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Transatlantic cooperation to advance in vitro methods in safety science using high throughput screening technology

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Jan 21, 2014
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JRC's EURL ECVAM and NIH's NCATS meet to devise a work plan for collaboration

On Monday 14th January, representatives from the Joint Research Centre's European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and the US National Centre for Advancing Translation Sciences (NCATS) at the National Institutes of Health (NIH) met at the NCATS's site in Bethesda (MD, USA) to review progress and plan future engagement in relation to their formal Collaboration Agreement, in place since July 2012. 

The collaboration was motivated by a common goal of exploiting (ultra) High Throughput and High Content Screening (HTS/HCS) platforms based on advanced robotics and imaging technologies to advance the development, validation and utilisation of in vitro cell-based methods for the safety assessment of chemicals used in a variety of sectors. 

In particular, the collaboration is aimed in part to support Tox 21 (Toxicology in the 21st Century), a US federal collaboration involving the NIH's NCATS, the NIH's National Institutes for Environmental Health Sciences, the Environmental Protection Agency and the Food and Drug Administration, and the EU-based SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing), launched in 2011 and comprising over 70 research partners including JRC's EURL ECVAM. SEURAT-1 is a 50 million Euro 5-year initiative and is co-funded equally by the European Commission's Directorate General for Research and Innovation and Cosmetics Europe, the industry personal care association.

At the NCATS’ NIH Chemical Genomics Center (NCGC), scientists are using the center’s high-throughput screening robotic system to test the Tox21's unique library of 10,000 compounds, composed of environmental chemicals and approved drugs, in a comprehensive set of in vitro assays. Measuring the activity of a compound across a range of HTS/HCS cellular and biochemical assays can help determine its potential to disrupt biological pathways that may result in toxicity and adverse health effects in certain conditions. Although on a smaller scale, EURL ECVAM has been operating its own HTS/HSC facility for several years for the generation of toxicity data on carefully selected sets of reference chemicals to expedite the development and validation of cell-based in vitro methods that demonstrate potential for application in regulatory safety assessment.

The joint work plan foresees cooperation on using in vitro HTS/HCS methods to explore how chemicals can affect the mitochondria, the energy production components of cells, and how this may lead to adverse effects in humans, for example in the liver, heart or brain. Another area of cooperation will be in the performance assessment of HTS/HCS assays designed to indicate a chemical's potential to interact with the hormone system. Comparing results obtained from assays using different cell types and read-outs but which address similar biological effects will help identify the strengths and limitations of each method and thus facilitate its optimum use in HTS/HCS screening batteries. EURL ECVAM will also act as a European focal point to identify and evaluate novel assays being developed typically with EU research consortia that could be tailored for implementation on the NCATS HTS/HCS platforms to generate data on the 10k Tox21 library.  

Photo: Robotic platform at NCATS for ultra-high throughput in vitro toxicological screening of 10,000 chemicals in one experiment. Reproduced courtesy of NCATS.