SETTING SAFE ACUTE EXPOSURE LIMITS FOR HALON REPLACEMENT CHEMICALS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING

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. Link...

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Bibliographic Details
Published in:Inhalation toxicology 2000-08, Vol.12 (8), p.751-763
Main Author: Allen Vinegar, Gary W. Jepson, Mark Cisneros, Reva Rubenstein, William J. Brock
Format: Article
Language:English
Subjects:
Animals
Bromochlorofluorocarbons
Chlorofluorocarbons, Methane - pharmacokinetics
Chlorofluorocarbons, Methane - toxicity
Dogs
Epinephrine - administration & dosage
Flame Retardants - pharmacokinetics
Flame Retardants - toxicity
Fluorocarbons - pharmacokinetics
Fluorocarbons - toxicity
Heart Rate - drug effects
Humans
Hydrocarbons, Fluorinated - pharmacokinetics
Hydrocarbons, Fluorinated - pharmacology
Hydrocarbons, Fluorinated - toxicity
Hydrocarbons, Halogenated - pharmacokinetics
Hydrocarbons, Halogenated - toxicity
Inhalation Exposure
Models, Biological
Monte Carlo Method
No-Observed-Adverse-Effect Level
Solubility
Toxicity Tests, Acute
Online Access:Get full text
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Summary: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), CF3I (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
ISSN:0895-8378
1091-7691
DOI:10.1080/08958370050085174