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ToxSci Advance Access published online on May 5, 2004

Toxicological Sciences, doi:10.1093/toxsci/kfh159
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received March 29, 2004
Accepted April 21, 2004

Forum

Human Carcinogenic Risk Evaluation: An Alternative Approach to the Two-Year Rodent Bioassay

Samuel M. Cohen 1*

1 Department of Pathology and Microbiology, Havlik-Wall Professor of Oncology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, Nebraska 68198-3135

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


   Abstract

An approach to the evaluation of carcinogenic risk resulting from exposure to a given chemical is presented in place of a reliance on two year rodent bioassays. An emphasis is placed on evaluation of the potential DNA reactivity or increased cell proliferation that can be produced by a chemical. The special cases of immunosuppressive and estrogenic chemicals are considered. These evaluations are proposed to involve a combination of in vitro assays, computerized models, and short term (up to 13 weeks) bioassays in rodents. The emphasis is on mechanistic understanding and evaluation of the dose response and relevance to humans.


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