To fulfill its mission to protect human health and the environment, EPA must evaluate the risks of adverse health effects resulting from exposure to chemicals in the environment. The traditional risk assessment approach relies heavily on data generated through the intentional dosing of experimental animals. While this approach has provided EPA with sound science to support regulatory decision making over the past several decades, EPA must address ever-increasing demands, including consideration of complex issues such as cumulative exposures, life-stage vulnerabilities, and genetic susceptibilities, not to mention the increasing number of chemicals and cost of toxicity testing. A new approach is proposed to address these demands, an approach based on the application of advances in molecular biology and computational sciences to transform toxicity testing and risk assessment practices. EPA recently took the lead in commissioning the National Research Council (NRC) of the National Academies to develop a long-range vision for toxicity testing and risk assessment. Their 2007 report, Toxicity Testing in the 21st Century: a Vision and a Strategy, envisions a landmark transformation that focuses on identifying and evaluating 'toxicity pathways,' i.e., cellular response pathways responsible for adverse health effects when sufficiently perturbed by environmental agents under realistic exposure conditions. To build upon the transformative changes advocated in the NRC document, while ensuring an internally coordinated and integrated approach, EPA established a cross-Agency workgroup under the auspices of its internal Science Policy Council. This workgroup produced this report that provides a framework for EPA to comprehensively move forward to incorporate this new scientific paradigm into future toxicity testing and risk assessment practices.

"March 2009." "EPA 100/K-09/001." Includes bibliographical references.