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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2012/791431 |
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| author | Michael D. Taylor Harvey J. Clewell Melvin E. Andersen Jeffry D. Schroeter Miyoung Yoon Athena M. Keene David C. Dorman |
| author_facet | Michael D. Taylor Harvey J. Clewell Melvin E. Andersen Jeffry D. Schroeter Miyoung Yoon Athena M. Keene David C. Dorman |
| author_sort | Michael D. Taylor |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-01ec34325f7340a2b8792e11280c454e |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-01ec34325f7340a2b8792e11280c454e2025-02-03T06:44:41ZengWileyJournal of Toxicology1687-81911687-82052012-01-01201210.1155/2012/791431791431Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk AssessmentMichael D. Taylor0Harvey J. Clewell1Melvin E. Andersen2Jeffry D. Schroeter3Miyoung Yoon4Athena M. Keene5David C. Dorman6Health, Safety, Environment, and Security, Afton Chemical Corp., Richmond, VA 23219, USAInstitute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USAInstitute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USAInstitute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USAInstitute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USAHealth, Safety, Environment, and Security, Afton Chemical Corp., Richmond, VA 23219, USACollege of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USARecently, 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.http://dx.doi.org/10.1155/2012/791431 |
| spellingShingle | Michael D. Taylor Harvey J. Clewell Melvin E. Andersen Jeffry D. Schroeter Miyoung Yoon Athena M. Keene David C. Dorman Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment Journal of Toxicology |
| 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 |
| url | http://dx.doi.org/10.1155/2012/791431 |
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