Maja Kirkegaard

What are the toxicological effects of mercury in Arctic biota

This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health.

Is Bone Mineral Composition Disrupted by Organochlorines in East Greenland Polar Bears (Ursus maritimus)

We analyzed bone mineral density (BMD) in skulls of polar bears (Ursus maritimus) (n = 139) from East Greenland sampled during 1892–2002. Our primary goal was to detect possible changes in bone mineral content (osteopenia) due to elevated exposure to organochlorine [polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane (DDT) and its metabolites, chlordanes (CHLs), dieldrin, hexacyclohexanes, hexachlorobenzene] and polybrominated diphenyl ether (PBDE) compounds. To ensure that the BMD value in skull represented the mineral status of the skeletal system in general, we compared BMD values in femur and three lumbar vertebrae with skull in a subsample. We detected highly significant correlations between BMD in skull and femur (r = 0.99; p < 0.001; n = 13) and skull and vertebrae (r = 0.97; p < 0.001; n = 8). BMD in skulls sampled in the supposed pre-organochlorine/PBDE period (1892–1932) was significantly higher than that in skulls sampled in the supposed pollution period (1966–2002) for subadult females, subadult males, and adult males (all, p < 0.05) but not adult females (p = 0.94). We found a negative correlation between organochlorines and skull BMD for the sum of PCBs (∑PCB; p < 0.04) and ∑CHL (p < 0.03) in subadults and for dieldrin (p < 0.002) and ∑DDT (p < 0.02) in adult males; indications for ∑PBDE in subadults were also found (p = 0.06). In conclusion, the strong correlative relationships suggest that disruption of the bone mineral composition in East Greenland polar bears may have been caused by organochlorine exposure.

Are organohalogen contaminants a cofactor in the development of renal lesions in East Greenland polar bears (Ursus maritimus)

Tissues of polar bears (Ursus maritimus) from East Greenland contain the highest concentrations of organohalogen contaminants (OHCs) among subpopulations of any mammalian species in the Arctic. Negative associations also have been found between OHC concentrations and bone mineral density and liver histology parameters for this subpopulation of polar bears. The present study examined the OHC concentrations and adverse effects on renal tissue for 75 polar bears collected during 1999 to 2002. Specific lesions were diffuse glomerular capillary wall thickening, mesangial glomerular deposits, tubular epithelial cell hyperplasia, hyalinization of the tubular basement membrane, tubular dilatation, atrophy and necrosis, tubular medullary hyalin casts, interstitial fibrosis, and mononuclear cell infiltration. With the exception of mononuclear cell infiltrations, all these parameters were correlated with age, whereas none was associated with the sex of the animals. In an age-controlled statistical analysis of covariance, increases in glomerular mesangial deposits and interstitial fibrosis were significantly (p < 0.05) correlated with polybrominated diphenyl ether (sigmaPBDE) concentrations in subadults. In adult males, statistically significant (p < 0.05) positive correlations were found for tubular epithelial cell hyperplasia and dieldrin concentration; diffuse glomerular capillary wall thickening and chlordane (sigmaCHL) concentrations, and tubular medullary hyalin casts and sigmaCHL, sigmaPBDE, polychlorinated biphenyl, and hexachlorocyclohexane concentrations. The lesions were consistent with those reported previously in highly OHC-contaminated Baltic seal populations and exposed laboratory animals. The renal lesions were a result of aging. However, based on the above statistical findings as well as the nature of the findings, we suggest that long-term exposure to OHCs may be a cofactor in renal lesion occurrence, although other cofactors, such as exposure to heavy metals and recurrent infections from microorganisms, cannot be ruled out. This is new and important knowledge in the assessment of health status among wildlife populations and humans relying on food resources that are contaminated with OHCs.

Are liver and renal lesions in East Greenland polar bears (Ursus maritimus) associated with high mercury levels

BackgroundIn the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury as they prey on polluted ringed seals (Phoca hispida) and bearded seals (Erignathus barbatus). Studies have shown that polar bears from East Greenland are among the most mercury polluted species in the Arctic. It is unknown whether these levels are toxic to liver and kidney tissue.MethodsWe investigated the histopathological impact from anthropogenic long-range transported mercury on East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues.ResultsLiver mercury levels ranged from 1.1–35.6 μg/g wet weight and renal levels ranged from 1–50 μg/g wet weight, of which 2 liver values and 9 kidney values were above known toxic threshold level of 30 μg/g wet weight in terrestrial mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were significantly higher in individuals with visible Ito cells (p < 0.02) and a similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels were significantly lower in individuals with portal bile duct proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal convoluted tubular hyalinisation in renal tissue (p = 0.07).ConclusionBased on these relationships and the nature of the chronic inflammation we conclude that the lesions were likely a result of recurrent infections and ageing but that long-term exposure to mercury could not be excluded as a co-factor. The information is important as it is likely that tropospheric mercury depletion events will continue to increase the concentrations of this toxic heavy metal in the Sub Arctic and Arctic marine food webs.

Do organohalogen contaminants contribute to histopathology in liver from East Greenland polar bears (Ursus maritimus)

In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.

Two decades of biomonitoring polar bear health in Greenland: a review

SummaryWe present an overview of studies of anthropogenic pollutants in East Greenland polar bears over the period of 1999-2011. East Greenland polar bears are among the most polluted species, not just in the Arctic but globally, and represent an excellent biomonitoring species for levels and effects of global pollution in an apex predator. Therefore, an international multidisciplinary team joined to monitor and assess the patterns and concentrations of contaminants and their potential negative impact on polar bears. The review showed that East Greenland polar bears are exposed to a mix of chlorinated, brominated and fluorinated organic compounds as well as mercury which are all known to have endocrine, immune and organ-system toxic properties. For example, the concentrations of PCBs (polychlorinated biphenyls) in blubber ranged approximately 800-21,000 ng/g lw while mercury concentrations in liver and kidney ranged 0.1-50 μg/g ww. Regarding health endpoints, bone density seemed to decrease as a function of time and OHC (organohalogen compound) concentrations and further T-score for adult males indicated risk for osteoporosis. .The size of sexual organs decreased with increasing OHC concentrations. In the lower brain stem, mercury-associated decreases in NMDA-receptor levels and DNA-methylation was found The present review indicated that age was one of the major drivers for liver and renal lesions, although contaminants and infectious diseases may also play a role. Lesions in thyroid glands were most likely a result of infectious and genetic factors and probably, together with endocrine disrupting chemical (EDCs), the reason for disturbances/fluctuations in blood plasma thyroid hormone concentrations. Except for bone density reductions and neurological measures, all findings were supported by case-control studies of Greenland sledge dogs exposed long-term orally to similar combinations of contaminant concentrations. The studies of sledge dogs also indicated that the mixture of contaminants and fatty acids in the blubber of prey similar to that of polar bears induces cellular as well as humoral immune toxic changes. These controlled studies using model species for polar bears indicate that the correlative findings between health endpoint and contaminants in polar bears could be a cause-and-effect relationship. Physiologically based pharmacokinetic (PBPK) modelling showed that the risk quotients were ≥1 for ΣPCB, dieldrin and PFOS, which indicate an increased risk of prenatally reproductive pathology. In conclusion polar bears are susceptible to long-range transported chemicals that may have various adverse effects on multiple organ systems such as the reproductive and immune system.

Renal lesions in Greenland sledge dogs ( Canis familiaris ) exposed to a natural dietary cocktail of persistent organic pollutants

Persistent organic pollutants such as Polychlorinated biphenyls (PCB) and dichloro diphenyl trichloroethane (DDT) are known to exert various adverse health effects in wildlife mammals. The impact from dietary intake of minke whale (Balaenoptera acutorostrata) blubber high in organohalogen and other chemical contaminants on renal morphology and function was investigated via a controlled study on West Greenland sledge dogs (Canis familiaris). Our results showed significantly higher frequencies of glomerular, tubular, and interstitial lesions in the exposed group. Furthermore, higher urine protein : creatinine ratio and plasma urea levels were found in the exposed group, which indicated a negative impact on kidney function via tubular and glomerular dysfunctions. The lesions were similar to those observed in top predator marine species–such as seals and polar bears–and humans exposed via diet to persistent environmental pollutants. The lesions may have impacts on the overall health of these animals. It is reasonable to suggest that chronic exposure to organic pollutants via a country diet of high trophic level marine organisms may have an impact on renal morphology and function in Arctic apex predators in general as well as Inuit people.

Alterations in thyroid hormone status in Greenland sledge dogs exposed to whale blubber contaminated with organohalogen compounds

As a model of high trophic level carnivores, sledge dogs were fed from 2 to 18 months of age with minke whale blubber containing organohalogen compounds (OHC) corresponding to 128 μg PCB/day. Controls were fed uncontaminated porcine fat. Thyroid hormone levels were assessed in 7 exposed and 7 control sister bitches (sampled at age 6-18 months) and 4 exposed and 4 control pups, fed the same diet as their mothers (sampled age 3-12 months). Lower free and total T3 and T4 were seen in exposed vs. control bitches beyond 10 months of age, and total T3 was lower through 3-12 months of age in exposed pups. A negative correlation with thyroid gland weight was significant for ΣDDT, as was a positive association with total T3 for dieldrin. This study therefore supports observational data that OHCs may adversely affect thyroid functions, and it suggests that OHC exposure duration of 10 months or more may be required for current OHC contamination levels to result in detectable adverse effects on thyroid hormone dynamics.

Chronic dietary exposure to environmental organochlorine contaminants induces thyroid gland lesions in Arctic foxes (Vulpes lagopus).

The impact of dietary organochlorine (OC) exposure on thyroid gland pathology was studied in farmed male Arctic foxes (Vulpes lagopus). The exposed group (n=16) was fed a diet based on wild minke whale (Balaenoptera acutorostrata) blubber as a main fat source in order to mimic the exposure to OC cocktails in the Artic environment. This resulted in an exposure of approximately 17 microg Sigma OC/kg day and a Sigma OC residue adipose tissue and liver concentration of 1700 and 4470 ng/gl.w., respectively, after 16 months of exposure. Control foxes (n=13) were fed a diet with pork (Sus scrofa) fat as a main fat source containing significantly lower OC concentrations. The food composition fed to the control and exposed group was standardized for nutrient contents. Four OC-related histopathological changes were found: (1) flat-epithelial-cell true thyroid cysts (TC) characterized by neutral content; (2) remnants of simple squamous epithelial-cell embryonic ducts containing neutral debris (EDN); (3) remnants of stratified squamous epithelial-cell embryonic ducts containing acid mucins often accompanied with debris of leukocyte inflammatory nature (EDM) and (4) disseminated thyroid C-cell hyperplasia (HPC). Of these, the prevalence of TC, EDN and HPC was significantly highest in the exposed group (chi(2) test: all p<0.04). The study shows that the OC mixture in minke whale blubber may cause development of thyroid gland cysts, C-cell hyperplasia and increase the prevalence of cystic remnants of embryonic ducts. The mechanism causing these effects could include endocrine disruption of the hypothalamus-pituitary-thyroid (HPT) axis, a disturbance of the calcium homeostasis/metabolism or energy metabolism or immune suppression. Because concentrations of OCs are higher in wild Arctic foxes, it is likely that these animals could suffer from similar OC-induced thyroid gland pathological and functional changes.

Does the nutrition profile of vitamins, fatty acids and microelements counteract the negative impact from organohalogen pollutants on bone mineral density in Greenland sledge dogs (Canis familiaris)?

There is a great need for understanding the impact from dietary OHCs (organohalogen compounds) on bone mineral composition - and thereby osteoporosis - in especially arctic wildlife such as polar bears (Ursus maritimus) as well as humans. For that purpose, we measured BMD (bone mineral density) by DXA scanning (g/cm(-2)) in 15 age and weight normalized sledge dog (Canis familiaris) bitches and their 26 pups divided into a control group (n=26) given 50-200 g/day clean pork (Suis scrofa) fat and a treated group (n=15) given 50-200 g/day OHC polluted minke whale (Balaenoptera acutorostrata) blubber as main lipid sources. The results showed that BMD increased significantly with age (linear regression: p<0.0001, r(2)=0.83, n=41) while no sex difference was found in the F-generation (two-way ANOVA: all p>0.3). No differences in BMD(femur) or BMD(vertebrae) between exposed and control individuals in the bitch generation were found (linear mixed effect model: both p>0.38). Likewise, no difference between exposed and control subadults and juveniles in the F-generation was found (two-way ANOVA: all p>0.33). Correlation analyses between BMD(femur), BMD(vertebrae) and groups of OHCs, respectively, did not show any statistically significant relationships nor a clear or decreasing trend (Pearsons: p: 0.07-0.78; r: -0.2-0.59; n: 10-18). As the groups were similar regarding genetics, age and sex are the only factors that can explain this observation. Either the pollutants did not have an impact on BMD using the present time frame and OHC concentrations (threshold levels not reached), or the difference in food composition (mainly vitamins and n3 fatty acids) conceal the potential OHC impact on BMD. Such information is important when evaluating the positive and negative health consequences from eating polluted marine species.