Friday, February 15, 2008

Improving Toxicity Tests

A new initiative will work on cell-based toxicity tests for chemicals.

By Anna Davison

Credit: Technology Review

As chemical companies develop more pesticides, cleaners, and other potentially toxic compounds, traditional methods of safety testing can hardly keep up. Animal tests, which have been the gold standard for decades, are slow and expensive, and these sorts of tests are increasingly socially unacceptable, too. What's more, the results of animal testing sometimes don't translate to humans, so researchers are eager for better alternatives.

This week, at the annual meeting of the American Association for the Advancement of Science in Boston, the U.S. Environmental Protection Agency and the National Institutes of Health (NIH) announced a multiyear research partnership to develop a cell-based approach that they hope can replace animal testing in toxicity screening. Work has already begun, although it will take years to refine the techniques.

Using systems that are already employed in the search for new drugs, researchers hope to develop quick, accurate methods of toxicity testing for chemicals that are carried out on cells, rather than on whole animals.

That way, instead of having to spend weeks dosing and dissecting roomfuls of rabbits or rats, thousands of chemicals could be tested in a matter of hours using automated systems and human cells grown in a lab. Different kinds of cells could be used as proxies for particular tissues, providing a way for researchers to test the effects of a chemical on the liver, for example, and, ultimately, to predict toxic effects.

The approach "really has the potential to revolutionize the way toxic chemicals are identified," says Francis Collins, director of the National Human Genome Research Institute. Automated cell-based tests could screen many thousands of chemicals in a single day, compared with the decades spent so far gathering detailed information on a few thousand toxic chemicals.

"We need to be able to test thousands of compounds in thousands of conditions much faster than we did before," says Elias Zerhouni, director of the NIH. The new approach repurposes a technique that's a mainstay in pharmaceutical labs, where high-throughput screening is used to help identify new drugs. Automated systems can test hundreds of thousands of candidate compounds in a single day and identify those that have any effect on cells, and hence may have therapeutic value. The aim of the toxicity-testing research is "to try to turn that around to find compounds that might be toxic," Collins says. Their effects could be assessed according to the number of cells they kill, or by using markers that indicate whether certain functions in a cell are affected.

Because high-throughput screening can handle many thousands of tests at a time, a given chemical can be tested at different concentrations and for different exposure times during a single screening process, producing comprehensive and reliable data that's "not a statistical approximation," says Christopher Austin, director of the NIH Chemical Genomics Center. "It's pharmacology."