Advancing Chemical Testing by the Thousands

Studying thousands of chemicals at a time with the use of high-tech computer screening models and automated, often robot-assisted processes sounds like science fiction. But it’s not. EPA scientists are doing just that, leading the advancement of “high-throughput screening,” fast, efficient processes used to expose hundreds of living cells or isolated proteins to chemicals and then screen them for changes in biological activity—clues to potential adverse health effects related to chemical exposure.

This scientific advance is positioned to transform how we understand the safety of chemicals going forward. Twenty years ago, using high-throughput screening to test chemicals for potential human health risks seemed like technology that belonged in a science fiction television series rather than in real life.

Back then there were several large data gaps that would not allow us to extrapolate from the isolated biological changes we observe on a cellular level to adverse human health effects. However, through our computational toxicology (CompTox) research, which integrates, biology, biotechnology, chemistry, and computer science, that is changing. We are helping to transform the paradigm of chemical testing from one that relies almost solely on expensive and time-consuming animal testing methods to one that uses the full power of modern molecular biology and robotics.

A significant part of this effort is the Toxicity Forecaster (ToxCast), launched in 2007. ToxCast allows us to prioritize potentially toxic chemicals for more extensive testing as well as giving us the opportunity to test newer, possibly safer alternatives to existing chemicals. By 2013, we evaluated more than 2,000 chemicals from industrial and consumer products to food additives using more than 500 high-throughput screening assays.

Some recent research—published and released online by Nature Biotechnology—was conducted to evaluate whether ToxCast can be used to predict the potential toxicity of chemicals. EPA researchers analyzed the screening results generated by BioSeek, a San Francisco based company, and compared the results to known chemical information to determine if this new technology can be used to predict the potential toxicity and therapeutic effect of 776 chemicals found in pharmaceuticals, pesticides, and other commonly used consumer products.

The experiments included several chemicals we know to be toxic in order to test the accuracy and efficacy of ToxCast methods. Analysis of the data showed that the screening consistently and accurately identified those chemicals as toxic, confirming ToxCast’s ability to detect toxicity. Other examples used in the paper showed that the analysis of the screening data identified pesticides and failed pharmaceutical drugs as the most active which is to be expected since they are designed to activate biological activity. ToxCast was also able to cluster chemicals with similar biological activity together.

Our paper describes the analysis of all screening results and then compares them to animal toxicity studies and other proven toxicity information, demonstrating that these new technologies can be used to predict potential health hazards.  We can then use this information to identify how the chemicals will target exposed cells and to show the linkages between chemical interactions and important biological processes.

New chemicals are introduced on the market each day, but the rate at which we can test them using traditional methods is not sufficient. My colleagues and I are working diligently to provide safer, more efficient testing protocols to evaluate chemicals for potential adverse human health effects. These innovative testing methods are no longer a work of science fiction.

To learn more about our recent collaboration with BioSeek and our use of BioMAP systems visit Nature Biotechnology and read our paper: Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms.

About the author:  Robert J. Kavlock, Ph.D., is the Deputy Assistant Administrator for science in EPA’s Office of Research and Development and EPA interim Science Advisor.

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