS program. Further, the
process used to develop IRIS assessments was revised in May 2009 (www.epa.gov/iris/process'):
the new process allows for more rapid completion of assessments while retaining transparency
and opportunity for Agency and Interagency comments, as well as vigorous independent external
peer review and public review and comment. The table below illustrates how the new process has
greatly improved the ability of the IRIS program to provide high quality human health risk
information to EPA's programs and regions in a timely fashion. After the announcement of the
new process, the fourth quarter of fiscal year 2009 began. More final assessments were posted on
IRIS in that single quarter of one year than in each of the previous three years. Thus, the HHRA's
IRIS program has quickly demonstrated progress under the new process and will continue to show
significant results in 2010 and beyond.
J
FY2006
FY2007
FY2008
FY2009
Draft Assessments
Start Interagency
Review/Consultation
11
2nd
air
3rd
qtr.
May 21,2009 4th I
New IRIS Process qtr.
FY 1009 Total
FY2010
(Qu. 1-3)
FY2010
Projected
10
Draft Assessments
Start Independen'
External Peer Rev!
12
12
10
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Additionally, we have developed an IRIS Logistics Team to coordinate all aspects of
administrative support for the IRIS program. The development of this team has created
efficiencies by centralizing logistical activities and relieving scientific staff of administrative
burdens. This is a matrix managed team that includes project officers of contracts for IRIS
document development, technical editing, and peer review; the NCEA Webmaster; the IRIS
coordinator, who maintains the public tracking system for IRIS assessments, organizes listening
sessions, and works with the chemical manager to develop project schedules; members of the
NCEA Technical Information Staff, who develop and coordinate FRNs and clearance for
documents; the interagency point of contact, who handles all correspondence with interagency
reviewers; and the NCEA communications director, who coordinates all communications dealing
with IRIS draft and final assessments. Administrative support staff schedule, organize and
administer IRIS-related meetings and briefings and coordinate with the SAB and NAS when these
bodies conduct peer reviews of IRIS assessments.
NCEA has met extensively with EPA's Program and Regional offices to better understand their
assessment needs. Additionally, NCEA is working with Cal/EPA's OEHHA and ATSDR under
separate MOUs. It is anticipated that these efforts will eventually increase efficiency and
assessment output. NCEA has also begun a program to update older IRIS assessments.
Additional details on this program are described in our progress under Recommendation #2.
We have taken steps to facilitate more efficient production of PPRTV assessments by: (1)
developing a PPRTV review team within NCEA; (2) streamlining the information included in a
PPRTV assessment to focus on pertinent data and decision-making sections; (3) educating EPA
contractors about expectations for PPRTV assessment documents; and (4) batching assessment
development and internal and external reviews. This has proven to be a successful effort. In FY
2009, NCEA produced 69 new PPRTV assessments. These 69 PPRTV assessments included a
total of 140 new individual toxicity values (e.g., RfD, RfC, Oral Cancer Slope Factor, etc.) that
were added to the PPRTV database.
NCEA has also negotiated new program metrics with OMB. Specifically, NCEA's newly
negotiated performance metric indicates the HHRA program will complete health hazard and
dose response assessments of high priority chemicals as interagency science consultation drafts or
external peer review drafts with a program-defined value of 50 points applied to a 3-year rolling
average. Additionally, the HHRA program will post on the IRIS Web page completed health
hazard assessments of high priority chemicals for public dissemination with a program defined
value of 20 points applied to a 3 year rolling average. To account for differences in the level of
complexity of assessments, the HHRA program has also negotiated with OMB a tiering system
that provides three different levels of complexity and associated points for reaching milestones for
assessments. Tier 1 assessments are standard assessments that are expected to require a typical
level of effort from NCEA scientists and be limited in controversy and the complexity of the
25
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science as well as the level of effort required for the assessment. Tier 1 assessments are assigned
a point value of "1" for each major negotiated milestone met. Tier 2 assessments are more
extensive in that they require more FTE effort, have a greater level of controversy or visibility,
and are more scientifically complex than Tier 1. Tier 2 assessments are assigned a point value of
"2" for each major negotiated milestone met. Tier 3 assessments are the most complex. They
require an exceptional level of FTE support, are highly controversial and/or visible, and are
exceptional in the complexity of the science involved in the assessment. Tier 3 assessments are
assigned a point value of "5" for each major negotiated milestone met.
Additionally, the HHRA program has begun a pilot project on advancing the next generation of
risk assessment (NexGen) that will explore the feasibility of using advances in molecular and
systems biology for developing health assessments. It is anticipated this pilot project will help
pave the way for using high throughput data to develop rapid health assessments. This is a
collaborative effort across ORD and with NIEHS, NHGRI, and Cal/EPA.
Recommendation #2:
Mechanisms should be
considered for retaining IRIS
assessments older than 10
years that have not been
updated, rather than allowing
these assessments to expire
and be removed from the
IRIS database and Web site.
One option is to simply
annotate them as such.
Original Response:
Implementation of the IRIS
update process is underway.
Updated Response: No
changes to the ORD action.
Original Timeline: Progress regarding these efforts will be discussed at the mid-cycle review of
the HHRA Program in 2010.
Current Progress: NCEA has decided that IRIS assessments older than 10 years will not be
removed from the IRIS database. Additionally, a process for updating old IRIS chemical
assessments has been developed and is nearing the implementation stages. The HHRA program
issued a FRN in October 2009 announcing the establishment of this IRIS Update Project.
Additionally, the HHRA program has developed a two-tiered peer review process consisting of a
Federal Standing Science Committee followed by a Standing External Review Panel of the SAB
under FACA. The SAB issued a FRN in March 2009 requesting the nomination of experts to
serve on this committee. Committee members have since been identified and the panel has been
established.
The intent of the IRIS Update project is to re-visit all dose-response assessment values (RfDs,
RfCs, Oral Cancer Slope Factors, and Inhalation Cancer Unit Risks) in IRIS with a posting date
more than 10-years old. The values under current assessment by the standard IRIS process (on
IRIS Track) and the values for pesticides not in active use are eliminated from the list of IRIS
values greater than 10-years old. Then the remaining values are prioritized for being updated.
This prioritization takes into consideration several factors, including frequency of occurrence in
NPL waste sites, occurrence as hazardous air pollutants used in residual risk assessments, the
presence of chemicals on the CCL, and other intra- and inter-agency interests. From this list,
smaller batches of assessments (~10) are selected for literature searches by a contractor. After the
literature search, the path for development of a revised dose-response assessment value is based
on whether new data exists or not and whether new values are proposed or not (binning).
Recommendation #3: The
HHRA Program should
Original Response: The
HHRA Program has
Original Timeline: Further efforts will be presented at the mid-cycle review of the HHRA
Program in 2010.
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continue to develop ties with
NCCT, and should provide
formal input to that Program
on the aspects of its research
that will be of value to
HHRA.
initiated and will continue to
seek opportunities to further
collaborations with NCCT
and to share data and
information. In addition,
NCEA is continuing to build
and strengthen expertise in
the area of computational
toxicology.
Updated Response: No
change to the ORD action.
Current Progress: NCEA has taken several steps to further develop ties between NCEA and
NCCT. For example, NCEA scientists participated in the NCCT ToxCast meeting in May 2009.
NCEA facilitated that participation by organizing a half-day seminar prior to the meeting to
provide an overview of ToxCast and computational toxicology tools in preparation for that
meeting.
Additionally, NCEA has developed a pilot project, which involves NCCT, to focus on the next
generation (NexGen) of risk assessment. This is driven by 1) new scientific advances, particularly
in understanding the gene environment; 2) challenges to current risk assessment practices as
articulated by the NRC in their 2009 report Science and Decisions: Advancing Risk Assessment:
and 3) the European Union's REACH legislation that will require new testing and assessment of
tens to hundreds of thousands of chemicals in commerce. In developing this program, the HHRA
program has worked with NCCT, as well as ORD's other labs and centers and EPA's program
and regional offices. NexGen assessments will be developed at three levels of complexity to be
responsive to the risk context. Category 1 would use reliable high and medium throughput assays
and structure-activity analyses to conduct a screening assessment and rank chemicals for further
analysis. Depending on the priority established in Category 1, the risk context and the available
data, two levels of additional analyses could be conducted: assessments prepared for data poor
chemicals based upon a relatively narrow context of use and relying on standard practices
(Category 2, e.g., PPRTV-like); or a broader, more complex assessment relying on state-of-the-
science practices (Category 3).
The HHRA program has provided information on chemicals of key concern to the NCCT program
for inclusion in the ToxCast Program. Included are those chemicals currently on the IRIS agenda
or under assessment in the PPRTV program. Additionally, NCEA has developed a list of
thousands of chemicals that appear on a variety of priority lists (HAP, CCL3, etc.) and compiled
public health information (both exposure and toxicity) about each chemical. This information was
also provided to the NCCT program. All of these chemicals will be added to Phase 2 of the
NCCT's ToxCast program, per NCEA's suggestion.
NCEA is also actively involved in an effort to expand the ToxRef database to include
developmental neurotoxicity data. In collaboration with NCCT, NCEA has provided funding for
data entry, and NCEA scientists are serving as advisors in developing the database structure and
in assuring accurate interpretation of the data for entry.
NCCT and NCEA share postdocs through the Cross-ORD Postdoctoral fellowship program. Dr.
Holly Mortensen works with both NCCT and NCEA. At NCCT, she has developed a toxicity
pathway database that will be used to assess ToxCast assay results. This approach is in line with
NAS' Toxicity Testing in the 21st Century's long range vision of moving toward a toxicity
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pathway perturbation based risk assessment approach. At NCEA, she is working on the use of
genomics to inform intraspecies differences in response to toxic agents. She is currently co-
authoring a manuscript on the use of 'omics data to inform susceptibility.
On several occasions, the Center Directors for NCCT and NCEA have done joint presentations on
the future of toxicology and risk assessment, including a briefing for the Senate Appropriations
Committee staff on June 9, 2009. Other events where the importance of the two centers working
together was presented include: The NAS' May 2009 symposium on toxicity-pathway-based risk
assessment (http://dels-old.nas.edu/best/risk analysis/symposium.shtml) and the BOSC's
Computational Toxicology Subcommittee in September 2009.
NCEA and NCCT are collaborating through the RAF to provide training for scientists in the ORD
on the application of computational methods in risk assessment, training for risk assessors on
computational tools that are available for application in risk assessment (hazard and dose
response), and training for decision makers on the implications of these new technologies.
Finally, several NCEA scientists have joined NCCT on detail assignments to the NCCT
fellowship program. This relationship has been beneficial to both NCEA and NCCT and has led
to additional collaborations between the two Centers and also between NCEA and other labs
within ORD. This work will develop assessment applications for high throughput and high
content data, methods and models. It will feed into and complement ORD's new integrated
transdisciplinary research program on Safe Products for a Sustainable World.
Recommendation #4: The
Subcommittee considers the
responsiveness of the staff
members to national
emergencies and the HHRA
Program's contributions to
particularly difficult cleanup
sites as being of such high
value that this should
somehow be captured in the
APGs.
Original Response: The
HHRA Program has started
to better track these
activities and the resources
expended both internally
and across ORD. The
program will also work
more closely withEPA's
Office of Emergency
Management to be better
prepared to respond to such
events.
Updated Response: No
change to the ORD action.
Original Timeline: The next update of the HHRA MYP will include a section or description
relating to these response efforts.
Current Progress: NCEA is tracking these emergency support activities and is holding
discussions internally about how this should be described in the next version of the HHRA MYP.
While it is impossible to predict the number and type of emergency response activities that may
arise, we expect this tracking will give us a better idea of what level of commitment we could
reasonably expect in the future for this type of support.
Over the past calendar year, NCEA has assisted with several high-profile support activities. In the
summer of 2009, NCEA scientists provided extensive support to the Agency as it dealt with
characterizing the risk of PCBs in caulk in schools and other buildings. HHRA scientists
developed a PCB exposure estimation tool and developed advisory limits for indoor school air
concentrations. NCEA also provided support in 2009 to Region 5 and OSWER, completing an
evaluation of the UMDES. This evaluation provided perspective on how the UMDES results
could inform Agency decision-making concerning dioxin in soils in Region 5. NCEA also
provided rapid support to Region 7 as they dealt with an emergency situation involving
hexavalent chromium. NCEA coordinated a conference call and presentation to provide
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information to Region 7 about the health effects of hexavalent chromium. As a result of this
request, NCEA convened a meeting with other EPA programs and regions with an interest in
hexavalent chromium to discuss accelerating an IRIS assessment for the chemical. Because of
these meetings, NCEA has rapidly developed a draft health assessment document for hexavalent
chromium that meets the identified needs of the programs and regions; that assessment is moving
through the IRIS process at an accelerated rate.
NCEA has maintained a consistent level of support and visibility to EPA's programs and regions.
Through high profile, timely, and high quality support as identified above, as well as through
established programs like the Superfund Technical Support Center and the PPRTVs, NCEA has
become the "go to" organization for high quality and rapid scientific support.
NCEA has enhanced this visibility by conducting outreach to EPA's regional offices through 1-2
day regional visits. These visits typically consist of both informal discussions and formal
presentations on a variety of topics. The goals of the meeting are to inform the regions of NCEA's
products and capabilities, better understand regional issues and concerns, and strengthen ties at
the management and staff levels. So far, NCEA has visited regions 2, 3, 6, 8, and 9 with very
successful results. Additional visits are being planned.
Finally, NCEA is currently helping the Agency respond to the Gulf oil spill emergency by
providing information on the potential toxicity of constituents in crude oil and the dispersants
used in cleaning up the spill.
Recommendation #5: The
Subcommittee recommends
that, in addition to the goals
of 16 new IRIS and 50 new
or revised PPRTV
assessments per year, goals
be established for increasing
the number of IRIS
assessments. The
Subcommittee recognizes that
it may not be possible to do
more, given current staffing
and budgetary limitations.
Original Response: Given
current limitations, the
HHRA Program has begun a
number of efforts to
streamline and increase the
number of assessments
produced per year such as:
1) the development of an
IRIS Update Process; 2)
significant modifications to
the PPRTV development
process; 3) the modification
of PPRTVs with sufficient
data for entry into the IRIS
process and 4) PPRTV
assessments are being
evaluated for use in IRIS
Update Process
Original Timeline: Ongoing. Progress regarding these efforts will be discussed at the mid-
cycle review of the HHRA Program in 2010.
Current Progress: The HHRA program has taken several steps to meet this recommendation.
The FY 2010 enacted budget includes additional resources for the IRIS program. Further, the
process used to develop IRIS assessments was revised in May 2009; the new process will allow
for more rapid completion of assessments while retaining transparency and opportunity for
Agency and Interagency comments, as well as vigorous independent external peer review and
public review and comment. The table provided in the response to Recommendation #1 illustrates
how the new process has greatly improved the ability of EPA's IRIS program to provide high
quality human health risk information to EPA's programs and regions in a timely fashion. After
the announcement of the new process, the fourth quarter of fiscal year 2009 began. More final
assessments were posted on IRIS in that single quarter of one year than in each of the previous
three years. Thus, HHRA's IRIS program has quickly demonstrated progress under the new
process, and will continue to show significant results in 2010 and beyond.
Additionally, we have developed an IRIS Logistics team that coordinates all IRIS-related
administrative support. Additional details are provided in the response to Recommendation #1.
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Recommendation #6: The
Subcommittee recommends
Consultations are also
ongoing with OMB on new
measures and metrics for the
program.
Updated Response : No
change to the ORD action.
Original Response:
HHRA management is
We have met extensively with EPA's Program and Regional offices to better understand their
assessment needs. Additionally, we are working with Cal/EPA and ATSDR under Memoranda of
Understanding; we expect these efforts to eventually increase our efficiency and assessment
output.
We have also begun a program to update older IRIS assessments. Additional details on this
program are described in our progress under Recommendation #2.
We have taken steps to facilitate more efficient production of PPRTV assessments by: (1)
developing a PPRTV review team within NCEA; (2) streamlining the information included in a
PPRTV assessment to focus on pertinent data and decision-making sections; (3) educating EPA
contractors about expectations for PPRTV assessment documents; and (4) batching assessment
development and internal and external reviews. This has proven to be a successful effort. In FY
2009, NCEA produced 69 new PPRTV assessments. These 69 PPRTV assessments included a
total of 140 new individual toxicity values (e.g., RfD, RfD, Oral Cancer Slope Factor, etc.) that
were added to the PPRTV database.
NCEA has also negotiated new program metrics with OMB. Specifically, NCEA's newly
negotiated performance metric indicates the HHRA program will complete health hazard and
dose response assessments of high priority chemicals as interagency science consultation drafts or
external peer review drafts with a program-defined value of 50 points applied to a 3 -year rolling
average. Additionally, the HHRA program will post on the IRIS Web page completed health
hazard assessments of high priority chemicals for public dissemination with a program defined
value of 20 points applied to a 3 year rolling average. To account for differences in the level of
complexity of assessments, the HHRA program has also negotiated with OMB a tiering system
that provides three different levels of complexity and associated points for reaching milestones for
assessments. Tier 1 assessments are standard assessments that are expected to require a typical
level of effort from NCEA scientists and be limited in controversy and the complexity of the
science required for the assessment. Tier 1 assessments are assigned a point value of "1" for each
major negotiated milestone met. Tier 2 assessments are more extensive in that they require more
FTE effort, have a greater level of controversy or visibility, and are scientifically more complex
than Tier 1 . Tier 2 assessments are assigned a point value of "2" for each major negotiated
milestone met. Tier 3 assessments are the most complex. They require an exceptional level of
FTE support, are highly controversial and/or visible, and are exceptional in the complexity of the
science involved in the assessment. Tier 3 assessments are assigned a point value of "5" for each
major negotiated milestone met. The figures provided in the report text illustrate the HHRA
Program's progress in meeting these program metrics.
Original Timeline: Progress regarding these efforts will be discussed at the mid-cycle review of
the HHRA Program in 2010.
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that well-developed PPRTVs
be considered as a source of
prioritization in the
development of full IRIS
documents
routinely evaluating new
and renewed PPRTVs for
potential development of
new IRIS assessments or
updating existing IRIS
assessments. Thus far
PPRTVs for vanadium
pentoxide and cobalt have
been selected for
modification into IRIS
assessments.
Updated Response: In late
2008, the Program made a
decision to focus resources
on ongoing assessments that
were at or beyond the
Agency review step of the
assessment development
process in order to
accelerate the agenda. The
specific examples chosen
from the PPRTV program
were in the earlier stages of
assessment. The feasibility
of using PPRTVs for
development of IRIS
assessments continues to be
explored.
Current Progress: NCEA has looked at the possibility of using the PPRTVs for cobalt and
vanadium pentoxide as sources for IRIS assessments. In 2008, NCEA decided to focus
assessment efforts on those chemicals on the IRIS agenda that were further along in the
assessment process. Those chemicals at the earlier stages of work, or for which work had not yet
begun, were temporarily put on hold so staff could focus their efforts on completing those
assessments that were further along in the process. Cobalt and vanadium pentoxide were in this
group, called "Table 2", in the earlier stages of assessment.
To better understand the Agency's needs, NCEA has proactively sought advice from EPA's
Program Offices and Regions in an effort to identify the highest priority assessment needs across
the Agency for chemicals currently on the IRIS agenda. Those highest priority needs will be
addressed through the IRIS program. Where needs have been identified as a lower priority,
NCEA has consulted with the Programs and Regions to determine if a PPRTV would meet the
identified need. This would allow the assessment to be completed in a more rapid timeframe and
free up capability within the IRIS program for the highest priority needs. This exercise also
helped us to set priorities for those chemicals on "Table 2" so as staff time becomes available as
chemical assessments are completed, we can focus efforts on the highest priority chemicals first.
Recommendation #7: In
order to maintain the high
level of quality that is evident
in the HHRA work products,
the Subcommittee strongly
recommends that steps be
taken to ensure the
transparency of decisions
made in the process of
performing IRIS and PPRTV
assessments and ISA
Original Response: The
HHRA program is
developing and
implementing a new IRIS
development process which
includes extensive intra- and
interagency and public
involvement, revised
approaches to chemical
prioritization and
accountability, and a new
Original Timeline: An update on the development of IRIS assessments, PPRTVs, and ISAs will
be provided at the mid-cycle review in 2010.
Current Progress: In May 2009, the Administrator of the EPA announced a new IRIS process
that is more streamlined yet retains a strong commitment to transparency through multiple
opportunities for intra and inter-Agency review, external peer review, and public comment.
Additionally, in March 2010, EPA announced the availability of the Health and Environmental
Research Online (HERO) database, which was praised by EPA as "a milestone in transparency"
and a part of EPA's "open government directive to conduct business with transparency,
participation, and collaboration." The publicly accessible HERO database provides an easy way
to review the scientific literature behind NCEA's science assessments.
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assessments
Update Process. ISAs are
being developed as part of
the new NAAQS process
which includes extensive
collaboration and
consultation between ORD
and OAR and public
involvement throughout the
entire review.
Updated Response: NCEA
has also developed and is
using the Health and
Environmental Research
Online (HERO) system,
which houses the scientific
literature used to develop
ISA, IRIS and PPRTV
assessments. Additionally,
several steps have been
taken to further increase
transparency and
communication.
www.epa. gov/hero
The database includes more than 300,000 scientific articles including the authors, titles, dates, and
abstracts. In addition, through a simple keyword search, anyone can see information from the
articles that were used to develop specific risk assessments. HERO includes peer-reviewed
literature used by EPA to develop its ISAs that support the NAAQS review. It also includes
references and data from IRIS, a database that supports critical agency policymaking for chemical
regulation, and from PPRTVs.
At the time of the BOSC review, EPA was in the process of implementing revisions to the
NAAQS review process, and NCEA was developing ISAs for reviews of the NAAQS for nitrogen
oxides and sulfur oxides. In the past three years, NCEA has completed the initial set of ISAs for
oxides of nitrogen and sulfur (NOx- health effects, SOx - health effects, and ecological effects of
NOx and SOx) along with ISAs for PM and CO, meeting several court-ordered deadlines along
the way. In the process, NCEA has restructured the ISA to place a concise summary and
integrative synthesis of the key findings at the beginning of the assessment, focusing on the key
policy-relevant findings with figures that present the findings from across health studies relevant
to pollutant concentrations to better inform decision-makers. NCEA has developed a causality
framework that has been used in all five ISAs, and provides transparency and consistency in the
process of drawing conclusions and causal judgments. CASAC panels have lauded the
implementation of the causal framework, the process for developing the ISA and the structure of
the ISA; positive comments have been received during the peer reviews of draft ISAs for both PM
and CO.
Also, in the recent draft dioxin report entitled, EPA's Reanalysis of Key Issues Related to Dioxin
Toxicity and Response to NAS Comments fhttp://www.epa.gov/dioxin). there is lengthy discussion
and accompanying schematics detailing the delineated study selection process for the
identification of appropriate studies for TCDD dose-response analysis. In addition, in February
2009, to assist NCEA in responding to the NAS, NCEA convened a scientific workshop to
identify and address issues related to the dose-response assessment of TCDD and to ensure that
EPA's response to the NAS focused on the key issues and reflected the most meaningful science.
This workshop was open to the public and included scientific experts from academia, industry,
non-profit organizations, and government. These experts discussed potential approaches to TCDD
dose-response assessment and considerations for EPA's response to NAS. As a result, the process
used by EPA to determine key scientific approaches and decisions in the development of the
recent draft dioxin report can be held up as a model for transparency and public participation.
NCEA has also been providing listening sessions for the public and stakeholders for chemicals on
the IRIS agenda. Additionally, for high profile chemicals like formaldehyde, dioxin, and arsenic,
NCEA has provided briefings for other Agencies and stakeholders at key points in the assessment
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process.
Finally, NCEA has taken steps to standardize assessment practices within the Center. Standard
Operating Procedures for developing IRIS assessment documents have been written, and NCEA
has started to convene regular science policy discussion meetings with staff to make sure science
policy practices are consistent across assessments.
Recommendation #8: The
HRRA Program should
consider using available
resources to recruit one or
two additional senior
scientists, especially into the
LTG 2 Program where efforts
are underway to integrate
emerging technologies into
the risk assessment processes.
Original Response:
Recently, HHRA program
recruited a senior scientist
from NHEERL Dr. Linda
Birnbaum. In addition, ORD
has obtained authority to
hire experts and senior
scientists under Title 42.
The HHRA Program has
initiated one recruitment
action under this program
and will announce an
additional recruitment in
2009.
Updated Response: Dr.
Birnbaum has taken a new
job. She is now the Director
ofNIEHS.
Original Timeline: Ongoing.
Current Progress: For the last three years NCEA has had the benefit of input from two senior
statisticians who participate in the ORISE fellows program. Dr. Kenny Crump has been a leading
investigator in the field of dose response modeling over the past 30 years. His participation in the
ORISE fellows program has allowed him to contribute to important science issues faced by EPA
in the area of quantitative risk assessment. In particular he has delved deeply into issues
regarding application of biologically based dose response models for risk assessment needs. This
effort has sharpened our understanding of the strengths and limitations of such models in
advancing understanding of chemical risks. Dr. Crump is currently working on the quantitative
application of genomics and other high-throughput data in chemical risk assessment. Dr. Bimal
Sinha, Professor of Statistics with University of Maryland Baltimore County, has worked with
NCEA to advance statistical methods for several areas of quantitative risk assessment. These
areas have included application of more robust statistical procedures in modeling data from
pharmacokinetic studies, extension of methods for incorporating experimental error estimates in
benchmark dose modeling, and analysis of exposure statistics data.
The HHRA program has used the ORISE program to bring on board a few senior scientists to help
address some of the complex scientific issues discussed in the 2009 National Research Council
(NRC) Report, Science and Decisions: Advancing Risk Assessment. Additionally, scientists from
the HHRA program are actively engaged with scientists in academia, state governments, and
industry, both across the U.S. and internationally, to discuss issues, conduct research, and develop
pertinent case studies that will be useful in addressing the NRC recommendations. Complex
scientific issues being discussed include probabilistic methods and accounting for uncertainty and
variability in quantitative dose-response; mode of action, background exposures and disease
processes, and vulnerable populations in low dose extrapolation; and applying similar quantitative
approaches for cancer and non-cancer health assessment.
In particular, ORISE's Faculty Fellow Dr. Gary Ginsberg (University of Connecticut) is working
with NCEA on developing new methods and models for incorporating information regarding
susceptible populations into EPA risk assessments. ORISE Faculty Fellow Dr. David Eastmond is
working with NCEA scientists to develop a database on the mutagenic mode of action of certain
chemicals of interest to the IRIS Program. Drs. Ginsberg and Eastmond have made several
seminar presentations to NCEA staff on risk assessment issues. Additionally, Dr. Brian
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Patchkowski was recently hired as an ORISE post-doctoral fellow in NCEA.
NCEA has also recruited and hired a Title 42 Division Director to manage NCEA's RTF
Division. NCEA intends to recruit additional Title 42 and/or SL (senior level) scientists to fill
critical hiring needs in the organization.
Additionally, NCEA plans to add five ORISE post docs to the IRIS program to work on IRIS
assessments. Two scientists have been hired under this program so far and will start in the
summer 2010. Interviews for the remaining three positions are ongoing.
Several postdocs and fellows have been added to LTG2 as part of the HHRA's NexGen effort.
Additionally, a collaborative NexGen effort among other labs and centers has effectively
expanded the LTG2 effort. See description of NexGen in response to Recommendation # 1.
Recommendation #9:
PPRTVs have been
developed specifically to
address the site specific needs
ofEPA's Superfund Program.
Currently, PPRTVs and their
supporting documentation are
only available on a Web site
restricted to use by EPA staff
or to those who obtain special
permission from EPA. The
Subcommittee encourages
EPA to make the PPRTVs
publicly available for use in
hazardous waste site risk
assessment and promote their
use where appropriate.
Original Response:
PPRTVs are available to the
states and other partners
involved in waste site
assessments. Updates are
provided on a quarterly
basis. Within EPA, PPRTVs
are being made available to
other program offices for
screening and prioritization
of research needs.
Updated Response: No
change to ORD action.
Original Timeline: Further efforts will be discussed at the mid-cycle review of the HHRA
Program in 2010.
Current Progress: PPRTVs are currently available to all EPA staff. NCEA has been doing
more outreach to EPA's Programs and Regions, including providing them with information about
PPRTVs. As a result, the PPRTV Web site (which is available to any EPA employee) has been
shared with several EPA program offices outside of the Superfund Program. These programs
have indicated this information will help them address screening and prioritization needs as well
as the need for toxicity numbers.
At this time, NCEA does not think it is possible to make the PPRTV database publicly available.
We have explored the feasibility and think there are potential issues and complicating factors.
However, we have planned a follow-up conversation with OSWER to discuss this once again, and
we continue to explore the possibility of making the PPRTV database publicly available.
PPRTVs are currently available to all EPA staff and by request to states and other partners
involved in waste site assessments. Updates are provided on a quarterly basis.
Recommendation #10: The
HHRA Program needs to
consider information on the
potential public health
concern of various chemicals
as it prioritizes them for IRIS
or PPRTV review. It appears
that some of this information
is being provided by the
program and regional offices,
Original Response: NCEA
is meeting with the program
offices and regions to
provide more explicit
information on the IRIS
process and setting
priorities.
Updated Response: NCEA
has met extensively with
Original Timeline: Progress regarding these efforts will be discussed at the mid-cycle review of
the HHRA Program in Fall 2009.
Current Progress: NCEA has held extensive meetings with EPA's Program and Regional
offices to discuss the process that is used to prioritize nominated chemicals for assessment
through the IRIS program. After extensive conversation and feedback from these offices, we
have developed a revised process for prioritizing how chemicals will be added to the IRIS agenda.
This process includes collecting information about the public health concerns of the nominated
chemicals. It also involves more transparency, as well as a "feed-back" loop to the programs and
regions. Additionally, NCEA recently conducted an exercise where we asked the Programs and
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but it would be of value for
the Program to make
transparent the basis for its
prioritization decisions for
IRIS and PPRTVs.
EPA's programs and
regions, and recently
completed a prioritization
exercise using feedback
from the programs and
regions along with public
health information.
Regions for input on regulatory and other needs for assessments for chemicals currently on the
IRIS agenda for which work has not yet begun. The purpose of this exercise was to help the
HHRA program set priorities for completing currently backlogged assessments.
The HHRA program will soon issue a FRN requesting nominations for chemicals to be added to
the IRIS agenda. This notice will provide more detail than previous notices in an effort to
increase transparency about the IRIS program and how decisions are made to add chemicals to the
agenda.
NCEA has also developed a list of thousands of chemicals that appear on a variety of priority lists
(HAP, CCL3, etc.) and compiled public health information (both exposure and toxicity) about
each chemical. This information may be used in the future to help the HHRA program
proactively identify chemicals that may be a concern for public health, which would then be
presented to EPA's Program and Regional Offices for input.
NCEA meets regularly with OSWER to set priorities for chemicals to assess under the PPRTV
program. NCEA is quite flexible in adding chemicals and reprioritizing when a high priority need
is indentified by OSWER. Additionally, as part of NexGen efforts, the HHRA program is
investigating the use of ToxCast and ExpoCast information to help set priorities for adding
chemicals to the list for PPRTV development.
The HHRA program is also looking at options for incorporating public heath information into the
program's prioritization process for health assessments using value of information tools.
Examples of options that are being considered include consultation with the BOSC workgroup on
decision analysis and value of information and other mechanisms.
Additionally, NCEA is currently performing an IRIS human health assessment for six phthalates
and developing a cumulative risk assessment for these chemicals as recommended by the NRC in
its report Phthalates and Cumulative Risk: The Tasks Ahead. It is expected that this cumulative
assessment will serve as a framework for extension to other compounds that act by a similar
effect. Specifically, the assessment includes the following phthalates: dibutyl phthalate (DBF),
di(2-ethylhexyl)phthalate (DEHP), butyl benzyl phthalate (BBP), di-isobutyl phthalate (DIBP),
di-isononyl phthalate (DINP), and dipentyl phthalate (DPP). The IRIS Human Health Risk
Assessment for Selected Phthalates will include noncancer and cancer qualitative and quantitative
human health effects information and estimation of risk where the data are available for each of
the phthalates. Several of the phthalates included in this assessment were already on the IRIS
agenda. However, after release of the NRC report, the HHRA program decided to add a few
phthalates, as recommended by the NRC, based on their impact on a common health endpoint.
Considering this public health information facilitated the addition of a few new chemicals to the
IRIS agenda.
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