[Federal Register Volume 78, Number 145 (Monday, July 29, 2013)]
[Pages 45542-45543]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-18058]



National Institutes of Health

Request for Information: The National Institute of Environmental 
Health Sciences/National Toxicology Program Requests the Nomination and 
Prioritization of Environmentally Responsive Genes for Use in Screening 
Large Numbers of Substances Using Toxicogenomic Technologies

SUMMARY: The National Institute of Environmental Health Sciences 
(NIEHS)/National Toxicology Program (NTP) is interested in the 
identification and prioritization of a comprehensive list of 
environmentally responsive genes that might be targets for screening 
cells or tissues obtained from humans, rats, mice, zebrafish, and 
Caenorhabditis elegans against large numbers of substances. The goal is 
to generate a minimum list of 1000 genes for each species that would 
provide the maximal toxicogenomic information on (1) effects that 
reflect general cellular responses, independent of cell type or 
species, and (2) gene expression changes that are specific by organ 
and/or cell type. The NIEHS/NTP also seeks recommendations on criteria 
to use for prioritizing the genes in order to identify those 
potentially most useful in a screening paradigm. Such a list of 
environmentally responsive genes may be useful also in biomarker 
development and basic research efforts.

DATES: The deadline for receipt of information is August 23, 2013.

ADDRESSES: Nominated genes and/or recommendations on prioritization 
criteria should be submitted electronically in Microsoft Excel or Word 
formats to [email protected].

12233 (MD K2-17), Research Triangle Park, NC 27709; email: 
[email protected].



    In 2008, the 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.
    In Tox21, the 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. Currently, the primary Tox21 activity is the 
screening of a 10,000 compound library in a number of nuclear receptor 
agonist/antagonist and stress response pathway assays primarily using 
reporter gene platforms. In the next phase, the focus will be on 
assaying large numbers of chemicals in high content screens and mid to 
high throughput, targeted gene expression platforms.
    To conduct the next phase, the NIEHS/NTP in collaboration with its 
Tox21 partners seeks to identify a prioritized set of at least 1000 
genes that would provide comprehensive toxicogenomic information on (1) 
gene induction or repression reflecting general cellular responses that 
are largely independent of cell type or species, and (2) gene 
expression changes that are organ and/or cell type specific. Examples 
of processes likely to be cell-type independent include genes involved 
in stress-response pathways (e.g., DNA repair, hypoxia, heat shock), 
chromatin remodeling, and those that regulate cell division and death. 
Examples of processes more likely to be cell-type specific include 
induction or repression of expression of enzymes that modify or 
activate chemical toxicants, regulation of the hypothalamic-pituitary-
adrenal axis, and inflammatory responses. In keeping with the Tox21 
goal of facilitating cross-species extrapolation, the NIEHS/NTP is 
especially interested in the nomination of genes or gene sets 
specifically relevant for comparisons between humans, rats, mice, 
zebrafish, and C. elegans and especially those for which complementary 
functional pathways exist. Such a list of environmentally responsive 
genes may be useful also in biomarker development and basic research 
efforts. To facilitate identification of the most useful genes to 
include in a screening paradigm, the NIEHS/NTP also requests 
recommendations on criteria to use for their prioritization.

Request for Information

    The NIEHS/NTP seeks to establish a prioritized list of 
environmentally responsive genes to screen cells/tissues from humans, 
rats, mice, zebrafish, and C. elegans for agent-induced alterations 
using mid to high throughput, targeted transcriptomics platforms. The 
goal is to screen a large number of compounds and obtain information 
useful for understanding the potential for adverse health outcomes. To 
that end, the NIEHS/NTP requests that respondents provide information 
for either or both of the following:
     Nominations of specific genes or gene sets. Nominated 
genes should be identified using Entrez and/or Ensembl gene IDs. 
Desirable supporting information for the nominated gene(s) would 
include the associated pathway(s) or biological process(s), the 
cellular context(s) where demonstrated, and the technology used to 
measure expression of the nominated gene. If available, please include 
relevant citations as a part of the supporting information.
     Criteria for prioritization of the genes or gene sets. The 
NIEHS/NTP is interested in criteria that could be used to develop a 
prioritized list of genes that would provide the greatest level of

[[Page 45543]]

insight and discrimination of toxicological response in a variety of 
applications including cross-species comparisons and differential 
tissue responses.
    The nominated genes and/or criteria recommendations should be 
submitted electronically in Microsoft Excel or Word format.
    Respondents to this request for information are asked also to 
provide their name, affiliation, address, and contact information 
(including telephone and fax numbers, and email address). The deadline 
for receipt of the requested information is August 23, 2013.
    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 

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 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 the NTP and NIEHS is found at http://www.niehs.nih.gov and http://ntp.niehs.nih.gov, respectively.

    Dated: July 23, 2013.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2013-18058 Filed 7-26-13; 8:45 am]