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Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic.
Environ Res. 2015 Jul; 140:45-55.ER

Abstract

Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17<RQ<1.4), whereas PFOS was the second highest effect contributor for carcinogenic (genotoxic) effects (0.35<RQ<2.5). The results from this study corroborate and lend further support to previous assessments of the possible adverse health effects of exposure to known and measured OHCs in polar bears. We therefore suggest that Critical Daily Doses (CDD) should be investigated in "ex vivo" dose-response studies on polar bears to replace laboratory studies on rats (Rattus rattus) to reveal whether high RQs are maintained.

Authors+Show Affiliations

Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Electronic address: rdi@bios.au.dk.Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Electronic address: kig@bios.au.com.Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Electronic address: csh@bios.au.dk.Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Electronic address: jpd@bios.au.dk.Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark. Electronic address: ffr@dmu.dk.Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark.Department of Natural Resources and the Environment, University of Connecticut, Storrs, CT 06269, USA; Center for Environmental Sciences and Engineering, University of Connecticut, Storrs, CT 06269, USA. Electronic address: melissa.mckinney@uconn.edu.Ecotoxicology and Wildlife Health Division, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, Canada K1A 0H3. Electronic address: Robert.Letcher@ec.gc.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25825130

Citation

Dietz, Rune, et al. "Physiologically-based Pharmacokinetic Modelling of Immune, Reproductive and Carcinogenic Effects From Contaminant Exposure in Polar Bears (Ursus Maritimus) Across the Arctic." Environmental Research, vol. 140, 2015, pp. 45-55.
Dietz R, Gustavson K, Sonne C, et al. Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic. Environ Res. 2015;140:45-55.
Dietz, R., Gustavson, K., Sonne, C., Desforges, J. P., Rigét, F. F., Pavlova, V., McKinney, M. A., & Letcher, R. J. (2015). Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic. Environmental Research, 140, 45-55. https://doi.org/10.1016/j.envres.2015.03.011
Dietz R, et al. Physiologically-based Pharmacokinetic Modelling of Immune, Reproductive and Carcinogenic Effects From Contaminant Exposure in Polar Bears (Ursus Maritimus) Across the Arctic. Environ Res. 2015;140:45-55. PubMed PMID: 25825130.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic. AU - Dietz,Rune, AU - Gustavson,Kim, AU - Sonne,Christian, AU - Desforges,Jean-Pierre, AU - Rigét,Frank F, AU - Pavlova,Viola, AU - McKinney,Melissa A, AU - Letcher,Robert J, Y1 - 2015/03/29/ PY - 2015/02/09/received PY - 2015/03/13/revised PY - 2015/03/14/accepted PY - 2015/4/1/entrez PY - 2015/4/1/pubmed PY - 2015/9/26/medline KW - Critical body residue KW - Immune suppression KW - Organohalogen contaminants KW - PBPK modelling KW - Polar bear KW - Reproductive toxicity KW - Risk quotient SP - 45 EP - 55 JF - Environmental research JO - Environ Res VL - 140 N2 - Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17<RQ<1.4), whereas PFOS was the second highest effect contributor for carcinogenic (genotoxic) effects (0.35<RQ<2.5). The results from this study corroborate and lend further support to previous assessments of the possible adverse health effects of exposure to known and measured OHCs in polar bears. We therefore suggest that Critical Daily Doses (CDD) should be investigated in "ex vivo" dose-response studies on polar bears to replace laboratory studies on rats (Rattus rattus) to reveal whether high RQs are maintained. SN - 1096-0953 UR - https://www.unboundmedicine.com/medline/citation/25825130/Physiologically_based_pharmacokinetic_modelling_of_immune_reproductive_and_carcinogenic_effects_from_contaminant_exposure_in_polar_bears__Ursus_maritimus__across_the_Arctic_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0013-9351(15)00082-1 DB - PRIME DP - Unbound Medicine ER -