Toxicogenomics has been described as a discipline combining expertise in toxicology, genetics, molecular biology, and environmental health to elucidate the response of living organisms to stressful environments. It includes, but is not limited to, the study of how genomes respond to toxicant exposures and how genotype affects responses to toxicant exposures. As the technology rapidly develops, it is critical that scientists and the public communicate about the promises and limitations of this new field. Despite the dependence on animal models in toxicologic research for predicting human health effects in the regulatory arena, there can be important differences between how animals and humans respond to different chemicals. The Committee on Applications of Toxicogenomics to Cross-Species Extrapolation designed a workshop to consider using toxicogenomics in cross-species extrapolation from animals to humans. The workshop reflected on the promises and limitations of emerging data-rich approaches—such as genotyping (genomics), mRNA analysis (transcriptomics), protein analysis (proteomics), and metabolite analysis (metabolomics)—to inform cross-species extrapolation. Specifically, the workshop considered whether the data-rich technologies offer new ways of determining whether the effects of chemicals in test animals can be used to predict human responses.

Contents

• The National Academies
• Committee on Applications of Toxicogenomics to Cross-Species Extrapolation: A Workshop
• Committee on Emerging Issues and Data on Environmental Contaminants
• Board on Environmental Studies and Toxicology
• Board on Life Sciences
• Preface
• Summary of the Workshop
  • INTRODUCTION
  • EMERGING MOLECULAR AND COMPUTATIONAL APPROACHES FOR CROSS-SPECIES EXTRAPOLATION
  • POTENTIAL IMPLICATIONS OF GENOMICS FOR RISK ASSESSMENT
  • TECHNOLOGICAL CHALLENGES OF CROSS-SPECIES EXTRAPOLATION USING PROTEOMICS
  • MODELING GENE-EXPRESSION DATA TO PREDICT HUMAN HEPATOTOXICITY AFTER INCONSISTENT ANIMAL RESPONSES
  • USING METABOLOMICS TO EXPLORE SPECIES DIFFERENCES IN METABOLISM AND DISTRIBUTION
  • A SYSTEMS-BIOLOGY APPROACH TO CROSS-SPECIES EXTRAPOLATION
  • COMBINING TRANSCRIPTIONAL AND TOXICOLOGIC APPROACHES TO UNDERSTANDING THE BASIS OF SPECIES DIFFERENCES IN CONAZOLE CARCINOGENESIS
  • SPECIES DIFFERENCES IN RESPONSE TO PERFLUOROOCTANOIC ACID
  • SUMMARY OF ROUNDTABLE DISCUSSION
  • CONCLUSION
• References
• Appendixes
  • Appendix A WORKSHOP AGENDA
  • Appendix B BIOGRAPHICAL INFORMATION ON WORKSHOP SPEAKERS
  • Appendix C BIOGRAPHICAL INFORMATION ON WORKSHOP PLANNING COMMITTEE

This project was supported by Contract No. N01-OD-4-2139 between the National Academy of Sciences and National Institute of Environmental Health Sciences. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.