Evaluating the human relevance of chemically induced animal tumors

Samuel M. Cohen, James Klaunig, M. Elizabeth Meek, Richard N. Hill, Timothy Pastoor, Lois Lehman-McKeeman, John Bucher, David G. Longfellow, Jennifer Seed, Vicki Dellarco, Penelope Fenner-Crisp, Dorothy Patton

Research output: Contribution to journalArticle

122 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalToxicological Sciences
Volume78
Issue number2
DOIs
StatePublished - Apr 2004

Keywords

  • Carcinogenic mode of action
  • Human relevance of animal tumors
  • PPARα agonists
  • Risk assessment

ASJC Scopus subject areas

  • Toxicology

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    Cohen, S. M., Klaunig, J., Meek, M. E., Hill, R. N., Pastoor, T., Lehman-McKeeman, L., Bucher, J., Longfellow, D. G., Seed, J., Dellarco, V., Fenner-Crisp, P., & Patton, D. (2004). Evaluating the human relevance of chemically induced animal tumors. Toxicological Sciences, 78(2), 181-186. https://doi.org/10.1093/toxsci/kfh073