The Tox21 robotic platform for the assessment of environmental chemicals – from vision to reality

•The Tox21 effort is to advance in vitro toxicological testing in the 21st century.•Tox21 chemical library contains approximately 10,000 environmental chemicals.•A battery of in vitro assays will be validated and screened in a qHTS platform.•Tox21 robotic system is capable of screening the Tox21 chemical library in triplicates in a week.

Since its establishment in 2008, the US Tox21 inter-agency collaboration has made great progress in developing and evaluating cellular models for the evaluation of environmental chemicals as a proof of principle. Currently, the program has entered its production phase (Tox21 Phase II) focusing initially on the areas of modulation of nuclear receptors and stress response pathways. During Tox21 Phase II, the set of chemicals to be tested has been expanded to nearly 10,000 (10K) compounds and a fully automated screening platform has been implemented. The Tox21 robotic system combined with informatics efforts is capable of screening and profiling the collection of 10K environmental chemicals in triplicate in a week. In this article, we describe the Tox21 screening process, compound library preparation, data processing, and robotic system validation.