Improving the Human Hazard Characterization of Chemicals: A Tox21 Update

By R. Tice, C. Austin, R. Kavlock, J. Bucher. 2013

579 citations recorded by the source corpus.

Background: In 2008, the National Institute of Environmental Health Sciences/National Toxicology Program, the U.S. Environmental Protection Agency’s National Center for Computational Toxicology, and the National Human Genome Research Institute/National Institutes of Health Chemical Genomics Center entered into an agreement on “high throughput screening, toxicity pathway profiling, and biological interpretation of findings.” In 2010, the U.S. Food and Drug Administration (FDA) joined the collaboration, known informally as Tox21. Objectives: The Tox21 partners agreed to develop a vision and devise an implementation strategy to shift the assessment of chemical hazards away from traditional experimental animal toxicology studies to one based on target-specific, mechanism-based, biological observations largely obtained using in vitro assays. Discussion: Here we outline the efforts of the Tox21 partners up to the time the FDA joined the collaboration, describe the approaches taken to develop the science and technologies that are currently being used, assess the current status, and identify problems that could impede further progress as well as suggest approaches to address those problems. Conclusion: Tox21 faces some very difficult issues. However, we are making progress in integrating data from diverse technologies and end points into what is effectively a systems-biology approach to toxicology. This can be accomplished only when comprehensive knowledge is obtained with broad coverage of chemical and biological/toxicological space. The efforts thus far reflect the initial stage of an exceedingly complicated program, one that will likely take decades to fully achieve its goals. However, even at this stage, the information obtained has attracted the attention of the international scientific community, and we believe these efforts foretell the future of toxicology.

Subfields: Health, Toxicology and Mutagenesis, Molecular Biology, Small Animals

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In Health, Toxicology and Mutagenesis

1. Richard S. Judson
2. Ann M. Richard

In Molecular Biology

1. Antony J. Williams
2. David Broadhurst
3. Douglas B. Kell

In Small Animals

1. Richard S. Judson
2. Ann M. Richard

Citations in the corpus

• The Next Generation Blueprint of Computational Toxicology at the U.S. Environmental Protection Agency. (2019, methodology): “The Tox21 federal partners contributed to a combined library of over 8500 chemicals and screened those chemicals across more than 80 assay endpoints (Thomas et al. , 2018; Tice et al. , 2013).”
• The CompTox Chemistry Dashboard: a community data resource for environmental chemistry (2017, methodology): “NCCT’s ToxCast program [30], and the affiliated multi-agency Tox21 program [31], are engaged in the generation and analysis of in vitro bioassay data for thousands of chemicals evaluated in hundreds of high-throughput and high-content screening (HTS and HCS) assays.”
• EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals. (2015, background): “The US EPA Toxicity Forecaster (ToxCast) and theToxicityTesting in the21stCentury (Tox21) (158, 159) are two federally funded efforts that have the potential to prioritize chemicals for potential human health effects.”