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  • 1. Al-Anati, Lauy
    et al.
    Viluksela, Matti
    Strid, Anna
    Bergman, Åke
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenius, Ulla
    Högberg, Johan
    Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene2015In: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 239, p. 164-173Article in journal (Refereed)
    Abstract [en]

    Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.

  • 2.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Berg, A. H.
    Bjerselius, R.
    Norrgren, L.
    Olsson, P.-E.
    Örn, S.
    Tysklind, Mats
    Uptake and elimination of selected PCBs in zebra fish, three-spined stickleback and arctic char after three different routes of exposure2001In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341, E-ISSN 1432-0703, Vol. 40, no 4, p. 519-530Article in journal (Refereed)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 3.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Berg, A H
    Bjerselius, R
    Norrgren, L
    Olsén, H
    Olsson, P-E
    Örn, S
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Bioaccumulation of Selected PCBs in Zebrafish, Three-Spined Stickleback, and Arctic Char After Three Different Routes of Exposure2001In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341 (Print) 1432-0703 (Online), Vol. 40, no 4, p. 519-30Article in journal (Refereed)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 4.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rappe, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ultraviolet absorption characteristics and calculated semi-empirical parameters as chemical descriptors in multivariate modelling of polychlorinated biphenyls1996In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 10, no 2, p. 171-185Article in journal (Refereed)
    Abstract [en]

    The structural variation within the polychlorinated biphenyls (PCBs) was characterized by using principal component analysis (PCA). A multivariate model was evolved from 52 physicochemical descriptors including measured ultraviolet (UV) absorption spectra, calculated semiempirical parameters (AM1) and properties captured from the literature. Parameters calculated by using the AM1-Hamiltonian were e.g. heat of formation, dipole moments, ionization potential and the barrier of internal rotation. The UV spectra were measured and digitized in the range 200-300 nm. The multivariate model revealed that most of the information within the set of physicochemical parameters was related to molecular size. Descriptors depending on size were e.g. GC retention times, partition coefficients and a subset of semiempirically derived energy terms. Important also were parameters reflecting differences in substitution patterns and related to electronic and steric properties, such as UV absorption in the wavelength region 245-300 nm, the barrier of internal rotation and the ionization potential. The developed model describes the large variation in physicochemical characteristics within the PCBs. The importance of a broad chemical characterization is illustrated by a quantitative structure-activity relationship (QSAR) for the potency of inhibition of intercellular communication for 27 structurally diverse tetra- to heptachlorinated PCBs.

  • 5.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ultraviolet absorption spectra of all 209 polychlorinated biphenyls evaluated by principal component analysis1997In: Fresenius' Journal of Analytical Chemistry, ISSN 0937-0633, E-ISSN 1432-1130, Vol. 357, no 8, p. 1088-1092Article in journal (Refereed)
    Abstract [en]

    The ultraviolet absorption spectra of all 209 polychlorinated biphenyls (PCBs) were recorded in the range 200-300 nm and displayed two important absorption maxima, viz., the main-band, lambda(max) 200-225 nm, and the kappa-band, lambda(max) 245-265 nm. By utilising principal component analysis, substitution related spectral characteristics of the PCBs, underlying the main patterns of the spectra, were examined. Captured in the multivariate evaluation were e.g., the importance of chlorine atoms in ortho positions, determining the intensity and existence of the kappa-band, chlorine substitution in para-para position, and the total number of chlorine atoms. The measured UV-spectra of all 209 polychlorinated biphenyls provide important physico-chemical descriptors for use in future quantitative structure-activity and structure-property relationship (QSAR/QSPR) studies.

  • 6.
    Andersson, Patrik L
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fick, Jerker
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rännar, Stefan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A Multivariate Chemical Similarity Approach to Search for Drugs of Potential Environmental Concern2011In: Journal of chemical information and modeling, ISSN 1549-960X, Vol. 51, no 8, p. 1788-1794Article in journal (Refereed)
    Abstract [en]

    A structural similarity tool was developed and aimed to search for environmentally persistent drugs. The basis for the tool was a selection of so-called anchor molecules and a multidimensional chemical map of drugs. The map was constructed using principal component analysis covering 899 drugs described by 67 diverse calculated chemical descriptors. The anchor molecules (diclofenac, trimethoprim, and carbamazepine) were selected to represent drugs of known environmental concern. In addition 12 chemicals listed by the Stockholm Convention on persistent organic pollutants were used representing typical environmental pollutants. Chemical similarity was quantified by measuring relative Euclidean distances in the five-dimensional chemical map, and more than 100 nearest neighbors (kNNs) were found within a relative distance of less than 10% from each drug anchor. The developed chemical similarity approach not only identified persistent or semipersistent drugs but also a large number of potentially persistent drugs lacking environmental fate data.

  • 7.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Maran, Uko
    Fara, Dan
    Karelson, Mati
    Hermens, Joop L M
    General and Class Specific Models for Prediction of Soil Sorption Using Various Physicochemical Descriptors2002In: Journal of Chemical Information and Modeling, Vol. 42, no 6, p. 1450-9Article in journal (Refereed)
    Abstract [en]

    Diverse chemical descriptors were explored for use in QSAR models aimed to screen the soil sorption potential of organic compounds. The descriptors included logP, HyperChem QSARProperties descriptors, a combination of connectivity indices, geometrical, and quantum chemical measures, and two sets from the DRAGON and CODESSA program packages, respectively. Generally, the univariate logP models were capable of capturing most of the variation and give an indication of the sorption potential. The multivariate models required refined variable selection procedures but were shown to include crucial descriptors for modeling compound classes with specific chemical characteristics.

  • 8.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Stenberg, Maria
    Umeå University, Faculty of Science and Technology, Chemistry.
    Mariussen, E
    Fonnum, F
    Structure-Activity Relationships of PCBS Potency as neurotoxicants2006In: Organohalogen Compounds, Vol. 68, p. 117-20Article in journal (Refereed)
  • 9.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    An introduction to QSARs2006In: Using chemistry in environmental and health risk assessment, US-AB Universitetsservice, Stockholm , 2006, p. 51-74Chapter in book (Refereed)
  • 10.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    van der Burght, Aafje S.A.M.
    van den Berg, Martin
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species: ranking scales and species differences2000In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 19, no 5, p. 1454-1463Article in journal (Refereed)
    Abstract [en]

    Cytochrome P4501A–induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physi-cochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-ortho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.

  • 11.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    van der Burght, ASAM
    van den Berg, M
    Tysklind, Mats
    Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences2000In: ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, ISSN 0730-7268, Vol. 19, no 5, p. 1454-63Article in journal (Refereed)
    Abstract [en]

    Cytochrome P4501A-induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physicochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-or rho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.

  • 12.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Öberg, Kjell
    Örn, U
    Chemical characterization of brominated flame retardants and identification2006In: Environmental Toxicology and Chemistry, ISSN 0730-7268, Vol. 25, no 5, p. 1275-82Article in journal (Refereed)
    Abstract [en]

    Three training sets were selected, each consisting of 10 structurally diverse compounds representative of brominated flame retardants (BFRs) that are either in use or have been used. Just three compounds account for nearly all the total production volume of BFRs. In the present study, however, the physicochemical characteristics of a far more structurally diverse set of 65 BFRs was explored using 15 molecular descriptors (including log P, constitutional counts, and semiempirical quantum mechanical parameters) and principal component analysis (PCA). The PCA generated an overview of the structural variation among BFRs, and certain compounds with unique physicochemical properties and specific clusters of compounds with distinct properties were identified. The training-set compounds were selected by applying the condensed information obtained from the PCA and statistical experimental design. The three training sets, which were designated as optimal, practical, and alternative, were selected either to maximize the structural variation (optimal) or to combine structural variation with practical advantages, such as ease of experimental handling and commercial availability (practical and alternative). Inclusion of the suggested compounds in assessments of the persistence, bioaccumulation, and toxicity properties of BFRs and related programs should help to increase our understanding of the effects and environmental fate of these compounds.

  • 13.
    Andersson, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Örn, U
    Öberg, Kjell
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Chemical characterization and strategic selection of BFRs for PBT assessment2004In: Abstract BFR2004 Toronto, 2004Conference paper (Other academic)
  • 14.
    Arnoldsson, Kristina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Formation of environmentally relevant brominated dioxins from 2,4,6-tribromophenol via bromoperoxidase-catalyzed dimerisationManuscript (preprint) (Other academic)
    Abstract [en]

    Polybrominated dibenzo-p-dioxins (PBDD) are emerging environmental pollutants with structural similarities to the highly characterized toxicants polychlorinated dibenzo-p-dioxins. The geographical and temporal variations of PBDD in biota samples from the Baltic Sea do not display features that are normally related to anthropogenic sources, and therefore the natural formation of PBDDs has been suggested. This study of the bromoperoxidase mediated oxidative coupling of 2,4,6-tribromophenol (an abundant substance that is naturally formed in marine systems) identified the formation of ppb-level yields of 1,3,6,8-tetrabromodibenzo-p-dioxin (1,3,6,8-TeBDD) through direct condensation. Additional TeBDDs (1,3,7,9-TeBDD, 1,2,4,7-TeBDD and/or 1,2,4,8-TeBDD) and tri-BDDs (1,3,7-TrBDD and 1,3,8-TrBDD) were frequently formed, but at lower yields. The formation of these TeBDDs probably proceeds via bromine shifts or Smiles rearrangements, while the TrBDDs may result from subsequent debromination processes. Since all of the congeners formed by oxidative coupling and subsequent reactions are also found in Baltic Sea biota, the results support the theory that PBDDs are formed from natural precursors.

  • 15.
    Arnoldsson, Kristina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Formation of environmentally relevant brominated dioxins from 2,4,6,-tribromophenol via bromoperoxidase-catalyzed dimerization2012In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 46, no 13, p. 7239-7244Article in journal (Refereed)
    Abstract [en]

    Polybrominated dibenzo-p-dioxins (PBDD) are emerging environmental pollutants with structural similarities to the highly characterized toxicants polychlorinated dibenzo-p-dioxins. The geographical and temporal variations of PBDD in biota samples from the Baltic Sea do not display features that are normally related to anthropogenic sources such as incineration, and therefore the natural formation of PBDDs has been suggested. This study of the bromoperoxidase mediated oxidative coupling of 2,4,6-tribromophenol (an abundant substance that is naturally formed in marine systems) identified the formation of ppb-level yields of 1,3,6,8-tetrabromodibenzo-p-dioxin (1,3,6,8-TeBDD) through direct condensation. Additional TeBDDs (1,3,7,9-TeBDD, 1,2,4,7-TeBDD and/or 1,2,4,8-TeBDD) and tri-BDDs (1,3,7-TrBDD and 1,3,8-TrBDD) were frequently formed, but at lower yields. The formation of these TeBDDs probably proceeds via bromine shifts or Smiles rearrangements, while the TrBDDs may result from subsequent debromination processes. Since all of the congeners formed by oxidative coupling and subsequent reactions are also found in Baltic Sea biota, the results support the theory that PBDDs are formed from natural precursors.

  • 16.
    Arnoldsson, Kristina
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Photochemical formation of polybrominated dibenzo-p-dioxins from environmentally abundant hydroxylated polybrominated diphenyl ethers2012In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 46, no 14, p. 7567-7574Article in journal (Refereed)
    Abstract [en]

    High levels of polybrominated dibenzo-p-dioxins (PBDDs) have been found in Baltic Sea biota, where the toxic load owing to, for example, polychlorinated dibenzo-p-dioxins and other organic pollutants is already high. The levels and geographic pattern of PBDDs suggest biogenic rather than anthropogenic origin, and both biotic and abiotic formation pathways have been proposed. Photochemical formation from hydroxylated polybrominated diphenyl ethers (OH-PBDE) is a proposed pathway. for PBDDs in marine environments. Ultraviolet radiation-initiated transformations of OH-BDEs 47, 68, 85, 90, 99, and 123, which all are abundant in the environment, were investigated. It was shown that the most abundant PBDDs in the environment (1,3,7-triBDD and 1,3,8-triBDD) can be formed from the most abundant OH-BDEs (OH-BDE 47 and OH-BDE 68) at high rates and with percentage yields. In fact, most of the PBDDs that have been identified in the Baltic Sea environment were formed with high yield from the six studied OH-PBDE, through initial cyclization and subsequent debromination reactions. The high formation yields point to this route as an important source of PBDDs in biota. However, congeners showing relatively high retention in fish, specifically 1,3,6,8- and 1,3,7,9-tetraBDD, were not formed. These are likely formed by enzymatic coupling of brominated phenols.

  • 17. Arp, Hans Peter H
    et al.
    Møskeland, Thomas
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nyholm, Jenny Rattfelt
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Presence and partitioning properties of the flame retardants pentabromotoluene, pentabromoethylbenzene and hexabromobenzene near suspected source zones in Norway2011In: Journal of Environmental Monitoring, ISSN 1464-0325, E-ISSN 1464-0333, Vol. 13, no 3, p. 505-513Article in journal (Refereed)
    Abstract [en]

    The brominated flame retardants (BFRs), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB) and hexabromobenzene (HBB), exhibit physical-chemical properties similar to other persistent organic pollutants, and have been in use as flame retardants for several decades. Data on these BFRs in diverse environmental samples can be found in studies from the 1970s and 1980s, as well as in recent years, though very little in the years in between. Due to a lack of data, the cause for the apparent re-emergence of these BFRs in recent studies is unclear, and could reflect changes in production volumes, accumulation of transformation products from BFR precursors, improved analytical techniques or simply a re-emergence in concern. Very little data are available on their environmentally relevant partitioning properties, which could help to explain the occurrence and fate of these BFRs. In this study we analysed for the presence of HBB, PBT, and PBEB in diverse environmental samples from potential Norwegian BFR source zones. Additionally, environmental partitioning properties of these BFRs as well as brominated benzenes were estimated and validated using experimental data for brominated benzenes. Of the three BFRs, HBB was identified in detectable quantities at most source zones, PBEB only near a metal recycling factory, and PBT only in a few additional locations from where PBEB was detected. Data from this study show that HBB is likely widely distributed, as verified both by chemical analysis and estimated properties. Measured HBB levels in wastewater treatment plants indicate that the treatment practices used in the study locations are not effective at lowering HBB levels, perhaps due to association with low density suspended solids (e.g. microplastics).

  • 18.
    Augulyte, Lijana
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Kliaugaite, D
    Racys, V
    Jankunaite, D
    Zaliauskiene, A
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Bergqvist, Per-Anders
    Umeå University, Faculty of Science and Technology, Chemistry.
    Chemical and Ecotoxicological Assessment of Selected Biologically Activated Sorbents for Treating Wastewater Polluted with Petroleum Products with Special Emphasis on Polycyclic Aromatic Hydrocarbons2008In: Water, Air, & Soil Pollution, ISSN 0049-6979 (Print) 1573-2932 (Online), Vol. 195, no 1-4, p. 243-56Article in journal (Refereed)
    Abstract [en]

    A chemical and ecotoxicological assessment of treatment of wastewater that had been polluted with petroleum products using only Activated Sludge (AS) and four biologically activated sorbents (BASs), consisting of activated sludge plus: coal-based activated carbon (-C1), coconut shell-based activated carbon (-C2), zeolite (-Z), and anthracite (-A) were conducted. The efficiency and robustness of the four wastewater treatment systems were evaluated by calculating the reduced total petroleum hydrocarbon (TPH) and polycyclic aromatic hydrocarbon (PAH) contents and the acute ecotoxicity of the effluents. The chemical analysis showed that the combined treatment systems were very effective for reducing the total petroleum hydrocarbon and readily bioavailable PAH contents. The most efficient systems were the BAS-C1 and -C2, which removed 60–88% and 99.5–99.6% of TPH and PAH, respectively. The activated sludge-only treatment was the least effective for purifying the wastewater. Chemical oxygen demand was reduced by >90% by all carbon-based BASs (BAS-C1, BAS-C2 and BAS-A). Shifts in the relative composition of the individual PAHs were identified in samples taken before and after treatment. Algal and bacterial bioassays showed that the toxicities of effluents following treatment by all four systems (except AS for algae) were reduced by more than 80% and 90%, respectively. However, crustacean tests indicated that the carbon-based BASs reduced the toxicity [V tox(50)] only by 19–67%. Our results indicated that the combination of sorption and biodegradation processes have great potential in the treatment of petroleum products polluted wastewater and is less sensitive for inhibitors of the biological process than treatments in which activated sludge alone is used. The assessment of chemical and ecotoxicological endpoints provided valuable information, but contrasting results for one of the assays indicates that further analysis on the capacity of the different treatment systems is warranted.

  • 19.
    Augulyte, Lijana
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kliaugaite, Daina
    Racys, Viktoras
    Jankunaite, Dalia
    Zaliauskiene, Audrone
    Bergqvist, Per-Anders
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate analysis of a biologically activated carbon (BAC) system and its efficiency for removing PAHs and aliphatic hydrocarbons from wastewater polluted with petroleum products2009In: Journal of Hazardous Materials, ISSN 0304-3894, E-ISSN 1873-3336, Vol. 170, no 1, p. 103-110Article in journal (Refereed)
    Abstract [en]

    The efficiency of a biologically activated carbon system for treating wastewater polluted with petroleum products was examined and the effects of process parameters on its efficacy were evaluated. In each experiment 17 alkylated and 19 non-alkylated polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs, C10-C40) were extracted using semipermeable membrane devices from wastewater before and after treatment. The acquired data during experiments were analyzed using principal component analysis (PCA). The treatment system robustly removed dissolved PAHs across the studied ranges of the process parameters, providing overall removal efficiencies of 96.9-99.7% for the sum of 36 PAHs. However, the major contributor to their removal was sorption rather than biodegradation, and despite the general efficiency of the process there was up to a 9-fold range in the sums of quantified PAHs in the effluents between experiments. Combinations of long process contact time (24 h) with high temperature (24 degrees C) and moderate oxygen concentration (6-7mg O2 L-1) resulted in good removal of bioavailable PAHs. The removal of TPHs was more dependent on biological activities during the wastewater treatment, and consequently more dependent on the process parameters. In addition, small but significant proportions of PAHs were volatilized and released during the wastewater treatment.

  • 20.
    Augulyte, Lijana
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Lindberg, Richard H
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Chemistry.
    Söderström, Hanna
    Laboratory evaluation of the temperature effect on the uptake of selected pharmaceuticals by the polar organic chemical integrative sampler (POCIS)Manuscript (Other academic)
  • 21.
    Bergknut, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Eriksson, Lennart
    Nyman, Madeleine
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Novel multivariate methods for evaluation of PCB levels, and of CYP1A, vitamin E, and haematological parameters as PCB-exposure biomarkers, in seal2005In: Organohalogen Compounds, Vol. 67, p. 1867-70Article in journal (Refereed)
  • 22.
    Bergknut, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Kucera, Adam
    Frech, Kristina
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Erika
    Engwall, Magnus
    Rannung, Ulf
    Koci, Vladimir
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Identification of potentially toxic compounds in complex extracts of environmental samples using GC-MS and multivariate data analysis2007In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, no 2, p. 208-17Article in journal (Refereed)
    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.

  • 23.
    Bergknut, Magnus
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Sehlin, Emma
    Umeå University, Faculty of Science and Technology, Chemistry.
    Lundstedt, Staffan
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Comparison of techniques for estimating PAH bioavailability: uptake in Eisenia fetida, passive samplers and leaching using various solvents and additives.2007In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 145, no 1, p. 154-60Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate different techniques for assessing the availability of polycyclic aromatic hydrocarbons (PAHs) in soil. This was done by comparing the amounts (total and relative) taken up by the earthworm Eisenia fetida with the amounts extracted by solid-phase microextraction (SPME), semi-permeable membrane devices (SPMDs), leaching with various solvent mixtures, leaching using additives, and sequential leaching. Bioconcentration factors of PAHs in the earthworms based on equilibrium partitioning theory resulted in poor correlations to observed values. This was most notable for PAHs with high concentrations in the studied soil. Evaluation by principal component analysis (PCA) showed distinct differences between the evaluated techniques and, generally, there were larger proportions of carcinogenic PAHs (4–6 fused rings) in the earthworms. These results suggest that it may be difficult to develop a chemical method that is capable of mimicking biological uptake, and thus estimating the bioavailability of PAHs.

    The total and relative amounts of PAHs extracted by abiotic techniques for assessing the bioavailability of PAHs was found to differ from the amounts taken up by Eisenia fetida.

    Keywords: Bioavailability; Polycyclic aromatic hydrocarbons; Earthworms; Leaching; Hydroxypropyl-β-cyclodextrin; Solid-phase microextraction; Semi-permeable membrane device

  • 24.
    Blum, Kristin M.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ahrens, Lutz
    Wiberg, Karin
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Persistence, mobility and bioavailability of emerging organic contaminants discharged from sewage treatment plants2018In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 612, p. 1532-1542Article in journal (Refereed)
    Abstract [en]

    Little is known about the impact of emissions of micropollutants from small and large-scale sewage treatment plants (STPs) on drinking water source areas. We investigated a populated catchment that drains into Lake Malaren, which is the drinking water source for around 2 million people including the inhabitants of Stockholm, Sweden. To assess the persistence, mobility, bioavailability and bioaccumulation of 32 structurally diverse emerging organic contaminants, sediment, integrated passive and grab water samples were collected along the catchment of the River Fyris, Sweden. The samples were complemented with STP effluent and fish samples from one sampling event. Contaminants identified as persistent, mobile, and bioavailable were 4,6,6,7,8,8-hexamethyl-1,3,4,7-tetrahydrocyclopenta[g] isochromene (galaxolide), 2,4,7,9-tetramethyl-5-decyn-4,7-diol, tris(2-chloroethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, and tris(1-chloro-2-propyl) phosphate. Galaxolide and 2,4,7,9-tetramethyl-5-decyn-4,7-diol were additionally found to be bioaccumulative, whereas n-butylbenzenesulfonamide was found to be only persistent and mobile. The total median mass flux of the persistent and mobile target analytes from Lake Ekoln into the drinking water source area of Lake Malaren was estimated to be 27 kg per year. Additionally, 10 contaminants were tentatively identified by non-target screening using NIST library searches and manual review. Two of those were confirmed by reference standards and further two contaminants, propylene glycol and rose acetate, were discharged from STPs and travelled far from the source. Attenuation of mass fluxes was highest in the summer and autumn seasons, suggesting the importance of biological degradation and photodegradation for the persistence of the studied compounds.

  • 25.
    Blum, Kristin M.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Renman, Gunno
    Ahrens, Lutz
    Gros, Meritxell
    Wiberg, Karin
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Non-target screening and prioritization of potentially persistent, bioaccumulating and toxic domestic wastewater contaminants and their removal in on-site and large-scale sewage treatment plants2017In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 575, p. 265-275Article in journal (Refereed)
    Abstract [en]

    On-site sewage treatment facilities (OSSFs), which are used to reduce nutrient emissions in rural areas, were screened for anthropogenic compounds with two-dimensional gas chromatography–mass spectrometry (GC × GC–MS). The detected compounds were prioritized based on their persistence, bioaccumulation, ecotoxicity, removal efficiency, and concentrations. This comprehensive prioritization strategy, which was used for the first time on OSSF samples, ranked galaxolide, α-tocopheryl acetate, octocrylene, 2,4,7,9-tetramethyl-5-decyn-4,7-diol, several chlorinated organophosphorus flame retardants and linear alkyl benzenes as the most relevant compounds being emitted from OSSFs. Twenty-six target analytes were then selected for further removal efficiency analysis, including compounds from the priority list along with substances from the same chemical classes, and a few reference compounds. We found significantly better removal of two polar contaminants 2,4,7,9-tetramethyl-5-decyn-4,7-diol (p = 0.0003) and tris(2-butoxyethyl) phosphate (p = 0.005) in soil beds, a common type of OSSF in Sweden, compared with conventional sewage treatment plants. We also report median removal efficiencies in OSSFs for compounds not studied in this context before, viz. α-tocopheryl acetate (96%), benzophenone (83%), 2-(methylthio)benzothiazole (64%), 2,4,7,9-tetramethyl-5-decyn-4,7-diol (33%), and a range of organophosphorus flame retardants (19% to 98%). The environmental load of the top prioritized compounds in soil bed effluents were in the thousands of nanogram per liter range, viz. 2,4,7,9-tetramethyl-5-decyn-4,7-diol (3000 ng L− 1), galaxolide (1400 ng L− 1), octocrylene (1200 ng L− 1), and α-tocopheryl acetate (660 ng L− 1).

  • 26.
    Blum, Kristin M.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gao, Qiuju
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ahrens, L.
    Gros, M.
    Wiberg, K.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mass fluxes per capita of organic contaminants from on-site sewage treatment facilities2018In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, no 201, p. 864-873Article in journal (Other academic)
    Abstract [en]

    This study is the first attempt to quantify environmental fluxes per capita of organic contaminants discharged from on-site sewage treatment facilities (OSSFs) in affected recipients. Five sites were monitored around the River Fyris in Sweden: three mainly affected by OSSFs and two mainly affected by municipal sewage treatment plants (STPs). Gas chromatography-mass spectrometry was used to determine environmental concentrations of 30 anthropogenic contaminants, including organophosphorus compounds, rubber and plastic additives, UV stabilizers, fragrances, surfactant ingredients and polycyclic aromatic hydrocarbons. Uni- and multivariate statistical analysis of the most frequently detected contaminants showed that median fluxes per capita of tris(1,3-dichloro-2-propyl) phosphate, tris(1-chloro-2-propyl) phosphate, tris(2-chloroethyl) phosphate, and n-butylbenzene sulfonamide were similar at OSSF and STP sites, but the mass fluxes per capita of tris-(2-butoxyethyl) phosphate, 2-(methylthio)benzothiazole, and galaxolide, were significantly lower (~2 to 3-fold) at OSSF sites than at STP sites (Mann-Whitney, α = 0.05). Differences between these sites were larger in samples collected in summer and autumn than in samples collected in winter. Deviations likely originated from differences in treatment technology and distances between source and sampling sites. Further studies are needed to characterize mass fluxes per capita of contaminants in waters that directly receive discharges from OSSFs.

  • 27. Breitholtz, Magnus
    et al.
    Nyholm, Jenny Rattfelt
    Umeå University, Faculty of Science and Technology, Chemistry.
    Karlsson, Jenny
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Are individual NOEC levels safe for mixtures? A study on mixture toxicity of brominated flame-retardants in the copepod Nitocra spinipes.2008In: Chemosphere, ISSN 0045-6535, Vol. 72, no 9, p. 1242-9Article in journal (Refereed)
    Abstract [en]

    In aquatic ecosystems organisms are exposed to mixtures of pollutants. Still, risk assessment focuses almost exclusively on effect characterization of individual substances. The main objective of the current study was therefore to study mixture toxicity of a common group of industrial substances, i.e., brominated flame–retardants (BFRs), in the harpacticoid copepod Nitocra spinipes. Initially, 10 BFRs with high hydrophobicity but otherwise varying chemical characteristics were selected based on multivariate chemical characterization and tested individually for effects on mortality and development using a partial life cycle test (six days) where silica gel is used as a carrier of the hydrophobic substances. Based on these findings, six of the 10 BFRs were mixed in a series of NOEC proportions (which were set to 0.008, 0.04, 0.2, 1, and five times the NOEC concentrations for each individual BFR), loaded on silica gel and tested in a full life cycle test (26 days). Significantly increased mortality was observed in N. spinipes after six and 26 days exposure at a NOEC proportion that equals the NOECLDR value (×1) for each BFR in the mixture (p = 0.0015 and p = 0.0105, respectively). At the NOEC × 5 proportion all animals were dead. None of the other NOEC proportions caused significant negative responses related to development and reproduction. This shows that low concentrations of individual substances can cause toxicity if exposed in mixtures, which highlights the need to consider mixture toxicity to a greater extent in regulatory work.

  • 28.
    Brenerová, Petra
    et al.
    Department of Chemistry and Toxicology, Veterinary Research Institute.
    Hamers, Timo
    Institute for Environmental Studies, VU University Amsterdam.
    Kamstra, Jorke H.
    Institute for Environmental Studies, VU University Amsterdam.
    Vondracek, Jan
    Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic.
    Strapacova, Simona
    Department of Chemistry and Toxicology, Veterinary Research Institute.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Machala, Miroslav
    Department of Chemistry and Toxicology, Veterinary Research Institute.
    Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells2016In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 23, no 3, p. 2099-2107Article in journal (Refereed)
    Abstract [en]

    The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 mu M), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.

  • 29. Cao, Lin-Ying
    et al.
    Zheng, Ziye
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ren, Xiao-Min
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Guo, Liang-Hong
    Structure-dependent activity of polybrominated diphenyl ethers and their hydroxylated metabolites on estrogen related receptor gamma: in vitro and in silico study2018In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 52, no 15, p. 8894-8902Article in journal (Refereed)
    Abstract [en]

    Estrogen-related receptor gamma (ERR gamma) is an orphan nuclear receptor having functional cross-talk with classical estrogen receptors. Here, we investigated whether ERR gamma is a potential target 8 of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs). By using a fluorescence competitive binding method established in our laboratory, the binding potencies of 30 PBDEs/OH-PBDEs with ERR gamma were determined for the first time. All of the tested OH-PBDEs and some PBDEs bound to ERR gamma with K-d values ranging from 0.13-13.61 mu M. The OH-PBDEs showed much higher binding potency than their parent PBDEs. A quantitative structure-activity relationship (QSAR) model was developed to analyze the chemical binding potencies in relation to their structural and chemical characteristics. The QSAR model indicated that the molecular size, relative ratios of aromatic atoms, and hydrogen bond donors and acceptors were crucial factors for PBDEs/OH-PBDEs binding. By using a reporter gene assay, we found that most of the low-brominated PBDEs/OH-PBDEs exerted agonistic activity toward ERR gamma, while high-brominated PBDEs/OH-PBDEs had no effect on the basal ERR gamma activity. The docking results showed that the low-brominated PBDEs/OH-PBDEs tended to take an agonistic binding mode while the high-brominated ones tended to take an antagonistic binding mode. Overall, our results suggest ERR gamma to be a potential novel target for PBDEs/OH-PBDEs.

  • 30.
    Danielsson, Conny
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Harju, Mikael
    Halldin, Krister
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Comparison of Levels of PCDD/Fs and non-Ortho PCBs in PCB 153 from seven different suppliers2008In: Organohalogen Compounds, Vol. 70, p. 001201-3Article in journal (Refereed)
    Abstract [en]

    Twelve PCBs with dioxin-like (DL) properties have been carefully studied through the years to facilitate risk assessment and they have been assigned WHO-TEF values [1] based on their relative toxicity and endocrine effects compared to 2,3,7,8-TCDD. From a toxicological point of view, the non-dioxin-like PCBs (NDL-PCBs) are less characterized but usually account for more than 90% of the total mass of PCBs in food samples [2]. Furthermore, over 90% of the NDL-PCB exposure in the general population is via food and the average daily intake can be estimated to be 10-45 ng/kg (bw)/day according to the European Food Safety Authority EFSA [3]. The EFSA committee concluded that a proper risk assessment of this abundant and environmentally significant class of compounds could not be accomplished. In 2006, the European Commission initiated a project which has as its aim to better examine the toxicity of NDL-PCBs: ATHON- "Assessing the toxicity and hazard of nondioxin-like PCBs present in food". The ATHON project will perform all in vivo and in vitro studies with ultra pure PCBs with known levels of DL-PCBs, PCDD/Fs and total TEQ-levels. As a first step in this study the major suppliers of PCB 153 were identified and the aim of the research was to investigate if there were any clear differences in the quality of their products based on possible impurities of PCDD/Fs and non-ortho PCBs. PCB 153 was selected because of its relatively high presence in environmental compartments and biota and since it has been the most frequently studied NDL-PCB in a few major in vivo studies [2]. Impurities of PCDD/Fs and DL-PCBs, even at trace levels, in PCB 153 may make a significant contribution to the effects seen in in vivo studies as the highest concentrations being studied are at mg/g (bw)/day during a period of time. These high daily exposure levels in combination with possible accumulation of toxic impurities may by time pose a threat to the significance of observed effects. Within the ATHON project all NDL-PCBs used for both in vitro and in vivo tests are analyzed and in many cases purified to remove possible traces of PCDD/Fs and non-ortho PCBs.

  • 31. Eriksson, Lennart
    et al.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Johansson, Erik
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Multivariate biological profiling and principal toxicity regions of compounds: the PCB case study2002In: Journal of Chemometrics, Vol. 16, no 8-10, p. 497-509Article in journal (Refereed)
    Abstract [en]

    The chemometric QSAR strategy, as applied in environmental sciences and drug design, is based on (1) multivariate characterization of chemical structure, (2) multivariate design in the principal properties of a set of compounds to select a representative training set, and (3) multivariate modelling of the structure-activity relationships. A multivariate QSAR investigation is often commenced by applying a screening design, and the selected compounds are tested biologically in a broad battery of test systems (multivariate biological profiling). In many cases the result is such that for certain biological end-points only some of the tested compounds are active, while for another set of biological end-points other tested chemicals are active. In other words, when looking at the chemical property space, there may be both responding and non-responding toxicity regions, or even regions of very specific toxicity mechanisms. This may lead to loss of resolution and balance in the resulting QSAR models. Therefore it might sometimes be worthwhile to focus the QSAR modelling on parts of the chemical space where high toxicity is expected or known to be the case. In this paper we describe a multi-stage modification of the chemometric QSAR strategy, aimed at identifying focused sets of compounds that provide a good mapping of such principal toxicity regions. This strategy is based on PCA, PLS and multivariate design in several stages. The strategy is illustrated using a data set of polychlorinated biphenyls, a set of compounds for which seven biological end-points were determined. Copyright © 2002 John Wiley & Sons, Ltd.

  • 32. Eriksson, Lennart
    et al.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Erik
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sandberg, Maria
    Wold, Svante
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The Constrained Principal Property (CPP) Space in QSAR---Directional and Non-Directional Modelling Approaches2000In: Molecular Modeling and Prediction of Bioactivity, Kluwer Academic/Plenum Publishers , 2000, p. 65-70Chapter in book (Other academic)
  • 33. Fernandes, Elsa C Antunes
    et al.
    Hendriks, Hester S
    van Kleef, Regina G D M
    Reniers, Ad
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    van den Berg, Martin
    Westerink, Remco H S
    Activation and potentiation of human GABAA receptors by non-dioxin-like PCBs depends on chlorination pattern2010In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 118, no 1, p. 183-90Article in journal (Refereed)
    Abstract [en]

    The neurotoxic potential of non-dioxin-like polychlorinated biphenyls (NDL-PCBs) is characterized by disruption of presynaptic processes, including calcium homeostasis and neurotransmitter transport. Recently, using a limited set of congeners, we demonstrated that PCB28 and PCB52 can potentiate postsynaptic GABA(A) receptors. In the present study, effects of 20 NDL-PCBs and 2 dioxin-like PCBs, selected based on their chemical variation and abundance in the environment, on human GABA(A) receptors were investigated. GABA(A) receptors were expressed in Xenopus oocytes, and NDL-PCB effects were determined using the two-electrode voltage-clamp technique. Results demonstrate that lower chlorinated PCB19, PCB28, PCB47, PCB51, PCB52, PCB95, and PCB100 act as a partial agonists (at low receptor occupancy), i.e., potentiating the receptor response during coapplication with GABA (at EC(20)). Importantly, PCB19, PCB47, PCB51, and PCB100 can also act as full agonist, i.e., activate the GABA(A) receptor in the absence of GABA. Potentiation and activation of the GABA(A) receptor is concentration dependent and limited to NDL-PCBs that have 3-5 chlorine atoms, 1-3 ortho-substitutions, an equal number (0-1) of meta-substitutions on both phenyl rings, and do not have an adjacent para- and meta-substitution on the same phenyl ring. Activation and potentiation of the GABA(A) receptor by PCB47, the most potent congener (lowest observed effect concentration of 10nM), is attenuated when coapplied with PCB19, PCB28, PCB153, or PCB180, indicative for competitive binding. Considering the importance of GABA-ergic signaling for brain development, motor coordination, learning, and memory, this mode of action can contribute to the previously observed NDL-PCB-induced neurobehavioral and neurodevelopmental effects and should be included in human risk assessment.

  • 34.
    Fick, Jerker
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Johansson, M
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Selection of antibiotics: A chemometric approach2004In: 4th International Conference on Pharmaceuticals and Endocrine Disrupting Chemicals in Water, Minneapolis, USA, 2004, p. 143-50Conference paper (Other academic)
  • 35. Gaehrs, Maike
    et al.
    Roos, Robert
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Schrenk, Dieter
    Role of the nuclear xenobiotic receptors CAR and PXR in induction of cytochromes P450 by non-dioxinlike polychlorinated biphenyls in cultured rat hepatocytes2013In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 272, no 1, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) are among the most ubiquitously detectable 'persistent organic pollutants'. In contrast to 'dioxinlike' (DL) PCBs, less is known about the molecular mode of action of the larger group of the 'non-dioxinlike' (NDL) PCBs. Owing to the life-long exposure of the human population, a carcinogenic, i.e., tumor-promoting potency of NDL-PCBs has to be considered in human risk assessment. A major problem in risk assessment of NDL-PCBs is dioxin-like impurities that can occur in commercially available NDL-PCB standards. In the present study, we analyzed the induction of CYP2B1 and CYP3A1 in primary rat hepatocytes using a number of highly purified NDL-PCBs with various degrees of chlorination and substitution patterns. Induction of these enzymes is mediated by the nuclear xenobiotic receptors CAR (Constitutive androstane receptor) and PXR (Pregnane X receptor). For CYP2B1 induction, concentration-response analysis revealed a very narrow window of EC50 estimates, being in the range of 1-4 mu M for PCBs 28 and 52, and between 0.4 and 1 mu M for PCBs 101, 138, 153 and 180. CYP3A1 induction was less sensitive to NDL-PCBs, the most pronounced induction being achieved at 100 mu M with the higher chlorinated congeners. Using okadaic acid and small interfering RNAs targeting CAR and PXR, we could demonstrate that CAR plays a major role and PXR a minor role in NDL-PCB-driven induction of CYPs, both effects showing no stringent structure-activity relationship. As the only obvious relevant determinant, the degree of chlorination was found to be positively correlated with the inducing potency of the congeners. (C) 2013 Elsevier Inc. All rights reserved.

  • 36.
    Ghorbanzad‘e, Mehdi
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fatemi, Mohammad H
    Karimpour, Masoumeh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Quantitative and qualitative prediction of corneal permeability for drug-like compounds2011In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 85, no 5, p. 2686-2694Article in journal (Refereed)
    Abstract [en]

    A set of 69 drug-like compounds with corneal permeability was studied using quantitative and qualitative modeling techniques. Multiple linear regression (MLR) and multilayer perceptron neural network (MLP-NN) were used to develop quantitative relationships between the corneal permeability and seven molecular descriptors selected by stepwise MLR and sensitivity analysis methods. In order to evaluate the models, a leave many out cross-validation test was performed, which produced the statistic Q2 = 0.584 and SPRESS = 0.378 for MLR and Q2 = 0.774 and SPRESS = 0.087 for MLP-NN. The obtained results revealed the suitability of MLP-NN for the prediction of corneal permeability. The contribution of each descriptor to MLP-NN model was evaluated. It indicated the importance of the molecular volume and weight. The pattern recognition methods principal component analysis (PCA) and hierarchical clustering analysis (HCA) have been employed in order to investigate the possible qualitative relationships between the molecular descriptors and the corneal permeability. The PCA and HCA results showed that, the data set contains two groups. Then, the same descriptors used in quantitative modeling were considered as inputs of counter propagation neural network (CPNN) to classify the compounds into low permeable (LP) and very low permeable (VLP) categories in supervised manner. The overall classification non error rate was 95.7% and 95.4% for the training and prediction test sets, respectively. The results revealed the ability of CPNN to correctly recognize the compounds belonging to the categories. The proposed models can be successfully used to predict the corneal permeability values and to classify the compounds into LP and VLP ones.

    Highlights

    ► Linear and nonlinear prediction of corneal permeability using molecular descriptors. ► MLP-NN model was found to be more successful than MLR equation. ► Molecular volume and molecular weight were identified as the most important descriptors. ► Categorizing drugs in two low permeable and very low permeable compounds groups. ► CPNN model can correctly recognize objects belonging to the groups.

  • 37.
    Ghorbanzadeh, Mehdi
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    van Ede, Karin I.
    Univ Utrecht, Inst Risk Assessment Sci, Endocrine Toxicol Grp, NL-3508 TD Utrecht, Netherlands.
    Larsson, Malin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    van Duursen, Majorie B. M.
    Univ Utrecht, Inst Risk Assessment Sci, Endocrine Toxicol Grp, NL-3508 TD Utrecht, Netherlands.
    Poellinger, Lorenz
    Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
    Lucke-Johansson, Sandra
    Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
    Machala, Miroslav
    Vet Res Inst, Dept Chem & Toxicol, CS-62132 Brno, Czech Republic.
    Pencikova, Katerina
    Vet Res Inst, Dept Chem & Toxicol, CS-62132 Brno, Czech Republic.
    Vondracek, Jan
    Vet Res Inst, Dept Chem & Toxicol, CS-62132 Brno, Czech Republic.
    van den Berg, Martin
    Univ Utrecht, Inst Risk Assessment Sci, Endocrine Toxicol Grp, NL-3508 TD Utrecht, Netherlands.
    Denison, Michael S.
    Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA.
    Ringsted, Tine
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    In vitro and in silico derived relative effect potencies of Ah-Receptor-mediated effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX Cell Lines2014In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 27, no 7, p. 1120-1132Article in journal (Refereed)
    Abstract [en]

    For a better understanding of species-specific relative effect potencies (REPs), responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated using chemical-activated luciferase gene expression assays (CALUX) derived from guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the rodent cell lines were partial agonists and less efficacious than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for each congener using concentrations at which 20% of the maximal TCDD response was reached,(REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with their toxic equivalency factors assigned by the World Health Organization (WHO-TEF), while those for PCBs were in general lower than the WHO-TEF values. Moreover, the guinea pig cell line was the most sensitive as indicated by the 20% effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and mouse cells, respectively. A similar response pattern was observed using multivariate statistical analysis between the three CALLTX assays and the WHO-TEFs. The mouse assay showed minor deviation due to higher relative induction potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8-hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was more than two times more potent in the mouse assay as compared with that of rat and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In order to provide REP20TCDD values for all WHO-TEF assigned compounds, quantitative structure activity relationship (QSAR) models were developed. The QSAR models showed that specific electronic properties and molecular surface characteristics play important roles in the AhR-mediated response. In silica derived REP20TCDD values were generally consistent with the WHO-TEFs with a few exceptions. The QSAR models indicated that, e.g., 1,2,3,7,8-pentachlorodibenzofuran and 1,2,3,7,8,9-hexachlorodibenzofuran were more potent than given by their assigned WHO-TEF values, and the non-ortho PCB 81 was predicted, based on the guinea-pig model, to be 1 order of magnitude above its WHO-TEF value. By combining in vitro and in silico approaches, REPs were established for all WHO-TEF assigned compounds (except OCDD), which will provide future guidance in testing AhR-mediated responses of DLCs and to increase our understanding of species variation in AhR-mediated effects.

  • 38.
    Ghorbanzadeh, Mehdi
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zhang, Jin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Binary classification model to predict developmental toxicity of industrial chemicals in zebrafish2016In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 30, no 6, p. 298-307Article in journal (Refereed)
    Abstract [en]

    The identification of industrial chemicals, which may cause developmental effects, is of great importance for an early detection of hazardous chemicals. Accordingly, categorical quantitative structure-activity relationship (QSAR) models were developed, based on developmental toxicity profile data for zebrafish from the ToxCast Phase I testing, to predict the toxicity of a large set of high and low production volume chemicals (H/LPVCs). QSARs were created using linear (LDA), quadratic, and partial least squares-discriminant analysis with different chemical descriptors. The predictions of the best model (LDA) were compared with those obtained by the freely available QSAR model VEGA, created based on a dataset with a different chemical domain. The results showed that despite similar accuracy (AC) of both models, the LDA model is more specific than VEGA and shows a better agreement between sensitivity (SE) and specificity (SP). Applying a 90% confidence level on the Lou model led to even better predictions showing SE of 0.92, AC of 0.95, and geometric mean of SE and SP (G) of 0.96 for the prediction set. The LDA model predicted 608 H/LPVCs as toxicants among which 123 chemicals fall inside the AD of the VEGA model, which predicted 112 of those as toxicants. Among the 112 chemicals predicted as toxic H/LPVCs, 23 have been previously reported as developmental toxicants. The here presented LDA model could be used to identify and prioritize H/LPVCs for subsequent developmental toxicity assessment, as a screening tool of potential developmental effects of new chemicals, and to guide synthesis of safer alternative chemicals.

  • 39. Gros, Meritxell
    et al.
    Blum, Kristin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jernstedt, Henrik
    Renman, Gunno
    Rodríguez-Mozaz, Sara
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wiberg, Karin
    Ahrens, Lutz
    Screening and prioritization of micropollutants in wastewaters from on-site sewage treatment facilities2017In: Journal of Hazardous Materials, ISSN 0304-3894, E-ISSN 1873-3336, Vol. 328, p. 37-45Article in journal (Refereed)
    Abstract [en]

    A comprehensive screening of micropollutants was performed in wastewaters from on-site sewage treatment facilities (OSSFs) and urban wastewater treatment plants (WWTPs) in Sweden. A suspect screening approach, using high resolution mass spectrometry, was developed and used in combination with target analysis. With this strategy, a total number of 79 micropollutants were successfully identified, which belong to the groups of per- and polyfluoroalkyl substances (PFASs), pesticides, phosphorus-containing flame retardants (PFRs) and pharmaceuticals and personal care products (PPCPs). Results from this screening indicate that concentrations of micropollutants are similar in influents and effluents of OSSFs and WWTPs, respectively. Removal efficiencies of micropollutants were assessed in the OSSFs and compared with those observed in WWTPs. In general, removal of PFASs and PFRs was higher in package treatment OSSFs, which are based on biological treatments, while removal of PPCPs was more efficient in soil bed OSSFs. A novel comprehensive prioritization strategy was then developed to identify OSSF specific chemicals of environmental relevance. The strategy was based on the compound concentrations in the wastewater, removal efficiency, frequency of detection in OSSFs and on in silico based data for toxicity, persistency and bioaccumulation potential.

  • 40. Haldén, Anna Norman
    et al.
    Nyholm, Jenny Rattfelt
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holbech, Henrik
    Norrgren, Leif
    Oral exposure of adult zebrafish (Danio rerio) to 2,4,6-tribromophenol affects reproduction2010In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 100, no 1, p. 30-7Article in journal (Refereed)
    Abstract [en]

    The bromophenol 2,4,6-tribromophenol (TBP) is widely used as an industrial chemical, formed by degradation of tetrabromobisphenol-A, and it occurs naturally in marine organisms. Concentrations of TBP in fish have been related to intake via feed, but little is known about effects on fish health after oral exposure. In this study, we exposed adult male and female zebrafish (Danio rerio) to TBP via feed in nominal concentrations of 33, 330, and 3300 μg/g feed (or control feed) for 6 weeks to assess the effects of TBP on reproductive output, gonad morphology, circulatory vitellogenin levels, and early embryo development. The aim was also to investigate the extent to which TBP was metabolised to 2,4,6-tribromoanisole (TBA) in dietary exposed zebrafish, and the amounts of TBP and TBA found in offspring. After 6 weeks of exposure, we found about 3% of the daily dose of TBP in adult fish and the mean concentration of TBA was 25-30% of the TBP concentration. TBP and TBA were detected in offspring with wet weight-based egg/fish concentration ratios well below one. Exposure to TBP significantly reduced the fertilization success and disturbed the gonad morphology, i.e. fewer spermatid cysts in males and increased presence of atretic follicles and oocytes with decreased vitellogenesis in females. In females, the disturbed gonad morphology was accompanied by increased levels of circulating vitellogenin. Significant effects were observed at 3300 μg/g feed. Offspring early development was not significantly affected, but yolk-sac oedema tended to increase in frequency in exposed groups with time. Our results show that dietary exposure to TBP, at concentrations found in marine organisms that are part of the natural diet of wild fish, can interfere with reproduction in zebrafish. We also observed low accumulation from feed of TBP in zebrafish and biotransformation of TBP to TBA. This is the first paper showing gonadal histopathological changes and effects on fertility in TBP exposed fish.

  • 41. Hamers, T
    et al.
    Kamstra, J H
    Sonneveld, E
    Murk, A J
    Zegers, B N
    Boon, J P
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Brouwer, A
    In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites2004In: Abstract BFR2004 Toronto, 2004Conference paper (Other academic)
  • 42. Hamers, Timo
    et al.
    Kamstra, Jorke H
    Cenijn, Peter H
    Pencikova, Katerina
    Palkova, Lenka
    Simeckova, Pavlina
    Vondracek, Jan
    Andersson, Patrik L
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenberg, Mia
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Machala, Miroslav
    In Vitro toxicity profiling of ultrapure non-dioxin-like polychlorinated biphenyl congeners and their relative toxic contribution to PCB mixtures in humans2011In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 121, no 1, p. 88-100Article in journal (Refereed)
    Abstract [en]

    The toxic equivalency concept used for the risk assessment of polychlorinated biphenyls (PCBs) is based on the aryl hydrocarbon receptor (AhR)-mediated toxicity of coplanar dioxin-like (DL) PCBs. Most PCBs in the environment, however, are non-dioxin-like (NDL) PCBs that cannot adopt a coplanar structure required for AhR activation. For NDL-PCBs, no generally accepted risk concept is available because their toxicity is insufficiently characterized. Here, we systematically determined in vitro toxicity profiles for 24 PCBs regarding 10 different mechanisms of action. Prior to testing, NDL-PCB standards were purified to remove traces of DL compounds. All NDL-PCBs antagonized androgen receptor activation and inhibited gap junctional intercellular communication (GJIC). Lower chlorinated NDL-PCBs were weak estrogen receptor (ER) agonists, whereas higher chlorinated NDL-PCBs were weak ER antagonists. Several NDL-PCBs inhibited estradiol-sulfotransferase activity and bound to transthyretin (TTR) but with much weaker potencies than reported for hydroxylated PCB metabolites. AhR-mediated expression of uridine-glucuronyl transferase isozyme UGT1A6 was induced by DL-PCBs only. Hierarchical cluster analysis of the toxicity profiles yielded three separate clusters of NDL-PCBs and a fourth cluster of reference DL-PCBs. Due to small differences in relative potency among congeners, the highly abundant indicator PCBs 28, 52, 101, 118, 138, 153, and 180 also contributed most to the antiandrogenic, (anti)estrogenic, antithyroidal, tumor-promoting, and neurotoxic potencies calculated for PCB mixtures reported in human samples, whereas the most potent AhR-activating DL-PCB-126 contributed at maximum 0.2% to any of these calculated potencies. PCB-168 is recommended as an additional indicator congener, given its relatively high abundance and antiandrogenic, TTR-binding, and GJIC-inhibiting potencies.

  • 43.
    Harju, M
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Hamers, T
    Sonneveld, E
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Multivariate QSAR modelling of the endocrine effects of polybrominated diphenyl ethers2004In: Abstract BFR2004 Toronto, 2004Conference paper (Other academic)
  • 44.
    Harju, Mikael
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Chemistry.
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Multivariate physicochemical characterisation and quantitative structure–property relationship modelling of polybrominated diphenyl ethers2002In: Chemosphere, Vol. 47, no 4, p. 375-84Article in journal (Refereed)
    Abstract [en]

    Levels of polybrominated diphenyl ethers (PBDEs) are increasing in the environment and may cause long-term environmental problems. Developing a model describing the chemical variation among the 209 possible congeners would be a useful step in any systematic approach for assessing the fate and risk posed by the PBDEs. Therefore, 40 physicochemical descriptors were derived for all PBDEs using a semi-empirical method (AM1), molecular mechanics, and empirically estimated parameters. Descriptors included heats of formation, frontier molecular orbital energies, atomic charges, dipole moments, logP values, and molecular surface areas. Principal component analysis (PCA) was used to evaluate the descriptors. The first four PCs, explaining 76% of the variation in the data, described the size, charge distribution and symmetric elements of the congeners. A quantitative structure–activity relationship model was constructed based on data for dioxin-like activity (using the luciferase bioassay) for 17 PBDEs with the partial least squares method. In addition, quantitative structure–property relationship models for gas chromatographic relative retention times on four capillary columns were developed. These models proved suitable to assist in the identification of untested PBDEs. Based on the results of the PCA, a factorial design was applied for selecting 21 representative congeners, PBDEs 11, 13, 17, 32, 35, 47, 53, 77, 85, 99, 119, 135, 153, 155, 156, 169, 176, 181, 190, 192, and 209. The spacing of these congeners in the physicochemical domain maximises the coverage of key factors such as molecular size and substitution pattern. Consideration of the selected congeners should be useful for guiding the synthesis of new compounds for use in future studies of the fate and biological effects of PBDEs.

  • 45.
    Harju, Mikael
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Hamers, Timo
    Kamstra, Jorke H
    Sonneveld, Edwin
    Boon, Jan P
    Tysklind, Mats
    Umeå University, Faculty of Science and Technology, Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Quantitative Structure–Activity Relationship Modeling on in Vitro Endocrine Effects and Metabolic Stability Involving 26 Selected Brominated Flame Retardants2007In: Environmental Toxicology and Chemistry, ISSN 1552-8618, Vol. 26, no 4, p. 816-26Article in journal (Refereed)
    Abstract [en]

    In this work, quantitative structure–activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure–activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecular properties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200–320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure–activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

  • 46. Heikkinen, Päivi
    et al.
    van der Ven, Leo
    Korkalainen, Merja
    Lensu, Sanna
    Niittynen, Marjo
    Sankari, Satu
    Savolainen, Kari
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Schrenk, Dieter
    Viluksela, Matti
    A 28-day toxicity study with highly purified PCB 180 in Sprague–Dawley rats2008In: Toxicology Letters: Volume 180, Supplement 1, Page S205, 2008, p. 205-Conference paper (Other academic)
    Abstract [en]

    PCB 180 is a persistent and accumulative heptachlorinated non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterisation of NDL-PCBs has been confounded by the presence of highly potent dioxin-like (DL) impurities. We used therefore highly purified PCB 180 (DL impurities 2.7 ng TEqWHO/g PCB 180) for the 28-day toxicity study in adult rats. Groups of 5 males and 5 females were given total doses of 3, 10, 30, 100, 300, 1000 or 1700 mg/kg PCB 180 by gavage. Total dose was divided into 6 daily loading doses and 3 weekly maintenance doses. Bodyweight development was retarded at 1700 mg/kg during loading dosing, but recovered by the end of the study. Hepatic effects are reported separately (Roos et al., ibid.). Thyroid weight was increased in males. Plasma free T4 was dose-dependently decreased (maximally by 69% in males and 50% in females) in association with thyroid follicle depletion, but T3 was not affected. Increased thyroid follicle cell vacuolization is suggestive of thyroid activation. In males, vacuolization and extracellular deposits were observed in the frontal part of pituitary. Activation of adrenal cortex is demonstrated by vacuolization and hypertrophy observed in cells of zona fasciculata of the adrenal cortex. Erythrocyte parameters (red blood cell count, haematocrit, haemoglobin) were dose-dependently decreased in both genders. The results demonstrate a distinct toxicological profile of PCB 180 with some similarities with that of DL compounds, but clearly lower potency.

    Acknowledgement: Funded by the European Commission (ATHON, FOOD-CT-2005-022923

  • 47. Heimstad, Eldbjørg S
    et al.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Chemistry.
    Docking and QSAR studies of an indirect estrogenic effect of hydroxylated PCBs2002In: Quantitative Structure-Activity Relationships, Vol. 21, no 3, p. 257-66Article in journal (Refereed)
    Abstract [en]

    A quantitative structure-activity relationship (QSAR) of hydroxylated polychlorinated biphenyls (OH-PCBs) potency to inhibit human estrogen sulfotransferase (hEST), was modeled using multivariate methods and calculated semi-empirical descriptors. The QSAR model included 10 selected OH-PCBs, recently reported experimental inhibition potencies of hEST and 17 physico- chemical parameters. The cross-validated explained variance of 0.71 indicates a high predictive capacity of the model. The most important parameters were sub-molecular electronic parameters, such as partial atomic charges and nucleophilic electron densities. The natural substrate estradiol and OH-PCBs have been suggested to inhibit hEST by non-competitive binding to a not yet identified allosteric site. Potential allosteric binding sites in the crystal structure of mouse estrogen sulfotransferase (mEST) and in a homology model of hEST were investigated and discussed using the programs CAST and GRAMM. In general, the most abundant docking sites using GRAMM were in agreement with pockets defined by CAST. These preliminary results should be verified and more detailed studies undertaken when the active dimer of hEST is available. The results indicate that other similar pollutants may well interfere with the sulfonation of estradiol.

  • 48. Hellgren, Dennis
    et al.
    Wu, Jianyao
    Roos, Robert
    Westerholm, Emma
    Adfeldt-Still, Oliver
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Halldin, Krister
    Håkansson, Helen
    The PCB effect database: a tool for translational research and health risk assessment2013In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 221, no Suppl., p. S229-S229Article in journal (Other academic)
  • 49.
    Holmgren, Tomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Measurement and modelling of organophosphates leaching from concrete to waterManuscript (preprint) (Other academic)
    Abstract [en]

    Organophosphate triesters used as additives in materials are leaching into the environment and have been found as pollutants in both water and sewage samples. Concrete is one of the most commonly used materials in the world and often contains tributyl phosphate (TBP) and triisobutyl phosphate (TiBP) as anti-foaming agents. In the present study, leaching of TBP and TiBP from concrete to water was measured over 16 weeks under laboratory conditions. The release was initially high (TBP 2900 ± 1060 10 μg/m2h; TiBP 8500 ± 800 μg/m2h), and then dropped to a low stable level over a six-week period. A generic model was developed to predict leaching of organic compounds to water. Three types of diffusion were modelled, dissolution from the surface, diffusion in cracks and pores, and diffusion in micro-pores in the concrete. The former type was assessed using the Nernst-Brunner dissolution and Fickian diffusion theory. The latter types required the use of three modules to model diffusion, solubilisation and 15 convective mass transfer processes separately. The boundary layer solubilisation was modelled using the Abraham solubility equation and solvation parameters taken from literature data. The results showed that the initial release of organophosphates from concrete to water can be significant (in some cases, >40% of the additive leaches out over the first few weeks) and that the long-term release of organophosphates from concrete constructions to the surrounding water can be accurately modelled. The model was applied to 20 estimate the release of TiBP to river water from the foundation of a bridge, resulting in a total loss of 2% of the additive over 8 years, with seasonal fluctuations in loss rate following changes in temperature and water flow. Due to the generic nature of the model, it can also be used to assess the leaching of other additives from concrete constructions to aquatic environments.

  • 50.
    Holmgren, Tomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Patrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Modeling and measurement of triphenyl phosphate emissions from flat screensManuscript (preprint) (Other academic)
123 1 - 50 of 116
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