Document Detail


Setting safe acute exposure limits for halon replacement chemicals using physiologically based pharmacokinetic modeling.
MedLine Citation:
PMID:  10880155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most proposed replacements for Halon 1301 as a fire suppressant are halogenated hydrocarbons. The acute toxic endpoint of concern for these agents is cardiac sensitization. An approach is described that links the cardiac endpoint as assessed in dogs to a target arterial concentration in humans. Linkage was made using a physiologically based pharmacokinetic (PBPK) model. Monte Carlo simulations, which account for population variability, were used to establish safe exposure times at different exposure concentrations for Halon 1301 (bromotrifluoromethane), CF(3)I (trifluoroiodomethane), HFC-125 (pentafluoroethane), HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (1,1,1,3,3,3-hexafluoropropane). Application of the modeling technique described here not only makes use of the conservative cardiac sensitization endpoint, but also uses an understanding of the pharmacokinetics of the chemical agents to better establish standards for safe exposure. The combined application of cardiac sensitization data and physiologically based modeling provides a quantitative approach, which can facilitate the selection and effective use of halon replacement candidates.
Authors:
A Vinegar; G W Jepson; M Cisneros; R Rubenstein; W J Brock
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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:  Inhalation toxicology     Volume:  12     ISSN:  0895-8378     ISO Abbreviation:  Inhal Toxicol     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-10-16     Completed Date:  2000-10-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8910739     Medline TA:  Inhal Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  751-63     Citation Subset:  IM    
Affiliation:
AFRL/HEST, ManTech Environmental Technology, Inc., Wright-Patterson Air Force Base, PO Box 31009, Dayton, OH 45437, USA. allen.vinegar@he.wpafb.af.mil
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MeSH Terms
Descriptor/Qualifier:
Acute Toxicity Tests
Animals
Chlorofluorocarbons, Methane / pharmacokinetics*,  toxicity
Dogs
Epinephrine / administration & dosage
Flame Retardants / pharmacokinetics*,  toxicity
Fluorocarbons / pharmacokinetics,  toxicity
Heart Rate / drug effects
Humans
Hydrocarbons, Fluorinated / pharmacokinetics,  pharmacology,  toxicity
Hydrocarbons, Halogenated / pharmacokinetics,  toxicity
Inhalation Exposure*
Models, Biological
Monte Carlo Method
No-Observed-Adverse-Effect Level
Solubility
Chemical
Reg. No./Substance:
0/Chlorofluorocarbons, Methane; 0/Flame Retardants; 0/Fluorocarbons; 0/Hydrocarbons, Fluorinated; 0/Hydrocarbons, Halogenated; 2314-97-8/trifluoroiodomethane; 354-33-6/pentafluoroethane; 431-89-0/HFA 134a; 51-43-4/Epinephrine; 690-39-1/1,1,1,3,3,3-hexafluoropropane; 75-63-8/bromotrifluoromethane

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


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