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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| Veröffentlicht in: | Inhalation toxicology 2000-08, Vol.12 (8), p.751-763 |
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| container_title | Inhalation toxicology |
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| creator | Allen Vinegar, Gary W. Jepson, Mark Cisneros, Reva Rubenstein, William J. Brock |
| description | 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 |
| doi_str_mv | 10.1080/08958370050085174 |
| format | Article |
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Jepson, Mark Cisneros, Reva Rubenstein, William J. Brock</creatorcontrib><title>SETTING SAFE ACUTE EXPOSURE LIMITS FOR HALON REPLACEMENT CHEMICALS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING</title><title>Inhalation toxicology</title><addtitle>Inhal Toxicol</addtitle><description>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</description><subject>Animals</subject><subject>Bromochlorofluorocarbons</subject><subject>Chlorofluorocarbons, Methane - pharmacokinetics</subject><subject>Chlorofluorocarbons, Methane - toxicity</subject><subject>Dogs</subject><subject>Epinephrine - administration & dosage</subject><subject>Flame Retardants - pharmacokinetics</subject><subject>Flame Retardants - toxicity</subject><subject>Fluorocarbons - pharmacokinetics</subject><subject>Fluorocarbons - toxicity</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>Hydrocarbons, Fluorinated - pharmacokinetics</subject><subject>Hydrocarbons, Fluorinated - pharmacology</subject><subject>Hydrocarbons, Fluorinated - toxicity</subject><subject>Hydrocarbons, Halogenated - pharmacokinetics</subject><subject>Hydrocarbons, Halogenated - toxicity</subject><subject>Inhalation Exposure</subject><subject>Models, Biological</subject><subject>Monte Carlo Method</subject><subject>No-Observed-Adverse-Effect Level</subject><subject>Solubility</subject><subject>Toxicity Tests, Acute</subject><issn>0895-8378</issn><issn>1091-7691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFOq0AUhidGo7X6AHdzMyt36JnCMEOuG8SpJUJpCk10NRlgiBha6tDG-PZCrIsb4-ok__m-f3EOQn8IXBPgcAPco9xmABSAU8KcIzQi4BGLuR45RqNhb_UAP0PnXfcKAC7Y7BSd9TYHQukIvaciy8L5A079qcB-sMoEFk-LJF0tBY7COMxSPE2WeOZHyRwvxSLyAxGLeYaDmYjDwI9SvEqHgsXsOQ2TKHkYwugZ3_mpuO9Tfxn7QfIYzkUWBjhO7kXU4xfopFJNpy8Pc4xWU5EFM-tQYNW2Y-8sl_Oc5pVdUFXp3HNKxqjLXVtNGFNqQktVFUqVVUkZJSR3iVsRrhl3KIG8ZI49RldfvVvTvu11t5Pruit006iNbvednIDrsaFxjP4ewH2-1qXcmnqtzIf8PlUP3H4B9aZqzVq9t6Yp5U59NK2pjNoUdSdtAoMA8sdnev3ff_qLVs3upVBGy9d2bzb9EeTv9icdgodO</recordid><startdate>20000801</startdate><enddate>20000801</enddate><creator>Allen Vinegar, Gary W. 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Jepson, Mark Cisneros, Reva Rubenstein, William J. Brock</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Inhalation toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allen Vinegar, Gary W. Jepson, Mark Cisneros, Reva Rubenstein, William J. Brock</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SETTING SAFE ACUTE EXPOSURE LIMITS FOR HALON REPLACEMENT CHEMICALS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING</atitle><jtitle>Inhalation toxicology</jtitle><addtitle>Inhal Toxicol</addtitle><date>2000-08-01</date><risdate>2000</risdate><volume>12</volume><issue>8</issue><spage>751</spage><epage>763</epage><pages>751-763</pages><issn>0895-8378</issn><eissn>1091-7691</eissn><abstract>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</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>10880155</pmid><doi>10.1080/08958370050085174</doi><tpages>13</tpages></addata></record> |
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| source | Taylor & Francis; MEDLINE; Taylor & Francis Medical Library - CRKN |
| 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 |
| title | SETTING SAFE ACUTE EXPOSURE LIMITS FOR HALON REPLACEMENT CHEMICALS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING |
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