Organohalogenated contaminants (OHCs) in polar bear mother-cub pairs from Svalbard, Norway: Maternal transfer, exposure assessment and thyroid hormone disruptive effects in polar bear cubs
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- Institutt for biologi 
As the top predator of the arctic marine food chain, polar bears (Ursus maritimus) accumulate high levels of organohalogenated compounds (OHCs) such as polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), various pesticides, and perfluoroalkyl substances (PFASs) (e.g. perfluorinated carboxylic acids [PFCAs] and perfluorinated sulfonic acids [PFSAs]). Most of these OHCs and their metabolites (e.g. hydroxylated PCBs [OH-PCBs] and hydroxylated polybrominated diphenyl ethers [OH-PBDEs]) disrupt the thyroid hormone (TH)-system of vertebrates. Developing mammals are particularly vulnerable to the effects of TH disrupting chemicals (TDCs) because THs influence activities in multiple and essential growth and developmental processes. TDCs transferred from mothers to foetus or nursing offspring may cause developmental, cognitive and neurobehavioral effects in the offspring, raising the risk of potential health-effects in highly contaminated polar bear cubs. Although TDCs may act through several modes of action, OH-PCBs and PFASs are of particular concern due to their ability to compete with thyroxine (T4) in binding to TH-transport proteins in blood such as transthyretin (TTR), and thereby deplete T4 levels in blood. The present thesis reports levels, pattern and cub-mother ratios (maternal transfer ratios) of PCBs, OH-PCBs, and PFASs in polar bear mothers and their approximately four-month old cubs from Svalbard (Norway). A method for extracting TTR-binding compounds from polar bear plasma samples was developed and validated, and applied to plasma samples of polar bear cubs to measure the total TTR-binding activity, expressed as T4-equivalents (T4-EQMeas), using a radioligand 125I-T4-TTR-binding assay. Orthogonal partial least square (OPLS) modelling was used to assess the potential disruptive effects of PCBs, calculated dioxin-like activity of PCBs (ΣTEQ-PCBs7), OH-PCBs, PFASs and T4-EQMeas on circulating THlevels (total and free T4 [TT4 and FT4], total and free triiodothyonine [TT3 and FT3], total reverse T3 [rT3]) and TH-ratios (TT4/TT3 and TT3/rT3) in polar bear cubs. Whether the mechanism of competitive binding to TTR could be involved in observed TH-disruptive effects were discussed. Samples from both 1998 and 2008 were included to investigate possible recent temporal trends in levels and effects of TDCs in polar bears. Mean levels of Σ21PCBs in the nursing cubs were 2.7±0.7 times the levels of their mothers, while Σ6OH-PCBs, Σ7PFCAs and Σ2PFSAs were 0.53±0.16, 0.24±0.07 and 0.22±0.05 times the levels in their mothers, respectively. Although it was not possible to differ between the relative importance of prenatal and postnatal transfer and the influence of toxicokinetical factors, the results indicate that in polar bears, the maternal transfer of hydrophobic PCBs is considerably higher than for protein-binding compounds such as OH-PCBs and PFASs. Assessment of levels, patterns, and metabolite/precursor ratios of PCBs and OH-PCBs in mothers and cubs indicates that polar bear cubs do biotransform PCBs. Although the relative pattern of enzyme activities involved in the biotransformation of PCBs to OH-PCBs in mothers and cubs appear to be similar, cubs seem to have a lower ability to biotransform PCBs compared to adult bears. Between-year comparisons of exposure levels show that the PCB, OHPCB and perfluorooctane sulfonate (PFOS) levels in mothers and cubs were lower in 2008 than in 1998. Conversely, the levels of most PFCAs were higher in 2008 than in 1998, while the levels of perfluorohexanoic sulfonate (PFHxS) did not differ between the sampling years. Much of these between-year differences are likely due to a temporal decrease of PCBs and PFOS and a temporal increase of PFCAs in the environment, and thus, in exposure levels in polar bear mothers and cubs from Svalbard. However, because sampling in 2008 was conducted 6° further west than in 1998, the between-year differences could partly be explained by between-year differences in capture location. A method to extract TTR-binding compounds from plasma sample was successfully established. The extraction method was successfully applied to polar bear plasma samples, and the total TTR-binding activity in cub plasma was quantified. Approximately 50% of the T4-EQMeas, in the cubs’ blood was accounted for by chemically determined OH-PCBs, while only about 1% was accounted for by PFASs. This indicates that significant burdens of unidentified TTR-binding TDCs were present in blood of polar bear cubs. Examining the associations between plasma TH-levels, TH–ratios, and OHC-levels in cubs showed that OHCs only inflicted TH-effects in the 1998 cubs. Inverse correlations were observed between plasma T4 (TT4 and FT4), and dioxin-like PCBs (DL-PCBs) (i.e. PCB-156, - 157), ΣTEQ-PCB7, and non-DL PCBs (NDL-PCBs) (i.e. PCB-47, -99, -137, -153, -170, -180, -183) in these cubs. Likewise, PFCAs showed a weak impact on plasma TH-levels in the 1998 cubs (TT4, FT4 and TT4/TT3). It is notable that T4-EQMeas and plasma levels of OH-PCBs did not affect plasma THlevels, including T4 levels, suggesting that the PCB affects circulating T4 levels through other mechanisms than competitive binding to TTR. There were no observed effects of OHCs on plasma TT3, FT3, rT3 or TT3/rT3. In the 2008 cubs, all TH-variables were unaffected by contaminant variables, suggesting that recent lower burdens of PCBs may have improved the TH-health of polar bear cubs. It is noteworthy that in both the 1998 and 2008 cubs, the molar plasma concentrations of OH-PCBs, PFASs, and T4-EQMeas were considerably higher than the concentration of plasma T4 levels. This suggests that the T4 binding sites of TTR are fully saturated by contaminants, which could explain the lack of association between plasma T4 levels, OH-PCBs and T4-EQMeas. Although other plasma transport protein than TTR likely are involved in plasma transport of THs in polar bears, these findings raise concern because alterations of the TH-homeostasis and TTR-transport of THs in developing cubs may affect hunting and mating behaviour later in life, and hence, affect the fitness and populations of polar bears. While it is clear that OHCs present a physiological challenge to developing polar bears, further research is required to understand the complexity of these effects.