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The Future of Toxicity Testing is Here

EPA Tox21 partnership taps high-tech robots to advance toxicity testing.

Robot During Testing

Today there are around 80,000 chemicals that exist in food and consumer products, and 1,500 new synthetic chemicals are introduced into the marketplace every year. Most of these chemicals, both new and old, have not been tested for toxicological information, presenting a serious challenge to those tasked with protecting human health from potentially harmful chemical exposures.
 
EPA researchers are working to change that. They and their partners are advancing the scientific basis for hazard identification and risk assessment by helping usher in innovative new fields of study and by tapping powerful modern technologies such as super computers and other emerging technologies—including robots.

As part of the Agency’s Computational Toxicology Research Program (CompTox), EPA has partnered with the National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program, the National Institute of Health (NIH) Chemical Genomics Center, and the Food and Drug Administration (FDA) in a collaboration known as Tox21. By combining their collective expertise and pooling existing resources—including research results, funding, and testing tools—Tox21 aims to revolutionize chemical toxicity test methods by advancing high throughput, mechanism-based test methods. The partnership is ushering in the future of toxicity testing.

That’s where the robots come in.

The collaboration recently unveiled a high speed screening system that tests chemicals for harmful human health effects.  The mechanized system greatly reduces the need for lab animals in toxicity testing, working instead with 3-by-5-inch test plates that are moved precisely through a series of steps by giant yellow, constantly moving robot arms. Each plate contains 1536 small wells that can hold various living animal cells—typically skin, liver, or brain cells of rats or humans—and a  sample of a particular chemical.  

“Each one of those wells is filled with a single chemical sample that we use to expose the cells to, so in essence we have 1536 chemical toxicity tests on a single plate,” explains Dr. Robert Kavlock, Director of EPA’s National Center for Computational Toxicology. The robot uses a pin tool, which has corresponding pins for each well, in order to dispense a drop or two of the chemical being tested.  The robot’s arm then puts the tray in a digital imaging device that scans the sample for changes in the cell that could mean biological activity.

The robot receives software instructions on what types of biological activity to “look for” in the exposed cells. Positive results are flagged, triggering an alert that the computer sends to project scientists’ computers outside the 20-by-20 foot robot lab.

Scientists interpret the results so they can then identify chemicals that warrant further screening or study. Just because a chemical shows a reaction with an isolated cell (skin, liver, etc.) does not necessarily mean that it will have the same effect when interacting with a living person. To address this, Dr. Kavlock’s team at EPA is developing algorithms that predict whether a person’s organs and body as a whole will react to chemical exposure the same way their individual cells did in the preliminary tests.  

Tox21 is revolutionizing the way chemical testing is done.  Traditional toxicity testing is built on animal-based studies that require relatively large investments in time and resources, including money. In the past, EPA has had to test one chemical at a time, completing only a couple dozen assessments a year: “A single human researcher may work on ten chemicals a year, or 20," says Kavlock. "We are doing 10,000 in a week.”

Tox21’s new robot system significantly reduces the cost and duration of chemical testing, which will allow EPA to better identify potentially harmful chemicals and serve its core mission to safeguard human health and the environment. It also allows the FDA to better analyze unexpected toxicity, opening the door for better drug development.

The partnership built around Tox21 and the high-tech robot testing is also an exemplary government partnership. "You read a lot in the papers about the duplications of government," Kavlock explained in a recent New York Times article Exit EPA Disclaimer about the project. "This is the case where there's un-duplication. We are really bringing—between NIEHS, NIH Genomics Center and EPA—a really significant complementary expertise."      

Tox21’s robot system is now testing chemicals found in industrial and consumer products, food additives and drugs, for evidence they might lead to adverse health effects.  The end goal is to create a comprehensive database detailing tested chemicals with particular emphasis on toxic and harmful ones.  Thanks to the Tox21 collaboration and its new robot technology, the future of toxicity testing—and the protection of human health—is now.

 

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