[Federal Register Volume 80, Number 72 (Wednesday, April 15, 2015)]
[Notices]
[Pages 20237-20238]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-08529]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


List of Environmentally Responsive Human Genes Selected for Use 
In Screening Large Numbers of Substances Using Toxicogenomic Approaches

    Request for Comments: The National Institute of Environmental 
Health Sciences/National Toxicology Program requests comments on a list 
of environmentally responsive human genes selected for use in screening 
large numbers of substances using toxicogenomic approaches.

SUMMARY: The National Institute of Environmental Health Sciences 
(NIEHS)/National Toxicology Program (NTP) requests comments on a set of 
human genes that have been identified and prioritized as 
environmentally responsive genes. These genes will be used in 
toxicogenomics approaches to screen cells or tissues obtained from 
humans against large numbers of chemicals. The goal was to generate a 
set of approximately 1500 human genes to evaluate transcriptional 
changes in response to chemical exposures. Similar gene sets will be 
developed for screening cells or tissues from other species such as 
rats, mice, zebrafish, and Caenorhabditis elegans. The human gene set 
should provide maximal toxicogenomic information on effects from 
chemical exposures that reflect general cellular responses, independent 
of cell type or species, and gene expression changes that are specific 
by organ and/or cell type. Such a list of environmentally responsive 
genes may also be useful in biomarker development and basic research 
efforts. This list of genes, referred to as the ``S1500'' gene list, or 
gene set, is available for public comment.

DATES: The deadline for receipt of comments is May 15, 2015.

ADDRESSES: Comments on the human S1500 gene set should be submitted 
electronically in Microsoft Excel or Word formats to 
<a href="/cdn-cgi/l/email-protection#c285a7aca7aeabb1b682acaba7aab1ecacabaaeca5adb4"><span class="__cf_email__" data-cfemail="e6a18388838a8f9592a6888f838e95c8888f8ec8818990">[email protected]</span></a>. Nominations for genes to be added to the S1500 
must be accompanied with a strong scientific justification for 
inclusion.

FOR FURTHER INFORMATION CONTACT: Dr. Elizabeth Maull, NIEHS, P.O. Box 
12233 (MD K2-17), Research Triangle Park, NC 27709; email: 
<a href="/cdn-cgi/l/email-protection#c7aaa6b2abab87a9aea2afb4e9a9aeafe9a0a8b1"><span class="__cf_email__" data-cfemail="1b767a6e77775b75727e736835757273357c746d">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:
    Background: In 2008, NIEHS/NTP, the U.S. Environmental Protection 
Agency's (EPA) National Center for Computational Toxicology (NCCT), and 
the National Human Genome Research Institute (NHGRI)/NIH Chemical 
Genomics Center (NCGC) (now located within the National Center for 
Advancing Translational Sciences (NCATS)) entered into a formal 
agreement to develop a vision and devise an implementation strategy to 
shift the assessment of chemical hazards from traditional, experimental 
animal, toxicology studies to target-specific, mechanism-based, 
biological observations largely obtained using in vitro assays. In mid-
2010, the U.S. Food and Drug Administration (FDA) joined the 
collaboration that is known informally as Tox21.
    Tox21 partner agencies collaborate to research, develop, validate, 
and translate innovative testing methods for characterization of 
toxicity pathways; identify compounds, assays, informatic analyses, and 
targeted testing needed to support the development of new methods; 
identify patterns of compound-induced biological response(s) in order 
to characterize toxicity pathways; facilitate cross-species and low-
dose extrapolation; prioritize compounds for more extensive 
toxicological evaluation; and develop predictive models for biological 
response in humans. The primary activity of Tox21 Phase I was the 
development of a quantitative high throughput screening (qHTS) approach 
for toxicology. The goal of Phase II was the implementation of the qHTS 
approach in screening a 10,000 compound library through a variety of 
nuclear receptor agonist/antagonist and stress response pathway assays, 
utilizing primarily reporter gene platforms. In Phase III, the focus is 
on assaying chemicals in high-content screens and mid to high 
throughput transcriptomic screens. High throughput gene expression 
changes will be the primary metric that is employed in Phase III to 
measure biological effects from chemical exposures.
    To conduct Tox21 Phase III, Tox21 partners initiated the ``S1500 
Genes High Throughput Transcriptomics'' project to capture information 
from the whole transcriptome (i.e., the entirety of all expressed RNA 
molecules in a cell or biological sample). This project will use a 
targeted subset of genes in a HTS or semi-HTS platform to gain insight 
into how biological systems respond to chemical exposures. Neither the 
actual number of genes to be utilized, nor the specific transcriptomics 
platform(s) needed to carry out the project, have been finalized.
    In an effort to select an appropriate subset of key representative 
or ``sentinel'' genes, the NTP previously requested input from the 
scientific community (78 FR 45542, July 29, 2013) on the ``Nomination 
and Prioritization of Environmentally Responsive Genes for Use in 
Screening Large Numbers of Substances Using Toxicogenomic 
Technologies.'' An interagency working group composed of members of the 
Tox21 partnership considered the input provided in response to the 
Federal Register notice as they developed a consensus strategy to 
select appropriate genes.
    The working group's goal was to select the most relevant and 
biologically diverse set of sentinel genes to represent transcriptomic 
responses to injury. Criteria for the selection and evaluation of an 
appropriate gene set are: (1) Representative of highly diverse gene 
expression changes reported to date, (2) capable of predicting the gene 
expression changes observed across the transcriptome, and (3) coverage 
of all major biological pathways.
    The current version of the human S1500 gene set can be found at 
http://ntp.niehs.nih.gov/go/S1500. This site will be updated as changes 
to the list are made. The consensus strategy for selection of an 
appropriate sentinel gene set can be accessed at the same site.
    Comments on the human S1500 gene set should be submitted 
electronically in Microsoft Excel or Word format to 
<a href="/cdn-cgi/l/email-protection#2463414a41484d5750644a4d414c570a4a4d4c0a434b52"><span class="__cf_email__" data-cfemail="d592b0bbb0b9bca6a195bbbcb0bda6fbbbbcbdfbb2baa3">[email protected]</span></a>.
    Respondents to this request are asked to provide their name, 
affiliation, address, and contact information (including telephone and 
fax numbers, and email address). The deadline for receipt of comments 
is May 15, 2015.

[[Page 20238]]

    Responses to this request are voluntary. This notice does not 
obligate the U.S. Government to award a contract or otherwise pay for 
the information provided in response to this request. The U.S. 
Government reserves the right to use information provided by 
respondents for any purpose deemed necessary and legally appropriate. 
Any organization responding to this request should ensure that its 
response is complete and sufficiently detailed. Respondents are advised 
that the U.S. Government is under no obligation to acknowledge receipt 
of the information received or provide feedback to respondents with 
respect to any information submitted. No proprietary, classified, 
confidential, or sensitive information should be included in your 
response.
    Background Information on the NTP: The NTP is an interagency 
program established in 1978 (43 FR 53060) to strengthen the 
Department's activities in toxicology research and testing and to 
develop and validate new and better testing methods. Other activities 
of the program focus on strengthening the science base in toxicology 
and providing information about potentially toxic chemicals to health-
regulatory and research agencies, scientific and medical communities, 
and the public. The NTP is located administratively at the NIEHS. 
Information about NTP and NIEHS is available at http://ntp.niehs.nih.gov and http://www.niehs.nih.gov, respectively.

    Dated: April 8, 2015.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2015-08529 Filed 4-14-15; 8:45 am]
 BILLING CODE 4140-01-P


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