Eldbjørg Sofie Heimstad

Halogenated organic contaminants and their correlations with circulating thyroid hormones in developing Arctic seabirds

Thyroid hormones are essential for normal growth and development and disruption of thyroid homeostasis can be critical to young developing individuals. The aim of the present study was to assess plasma concentrations of halogenated organic contaminants (HOCs) in chicks of two seabird species and to investigate possible correlations of HOCs with circulating thyroid hormone (TH) concentrations. Plasma from black-legged kittiwake (Rissa tridactyla) and northern fulmar (Fulmarus glacialis) chicks were sampled in Kongsfjorden, Svalbard in 2006. The samples were analyzed for thyroid hormones and a wide range of HOCs (polychlorinated biphenyls (PCBs), hydroxylated (OH-) and methylsulphoned (MeSO-) PCB metabolites, organochlorine pesticides (OCPs), brominated flame retardants (BFRs), and perfluorinated compounds (PFCs)). Concentrations of HOCs were generally low in kittiwake and fulmar chicks compared to previous reports. HOC concentrations were five times higher in fulmar chicks compared to in kittiwake chicks. PFCs dominated the summed HOCs concentrations in both species (77% in kittiwakes and 69% in fulmars). Positive associations between total thyroxin (TT4) and PFCs (PFHpS, PFOS, PFNA) were found in both species. Although correlations do not implicate causal relationships per se, the correlations are of concern as disruption of TH homeostasis may cause developmental effects in young birds.

Comparative Molecular Dynamics of Mesophilic and Psychrophilic Protein Homologues Studied by 1.2 ns Simulations

It is well established that the dynamic motion of proteins plays an important functional role, and that the adaptation of a protein molecule to its environment requires optimization of internal non-covalent interactions and protein-solvent interactions. Serine proteinases in general, and trypsin in particular has been used as a model system in exploring possible structural features for cold adaptation. In this study, a 500 p.s. and a 1200 p.s. molecular dynamics (MD) simulation at 300 K of both anionic salmon trypsin and cationic bovine trypsin are analyzed in terms of molecular flexibility, internal non-covalent interactions and protein-solvent interactions. The present MD simulations do not indicate any increased flexibility of the cold adapted enzyme on an overall basis. However, the apparent higher flexibility and deformability of the active site of anionic salmon trypsin may lower the activation energy for ligand binding and for catalysis, and might be a reason for the increased binding affinity and catalytic efficiency compared to cationic bovine trypsin.

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST

Abstract In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project (www.nanotest-fp7.eu) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.

Influence of season, location, and feeding strategy on bioaccumulation of halogenated organic contaminants in Arctic marine zooplankton

The influence of season, location, feeding strategy, and trophic position on concentration, compositional pattern, and bioaccumulation factors (BAFs) of halogenated organic contaminants (HOCs; polychlorinated biphenyls, chlorinated pesticides, and brominated flame retardants) was investigated within an Arctic zooplankton food web. Water (dissolved fraction) and seven Arctic marine pelagic zooplankton species (including herbivores, omnivores, and predators) were sampled in May, July, and October 2007 at two stations in Kongsfjorden, Svalbard, Norway. The HOC concentrations in both water and zooplankton generally decreased from May to October. The HOC concentrations and patterns among zooplankton species were explained by their feeding strategies, roughly categorized as herbivores, omnivores, and predators, and not stable isotope-derived trophic position. Field-derived BAFs varied greatly, with higher BAFs in May compared with July and October. Furthermore, BAFs differed among the species according to their feeding strategies. The relationship between BAFs from the different seasons and K(OW) (octanol:water partitioning coefficient) showed comparable intercepts and different slopes between May and October, with all relationships diverging from the assumed 1:1 relationship between BAF and K(OW). Differences in HOC concentrations and BAFs from herbivores to predators showed that biomagnification occurred in zooplankton. The results suggest that concentrations and patterns of HOCs in zooplankton species are influenced not only by equilibrium partitioning with water but also by feeding strategy.

Assessment of chemical screening outcomes based on different partitioning property estimation methods

Screening is widely used to prioritize chemicals according to their potential environmental hazard, as expressed in the attributes of persistence, bioaccumulation (B), toxicity and long range transport potential (LRTP). Many screening approaches for B and LRTP rely on the categorization of chemicals based on a comparison of their equilibrium partition coefficients between octanol and water (K(OW)), air and water (K(AW)) and octanol and air (K(OA)) with a threshold value. As experimental values of the properties are mostly unavailable for the large number of chemicals being screened, the use of quantitative structure-property relationships (QSPRs) and other computational chemistry methods becomes indispensable. Predictions by different methods often deviate considerably, and flawed predictions may lead to false positive/negative categorizations. We predicted the partitioning properties of 529 chemicals, culled from previous prioritization efforts, using the four prediction methods EPI Suite, SPARC, COSMOtherm, and ABSOLV. The four sets of predictions were used to screen the chemicals against various LRTP and B criteria. Screening results based on the four methods were consistent for only approximately 70% of the chemicals. To further assess whether the means of estimating environmental phase partitioning has an impact, a subset of 110 chemicals was screened for elevated arctic contamination potential based on single-parameter and poly-parameter linear free energy relationships respectively. Different categorizations were observed for 5 out of 110 chemicals. Screening and categorization methods that rely on a decision whether a chemicals predicted property falls on either side of a threshold are likely to lead to a significant number of false positive/negative outcomes. We therefore suggest that screening should rather be based on numerical hazard or risk estimates that acknowledge and explicitly take into account the uncertainties of predicted properties.

Biotransformation of PCBs in Arctic seabirds: Characterization of phase I and II pathways at transcriptional, translational and activity levels

Arctic seabirds are exposed to a wide range of halogenated organic contaminants (HOCs). Exposure occurs mainly through food intake, and many pollutants accumulate in lipid-rich tissues. Little is known about how HOCs are biotransformed in arctic seabirds. In this study, we characterized biotransformation enzymes in chicks of northern fulmars (Fulmarus glacialis) and black-legged kittiwakes (Rissa tridactyla) from Kongsfjorden (Svalbard, Norway). Phase I and II enzymes were analyzed at the transcriptional, translational and activity levels. For gene expression patterns, quantitative polymerase chain reactions (qPCR), using gene-sequence primers, were performed. Protein levels were analyzed using immunochemical assays of western blot with commercially available antibodies. Liver samples were analyzed for phase I and II enzyme activities using a variety of substrates including ethoxyresorufin (cytochrome (CYP)1A1/1A2), pentoxyresorufin (CYP2B), methoxyresorufin (CYP1A), benzyloxyresorufin (CYP3A), testosterone (CYP3A/CYP2B), 1-chloro-2,4-nitrobenzene (CDNB) (glutathione S-transferase (GST)) and 4-nitrophenol (uridine diphosphate glucuronyltransferase (UDPGT)). In addition, the hydroxylated (OH-) polychlorinated biphenyls (PCBs) were analyzed in the blood, liver and brain tissue, whereas the methylsulfone (MeSO(2)-) PCBs were analyzed in liver tissue. Results indicated the presence of phase I (CYP1A4/CYP1A5, CYP2B, and CYP3A) and phase II (GST and UDPGT) enzymes at the activity, protein and/or mRNA level in both species. Northern fulmar chicks had higher enzyme activity than black-legged kittiwake chicks. This in combination with the higher SigmaOH-PCB to parent PCB ratios suggests that northern fulmar chicks have a different biotransformation capacity than black-legged kittiwake chicks.

Methylmercury biomagnification in an Arctic pelagic food web

Mercury (Hg) is a toxic element that enters the biosphere from natural and anthropogenic sources, and emitted gaseous Hg enters the Arctic from lower latitudes by long-range transport. In aquatic systems, anoxic conditions favor the bacterial transformation of inorganic Hg to methylmercury (MeHg), which has a greater potential for bioaccumulation than inorganic Hg and is the most toxic form of Hg. The main objective of the present study was to quantify the biomagnification of MeHg in a marine pelagic food web, comprising species of zooplankton, fish, and seabirds, from the Kongsfjorden system (Svalbard, Norway), by use of trophic magnification factors. As expected, tissue concentrations of MeHg increased with increasing trophic level in the food web, though at greater rates than observed in several earlier studies, especially at lower latitudes. There was strong correlation between MeHg and total Hg concentrations through the food web as a whole. The concentration of MeHg in kittiwake decreased from May to October, contributing to seasonal differences in trophic magnification factors. The ecology and physiology of the species comprising the food web in question may have a large influence on the magnitude of the biomagnification. A significant linear relationship was also observed between concentrations of selenium and total Hg in birds but not in zooplankton, suggesting the importance of selenium in Hg detoxification for individuals with high Hg concentrations.

Quantitative structure – Photodegradation relationships of polybrominated diphenyl ethers, phenoxyphenols and selected organochlorines

Among other developments, the technological revolution has lead to introduction of new chemicals to better serve in instruments and materials. The consequences of the extensive increase in use of new chemicals can be detected in the environment world wide, i.e. in wildlife and humans. To ensure this problem to be minimised in the future, new chemicals need to be subjected to predictive assessments before commercialised. To facilitate screening, qualitative structure-activity relationships, quantitative structure-activity relationships may be applied to describe reactivity of chemicals. Physico-chemical properties of chemicals such as partition coefficients and half-lives for the various environmental compartments are essential input data in multimedia environmental fate models. In this study we examine how structural characteristics can quantitatively describe laboratory determined photolytic half-lives of halogenated compounds of different classes, such as polybrominated diphenyl ethers (PBDEs), hydroxylated brominated diphenyl ethers (OH-PBDEs), and other organohalogens. A total of 30 chemicals with experimentally measured half-lives are used. Results reveal that the most important descriptors for describing the half-lives of the brominated compounds are the energy gap (GAP-1) between HOMO-1 and LUMO, the lowest partial charge on a halogen atom (Qhal-), topological polar surface area (TPSA), the atom with highest radical superdelocalizability (Rad-super+) and LUMO density (LUMO+).

Environmental fate of chlorinated bornanes estimated by theoretical descriptors

Theoretical molecular descriptors have been calculated for 36 polychlorinated bornanes, the majority compound class of the insecticide Toxaphene. The results demonstrate that thermodynamic stability by the use of molecular structural energies can be used as a general parameter for persistence. Since these descriptors agree well with polychlorinated bornanes found in the environment, these compounds should be included as important indicator compounds in future trace analytical investigations of polychlorinated bornanes and also within experimental metabolism studies to investigate potential toxic metabolites. Reactivity descriptors such as electronaffinity, hardness, LUMO location and atomic charges may guide to potential chemical reactions like the dechlorination of polychlorinated bornanes in reductive environment. Further it is advised to use these descriptors and other new potential ones in combination with experimental degradation and toxicology studies to explore the relationship between molecular structure and biological effects of chlorobornanes.

Effect of reduced food intake on toxicokinetics of halogenated organic contaminants in herring gull (Larus argentatus) chicks

The aim of the present study was to investigate how contaminant exposure and reduced food intake affect tissue distribution and biotransformation of halogenated organic contaminants (HOCs) in Arctic seabirds using herring gull (Larus argentatus) as a model species. Herring gull chicks were exposed for 44 d to cod liver oil containing a typical mixture of contaminants. Following exposure, food intake was reduced for a one-week period in a subgroup of the chicks. Polyclorinated biphenyls, organochlorine pesticides, and brominated flame retardants, as well as a wide range of hydroxy, methyl sulfone, and methoxy compounds were measured in liver, brain, and plasma samples. Additionally, phase I biotransformation enzyme activities and phase I and II messenger ribonucleic acid (mRNA) expression were investigated in the liver, brain, or both. Both contaminant exposure and reduced food intake had an increasing effect on the concentrations of HOCs and their metabolites. The HOC exposure and reduced food intake also led to increased 7-ethoxyresorufin-O-deethylation (EROD) activity, whereas mRNA expression of the biotransformation enzymes increased only following the reduced food intake. Tissue distribution of HOCs and their metabolites was not affected by either contaminant exposure or reduced food intake. In conclusion, the results indicate that biotransformation capacity and formation of HOC metabolites increase during reduced food intake. This finding supports the hypothesis that reduced food intake increases the susceptibility of Arctic animals to the effects of lipophilic HOCs.