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By Pat Rizzuto
Jan. 7 — Federal agencies are offering toxicity test developers up to $1 million to modify high throughput screens so the tests predict the toxicity of chemical metabolites.
The Environmental Protection Agency, the National Institutes of Health's National Center for Advancing Translational Sciences (NCATS) and the National Toxicology Program, which is managed by the National Institute of Environmental Health Sciences, plan to launch a Transform Tox Testing Challenge on Jan. 8.
Under the challenge, the agencies will invite biotech and other companies, academic researchers, federal agency researchers and nongovernmental organizations to compete in a three-stage challenge (see chart).
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Participants would receive up to $1 million to modify high throughput screens so the tests predict toxicities that may result from chemical metabolites.
“Right now, we're missing a significant part of the [toxicity] picture,” Rusty Thomas, director of the EPA's National Center for Computational Toxicology, told Bloomberg BNA Jan. 7.
Most of the automated high throughput screens that researchers use to determine when a chemical activates, deactivates or perturbs cellular function analyze solely the effects of the “parent chemical” to which the cells are exposed, he said.
When chemicals are ingested or inhaled by living organisms, however, they are rapidly broken down into metabolites by the liver and through other biological processes, Thomas said.
The inability of high throughput tests to mimic the biological process and break chemicals down into their metabolites means the tests could miss perturbations that are caused by the metabolite rather than the parent chemical, he said.
If successful, the Tox Testing Challenge would improve the relevance and predictive capacities of automated tests that can quickly and simultaneously evaluate hundreds, even thousands, of chemicals.
Better tests mean researchers could “more accurately assess chemical effects and better protect human health,” the agencies said on a website announcing the testing challenge.
The participating agencies have not often run competitive challenges such as this, said Thomas, who said he has been working to develop the competition since he became the EPA center's director in September 2013.
As this is the agencies' first venture into a technology competition, Thomas said he doesn't have a sense of how many applicants they will get.
“ I would be happy if we had more than a dozen. I'd be ecstatic if we had a couple of dozen,” Thomas said.
The challenge is divided into three stages that whittle down the original participants to a single organization that could be awarded up to $400,000 to deliver a method or device that will add metabolic capacity to high throughput screens.
The three agencies haven't set a hard deadline by which participants must complete the challenge, according to Thomas.
Ideally, a solution could be found in about a year and a half, he said, but “the main goal, however, is to get a good solution.”
The three funding agencies are inviting a range of organizations to participate because potential solutions could come from many places, Thomas said.
While the competition is proceeding, the funding agencies will continue their own research to add metabolic capacity to high throughput screens, he said.
Eventually, Thomas envisions several methods or technologies being developed that can address metabolism in different stages of a chemical's absorption, metabolism and distribution through the body.
The Tox Testing Challenge is the latest development in a multiyear research effort federal agencies launched after the National Academies of Sciences, Engineering, and Medicine issued its 2007 report, Toxicity Testing in the Twenty-First Century: A Vision and a Strategy.
Since then, federal agencies and biotech companies have refined various technologies so researchers can use them to quickly and simultaneously determine the potential of chemicals, pharmaceuticals, food additives or other compounds to activate, deactivate or perturb various cellular functions.
A key example is the Tox21 program, a high-throughput robotic screening system housed at NCATS that researchers have been using to test 10,000 chemicals and pharmaceuticals (48 DEN A-14, 3/11/11).
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