UNITED STATES FEDERAL GOVERNMENT COLLABORATION TOXICOLOGY IN THE 21ST CENTURY (TOX21) TESTING THOUSANDS OF ENVIRONMENTAL CHEMICALS USING NON-ANIMAL METHODS

Overview Toxicology in the 21st Century (Tox21) is a US federal research collaboration that is developing alternative, non-animal methods to quickly and efficiently test thousands of chemicals for potential health effects. These approaches use advances in robotics technology to test chemicals for their potential to disrupt processes in the human body, which may lead to negative health effects. Since its formation in 2008, Tox21 has screened approximately 10,000 chemicals in more than 70 The computational model and • Companies are using Tox21data rapid tests called “qualitative high- assays have been reviewed by a when they submit European throughput screening assays”. This Scientific Advisory Panel and were chemical registration dossiers. accepted as alternative tests within includes chemicals used in Greater acceptance of Tox21 industrial processes and consumer the current EDSP Tier 1 testing requirements. methods by the scientific products as well as food additives, community approved and investigational • The European Chemicals drugs, and chemical mixtures. Agency’s document “Scenarios to • Tox21 has published over 200 scientific peer-reviewed articles in Accomplishments be implemented for searching for potential substances of concern” approximately 55 journals. Articles Tox21 methods inform highlights Tox21 assays that can were most frequently published in policy and regulatory be used for identifying potential Toxicological Sciences, decisions made about the endocrine disrupting chemicals. Environmental Health Perspectives, Chemical Research in Toxicology, safety of chemicals • The California Environmental and Environmental Science and • US EPA’s Endocrine Disruption Protection Agency has Technology. Screening Program (EDSP) is incorporated Tox21 data in select • The top 5 Tox21 articles have using Tox21 assays as part of a pesticide assessments, and the been cited an average of more than panel of 18 high-throughput Minnesota Department of Health is 100 times. screening assays that measure using Tox21 data for assessing activity across different parts of the health risks associated with water • Over 80 Tox21 publications have estrogen receptor pathway. The contaminants. been cited in U.S. National results from the panel of 18 tests • The World Health Organization’s Academy of Sciences Reports. are incorporated into a International Agency for Research computational model to identify on Cancer (IARC) has used Tox21 chemicals that have the potential data as one area of evidence for estrogenic activity which could within a larger framework for lead to endocrine disruption. assessing the evidence of carcinogenesis.

1 plan that broadened the scope of History the collaboration to include other emerging toxicology approaches The Tox21 collaboration was and a focus on incorporating these formalized in 2008 through a scientific advances into policy and memorandum of understanding regulatory decisions. (MOU) between the National Institutes of Health, including the The primary goal of the Tox21 National Toxicology Program collaboration remains focused on (NTP) and National Human developing new tools and methods Genome Research Institute's that more efficiently and reliably National Chemical Genomics predict whether a chemical might Center (NCGC, now a part of be toxic to humans. Further NCATS), and the EPA’s National development and usage of these Center for Computational approaches will continue to Toxicology. The Food and Drug significantly reduce the use of Administration (FDA) joined the animals for chemical testing and Tox21 collaboration in 2010. Millions of Tox21 data points provide data to better protect are publicly available to public health. inform science and decisions Research activities under the new More information available – www.tox21.gov/ • Tox21 has screened thousands of strategic vision and operational chemicals in approximately 70 plan will be focused on the high-throughput assays covering following areas: over 125 important processes in 1. Developing and deploying the body and generating more than alternative test systems that are 70 million data points. predictive of human toxicity and • The Tox21 data is publicly dose response. available through the National 2. Addressing key technical Library of Medicine’s PubChem, limitations of current high- the EPA's Computational throughput screening systems. Toxicology Dashboard and NTP’s Chemical Effects in Biological 3. Consolidating chemical library Systems. management and developing more focused libraries. • Detailed assay annotations, protocols, and performance 4. Curating and characterizing statistics are publicly available on legacy animal toxicity studies for the EPA's Computational continued comparison to high- Toxicology website (www.epa.gov/ throughput screening results. comptox) and the NIH tripod web 5. Validating high-throughput site assays, integrated assay (https://tripod.nih.gov/tox21). batteries, computational models, Strategic Vision for the 3-D organ-like model systems, Next Five Years and other emerging Tox21 approaches. The predominant research activities of the Tox21 6. Refining and deploying high- collaboration have been throughput methods for developing and applying high- characterizing pharmacokinetics throughput screening to toxicity to better predict the relationship testing. In 2017, the Tox21 between target tissue collaborators developed a new concentrations and external strategic vision and operational doses of chemicals.

2 August 2017