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Citation
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HERO ID
41977
Reference Type
Journal Article
Title
Physiologically-based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans
Author(s)
Corley, RA; Bormett, GA; Ghanayem, BI
Year
1994
Is Peer Reviewed?
1
Journal
Toxicology and Applied Pharmacology
ISSN:
0041-008X
EISSN:
1096-0333
Volume
129
Issue
1
Page Numbers
61-79
Language
English
PMID
7974497
DOI
10.1006/taap.1994.1229
Web of Science Id
WOS:A1994PQ82200008
Abstract
A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans. A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid. Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol. It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data. While the model predicted that rats metabolize 2-butoxyethanol and eliminate the acid metabolite faster per kilogram body weight than humans, the balance of these two processes in addition to physiological differences between species resulted in higher predicted peak blood concentrations as well as total areas under the blood concentration time curves for 2-butoxyacetic acid for rats versus humans. These species differences in kinetics coupled with the fact that human blood is significantly less susceptible than rat blood to the hemolytic effects of 2-butoxyacetic acid indicate that there is considerably less risk for hemolysis in humans as a result of exposure to 2-butoxyethanol than would have been predicted solely from standard toxicity studies with rats.
Keywords
Administration, Cutaneous; Administration, Inhalation; Administration, Oral; Animals; Body Weight/drug effects/physiology; Computer Simulation; Ethylene Glycols/administration & dosage/blood/pharmacokinetics/urine; Glycolates/administration & dosage/blood/pharmacokinetics/urine; Hemolysis/drug effects; Humans; Infusions, Intravenous; Kidney/metabolism; Liver/metabolism; Male; Models, Biological; Rats; Rats, Inbred F344; Solubility; Species Specificity; Tissue Distribution/physiology; 0 (Ethylene Glycols); 0 (Glycolates); 111-76-2 (n-butoxyethanol); 2516-93-0 (n-butoxyacetic acid)
Tags
IRIS
•
Chloroform Combined (current)
•
Methanol (Non-Cancer)
Cited in Final (2013)
Cited in External Review Draft (2013)
Cited in External Review Draft (2011)
PBPK
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