In recent years, completion of the sequencing of the human genome as well as the genomes of dozens of other organisms and subsequent development of tools for comprehensive analysis of other cellular constituents have revolutionized biology. These new technologies, referred to broadly as “genomics,” have integrated biologic sciences with information sciences and engineering.

The application of these new technologies to toxicology has opened a new era in which genetic variation and expression signatures might be used to screen compounds for hazard identification, to assess cellular responses to different doses, to classify toxicants on the basis of mechanisms of action, to monitor exposure of individuals to toxicants, and to predict individual variability in sensitivity to toxicants. In pharmacology, these technologies have been used both to detect desired cellular responses to drugs and to monitor potential toxicity.

Although the combination of genomic technologies with toxicology has the potential to alter risk assessment by improving the predictive capabilities of toxicology for human health, it is equally clear that significant challenges remain to be overcome, and realistic limitations must be acknowledged.

An issue well highlighted by the development of toxicogenomic technologies is the wide impact of these technologies. The applications of these technologies affect two broad areas: assessment of risk from exposure to chemicals in the environment and assessment of pharmaceutical safety. The National Institutes of Health, regulatory agencies (Environmental Protection Agency, Occupational Safety and Health Administration, Food and Drug Administration), the chemical and pharmaceutical industries, health professionals, attorneys, and the entire public are affected by the applications that toxicogenomics brings to environmental health risk assessment as well as drug efficacy and toxicity.

Recognizing the challenges of dealing with these new types of scientific information, the director of the National Institute of Environmental Health Sciences (NIEHS) of the U.S. Department of Health and Human Services, Dr. Kenneth Olden, asked the National Academies in 2002 to convene a committee of experts to facilitate discussion and communication among stakeholders on technical, regulatory, and ethical issues that need to be considered when deciding how data from this rapidly evolving technology can be used most appropriately to inform public policy and promote human health. The National Academies’ standing Committee on Emerging Issues and Data on Environmental Contaminants was established to facilitate exchanges of information among the academic community, government, industry, environmental advocates, and public interest groups about these new approaches.

The Emerging Issues standing committee, chaired by David Eaton of the University of Washington and Kenneth Ramos of the University of Louisville, has held workshops to encourage discussion on a variety of topics, including toxicogenomics and bioinformatics, toxicogenomics and carcinogenic risk assessment, communicating toxicogenomic information, toxicogenomic application to cross-species extrapolation, sharing toxicogenomic data, validating toxicogenomic data, genomic signatures, toxicogenomics and early life exposures, and intellectual property concerns. These workshop discussions are briefly described in the committee’s newsletters (currently available at http://dels.nas.edu/emergingissues/newslet.shtml) and summarized in documents titled Communicating Toxicogenomics Information to Nonexperts: A Workshop Summary (http://www.nap.edu/catalog.php?record_id=11179), Toxicogenomic Technologies and Risk Assessment of Environmental Carcinogens: A Workshop Summary (http://www.nap.edu/catalog.php?record_id=11335), Application of Toxicogenomics to Cross-Species Extrapolation: A Report of a Workshop (http://www.nap.edu/catalog.php?record_id=11488), and Validation of Toxicogenomic Technologies: A Workshop Summary (http://www.nap.edu/catalog.php?record_id=11804).

The Emerging Issues standing committee was also asked to identify areas where an in-depth study from the National Research Council would be beneficial. As a result, the Emerging Issues standing committee described the need for a consensus report on the impacts of toxicogenomic technologies on predictive toxicology. Recognizing this need, in April 2004, NIEHS asked the National Academies to direct its investigative arm, the National Research Council (NRC), to examine the impacts of toxicogenomic technologies on predictive toxicology. In response, the NRC formed the Committee on Applications of Toxicogenomic Technologies for Predictive Toxicology, which authored this report. The committee has a panel of 16 members, including experts in toxicology, molecular and cellular biology, epidemiology, genetics, law and ethics, bioinformatics, statistics, medicine, and public health. The committee approached its charge by focusing on the current and potential uses of toxicogenomics in the study and risk assessment of human responses to environmental and pharmaceutical chemicals. The committee did not consider ecologic assessment within its focus.

The committee owes a great debt of gratitude to the NRC staff members who guided it through production of the final report. Marilee Shelton-Davenport, of the Board on Life Sciences (BLS); and Suzanne van Drunick, former member, and Karl Gustavson, of the Board on Environmental Studies and Toxicology (BEST), provided valuable guidance and contributions. Liza Hamilton, Morgan Motto, and Mirsada Karalic-Loncarevic, of BEST, provided excellent staff support throughout the study.

I, the NRC staff, and the committee are indebted to a number of scientists who presented background information, both orally and in writing, that made the committee’s understanding of these issues more complete. Several persons involved at the beginning of the study were Wylie Burke, Thomas Caskey, Barbara Culliton, and Rick Kittles. We also thank the external reviewers for their insightful criticisms and suggestions.

David Christiani, Chair

Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology