National Toxicology Program (NTP); Host Susceptibility Program (HSP); Genetic Variation and the Basis for Individual Susceptibility to Environmental Toxicant Associated Disease: Request for Information, 56358-56360 [E7-19462]
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Federal Register / Vol. 72, No. 191 / Wednesday, October 3, 2007 / Notices
Title of the Collection—(New)—OMB
No. 0990–NEW—Report of Medical
Examination and History.
Abstract: Health professionals
applying to the Commissioned Corps of
the U.S. Public Health Service (Corps)
must be medically qualified prior to
appointment. Applicants must have a
healthcare provider/physician complete
form PHS–7059, Report of Medical
Examination, documenting the health
status of the applicant. The Corps
Medical Evaluations Officer will review
the information to ascertain if the
applicant is medically qualified
presently and in the near future. This is
a one-time survey.
ESTIMATED ANNUALIZED BURDEN TABLE
Number of
respondents
Forms
PHS–7059
PHS–7060
PHS–7053
PHS–7054
PHS–7055
PHS–7056
PHS–7057
PHS–7061
Number of
responses per
respondent
Average
burden hours
per response
Total burden
hours
........................................................................................................
........................................................................................................
........................................................................................................
........................................................................................................
........................................................................................................
........................................................................................................
........................................................................................................
........................................................................................................
4,000
4,000
800
1320
2800
1600
600
2000
1
1
1
1
1
1
1
1
15/60
15/60
6/60
6/60
7/60
7/60
5/60
10/60
1000
1000
80
132
327
187
50
334
Total ..........................................................................................................
17,120
........................
........................
3,110
Dated: September 18, 2007.
Alice Bettencourt,
Office of the Secretary, Paperwork Reduction
Act Reports Clearance Officer.
[FR Doc. E7–19533 Filed 10–2–07; 8:45 am]
BILLING CODE 4150–28–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Toxicology Program (NTP);
Host Susceptibility Program (HSP);
Genetic Variation and the Basis for
Individual Susceptibility to
Environmental Toxicant Associated
Disease: Request for Information
National Institute of
Environmental Health Sciences
(NIEHS), National Institutes of Health
(NIH).
ACTION: Request for information.
rwilkins on PROD1PC63 with NOTICES
AGENCY:
SUMMARY: The NTP is developing the
Host Susceptibility Program (HSP), a
new research program, to identify and
functionally validate genes associated
with environmental exposure. This
program will make available NTP
expertise and resources to investigate
the genetic basis for population-level
differences in susceptibility to
environmental toxicants and/or disease
based upon gene and environment
interactions. This research will be
designed to ultimately lead to a better
understanding of why some individuals
are more susceptible than others to
exposure to an environmental toxicant
resulting in disease and morbidity.
Asthma, cardiovascular disease, cancer,
diabetes, and obesity are examples of
diseases associated with multiple
interacting genes that are influenced by
exposure to environmental agents.
VerDate Aug<31>2005
18:31 Oct 02, 2007
Jkt 211001
Through this Request for Information,
extramural and intramural scientists are
invited and encouraged to provide
information and comment relevant to
this proposed programmatic research
approach in order to help guide further
development and refinement of the
goals of the NTP HSP. Information on
this initiative can be submitted
electronically through the HSP Request
for Information Web site at: (https://
ntp.niehs.nih.gov/go/32130 ) or by
contacting Dr. John E. French (see FOR
FURTHER INFORMATION CONTACT below).
DATES: The deadline for response is
October 31, 2007.
ADDRESSES: Responses can be submitted
electronically at the HSP Request for
Information Web site: https://
ntp.niehs.nih.gov/go/32130.
FOR FURTHER INFORMATION CONTACT:
Other correspondence should be
directed to Dr. John E. French, Host
Susceptibility Program, NIEHS, P.O.
Box 12233, MD EC–17, Research
Triangle Park, NC 27709, (fax) 919–541–
0947, (email) hsp@niehs.nih.gov.
Courier address: Dr. John E. French,
Host Susceptibility Program, 111 T.W.
Alexander Drive, Building 101, Room
F167, Research Triangle Park, NC
27709.
SUPPLEMENTARY INFORMATION:
Background
The NTP was established as a
cooperative effort to (1) coordinate
toxicology testing programs within the
federal government, (2) strengthen the
science base in toxicology, (3) develop
improved testing methods, and (4)
provide information about potentially
toxic chemicals to health, regulatory,
and research agencies, scientific and
PO 00000
Frm 00028
Fmt 4703
Sfmt 4703
medical communities, and the public.
To meet these goals, NTP designs and
conducts large-scale laboratory animal
research and testing programs and
analyzes and reports their findings to
assess potential hazards to human
health from exposure to environmental
chemicals.
Recently, the NTP led and funded a
haplotype mapping project with
Perlegen Sciences to resequence 15
isogenic strains of mice selected for
their potential genetic diversity. Along
with the public sequence of isogenic
C57BL/6J, analysis of 16 sequenced
strains has revealed, conservatively,
more than 8 million single nucleotide
polymorphisms in this initial analysis of
laboratory and wild-derived isogenic
mouse strains (Frazer et al., 2007).
Identification and analysis of mouse
haplotypes will provide a valuable tool
for haplotype-phenotype association
studies in genetically diverse strains
that can be used to predict human
genetic variants of functional
significance (https://
mouse.perlegen.com/mouse/
index.html ). Toward that goal, the NTP
is developing a multidisciplinary
research program on genetic
susceptibility to environmental
exposures. This effort will partner
extramural and/or intramural
researchers with NTP scientists by
creating research partnerships using
NTP R&D contract resources. This
research program is not a funding
opportunity or a grant program.
The intent of HSP is to provide
researchers access to NTP R&D contract
resources and NTP expertise in public
health toxicology. Participation by
extramural and/or intramural scientists
will be based on competitive peer
E:\FR\FM\03OCN1.SGM
03OCN1
rwilkins on PROD1PC63 with NOTICES
Federal Register / Vol. 72, No. 191 / Wednesday, October 3, 2007 / Notices
review of proposed research projects.
NTP scientists will work with
extramural and/or intramural
investigators to define and refine the
most effective and cost-efficient
experimental protocols for
accomplishing the experimental aims
and for linking environmental exposure
with toxicity leading to disease.
Development of approved projects will
proceed sequentially from hypothesis
through specific aims, based upon a
consensus derived experimental plan.
Continued support of research projects
will depend upon satisfactory
completion of each phase of the
research plan.
Via this partnership, extramural and/
or intramural investigators will have
access to NTP contract resources to
investigate the relationship between
exposure to environmental toxicants
and development of quantitative
measures of toxicity and disease, using
genetically diverse experimental animal
models. Using research partnerships,
HSP scientists aim to develop the tools
and means necessary to accomplish the
multidisciplinary tasks that are often
rate-limiting to individual research
groups that may be interested in
investigating environmental toxicant
exposure and genetic susceptibility to
disease and determining allelic variants
of causally related genes and their
potentially dysregulated signaling
pathways. Once a project has been peer
reviewed and approved, NTP staff will
interact directly with the Principal
Investigator(s) (PIs) of the approved
projects to refine the research using NTP
contracted resources. NTP R&D
contractors will perform approved tasks
under the direction of NTP staff. Those
tasks necessary to accomplish the
experimental aims of any particular
study are expected to vary from project
to project. In some cases, NTP may only
support one or two key missing steps
necessary to complement the research;
in other cases, it may be necessary to
supply the entire scope of experimental
tasks needed to complete the specific
aims. Examples of tasks that can be
supported by NTP contracts and staff
include, but are not necessarily limited
to:
• Facilitating animal model selection
(multiple-isogenic strains,
heterogeneous, outbred stocks, etc.).
• Providing strain-specific data on
absorption, distribution, metabolism,
and excretion of metabolic products of
environmental toxicants.
• Defining or optimizing of exposure
route, dose and dose schedule of
environmental toxicants using rangefinding studies to determine
VerDate Aug<31>2005
18:31 Oct 02, 2007
Jkt 211001
quantitative measures of acute toxicity
in vivo in an appropriate animal model.
• Quantitatively identifying variants
of toxicity (phenotyping) in multiple
isogenic strains, genetically engineered
strains, and/or genetically defined
outbred stocks.
• Developing appropriate
experimental design protocols for
toxicity, biomarkers, expression arrays,
clinical and histopathology, and
statistical analysis.
• Acquiring test agent(s) in quantities
sufficient for non-GLP acute and
prechronic toxicity investigations,
development of analytical methods for
determination of quantity and purity of
test substances, production and stability
(storage) of dosage forms.
• Developing, optimizing, and
conducting study and route specific
toxicology and toxicity assays for
correlation between toxicity and
histopathologic determinants.
Output from such collaborative
research activities, which may include
providing biological samples and/or
data (genotyping, quantitative measures
of toxicity, expression phenotypes, etc.),
is to be made fully available to the
originating principal investigator (or
his/her replacement, in case of
withdrawal) for continued support of
the research project developed within
the partnership. Data and samples are to
be transferred to extramural or
intramural collaborators under terms of
a negotiated NIH Materials Transfer
Agreement.
Information Requested
The NTP is soliciting information
from the extramural and intramural
research communities on the strategies,
resources, and tools necessary to enable
this cooperative research program on
genetic variation and individual
susceptibility to environmental toxicant
exposure and associated polygenic
diseases to progress. Please respond
online at the HSP Request for
Information Web page (https://
ntp.niehs.nih.gov/go/32130) to any or
all of the following questions by October
31, 2007.
1. In general, what are the utility and
limitations of using model organisms
(e.g., multiple strains of isogenic mice,
heterogeneous mouse stocks, etc.) to
investigate and establish the genetic
determinants of biological response?
2. Are there particular environmental
toxicants associated with human disease
where this research approach is
immediately applicable and useful to
the identification of causally related
genes and their allelic variants?
3. Similarly, are there particular
physiologic or pathogenic pathways
PO 00000
Frm 00029
Fmt 4703
Sfmt 4703
56359
and/or disease endpoints for which the
proposed research approach is likely to
be especially insightful in advancing
our understanding of gene-environment
interactions?
4. What computational, statistical,
and bioinformatic methodologies might
be particularly useful for determining
toxicity phenotypes and identifying
associated genes, pathways, and
networks?
5. What high-data content
technologies, platforms, and statistical
approaches might be particularly
valuable and critical to elucidating the
genetic basis for toxicity and disease
based upon the experience and
knowledge gained over the past decade?
6. Are there high-throughput assays
and screens using cell-based systems
that might be employed to examine the
role of genetic variation in human
exposure?
7. Are in vitro and in vivo assays and
genetic models for functional validation
of genes useful in permitting
orthologous human genes and their
allelic variants to be identified and
tested in large-scale human populations
with defined environmental exposures?
8. Is the competitive research
partnership approach described for the
HSP using NTP R&D expertise in
toxicology and contract resources viable
and of general interest to researchers
interested in these questions? Why or
why not?
9. Are there specific concerns over
intellectual property or research
collaboration issues in a research
partnership that should be addressed
and negotiated?
All responses to individual questions
within this Request for Information are
optional. The information collected will
be analyzed and considered for use in
the further development of the NTP
HSP. The summarized data (without
identifiers) may appear in internal
reports. Although the NIH will provide
safeguards to prevent the release of
identifying information, there is no
guarantee of confidentiality. This
Request for Information is for planning
purposes and should not be construed
as a solicitation for applications or as an
obligation on the part of the
Government. The Government will not
pay for the preparation of any
information submitted or for the
Government’s use of that information.
Acknowledgement of receipt of
responses will not be made, nor will
respondents be notified of the
Government’s assessment of the
information received. No basis for
claims against the Government shall
arise as a result of response to this
Request for Information, or in the
E:\FR\FM\03OCN1.SGM
03OCN1
56360
Federal Register / Vol. 72, No. 191 / Wednesday, October 3, 2007 / Notices
Government’s use of such information
as part of our evaluation process.
Reference
Frazer, K.A., E. Eskin, H.M. Kang, M.A.
Bogue, D.A. Hinds, E.J. Beilharz, R.V. Gupta,
J. Montgomery, M.M. Morenzoni, G.B.
Nilsen, C.L. Pethiyagoda, L.L. Stuve, F.M.
Johnson, M.J. Daly, C.M. Wade, and D.R. Cox.
A sequence-based variation map of 8.27
million SNPs in inbred mouse strains. Nature
2007 July 29 Epub.
Dated: September 24, 2007.
Samuel H. Wilson,
Acting Director, National Institute of
Environmental Health Sciences and National
Toxicology Program.
[FR Doc. E7–19462 Filed 10–2–07; 8:45 am]
FOR FURTHER INFORMATION CONTACT:
Larry Elliott, Director, Office of
Compensation Analysis and Support,
National Institute for Occupational
Safety and Health (NIOSH), 4676
Columbia Parkway, MS C–46,
Cincinnati, OH 45226, Telephone 513–
533–6800 (this is not a toll-free
number). Information requests can also
be submitted by e-mail to
OCAS@CDC.GOV.
Dated: September 26, 2007.
John Howard,
Director, National Institute for Occupational
Safety and Health.
[FR Doc. E7–19528 Filed 10–2–07; 8:45 am]
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institute for Occupational
Safety and Health; Final Effect of
Designation of a Class of Employees
for Addition to the Special Exposure
Cohort
National Institute for
Occupational Safety and Health
(NIOSH), Department of Health and
Human Services (HHS).
ACTION: Notice.
AGENCY:
National Institute for Occupational
Safety and Health; Decision To
Evaluate a Petition To Designate a
Class of Employees at the Mound
Plant, Miamisburg, OH, To Be Included
in the Special Exposure Cohort
National Institute for
Occupational Safety and Health
(NIOSH), Department of Health and
Human Services (HHS).
AGENCY:
ACTION:
The Department of Health and
Human Services (HHS) gives notice
concerning the final effect of the HHS
decision to designate a class of
employees at the Rocky Flats Plant,
Golden, Colorado, as an addition to the
Special Exposure Cohort (SEC) under
the Energy Employees Occupational
Illness Compensation Program Act of
2000. On August 6, 2007, as provided
for under 42 U.S.C. 7384q(b), the
Secretary of HHS designated the
following class of employees as an
addition to the SEC:
Notice.
SUMMARY:
rwilkins on PROD1PC63 with NOTICES
Employees of the Department of Energy
(DOE), its predecessor agencies, or DOE
contractors or subcontractors who were
monitored or should have been monitored for
neutron exposures while working at the
Rocky Flats Plant in Golden, Colorado, for a
number of work days aggregating at least 250
work days from January 1, 1959, through
December 31, 1966, or in combination with
work days within the parameters established
for one or more other classes of employees
in the Special Exposure Cohort.
This designation became effective on
September 5, 2007, as provided for
under 42 U.S.C. 7384l(14)(C). Hence,
beginning on September 5, 2007,
members of this class of employees,
defined as reported in this notice,
became members of the Special
Exposure Cohort.
VerDate Aug<31>2005
18:31 Oct 02, 2007
Jkt 211001
SUMMARY: The Department of Health and
Human Services (HHS) gives notice as
required by 42 CFR 83.12(e) of a
decision to evaluate a petition to
designate a class of employees at the
Mound Plant, Miamisburg, Ohio, to be
included in the Special Exposure Cohort
under the Energy Employees
Occupational Illness Compensation
Program Act of 2000. The initial
proposed definition for the class being
evaluated, subject to revision as
warranted by the evaluation, is as
follows:
Facility: Mound Plant.
Location: Miamisburg, Ohio.
Job Titles and/or Job Duties: All
workers.
Period of Employment: February 1,
1949 through the present.
FOR FURTHER INFORMATION CONTACT:
Larry Elliott, Director, Office of
Compensation Analysis and Support,
National Institute for Occupational
Safety and Health (NIOSH), 4676
Columbia Parkway, MS C–46,
Cincinnati, OH 45226, Telephone 513–
533–6800 (this is not a toll-free
number). Information requests can also
be submitted by e-mail to
OCAS@CDC.GOV.
PO 00000
Frm 00030
Fmt 4703
BILLING CODE 4163–19–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institute for Occupational
Safety and Health; Final Effect of
Designation of a Class of Employees
for Addition to the Special Exposure
Cohort
National Institute for
Occupational Safety and Health
(NIOSH), Department of Health and
Human Services (HHS).
AGENCY:
BILLING CODE 4163–19–P
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: September 27, 2007.
John Howard,
Director, National Institute for Occupational
Safety and Health.
[FR Doc. E7–19522 Filed 10–2–07; 8:45 am]
Sfmt 4703
ACTION:
Notice.
SUMMARY: The Department of Health and
Human Services (HHS) gives notice
concerning the final effect of the HHS
decision to designate a class of
employees at the Rocky Flats Plant,
Golden, Colorado, as an addition to the
Special Exposure Cohort (SEC) under
the Energy Employees Occupational
Illness Compensation Program Act of
2000. On August 6, 2007, as provided
for under 42 U.S.C. 7384q(b), the
Secretary of HHS designated the
following class of employees as an
addition to the SEC:
Employees of the Department of Energy
(DOE), its predecessor agencies, or DOE
contractors or subcontractors who were
monitored or should have been monitored for
neutron exposures while working at the
Rocky Flats Plant in Golden, Colorado, for a
number of work days aggregating at least 250
work days from April 1, 1952 through
December 31, 1958, or in combination with
work days within the parameters established
for one or more other classes of employees
in the Special Exposure Cohort.
This designation became effective on
September 5, 2007, as provided for
under 42 U.S.C. 7384l(14)(C). Hence,
beginning on September 5, 2007,
members of this class of employees,
defined as reported in this notice,
became members of the Special
Exposure Cohort.
FOR FURTHER INFORMATION CONTACT:
Larry Elliott, Director, Office of
Compensation Analysis and Support,
National Institute for Occupational
Safety and Health (NIOSH), 4676
Columbia Parkway, MS C–46,
Cincinnati, OH 45226, Telephone 513–
533–6800 (this is not a toll-free
number). Information requests can also
be submitted by e-mail to
OCAS@CDC.GOV.
E:\FR\FM\03OCN1.SGM
03OCN1
]]>Agencies
[Federal Register Volume 72, Number 191 (Wednesday, October 3, 2007)]
[Notices]
[Pages 56358-56360]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-19462]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program (NTP); Host Susceptibility Program
(HSP); Genetic Variation and the Basis for Individual Susceptibility to
Environmental Toxicant Associated Disease: Request for Information
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH).
ACTION: Request for information.
-----------------------------------------------------------------------
SUMMARY: The NTP is developing the Host Susceptibility Program (HSP), a
new research program, to identify and functionally validate genes
associated with environmental exposure. This program will make
available NTP expertise and resources to investigate the genetic basis
for population-level differences in susceptibility to environmental
toxicants and/or disease based upon gene and environment interactions.
This research will be designed to ultimately lead to a better
understanding of why some individuals are more susceptible than others
to exposure to an environmental toxicant resulting in disease and
morbidity. Asthma, cardiovascular disease, cancer, diabetes, and
obesity are examples of diseases associated with multiple interacting
genes that are influenced by exposure to environmental agents. Through
this Request for Information, extramural and intramural scientists are
invited and encouraged to provide information and comment relevant to
this proposed programmatic research approach in order to help guide
further development and refinement of the goals of the NTP HSP.
Information on this initiative can be submitted electronically through
the HSP Request for Information Web site at: (https://ntp.niehs.nih.gov/
go/32130 ) or by contacting Dr. John E. French (see FOR FURTHER
INFORMATION CONTACT below).
DATES: The deadline for response is October 31, 2007.
ADDRESSES: Responses can be submitted electronically at the HSP Request
for Information Web site: https://ntp.niehs.nih.gov/go/32130.
FOR FURTHER INFORMATION CONTACT: Other correspondence should be
directed to Dr. John E. French, Host Susceptibility Program, NIEHS,
P.O. Box 12233, MD EC-17, Research Triangle Park, NC 27709, (fax) 919-
541-0947, (email) hsp@niehs.nih.gov. Courier address: Dr. John E.
French, Host Susceptibility Program, 111 T.W. Alexander Drive, Building
101, Room F167, Research Triangle Park, NC 27709.
SUPPLEMENTARY INFORMATION:
Background
The NTP was established as a cooperative effort to (1) coordinate
toxicology testing programs within the federal government, (2)
strengthen the science base in toxicology, (3) develop improved testing
methods, and (4) provide information about potentially toxic chemicals
to health, regulatory, and research agencies, scientific and medical
communities, and the public. To meet these goals, NTP designs and
conducts large-scale laboratory animal research and testing programs
and analyzes and reports their findings to assess potential hazards to
human health from exposure to environmental chemicals.
Recently, the NTP led and funded a haplotype mapping project with
Perlegen Sciences to resequence 15 isogenic strains of mice selected
for their potential genetic diversity. Along with the public sequence
of isogenic C57BL/6J, analysis of 16 sequenced strains has revealed,
conservatively, more than 8 million single nucleotide polymorphisms in
this initial analysis of laboratory and wild-derived isogenic mouse
strains (Frazer et al., 2007). Identification and analysis of mouse
haplotypes will provide a valuable tool for haplotype-phenotype
association studies in genetically diverse strains that can be used to
predict human genetic variants of functional significance (https://
mouse.perlegen.com/mouse/ ). Toward that goal, the NTP is
developing a multidisciplinary research program on genetic
susceptibility to environmental exposures. This effort will partner
extramural and/or intramural researchers with NTP scientists by
creating research partnerships using NTP R&D contract resources. This
research program is not a funding opportunity or a grant program.
The intent of HSP is to provide researchers access to NTP R&D
contract resources and NTP expertise in public health toxicology.
Participation by extramural and/or intramural scientists will be based
on competitive peer
[[Page 56359]]
review of proposed research projects. NTP scientists will work with
extramural and/or intramural investigators to define and refine the
most effective and cost-efficient experimental protocols for
accomplishing the experimental aims and for linking environmental
exposure with toxicity leading to disease. Development of approved
projects will proceed sequentially from hypothesis through specific
aims, based upon a consensus derived experimental plan. Continued
support of research projects will depend upon satisfactory completion
of each phase of the research plan.
Via this partnership, extramural and/or intramural investigators
will have access to NTP contract resources to investigate the
relationship between exposure to environmental toxicants and
development of quantitative measures of toxicity and disease, using
genetically diverse experimental animal models. Using research
partnerships, HSP scientists aim to develop the tools and means
necessary to accomplish the multidisciplinary tasks that are often
rate-limiting to individual research groups that may be interested in
investigating environmental toxicant exposure and genetic
susceptibility to disease and determining allelic variants of causally
related genes and their potentially dysregulated signaling pathways.
Once a project has been peer reviewed and approved, NTP staff will
interact directly with the Principal Investigator(s) (PIs) of the
approved projects to refine the research using NTP contracted
resources. NTP R&D contractors will perform approved tasks under the
direction of NTP staff. Those tasks necessary to accomplish the
experimental aims of any particular study are expected to vary from
project to project. In some cases, NTP may only support one or two key
missing steps necessary to complement the research; in other cases, it
may be necessary to supply the entire scope of experimental tasks
needed to complete the specific aims. Examples of tasks that can be
supported by NTP contracts and staff include, but are not necessarily
limited to:
Facilitating animal model selection (multiple-isogenic
strains, heterogeneous, outbred stocks, etc.).
Providing strain-specific data on absorption,
distribution, metabolism, and excretion of metabolic products of
environmental toxicants.
Defining or optimizing of exposure route, dose and dose
schedule of environmental toxicants using range-finding studies to
determine quantitative measures of acute toxicity in vivo in an
appropriate animal model.
Quantitatively identifying variants of toxicity
(phenotyping) in multiple isogenic strains, genetically engineered
strains, and/or genetically defined outbred stocks.
Developing appropriate experimental design protocols for
toxicity, biomarkers, expression arrays, clinical and histopathology,
and statistical analysis.
Acquiring test agent(s) in quantities sufficient for non-
GLP acute and prechronic toxicity investigations, development of
analytical methods for determination of quantity and purity of test
substances, production and stability (storage) of dosage forms.
Developing, optimizing, and conducting study and route
specific toxicology and toxicity assays for correlation between
toxicity and histopathologic determinants.
Output from such collaborative research activities, which may
include providing biological samples and/or data (genotyping,
quantitative measures of toxicity, expression phenotypes, etc.), is to
be made fully available to the originating principal investigator (or
his/her replacement, in case of withdrawal) for continued support of
the research project developed within the partnership. Data and samples
are to be transferred to extramural or intramural collaborators under
terms of a negotiated NIH Materials Transfer Agreement.
Information Requested
The NTP is soliciting information from the extramural and
intramural research communities on the strategies, resources, and tools
necessary to enable this cooperative research program on genetic
variation and individual susceptibility to environmental toxicant
exposure and associated polygenic diseases to progress. Please respond
online at the HSP Request for Information Web page (https://
ntp.niehs.nih.gov/go/32130) to any or all of the following questions by
October 31, 2007.
1. In general, what are the utility and limitations of using model
organisms (e.g., multiple strains of isogenic mice, heterogeneous mouse
stocks, etc.) to investigate and establish the genetic determinants of
biological response?
2. Are there particular environmental toxicants associated with
human disease where this research approach is immediately applicable
and useful to the identification of causally related genes and their
allelic variants?
3. Similarly, are there particular physiologic or pathogenic
pathways and/or disease endpoints for which the proposed research
approach is likely to be especially insightful in advancing our
understanding of gene-environment interactions?
4. What computational, statistical, and bioinformatic methodologies
might be particularly useful for determining toxicity phenotypes and
identifying associated genes, pathways, and networks?
5. What high-data content technologies, platforms, and statistical
approaches might be particularly valuable and critical to elucidating
the genetic basis for toxicity and disease based upon the experience
and knowledge gained over the past decade?
6. Are there high-throughput assays and screens using cell-based
systems that might be employed to examine the role of genetic variation
in human exposure?
7. Are in vitro and in vivo assays and genetic models for
functional validation of genes useful in permitting orthologous human
genes and their allelic variants to be identified and tested in large-
scale human populations with defined environmental exposures?
8. Is the competitive research partnership approach described for
the HSP using NTP R&D expertise in toxicology and contract resources
viable and of general interest to researchers interested in these
questions? Why or why not?
9. Are there specific concerns over intellectual property or
research collaboration issues in a research partnership that should be
addressed and negotiated?
All responses to individual questions within this Request for
Information are optional. The information collected will be analyzed
and considered for use in the further development of the NTP HSP. The
summarized data (without identifiers) may appear in internal reports.
Although the NIH will provide safeguards to prevent the release of
identifying information, there is no guarantee of confidentiality. This
Request for Information is for planning purposes and should not be
construed as a solicitation for applications or as an obligation on the
part of the Government. The Government will not pay for the preparation
of any information submitted or for the Government's use of that
information. Acknowledgement of receipt of responses will not be made,
nor will respondents be notified of the Government's assessment of the
information received. No basis for claims against the Government shall
arise as a result of response to this Request for Information, or in
the
[[Page 56360]]
Government's use of such information as part of our evaluation process.
Reference
Frazer, K.A., E. Eskin, H.M. Kang, M.A. Bogue, D.A. Hinds, E.J.
Beilharz, R.V. Gupta, J. Montgomery, M.M. Morenzoni, G.B. Nilsen,
C.L. Pethiyagoda, L.L. Stuve, F.M. Johnson, M.J. Daly, C.M. Wade,
and D.R. Cox. A sequence-based variation map of 8.27 million SNPs in
inbred mouse strains. Nature 2007 July 29 Epub.
Dated: September 24, 2007.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences
and National Toxicology Program.
[FR Doc. E7-19462 Filed 10-2-07; 8:45 am]
BILLING CODE 4140-01-P
