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Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling

Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and...

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Autores principales: Campbell, Jerry, Franzen, Allison, Van Landingham, Cynthia, Lumpkin, Michael, Crowell, Susan, Meredith, Clive, Loccisano, Anne, Gentry, Robinan, Clewell, Harvey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020340/
https://www.ncbi.nlm.nih.gov/pubmed/27569524
http://dx.doi.org/10.1080/08958378.2016.1214768
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author Campbell, Jerry
Franzen, Allison
Van Landingham, Cynthia
Lumpkin, Michael
Crowell, Susan
Meredith, Clive
Loccisano, Anne
Gentry, Robinan
Clewell, Harvey
author_facet Campbell, Jerry
Franzen, Allison
Van Landingham, Cynthia
Lumpkin, Michael
Crowell, Susan
Meredith, Clive
Loccisano, Anne
Gentry, Robinan
Clewell, Harvey
author_sort Campbell, Jerry
collection PubMed
description Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities.
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spelling pubmed-50203402016-09-29 Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling Campbell, Jerry Franzen, Allison Van Landingham, Cynthia Lumpkin, Michael Crowell, Susan Meredith, Clive Loccisano, Anne Gentry, Robinan Clewell, Harvey Inhal Toxicol Research Article Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. Taylor & Francis 2016-09-18 2016-08-28 /pmc/articles/PMC5020340/ /pubmed/27569524 http://dx.doi.org/10.1080/08958378.2016.1214768 Text en © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/Licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/Licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Article
Campbell, Jerry
Franzen, Allison
Van Landingham, Cynthia
Lumpkin, Michael
Crowell, Susan
Meredith, Clive
Loccisano, Anne
Gentry, Robinan
Clewell, Harvey
Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title_full Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title_fullStr Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title_full_unstemmed Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title_short Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
title_sort predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020340/
https://www.ncbi.nlm.nih.gov/pubmed/27569524
http://dx.doi.org/10.1080/08958378.2016.1214768
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