Summer 2007 Vol. 7 No. 2
Transforming Toxicity Testing
By countless paths, chemicals find their way into the environment -- and from there into our bodies. Farmers spray herbicides and pesticides on their fields, for example, and rain washes their residual chemicals into rivers and oceans. Chemical components of gasoline are released by car exhaust into the air we breathe. And chemicals such as flame retardants surround us in our homes and offices every day.
Tests are conducted on some of these chemicals to determine whether contact with them might be harmful to humans. These tests, many of which are overseen by the U.S. Environmental Protection Agency, inform regulations about what industrial, commercial, and agricultural chemicals should be permitted for use, and at what concentrations.
The tests are typically conducted by administering large doses to groups of animals and watching them for obvious symptoms of disease. But how relevant these experiments are for humans, who are usually exposed to far lower doses, has often been called into question. And this process is time-consuming and costly, leaving the testing system overburdened and many chemicals unexamined -- despite potential human exposure to them.
Recognizing the limitations of the current system, EPA asked the National Research Council to develop a new vision and strategy for toxicity testing.
Instead of relying so heavily on animal testing, the new report says, EPA should move in the direction of using "in vitro" tests -- lab tests that use cells or cell lines to assess a chemical's potential effects. The new approach would take advantage of evolving scientific understanding of how genes, proteins, and molecules interact to maintain normal cell function, and how some of these interactions can be altered in ways that could lead to health problems.
The new testing approach would focus on toxicity pathways -- cellular response pathways that, when sufficiently disrupted, are expected to lead to adverse health effects. The report recommends the use of "high-throughput" tests -- rapid, automated experiments that can test hundreds or thousands of chemicals over a wide range of concentrations -- to evaluate how a chemical affects these pathways. On the basis of data from these and other experiments, researchers can develop models to estimate the level of exposure needed to trigger a response in humans.
The new approach would generate data more relevant to humans and reduce the time and money needed for testing, the report says. Moreover, the need for animal testing could be greatly reduced over time, and possibly even eliminated someday. For the foreseeable future, however, targeted tests in animals should be used to complement the in vitro tests, because current methods cannot yet adequately mirror the metabolism of a whole animal.
Studies observing human populations will be needed to provide information on human susceptibility and "background" exposures to chemicals that people face every day, so that results of the in vitro tests can be properly interpreted. In addition, the data can be used to select appropriate doses for toxicity testing, based on realistic exposures. These studies may also reveal health risks not previously identified through toxicity testing.
A substantial research initiative will be needed to develop the new approach's components and confirm their effectiveness, the report says. It adds that creating a core institution that can foster and organize multidisciplinary research will be key to the effort's success.
Given how long current toxicity-testing practices have been established, and how deeply ingrained they are in some sectors, the new approach might encounter some resistance, the report acknowledges. But it emphasizes that the proposed changes will generate better data on the risks humans face from chemicals, which in turn will improve regulatory decisions to mitigate those risks. -- Sara Frueh
Toxicity Testing in the 21st Century: A Vision and a Strategy.Committee on Toxicity Testing and Assessment of Environmental Agents, Board on Environmental Studies and Toxicology and Institute for Laboratory Animal Research, Division on Earth and Life Studies (2007, approx. 146 pp.; ISBN 0-309-10992-2; available from the National Academies Press, tel. 1-800-624-6242; $35.00 plus $4.50 shipping for single copies).
The committee was chaired by Daniel Krewski, professor of epidemiology and community medicine at the University of Ottawa. The study was funded by the U.S. Environmental Protection Agency.