Evaluating the human relevance of chemically induced animal tumors.
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.
Cohen
Samuel M
SM
ILSI RSI Steering Committee, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135, USA. scohen@unmc.edu
Klaunig
James
J
Meek
M Elizabeth
ME
Hill
Richard N
RN
Pastoor
Timothy
T
Lehman-McKeeman
Lois
L
Bucher
John
J
Longfellow
David G
DG
Seed
Jennifer
J
Dellarco
Vicki
V
Fenner-Crisp
Penelope
P
Patton
Dorothy
D
D000818:Animals; D000830:Animals, Laboratory; D002274:Carcinogens, Environmental / Q000145:classification / Q000633:toxicity*; D017408:Guidelines as Topic; D006801:Humans; D007390:International Agencies / Q000592:standards; D007391:International Cooperation; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000209:etiology*; D018570:Risk Assessment / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency / Q000592:standards; D015262:Xenobiotics / Q000145:classification / Q000633:toxicity*
D002274:Carcinogens, Environmental; D015262:Xenobiotics