In an article published in the scientific journal Environmental Health Perspectives (EHP), Kellyn Betts, journalist for EHP and Environmental Science & Technology, summarizes the advances and obstacles of Phase I of the Tox21 project. Tox21 was initiated by a collaboration of U.S. federal agencies in 2005 to explore the possibility of a high-throughput screening (HTS) program for chemicals using mainly cell-based and biochemical in vitro tests. In Phase I, 2800 compounds were tested, a fraction of the number of chemicals on the market that will eventually require screening. Problems identified in the first phase include the limitation of tests to one or two measurable responses, the instability of purchased compounds during storage and use, and carry-over contamination. The ongoing Phase II attempts to resolve these issues by developing tests able to measure hundreds of thousands of signals, and analyzing test chemicals for identity, purity and stability. Carry-over contamination will be addressed by screening compounds multiple times in different locations of the test run. It is important that Phase II also improves the ability of tests to mimic metabolic processes, in order to account for metabolic intermediates more toxic than the original compounds. Raymond Tice, chief of the Biomolecular Screening Branch of the National Institute of Environmental Health Sciences’ (NIEHS) National Toxicology Program (NTP) Division and lead author of the peer-reviewed study on Phase I of Tox 21 published in EHP on June 1, 2013, concludes that there are still many obstacles, but data and information of Tox21 are nevertheless “foretelling the future of toxicology”.

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EHP – Tox21 to Date