Powered by OpenAIRE graph
Found an issue? Give us feedback
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Fundamental and Appl...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Fundamental and Applied Toxicology
Article . 1985 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
Toxicological Sciences
Article . 1985 . Peer-reviewed
Data sources: Crossref
versions View all 3 versions
addClaim

Issues in Carcinogenicity Testing: Dose Selection

Authors: J K, Haseman;

Issues in Carcinogenicity Testing: Dose Selection

Abstract

Dose selection in testing chemicals for possible carcinogenicity in rodents continues to be an area of scientific debate. In this paper the definition of "maximum tolerated dose" (MTD) is considered, and the advantages and disadvantages of using MTDs are given. There is no universally accepted definition of an MTD, and as a result, objections to utilizing high doses in carcinogenicity testing may reflect differing definitions of an MTD rather than basic disagreements in dose selection philosophy. Data from 52 National Toxicology Program (NTP) carcinogenicity studies indicate that while dose selection has caused difficulties in certain studies using the gavage route of chemical administration, there is little evidence that this has been a problem in NTP studies using the dietary (feed) route of exposure. These data also indicate that more than two-thirds of the carcinogenic effects detected in feeding studies would have been missed had the high dose been reduced from the estimated MTD to 1/2 MTD. The inherent insensitivity of laboratory animal studies for detecting weak-to-moderate carcinogenic responses also argues against reducing the highest dose level. The addition of a third, lower-dosed group provides for a margin of safety against the possibility of over-estimating the MTD. Primary emphasis should be given to improving procedures for estimating the MTD, particularly for gavage studies. Efforts should also be increased to obtain pharmacokinetic and metabolism data for the test chemical that might be factored into the dose selection and study evaluation processes.

Keywords

Dose-Response Relationship, Drug, Body Weight, Drug Tolerance, Neoplasms, Experimental, Toxicology, United States, Diet, Rats, Mice, Carcinogens, Animals

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    106
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
Found an issue? Give us feedback
selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
106
Top 10%
Top 1%
Top 10%
Upload OA version
Are you the author of this publication? Upload your Open Access version to Zenodo!
It’s fast and easy, just two clicks!