Linked Life Data

1471221

Source:http://linkedlifedata.com/resource/pubmed/id/1471221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1993-1-25
pubmed:abstractText
Because of the expense involved in conducting chronic studies, limited numbers of animals and dose groups are used. This has given rise to the practice of including as one of the dose groups the "Maximum Tolerated Dose" (MTD). This dose is operationally defined as the highest dose which can be administered to animals without adversely affecting their survival through effects other than cancer. Since many detoxification systems in animals are capacity-limited, they frequently become saturated in MTD studies. This may lead to difficulties in interpreting the results of MTD studies, particularly when it is necessary to estimate the hazard for human populations whose exposure is typically much lower than the MTD. For this reason, it is important to characterize the dose-dependency of absorption, distribution, metabolism, and elimination (pharmacokinetics) of test substances prior to the initiation of a chronic study. This provides a basis for determining the number and spacing of doses to be used in a chronic study. If the appropriate information is collected it may also be possible to develop a physiologically based pharmacokinetic model which facilitates extrapolation of the toxicity results between different species and routes of administration as well as between high and low doses. For instance, methylene chloride and vinyl chloride are predominantly metabolized by saturable oxidative pathway(s) at low exposure concentrations. In each case, the oxidative pathway saturates at exposures much lower than the MTD. Knowledge of the pharmacokinetic behavior of these substances provided a basis for appropriately interpreting the chronic studies which have been conducted with these materials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:volume
64-65 Spec No
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
669-76
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Dose-dependent metabolism and dose setting in chronic studies.
pubmed:affiliation
Dow Chemical Company, Toxicology Research Laboratory, Midland, MI 48674.
pubmed:publicationType
Journal Article, Review