Document Detail

Analysis of respiratory exchange of methanol in the lung of the monkey using a physiological model.
MedLine Citation:
PMID:  10696766     Owner:  NLM     Status:  MEDLINE    
A physiologically based pharmacokinetic (PBPK) model was developed for the monkey, to account for fractional systemic uptake of inhaled methanol vapors in the lung. Fractional uptake of inhaled [14C]-methanol was estimated using unreported exhaled breath time course measurements of [14C]-methanol from the D.C. Dorman et al. (1994, Toxicol Appl Pharmacol. 128, 229-238) lung-only exposure study. The cumulative amount of [14C]-methanol exhaled was linear with respect to exposure duration (0.5 to 2 h) and concentration (10 to 900 ppm). The model estimated that forty to eighty-one percent of the of inhaled [14C]-methanol delivered to the lung was taken into systemic circulation in female Cynomolgus monkeys exposed for two h to 10-900 ppm of [14C]-methanol. There was no apparent trend between the percent of inhaled [14C]-methanol absorbed systemically and the [14C]-methanol exposure concentration. Model simulations were conducted using a single saturable Michaelis-Menten equation with Vmaxc, the metabolic capacity set to 15.54 mg/kg/h and Km, the affinity constant, to 0.66 mg/l. The [14C]-methanol blood concentrations were variable across [14C]-methanol exposure groups and the PBPK model tended to over-predict systemic clearance of [14C]-methanol. Accounting for fractional uptake of inhaled polar solvents is an important consideration for risk assessment of inhaled polar solvents.
J W Fisher; D C Dorman; M A Medinsky; F Welsch; R B Conolly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  53     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-17     Completed Date:  2000-03-17     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  185-93     Citation Subset:  IM    
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Administration, Inhalation
Linear Models
Lung / metabolism*
Macaca fascicularis*
Methanol / pharmacokinetics*
Models, Biological
Pulmonary Gas Exchange*
Solvents / pharmacokinetics*
Reg. No./Substance:
0/Solvents; 67-56-1/Methanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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