ToxSci Advance Access published online on December 12, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn255
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Toxicity Testing in the 21st Century: Bringing the Vision to Life*
The Hamner Institutes for Health Sciences Research Triangle Park, NC USA 27709
University of Ottawa Ottawa, ON Canada K1N 6N5
Correspondence to: Melvin E. Andersen, PhD, CIH, DABT, FATS, Director, Computational Biology Division, The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, Tel: 919-558-1205; Fax: 919-558-1300, e-mail: MAndersen{at}TheHamner.org
Received July 3, 2008; revision received October 8, 2008; accepted November 6, 2008
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Abstract |
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In 2007, the US National Academy of Sciences released a report, Toxicity Testing in the 21st Century: A Vision and a Strategy, that envisions a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays using high throughput tests, implemented with robotic assistance. Risk assessment based on results of these types of tests would shift towards the avoidance of significant perturbations of these pathways in exposed human populations. Dose response modeling of perturbations of pathway function would be organized around computational systems biology models of the circuitry underlying each toxicity pathway. In vitro to in vivo extrapolations would rely on pharmacokinetic models to predict human blood and tissue concentrations under specific exposure conditions. All of the scientific tools needed to affect these changes in toxicity testing practices are either currently available or in an advanced state of development. A broad scientific discussion of this new vision for the future of toxicity testing is needed to motivate a departure from the traditional high dose animal-based toxicological tests, with its attendant challenges for dose and species extrapolation, towards a new approach more firmly grounded in human biology. The present paper, and invited commentaries on the report that will appear in Toxicological Sciences over the next year, are intended to initiate a dialog to identify challenges in implementing the vision and address obstacles to change.
* This contribution describes a new vision for toxicity texting with environmental agents as outlined in a National Academy of Sciences report, Toxicity Testing in the 21st Century: A Vision and A Strategy. The report was released in June 2007, representing the work of a committee of 22 individuals: Daniel Krewski (Chair), Daniel Acosta, Jr., Melvin Andersen, Henry Anderson, John Bailar III, Kim Boekelheide, Robert Brent, Gail Charnley, Vivian Cheung, Sidney Green, Karl Kelsey, Nancy Kerkvliet, Abby Li, Lawrence McCray, Otto Meyer, D. Reid Patterson, William Pennie, Robert Scala, Gina Solomon, Martin Stephens, James Yager, Jr., and Lauren Zeise. The NRC project director was Ellen Mantus. The full report is available online from the National Academy Press at www.nas.edu. This perspective reflects the views of two of the committee members on the future of toxicity testing, and has not been reviewed by the full committee. The views of the authors have been refined since the publication of the NRC report through a series of over 25 presentations at scientific forums in North America and Europe, as well as direct feedback from various stakeholders.
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