Skip Navigation

This Article
Right arrow Full Text (PDF)
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 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 HASEMAN, J. K.
Right arrow Articles by LOCKHART, A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by HASEMAN, J. K.
Right arrow Articles by LOCKHART, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1994 Oxford University Press

research-article

The Relationship between Use of the Maximum Tolerated Dose and Study Sensitivity for Detecting Rodent Carcinogenicity

JOSEPH K. HASEMAN* and ANN LOCKHART{dagger}

*Statistics and Biomathematics Branch, Division of Intramural Research, National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709 {dagger}Computer Sciences Corporation Research Triangle Park, North Carolina 27709

Received March 23, 1993; accepted October 8, 1993

The relationship between maximum tolerated dose (MTD) and study sensitivity for detecting rodent carcinogenicity was evaluated for 216 chemicals found to be carcinogens in laboratory animal studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). Approximately two-thirds of these rodent carcinogens would have been detected even without the top dose (estimated MTD), but in many of these studies, some site-specific carcinogenic effects would have been missed. Among the remaining one-third of the rodent carcinogens that required the top dose for statistical significance, approximately 80% had numerically elevated rates of the same site-specific tumors at lower doses as well. Only 13 of the NCI/NTP rodent carcinogens had increased tumor rates limited to the top dose for all sites of carcinogenicity. Alternatively, of the 838 site-specific carcinogenic effects observed in the NCI/NTP studies, 447 (53%) would have been detected even without the top dose. Of the remaining effects, 75% (294/391) showed numerically elevated site-specific tumor rates at lower doses. Our evaluation indicates that most carcinogenic effects ob served at the top dose in rodent studies are also present (with reduced incidence that might or might not be statistically significant) at the lower doses typically employed (1/2MTD, 1/4MTD).


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




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.