Skip Navigation



ToxSci Advance Access published online on January 21, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh073
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
78/2/181    most recent
kfh073v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Cohen, S. M.
Right arrow Articles by Patton, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cohen, S. M.
Right arrow Articles by Patton, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received December 23, 2003; accepted December 31, 2003
© 2004 Society of Toxicology

Forum

Evaluating the Human Relevance of Chemically-Induced Animal Tumors

Samuel M. Cohen 1*, James Klaunig 2, M. Elizabeth Meek 3, Richard N. Hill 4, Timothy Pastoor 5, Lois Lehman-McKeeman 6, John Bucher 7, David G. Longfellow 8, Jennifer Seed 4, Vicki Dellarco 4, Penelope Fenner-Crisp 9, and Dorothy Patton 9

1 Chair of ILSI RSI Steering Committee, University of Nebraska Medical Center, Omaha, Nebraska 68198-3135
2 Indiana University School of Medicine, Indianapolis, Indiana 46202-5120
3 Health Canada, Ottawa, Ontario K1A 0L2 Canada
4 U.S. Environmental Protection Agency, Washington, DC 20460
5 Syngenta Crop Protection, Greensboro, North Carolina 27419-8300
6 Bristol-Myers-Squibb Company, Princeton, New Jersey 08543
7 National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709
8 National Cancer Institute, National Institutes of Health, Rockville, MD 20892-7638
9 International Life Sciences Institute (ILSI), One Thomas Circle, Suite 900, Washington, DC 20005

* To whom correspondence should be addressed. E-mail: scohen{at}unmc.edu.


  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.

Key Words: carcinogenic mode of action, human relevance of animal tumors, risk assessment, PPAR{alpha} agonists .


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J PsychopharmacolHome page
P. W. Harvey, D. J. Everett, and C. J. Springall
Adverse effects of prolactin in rodents and humans: breast and prostate cancer.
J Psychopharmacol, March 1, 2008; 22(2 Suppl): 20 - 27.
[Abstract] [PDF]

Home page
 Toxicol PatholHome page
J. W. Allen, D. C. Wolf, M. H. George, S. D. Hester, G. Sun, S.-F. Thai, D. A. Delker, T. Moore, C. Jones, G. Nelson, et al.
Toxicity Profiles in Mice Treated with Hepatotumorigenic and Non-Hepatotumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil
Toxicol Pathol, December 1, 2006; 34(7): 853 - 862.
[Abstract] [Full Text] [PDF]

Home page
 Hum Exp ToxicolHome page
P W Harvey, D J Everett, and C J Springall
Hyperprolactinaemia as an adverse effect in regulatory and clinical toxicology: role in breast and prostate cancer
Human and Experimental Toxicology, July 1, 2006; 25(7): 395 - 404.
[Abstract] [PDF]

Home page
 Toxicol SciHome page
M. P. Holsapple, H. C. Pitot, S. H. Cohen, A. R. Boobis, J. E. Klaunig, T. Pastoor, V. L. Dellarco, and Y. P. Dragan
Mode of Action in Relevance of Rodent Liver Tumors to Human Cancer Risk
Toxicol. Sci., January 1, 2006; 89(1): 51 - 56.
[Abstract] [Full Text] [PDF]

Home page
 Hum Exp ToxicolHome page
J. M Battershill
The Multiple Chemicals and Actions Model of carcinogenesis. A possible new approach to developing prevention strategies for environmental carcinogenesis
Human and Experimental Toxicology, November 1, 2005; 24(11): 547 - 558.
[Abstract] [PDF]

Home page
 Toxicol SciHome page
T. Pastoor, P. Rose, S. Lloyd, R. Peffer, and T. Green
Case Study: Weight of Evidence Evaluation of the Human Health Relevance of Thiamethoxam-Related Mouse Liver Tumors
Toxicol. Sci., July 1, 2005; 86(1): 56 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H. Wong, L. D. Lehman-McKeeman, M. F. Grubb, S. J. Grossman, V. M. Bhaskaran, E. G. Solon, H. S. L. Shen, R. J. Gerson, B. D. Car, B. Zhao, et al.
Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats
Toxicol. Sci., April 1, 2005; 84(2): 232 - 242.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.