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Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations

BACKGROUND: Multiple epidemiological studies exist for some of the well-studied health endpoints associated with inorganic arsenic (iAs) exposure; however, results are usually expressed in terms of different exposure/dose metrics. Physiologically based pharmacokinetic (PBPK) models may be used to ob...

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Autores principales: El-Masri, Hisham A., Hong, Tao, Henning, Cara, Mendez, William, Hudgens, Edward E., Thomas, David J., Lee, Janice S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Environmental Health Perspectives 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108830/
https://www.ncbi.nlm.nih.gov/pubmed/30024383
http://dx.doi.org/10.1289/EHP3096
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author El-Masri, Hisham A.
Hong, Tao
Henning, Cara
Mendez, William
Hudgens, Edward E.
Thomas, David J.
Lee, Janice S.
author_facet El-Masri, Hisham A.
Hong, Tao
Henning, Cara
Mendez, William
Hudgens, Edward E.
Thomas, David J.
Lee, Janice S.
author_sort El-Masri, Hisham A.
collection PubMed
description BACKGROUND: Multiple epidemiological studies exist for some of the well-studied health endpoints associated with inorganic arsenic (iAs) exposure; however, results are usually expressed in terms of different exposure/dose metrics. Physiologically based pharmacokinetic (PBPK) models may be used to obtain a common exposure metric for application in dose–response meta-analysis. OBJECTIVE: A previously published PBPK model for inorganic arsenic (iAs) was evaluated using data sets for arsenic-exposed populations from Bangladesh and the United States. METHODS: The first data set was provided by the Health Effects of Arsenic Longitudinal Study cohort in Bangladesh. The second data set was provided by a study conducted in Churchill County, Nevada, USA. The PBPK model consisted of submodels describing the absorption, distribution, metabolism and excretion (ADME) of iAs and its metabolites monomethylarsenic (MMA) and dimethylarsenic (DMA) acids. The model was used to estimate total arsenic levels in urine in response to oral ingestion of iAs. To compare predictions of the PBPK model against observations, urinary arsenic concentration and creatinine-adjusted urinary arsenic concentration were simulated. As part of the evaluation, both water and dietary intakes of arsenic were estimated and used to generate the associated urine concentrations of the chemical in exposed populations. RESULTS: When arsenic intake from water alone was considered, the results of the PBPK model underpredicted urinary arsenic concentrations for individuals with low levels of arsenic in drinking water and slightly overpredicted urinary arsenic concentrations in individuals with higher levels of arsenic in drinking water. When population-specific estimates of dietary intakes of iAs were included in exposures, the predictive value of the PBPK model was markedly improved, particularly at lower levels of arsenic intake. CONCLUSIONS: Evaluations of this PBPK model illustrate its adequacy and usefulness for oral exposure reconstructions in human health risk assessment, particularly in individuals who are exposed to relatively low levels of arsenic in water or food. https://doi.org/10.1289/EHP3096
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spelling pubmed-61088302018-08-28 Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations El-Masri, Hisham A. Hong, Tao Henning, Cara Mendez, William Hudgens, Edward E. Thomas, David J. Lee, Janice S. Environ Health Perspect Research BACKGROUND: Multiple epidemiological studies exist for some of the well-studied health endpoints associated with inorganic arsenic (iAs) exposure; however, results are usually expressed in terms of different exposure/dose metrics. Physiologically based pharmacokinetic (PBPK) models may be used to obtain a common exposure metric for application in dose–response meta-analysis. OBJECTIVE: A previously published PBPK model for inorganic arsenic (iAs) was evaluated using data sets for arsenic-exposed populations from Bangladesh and the United States. METHODS: The first data set was provided by the Health Effects of Arsenic Longitudinal Study cohort in Bangladesh. The second data set was provided by a study conducted in Churchill County, Nevada, USA. The PBPK model consisted of submodels describing the absorption, distribution, metabolism and excretion (ADME) of iAs and its metabolites monomethylarsenic (MMA) and dimethylarsenic (DMA) acids. The model was used to estimate total arsenic levels in urine in response to oral ingestion of iAs. To compare predictions of the PBPK model against observations, urinary arsenic concentration and creatinine-adjusted urinary arsenic concentration were simulated. As part of the evaluation, both water and dietary intakes of arsenic were estimated and used to generate the associated urine concentrations of the chemical in exposed populations. RESULTS: When arsenic intake from water alone was considered, the results of the PBPK model underpredicted urinary arsenic concentrations for individuals with low levels of arsenic in drinking water and slightly overpredicted urinary arsenic concentrations in individuals with higher levels of arsenic in drinking water. When population-specific estimates of dietary intakes of iAs were included in exposures, the predictive value of the PBPK model was markedly improved, particularly at lower levels of arsenic intake. CONCLUSIONS: Evaluations of this PBPK model illustrate its adequacy and usefulness for oral exposure reconstructions in human health risk assessment, particularly in individuals who are exposed to relatively low levels of arsenic in water or food. https://doi.org/10.1289/EHP3096 Environmental Health Perspectives 2018-07-16 /pmc/articles/PMC6108830/ /pubmed/30024383 http://dx.doi.org/10.1289/EHP3096 Text en EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
spellingShingle Research
El-Masri, Hisham A.
Hong, Tao
Henning, Cara
Mendez, William
Hudgens, Edward E.
Thomas, David J.
Lee, Janice S.
Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title_full Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title_fullStr Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title_full_unstemmed Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title_short Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations
title_sort evaluation of a physiologically based pharmacokinetic (pbpk) model for inorganic arsenic exposure using data from two diverse human populations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108830/
https://www.ncbi.nlm.nih.gov/pubmed/30024383
http://dx.doi.org/10.1289/EHP3096
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