The toxicity challenge

Current HTS assays may miss chemicals that are metabolized to a more toxic form; government agencies are encouraging solutions

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BETHESDA, Md.—The U.S. Environmental Protection Agency (EPA), the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) and the National Toxicology Program (NTP), headquartered at the National Institute of Environmental Health Sciences, have announced a new challenge that will award $1 million for ideas that help innovate advanced toxicity testing methods.
Since current high-throughput screening (HTS) assays do not fully incorporate chemical metabolism, they may miss chemicals that are metabolized to a more toxic form. Adding metabolic competence to HTS assays will help researchers more accurately assess effects of chemicals and better protect human health. That’s why the EPA, NTP and NCATS say they are eager to launch the Transform Tox Testing Challenge, which seeks to find an innovative solution to retrofit HTS assays with chemical metabolic competence and fill this critical gap in environmental science and technology.
“A principal goal is to incorporate metabolism into screening,” says Kevin Crofton, deputy director of the National Center for Computational Toxicology of the EPA, about the challenge. “We’ve gone from data on hundreds of chemicals using animals to thousands today. We lack the resources to test all chemicals so we’re using HTS. Do environmental chemicals have a target? We’re trying to identify targets ahead of time.”
Explaining the process further, Kevin Kuhn, science advisor to the chief innovation officer of the Office of Research and Development at EPA, explains the important S9 fraction, which is the product of an organ tissue homogenate used in biological assays. The S9 fraction is most frequently used in assays that measure the metabolism of drugs and other xenobiotics.
“We’re looking for better ideas for doing this,” he states.
The Transform Tox Testing Challenge is proceeding in three stages, ending April 8.
  • Stage One: Up to 10 submissions will be selected as semi-finalists and awarded a prize of $10,000 each, with an invitation to participate in Stage Two.
  • Stage Two: Up to five Stage Two participants may be selected as finalists, awarded up to $100,000 each, and invited to participate in the final stage of the competition.
  • Stage Three: This final stage will seek a commercially viable method or technology for demonstration and testing by EPA and its partners. Based on the testing and overall feasibility, one winner may be awarded up to $400,000 for delivery of a commercially viable method or device that will ultimately result in technologies that can provide metabolic competence to commonly used testing.
Out of thousands of chemicals in use today, very few have been fully evaluated for potential health effects. Scientists from EPA, NIEHS/NTP and NCATS have used HTS assays to evaluate the potential health effects of thousands of chemicals. “Your innovative idea could be used to add chemical metabolism to new and existing HTS assays as well as increase confidence in assay results,” the challenge announcement states.
The first stage of the challenge ends April 8. To register, visit for further details.

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