title: Physiologically based pharmacokinetic modeling of POPs in Greenlanders.
abstract: 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 (18-35years) 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.
authors.affiliation: Department of Bioscience, Arctic Research Centre, Aarhus University, Denmark. Electronic address: csh@dmu.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Sonne
authors.affiliation: Department of Bioscience, Arctic Research Centre, Aarhus University, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Gustavson
authors.affiliation: Department of Bioscience, Arctic Research Centre, Aarhus University, Denmark.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Rigét
authors.affiliation: Department of Bioscience, Arctic Research Centre, Aarhus University, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Dietz
authors.affiliation: Department of Public Health, Centre for Arctic Health, Aarhus University, Denmark.
authors.forename: Tanja
authors.initials: T
authors.lastname: Krüger
authors.affiliation: Department of Public Health, Centre for Arctic Health, Aarhus University, Denmark.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D004032:Diet; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006116:Greenland; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D011078:Polychlorinated Biphenyls; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: DDE; Greenland; HCB; Humans; Oxychlordane; PBPK modeling