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  • 1.
    Asnake, Solomon
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Pradhan, Ajay
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Banjop-Kharlyngdoh, Joubert
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Modig, Carina
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells2014Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 33, nr 4, s. 891-899Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The incorporation of brominated flame retardants into industrial and household appliances has increased their occurrence in the environment, resulting in deleterious effects on wildlife. With the increasing restraints on available compounds, there has been a shift to using brominated flame retardants that has seen the production of alternative brominated flame retardants such as 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH), which has been detected in the environment. In previous in silico and in vitro studies the authors have shown that TBECH can activate both the human androgen receptor (hAR) and the zebrafish AR (zAR) suggesting that it is a potential endocrine disruptor. The present study was aimed at determining the interaction of TBECH with the chicken AR (cAR). In the present study, TBECH bound to cAR, but in vitro activation assay studies using the chicken LMH cell line showed it had a potency of only 15% compared with testosterone. Sequence difference between ARs from different species may contribute to the different responses to TBECH. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that TBECH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that TBECH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. This demonstrates that TBECH, apart from activating cAR, can also influence multiple biological pathways in the chicken.

  • 2. Bergknut, Magnus
    et al.
    Kucera, Adam
    Frech, Kristina
    Andersson, Erika
    Örebro universitet, Institutionen för naturvetenskap.
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap.
    Rannug, Ulf
    Koci, Vladimir
    Andersson, Patrik L.
    Haglund, Peter
    Tysklind, Mats
    Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis2007Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, nr 2, s. 208-217Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.

  • 3.
    Björkblom, Carina
    et al.
    Laboratory of Aquatic Pathobiology, Åbo Akademi University, Turku, Finland.
    Högfors, Eva
    Laboratory of Aquatic Pathobiology, Åbo Akademi University, Turku, Finland.
    Salste, Lotta
    Laboratory of Organic Chemistry, Åbo Akademi University, Turku, Finland.
    Bergelin, Eija
    Laboratory of Wood and Paper Chemistry, Åbo Akademi University, Turku, Finland.
    Olsson, Per-Erik
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Katsiadaki, Ioanna
    Cefas Weymouth Laboratory, Weymouth, United Kingdom.
    Wiklund, Tom
    Laboratory of Aquatic Pathobiology, Åbo Akademi University, Turku, Finland.
    Estrogenic and androgenic effects of municipal wastewater effluent on reproductive endpoint biomarkers in three-spined stickleback (Gasterosteus aculeatus)2009Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 28, nr 5, s. 1063-1071Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Municipal wastewater treatment plants have been associated with the release of endocrine-disrupting chemicals, which consequently lead to alterations of reproductive function in aquatic organisms. The three-spined stickleback (Gasterosteus aculeatus) has quantifiable biomarkers for assessment of both estrogen (vitellogenin) and androgen (spiggin) activity, which makes this species very valuable in the research of endocrine disruption. The estrogenic and androgenic biomarkers were used for evaluating exposure effects of municipal wastewater effluent. We evaluated the effects of 17alpha-ethinylestradiol (EE2), 17alpha-methyltestosterone (MT), and wastewater effluents on induction of vitellogenin and spiggin production, gonadosomatic index, hepatosomatic index, nephrosomatic index, plasma steroid levels, and histopathology. Adult female and male sticklebacks were exposed to 20 ng/L of EE2, 10 microg/L of MT, and wastewater effluent (10, 50, and 80% of original concentration) in a flow-through system for an exposure of one week and an extended exposure of four weeks. Chemical analyses of the steroids were done for verification of exposure concentrations and presence in the used wastewater. Our results show that municipal wastewater effluent exerts estrogenic action on three-spined stickleback as observed by elevated vitellogenin levels in exposed fish, corresponding to the effect seen in fish exposed to EE2. Furthermore, wastewater and EE2 exerted similar histopathological effects on testis of exposed fish. Although domestic effluent is suspected to have a high content of natural androgens, no obvious androgenic effect of wastewater was observed in the present study.

  • 4.
    Brunström, Björn
    et al.
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Engwall, Magnus
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Hjelm, Katarina
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Lindqvist, Lars
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Zebuhr, Yngve
    Aquatic Chemical Ecotoxicology, Department of Zoology, University of Stockholm, Stockholm, Sweden.
    EROD induction in cultured chick embryo liver: a sensitive bioassay for dioxin-like environmental pollutants1995Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 14, nr 5, s. 837-842Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A technique for studying 7-ethoxyresorufin O-deethylase (EROD) induction in chick embryo liver in vitro was developed. Livers from 8-d-old embryos were cultured in rotating vials at 37 degrees C for 48 h in a medium to which DMSO-dissolved test compounds had been added. This bioassay proved to be highly sensitive to dioxin-like compounds, and its usefulness for assessing the toxic potency of such compounds in environmental samples was demonstrated. Concentration-response curves were determined for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-penlachlorobiphenyl (PCB IUPAC no. 126), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,3',4,4'-pentachlorobiphenyl (PCB 105), and benzo[k]fluoranthene (BkF). TCDD induced EROD in a concentration-dependent manner, having an EC50 of 5.0 x 10(-12) M. The cultured embryo livers were extremely sensitive to TCDD, and about 30 fg of this compound per liver (2 x 10(-13) M) was enough to significantly induce EROD. The EC50 values obtained for PCBs 126, 77, 105, and BkF were 4,4 x 10(-11) M, 9.2 x 10(-9) M, 1.6 x 10(-8) M, and 6.2 x 10(-7) M, respectively. The maximal induction levels obtained for three different preparations of polychlorinated naphthalenes (PCNs) were less than those of the other compounds tested. When the technical PCN mixture Halowax 1014 was coadministered with TCDD, the induction was lower than that caused by TCDD alone. An organic extract of fly ash from a municipal waste combustion plant was very potent. Considering its contents of polychlorinated dibenzo-p-dioxins/furans, expressed as TCDD equivalents, the EC50 obtained was close to that for TCDD.

  • 5.
    Ding, Ling
    et al.
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
    Murphy, Margaret B.
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    He, Yuhe
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    Xu, Yan
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    Yeung, Leo W. Y.
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    Wang, Jingxian
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
    Zhou, Bingsheng
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
    Lam, Paul K. S.
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    Wu, Rudolf S. S.
    Center for Coastal Pollution and Conservation, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong.
    Giesy, John P.
    Department of Zoology, Institute for Environmental Toxicology, Michigan State University, East Lansing, MI, United States.
    Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line2007Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, nr 4, s. 764-772Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brominated flame retardants (BFRs) and brominated dioxins are emerging persistent organic pollutants that are ubiquitous in the environment and can be accumulated by wildlife and humans. These chemicals can disturb endocrine function. Recent studies have demonstrated that one of the mechanisms of endocrine disruption by chemicals is modulation of steroidogenic gene expression or enzyme activities. In this study, an in vitro assay based on the H295R human adrenocortical carcinoma cell line, which possesses most key genes or enzymes involved in steroidogenesis, was used to examine the effects of five bromophenols, two polybrominated biphenyls (PBBs 77 and 169), 2,3,7,8-tetrabromodibenzo-p-dioxin, and 2,3,7,8-tetrabromodibenzofuran on the expression of 10 key steroidogenic genes. The H295R cells were exposed to various BFR concentrations for 48 h, and the expression of specific genes - cytochrome P450 (CYP11A, CYP11B2, CYP17, CYP19, and CYP21), 3β- hydroxysteroid dehydrogenase (3βHSD2), 17β-hydroxysteroid dehydrogenase (17βHSD1 and 17βHSD4), steroidogenic acute regulatory protein (StAR), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) - was quantitatively measured using real-time polymerase chain reaction. Cell viability was not affected at the doses tested. Most of the genes were either up- or down-regulated, to some extent, by BFR exposure. Among the genes tested, 3βHSD2 was the most markedly up-regulated, with a range of magnitude from 1.6- to 20-fold. The results demonstrate that bromophenol, bromobiphenyls, and bromodibenzo-p-dioxin/furan are able to modulate steroidogenic gene expression, which may lead to endocrine disruption.

  • 6.
    Engwall, Magnus
    et al.
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Broman, Dag
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden; Inst. of Appl. Environ. Research, Laboratory for Aquatic Ecotoxicology, Stockholm University, Nyköping, Sweden .
    Dencker, Lennart
    Department of Toxicology, Uppsala University, Uppsala, Sweden.
    Näf, Carina
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden .
    Zebuhr, Yngve
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden .
    Brunström, Björn
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Toxic potencies of extracts of sediment and settling particulate matter collected in the recipient of a bleached pulp mill effluent before and after abandoning chlorine bleaching1997Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 16, nr 6, s. 1187-1194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracts of bottom sediment and settling particulate matter (SPM) samples collected in the recipient water body of a bleached pulp mill effluent were separated into three fractions: monoaromatic/aliphatic compounds, diaromatic compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans), and polyaromatic compounds assessment of dioxinlike potency were an in vitro assay, based on the induction of 7-ethoxyresorufin-O-deethylase (EROD) in chicken embryo livers, a test for EROD induction in ovo using chicken embryos, and an immunotoxicity test measuring inhibition of lymphoid cell development in cultured fetal mouse thymuses. The samples collected closest to the mill were the most potent. There was a time-dependent decrease in dioxinlike potency in the SPM samples collected near the mill, which coincided with the cessation of chlorine gas bleaching at the mill. The bioassays in general, and the in vitro chicken embryo liver bioassay in particular, proved useful in the assessment of dioxinlike compounds in the sediment and SPM samples. The polyaromatic fractions of the samples were generally more potent than the diaromatic fractions. Only a small part of the effects caused by the polyaromatic fractions could be explained by 15 analyzed PAHs, indicating the presence of unquantified polyaromatic compounds with dioxinlike effects. This investigation indicates that the cessation of chlorine bleaching in the pulp mill resulted in a reduced load of diaromatic dioxinlike compounds in the recipient water body.

  • 7.
    Engwall, Magnus
    et al.
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Broman, Dag
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden; Inst. of Appl. Environ. Research, Laboratory for Aquatic Ecotoxicology, Stockholm University, Nyköping, Sweden .
    Ishaq, Rasha
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden.
    Näf, Carina
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden.
    Zebuhr, Yngve
    Aquatic Chemical Ecotoxicology, Department of Zoology, Stockholm University, Stockholm, Sweden.
    Brunström, Björn
    Dept. of Environmental Toxicology, Uppsala University, Uppsala, Sweden .
    Toxic potencies of lipophilic extracts from sediments and settling particulate matter (SPM) collected in a PCB-contaminated river system1996Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 15, nr 2, s. 213-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sediments and settling particulate matter (SPM) were sampled in a polychlorinated biphenyl (PCB)-contaminated lake, Lake Jarnsjon, and in lakes located up-/and downstream from Lake Jarnsjon. The 7-ethoxyresorufin O-deethylase (EROD)-inducing potencies of lipophilic extracts from sediment and SPM were investigated in organ cultures of chicken embryo livers (denoted in vitro chicken embryo liver bioassay). The extract from sediments collected in Lake Jarnsjon had the greatest EROD-inducing potency of the extracts studied, and it also contained the highest concentrations of PCBs, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated dibenzodioxins/furans (PCDDs/Fs). The non-ortho-chlorinated PCBs in the extracts were probably major contributors to the EROD induction noted. The EROD-inducing potency of sediment extract from the lake downstream Lake Jarnsjon was higher than that of extract from the upstream lake. This indicates that EROD-inducing substances were transported from Lake Jarnsjon sediment to the lake downstream. The extracts from Lake Jarnsjon sediment and SPM were separated into three fractions containing aliphatic/monoaromatic, diaromatic, and polyaromatic compounds, respectively, which were tested in the in vitro chicken embryo Liver bioassay. In all extracts, the aliphatic/monoaromatic fractions were low in EROD-inducing potency, while the polyaromatic fractions from SPM were more potent than their corresponding diaromatic fractions, indicating that they contained high concentrations of aromatic hydrocarbon (Ah) receptor ligands. Only a small part of the EROD induction caused by the polyaromatic fractions could be attributed to the 15 analyzed PAHs in the samples. The EROD-inducing potencies of the diaromatic fractions correlated quite well with their concentrations of PCDDs/Fs and PCBs. The in vitro chicken embryo liver bioassay detected low concentrations of EROD inducers in the extracts and therefore proved useful for estimating the contents of Ah receptor ligands in environmental samples.

  • 8.
    Lam, Monika M.
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Bülow, Rebecca
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Giesy, John P.
    Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Canada.
    Larsson, Maria
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Methylated PACs Are More Potent than Their Parent Compounds: A Study on AhR-mediated Activity, Degradability and Mixture Interactions in the H4IIE-luc Assay2018Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 37, nr 5, s. 1409-1419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Twenty-six polycyclic aromatic compounds (PACs; including native polycyclic aromatic hydrocarbons [PAHs], hydroxylated PAHs, alkylated and oxygenated PAHs, and [alkylated] heterocyclic compounds) were investigated for their aryl hydrocarbon receptor (AhR)-mediated potencies in the H4IIE-luc bioassay. Potential degradabilities of PACs were investigated by use of various durations of exposure (24, 48, or 72 h), and various mixtures of PACs including PAHs, alkylated and oxygenated PAHs, and heterocyclic compounds were tested for their joint AhR-mediated potency. Additive behaviors of PACs in mixtures were studied by comparing observed mixture potencies with mixture potencies predicted by use of the concentration addition model. Methylated derivatives were more potent than their parent compounds in the H4IIE-luc assay. A time-dependent decrease in relative potency was observed for all AhR-active compounds, which may be indicative of in vitro biotransformation. Monomethylated compounds seemed to be more rapidly transformed than analogous unsubstituted compounds. In addition, the results showed that the predictive power of the concentration addition model increased with the number of compounds, suggesting additivity in multicomponent mixtures. Due to the greater potency of methylated derivatives and their ubiquitous occurrence, there is a need for further research on the toxicity and mixture behavior of these environmentally and toxicologically relevant compounds.

  • 9.
    Lam, Monika M.
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Denison, Michael S
    Department of Environmental Toxicology, University of California, Davis CA, USA.
    Larsson, Maria
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Methylated polycyclic aromatic hydrocarbons and/or their metabolites are important contributors to the overall estrogenic activity of polycyclic aromatic hydrocarbon-contaminated soils2018Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 37, nr 2, s. 385-397Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study 42 polycyclic aromatic compounds (PACs) were investigated for their estrogenic potential using the VM7Luc4E2 transactivation assay. Relative potencies were determined for mass-balance analysis. In addition, compounds were tested in combination with the estrogen receptor (ER) antagonist vertical bar C vertical bar 182,780 (vertical bar C vertical bar) and the aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone. Luciferase induction and CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD) activity were measured to assess whether the estrogenic activity was elicited by the compound itself and/or by its metabolites. Relative potencies ranged between 10(-7) and 10(-4). The ability of ICI to decrease luciferase activity stimulated by all compounds indicated that the induction responses were ER-dependent. The aryl hydrocarbon receptor antagonist/CYP1A1 inhibitor a-naphthoflavone decreased luciferase induction and EROD activity by several compounds, including the methylated chrysenes, suggesting that metabolites of these chemicals contributed to ER activation. Several PACs, such as acridine and its derivatives, appear to directly activate the ER. Furthermore, extracts of soils from industrial areas were examined using this bioassay, and estrogenic activity was detected in all soil samples. Mass-balance analysis using a combination of relative potencies and chemical analysis of the samples suggested that polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, such as 1-and 3-methylchrysene, are important contributors to the overall estrogenic activity. However, these results revealed that a considerable proportion of the estrogenic activity in the soil remained unexplained, indicating the presence of other significant estrogenic compounds.

  • 10.
    Larsson, Maria
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Hagberg, Jessika
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Giesy, John P.
    Dept Vet Biomed Sci, Univ Saskatchewan, Saskatoon SK, Canada; Toxicol Ctr, Univ Saskatchewan, Saskatoon SK, Canada; Dept Zool, Michigan State Univ, E Lansing, USA; Ctr Integrat Toxicol, Michigan State Univ, E Lansing, USA; Dept Biol & Chem, City Univ Hong Kong, Kowloon, Peoples R China; State Key Lab Marine Pollut, City Univ Hong Kong, Kowloon, Peoples R China; Sch Biol Sci, Univ Hong Kong, Hong Kong, Peoples R China; Sch Environm, State Key Lab Pollut Control & Resource Reuse, Nanjing Univ, Nanjing, Peoples R China .
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Time-dependent relative potency factors for polycyclic aromatic hydrocarbons and their derivatives in the H4IIE-luc bioassay2014Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 33, nr 4, s. 943-953Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The H4IIE-luc transactivation bioassay for aryl hydrocarbon receptor (AhR) agonists was used to investigate the relative potency factors (REPs) of 22 individual polycyclic aromatic hydrocarbons (PAHs) and their oxygenated-, methylated-, and N-containing derivatives (azaarenes), which are often present in PAH-contaminated soils. Naphthacene and dibenz[ah]acridine exhibited greater AhR-mediated potency, whereas lesser molecular-weight azaarenes were less potent AhR agonists. Six oxygenated PAHs had calculable REPs, but their potencies were less than their parent PAHs. Unlike the parent, unsubstituted PAHs, oxidation of methylated PAHs seemed to increase the AhR-mediated potency of the compounds, with 2-methylanthracene-9,10-dione being almost 2 times more potent than 2-methylanthracene. Both bioassay and gas chromatography-mass spectrometry analysis were used to examine the exposure time-dependent effects on the REPs at 24 h, 48 h, and 72 h of exposure in the H4IIE-luc transactivation bioassay. Changes in concentrations of 5 compounds including the model reference 2,3,7,8-tetrachlorodibenzo-p-dioxin in the cell culture wells were measured, and the amounts in the cell medium, in the cells, and adsorbed to the wells was determined and the influence on the REPs was studied. Declining REP values with increased duration of exposure were shown for all compounds, which we concluded were a consequence of the metabolism of PAHs and PAH derivatives in H4IIe-luc cells. The present study provides new knowledge regarding the degradation and distribution of compounds in the wells during exposure. Environ Toxicol Chem 2014;33:943-953. (c) 2014 SETAC

  • 11.
    Larsson, Maria
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Orbe, Dan
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Exposure time-dependent effects on the relative potencies and additivity of PAHs in the Ah receptor-based H4IIE-luc bioassay2012Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 31, nr 5, s. 1149-1157Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the present study, relative potency factors (REPs) of 16 individual polycyclic aromatic hydrocarbons (PAHs) were investigated using the H4IIE-luc bioassay. Exposure time-dependent effects on the REPs were examined using 24, 48, and 72?h of exposure. Seven different mixtures of PAHs were tested for additivity at an exposure time of 24?h. Three of the PAH mixtures were also studied at 48 and 72?h of exposure. The mixture toxicities were predicted using the REP concept and the concentration addition (CA) model. Relative potency factor values investigated in the present study were similar to those reported in earlier studies. Declining REPs with an increasing exposure time were shown for all PAHs, indicating that this bioassay approach could be developed to assess the persistency of aryl hydrocarbon receptor (AhR) agonistic PAHs and in the risk assessment of complex PAH mixtures. The results from the mixture studies indicated that additive interactions of PAHs are time dependent. Generally, 48- and 72-h exposures resulted in biological effects that were similar to the CA and REP model predictions, while these models tended to underestimate the effect, to some extent, in the 24-h exposure, at least for the mixtures containing two to four PAHs. Thus, it cannot be ruled out that in the 24-h exposures, the tested PAH mixtures had slight synergistic effects. Further research is needed to identify and test additional AhR activating PAHs and investigate whether the effects in the H4IIE-luc bioassay are additive for more complex samples containing both PAHs and other AhR-activating contaminants. Also, the observed superinduction of luciferase by PAH-mixes warrants studies of whether this also can occur for relevant AhR-mediated endpoints in vivo. 

  • 12.
    Olsman [Takner], Helena
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Engwall, Magnus
    Örebro universitet, Institutionen för naturvetenskap.
    Kammann, Ulrike
    Klempt, Martin
    Otte, Jens
    van Bavel, Bert
    Örebro universitet, Institutionen för naturvetenskap.
    Hollert, Henner
    Relative differences in aryl hydrocarbon receptor-mediated response for 18 polybrominated and mixed halogenated dibenzo-p-dioxins and -furans in cell lines from four different species2007Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, nr 11, s. 2448-2454Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    As a consequence of ubiquitous use of brominated organic chemicals, there is a concern for persistent or increasing environmental levels of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated dibenzo-p-dioxins/furans (PXDD/Fs). Hence, there is a need to broaden the toxicological and environmental knowledge about these compounds, as a basis for risk assessment. In the study presented here, the relative potencies (REPs) for 18 PBDD/F and PXDD/ F congeners were determined in four dioxin-specific bioassays from different species: dioxin receptor chemically activated luciferase expression assay (DR-CALUX, rat hepatoma cells), TV101L (human hepatoma cells), and GPC.2D (guinea pig adenoma cells), as well as ethoxyresorufin-O-deethylase induction in the fish cell line RTL-W1 (rainbow trout liver cells). The bioassay specific REP factors presented here enable the assessment of the contribution from PBDD/Fs and PXDD/Fs to total 2,3,7,8-tetrachl orodibenzop-dioxin (TCDD) equivalents (TEQs: toxic equivalents), using bioassay analysis. The PBDD/Fs were found to be equally potent as their chlorinated analogues in the three mammalian assays, whereas the PXDD/Fs showed relatively higher potencies. Of special concern were the 2,3,7,8-substituted penta- and tetrahalogenated congeners, for which mean REPs were >= 1. The 2-B-1,3,7,8-CDD (2-bromo-1,3,7,8-tetrachlorodibenzo-p-dioxin) was up to three times more potent than TCDD in individual experiments (on weight basis). The RTL-W1 was less sensitive to the tested compounds with overall 10-fold lower REPs than the mammalian cell lines. Although the REP factors exhibited species-specific differences, overall resembling rank orders of dioxin-like potency were obtained.

  • 13. Wiberg, Karin
    et al.
    Andersson, Patrik L.
    Berg, Håkan
    Örebro universitet, Institutionen för naturvetenskap.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap.
    Haglund, Peter
    The fate of chiral organochlorine compounds and selected metabolites in intraperitoneally exposed arctic char (Salvelinus alpinus)2006Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 25, nr 6, s. 1465-1473Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The fate of chiral organochlorine compounds (OCs) and selected metabolites in exposed Arctic char (Salvelinus alpinus) was investigated. The contaminants alpha-hexachlorocyclohexane (alpha-HCH), cis-chlordane, 13C4-heptachlor, o,p'-DDT, and the atropisomeric chlorinated biphenyls (CBs) 95, 132, 136, 149, and 174 were solved in peanut oil and injected into the peritoneal cavity. The exposed fish were sampled three times during a five-week period, and the OC residues and detected metabolites (heptachlorexo-epoxide) were quantified in muscle and liver tissues by chiral and achiral gas chromatography-mass spectrometry and gas chromatography-electron-capture detection. Peak concentrations were reached after one to two weeks, and thereafter, the levels declined. At the end of the experiment, liver concentrations had decreased 76 to 92% relative to peak concentrations, whereas muscle concentrations showed a moderate decline (5-38%), with the exception of alpha-HCH (91%). Hydrophobicity and steric hindrance were shown to influence the assimilation process, and a significant linear relationship between the product of the steric hindrance coefficients and the inverse of the octanol-water partition coefficients (Kow) versus peak concentration was found for the CBs (r2 = 0.86, p = 0.02). The assimilation of the contaminants into muscle and liver tissues generally resulted in racemic mixtures, whereas elimination was enantioselective for alpha-HCH, cis-chlordane, o,p'-DDT, CB-132, and CB-136. The chiral heptachlor metabolite 13C4-heptachlor-exo-epoxide was formed in the fish. The enantiomeric composition of the formed metabolite indicated racemic formation, whereas the elimination process appeared to be enantioselective.

  • 14. Wolkers, Hans
    et al.
    Corkeron, Peter J.
    van Parijs, Sofie M.
    Similä, Tiu
    van Bavel, Bert
    Örebro universitet, Institutionen för naturvetenskap.
    Accumulation and transfer of contaminants in killer whales (Orcinus orca) from Norway: indications for contaminant metabolism2007Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, nr 8, s. 1582-1590Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Blubber tissue of one subadult and eight male adult killer whales was sampled in Northern Norway in order to assess the degree and type of contaminant exposure and transfer in the herring-killer whale link of the marine food web. A comprehensive selection of contaminants was targeted, with special attention to toxaphenes and polybrominated diphenyl ethers (PBDEs). In addition to assessing exposure and food chain transfer, selective accumulation and metabolism issues also were addressed. Average total polychlorinated biphenyl (PCB) and pesticide levels were similar, approximately 25 microg/g lipid, and PBDEs were approximately 0.5 microg/g. This makes killer whales one of the most polluted arctic animals, with levels exceeding those in polar bears. Comparing the contamination of the killer whale's diet with the diet of high-arctic species such as white whales reveals six to more than 20 times higher levels in the killer whale diet. The difference in contaminant pattern between killer whales and their prey and the metabolic index calculated suggested that these cetaceans have a relatively high capacity to metabolize contaminants. Polychlorinated biphenyls, chlordanes, and dichlorodiphenyldichloro-ethylene (DDE) accumulate to some degree in killer whales, although toxaphenes and PBDEs might be partly broken down.

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