The Tox21 10K Compound Library
Published February 23, 2021
The library is the result of a decade-long effort and acts as the foundation for Toxicology Testing in the 21st Century (Tox21). The Tox21 consortium is a federal collaboration between EPA, the National Toxicology Program (NTP) headquartered at the National Institute of Environmental Health Sciences (NIEHS), the National Center for Advancing Translational Sciences (NCATS) and the Food and Drug Administration (FDA).
A paper written by EPA researcher Dr. Ann Richard and colleagues, The Tox21 10K Compound Library: Collaborative Chemistry Advancing Toxicology, describes how the library has advanced scientific understanding of chemical toxicology. The paper was recognized as an American Chemical Society (ACS) Editor’s Choice in November 2020.
In Richard et al. (2020), the authors reflect on the central role that chemical libraries play in supporting research to advance the ability to evaluate thousands of chemicals using high-throughput screening methods.
“This article describes how the chemical libraries contributed by each Tox21 federal partner came together, and how the libraries relate to one another,” says Dr. Richard. “Good coverage of potential toxicants spanning diverse chemical and property space across the Tox21 library is necessary from the standpoint of high-throughput screening, probing diverse biological mechanisms for toxicity and improving toxicity prediction models.”
Early in the Tox21 program, the participating federal agency scientists believed that combining chemical libraries would produce more valuable research than if efforts were kept separate. EPA not only contributed thousands of chemicals to the Tox21 library, but also helped to design the chemical informatics infrastructure of the library to best serve future research objectives.
In the latter half of the paper, Richard et al (2020) focused on the content of the chemical library, including chemistry information like chemical structure and property representations. This information shows how the full library provides excellent coverage of a broad landscape of chemicals of toxicological interest. The library allows scientists to identify chemical patterns in their analyses that would not be detected using smaller libraries.
The authors include helpful visualizations of data, workflows, schematics, and programs throughout the paper as they tell the story of how the Tox21 10K library came together and its value to the future of chemical research.
A common goal connects all Tox21 federal agency collaborators: to make all test results generated from this unique chemical library available to scientists through multiple public venues to fuel advances in toxicology. To date, the Tox21 program has produced upward of 120 million chemical assay data points for over 70 distinct assays, corresponding to more than 200 separate assay end point read outs. Since screening results have been made public, the broader scientific community has added hundreds of publications in areas ranging from predictive toxicity to exposure modeling and nontargeted screening. EPA’s involvement and leadership in the Tox21 consortium, including providing access to all Tox21 data through the CompTox Chemicals Dashboard, demonstrates EPA’s commitment to global collaboration to advance toxicological research.
By bringing together knowledge and resources from federal partners, the Tox21 10K Library has been instrumental in providing publicly available screening data for thousands of diverse chemicals. These data are helping decision-makers and scientists more quickly and efficiently evaluate chemicals. Among other accomplishments, scientists have been able to develop more robust targeted models with the data coming out of the Tox21 program. The library continues to assist research that increases knowledge about how chemicals interact with human systems and environmental pathways, which is key to informing policy.