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See detailRelationships between in vitro lymphoproliferative responses and levels of contaminants in blood of free-ranging adult harbour seals (Phoca vitulina) from the North Sea
Dupont, Aurélie ULg; Siebert, Ursula; Covaci, Adrian et al

in Aquatic Toxicology (2013), 142-143

tIn vitro culture of peripheral blood leucocytes (PBLs) is currently used in toxicological studies of marinemammals. However, blood cells of wild individuals are exposed in vivo to environmental ... [more ▼]

tIn vitro culture of peripheral blood leucocytes (PBLs) is currently used in toxicological studies of marinemammals. However, blood cells of wild individuals are exposed in vivo to environmental contaminantsbefore being isolated and exposed to contaminants in vitro. The aim of this study was to highlightpotential relationships between blood contaminant levels and in vitro peripheral blood lymphocyteproliferation in free-ranging adult harbour seals (Phoca vitulina) from the North Sea. Blood samplesof 18 individuals were analyzed for trace elements (Fe, Zn, Se, Cu, Hg, Pb, Cd) and persistent organiccontaminants and metabolites ( PCBs, HO-PCBs, PBDEs, 2-MeO-BDE68 and 6-MeO-BDE47, DDXs,hexachlorobenzene, oxychlordane, trans-nonachlor, pentachlorophenol and tribromoanisole). The samesamples were used to determine the haematology profiles, cell numbers and viability, as well as thein vitro ConA-induced lymphocyte proliferation expressed as a stimulation index (SI). Correlation tests(Bravais-Pearson) and Principal Component Analysis with multiple regression revealed no statisticallysignificant relationship between the lymphocyte SI and the contaminants studied. However, the numberof lymphocytes per millilitre of whole blood appeared to be negatively correlated to pentachlorophenol(r = −0.63, p = 0.005). In adult harbour seals, the interindividual variations of in vitro lymphocyte pro-liferation did not appear to be directly linked to pollutant levels present in the blood, and it is likelythat other factors such as age, life history, or physiological parameters have an influence. In a generalmanner, experiments with in vitro immune cell cultures of wild marine mammals should be designed soas to minimize confounding factors in which case they remain a valuable tool to study pollutant effectsin vitro. [less ▲]

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See detailApplication of Bayesian Population Physiologically Based Pharmacokinetic (PBPK) Modeling and Markov Chain Monte Carlo Simulations to Pesticide Kinetics Studies in Protected Marine Mammals: DDT, DDE, and DDD in Harbor Porpoises
Weijs, Liesbeth; Yang, Raymond S.H.; Das, Krishna ULg et al

in Environmental Science & Technology (2013), 47

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and ... [more ▼]

Physiologically based pharmacokinetic (PBPK) modeling in marine mammals is a challenge because of the lack of parameter information and the ban on exposure experiments. To minimize uncertainty and variability, parameter estimation methods are required for the development of reliable PBPK models. The present study is the first to develop PBPK models for the lifetime bioaccumulation of p,p′-DDT, p,p′-DDE, and p,p′- DDD in harbor porpoises. In addition, this study is also the first to apply the Bayesian approach executed with Markov chain Monte Carlo simulations using two data sets of harbor porpoises from the Black and North Seas. Parameters from the literature were used as priors for the first “model update” using the Black Sea data set, the resulting posterior parameters were then used as priors for the second “model update” using the North Sea data set. As such, PBPK models with parameters specific for harbor porpoises could be strengthened with more robust probability distributions. As the science and biomonitoring effort progress in this area, more data sets will become available to further strengthen and update the parameters in the PBPK models for harbor porpoises as a species anywhere in the world. Further, such an approach could very well be extended to other protected marine mammals. [less ▲]

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See detailUse of Physiologically Based Pharmacokinetic (PBPK) Models in Marine Mammal Toxicology
Weijs, Liesbeth; Yang, Raymond S.H.; Das, Krishna ULg et al

in Kawaguchi, M.; Misaki, K.; Sato, H. (Eds.) et al Interdisciplinary Studies on Environmental Chemistry—Environmental Pollution and Ecotoxicology (2012)

Physiologically based pharmacokinetic (PBPK) models are mathematical models that are largely based upon the physiological characteristics of the species and the biochemical properties of the chemical of ... [more ▼]

Physiologically based pharmacokinetic (PBPK) models are mathematical models that are largely based upon the physiological characteristics of the species and the biochemical properties of the chemical of interest. They quantitatively describe and predict the kinetics of pollutants inside the body and can be of major importance for risk assessment of chemicals in marine mammals. PBPK models which consist of five compartments (liver, blubber, kidney, brain, and the rest of the body) were made for selected polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in order to address the bioaccumulation of these compounds in tissues of harbour porpoises (Phocoena phocoena). Harbour porpoises have relatively long life spans, are common cetaceans in the North Sea, a heavily polluted area, and are known to be very sensitive to pollution. Models developed for all compounds (some PCBs and PBDEs) were evaluated using existing datasets from the literature and from analyses performed by GC-MS, the latter being obtained from stranded porpoises in the Black Sea and the North Sea over a period of 18 years (1990–2008) to assess spatial and temporal trends in bioaccumulation of the respective PCBs and PBDEs. We demonstrate that PBPK models are a feasible computational approach that can be used as a non-destructive tool for predicting the chemical pollution status of the marine mammals. [less ▲]

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See detailComputational toxicology: Physiologically based pharmacokinetic models (PBPK) for lifetime exposure and bioaccumulation of polybrominated dephenyl ethers (PBDEs) in marine mammals
Weijs, Liesbeth; Covaci, Adrian; Yang, Raymond S H et al

in Environmental Pollution (2012)

Due to migration of harbour porpoises towards more polluted areas like the North Sea and their sensitivity towards pollution, there is a need for proper conservation measures for this species. As a ... [more ▼]

Due to migration of harbour porpoises towards more polluted areas like the North Sea and their sensitivity towards pollution, there is a need for proper conservation measures for this species. As a consequence, knowledge about the pollutant’s kinetics is required. The present study is the first to investigate the kinetics of PBDEs in marine mammals using PBPK modeling as a non-destructive tool for describing the chemical’s kinetics in a protected animal species. The models were developed and parameterized using data from the literature and Black Sea harbour porpoises through computer opti- mization. The predictability of these models in time was assessed by reverse dosimetry modeling using data from North Sea porpoises (1990e2008). From these predictions, PBDE 99 levels were found to decrease the fastest, followed by PBDE 153, 47 and 100. Results show that the PBPK models can be applied for harbour porpoises from different regions and also simulate time trends. [less ▲]

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See detailPotential effects of blood contaminants on immune responses in harbour seals (Phoca vitulina)
Dupont, Aurélie ULg; Weijs, Liesbeth; Siebert, Ursula et al

Poster (2011, August 23)

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See detailThe harbor seal and the harbor porpoise from the North Sea: review of their ecotoxicological status based on stranded and free-ranging individuals and potential threaths to the population
Das, Krishna ULg; Weijs, Liesbeth; Habran, Sarah ULg et al

Conference (2011, May)

The harbor seal (Phoca vitulina) and the harbor porpoise (Phocoena phocoena) from the North Sea have experienced major fluctuations these last decades due to habitat loss, prey fluctuation and pollution ... [more ▼]

The harbor seal (Phoca vitulina) and the harbor porpoise (Phocoena phocoena) from the North Sea have experienced major fluctuations these last decades due to habitat loss, prey fluctuation and pollution of the marine environment. Recently, development of monitoring programs and non-invasive sampling techniques, including seal catches in Germany allowed blood sampling together with measurements of blubber thickness, body mass, sex and body length. This approach is complementary to the study of stranded and by-caught individuals sampled during necropsies. Essential (Se, Zn, Cu, Fe) and non-essential elements (T-Hg, MeHg, Cd, Pb), perfluorinated organochemicals (PFCs) polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) were measured in blubber and in blood (for selected compounds) of stranded, by-caught and free-ranging individuals from Belgian and German coasts. In contrast to Cd and Pb, hepatic T-Hg can reach concentrations as high as 2.1 μg.g-1 dry weight but depended on several factors including position in the trophic chain (inferred from δ13C and δ15N values), age group and the body mass. This level has been shown to generate in vitro toxicity on harbor seal lymphocytes. Organic compound analysis (PFCs, PCBs, PBDEs) revealed widespread dispersion of contaminants in the marine environment with higher concentrations in seals compared to porpoises in agreement with the higher trophic position of the harbor seal. However, metabolization of these compounds differed between the two species, as revealed by the higher contribution of the persistent BDE-47 and lower chlorinated and non-persistent congeners (e.g. CB 52, CB95) in tissues of harbor porpoises. T-Hg, PFCs, PCBs and PBDEs were detected in calves confirming maternal transfer to offspring. These pollutants are strongly suspected to affect the immune and endocrine systems as well as vitamin A metabolism and this raises concern about exposure-related health effects, especially in younger individuals. [less ▲]

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See detailNew insights in the toxicology and health status of marine marine mammals: Use of free-ranging harbour seals from the Wadden Sea
Das, Krishna ULg; Seibel, Henrike; Hasseilmeier, Ilka et al

Conference (2011, March 20)

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See detailPOTENTIAL EFFECTS OF BLOOD CONTAMINANTS ON IMMUNE RESPONSES IN HARBOUR SEALS (PHOCA VITULINA)
Dupont, Aurélie ULg; Weijs, Liesbeth; Siebert, Ursula et al

in Organohalogen Compounds (2011), 73

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See detailNew evidence of a relationship between PCB and the cause of death of North Sea harbour porpoises
Jauniaux, Thierry ULg; Das, Krishna ULg; Haelters, Jan et al

in proceeding of the annual conference (2011)

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See detailA non-invasive approach to study lifetime exposure and bioaccumulation of PCBs in protected marine mammals: PBPK modeling in harbor porpoises
Weijs, Liesbeth; Covaci, Adrian; Yang, Raymond S. H. et al

in Toxicology and Applied Pharmacology (2011), In Press, Corrected Proof

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically ... [more ▼]

In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically, these models provide a new, non-destructive tool that enables the integration of biomonitoring activities and in vitro studies. The goals of the present study were firstly to develop PBPK models for several environmental relevant PCB congeners in harbor porpoises (Phocoena phocoena), a species that is sensitive to pollution because of its limited metabolic capacity for pollutant transformation. These models were tested using tissue data of porpoises from the Black Sea. Secondly, the predictive power of the models was investigated for time trends in the PCB concentrations in North Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess metabolic capacities of harbor porpoises for the investigated PCBs. In general, results show that parameter values from other species (rodents, humans) are not always suitable in marine mammal models, most probably due to differences in physiology and exposure. The PCB 149 levels decrease the fastest in male harbor porpoises from the North Sea in a time period of 18†years, whereas the PCB 101 levels decrease the slowest. According to the models, metabolic breakdown of PCB 118 is probably of lesser importance compared to other elimination pathways. For PCB 101 and 149 however, the presence of their metabolites can be attributed to bioaccumulation of metabolites from the prey and to metabolic breakdown of the parent compounds in the harbor porpoises. [less ▲]

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See detailPCBs versus PBDEs: how similar compounds can behave differently in harbour porpoises
Weijs, Liesbeth; Yang, R. S. H.; Das, Krishna ULg et al

in Organohalogen Compounds (2011)

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See detailMaternal transfer of PCBs, PBDEs and their hydroxylated metabolites in grey seal (Halichoerus grypus) from the Isle of May, Scotland
Vanden Berghe, Marie; Weijs, Liesbeth; Habran, Sarah ULg et al

in Organohalogen Compounds (2011)

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See detailAnthropogenic and naturally-produced organobrominated compounds in marine mammals from Brazil
Dorneles, Paulo R; Lailson-Brito, José; Dirtu, Alin C et al

in Environment International (2010), 36(1), 60-67

Liver samples from 51 cetaceans, comprising 10 species, stranded between 1994 and 2006 in a highly industrialized and urbanized region in Southeast Brazil, were analyzed for polybrominated diphenyl ethers ... [more ▼]

Liver samples from 51 cetaceans, comprising 10 species, stranded between 1994 and 2006 in a highly industrialized and urbanized region in Southeast Brazil, were analyzed for polybrominated diphenyl ethers (PBDEs) and methoxylated-PBDEs (MeO-PBDEs). A concentration range of PBDEs (3-5960 ng/g lw) similar to that observed in Northern Hemisphere dolphins was found. MeO-PBDE concentrations in continental shelf (CS) dolphins from Brazil are among the highest detected to date in cetaceans (up to 250 µg/g lw). Higher [Sigma]MeO-PBDE concentrations were measured in CS and oceanic dolphins than in estuarine dolphins. The [Sigma]PBDE/[Sigma]MeO-PBDE ratio varied significantly ranging from a mean value of 7.12 to 0.08 and 0.01 for estuarine, CS and oceanic species, respectively. A positive correlation was observed between [Sigma]PBDE and year of stranding of male estuarine dolphins (Sotalia guianensis), which suggests temporal variation in the exposure. Placental transfer of organobrominated compounds was also evidenced in S. guianensis. [less ▲]

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See detailPersistent organic pollutants and methoxylated PBDEs in harbour porpoises from the North Sea from 1990 until 2008. Young wildlife at risk?
Weijs, Liesbeth; van Elk, Cornelis; Das, Krishna ULg et al

in Science of the Total Environment (2010), 409

n the European North Sea, harbour porpoises are top predators with relatively long life spans and a limited capacity for metabolic biotransformation of contaminants compared to some other marine mammal ... [more ▼]

n the European North Sea, harbour porpoises are top predators with relatively long life spans and a limited capacity for metabolic biotransformation of contaminants compared to some other marine mammal species. As such, they are exposed to a mixture of persistent pollutants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), DDT and metabolites (DDXs), hexachlorobenzene (HCB) and chlordanes (CHLs) that bioaccumulate in their tissues. We report here on the levels of persistent organic pollutants and of the naturally-produced methoxylated PBDEs (MeO-PBDEs) in blubber, liver and kidney of harbour porpoise neonates (n = 3), calves (n = 15), juveniles (n = 6) and adults (n = 4) of the southern North Sea. Concentrations of almost all contaminant classes decrease slightly in all age groups over the period 1990–2008. For some classes (e.g. PCBs and DDXs) however, levels seem to increase little in harbour porpoise calves. In all animals, blubber had the highest concentrations, followed by liver and kidney, whereas liver and kidney were the preferred tissues for several compounds, such as octa- and deca-PCBs. Our data suggest that harbour porpoises calves are exposed to higher or comparable concentrations of POPs and of MeO-PBDEs and somewhat different patterns of selected POPs than adults, potentially placing them, and the entire population, at a disproportionate risk for exposure-related health effects. [less ▲]

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See detailOccurrence of anthropogenic and naturally-produced organohalogenated compounds in tissues of Black Sea harbour porpoises
Weijs, Liesbeth; Das, Krishna ULg; Neels, Hugo et al

in Marine Pollution Bulletin (2010), 60

Harbour porpoises are one of the three cetacean species inhabiting the Black Sea. This is the first study to report on polybrominated diphenyl ethers (PBDEs) and naturally-produced compounds, methoxylated ... [more ▼]

Harbour porpoises are one of the three cetacean species inhabiting the Black Sea. This is the first study to report on polybrominated diphenyl ethers (PBDEs) and naturally-produced compounds, methoxylated PBDEs (MeO-PBDEs) and polybrominated hexahydroxanthene derivatives (PBHDs), in tissues (kidney, brain, blubber, liver, muscle) of male harbour porpoises (11 adults, 9 juveniles) from the Black Sea. Lipid-normalized concentrations decreased from muscle > blubber > liver > kidney > brain for the sum of polychlorinated biphenyls (PCBs) and for the sum of PBDEs. Among the naturally-produced compounds, levels of PBHDs were higher than of MeO-PBDEs, with tri-BHD and 6-MeO-BDE 47 being the dominant compounds for both groups, respectively. Concentrations of naturally-produced compounds decreased from blubber to brain, similarly to the sum of DDT and metabolites (DDXs). Concentrations of DDXs were highest, followed by PCBs, HCB, PBHDs, PBDEs and MeO-PBDEs. Levels of PCBs and PBDEs in blubber were lower than concentrations reported for harbour porpoises from the North Sea, while concentrations of DDXs were higher. [less ▲]

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See detailPhysiologically Based Pharmacokinetic (PBPK) Models for Lifetime Exposure to PCB 153 in Male and Female Harbor Porpoises (Phocoena phocoena): Model Development and Evaluation
Weijs, Liesbeth; Yang, Raymond; Covaci, Adrian et al

in Environmental Science & Technology (2010), 44

Physiologically based pharmacokinetic (PBPK) models were developed for the most persistent polychlorinated biphenyl (PCB 153) in male and female harbor porpoises (Phocoena phocoena) to elucidate processes ... [more ▼]

Physiologically based pharmacokinetic (PBPK) models were developed for the most persistent polychlorinated biphenyl (PCB 153) in male and female harbor porpoises (Phocoena phocoena) to elucidate processes such as uptake, distribution, and elimination. Due to its limited metabolic capacities, long life span, and top position in marine food chains, this species is highly sensitive to pollution. The models consist of 5 compartments, liver, blubber, kidney, brain, and a compartment which accounts for the rest of the body, all connected through blood. All physiological and biochemical parameters were extracted from the literature, except for the brain/blood partition coefficient and rate of excretion, which were both fitted to data sets used for validation of the models. These data sets were compiled from our own analyses performed with GCMS on tissue samples of harbor porpoises. The intake of PCB 153 was from milk from birth to 4 months, and after weaning fish was the main food source. Overall, these models reveal that concentrations of PCB 153 in males increase with age but suggest that,asthe animalsgrowolder, metabolic transformation can be a possible pathway for elimination as well. In contrast, the model for females confirms that gestation and lactation are key processes for eliminating PCB 153 as body burdens decrease with age. These PBPK models are capable of simulating the bioaccumulation of PCB 153 during the entire life span of approximately 20 years of the harbor porpoises. [less ▲]

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See detailConcentrations of chlorinated and brominated contaminants and their metabolites in serum of harbour seals and harbour porpoises
Weijs, Liesbeth; Das, Krishna ULg; Siebert, Ursula et al

in Environment International (2009), 35(6), 842-850

Harbour seals (Phoca vitulina) and harbour porpoises (Phocoena phocoena) are top predators in the North Sea and consequently accumulate a variety of pollutants in their tissues. Concentrations of ... [more ▼]

Harbour seals (Phoca vitulina) and harbour porpoises (Phocoena phocoena) are top predators in the North Sea and consequently accumulate a variety of pollutants in their tissues. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (HO-PCBs and HO-PBDEs) were measured in serum of wild harbour seals (n=47) and captive harbour porpoises (n=21). Both species exhibit long life spans and do not have extreme situations, such as complete fasting during periods of lactation, in their annual cycles. For PCBs, concentrations in adult males were slightly higher than in juveniles and lowest in juvenile females. For PBDEs, juveniles have higher levels than adult males and females, probably as a consequence of lactational transfer. However. differences between these age-gender groups were not statistical significant, indicating that individual variation was limited within each species, even without knowing the feeding status of the animals. Body condition. particularly emaciation, has a major influence on the levels of chlorinated and brominated contaminants in serum. Profiles of PCBs were CB 153>CB 138>CB 187>CB 180 and CB 153>CB 138>CB 149>CB 187>CB 180 for harbour seals and porpoises respectively. For PBDEs, BDE 47 was the predominant congener followed by BDE 100 and 99 in both species. In harbour seals, concentrations of sum PCBs (median: 39,200 pg/ml) were more than 200 times higher than levels of sum PBDEs (median: 130 pg/ml) and almost 10 times higher than concentrations of sum HO-PCBs (4350 pg/ml). In harbour porpoises, concentrations of sum PCBs (median: 24,300 pg/ml) were about 20 times higher than concentrations of PBDEs (median: 1300 pg/ml). HO-PCBs were detected in only 4 harbour porpoises and this at very low concentrations. Naturally-produced MeO-PBDEs were only found in harbour porpoises at concentrations ranging from 120 to 810 pg/ml. HO-PBDEs were not found in any species. In general, harbour seals accumulate less compounds and have mostly lower concentrations than harbour porpoises possibly as a result of a better developed metabolism. (C) 2009 Elsevier Ltd. All rights reserved. [less ▲]

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See detailInter-species differences for polychlorinated biphenyls and polybrominated diphenyl ethers in marine top predators from the Southern North Sea: Part 1. Accumulation patterns in harbour seals and harbour porpoises
Weijs, Liesbeth; Dirtu, Alin C; Das, Krishna ULg et al

in Environmental Pollution (2009), 157

Harbour porpoises (Phocoena phocoena) and harbour seals (Phoca vitulina) are two representative top predator species of the North Sea ecosystem. The median values of sum of 21 polychlorinated biphenyl ... [more ▼]

Harbour porpoises (Phocoena phocoena) and harbour seals (Phoca vitulina) are two representative top predator species of the North Sea ecosystem. The median values of sum of 21 polychlorinated biphenyl (PCB) congeners and sum of 10 polybrominated diphenyl ether (PBDE) congeners were 23.1 mg/g lipid weight (lw) and 0.33 mg/g lw in blubber of harbour seals (n ¼ 28) and 12.4 mg/g lw and 0.76 mg/g lw in blubber of harbour porpoises (n¼ 35), respectively. For both species, the highest PCB concentrations were observed in adult males indicating bioaccumulation. On the contrary, the highest PBDE concentrations were measured in juveniles, likely due to better-developed metabolic capacities with age in adults. A higher contribution of lower chlorinated and non-persistent congeners, such as CB 52, CB 95, CB 101, and CB 149, together with higher contributions of other PBDE congeners than BDE 47, indicated that harbour porpoises are unable to metabolize these compounds. Harbour seals showed a higher ability to metabolize PCBs and PBDEs. [less ▲]

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See detailBiomagnification of naturally-produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in harbour seals and harbour porpoises from the Southern North Sea
Weijs, Liesbeth; Losada, Sara; Das, Krishna ULg et al

in Environment International (2009), 35

Harbour seals and harbour porpoises are top predator species from the North Sea, have long life spans and hence, are known to accumulate high levels of anthropogenic contaminants. To gain knowledge about ... [more ▼]

Harbour seals and harbour porpoises are top predator species from the North Sea, have long life spans and hence, are known to accumulate high levels of anthropogenic contaminants. To gain knowledge about the behaviour of naturally-produced compounds in these marine mammals, the biomagnification of naturally-produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) was assessed. The biomagnification of MeO-PBDEs (2'-MeO-BDE 68 and 6-MeO-BDE 47) was lower in harbour seals (all biomagnification factors (BMFs) < 1) compared to the same age-gender groups of the harbour porpoises (all BMFs > 1). This may indicate a better metabolic breakdown of MeO-PBDEs in harbour seals, as was previously suggested for polybrominated diphenyl ethers (PBDEs). In both predators, 6-MeO-BDE 47 had the highest concentrations (range: 45-483 ng/g lw and 2-38 ng/g lw for harbour porpoises and seals, respectively) compared to 2'-MeO-BDE 68 (range: 2-28 ng/g lw and 1-6 ng/g lw for harbour porpoises and seals, respectively). In general, the highest concentrations were found in juveniles, suggesting an increased biotransformation capacity with age or the influence of dilution by growth for both species. Here we show that naturally-produced brominated organic compounds can biomagnify and accumulate in North Sea top predators, although to a lesser extent than anthropogenic lipophilic contaminants, such as polychlorinated biphenyls (PCBs) or PBDEs. [less ▲]

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