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  • 1. Dreij, Kristian
    et al.
    Mattsson, Åse
    Jarvis, Ian W. H.
    Lim, Hwanmi
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Hurkmans, Jennie
    Gustafsson, Johan
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Bergvall, Christoffer
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Johansson, Christer
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Environment and Health Administration, Sweden.
    Stenius, Ulla
    Cancer Risk Assessment of Airborne PAHs Based on in Vitro Mixture Potency Factors2017In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 51, no 15, p. 8805-8814Article in journal (Refereed)
    Abstract [en]

    Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants associated with adverse human health effects including cancer. However, the risk of exposure to mixtures is difficult to estimate, and risk assessment by whole mixture potency evaluations has been suggested. To facilitate this, reliable in vitro based testing systems are necessary. Here, we investigated if activation of DNA damage signaling in vitro could be an endpoint for developing whole mixture potency factors (MPFs) for airborne PAHs. Activation of DNA damage signaling was assessed by phosphorylation of Chid and H2AX using Western blotting. To validate the in vitro approach, potency factors were determined for seven individual PAHs which were in very good agreement with established potency factors based on cancer data in vivo. Applying the method using Stockholm air PAH samples indicated MPFs with orders of magnitude higher carcinogenic potency than predicted by established in vivo-based potency factors. Applying the MPFs in cancer risk assessment suggested that 45.4 (6% of all) cancer cases per year in Stockholm are due to airborne PAHs. Applying established models resulted in <1 cancer case per year, which is far from expected levels. We conclude that our in vitro based approach for establishing MPFs could be a novel method to assess whole mixture samples of airborne PAHs to improve health risk assessment.

  • 2.
    Gustafsson, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Förlin, Lars
    Karlson, Agnes M. L.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Bignert, Anders
    Dahlgren, Henrik
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Parkkonen, Jari
    Asplund, Lillemor
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Correlating seasonal changes of naturally produced brominated compounds to biomarkers in perch from the Baltic Sea2021In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 240, article id 105984Article in journal (Refereed)
    Abstract [en]

    Hydroxylated polybrominated diphenyl ethers (OH-PBDEs), naturally produced by algae and cyanobacteria in the Baltic Sea, are potent disrupters of energy metabolism as well as endocrine disruptors and neurotoxins. In this study, European perch (Perca fluviatilis) from the Baltic Sea were sampled from May until October. OH-PBDEs and ten biomarkers were measured in each individual (n = 84 over 18 sampling time points) to study potential correlations between exposure to OH-PBDEs and changes in biomarkers. Several biomarkers showed significant non-linear seasonal variation. In the perch, ethoxyresorufin-O-deethylase (EROD) activity, plasma lactate concentration, and plasma glucose concentration showed a significant positive log-linear correlation with OH-PBDEs, whereas lipid percentage and liver somatic index showed a significant negative log-linear correlation with OH-PBDEs. These results strengthen the concern that OH-PBDEs could cause negative health effects for fish in the Baltic Sea.

  • 3.
    Gustafsson, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science. Vrije Universiteit, the Netherlands.
    Legradi, Jessica
    Lamoree, Marja H.
    Asplund, Lillemor
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Leonards, Pim E. G.
    Metabolite alterations in zebrafish embryos exposed to hydroxylated polybrominated diphenyl ethers2023In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 857, article id 159269Article in journal (Refereed)
    Abstract [en]

    Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system. This is the first study focusing on the effects of OH-PBDEs at the metabolite level in vivo. The aim of the current study was to investigate the metabolic effects of exposure to OH-PBDEs using metabolomics, and to identify potential biomarker(s) for energy disruption of OH-PBDEs. Zebrafish (Danio rerio) embryos were exposed to two different concentrations of 6-OH-BDE47 and 6-OH-BDE85 and a mixture of these two compounds. In total, 342 metabolites were annotated and 79 metabolites were affected in at least one exposure. Several affected metabolites, e.g. succinic acid, glutamic acid, glutamine, tyrosine, tryptophan, adenine, and several fatty acids, could be connected to known toxic mechanisms of OH-PBDEs. Several phospholipids were strongly up-regulated with up to a six-fold increase after exposure to 6-OH-BDE47, a scarcely described effect of OH-PBDEs. Based on the observed metabolic effects, a possible connection between disruption of the energy metabolism, neurotoxicity and potential immunotoxicity of OH-PBDEs was suggested. Single compound exposures to 6-OH-BDE47 and 6-OH-BDE85 showed little overlap in the affected metabolites. This shows that compounds of similar chemical structure can induce different metabolic effects, possibly relating to their different toxic mechanisms. There were inter-concentration differences in the metabolic profiles, indicating that the metabolic effects were concentration dependent. After exposure to the mixture of 6-OH-BDE47 and 6-OH-BDE85, a new metabolic profile distinct from the profiles obtained from the single compounds was observed. Succinic acid was up-regulated at the highest, but still environmentally relevant, concentration of 6-OH-BDE47, 6-OH-BDE85, and the mixture. Therefore, succinic acid is suggested as a potential biomarker for energy disruption of OH-PBDEs.

  • 4.
    Gustafsson, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Ström, Karin
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Arvstrand, Linus
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Förlin, Lars
    Asplund, Lillemor
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Balk, Lennart
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Adult female European perch (Perca fluviatilis) from the Baltic Sea show no evidence of thiamine deficiency2021In: Journal of Sea Research, ISSN 1385-1101, E-ISSN 1873-1414, Vol. 174, article id 102081Article in journal (Refereed)
    Abstract [en]

    Deficiency of thiamine (vitamin B1) has been demonstrated in several species in the northern hemisphere and is suggested as a cause for declining populations. European perch from the Baltic Sea show negative temporal trends for several health biomarkers and poor recruitment of unknown cause. In this study, thiamine status of perch liver from the Baltic Sea was studied with emphasis on seasonal variation. During spring the thiamine concentration increased, reached a higher level during the summer and then decreased again during autumn. Despite this variation the thiamine concentration was always sufficient in the perch liver. These results indicate that direct thiamine deficiency is an unlikely explanation for the health effects observed in adult female perch from the Baltic Sea.

  • 5.
    Lindqvist, Dennis
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Gustafsson, Johan
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Degradation of naturally produced hydroxylated polybrominated diphenyl ethers in Baltic Sea sediment via reductive debromination2021In: Environmental Science and Pollution Research, ISSN 0944-1344, E-ISSN 1614-7499, no 28, p. 25878-25885Article in journal (Refereed)
    Abstract [en]

    Over the last two decades, the occurrence of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) has been observed to be nearly ubiquitous among Baltic Sea filamentous macroalgae. High concentrations are continuously recorded among red, green, and brown filamentous algae. Several of these algae species are ephemeral, and when large parts of the colonies decay at the end of their lifecycles, the OH-PBDEs are expected to largely partition to the sediment. In this study, the fate of OH-PBDEs in Baltic Sea sediment was investigated, with focus on the effect of reductive debromination. During chemical debromination, it was observed that the half-life could differ with as much as two orders of magnitude between a pentabrominated and a tetrabrominated congener. Using collected Baltic Sea sediment, it was further observed that the half-life of spiked pentabrominated OH-PBDEs spanned from a few days up to a few weeks in room temperature. At 4 degrees C, it took 6 months to achieve a 50% decrease in concentration of the fasted degrading congener. Clear differences in selectivity between chemical debromination and debromination in sediment were also observed when studying the major reaction products. Baltic Sea sediment seems to have a good capacity for reducing naturally produced OH-PBDEs.

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