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Improving the Human Hazard Characterization of Chemicals: A Tox21 Update
Citation:
Tice, R., C. Austin, Robert J. Kavlock, AND J. Bucher. Improving the Human Hazard Characterization of Chemicals: A Tox21 Update. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 121:756-765, (2013).
Impact/Purpose:
There is an increasing awareness that there are thousands of chemicals to which humans are exposed that have inadequate data on potential toxicological effects. There have also been dramatic technological advances in molecular and systems biology, computational toxicology, and bioinformatics that have provided researchers and regulators with powerful new public health tools (National Research Council 2006, 2007). High content and high throughput screening techniques are now routinely used in conjunction with computational methods and information technology to probe how chemicals interact with biological systems, both in vitro and in vivo. Progress is being made in recognizing the patterns of response in genes/pathways induced by certain chemicals or chemical classes that might be predictive of adverse health outcomes in humans. However, as with any new technology, both the reliability and the relevance of the approach need to be demonstrated in the context of current knowledge and practice.
Description:
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 cur-rently being used, assess the current status, and identify problems that could impede further prog¬ress as well as suggest approaches to address those problems. Conclusion: Tox21 faces some very difficult issues. However, we are making progress in inte-grating 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.
