History of Tox21

pipettes used in testing

A Vision of Toxicology in the 21st Century

In early 2004, the NTP Vision for the 21st Century was published. The goal was to develop more efficient approaches in predicting how substances impact human health.

Following the creation of the Tox21 vision, NTP developed a roadmap published in November 2004. This roadmap placed an emphasis on the use of alternative methods of testing. Using alternative methods, scientist can target key pathways, molecular events, or processes linked to disease or injury. The use of alternative methods is one factor in the reduction of animal testing.

Another objective of the Tox21 program has been 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." This report envisioned routine toxicity testing carried out in vitro in human cells or cell lines. High-throughput robotic-assisted methodologies would be used to evaluate alterations of cellular responses upon toxicity testing. 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.

Formalization of the Federal Collaboration

The Tox21 federal collaboration was formalized in 2008. Through a memorandum of understanding (MOU), Tox21 sought to further a 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. 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. The FDA's active participation is part of its commitment to developing new methods to evaluate the toxicity of the substances it regulates.

In summer of 2021, Tox21 collaborators renewed their commitment to the program through a third five-year MOU between NTP, NCATS, EPA, and the 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.