Physiologically based pharmacokinetic modeling of POPs in Greenlanders

Human exposure to persistent organic pollutants (POPs) and the potential health impact in the Arctic far from the emission sources have been highlighted in numerous studies. As a supplement to human POP biomonitoring studies, a physiologically based pharmacokinetic (PBPK) model was set up to estimat...

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Main Authors: Christian Sonne, Kim Gustavson, Frank F. Rigét, Rune Dietz, Tanja Krüger, Eva C. Bonefeld-Jørgensen
Format: Article
Language:English
Published: Elsevier 2014-03-01
Series:Environment International
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412013002869
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language English
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author Christian Sonne
Kim Gustavson
Frank F. Rigét
Rune Dietz
Tanja Krüger
Eva C. Bonefeld-Jørgensen
spellingShingle Christian Sonne
Kim Gustavson
Frank F. Rigét
Rune Dietz
Tanja Krüger
Eva C. Bonefeld-Jørgensen
Physiologically based pharmacokinetic modeling of POPs in Greenlanders
Environment International
author_facet Christian Sonne
Kim Gustavson
Frank F. Rigét
Rune Dietz
Tanja Krüger
Eva C. Bonefeld-Jørgensen
author_sort Christian Sonne
title Physiologically based pharmacokinetic modeling of POPs in Greenlanders
title_short Physiologically based pharmacokinetic modeling of POPs in Greenlanders
title_full Physiologically based pharmacokinetic modeling of POPs in Greenlanders
title_fullStr Physiologically based pharmacokinetic modeling of POPs in Greenlanders
title_full_unstemmed Physiologically based pharmacokinetic modeling of POPs in Greenlanders
title_sort physiologically based pharmacokinetic modeling of pops in greenlanders
publisher Elsevier
series Environment International
issn 0160-4120
publishDate 2014-03-01
description Human exposure to persistent organic pollutants (POPs) and the potential health impact in the Arctic far from the emission sources have been highlighted in numerous studies. As a supplement to human POP biomonitoring studies, a physiologically based pharmacokinetic (PBPK) model was set up to estimate the fate of POPs in Greenlandic Inuit's liver, blood, muscle and adipose tissue following long-term exposure to traditional Greenlandic diet. The PBPK model described metabolism, excretion and POP accumulation on the basis of their physicochemical properties and metabolic rates in the organisms. Basic correlations between chemically analyzed blood POP concentrations and calculated daily POP intake from food questionnaire of 118 middle age (18–35 years) Greenlandic Inuits from four cities in West Greenland (Qaanaaq: n = 40; Qeqertarsuaq: n = 36; Nuuk: n = 20; Narsaq: n = 22) taken during 2003 to 2006 were analyzed. The dietary items included were polar bear, caribou, musk oxen, several marine species such as whales, seals, bird and fish as well as imported food. The contaminant concentrations of the dietary items as well as their chemical properties, uptake, biotransformation and excretion allowed us to estimate the POP concentration in liver, blood, muscle and adipose tissue following long-term exposure to the traditional Greenlandic diet using the PBPK model. Significant correlations were found between chemically analyzed POP blood concentrations and calculated daily intake of POPs for Qeqertarsuaq, Nuuk and Narsaq Inuit but not for the northernmost settlement Qaanaaq, probably because the highest blood POP level was found in this district which might mask the interview-based POP calculations. Despite the large variation in circulating blood POP concentrations, the PBPK model predicted blood concentrations of a factor 2–3 within the actual measured values. Moreover, the PBPK model showed that estimated blood POP concentration increased significantly after consumption of meals. For individuals who had a high internal burden of POPs accumulated over years, the estimated blood levels were less influenced by recent meal intake. The model results also indicated that of the POPs accumulated in the body the concentrations were highest for CB-153 (oxychlordane: 0.6%; DDE and CB-99: 2.9%; HCB: 4.4%; CB-153: 34.5%). Furthermore, the model also estimated a significant internal body POP burden even several years after the mentioned dietetic shift and that contaminant accumulation was 2–6 folds faster than the decay after a shift to a diet low in contaminants. Using the PBPK model approach, we seek to improve the knowledge on contaminant body burden in humans of the Arctic. However, it should be noted that calculations of daily POP intake may be subject to considerable uncertainty due to imprecise information from the dietary interview. Based on these results we suggest that PBPK modeling is implemented as a tool in future human health exposure and effect assessments in Greenland. Keywords: DDE, Greenland, HCB, Humans, Oxychlordane, PBPK modeling
url http://www.sciencedirect.com/science/article/pii/S0160412013002869
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spelling doaj-504b8ca8ddba40079dc1afa8116385222020-11-25T01:38:32ZengElsevierEnvironment International0160-41202014-03-01649197Physiologically based pharmacokinetic modeling of POPs in GreenlandersChristian Sonne0Kim Gustavson1Frank F. Rigét2Rune Dietz3Tanja Krüger4Eva C. Bonefeld-Jørgensen5Department of Bioscience, Arctic Research Centre, Aarhus University, Denmark; Corresponding author at: Aarhus University, Faculty of Science and Technology, Department of Bioscience, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Tel.: +45 30 78 31 72; fax: +45 87 15 50 15.Department of Bioscience, Arctic Research Centre, Aarhus University, DenmarkDepartment of Bioscience, Arctic Research Centre, Aarhus University, DenmarkDepartment of Bioscience, Arctic Research Centre, Aarhus University, DenmarkDepartment of Public Health, Centre for Arctic Health, Aarhus University, DenmarkDepartment of Public Health, Centre for Arctic Health, Aarhus University, DenmarkHuman exposure to persistent organic pollutants (POPs) and the potential health impact in the Arctic far from the emission sources have been highlighted in numerous studies. As a supplement to human POP biomonitoring studies, a physiologically based pharmacokinetic (PBPK) model was set up to estimate the fate of POPs in Greenlandic Inuit's liver, blood, muscle and adipose tissue following long-term exposure to traditional Greenlandic diet. The PBPK model described metabolism, excretion and POP accumulation on the basis of their physicochemical properties and metabolic rates in the organisms. Basic correlations between chemically analyzed blood POP concentrations and calculated daily POP intake from food questionnaire of 118 middle age (18–35 years) Greenlandic Inuits from four cities in West Greenland (Qaanaaq: n = 40; Qeqertarsuaq: n = 36; Nuuk: n = 20; Narsaq: n = 22) taken during 2003 to 2006 were analyzed. The dietary items included were polar bear, caribou, musk oxen, several marine species such as whales, seals, bird and fish as well as imported food. The contaminant concentrations of the dietary items as well as their chemical properties, uptake, biotransformation and excretion allowed us to estimate the POP concentration in liver, blood, muscle and adipose tissue following long-term exposure to the traditional Greenlandic diet using the PBPK model. Significant correlations were found between chemically analyzed POP blood concentrations and calculated daily intake of POPs for Qeqertarsuaq, Nuuk and Narsaq Inuit but not for the northernmost settlement Qaanaaq, probably because the highest blood POP level was found in this district which might mask the interview-based POP calculations. Despite the large variation in circulating blood POP concentrations, the PBPK model predicted blood concentrations of a factor 2–3 within the actual measured values. Moreover, the PBPK model showed that estimated blood POP concentration increased significantly after consumption of meals. For individuals who had a high internal burden of POPs accumulated over years, the estimated blood levels were less influenced by recent meal intake. The model results also indicated that of the POPs accumulated in the body the concentrations were highest for CB-153 (oxychlordane: 0.6%; DDE and CB-99: 2.9%; HCB: 4.4%; CB-153: 34.5%). Furthermore, the model also estimated a significant internal body POP burden even several years after the mentioned dietetic shift and that contaminant accumulation was 2–6 folds faster than the decay after a shift to a diet low in contaminants. Using the PBPK model approach, we seek to improve the knowledge on contaminant body burden in humans of the Arctic. However, it should be noted that calculations of daily POP intake may be subject to considerable uncertainty due to imprecise information from the dietary interview. Based on these results we suggest that PBPK modeling is implemented as a tool in future human health exposure and effect assessments in Greenland. Keywords: DDE, Greenland, HCB, Humans, Oxychlordane, PBPK modelinghttp://www.sciencedirect.com/science/article/pii/S0160412013002869