The Tox21 program now has a 10-year track record of developing cutting-edge technology to better assess chemical toxicity in humans. In August, the 10th World Congress on Alternatives and Animal Use (see related story) dedicated a panel discussion to this milestone. Speakers highlighted the program’s achievements and plans for the next five years.
The road ahead
The first decade of Tox21 saw significant progress on developing and applying high-throughput screening (HTS) as a tool for chemical toxicity tests. At the World Congress meeting, Rick Paules, Ph.D., looked ahead to the next five years. Paules is the acting head of the National Toxicology Program (NTP) Biomolecular Screening Branch and serves as NTP lead for the multi-agency Tox21 program (see sidebar).
He said Tox21 scientists will concentrate on new and emerging alternatives, including computational models and 3-dimensional, organ-like model systems. Such alternatives may help address shortcomings of HTS, which include processing volatile chemicals and predicting dose-response relationships.
As new test systems come online, scientists will need to develop a framework for validating them. Interpreting results of alternative tests will be supported by a further focus on characterizing past, or legacy, in vivo toxicity studies.
Other priorities include incorporating individual variability, dose-response characteristics, and pharmacokinetics. These and other program goals are part of a strategic plan for the next five years that is nearing completion.
“As we continue our successful partnership [see sidebar], we will realign our teams as needed to pursue these goals,” Paules said. “For example, at NTP, we’re particularly interested in how transcriptome profiling can provide a better characterization of human responses to exposures.” The transcriptome refers to the set of all RNA molecules in a particular cell or population of cells. Transcriptome profiling provides a look at the genes that are active in those cells at a certain time, such as after exposure to a chemical.
A decade of accomplishments
A new fact sheet captures milestones from the first decade of Tox21. For example, Tox21 researchers have published more than 200 peer-reviewed articles. Highly cited papers have appeared in journals like Toxicological Sciences, Environmental Health Perspectives, and Chemical Research in Toxicology.
Many of those papers shared results of robotic HTS assays on nearly 10,000 chemicals, performed at the National Center for Advancing Translational Science. These chemicals, referred to as the Tox21 library, are used in consumer products, industrial processes, agriculture, and drug development. Management of this library is another Tox21 priority for the coming years.
The data from these screenings are publicly available through three sources.
- PubChem, from the National Library of Medicine.
- The U.S. Environmental Protection Agency (EPA) Computational Toxicology Dashboard.
- Chemical Effects in Biological Systems, from NTP.
Free access has made it possible for groups ranging from state governments, such as California, to international agencies, like the World Health Organization, to use results of these assays in their assessments of health risks.
Some of the test protocols developed under Tox21 have already been adopted by EPA to screen chemicals for their potential to disrupt hormone, or endocrine, activity. These new tests are part of the EPA Endocrine Disruption Screening Program.