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  • 201.
    Lundstedt-Enkel, K
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olse´n, K. H
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bjerselius, R
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects om oestrogen on male goldfish (Carassius auratus); Multivariate modelling to evaluate changes in "Physiological-Behavioural" pattern2000In: 6th international symposium on the reproductive physiology of fish, 2000, p. 499-Conference paper (Refereed)
  • 202.
    Lundstedt-Enkel, K.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Sellström, U.
    Häggberg, L.
    deWit, C.
    Örberg, J.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olsson, M.
    Multivariate modelling of concentrations of BDE-47, BDE-99, BDE-100 and HBCDD in relation to organochlorines in guillemot egg collected from the Baltic Proper 1996-2000.2001In: BFR 2001: Second international workshop on brominated flame retardants, 2001Conference paper (Refereed)
  • 203.
    Lundstedt-Enkel, Katrin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    QSBMR Quantitative Structure Biomagnification Relationships: Studies Regarding Persistent Environmental Pollutants in the Baltic Sea Biota2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    I have studied persistent environmental pollutants in herring (Clupea harengus), in adult guillemot (Uria aalge) and in guillemot eggs from the Baltic Sea. The studied contaminants were organochlorines (OCs); dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), and brominated flame retardants (BFRs); polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD). The highest concentration in both species was shown by p,p′DDE with a concentration in guillemot egg (geometric mean (GM) with 95% confidence interval) of 18200 (17000 – 19600) ng/g lipid weight. The BFR with the highest concentration in guillemot egg was HBCD with a GM concentration of 140 (120 – 160) ng/g lw.

    To extract additional and essential information from the data, not possible to obtain using only univariate or bivariate statistics, I used multivariate data analysis techniques; principal components analysis (PCA), partial least squares regression (PLS), soft independent modelling of class analogy (SIMCA), and PLS discriminant analysis (PLS-DA). I found e.g.; that there are significant negative correlations between egg weight and the concentrations of HCB and p,p'DDE; that concentrations of OCs and BFRs in the organisms co-varied so that concentrations of OCs can be used to calculate concentrations of BFRs; and, that several contaminants (e.g. HBCD) had higher concentration in guillemot egg than in guillemot muscle, that several (e.g. BDE47) showed no concentration difference between muscle and egg and that one contaminant (BDE154) showed higher concentration in the guillemot muscles than in egg.

    In this thesis I developed a new method, “randomly sampled ratios” (RSR), to calculate biomagnification factors (BMFs) i.e. the ratio between the concentration of a contaminant in an organism and the concentration of the same contaminant in its food. With this new method BMFs are denoted with an estimate of variation. Contaminants that biomagnify are e.g., p,p′DDE, CB118, HCB, βHCH and all of the BFRs. Those that do not biomagnify are e.g., p,p′DDT, αHCH and CB101.

    Lastly, to investigate which of the contaminants descriptors (physical-chemical/other properties and characteristics) that correlates to the biomagnification of the contaminants, I modeled the contaminants’ respective BMFRSR versus ~100 descriptors and showed that ~20 descriptors in combination were important, either favoring or counteracting biomagnification between herring and guillemot.

    List of papers
    1. Multivariate Data Analyses of Chlorinated and Brominated Contaminants and Biological Characteristics in Adult Guillemot (Uria aalge) from the Baltic Sea
    Open this publication in new window or tab >>Multivariate Data Analyses of Chlorinated and Brominated Contaminants and Biological Characteristics in Adult Guillemot (Uria aalge) from the Baltic Sea
    Show others...
    2005 (English)In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 39, no 22, p. 8630-8637Article in journal (Refereed) Published
    Abstract [en]

    Adult guillemot (Uria aalge) birds, 10 females and 10 males, drowned in trawl nets near Stora Karlsö in the Baltic Sea, were collected in 2000. Several of the animals' biological characteristics were recorded. The birds' pectoral muscles were individually analyzed for their concentrations of organochlorines (OCs) and brominated flame retardants (BFRs), dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls (PCBs), hexachlorocyclohexanes, trans-nonachlor, hexachlorobenzene, hexabromocyclododecane (HBCD), and polybrominated diphenyl ethers (PBDEs). The dominating contaminant was p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a geometric mean concentration of 12 900 ng/g lipid weight (lw). The concentration of ΣPBDE (80 ng/g lw) was similar to that of HBCD (65 ng/g lw). The total concentration of all OCs was approximately 150 times higher than that of all BFRs. For the statistical evaluation of the data, we used multivariate analysis techniques such as principal components analysis, partial least-squares (PLS) regression, and PLS discriminant analyses. No differences between the two sexes were found, either in contaminant concentrations or in biological characteristics. We found that some biological characteristics covaried with the concentrations of several OCs and BFRs, e.g., a negative correlation between liver weight and concentration of contaminants. The concentrations of most OCs but not of BFRs showed a decrease with increasing lipid content. Further, a PLS model with OCs as X and BFRs as Y showed that the contaminants formed two groups, each with distinctive correlation patterns. The PLS model could be used to predictwith varying accuracy the concentration of BFRs in the individual muscles from their concentration of OCs.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-93809 (URN)16323756 (PubMedID)
    Available from: 2005-11-24 Created: 2005-11-24 Last updated: 2017-12-14Bibliographically approved
    2. Organochlorines and Brominated Flame Retardants in Baltic Sea Guillemot (Uria aalge) Egg and Muscle
    Open this publication in new window or tab >>Organochlorines and Brominated Flame Retardants in Baltic Sea Guillemot (Uria aalge) Egg and Muscle
    Show others...
    2006 (English)In: Chemosphere, Vol. 65, p. 1591-1599Article in journal (Refereed) Published
    Abstract [en]

    Concentrations of organochlorines (OCs) and brominated flame-retardants (BFRs) were determined in guillemot (Uria aalge) eggsfrom the island of Stora Karlso¨ in the Baltic Sea where 10 eggs/year were collected in the years 2000, 2001 and 2002. The dominatingcontaminant in egg was p,p0-dichlorodiphenyldichloroethylene (p,p0-DDE) with a geometric mean (GM) concentration of 18200 ng/glipid weight (lw). The GM concentration in egg of hexabromocyclododecane (HBCD) of 140 ng/g lw, was significantly higher than thatof polybrominated diphenyl ether (PPBDE) of 77 ng/g lw.For the evaluation of the data multivariate data analysis techniques namely principal components analysis (PCA), partial leastsquares regression (PLS), soft independent modelling of class analogy (SIMCA classification), and PLS discriminant analysis (PLSDA),were used. We investigated whether the eggs’ biological characteristics co-varied with egg concentrations of OCs and BFRs,and found e.g., significant negative correlations between egg weight and concentrations of HCB and p,p0-DDE. A PLS model with analyzedBFRs as the Y matrix and OCs as the X matrix could, with varying accuracy, calculate the concentrations of BFRs in the individualegg from their concentrations of OCs (e.g., R2Y of 0.89 for BDE47, and of 0.50 for HBCD).Lastly, we compared the contaminant concentrations in the eggs to those in previously analyzed pectoral muscles from adult guillemotsfrom Stora Karlso¨ , from the year 2000. A PLS-DA model, showed that some of the contaminants (e.g., HBCD and CB28) hadsignificantly higher concentrations in egg than in muscle, although 7 of the 14 contaminants showed no difference in concentrationsbetween the two matrices.

    Keywords
    Guillemot, pollutants, PLS, PLS-DA
    Identifiers
    urn:nbn:se:uu:diva-93810 (URN)
    Available from: 2005-11-24 Created: 2005-11-24 Last updated: 2010-03-11Bibliographically approved
    3. A Statistical Resampling Method to Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea
    Open this publication in new window or tab >>A Statistical Resampling Method to Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea
    Show others...
    2005 (English)In: Environmental Science and Technology, Vol. 39, no 21, p. 8395-8402Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93811 (URN)
    Available from: 2005-11-24 Created: 2005-11-24 Last updated: 2009-04-02Bibliographically approved
    4. QSBMR - Quantitative Structure Biomagnification Relationships: Physicochemical and Structural Descriptors Important for the Biomagnification of Organochlorines and Brominated Flame Retardants
    Open this publication in new window or tab >>QSBMR - Quantitative Structure Biomagnification Relationships: Physicochemical and Structural Descriptors Important for the Biomagnification of Organochlorines and Brominated Flame Retardants
    2006 (English)In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 20, no 8-10, p. 392-401Article in journal (Refereed) Published
    Abstract [en]

    The aim of this project is to establish models to predict the biomagnification of contaminants present in Baltic Sea biota. In this paper a quantitative model that we term QSBMR-Quantitative Structure Biomagnification Relationships is presented. This model describes the relationship between the biomagnification factors (BMFs) for several organochlorines (OCs) and brominated flame retardants (BFRs), for example, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD), and their descriptors, for example, physico-chemical properties and structural descriptors. The concentrations of contaminants in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg from the Baltic Sea were used. The BMFs were calculated with the randomly sampled ratios (RSR) method that denotes the BMFs with a measure of the variation. In order to describe the physico-chemical properties and chemical structures, approximately 100 descriptors for the contaminants were generated: (a), by using the software (TSAR); (b) finding log Kow values from the literature, and (c) creating binary fingerprint variables that described the position of the chlorine and bromine for the respective PCB and PBDE molecules. Partial least squares (PLS) regression was used to model the relationship between the contaminants' BMF and the descriptors and the resulting QSBMR revealed that more than 20 descriptors in combination were important for the biomagnification of OCs and BFRs between herring and guillemot. The model including all contaminants (R2X=0.73, R2Y=0.87 and Q2=0.63, three components) explained approximately as much of the variation as the model with the PCBs alone (R2X=0.83, R2Y=0.87 and Q2=0.58, two components). The model with the BFRs alone (R2X=0.68, R2Y=0.88 and Q2 = 0.41, two components) had a slightly lower Q2 than the model including all contaminants. For validation, a training set of seven contaminants was selected by multivariate design (MVD) and a model was established. This model was then used to predict the BMFs of the test set (seven contaminants not included in the model). The resulting R2 for the regression Observed BMF versus Predicted BMF was high (0.65). The good models showed that descriptors important for the biomagnification of OCs and BFRs had been used. These types of models will be useful for in silico predictions of the biomagnification of new, not yet investigated, compounds as an aid in risk assessments.

    Keywords
    Biomagnification, preditictive models, Risk assessment, persistent organic pollutants
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-93812 (URN)10.1002/cem.1014 (DOI)000247019400009 ()
    Available from: 2005-11-24 Created: 2005-11-24 Last updated: 2017-12-14Bibliographically approved
  • 204.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Asplund, Lillemor
    Nylund, Kerstin
    Bignert, Anders
    Tysklind, Mats
    Olsson, Mats
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Multivariate data analysis of organochlorines and brominated flame retardants in Baltic Sea guillemot (Uria aalge) egg and muscle2006In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 65, no 9, p. 1591-1599Article in journal (Refereed)
    Abstract [en]

    Concentrations of organochlorines (OCs) and brominated flame-retardants (BFRs) were determined in guillemot (Uria aalge) eggs from the island of Stora Karlsö in the Baltic Sea where 10 eggs/year were collected in the years 2000, 2001 and 2002. The dominating contaminant in egg was p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) with a geometric mean (GM) concentration of 18 200 ng/g lipid weight (lw). The GM concentration in egg of hexabromocyclododecane (HBCD) of 140 ng/g lw, was significantly higher than that of polybrominated diphenyl ether (∑PBDE) of 77 ng/g lw.

    For the evaluation of the data multivariate data analysis techniques namely principal components analysis (PCA), partial least squares regression (PLS), soft independent modelling of class analogy (SIMCA classification), and PLS discriminant analysis (PLS-DA), were used. We investigated whether the eggs’ biological characteristics co-varied with egg concentrations of OCs and BFRs, and found e.g., significant negative correlations between egg weight and concentrations of HCB and p,p′-DDE. A PLS model with analyzed BFRs as the Y matrix and OCs as the X matrix could, with varying accuracy, calculate the concentrations of BFRs in the individual egg from their concentrations of OCs (e.g., R2Y of 0.89 for BDE47, and of 0.50 for HBCD).

    Lastly, we compared the contaminant concentrations in the eggs to those in previously analyzed pectoral muscles from adult guillemots from Stora Karlsö, from the year 2000. A PLS-DA model, showed that some of the contaminants (e.g., HBCD and CB28) had significantly higher concentrations in egg than in muscle, although 7 of the 14 contaminants showed no difference in concentrations between the two matrices.

  • 205.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bjerselius, R.
    Aune, M.
    Darnerud, P-P.
    Atuma, S.
    Tysklind, M.
    Bergek, S.
    Karlsson, L.
    Appelberg, A.
    Glynn, A.
    Different PCDD/PCDF congener composition in Salmon and Brown trout from Swedish waters.2002In: Organohalogen Compounds volume 57, 2002, p. 185-188Conference paper (Refereed)
  • 206.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Gabrielsson, Jon
    Olsman, Helena
    Seifert, Elisabeth
    Petterssen, Jarle
    Lek, Per M.
    Boman, Arne
    Lundstedt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Different multivariate approaches to material discovery, process development, PAT and environmental process monitoring2006In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 84, no 1-2, p. 201-207Article in journal (Refereed)
    Abstract [en]

    The aim with the present paper is to illustrate the use of multivariate strategies (i.e. integration of different multivariate methods) with five examples, four from the pharmaceutical industry and one from environmental research.

    In the first part, two examples wherein hierarchical models are applied to quality control (QC) and process control are discussed. In the second part a more complex problem and a strategy for material discovery/development are presented wherein a combination of multivariate calibration, multivariate analysis and multivariate design is needed. In the third part, a process analytical/optimization problem is illustrated with a two-step process, demanding that different multivariate tools are combined in a sequential way so that a useful model can be established and the process can be understood. In the final part the usefulness of principal component analysis followed by soft independent modelling of class analogy is illustrated with an example from environmental process monitoring. The five examples from quite different areas show that the chemometric tools are even more powerful if used integrated. However, different strategies and combinations of the tools have to be applied, depending on the problem and the aim.

  • 207.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Johansson, Anna-Karin
    Tysklind, Mats
    Asplund, Lillemor
    Nylund, Kerstin
    Olsson, Mats
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Multivariate Data Analyses of Chlorinated and Brominated Contaminants and Biological Characteristics in Adult Guillemot (Uria aalge) from the Baltic Sea2005In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 39, no 22, p. 8630-8637Article in journal (Refereed)
    Abstract [en]

    Adult guillemot (Uria aalge) birds, 10 females and 10 males, drowned in trawl nets near Stora Karlsö in the Baltic Sea, were collected in 2000. Several of the animals' biological characteristics were recorded. The birds' pectoral muscles were individually analyzed for their concentrations of organochlorines (OCs) and brominated flame retardants (BFRs), dichlorodiphenyltrichloroethanes (DDTs), polychlorinated biphenyls (PCBs), hexachlorocyclohexanes, trans-nonachlor, hexachlorobenzene, hexabromocyclododecane (HBCD), and polybrominated diphenyl ethers (PBDEs). The dominating contaminant was p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a geometric mean concentration of 12 900 ng/g lipid weight (lw). The concentration of ΣPBDE (80 ng/g lw) was similar to that of HBCD (65 ng/g lw). The total concentration of all OCs was approximately 150 times higher than that of all BFRs. For the statistical evaluation of the data, we used multivariate analysis techniques such as principal components analysis, partial least-squares (PLS) regression, and PLS discriminant analyses. No differences between the two sexes were found, either in contaminant concentrations or in biological characteristics. We found that some biological characteristics covaried with the concentrations of several OCs and BFRs, e.g., a negative correlation between liver weight and concentration of contaminants. The concentrations of most OCs but not of BFRs showed a decrease with increasing lipid content. Further, a PLS model with OCs as X and BFRs as Y showed that the contaminants formed two groups, each with distinctive correlation patterns. The PLS model could be used to predictwith varying accuracy the concentration of BFRs in the individual muscles from their concentration of OCs.

  • 208.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lek, Per M.
    Lundstedt, Torbjörn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Örberg, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Computational ecotoxicology; Modelling the biomagnification of organochlorines and brominated flame retardants in a Baltic Sea food web2008In: Dioxin 2008, Birmingham, 2008Conference paper (Refereed)
  • 209.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lek, Per M.
    Lundstedt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Computational ecotoxicology to predict biomagnification of contaminants2008In: Abstract book for Euro-QSAR 2008: Uppsala September 2008, 2008, p. 1-2Conference paper (Refereed)
  • 210.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lek, Per M.
    Lundstedt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    QSBMR - Quantitative Structure Biomagnification Relationships: Physicochemical and Structural Descriptors Important for the Biomagnification of Organochlorines and Brominated Flame Retardants2006In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 20, no 8-10, p. 392-401Article in journal (Refereed)
    Abstract [en]

    The aim of this project is to establish models to predict the biomagnification of contaminants present in Baltic Sea biota. In this paper a quantitative model that we term QSBMR-Quantitative Structure Biomagnification Relationships is presented. This model describes the relationship between the biomagnification factors (BMFs) for several organochlorines (OCs) and brominated flame retardants (BFRs), for example, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD), and their descriptors, for example, physico-chemical properties and structural descriptors. The concentrations of contaminants in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg from the Baltic Sea were used. The BMFs were calculated with the randomly sampled ratios (RSR) method that denotes the BMFs with a measure of the variation. In order to describe the physico-chemical properties and chemical structures, approximately 100 descriptors for the contaminants were generated: (a), by using the software (TSAR); (b) finding log Kow values from the literature, and (c) creating binary fingerprint variables that described the position of the chlorine and bromine for the respective PCB and PBDE molecules. Partial least squares (PLS) regression was used to model the relationship between the contaminants' BMF and the descriptors and the resulting QSBMR revealed that more than 20 descriptors in combination were important for the biomagnification of OCs and BFRs between herring and guillemot. The model including all contaminants (R2X=0.73, R2Y=0.87 and Q2=0.63, three components) explained approximately as much of the variation as the model with the PCBs alone (R2X=0.83, R2Y=0.87 and Q2=0.58, two components). The model with the BFRs alone (R2X=0.68, R2Y=0.88 and Q2 = 0.41, two components) had a slightly lower Q2 than the model including all contaminants. For validation, a training set of seven contaminants was selected by multivariate design (MVD) and a model was established. This model was then used to predict the BMFs of the test set (seven contaminants not included in the model). The resulting R2 for the regression Observed BMF versus Predicted BMF was high (0.65). The good models showed that descriptors important for the biomagnification of OCs and BFRs had been used. These types of models will be useful for in silico predictions of the biomagnification of new, not yet investigated, compounds as an aid in risk assessments.

  • 211.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Lek, Per M.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lundstedt, Torbjörn
    Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Relationships between physicochemical and structural descriptors and biomagnification of organochlorines and brominated flame retardants2007In: BFR2007, The Fourth International Workshop on Brominated Flame Retardants: Amsterdam, the Netherlands from 24 to 27 April 2007, 2007Conference paper (Refereed)
  • 212.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Roos, Anna
    Naturhistoriska Riksmuseet.
    Nylund, Kerstin
    Asplund, Lillemor
    Contaminants in Baltic Sea male and female grey seals (Halichoerus grypus) of different ages2008In: Dioxin 2008, Birmingham, 2008Conference paper (Refereed)
  • 213.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Sellström, U.
    Häggberg, L.
    deWit, C.
    Örberg, J.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olsson, M.
    Concentrations of BDE-47, BDE-99, BDE-100, BDE-153, BDE-154 and HBCDD in guillemot egg from the Baltic Proper 1996-2000.2001In: BFR 2001, 2001Conference paper (Refereed)
  • 214.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Tysklind, Mats
    Asplund, Lillemor
    Nylund, Kerstin
    Olsson, Mats
    Bignert, Anders
    Örberg, Jan
    Organochlorines and Brominated Flame Retardants in Baltic Sea Guillemot (Uria aalge) Egg and Muscle2006In: Chemosphere, Vol. 65, p. 1591-1599Article in journal (Refereed)
    Abstract [en]

    Concentrations of organochlorines (OCs) and brominated flame-retardants (BFRs) were determined in guillemot (Uria aalge) eggsfrom the island of Stora Karlso¨ in the Baltic Sea where 10 eggs/year were collected in the years 2000, 2001 and 2002. The dominatingcontaminant in egg was p,p0-dichlorodiphenyldichloroethylene (p,p0-DDE) with a geometric mean (GM) concentration of 18200 ng/glipid weight (lw). The GM concentration in egg of hexabromocyclododecane (HBCD) of 140 ng/g lw, was significantly higher than thatof polybrominated diphenyl ether (PPBDE) of 77 ng/g lw.For the evaluation of the data multivariate data analysis techniques namely principal components analysis (PCA), partial leastsquares regression (PLS), soft independent modelling of class analogy (SIMCA classification), and PLS discriminant analysis (PLSDA),were used. We investigated whether the eggs’ biological characteristics co-varied with egg concentrations of OCs and BFRs,and found e.g., significant negative correlations between egg weight and concentrations of HCB and p,p0-DDE. A PLS model with analyzedBFRs as the Y matrix and OCs as the X matrix could, with varying accuracy, calculate the concentrations of BFRs in the individualegg from their concentrations of OCs (e.g., R2Y of 0.89 for BDE47, and of 0.50 for HBCD).Lastly, we compared the contaminant concentrations in the eggs to those in previously analyzed pectoral muscles from adult guillemotsfrom Stora Karlso¨ , from the year 2000. A PLS-DA model, showed that some of the contaminants (e.g., HBCD and CB28) hadsignificantly higher concentrations in egg than in muscle, although 7 of the 14 contaminants showed no difference in concentrationsbetween the two matrices.

  • 215.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Tysklind, Mats
    Trygg, Johan
    Schüller, Peter
    Asplund, Lillemor
    Eriksson, Ulla
    Häggberg, Lisbeth
    Odsjö, Tjelvar
    Hjelmberg, Mats
    Olsson, Mats
    Orberg, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    A statistical resampling method to calculate biomagnification factors exemplified with organochlorine data from herring (Clupea harengus) muscle and guillemot (Uria aalge) egg from the Baltic sea.2005In: Environ Sci Technol, ISSN 0013-936X, Vol. 39, no 21, p. 8395-402Article in journal (Refereed)
  • 216.
    Lundstedt-Enkel, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Tysklind, Mats
    Trygg, Johan
    Schüller, Peter
    Asplund, Lillemor
    Ulla, Eriksson
    Häggberg, Lisbeth
    Odsjö, Tjelvar
    Hjelmberg, Mats
    Olsson, Mats
    Örberg, Jan
    A Statistical Resampling Method to Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea2005In: Environmental Science and Technology, Vol. 39, no 21, p. 8395-8402Article in journal (Refereed)
  • 217. Magnusson, Ulf
    et al.
    Brunström, BjörnUppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Reproductive behaviour and environmental pollutants: Proceedings from a symposium in Stockholm, September 15-16, 20052006Conference proceedings (editor) (Refereed)
  • 218. Magnusson, Ulf
    et al.
    Brunström, BjörnUppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Reproductive Toxicology in Environmental Research: a report from the ReproSafe-programme2007Collection (editor) (Other (popular scientific, debate etc.))
  • 219. Magnusson, Ulf
    et al.
    Brunström, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Norrgren, Leif
    Fortplantningsstörningar och kemikalier: En kunskapsbakgrund om observerade störningar i naturen2005Other (Other scientific)
  • 220. Malmberg, Tina
    et al.
    Athanasiadou, Maria
    Marsh, G
    Brandt, Ingvar
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bergman, Ake
    Identification of hydroxylated polybrominated diphenyl ether metabolites in blood plasma from polybrominated diphenyl ether exposed rats.2005In: Environ Sci Technol, ISSN 0013-936X, Vol. 39, no 14, p. 5342-8Article in journal (Refereed)
  • 221.
    Mank, Judith E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Nam, Kiwoong
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Ellegren, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Ontogenetic Complexity of Sexual Dimorphism and Sex-Specific Selection2010In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 27, no 7, p. 1570-1578Article in journal (Refereed)
    Abstract [en]

    Sex-biased gene expression is becoming an increasingly important way to study sexual selection at the molecular genetic level. However, little is known about the timing, persistence, and continuity of gene expression required in the creation of distinct male and female phenotypes, and even less about how sex-specific selection pressures shift over the life cycle. Here, we present a time-series global transcription profile for autosomal genes in male and female chicken, beginning with embryonic development and spanning to reproductive maturity, for the gonad. Overall, the amount and magnitude of sex-biased expression increased as a function of age, though sex-biased gene expression was surprisingly ephemeral, with very few genes exhibiting continuous sex bias in both embryonic and adult tissues. Despite a large predicted role of the sex chromosomes in sexual dimorphism, our study indicates that the autosomes house the majority of genes with sex-biased expression. Most interestingly, sex-specific evolutionary pressures shifted over the course of the life cycle, acting equally strongly on female-biased genes and male-biased genes but at different ages. Female-biased genes exhibited high rates of divergence late in embryonic development, shortly before arrested meiosis halts oogenesis. The level of divergence on female-biased late embryonic genes is similar to that seen in male-biased genes expressed in adult gonads, which correlates with the onset of spermatogenesis. These analyses reveal that sex-specific selection pressure varies over the life cycle as a function of male and female biology.

  • 222.
    Mattsson, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Exposure to xenoestrogens during development has been shown to impair sexual differentiation in various species. The major aim of this thesis was to elucidate the respective roles of the two estrogen receptors ERα and ERβ in normal and disrupted differentiation of sex organs and copulatory behavior in the Japanese quail (Coturnix japonica). The expression of ERα mRNA was much stronger than that of ERβ mRNA in the gonads and Müllerian ducts (embryonic oviducts) in early embryos. By contrast, ERβ seemed to be predominantly expressed in regions of the embryonic brain that are associated with male sexual behavior. Embryos were exposed to the selective ERα agonists propyl-pyrazole-triol (PPT) and 16α-lactone-estradiol (16α-LE2). The estrogens 17β-estradiol (E2) and 17α-ethynylestradiol (EE2), which activate both ERα and ERβ, were used as positive controls. All substances impaired reproductive organ differentiation. The effects observed included oviductal malformations in females and partial development of oviducts in males. All substances also induced testis feminization (ovotestis) in male embryos. The male copulatory behavior was severely impaired by the positive controls but was unaffected by PPT and 16α-LE2 at doses that disrupted sex organ differentiation. A higher dose of 16α-LE2 significantly suppressed the behavior. However, it is possible that this effect was caused by cross-activation of ERβ. The substances also induced hepatic expression of mRNA encoding the egg-yolk proteins vitellogenin II and very low-density apolipoprotein II, which are commonly used as indicators of estrogen exposure. In conclusion, the results suggest that ERα is important for female reproductive organ differentiation. Excess activation of ERα by xenoestrogens impairs differentiation in both females and males and induces hepatic expression of egg-yolk proteins. The results also indicate that ERα alone cannot mediate demasculinization of male copulatory behavior in quail, although further studies are needed to test this hypothesis.

    List of papers
    1. Expression of estrogen receptor-alpha and -beta mRNA in the brain of Japanese quail embryos
    Open this publication in new window or tab >>Expression of estrogen receptor-alpha and -beta mRNA in the brain of Japanese quail embryos
    2007 (English)In: Developmental Neurobiology, ISSN 1932-8451, Vol. 67, no 13, p. 1742-1750Article in journal (Refereed) Published
    Abstract [en]

    The present study was conducted to investigate the mRNA expression of the two estrogen receptor (ER) subtypes ERα and ERβ in the brain of Japanese quail embryos. We found expression of both ERα and ERβ mRNA in homogenate of whole head from 6-day-old embryos, and in brain homogenate from 9- and 12-day-old embryos using real-time PCR. In 9- and 12-day-old embryos the ERα expression was higher in females than in males. We used in situ hybridization to examine the localization of the ERs in sections from male and female brains on day 9 and day 17 of incubation. On day 9, ERβ mRNA was detected in the developing medial preoptic nucleus (POM), in the medial part of the bed nucleus of the striae terminalis (BSTm), and in the tuberal region of the hypothalamus. ERα signal could not be detected in the POM, the BSTm or the tuberal region in 9-day-old embryos. In 17-day-old embryos, ERβ was highly expressed in the preoptic area, the nucleus Taeniae of the Amygdala (TnA) and the BSTm. Expression of ERα mRNA was detected in parts of the preoptic area and in the telencephalic TnA. No ERα expression was found in the BSTm, an area known to be sexually dimorphic in adults. The high embryonic expression of ERβ in brain areas linked to sexual behavior indicates that ERβ plays a role in sexual differentiation of the Japanese quail brain.

    Keywords
    Japanese quail, estrogen receptors, embryo brain, real-time PCR, sexual differentiation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-96944 (URN)10.1002/dneu.20544 (DOI)000250606300005 ()17638389 (PubMedID)
    Available from: 2008-03-28 Created: 2008-03-28 Last updated: 2012-02-03
    2. Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos
    Open this publication in new window or tab >>Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos
    2008 (English)In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 136, no 2, p. 175-186Article in journal (Refereed) Published
    Abstract [en]

    The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors alpha and beta (ER alpha and ER beta) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ER alpha (ESR1) mRNA is expressed in both right and left gonads and Mullerian ducts (MDs) in both sexes during early morphological differentiation. ER beta (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ER alpha-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ER alpha. Taken together, our results suggest that activation of ER alpha is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ER alpha mediates xenoestrogen-induced toxicity during reproductive development in birds.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-97339 (URN)10.1530/REP-08-0100 (DOI)000258671500005 ()
    Available from: 2008-05-22 Created: 2008-05-22 Last updated: 2017-12-14Bibliographically approved
    3. Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behavior or the parvocellular vasotocin system
    Open this publication in new window or tab >>Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behavior or the parvocellular vasotocin system
    Show others...
    2008 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 159, no 2-3, p. 150-157Article in journal (Refereed) Published
    Abstract [en]

    Estradiol is crucial for normal female differentiation in birds. Developmental effects of estrogen are believed to be mediated by slow genomic actions through the nuclear estrogen receptors alpha (ERα) and/or beta (ERβ). Consequently, exogenous compounds that interfere with the ERs may disrupt sexual differentiation of the reproductive organs and of the brain areas controlling sexual behaviors. The present study was conducted to elucidate the role of ERα in xenoestrogen-induced disruption of sexual differentiation in the Japanese quail (Coturnix japonica). Embryonic treatment with the synthetic estrogen, ethinylestradiol (EE2), and with the ERα-selective agonist, propyl pyrazole triol (PPT), induced oviductal malformations in females and retention of oviducts in males. Both EE2 and PPT caused weight asymmetry between left and right testes and reduced the cloacal gland area in males. EE2 significantly reduced the copulatory behavior in males whereas PPT had no effect on this behavior. The sexually dimorphic parvocellular vasotocin-immunoreactive (VT-ir) system in the medial preoptic nucleus (POM), the lateral septum (SL) and the medial part of the nucleus of the stria terminalis (BSTm), was not affected by EE2 or PPT. Our results suggest that xenoestrogen-induced effects on reproductive organ differentiation are mediated by ERα, whereas demasculinization of male copulatory behavior and the VT-ir system appears not to be induced by activation of ERα alone.

    Keywords
    Japanese quail, Estrogen receptor, Sex differentiation, Sexual behavior, Vasotocin
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-97340 (URN)10.1016/j.ygcen.2008.08.012 (DOI)000261356300006 ()
    Available from: 2008-05-22 Created: 2008-05-22 Last updated: 2017-12-14
    4. Effects on differentiation of reproductive organs and sexual behaviour in Japanese quail by excessive embryonic ERα activation
    Open this publication in new window or tab >>Effects on differentiation of reproductive organs and sexual behaviour in Japanese quail by excessive embryonic ERα activation
    2010 (English)In: Reproduction, Fertility and Development, ISSN 1031-3613, E-ISSN 1448-5990, Vol. 22, no 2, p. 416-425Article in journal (Refereed) Published
    Abstract [en]

    Exposure of Japanese quail (Coturnix japonica) embryos to oestrogenic substances disrupts sexual differentiation of the reproductive tract of both sexes and impairs the copulatory behaviour of the adult male. To examine whether these effects can be induced by selective activation of oestrogen receptor alpha (ER alpha), Japanese quail eggs were injected with various doses of the selective ER alpha agonist 16 alpha-lactone-oestradiol (16 alpha-LE2). The natural oestrogen 17 beta-oestradiol (E-2) was used as a positive control. Both 16 alpha-LE2 and E-2 induced formation of an ovary-like cortex in the left testis (ovotestis) and reduced the size of the right testis in male embryos. The asymmetry in testis size remained in sexually mature males. Both substances induced retention and malformation of the Mullerian ducts in embryos of both sexes and malformed oviducts in juveniles. Male copulatory behaviour was suppressed by embryonic exposure to E-2 and the highest dose of 16 alpha-LE2. However, the lower dose of 16 alpha-LE2, which markedly affected development of the reproductive organs, was without effects on behaviour. It can therefore not be excluded that the behavioural demasculinisation at the 100-fold higher dose involved cross-activation of oestrogen receptor beta (ER beta). In conclusion, our results suggest that oestrogen-induced disruption of reproductive organ development in Japanese quail can be mediated via ER alpha, whereas the role of ER alpha in demasculinisation of copulatory behaviour remains to be clarified.

    Keywords
    endocrine disruption; oestrogen receptors; ovotestis; sex differentiation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-97341 (URN)10.1071/RD08293 (DOI)000273208800003 ()
    Available from: 2008-05-22 Created: 2008-05-22 Last updated: 2017-12-14Bibliographically approved
  • 223.
    Mattsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects on differentiation of reproductive organs and sexual behaviour in Japanese quail by excessive embryonic ERα activation2010In: Reproduction, Fertility and Development, ISSN 1031-3613, E-ISSN 1448-5990, Vol. 22, no 2, p. 416-425Article in journal (Refereed)
    Abstract [en]

    Exposure of Japanese quail (Coturnix japonica) embryos to oestrogenic substances disrupts sexual differentiation of the reproductive tract of both sexes and impairs the copulatory behaviour of the adult male. To examine whether these effects can be induced by selective activation of oestrogen receptor alpha (ER alpha), Japanese quail eggs were injected with various doses of the selective ER alpha agonist 16 alpha-lactone-oestradiol (16 alpha-LE2). The natural oestrogen 17 beta-oestradiol (E-2) was used as a positive control. Both 16 alpha-LE2 and E-2 induced formation of an ovary-like cortex in the left testis (ovotestis) and reduced the size of the right testis in male embryos. The asymmetry in testis size remained in sexually mature males. Both substances induced retention and malformation of the Mullerian ducts in embryos of both sexes and malformed oviducts in juveniles. Male copulatory behaviour was suppressed by embryonic exposure to E-2 and the highest dose of 16 alpha-LE2. However, the lower dose of 16 alpha-LE2, which markedly affected development of the reproductive organs, was without effects on behaviour. It can therefore not be excluded that the behavioural demasculinisation at the 100-fold higher dose involved cross-activation of oestrogen receptor beta (ER beta). In conclusion, our results suggest that oestrogen-induced disruption of reproductive organ development in Japanese quail can be mediated via ER alpha, whereas the role of ER alpha in demasculinisation of copulatory behaviour remains to be clarified.

  • 224.
    Mattsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Halldin, Krister
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Embryonic exposure to an ERalpha-agonist affects reproductive organ development but not copulatory behaviour in Japanese quail2006In: Toxicology Letters 164, Supplement 1, 2006, p. S166-S167Conference paper (Other academic)
  • 225.
    Mattsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Mura, Elena
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Panzica, GianCarlo
    Halldin, Krister
    Selective activation of estrogen receptor alpha in Japanese quail embryos affects reproductive organ differentiation but not the male sexual behavior or the parvocellular vasotocin system2008In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 159, no 2-3, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Estradiol is crucial for normal female differentiation in birds. Developmental effects of estrogen are believed to be mediated by slow genomic actions through the nuclear estrogen receptors alpha (ERα) and/or beta (ERβ). Consequently, exogenous compounds that interfere with the ERs may disrupt sexual differentiation of the reproductive organs and of the brain areas controlling sexual behaviors. The present study was conducted to elucidate the role of ERα in xenoestrogen-induced disruption of sexual differentiation in the Japanese quail (Coturnix japonica). Embryonic treatment with the synthetic estrogen, ethinylestradiol (EE2), and with the ERα-selective agonist, propyl pyrazole triol (PPT), induced oviductal malformations in females and retention of oviducts in males. Both EE2 and PPT caused weight asymmetry between left and right testes and reduced the cloacal gland area in males. EE2 significantly reduced the copulatory behavior in males whereas PPT had no effect on this behavior. The sexually dimorphic parvocellular vasotocin-immunoreactive (VT-ir) system in the medial preoptic nucleus (POM), the lateral septum (SL) and the medial part of the nucleus of the stria terminalis (BSTm), was not affected by EE2 or PPT. Our results suggest that xenoestrogen-induced effects on reproductive organ differentiation are mediated by ERα, whereas demasculinization of male copulatory behavior and the VT-ir system appears not to be induced by activation of ERα alone.

  • 226.
    Mattsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olsson, Jan A
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos2008In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 136, no 2, p. 175-186Article in journal (Refereed)
    Abstract [en]

    The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors alpha and beta (ER alpha and ER beta) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ER alpha (ESR1) mRNA is expressed in both right and left gonads and Mullerian ducts (MDs) in both sexes during early morphological differentiation. ER beta (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ER alpha-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ER alpha. Taken together, our results suggest that activation of ER alpha is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ER alpha mediates xenoestrogen-induced toxicity during reproductive development in birds.

  • 227. Merino, Ruben
    et al.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Avd för ekotoxikologi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Halldin, Krister
    Heart morphology and liver EROD induction in Japanese quail embryos exposed to TCDD in ovo.2005In: Organohalogen Compounds 67, 2005, p. 2396-2398Conference paper (Refereed)
  • 228. Montforts, M.
    et al.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Hutchinson, Thomas H.
    Summary of Workshop on Environmental Assessment of Human Medicines: Development and use of aquatic toxicity data2007In: Drug information journal, ISSN 0092-8615, E-ISSN 2164-9200, Vol. 41, no 2, p. 203-209Article in journal (Refereed)
    Abstract [en]

    Current approaches to generating and interpreting ecotoxicological effects data in aquatic organisms were discussed in a workshop. Scientific principles underpinning historical "base set" acute testing (typically using freshwater algae, daphnids, fish) and the more recent requirement to adopt chronic sublethal test guidelines were discussed. Participants discussed ideas to develop improved testing methods for chronic pharmacological and toxic effects based on the premise that useful ecotoxicity information can be leveraged from both in vitro and in vivo preclinical studies. For example, one approach is to consider a primary pharmacological mechanism in mammals (the mammalian-fish leverage model) and to use these mechanistic biomarker data as "signposts" to guide the efficient assessment of sublethal chronic testing in aquatic life. The usefulness of data obtained in test systems on the molecular, cellular, organ-organismal, and population levels of biological organization for environmental risk assessment was evaluated and integrated with animal (vertebrate) welfare considerations.

  • 229.
    Niclas Johansson, Niclas
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    PBDE 209 and PFOA interact during neonatal brain development affecting developmental marker proteins synaptophysin and tau levels in the neonatal mouseManuscript (Other academic)
  • 230. Olsman, Helena
    et al.
    Ghebreab, Kifle
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lundstedt-Enkel, Katrin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Berg, Håkan
    Brunström, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Engwall, Magnus
    Olsson, Per-Erik
    Örberg, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bjerselius, Rickard
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Exposure to sewage water alters goldfish reproductive behaviour2001In: Hormones in the Environment and Animal Production - A Public Health Concern?: Proceedings from a symposium at the Ultuna Campus, Uppsala, March 13, 2001, 2001Conference paper (Other scientific)
  • 231.
    Olsén, K Håkan
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bjerselius, Rickard
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Mayer, I
    Kindahl, H
    Both ovarian fluid and female urine increase sex steroid hormone levels in mature Atlantic salmon (Salmo salar) male parr.2001In: J Chem Ecol, ISSN 0098-0331, Vol. 27, no 11, p. 2337-49Article in journal (Refereed)
  • 232.
    Otte, Jens C
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Andersson, Carin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Abrahamson, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Olsman, Helena
    Keiter, Steffen
    Engwall, Magnus
    Hollert, Henner
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    A bioassay approach to determine the dioxin-like activity in sediment extracts from the Danube River: Ethoxyresorufin-O-deethylase induction in gill filaments and liver of three-spined sticklebacks (Gasterosteus aculeatus L.)2008In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 34, no 8, p. 1176-1184Article in journal (Refereed)
    Abstract [en]

    Sediment samples from the upper Danube River in Germany have previously been characterized as ecotoxicologically hazardous and contaminants in these sediments may contribute to the observed decline of fish populations in this river section. For the investigation of sediment toxicity there is a need for development, standardization and implementation of in vivo test systems using vertebrates. Therefore, the main objective of this study was to apply and evaluate a recently established fish gill EROD assay as a biomarker in sediment toxicity assessment by using extracts of well characterised sediment samples from the upper Danube River. This to our knowledge is the first application of this novel assay to sediment extracts. Sediments from four different sites along the upper Danube River were Soxhlet-extracted with acetone and dissolved in DMSO. Three-spined sticklebacks (Gasterosteus aculeatus L.) were exposed for 48 h to various concentrations of the extracts, to the positive control beta-naphthoflavone or to the solvent. Measurements of EROD activity in gill filaments and liver microsomes followed the exposure. Concentration-dependent induction of EROD in both gill and liver was found for all sediment extracts. The highest EROD-inducing potency was determined for extracts of sediments from the sites "Opfinger See" and "Sigmaringen" and the EROD activities in gill and liver correlated well. The results from the gill and liver assays were in accordance with in vitro results of previous investigations. The EROD activities measured in the present study corresponded with the concentrations of PAHs, PCBs and PCDD/Fs in the sediment samples derived in a previous study. The sticklebacks in this study were in the reproductive phase and a stronger EROD induction was obtained in the females than in the males. Implementation of the EROD assay in testing of sediment extracts gave highly reliable results which make this assay an ecotoxicologically relevant method for assessment of contamination with Ah receptor agonists in sediments.

  • 233.
    Pettersson, Irina
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Ekotoxikologi.
    Endocrine disruption by an estrogenic environmental pollutant in frogs: Developmental effects on the reproductive system2006Licentiate thesis, monograph (Other scientific)
  • 234.
    Pettersson, Irina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Arukwe, Augustine
    Lundstedt-Enkel, Katrin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Mortensen, Anne
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Persistent sex-reversal and oviducal agenesis in adult Xenopus (Silurana) tropicalis frogs following larval exposure to the environmental pollutant ethynylestradiol2006In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 79, no 4, p. 356-365Article in journal (Refereed)
    Abstract [en]

    It is known that estrogen-like environmental pollutants can feminise gonadal differentiation in frogs resulting in female-biased sex-ratios at metamorphosis. The long-term effects on reproductive function in frogs following larval exposure to pollutants are less known. Amphibian test systems which allow life-cycle studies are therefore needed. The aim of the present study was to characterise long-term estrogenic effects on the reproductive system of the emerging model species Xenopus (Silurana) tropicalis following larval exposure to ethynylestradiol (EE2). EE2 is a synthetic estrogen that has been detected in sewage effluents and in surface waters. Newly hatched tadpoles (Niewkoop Faber (NF) stage 48) were exposed to the nominal EE2 concentrations 0 (control), 1, 10, and 100 nM (with analytical chemistry support) until complete metamorphosis (NF stage 66). Effects on the reproductive organs were determined in juveniles (I month after metamorphosis) and in 9-month-old frogs. Larval exposure to EE2 caused female-biased phenotypic sex-ratios in both juvenile and adult frogs, which is in agreement with previous work on other frog species. Nearly all (97%) of the 63 EE2-exposed 9-month-old frogs had ovaries. Histological evaluation of the gonads of the 9-month-old frogs showed that they were sexually mature. Among the adult frogs with ovaries there was a dose-dependent increase in the frequency of individuals lacking oviducts. Adult frogs exposed to 100 nM EE2 that had ovaries but no oviducts had lower levels of estrogen receptor alpha (ER alpha) mRNA in the brain than control animals and those exposed to 100 nM EE2 that had ovaries as well as oviducts. EE2 exposure did not cause any significant changes in ER alpha mRNA levels in the ovaries of the adult frogs. The reduced level of ER alpha mRNA in the brain of individuals with ovaries lacking oviducts suggests an organizing effect of EE2 on the central nervous system. The results show that transient early life-stage exposure to an environmental pollutant can induce effects on the reproductive organs and the central nervous system that persist into adulthood. Overall, our data suggest that X. tropicalis, which has a shorter generation time than the well-established model species Xenopus laevis, is a suitable model organism for research on developmental reproductive toxicity in anuran species.

  • 235.
    Pettersson, Irina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Environmentally Relevant Concentrations of Ethynylestradiol Cause Female-Biased Sex Ratios in Xenopus tropicalis and Rana temporaria2007In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, no 5, p. 1005-1009Article in journal (Refereed)
    Abstract [en]

    The susceptibility of Xenopus (Silurana) tropicalis and Rana temporaria to ethynylestradiol (EE2), a potent estrogenic pharmaceutical and environmental pollutant, was investigated. Larval EE2 exposure caused female-biased sex ratios at concentrations as low as 0.06 nM, which is comparable to levels found in the environment. The susceptibility of the two frog species to EE2 was comparable, supporting the use of X. tropicalis as a model organism for research on developmental reproductive toxicity of estrogenic pollutants.

  • 236.
    Raloff, J.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Nonstick chemicals upset behaviour2006In: Science News, no 169, p. 190-Article in journal (Other (popular scientific, debate etc.))
  • 237. Saglio, P
    et al.
    Olsén, K Håkan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Bretaud, S
    Behavioral and olfactory responses to prochloraz, bentazone, and nicosulfuron-contaminated flows in goldfish.2001In: ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, ISSN 0090-4341, Vol. 41, no 2, p. 192-200Article in journal (Refereed)
  • 238. Sand, S
    et al.
    von Rosen, D
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Victorin, K
    Falk-Filipsson, A
    Dose-response modelling and benchmark calculations from spontaneous behaviour data on mice neonatally exposed to 2,2´,4, 4´, 5-pentabromodiphenyl ether2005In: Toxicologist 84, 2005, p. 405-Conference paper (Refereed)
  • 239. Sand, Salomon
    et al.
    von Rosen, D.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viktorin, K.
    Falk Filipsson, A.
    Dose-response modelling and Benchmark calculations from spontaneous behaviour data on mice neonatally exposed to 2,2',4,4',5-pentabromodiphenyl ether2004In: The Toxicologist, 2004, p. 405-Conference paper (Refereed)
  • 240. Sand, Salomon
    et al.
    von Rosen, Dietrich
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Fredriksson, Anders
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Victorin, Katarina
    Filipsson, Agneta Falk
    Dose-response modeling and benchmark calculations from spontaneous behavior data on mice neonatally exposed to 2,2',4,4',5-pentabromodiphenyl ether.2004In: Toxicol Sci, ISSN 1096-6080, Vol. 81, no 2, p. 491-501Article in journal (Refereed)
  • 241.
    Scholz, Birger
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Toxicology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Toxicology.
    Mattsson, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Axelsson, Jeanette
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.