National Toxicology Program

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:

• National Toxicology Program
• National Center for Advancing Translational Sciences
• Environmental Protection Agency

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:

1. Relevance to the goals of the Tox21 Initiative
2. 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 )
3. Evaluation of preliminary assay performance using appropriate reference compounds
4. Validation status of the assay
5. Availability of complete detailed protocols
6. 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]