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Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment

Recently, a variety of physiologically based pharmacokinetic (PBPK) models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal...

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Autores principales: Taylor, Michael D., Clewell, Harvey J., Andersen, Melvin E., Schroeter, Jeffry D., Yoon, Miyoung, Keene, Athena M., Dorman, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356703/
https://www.ncbi.nlm.nih.gov/pubmed/22645610
http://dx.doi.org/10.1155/2012/791431
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author Taylor, Michael D.
Clewell, Harvey J.
Andersen, Melvin E.
Schroeter, Jeffry D.
Yoon, Miyoung
Keene, Athena M.
Dorman, David C.
author_facet Taylor, Michael D.
Clewell, Harvey J.
Andersen, Melvin E.
Schroeter, Jeffry D.
Yoon, Miyoung
Keene, Athena M.
Dorman, David C.
author_sort Taylor, Michael D.
collection PubMed
description Recently, a variety of physiologically based pharmacokinetic (PBPK) models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal humans) and relevant risk assessment applications. Each PBPK model incorporates critical features including dose-dependent saturable tissue capacities and asymmetrical diffusional flux of manganese into brain and other tissues. Varied influx and efflux diffusion rate and binding constants for different brain regions account for the differential increases in regional brain manganese concentrations observed experimentally. We also present novel PBPK simulations to predict manganese tissue concentrations in fetal, neonatal, pregnant, or aged individuals, as well as individuals with liver disease or chronic manganese inhalation. The results of these simulations could help guide risk assessors in the application of uncertainty factors as they establish exposure guidelines for the general public or workers.
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spelling pubmed-33567032012-05-29 Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment Taylor, Michael D. Clewell, Harvey J. Andersen, Melvin E. Schroeter, Jeffry D. Yoon, Miyoung Keene, Athena M. Dorman, David C. J Toxicol Research Article Recently, a variety of physiologically based pharmacokinetic (PBPK) models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal humans) and relevant risk assessment applications. Each PBPK model incorporates critical features including dose-dependent saturable tissue capacities and asymmetrical diffusional flux of manganese into brain and other tissues. Varied influx and efflux diffusion rate and binding constants for different brain regions account for the differential increases in regional brain manganese concentrations observed experimentally. We also present novel PBPK simulations to predict manganese tissue concentrations in fetal, neonatal, pregnant, or aged individuals, as well as individuals with liver disease or chronic manganese inhalation. The results of these simulations could help guide risk assessors in the application of uncertainty factors as they establish exposure guidelines for the general public or workers. Hindawi Publishing Corporation 2012 2012-05-07 /pmc/articles/PMC3356703/ /pubmed/22645610 http://dx.doi.org/10.1155/2012/791431 Text en Copyright © 2012 Michael D. Taylor et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Taylor, Michael D.
Clewell, Harvey J.
Andersen, Melvin E.
Schroeter, Jeffry D.
Yoon, Miyoung
Keene, Athena M.
Dorman, David C.
Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title_full Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title_fullStr Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title_full_unstemmed Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title_short Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment
title_sort update on a pharmacokinetic-centric alternative tier ii program for mmt—part ii: physiologically based pharmacokinetic modeling and manganese risk assessment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356703/
https://www.ncbi.nlm.nih.gov/pubmed/22645610
http://dx.doi.org/10.1155/2012/791431
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