The U.S. government's multiagency "Tox21" research initiative aims to improve regulatory
hazard assessment of substances potentially
harmful to humans and the environment. Laboratories participating in this research initiative will
use integrated in vitro high throughput screens (HTS) to assess the effects of a broad variety of substances on
biological pathways related to toxicity.
The HTS data will then be used to develop a better understanding of these adverse outcome pathways,
enabling the eventual use of in vitro assay data to predict the toxic (or adverse) effects of
chemical exposures in vivo.
On behalf of the Tox21 Consortium and its Assays and Pathways Working Group, NICEATM is accepting nominations for
HTS assays. Assays that are
found to be compatible with the HTS program will support Tox21 by providing data on endpoints
that serve as markers for initiating or downstream events in adverse outcome pathways.
Of particular current interest are assays that evaluate effects to the following pathways:
- Biological pathways: Wnt, SHH (aka SONIC hedgehog), Delta-notch, TGF-beta, receptor tyrosine kinase (aka RTK) and retinoid
- Endocrine pathways: estrogen, thyroid, adrenal, and androgen
For more information about nominating an assay, please contact NICEATM Deputy Director
Dr. Warren Casey.
Submit an assay to Tox21 via online form
Background
The Tox21 Consortium is a collaboration of the National Toxicology Program, the
National Institutes of Health's National Center for
Advancing Translational Sciences (NCATS), the Environmental Protection Agency's National Center for
Computational Toxicology, and the Food and Drug Administration. The Tox21 partner agencies work together to develop,
validate, and translate innovative in vitro HTS methods to
characterize the impact of chemicals on key steps in toxicity pathways.
Data collected in the Tox21 initiative will be used in the near term to prioritize uncharacterized
substances for regulatory testing using both traditional and novel test methods. The eventual goal
of Tox21 is to use HTS methods to generate data that will allow risk assessors to more accurately
predict the effects of regulated substances on human health and the environment.
More information about some partner agencies' activities in support of Tox21 can be found on the
agency websites:
In addition to providing more accurate human health effects data more efficiently, the Tox21 initiative
also offers the potential for this data to be obtained without using animals. The mission of
NICEATM and ICCVAM is to facilitate development, validation, and regulatory acceptance of new and revised
regulatory test methods that reduce, refine, and replace the use of animals in testing while
maintaining and promoting scientific quality and the protection of human health, animal health,
and the environment.
The draft 2013-2017 ICCVAM Five-Year Plan further states that NICEATM and ICCVAM will
- Work with Federal agencies and other ICCVAM stakeholders to identify and promote innovative research that may yield improved test methods and strategies
- Work closely with partner agencies to broker translation of emerging science into candidate test methods that address regulatory needs
NICEATM and ICCVAM support of Tox21 is consistent with both of these goals and with the NICEATM–ICCVAM mission.
Request for Nominations of HTS Assays
The Tox21 Initiative will use its collection of 10,000 chemicals to develop
a systematic view of how chemicals interact with and affect biological systems. To achieve this,
assays are needed that assess the effects of chemicals on targets encompassing all pathways relevant to toxicity,
in particular those pathways listed above.
NICEATM requests nominations of in vitro HTS toxicity assays that might be used in the
Tox21 testing program. Nominated assays will be assessed for their
overall applicability to the Tox21 HTS program in terms of biological relevance, cost, and potential
to be adapted to a HTS format. Suitable assays will then be prioritized for use in the program.
Nominations should consider the following general criteria:
- Relevance to the goals of the Tox21 Initiative
- High throughput capability of the assay (96-well format or higher, with no obvious impediments
to miniaturization to a 1536-well format: see
guidance criteria )
- Evaluation of preliminary assay performance using appropriate reference compounds
- Validation status of the assay
- Availability of complete detailed protocols
- Efficiency and cost of the assay
Assay nominations should be sent to the
Deputy Director of NICEATM. Please note that protocol information and test data submitted may be
incorporated in future NCATS and NICEATM reports and publications as appropriate. When submitting
HTS assay nominations and protocol information, please reference Federal Register notice 77 FR 22321 and
provide appropriate contact information (name, affiliation, mailing address, phone, fax, email, and
sponsoring organization as applicable). NICEATM prefers the nominations to be submitted
electronically, but will accept nominations by the means that is most convenient for the
submitter.
For more information, please contact NICEATM
Federal Register notice:
Call for Nominations: High-Throughput Screening (HTS) Assays for Use in the Tox21 Initiative
(77 FR 22321, May 13, 2012) [PDF
- Text]
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