History of Tox21

A Vision of Toxicology in the 21st Century

pipettes used in testing The NTP Vision for the 21st Century is to move toxicology from a predominantly observational science at the level of disease-specific models to a predominantly predictive science focused on a broad inclusion of target-specific, mechanism-based biological observations.

To implement the Vision, NTP developed a Roadmap that places an increased emphasis on the use of alternative assays for targeting key pathways, molecular events, or processes linked to disease or injury, and incorporates them into a research and testing framework. The Roadmap positions NTP to provide scientific data and the interpretation of those data for public health decision-making. As a logical outgrowth of the Roadmap, NTP established a High Throughput Screening (HTS) program, representing a new paradigm in toxicological testing.

In 2007, the National Academy of Sciences published its report "Toxicity Testing in the 21st Century: A Vision and Strategy" that envisioned routine toxicity testing being conducted in vitro in human cells or cell lines. High throughput robotic-assisted methodologies would be used to evaluate perturbations of cellular responses in a suite of toxicity assays. In response to this report, NTP entered into a partnership with two other government agencies to build on existing expertise, overcome the resource limitations of a single agency, and advance this vision.

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Formalization of the Federal Collaboration

The Tox21 federal collaboration was formalized in 2008 through a memorandum of understanding (MOU) to further the new vision of toxicology testing. On February 14, 2008, NTP, the National Human Genome Research Institute's National Chemical Genomics Center (NCGC, now a part of the National Center for Advancing Translational Sciences, NCATS), and the Environmental Protection Agency's (EPA) National Center for Computational Toxicology entered into a five-year MOU. The new Tox21 partners, Drs. Francis Collins (NHGRI), George Gray (EPA), and John Bucher (NTP), published “Transforming Environmental Health Protection” in Science, describing how the partnership would transform environmental health protection.

In 2010, the Food and Drug Administration (FDA) joined the Tox21 collaboration through another five-year MOU. The FDA brings experience in human diseases, animal models of human disease, toxicity pathway analysis, and computational toxicology. FDA’s active participation is in recognition of its commitment to developing new methods to evaluate the toxicity of the substances it regulates.

On June 16, 2015, the Tox21 collaborators renewed their commitment to the program through a third five-year MOU between NTP, NCATS, EPA, and FDA. The federal partners agreed to continue their work improving toxicology by:

  • Identifying mechanism of chemically induced biological activity.
  • Prioritizing chemicals for more extensive toxicological evaluation.
  • Developing more predictive models of in vivo biological response.