Evaluating the Human Relevance of Chemically Induced Animal Tumors

Authors

Samuel M. Cohen, University of Nebraska Medical Center, Omaha, NebraskaFollow
James Klaunig, Indiana University School of Medicine, Indianapolis, Indiana
M. Elizabeth Meek, Health Canada, Ottawa, Ontario K1A 0L2 Canada
Richard N. Hill, U.S. Environmental Protection Agency, Washington, District of Columbia 20460
Timothy Pastoor, Syngenta Crop Protection, Greensboro, North Carolina
Lois Lehman-McKeeman, Bristol-Myers-Squibb Company, Princeton, New Jersey
John Bucher, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
David G. Longfellow, National Cancer Institute, National Institutes of Health, Rockville, Maryland
Jennifer Seed, U.S. Environmental Protection Agency, Washington, District of Columbia 20460
Vicki Dellarco, U.S. Environmental Protection Agency, Washington, District of Columbia 20460
Penelope Fenner-Crisp, International Life Sciences Institute (ILSI), Washington, District of Columbia
Dorothy Patton, International Life Sciences Institute (ILSI), Washington, District of Columbia

Document Type

Article

Date of this Version

2004

Comments

Published in TOXICOLOGICAL SCIENCES 78, 181–186 (2004).

Abstract

Defining the mode(s) of action by which chemicals induce tumors in laboratory animals has become a key to judgments about the relevance of such tumor data for human risk assessment. Frameworks for analyzing mode of action information appear in recent U.S. EPA and IPCS publications relating to cancer risk assessment. This FORUM paper emphasizes that mode of action analytical frameworks depend on both qualitative and quantitative evaluations of relevant data and information: (1) presenting key events in the animal mode of action, (2) developing a “concordance” table for side-by-side comparison of key events as defined in animal studies with comparable information from human systems, and (3) using data and information from mode of action analyses, as well as information on relative sensitivity and exposure, to make weight-of-evidence judgments about the relevance of animal tumors for human cancer assessments. The paper features a systematic analysis for using mode of action information from animal and human studies, based in part on case examples involving environmental chemicals and pharmaceuticals.