ENDOCRINE DISRUPTORS RESEARCH PROGRAM:

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ENDOCRINE DISRUPTORS RESEARCH PROGRAM OVERALL
PROGRESS REVIEW
Elaine Z. Francis National Program Director,
Pesticides and Toxics Research
EDCs Research Program Mid-Cycle BOSC Review
August 21, 2007
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OUTLINE

• Overview of the Endocrine Disruptors Research
  Program
• Summary of the Board of Scientific Counselors
  Review in 2004/2005
• Summary of Progress to Address Recommendations

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EDCs research under Goal 4.4
INTEGRATION OF ORD PLANNING
Last update 2000 EDCs research a high priority
EDCs Res. Strat. Published 1998
EDCs MYP (99,00,03) 07
NHEERL IP 00,04 NRMRL RME 03
Division-Level Peer Reviews
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ORD Research Planning Process Input for EDCs
Research Program

• Customer/User Needs
• OPPTS
• Regions
• OW
• Federal research partners

• EPA Strategic Plan
• Clean Air
• Clean and Safe Water
• Land Preservation Restoration
• Healthy Communities Ecosystems
• Compliance Environmental Stewardship

• Through Planning Teams
• Deputy AAs/RAs
• Collaborations

EDCs Research Products
ORD Research Planning

• ORD Strategic Planning
• ORD Strategic Plan
• EDCs Research Plan
• EDCs Multi-Year Plan
• NHEERL EDCs Implementation Plan
• NRMRL RME
• Computational Toxicology Implementation Plan

• Outside Peer Advice
• Lab/Center Division-level Peer Reviews
• SAP
• BOSC Subcommittee
• NAS
• ILSI

OMB Congress
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Endocrine Disruptors Research 1998 - 2008
12.8
12.6
12.1
10.9

10.7
10.4
10.5
10.5
10.1
8.9
8.0
40.7 Total FTEs (08) 31.8 NHEERL 3.9 NERL
2.0 NRMRL 3.0 NCER
Funding levels reflect total program including
payroll, travel, WCF, and operating
expenses. STAR Science to Achieve Results
extramural grants
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Funding levels reflect total program including
payroll, travel, WCF, and operating
expenses. STAR Science to Achieve Results
extramural grants
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04 Program Review by BOSC
03 NRMRL Impl Plan
01 Finalized Multi-Year Plan
05 Issued Exposure RFA
95 Held 2 Intl Workshops
99 Named Natl Prog Director
03 Issued Sys Bio RFA
97 RAF Published Interim Guidance Document
02 Began Comp Tox Program
06 Issued CAFOs RFA
04 Issued Low Dose RFA
00 NHEERL Impl. Plan
95 Issued Broad RFA
98 Pub. Peer-Rev. Research Plan
94 RAF IDs EDCs as an Issue
02 Issued HTPS RFA
06 Held Workshop
04 PART Review by OMB
96 ORD IDs EDCs as High Priority
00 Held Workshop
98 Issued Interagency RFA on Pop. Effects
02 Held Workshop
07 Held Interagency Workshop
07 Held CAFOs Workshop
04 Updated NHEERL Impl Plan
00 Issued Interagency RFA on Epi
96 Issued Broad RFA
03 Updated MYP
07 Updated MYP
Annotated History of EPAs EDCs Research Program
07 BOSC Mid-Cycle Review
04 Held Progress Review of Epi Grants
1994
2007
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Input for Update of the EDCs MYP

• OMB Program Assessment Rating Tool (PART) Review
  April 2004
• LTGs to outcome-oriented
• Evaluation of how products are used in
  decisionmaking
• Rated jointly with Agencys Endocrine Disruptors
  Research Program Adequate
• BOSC December 2004
• Continuous discussions with OSCP/OPPTS Senior
  Management
• Input from advisory committees
• Recent interest from OW Senior Management
• EDCs Research Planning Team (ORD, OPPTS, Regions,
  OW)
• National Program Directors (HH, Eco, DW, SP2, WQ)
• Director of National Center for Computational
  Toxicology
• Interagency Working Groups under CENR

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Overall Assessment of EDCs Research Program by
BOSC December 2004

• Design - goals and scientific questions of the
  Research Program deemed appropriate
  multi-disciplinary set of research areas for both
  human health and wildlife that cuts across the
  risk assessment/risk management paradigm
• Relevance of direct relevance to legislation
  that EPA administers and that it serves the
  Program Offices well
• Progress research has been productive and of
  high scientific quality of particular note is
  the excellent progress under LTG 3
• Leadership - nationally and internationally
  recognized research is disseminated in top-tier
  scientific journals scientists at the forefront
  of EDC research in screening and testing
  methodologies
• Resources resources have been used efficiently
  astute in leveraging with other federal agencies
  continuation of extramural grants program is vital

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Multi-Year Plan Long-Term Goals

• LTG 1 - Reduction in uncertainty to Provide a
  better understanding of the science underlying
  the effects, exposure, assessment, and management
  of endocrine disruptors so that EPA has a sound
  scientific foundation for environmental
  decision-making
• LTG 2 - Reduction in uncertainty to Determine the
  extent of the impact of endocrine disruptors on
  humans, wildlife, and the environment so that EPA
  has a sound scientific foundation for
  environmental decision-making
• LTG 3 - OPPTS uses endocrine disruptor screening
  and testing assays developed by ORD to create
  validated methods that evaluate the potential for
  chemicals to cause endocrine-mediated effects in
  order to reduce or prevent risks to humans and
  wildlife from exposure to EDCs (Support EPAs
  screening and testing program)

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Breakdown of Recommendations

• Thirteen unique recommendations some repeated
  across elements
• Overarching Conclusions and Recommendations (2)
• LTG 1 (4)
• LTG 2 (5)
• LTG 3 (4)
• Program Resources (1)

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Overall Conclusions and Recommendations

• Action the guiding definition and scope of
  research program will be further clarified in the
  updating of MYP and in future program reviews
• Time Line draft of MYP update will be available
  in early 2006 mid-course review of the research
  program will take place in late 2006
• Reality addressed in draft of MYP in 2007
  mid-cycle review in 2007

• EPA should clarify what is and is not covered by
  the EDC program whenever the program is reviewed

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Overall Conclusions and Recommendations

• Strengthen NPDs ability to oversee program (1)
  hire additional personnel (2) elevate the
  position of the EDC Program Director to the level
  of the Laboratory/Center Directors and (3)
  provide the EDC Program Director budget authority
  

• Action (1) federal limits on number of
  personnel will supplement EPA scientists e.g.,
  post docs, other fellows, and explore recent
  graduates contract (2) NPD positions created
  details regarding their relationship to
  Lab/Center Directors, Executive Council, Science
  Council, etc. are being delineated in a document
  under development (3) budget authority resides
  with the Senior Budget Officer (SBO) in ORD
  budget advice and recommendations is sought from
  the NPDs
• Time Line (1) finding innovative ways to
  supplement EDCs workforce is an ongoing effort
  as NPDs begin to work together, they may be in a
  better position to characterize leveraging of
  personnel across the research programs (2) and
  (3) details of the relationship of the NPDs
  within the ORD management structure are being
  worked out in document that will be available by
  January
• Reality (1) a few new hires were made and EPA
  workforce was supplemented with post docs, ASPH
  fellows, graduate students, recent student
  contractors better leveraging personnel across
  research programs, sometimes by realigning them
  (2) and (3) working out the relationship of the
  NPDs and other ORD senior managers has been an
  ongoing effort draft document on roles and
  responsibilities (August 2007)

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Long Term Goal 1

• EDC program should dedicate full-time EPA
  personnel to work in wildlife toxicity

• Action will continue to engage academic wildlife
  toxicologists through the STAR program will
  increase efforts to collaborate across federal
  agencies to leverage the talent of their wildlife
  toxicologists developing a synthesis document
  that integrates published results from ORDs STAR
  and intramural programs on the impacts of EDCs on
  wildlife
• Time Line will work through the IWG on EDCs to
  increase sharing of information and leveraging
  research activities, such as joint workshop on
  the impact of wastewater treatment plants and
  CAFOs on ecosystems to be held in 2006 synthesis
  report on wildlife will be completed late in 2005
• Reality improved leveraging across ORD
  research programs and across federal agencies
  held interagency working group workshop on
  ecosystems and separate workshop on CAFOs in
  2007 report that synthesizes intramural and
  extramural research programs includes a chapter
  on wildlife (draft 2007)

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Long Term Goal 1

• ORD should continue to collaborate with other
  federal, academic, nongovernmental (NGO), and
  industry partners to characterize better the
  range of variability among species

• Action will continue to evaluate potential
  interspecies differences and similarities among
  cellular MOAs in-house and with partners in
  academia, industry, and other Agencies
• Time-line research on species extrapolation is
  scheduled to continue through FY07 at fall
  meeting of IWG will determine if there is any
  interest in having a future workshop on this
  topic
• Reality intramural research continuing through
  FY13 possibility of collaborations with other
  agencies discussed at 2007 workshop Comp Tox
  program is assisting in the development of
  databases for PBPK models data from ToxCast and
  EDSP will enable us to better understand species
  similarities/differences

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Long Term Goal 1

• Integrate predictive tools for prioritization
  into EPAs EDC program

• Action being addressed through Comp Tox research
  program NPD, planning team, and NCCT Director
  will ensure greater linkages among the EDCs, Comp
  Tox, and SP2 research programs
• Time Line Comp Tox research program underwent a
  BOSC review in April 2005 held STAR grantees and
  EPA scientists workshop in July 2005 updated
  draft of the EDCs MYP in early 2006 will include
  clearer linkages among the EDCs, Comp Tox, and
  SP2 programs
• Reality research ongoing in EDCs, SP2, and Comp
  Tox (e.g., STAR and ToxCast) programs EDCs MYP
  draft more clearly identifies linkages with the
  other programs Comp Tox and SP2 programs have
  had their own BOSC reviews workshops have
  brought intramural and extramural scientists
  together to share approaches and findings issued
  2007 Comp Tox RFA for 2 new centers on
  development of predictive environmental and
  biomedical computer-based simulations and models

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Long Term Goal 1

• Action EPAs position is that current
  approaches for risk assessment under specific
  endpoints are appropriate for use in evaluating
  EDCs will continue to monitor research results
  that may affect current risk assessment
  practices if, and when, Agency determines that
  risk assessment approaches need modification,
  they will use guideline development process
• Time Line research that may affect current risk
  assessment practices will be monitored on an
  ongoing basis
• Reality ORD research is studying the impact of
  cumulative risk for groups of chemicals with
  similar modes of action a number of IRIS
  assessments are underway for chemicals with
  similar MOA ORD has developed a case study for
  incorporation of toxicogenomics data into a risk
  assessment of an endocrine disruptor in the
  meantime, EPAs position remains the same - that
  current approaches for risk assessment under
  specific endpoints are appropriate for use in
  evaluating EDCs research by other scientists is
  routinely monitored

• Efforts should focus on the development of risk
  assessment paradigms for EDCs and application of
  the research findings

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Long Term Goal 2

• EPA should continue to improve its interactions
  with other agencies that have a strong interest
  in EDCs to identify new sources of environmental
  and human exposures, including investigating the
  role of pharmaceuticals as sources of EDCs EPA
  should mine data made available from the HPV
  Program

• Action will use IWG to strengthen relationships
  with other Agencies efforts underway to organize
  a multi-Agency sponsored workshop related to
  sources of exposure will continue to work
  closely with the co-chairs of the interagency
  PPCP task group and look for opportunities for
  joint efforts will work with NPD for WQRP to
  explore leveraging and linking PPCP activities
  will work with OPPTS to make the data not only
  from HPV but also from VCCEP, available to ORD
  for mining.
• Time Line interagency workshop on wastewater
  treatment plants and CAFOs will be held in 2006
  STAR grantee and EPA scientists meeting on
  pharmaceuticals in the environment held August
  23-25 interagency Task Force held a workshop
  July 25-26 -products will contribute to
  development of Framework document, anticipated by
  December 2005 NPD will be meeting with the OPPTS
  Office Directors in September about ways in which
  to improve communications of research results and
  will use that opportunity to request access to
  HPV and other data for the EDCs scientists
• Reality interagency workshop on impacts of EDCs
  on ecosystems held 2007 to identify further
  collaborations CAFOs workshop held 2007
  separate IWG on pharmaceuticals in the
  environment is developing research framework
  (December 2008) updated EDCs MYP includes small
  amount of research on endocrine active
  pharmaceuticals and will leverage with other ORD
  research programs that will address other classes
  of pharmaceuticals Comp Tox program is leading
  coordinated international efforts on molecular
  screening initiatives and developing one-stop
  tox data bases e.g., Comp Tox program is in
  discussions with OPPT to incorporate tox data
  from HPV information system into an aggregated
  computational toxicology system

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Long Term Goal 2

• Action grantees will be brought together next
  summer for another progress review will avoid
  scheduling progress reviews of grantees near the
  time of anticipated Program Reviews epi grantees
  will be invited to next Program Review
• Time Line NPD and IWG will continue to monitor
  epi research another progress review planned
  for next summer grantees will be invited to 2008
  EDCs Program Review
• Reality epi grantees included in 2006 progress
  review workshop STAR program using its normal
  processes to continue monitoring these studies
  grants have been extended and grantees will be
  invited to the next EDCs BOSC review (likely in
  early 2009)
• Action will take on the challenge to develop
  approaches that integrate human health and
  ecological assessments will consider improving
  the integration of projects that will contribute
  to evaluate human and ecological health (e.g.,
  using the MOA approach) pilot may be centered
  around CAFOs
• Time Line future research directions under
  discussion with updating of MYP by early 2006
  within the next year, several post docs will be
  hired to expand efforts on CAFOs and RFA on CAFOs
  will be issued this fall MOA case study was
  finalized in June 2005
• Reality limited effort to address this
  recommendation previously reported case study on
  MOA of BPA published 2005 research on aromatase
  in fish and rat to explore bridge between eco and
  human health potential interagency
  collaborations discussed at IWG workshop in 2007
  cross-lab/center CAFOs project has begun but not
  looking at impacts on human health

• Subsequent reviews should include poster
  presentations by each of the epidemiologists
  funded by this interagency program
• EPA should continue to investigate the common
  ground between ecological and human health
  because the Agency is in a unique position to do
  so

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Long Term Goal 2

• Action EPA is positioning itself as a leader in
  the omics field through research and policy
  developments EDC scientists will continue to
  play a critical role in both of these areas
  Director of NCCT and NPD will continue to hold
  frequent meetings to coordinate activities and
  will work with the planning team to ensure that
  the linkages among the Comp Tox, EDCs, and SP2
  programs are captured in the updated MYPs
• Time Line update of MYP in early 2006
  interaction with the Office of the Science
  Advisors Genomic Workgroups will continue, as
  confirmed at the Genomics Training and Tools
  collaboration meeting with FDA/NIEHS/ICCVAM held
  August 4, 2005 draft case study on use of
  toxicogenomics data in risk assessment on an
  endocrine active agent for internal review by
  June 2006 and workshop review of it by September
  2007
• Reality EDC scientists playing a role in
  research and policy developments participate in
  activities under the Agencys Genomics Task
  Force ORD developing repository for array data
  and holding training workshops for EPA
  high-density data approaches incorporated into
  ecologic and human health risk assessment based
  research for multiple research programs (e.g.,
  EDCs, Human Health , Drinking Water, SP2)
  developed case study on incorporation of
  toxicogenomics data on an EDC into risk
  assessment and will review through colloquium
  (2007)

• EPA should take the leadership role in the
  application of the omics technologies for
  evaluating environmental and human health effects
  of EDCs

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Long Term Goal 3

• Action hired two bioinformaticians already and
  issued job announcements for two more issued
  solicitation through STAR for Environmental
  Bioinformatics Research Center that will be
  awarded in the form of cooperative agreement so
  that there will be strong interactions between
  extramural scientists and those of ORD
• Time Line two positions have been advertised,
  applications received, and selections will be
  made by October 15, with the persons joining NCCT
  soon thereafter awards for the EBRCs will be
  made by September 30
• Reality NHEERL established a genomics core NERL
  established a metabolomics core labs working
  with the NCCT and the 2 EBRCs cooperative
  agreements established with 2 EBRCs for strong
  interactions frequent communication and yearly
  workshops NCER issued 2007 RFA for 2 new centers
  on development of predictive environmental and
  biomedical computer-based simulations and models
  NHEERL hired a toxicogenomic expert and systems
  biologist NERL hired a bioinformatician NCCT
  has hired three senior level scientists to work
  in the areas of bioinformatics and computational
  systems biology and has added 5 post docs working
  on various computational models

• It will be important for ORD to train or hire
  experts in bioinformatics to work with the life
  sciences experts already on staff

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Long Term Goal 3

• Action OPPTS senior management and the NPD will
  be meeting with NHEERL senior management to
  emphasize OPPTS priorities and time lines and to
  reach agreement on how to meet their
  expectations.
• Time Line meetings are being set up in RTP and
  Duluth for September/October
• Reality significant progress has been made in
  completing research needed to develop and
  standardize assays for EDSP assays are in
  various stages of validation by OPPTS for use in
  implementation of EDSP ORD scientists continue
  to serve as valuable resources to OPPTS as the
  assays are validated and peer reviewed
• Action updated MYP will include a more coherent
  way to summarize accomplishments, characterize
  their impact, and cite linkages to other relevant
  documents (e.g., lab specific EDCs implementation
  plans, research frameworks, other MYPs) research
  is also being summarized in three topical
  synthesis documents (Effects in Wildlife, Effects
  on Development, Screening Testing) that will
  compile and integrate the intramural and STAR
  extramural research accomplishments
• Time Line NHEERL Implementation Plan that
  summarizes research was developed October 2004
  synthesis documents will be available late in
  2005 draft of the updated EDCs MYP will be
  available early in 2006
• Reality it remains a challenge to portray the
  significant accomplishments in a coherent way in
  the updated MYP draft aligned under annual
  performance goals draft synthesis document
  summarizes and integrates intramural and
  extramural accomplishments

• There should be a mechanism in place to ensure
  the timely transfer of protocols to OPPTS
• Provide summary of research and its relevance to
  EDC identification in subsequent reports and
  revisions of the MYP