The U.S. “Tox21 community” and the future of toxicology testing

In early 2008, the National Institute of environmental Health Sciences/National toxicology Program, the NIH Chemical Genomics Center, and the environmental Protection Agency’s National Center for Computational toxicology entered into a Memorandum of Understanding to collaborate on the research, development, validation and translation of new and innovative test methods that characterize key steps in toxicity pathways. A central component is the exploration of high throughput screening assays and tests using phylogenetically lower animal species (e.g. fish, worms), as well as high throughput whole genome analytical methods, to evaluate mechanisms of toxicity. the goals of the “tox21 Community” are to investigate the use of these new tools to (1) prioritize substances for further indepth toxicological evaluation, (2) identify mechanisms of action for further investigation, and (3) develop predictive models for in vivo biological response. Success is expected to result in test methods for toxicity testing that are more mechanistically based and economically efficient; as a consequence, a reduction or replacement of animals in regulatory testing is anticipated to occur in parallel with an increased ability to evaluate the large numbers of chemicals that currently lack adequate toxicological evaluation. the initial focus of this collaboration has been on identifying toxicity-related pathways (and assays for those pathways), establishing a Tox21 library of ~10,000 compounds, and developing the databases and bioinformatic tools needed to mine the resulting data. this presentation will summarize the coordinated approaches being taken to achieve our goals, the lessons learned, and expectations for the future. The U.S. “Tox21 community” and the future of toxicology testing R. Tice 1, R. Kavlock 2 and C. Austin 3 1U.S. National Institute Of Environmental Health Sciences/National Toxicology Program, Research Triangle Park, USA; 2U.S. Environmental Protection Agency, Research Triangle Park, USA; 3U.S. National Institutes of Health Chemical Genomics Center, Rockville, USA