&EPA
United States
Environmental Protection
Agency
BOSC Review (Dec. 2007) of
Computational Toxicology
Research Program
Summary of Review Comments and ORD Response
OO 0 I 1 <
1 000 U
00 00
oo
0110
DO 001
STATES EN VI RON MEN
. - - . ,
TECTiON AGENCY
• • o o •oo • o
1 0 1 l 0 0 0 0 I I O O I I
iQll
' 00
0 00011 OMOO
1000110 1110111
.00 OO 00 100 00
COMPUTATIONAL
TOXICOLOGY
Office of Research and Development
National Center for Computational Toxicology
-------
FPA
Subcommittee
United States
Environmental Protection
Agency
Dr. George Daston (Chair)
Dr. James Clark
Dr. Richard DiGiulio
Dr. Muiz Mumtaz
Dr. John Quackenbush
Dr. Cynthia Stokes
Office of Research and Development
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Goals of the Review
To provide NCCT with advice on the progress the Center has made, in the
past year, in fulfilling its mission and strategic goals.
Particularly, the Subcommittee addressed six charge questions for five
NCCT activities (ToxCast, Informatics Technology/Information
Management (IT/IM) activities, Virtual Liver, Developmental Systems
Biology, and Arsenic BBDR).
Office of Research and Development
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Summary of Charge Questions
Does the scope and involvement of expertise in the project reflect activities
consistent with the function of a Center?
Are the goals and milestones suitably described, ambitious, and
innovative?
Are there significant gaps in the approach that can be pointed out at this
point in the evolution of the project?
Does the work offer to significantly improve environmental health impacts
and is the path toward regulatory acceptance and utilization apparent?
Have appropriate data management and analysis tools been incorporated
into the project?
How would you assess the outreach to other groups in executing the
projects?
Office of Research and Development
National Center for Computational Toxicology
-------
FPA
cm Overall Finding
United States
Environmental Protection
Agency
"The Subcommittee was very pleased with the progress that the Center
has made towards its goals. NCCT first became operational in February
2005; during the 2.5 years between its establishment and this review,
NCCT has made substantial progress in establishing priorities and goals;
making connections within and outside EPA to leverage the staffs
considerable modeling expertise; expanding its capabilities in informatics;
and making significant contribu-tions to research and decision-making
throughout the Agency. We are pleased to see that informatics tools
developed by the Center already are being used by program offices, and
that the program offices are taking advantage of the expertise of the
Center in developing critical elements for risk assessment..."
Office of Research and Development
National Center for Computational Toxicology
-------
&EPA
Summary of Specific Recommendations
United States
Environmental Protection
Agency
Stakeholder identification and involvement
Discussions with risk assessment practitioners
Develop effective ways of dealing with wealth of data
Look for relevance of ToxCast™ beyond toxicity
prioritization including exposure paths and ecology
Detailed milestones and time table
Detailed project plans for v-tissues
Office of Research and Development
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Summary of Responses
Stakeholders, risk assessment practitioners, and outreach
- Identify and invite key stakeholders to next BOSC review
- Regular discussions with NCEA and others are underway
- Expansion of Communities of Practice
- Project team for v-Liver project includes risk assessors
- v-tissues workshop with European Union in April 2009 at EPA
-ToxCast™ data summit in May 2009 at EPA
• Provide forum for external scientists to discuss with EPA alternatives
for deriving predictive signatures from ToxCast™
Office of Research and Development
National Center for Computational Toxicology
-------
v>EPA
Responses Continued
United States
Environmental Protection
Agency
Effective ways for dealing with data
- Extensive suite of interactive databases is under development and
prioritization of data input is in consultation with program offices and
others
• ACToR, ( ; : ; ,; ) is the global repository of data
that is relevant to environmental chemicals
• ToxRefDB, in vivo toxicology data on chemicals in the ToxCast™
program
• ToxMiner, a compilation of statistical tools capable of analyzing
relationships between ToxCast™ and ToxRefDB data, and
performing predictive signatures
• the ToxCast™ chemical registry, used to track nominations for
ToxCastTM screening, to track sample identity and sample QC, and
fto link actual samples to ToxCast™ data
• DSSTox, chemical structure layer added to the data sets
Office of Research and Development
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Responses Continued
Relevance of ToxCast™ beyond toxicity prioritization including exposure
paths and ecology
- Expanded workgroups to address exposure pathways through
"ExpoCast" - exposure relevance to toxicity signature predictions
- Partnering with NHEERL and NERL for HTS for ecological species
other than human
-Testing of Pharmaceuticals in Phase II of ToxCast™ to compare results
to known human toxicities
Office of Research and Development
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Responses Continued
Detailed milestones for projects and more detailed project plans for v-
tissues
-Milestones have been put in place for ToxCast™-v-tissues, and IT/IM
and are included in an appendix to response memo
- Short-term and long-term goals for v-Liver have been identified and are
in response memo
- Detailed project plan for v-embryo developed and in memo.
- Milestones for BBDR for Arsenic have not been developed due to
significant change in the plans for this work which has been described
in memo
• The lead and partner laboratory, NHEERL after considerable peer
review and consultation with program office no longer are
concentrating on this project
• NCCT efforts being redirected to v-tissues and related projects
Office of Research and Development + «
National Center for Computational Toxicology
-------
United States
Environmental Protection
Agency
Next Steps
NCCT is developing the next ORD Computational Toxicology Research
Implementation Plan
-Will cover 2009-2012
-Will reflect recommendation from most recent BOSC review
-Will be presented to BOSC Computational Sub-committee for review in
2009 (exact date TBD)
-Milestones and plans developed as result of these recommendations
will be incorporated
Office of Research and Development + A
National Center for Computational Toxicology
------- |