Endre søk
Begrens søket
1234 1 - 50 of 178
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Abramsson-Zetterberg, Lilianne
    et al.
    Vikström, Anna C
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hellenäs, Karl-Erik
    Differences in the frequency of micronucleated erythrocytes in humans in relation to consumption of fried carbohydrate-rich food.2008Inngår i: Mutat Res, ISSN 0027-5107, Vol. 653, nr 1-2, s. 50-6Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Alsberg, T.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för tillämpad miljövetenskap (ITM).
    Minten, J.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för tillämpad miljövetenskap (ITM).
    Haglund, J.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Determination of hydroxyalkyl derivatives of cobalamin (vitamin B12) using reversed phase high performance liquid chromatography with electrospray tandem mass spectrometry and ultraviolet diode array detection2001Inngår i: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 15, nr 24, s. 2438-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Electrospray ionization tandem mass spectrometry (ESI-MS/MS) and ultraviolet diode array detection (UV-DAD), coupled on-line to reversed phase high performance liquid chromatography (HPLC), was used for the characterization of hydroxyalkyl derivatives of cob(I)alamin. The reduced form of vitamin B12, cob(I)alamin, denoted a supernucleophile due to its high nucleophilic strength, has shown promise as an analytical tool in studies of electrophilically reactive compounds in vitro and in vivo. A method for analysis of DNA-phosphate adducts was developed earlier utilizing the supernucleophilicity of cob(I)alamin to transfer alkyl groups from the phosphotriester configuration in DNA, with the formation of a Co-substituted alkyl-cobalamin (alkyl-Cbl) complex. For the purpose of identification and quantification of alkyl-Cbls at high sensitivity, an MS/MS method has been developed with application to a number of 2-hydroxyalkyl-cobalamins (OHalkyl-Cbls). The precursor oxiranes were reacted with cob(I)alamin, followed by clean-up and mass spectrometric analysis of the resulting OHalkyl-Cbls. It was found that ionization was highly dependent on solvent composition. By using acetonitrile/water/trifluoroacetic acid (TFA) (eluent I), the base peak was the doubly protonated molecule [M + 2H](2+), whereas acetonitrile/water/1-methylpiperidine (eluent II) yielded the singly protonated molecule [M + H](+) as the base peak. Excellent separation was obtained with eluent II, with good separation between stereoisomers, thus enabling the characterization of these by means of UV spectra. Limits of quantitation for 2-hydroxypropyl-cobalamin (OHPr-Cbl) were 0.2 and 2 pg/microL (or 0.1 and 1 fmol/microL) using selected ion recording (SIR) with eluent I and II, respectively. The obtained detection level should be sufficient for analysis of alkyl-Cbls from a wide range of toxicological applications.

  • 3.
    Asp, V
    et al.
    Department of Environmental Toxicology, Uppsala University.
    Cantillana, T
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Brandt, I
    Department of Environmental Toxicology, Uppsala University.
    Chiral effects in adrenocorticolytic action of o,p'-DDD (mitotane) in human adrenal cells2010Inngår i: Xenobiotica, ISSN 0049-8254, E-ISSN 1366-5928, Vol. 40, nr 3, s. 177-183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    1. Adrenocortical carcinoma (ACC) is a rare malignant disease with poor prognosis. The main pharmacological choice, o,p'-DDD (mitotane), produces severe adverse effects. 2. Since o,p'-DDD is a chiral molecule and stereoisomers frequently possess different pharmacokinetic and/or pharmacodynamic properties, we isolated the two o,p'-DDD enantiomers, (R)-(+)-o,p'-DDD and (S)-(-)-o,p'-DDD, and determined their absolute structures. 3. The effects of each enantiomer on cell viability and on cortisol and dehydroepiandrosterone (DHEA) secretion in the human adrenocortical cell line H295R were assessed. We also assayed the o, p'-DDD racemate and the m,p'- and p,p'-isomers. 4. The results show small but statistically significant differences in activity of the o, p'-DDD enantiomers for all parameters tested. The three DDD isomers were equally potent in decreasing cell viability, but p, p'- DDD affected hormone secretion slightly less than the o,p'- and m,p'-isomers. 5. The small chiral differences in direct effects on target cells alone do not warrant single enantiomer administration, but might reach importance in conjunction with possible stereochemical effects on pharmacokinetic processes in vivo.

  • 4.
    Athanasiadou, Maria
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Cuadra, Steven N
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Jakobsson, Kristina
    Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua.2008Inngår i: Environ Health Perspect, ISSN 0091-6765, Vol. 116, nr 3, s. 400-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum.

  • 5.
    Athanasiadou, Maria
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Asplund, Lillemor
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Gas chromatography and mass spectrometry of methoxylated polybrominated diphenyl ethers (MeO-PBDEs).2006Inngår i: J Mass Spectrom, ISSN 1076-5174, Vol. 41, nr 6, s. 790-801Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Bastos, Patricia Moreira
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Green, Nicholas
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    A standardized method for assessment of oxidative transformations of brominated phenols in water.2008Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 70, nr 7, s. 1196-202Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    BFR Exposure: Air, particles and food matters2007Inngår i: 4th International Workshop on Brominated Flame Retardants: BFR 2007 Amsterdam, 2007Konferansepaper (Annet (populærvitenskap, debatt, mm))
  • 8.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Perspective on recent developments of persistent and bioaccumulative BFRs2008Inngår i: BFR 2008: 10th Annual workshop on brominated flame retardants, 2008, s. 9-Konferansepaper (Annet (populærvitenskap, debatt, mm))
  • 9.
    Bergman, Åke
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    van den Berg, Martin
    Some bifocal views of risks of BFRs2007Inngår i: Organohalogen Compounds: Plenary Lecture, 2007, s. 7-9Konferansepaper (Fagfellevurdert)
  • 10. Björk, C
    et al.
    Nenonen, H
    Giwercman, Alexander
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Rylander, Lars
    Lundberg Giwercman, Yvonne
    The impact of CB-153 and p,p’-DDE on androgen receptor function2009Inngår i: Organohalogen Compounds, Vol. 71, Peking, 2009, s. 816-819Konferansepaper (Fagfellevurdert)
  • 11. Borg, Daniel
    et al.
    Bogdanska,, Jasna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Sundström, Maria
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Nobel, Stefan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Håkansson, Helen
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    DePierre, Joseph
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Halldin, Krister
    Bergström, Ulrika
    Perinatal tissue distribution of perfluorooctane sulphonate (PFOS) in mice2009Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 189, nr SI, s. S147-S147Artikkel i tidsskrift (Fagfellevurdert)
  • 12.
    Cantillana , T.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Sundström, M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Å.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE) via Newman-Kwart rearrangement - A precursor for synthesis of radiolabeled and unlabeled alkylsulfonyl-DDEsManuskript (Annet vitenskapelig)
    Abstract [en]

    For the first time, a pathway for synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE), is presented. The compound is of particular interest as a precursor for synthesis of alkylsulfonyl-DDE containing different alkyl groups to discover structural activity relationships, and to promote synthesis of radiolabeled methylsulfonyl-DDE. 2-Chloro-5-methylphenol was first methylated and further oxidized to the corresponding benzoic acid. The acid was reduced to the corresponding aldehyde (4-chloro-3-methoxy benzaldehyde) via 4-chloro-3-methoxy-benzene methanol. A lead/aluminium bimetal system was used to carry out the reductive addition of tetrachloromethane to 4-chloro-3-methoxy benzaldehyde to obtain 2,2,2-trichloro-1-(4-chloro-3-methoxyphenyl)ethanol, the desired starting material to synthesize the DDT-analogue (2-(4-chlorophenyl)-2-(4-chloro-3-methoxy-phenyl)-1,1,1-trichloroethane). Elimination of hydrochloric acid and removal of the methyl group led to the 3-OH-DDE. The Newman-Kwart rearrangement was applied to convert 3-OH-DDE to 3-SH-DDE via the dimethylcarbamothioate derivative. 3-SH-DDE is then used as a precursor for the radiolabel synthesis. The overall yield to acquire 3-SH-DDE after 11 steps was 3%. The step with the lowest yield was the DDT-analog synthesis with a yield of 30%. All other step had a yield of >50%. 3-SH-DDE was methylated with 14C-labeled iodomethane and oxidized by hydrogen peroxide to obtain 3-[14C]MeSO2-DDE in an overall yield of 30%.

  • 13.
    Cantillana, T
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    (2S)-1,1-dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane2009Inngår i: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 65(Pt 1), s. m9-m10Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    In the mol­ecule of the title compound, [HgCl2(C10H9N3)], the HgII atom is four-coordinated in a distorted tetra­hedral configuration by two N atoms from the chelating di-2-pyridylamine ligand and by two Cl atoms. In the crystal structure, inter­molecular N—HCl hydrogen bonds link the mol­ecules into centrosymmetric dimers. There is a π–π contact between the pyridine rings [centroid–centroid distance = 3.896 (5) Å].

  • 14.
    Cantillana, T.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Kismul, H.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Aleksandersen, M.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Tanum, M.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Sörvik, I.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Verhaegen, S.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Hovander, L.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Å.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Ropstad, E.
    Department of Production Animal Clinical Sciences, Section of stationary clinic, Norwegian School of Veterinary Science.
    Brandt, I.
    Department of Environmental Toxicology, Uppsala University.
    Toxicokinetics of the CYP11B1-activated adrenal toxicant 3-MeSO2-DDE in mother and offspring following oral administration to lactating minipigsManuskript (Annet vitenskapelig)
    Abstract [en]

    3-Methylsulfonyl-4,4’-DDE (3-MeSO2-DDE) is a persistent and bioaccumulative metabolite of 4,4’-DDT, formed through biotransformation of 4,4’-DDE and characterized by a high and tissue-specific toxicity in the adrenal cortex in mouse fetuses, suckling pups and adult mice. 3-MeSO2-DDE also targets the human adrenal cortex kept in tissue-culture ex-vivo and human adrenocortical H295R cells in vitro. The present study was designed to examine the excretion of 3-MeSO2-DDE in milk and the maternal and neonatal toxicokinetics following a single oral dose to lactating minipigs. Milk, maternal fat, and plasma from five pigs and their suckling offspring were collected at regular intervals during four weeks. At autopsy on day 30 post partum, adrenals, liver and body fat were sampled from mothers and piglets. The levels of 3-MeSO2-DDE were measured by gas chromatography and the toxicokinetics in mothers and offspring were computed. The levels of 3-MeSO2-DDE in milk were considerably higher than in maternal and offspring plasma throughout the investigation. Based on both fresh weight and fat contents, the 3-MeSO2-DDE plasma levels in the piglets were about five times higher than in the mothers. A strong accumulation of 3-MeSO2-DDE was observed in fat tissue and a moderate accumulation in adrenals and liver of mothers and offspring. The retained tissue levels in the piglets were consistently higher than in the mothers. It is concluded that suckling offspring were more exposed than their mothers, which were given 3-MeSO2-DDE orally. The results suggest that human risk assessment of the adrenocorticolytic environmental pollutant 3-MeSO2-DDE should be focussed on breast-fed infants. Also in highly 4,4’-DDE- and 3-MeSO2-DDE-exposed marine mammals, the risks posed by 3-MeSO2-DDE are likely most pronounced during the postnatal period

  • 15.
    Cantillana, T.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Lindström, V.
    Eriksson, L.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Brandt, I.
    Bergman, Å.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Interindividual differences in o,p '-DDD enantiomer kinetics examined in Göttingen minipigs2009Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Chemosphere, Vol. 76, nr 2, s. 167-172Artikkel i tidsskrift (Fagfellevurdert)
  • 16.
    cantillana, T.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Lindström, V.
    Department of Environmental Toxicology, Uppsala University.
    Eriksson, L.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Brandt, I.
    Department of Environmental Toxicology, Uppsala University.
    Bergman, Å.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigsManuskript (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Five minipigs were given a single oral dose of a racemic mixture of o,p’-DDD (30 mg kg-1 b.w., EF = 0.49). Blood plasma and subcutaneous adipose tissue were collected for analysis, at different time-points over 180 d. At the end of the experiment also liver, kidney and brain tissue were collected. Low concentrations of o,p’-DDD still remained after 180 d in plasma (mean 0.5 ±0.3 ng g-1 f.w.) and in adipose tissue (mean 40 ±40 ng g-1 f..w.). The mean concentrations in liver and kidney were 500 ±300 pg g-1 f.w. and 90 ±50 pg g-1 f.w. respectively. The enantiomers of o,p’-DDD were isolated by HPLC and the absolute configuration of the enantiomers were determined by X-ray crystallography and polarimetry as R-(+)-o,p’-DDD and S-(-)-o,p’-DDD. The enantiomer fractions (EFs) of o,p’-DDD were determined in plasma, adipose tissue and kidney using GC/ECD equipped with a chiral column. The EFs of o,p’-DDD in the individual minipigs showed large variability, ranging from 0.2-0.6 after 24 h in plasma and from 0.2-0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)-o,p’-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p’-DDD was dominating in three minipigs. We propose that a yet not identified factor related to polymorphism, regulating the metabolism and/or elimination of the enantiomeric o,p´-DDD, is responsible for the differences in enantiomeric retention of the compound in the minipigs.

  • 17.
    Cantillana, Tatiana
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Toxicologically important DDT metabolites: Synthesis, enantioselective analysis and kinetics2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    DDT was extensively and globally used as a pesticide in agriculture and for malaria vector control from the 1940’s until the 1970’s. Due to its heavy use, DDT became ubiquitously distributed throughout the environment. DDT and several DDT metabolites are persistent organic pollutants. Two DDT metabolites, 3-MeSO2-DDE and o,p’-DDD have been proved to be tissue specific toxicants in the adrenal cortex. They are bioactivated to reactive intermediates which bind covalently to the adrenal cortex causing cell death. Due to its tissue specific toxicity o,p’-DDD has been used as a chemotherapy drug for adrenal cancer in humans. The efficacy and potency is however low and o,p’-DDD treatment is associated with serious side effects. 3-MeSO2-DDE has been suggested as a potential alternative therapeutic agent.

    A key aim of this thesis has been to improve the understanding of the kinetics of the two adrenocorticolytic compounds o,p’-DDD, its two enantiomers and 3-MeSO2-DDE. To meet this objective chemical synthesis and enantioselective analysis were required. Furthermore, in vitro toxicity of o,p’-DDD enantiomers and diastereomers were performed.

    An 11 step synthesis of 3-SH-DDE has been developed to promote both labelled and unlabelled synthesis of 3-alkylsulfonyl-DDE. Toxicokinetic studies showed that 3-MeSO2-DDE and o,p’-DDD were accumulated in tissues and retained in adipose tissue in minipigs. 3-MeSO2-DDE however had a twice as long biological t1/2 and a considerably lower Vd compared to o,p’-DDD. Suckling offspring were more exposed to 3-MeSO2-DDE than their mothers who were given 3-MeSO2-DDE orally. Interindividual differences in enantiomer kinetics in minipigs were observed suggesting polymorphism among the minipigs. Preparative isolation of the o,p’-DDD enantiomers is presented allowing determination of the absolute structures of the o,p’-DDD enantiomers by X-ray. The pure enantiomer of o,p’-DDD showed significant differences in toxicity in human adrenocortical cells.

  • 18.
    Cantillana, Tatiana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hermansson, Veronica
    Brandt, Ingvar
    Bergman, Åke
    Enantiomer fractions of o,p'-DDD in plasma and tissues from Göttingen minipigs2007Inngår i: Organohalogen Compounds: Chiral Compounds, 2007, s. 271-274Konferansepaper (Fagfellevurdert)
  • 19.
    Cantillana, Tatiana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Sundström, Maria
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE) via Newman-Kwart rearrangement - A precursor for synthesis of radiolabeled and unlabeled alkylsulfonyl-DDEs2009Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, ISSN 0045-6535, Vol. 76, nr 6, s. 805-810Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For the first time, a pathway for synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE), is presented. The compound is of particular interest as a precursor for synthesis of alkylsulfonyl-DDE containing different alkyl groups to discover structural activity relationships, and to promote synthesis of radiolabeled methylsulfonyl-DDE. 2-Chloro-5-methyl phenol was first methylated and further oxidized to the corresponding benzoic acid. The acid was reduced to the corresponding aldehyde (4-chloro-3-methoxy benzaldehyde) via 4-chloro-3-methoxy-benzene methanol. A lead/aluminium bimetal system was used to carry out the reductive addition of tetrachloromethane to 4-chloro-3-methoxy benzaldehyde to obtain 2,2,2-trichloro-1-(4-chloro-3-methoxyphenyl)ethanol,the desired starting material to synthesize the DDT-analogue (2-(4-chlorophenyl)-2-(4-chloro-3-methoxy-phenyl)-1,1,1-trichloroethane). Elimination of hydrochloric acid and removal of the methyl group led to the 3-OH-DDE. The Newman-Kwart rearrangement was applied to convert 3-OH-DDE to 3-SH-DDE via the dimethyl-carbarnothioate derivative. 3-SH-DDE is then used as a precursor for the radiolabel synthesis. The overall yield to acquire 3-SH-DDE after 11 steps was 3%. The step with the lowest yield was the DDT-analog synthesis with a yield of 30%. All other step had a yield of >50%. 3-SH-DDE was methylated with C-14-labeled iodomethane and oxidized by hydrogen peroxide to obtain 3-[C-14]MeSO2-DDE in an overall yield of 30%.

  • 20. Cantón, Rocío F
    et al.
    Scholten, Deborah E A
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    de Jong, Paul C
    van den Berg, Martin
    Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs).2008Inngår i: Toxicol Appl Pharmacol, ISSN 0041-008X, Vol. 227, nr 1, s. 68-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC(50) values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K(i)/K(i)' of 7.68/0,02 microM and 5.01/0.04 microM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a wide range of OH-PBDEs have the potential to disturb steroidogenesis and indicate a potential mechanism of action of these brominated flame retardant derivatives as endocrine disruptors in humans and wildlife.

  • 21. Cantón, Rocío F
    et al.
    Scholten, Deborah E A
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    de Jong, Paul C
    van den Berg, Martin
    Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs).2007Inngår i: Toxicol Appl Pharmacol, ISSN 0041-008XArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC(50) values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K(i)/K(i)' of 7.68/0,02 muM and 5.01/0.04 muM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a wide range of OH-PBDEs have the potential to disturb steroidogenesis and indicate a potential mechanism of action of these brominated flame retardant derivatives as endocrine disruptors in humans and wildlife

  • 22.
    Christiansson, Anna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Synthesis of highly brominated diphenyl ethers and aspects on photolysis and indoor spreading2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Adding chemicals to materials to decrease flammability can be dated back to as early as 450 BC when the Egyptians used alum to reduce flammability of wood. Almost 2500 years later brominated flame retardants (BFRs) are used to prevent ignition of textiles, electronics and polymers. BFRs in major use today are polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), including derivatives. There have been three industrial PBDE mixtures produced. Extensive scientific reporting has shown increasing concentrations of PBDEs in wildlife and in humans. This in combination with reports on their physico-chemical characteristics and chemical reactivity have led to that two of the PBDE products have been classified as being persistent, bioaccumulative and toxic, which has led to legislative measures, in e.g. EU, Norway and the USA.

    The availability of pure reference standards is a prerequisite for much toxicologically related research. Hence the main objective of this thesis was to develop additional methods for synthesis of highly brominated diphenyl ethers. Further, to quantify and identify photolysis products of decabromodiphenyl ether (decaBDE) and to perform a case study regarding PBDE exposure in aircrafts.

    Synthesis of highly brominated BDE congeners by perbromination of mono- or diaminodiphenyl ethers followed by diazotization of the amino group(s) and introduction of hydrogen(s) in the molecules is a convenient route for synthesis of some octaBDEs and all nonaBDEs. Selective bromination of diaminodiphenyl ether, followed by diazotization of the amino groups and substitution with bromines yielded a hexaBDE or a heptaBDE which were then further brominated to octaBDE congeners.

    Even though several studies have been performed on photolysis of decaBDE a new study with a more quantitative approach was performed as part of this thesis. Debrominated PBDE products were identified and quantified and a marker PBDE for UV degradation of DecaBDE was identified i.e., 2,2’,3,3’,5,5’,6,6-octabromodiphenyl ether (BDE-202). Polybrominated dibenzofuranes, methoxlated brominated dibenzofuranes, pentabromophenol and hydroxylated bromobenzenes were also detected. The PBDEs accounted for approximately 90% of the total amount of substances in each sample and the PBDFs for about 10%. Also, a case study on potential exposure to PBDEs in humans travelling long distances by aircraft was done. It was shown that PBDE concentrations in dust onboard aircrafts may be high and increased PBDE serum levels were indicated in a majority of the travellers.

    The present thesis has contributed to make higher brominated diphenyl ethers available as reference standards, allowing better quantitative assessments possible regarding both abiotic studies and exposure assessments. New toxicological testing can also be pursued.

  • 23.
    Christiansson, Anna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Teclechiel, Daniel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Identification and quantification of products formed via photolysis of decabromodiphenyl ether2009Inngår i: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 16, nr 3, s. 312-321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND, AIM, AND SCOPE: Decabromodiphenyl ether (DecaBDE) is used as an additive flame retardant in polymers. It has become a ubiquitous environmental contaminant, particularly abundant in abiotic media, such as sediments, air, and dust, and also present in wildlife and in humans. The main DecaBDE constituent, perbrominated diphenyl ether (BDE-209), is susceptible to transformations as observed in experimental work. This work is aimed at identifying and assessing the relative amounts of products formed after UV irradiation of BDE-209. MATERIALS AND METHODS: BDE-209, dissolved in tetrahydrofuran (THF), methanol, or combinations of methanol/water, was exposed to UV light for 100 or 200 min. Samples were analyzed by gas chromatography/mass spectrometry (electron ionization) for polybrominated diphenyl ethers (PBDEs), dibenzofurans (PBDFs), methoxylated PBDEs, and phenolic PBDE products. RESULTS: The products formed were hexaBDEs to nonaBDEs, monoBDFs to pentaBDFs, and methoxylated tetraBDFs to pentaBDFs. The products found in the fraction containing halogenated phenols were assigned to be pentabromophenol, dihydroxytetrabromobenzene, dihydroxydibromodibenzofuran, dihydroxytribromodibenzofuran, and dihydroxytetrabromodibenzofuran. The PBDEs accounted for approximately 90% of the total amount of substances in each sample and the PBDFs for about 10%. DISCUSSION: BDE-209 is a source of PBDEs primarily present in OctaBDEs but also to some extent in PentaBDEs, both being commercial products now banned within the EU and in several states within the USA. It is notable that OH-PBDFs have not been identified or indicated in any of the photolysis studies performed to date. Formation of OH-PBDFs, however, may occur as pure radical reactions in the atmosphere. CONCLUSIONS: Photolysis of decaBDE yields a wide span of products, from nonaBDEs to hydroxylated bromobenzenes. It is evident that irradiation of decaBDE in water and methanol yields OH-PBDFs and MeO-PBDFs, respectively. BDE-202 (2,2',3,3',5,5',6,6'-octabromodiphenyl ether) is identified as a marker of BDE-209 photolysis. RECOMMENDATIONS AND PERSPECTIVES: BDE-209, the main constituent of DecaBDE, is primarily forming debrominated diphenyl ethers with higher persistence which are more bioaccumulative than the starting material when subjected to UV light. Hence, DecaBDE should be considered as a source of these PBDE congeners in the environment

  • 24.
    Christiansson, Anna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hovander, Lotta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Jakobsson, Kristina
    Department of Occupational and Environmental Medicine, Lund University Hospital.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Polybrominated diphenyl ethers in aircraft cabins – a source of human exposure?2008Inngår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 73, nr 10, s. 1654-1660Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Commercial aircrafts need a high degree of fire protection for passenger safety. Brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs), may be used for this purpose. Because PBDEs readily absorb to dust particles, aircraft crew and passengers may receive significant PBDEs exposure via inhalation. The aims of this work were to assess whether PBDEs could be found in aircraft cabin dust and whether serum levels of PBDEs increased in passengers after long-distance flights. Hence nine subjects on intercontinental flights collected cabin dust samples, as well as donated blood samples before departure and after return to Sweden. Two subjects who were domestic frequent flyers were also investigated. The levels of PBDEs in dust and serum were determined by GC/MS in electron capture negative ionization (ECNI) mode. Authentic reference substances were used for identification and quantitation. PBDEs were found in all aircraft dust samples at high concentrations, higher than in common household dust. Congener patterns indicated that the technical products PentaBDE, OctaBDE and DecaBDE were used in the aircrafts. Serum concentrations in the travellers were similar to those observed in Swedish residents in general. Post-travel serum levels of BDE-28, BDE-99, BDE-100, BDE-153, and BDE-154 were significantly higher (p < 0.05) than concentrations prior to travel. The findings from this pilot study call for investigations of occupational exposures to PBDEs in cabin and cockpit crews.

  • 25.
    Christiansson, Anna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Teclechiel, Daniel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Methods for synthesis of nonabromodiphenyl ethers and a chloro-nonabromodiphenyl ether2006Inngår i: Chemosphere, Vol. 63, nr 4, s. 562-569Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) have been used extensively as brominated flame retardants (BFRs) in textiles, upholstery and electronics. They are ubiquitous contaminants in wildlife and humans. A low concentration of nonabrominated diphenyl ethers (nonaBDEs) is present in commercial DecaBDE and they are also abiotic and biotic debromination products of decabromodiphenyl ether (BDE-209). The objective of the present work was to develop methods for synthesis of the three nonaBDEs, 2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether (BDE-206), 2,2',3,3',4,4',5,6,6'-nonabromodiphenyl ether (BDE-207) and 2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether (BDE-208), with the intention of making them available as authentic standards for analytical, toxicological and stability studies, as well as studies regarding physical-chemical properties. Two methods were developed, one based on perbromination of phenoxyanilines and the other via reductive debromination of BDE-209 by sodium borohydride followed by chromatographic separation of the three nonaBDE isomers formed. An additional nonabrominated compound, 4'-chloro-2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether (Cl-BDE-208), was also synthesized in the present work. Cl-BDE-208, prepared by the perbromination of 4-chlorodiphenyl ether, may be used as an internal standard in analysis of highly brominated diphenyl ethers. BDE-206, BDE-207, BDE-208 and Cl-BDE-208 were characterized by 1H NMR, 13C NMR, electron ionization mass spectra and by their melting points. The structures of all three nonaBDEs have been characterized previously by X-ray crystallography.

  • 26.
    Christiansson, Anna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Teclechiel, Daniel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Methods for synthesis of nonabromodiphenyl ethers and a chloro-nonabromodiphenyl ether2006Inngår i: Chemosphere, Vol. 63, nr 4, s. 562-569Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) have been used extensively as brominated flame retardants (BFRs) in textiles, upholstery and electronics. They are ubiquitous contaminants in wildlife and humans. A low concentration of nonabrominated diphenyl ethers (nonaBDEs) is present in commercial DecaBDE and they are also abiotic and biotic debromination products of decabromodiphenyl ether (BDE-209). The objective of the present work was to develop methods for synthesis of the three nonaBDEs, 2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether (BDE-206), 2,2',3,3',4,4',5,6,6'-nonabromodiphenyl ether (BDE-207) and 2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether (BDE-208), with the intention of making them available as authentic standards for analytical, toxicological and stability studies, as well as studies regarding physical-chemical properties. Two methods were developed, one based on perbromination of phenoxyanilines and the other via reductive debromination of BDE-209 by sodium borohydride followed by chromatographic separation of the three nonaBDE isomers formed. An additional nonabrominated compound, 4'-chloro-2,2',3,3',4,5,5',6,6'-nonabromodiphenyl ether (Cl-BDE-208), was also synthesized in the present work. Cl-BDE-208, prepared by the perbromination of 4-chlorodiphenyl ether, may be used as an internal standard in analysis of highly brominated diphenyl ethers. BDE-206, BDE-207, BDE-208 and Cl-BDE-208 were characterized by 1H NMR, 13C NMR, electron ionization mass spectra and by their melting points. The structures of all three nonaBDEs have been characterized previously by X-ray crystallography.

  • 27.
    Cui, Daqing
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Ranebo, Ylva
    Low, Jeanette
    Rondinella, V.V
    Pan, J
    Spahiu, K
    Immobilization of Radionuclides on Iron Canister Material at Simulated Near-field Conditions2009Inngår i: Scientific basis for nuclear waste management XXXII / [ed] Neil C. Hyatt, David A. Pickett, Raul B. Rebak, Warrendale, Pa: Materials Research Society , 2009, Vol. 1124, s. 111-116Konferansepaper (Fagfellevurdert)
    Abstract [en]

    This work is a continuation of a long-term spent fuel leaching and radionuclides immobilization (by iron canister) experiment under simulated near-field conditions, in deoxygenated 2 mM NaHCO3 solution with 1 Gy/h g irradiation. The corrosion of iron canister material was investigated by electrochemical and microanalytical methods. Significant amounts of radionuclides (U, Np, Tc, Sr) were found to be immobilized on the corrosion layer of iron canister material by using SEM_WDS and SIMS methods. The observation is useful for bettering our understanding of near-field chemical processes at earlier canister failure conditions.

  • 28.
    Davies, R.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hedebrant, U.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Athanassiadis, I.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Rydberg, P.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Improved method to measure aldehyde adducts to N-terminal valine in hemoglobin using 5-hydroxymethylfurfural and 2,5-furandialdehyde as model compounds2009Inngår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 47, nr 8, s. 1950-1957Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hemoglobin (Hb) adducts are used to measure reactive compounds/metabolites in vivo. Schiff base adducts from aldehydes to N-termini in Hb have been measured by GC-MS/MS after stabilisation through reduction, and detachment by a modified Edman procedure. This paper describes a further development using 5-hydroxymethylfurfural (HMF) and its probable metabolite, 2,5-furandialdehyde (FDA), as model compounds. Reference compounds were synthesized and characterized. The conditions for the reduction of the Schiff bases were optimized using NaBH(3)CN as a mild reducing agent, and steps used in the earlier method could be deleted. The adduct from FDA could not be specifically analysed, as selective reduction of the imine could not be achieved. In a few samples of human blood, background levels of 10-35 pmol/g globin of the HMF adduct were observed. Half-lifes of the reversible Schiff base adduct from HMF were determined to 3.4h at 37 degrees C and 10.9h at 25 degrees C. The developed method showed good sensitivity and reproducibility for the analysis of the Schiff base from HMF, with improvements regarding simplicity of work-up procedures due to mild conditions. The developed method could be explored for application to adducts from other aldehydes bound as Schiff bases to N-termini in Hb.

  • 29.
    Davies, Ronnie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    New approaches for synthesis and analysis of adducts to N-terminal valine in hemoglobin from isocyanates, aldehydes, methyl vinyl ketone and diepoxybutane2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Human exposure to harmful compounds in the environment, from intake via food, occupational exposures or other sources, could have health implications. Exposure to reactive compounds/metabolites can be identified and quantified as hemoglobin (Hb) adducts by mass spectrometry. This thesis aimed at improved synthetic pathways for reference standards, and improved analytical methods for adducts to N-terminal valine in Hb from a range of reactive compounds; isocyanates, aldehydes, methyl vinyl ketone (MVK), and diepoxybutane (DEB).

    Isocyanates form urea adducts with N-terminal valine by carbamoylation, which are detachable as hydantoins by hydrolysis. A new synthetic pathway for reference standards of adducts from isocyanates and a method for their analysis by liquid chromatography/mass spectrometry (LC/MS) were developed.

    Aldehydes form reversible imines (Schiff bases) with N-termini in Hb. After stabilisation by reduction and detachment by isothiocyanates using modified Edman methods, these adducts could be analysed by gas chromatography/mass spectrometry (GC/MS) or LC/MS. 5-Hydroxymethylfurfural, its metabolites, and other aldehydes related to exposure via food, were studied with regard to analysis by these methods with synthesised standard references. A considerably improved analytical method for imines was developed. Many of the studied adducts are too short-lived in vivo or in vitro to be used for long-term biomonitoring. However, different approaches for the analysis were evaluated.

    Through synthesised reference standards, an observed unknown adduct in blood was verified as the adduct from MVK. There exist both natural and anthropogenic sources for MVK.

    DEB, metabolite of butadiene, forms a cyclic adduct to valine-N. A new approach using hydrazinolysis of protein and enrichment by molecularly imprinted solid-phase extraction was tested on synthesised reference DEB-adduct and gave promising results.

    Synthesised standards were characterized by NMR, LC/MS and GC/MS.

  • 30.
    Davies, Ronnie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hedebrant, Ulla
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Improved method for the analysis of reactive aldehydes in human blood2008Inngår i: 6:e Svensk-norskt miljökemiskt möte: SNMM 2008 22-24 September, 2008Konferansepaper (Fagfellevurdert)
  • 31. Dingemans, Milou M L
    et al.
    Ramakers, Geert M J
    Gardoni, Fabrizio
    van Kleef, Regina G D M
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Di Luca, Monica
    van den Berg, Martin
    Westerink, Remco H S
    Vijverberg, Henk P M
    Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus.2007Inngår i: Environ Health Perspect, ISSN 0091-6765, Vol. 115, nr 6, s. 865-70Artikkel i tidsskrift (Fagfellevurdert)
  • 32.
    Eriksson, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Polybrominated diphenyl ethers and Tetrabromobisphenol A: Chemical synthesis, X-ray crystallography and Photochemical degradation2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In the 1960s’ several manmade chemicals were detected in the environment, far from their sources. The most well known, and most likely those with the largest impact on the society, were DDT and its related compounds, and PCBs. These anthropogenic compounds were characterised as persistent organic pollutants (POPs). Following these POPs, several other chemicals have found their way to the environment. Over the last two decades, brominated flame retardants (BFRs) have become a matter of concern. Among all BFRs being commercially produced, tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) are the ones with the largest annual production. TBBPA is a very well defined compound while PBDEs consist of a large number of isomers and homologues (congeners). TBBPA does not seem to accumulate in biota as the PBDEs do, but is still of concern since it is found in e.g. sediments. The PBDEs can reach accumulation levels up in the ppm range. Still there is a lack of basic data for both TBBPA and PBDEs. Hence the present thesis is aimed to fill some of the data gaps by pursuing work on 1) photochemical degradation of TBBPA, some related compounds, and PBDEs; 2) synthesis of PBDE congeners and of TBBPA degradation products and 3) structural identifications of a selected set of BFRs by X-ray crystallography.

    An apparatus was designed for carrying out photochemical degradation test of chemicals in general but in particular for BFRs. Quantum yield, rate of degradation and to some extent, identification of degradation products were performed on TBBPA, the corresponding chlorinated compound and a number of TBBPA degradation products and on 15 single PBDE congeners. In order to make this work possible all three nonaBDE isomers were synthesised via a reductive pathway applying sodium borohydride as a reducing agent. The three nona-BDEs were all characterised by X-ray crystallography.

    The results of the photochemical degradation of TBBPA in water show a rapidly degradable compound also at pH’s that are environmentally relevant. Hence it is likely that TBBPA is not transported long distances, when exposed to sunlight, without undergoing photochemical degradation. It is notable that the TBBPA is degraded through cleavage between the two phenol rings. When the method was applied to study quantum yields and rate constants for the reaction of PBDE congeners it is evident that the decabromodiphenyl ether (BDE-209) is rapidly transformed. The reaction rate differ drastically from PBDEs with four or five bromine substituents that have very long half-lives when subjected to UV-light under the same conditions as for BDE-209. Lower brominated diphenyl ethers and polybrominated dibenzofurans were identified as PBDE degradation products. The synthesis of PBDEs and of TBBPA degradation products expanded the study as did the X-ray structure identifications.

  • 33.
    Eriksson, Johan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi, Avdelningen för strukturkemi.
    2,2’,6,6’-Tetrachloro-4,4’-propane-2,2-diyldiphenol, 2,2’,6-tribromo-4,4’-propane-2,2-diyldi phenol and 2,2’,6,6’-tetrabromo-4,4’-propane-2,2-diyldiphenol2001Inngår i: Acta crystallographica Section C, ISSN 0108-2701, Vol. 57, nr 11, s. 1308-1312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Three flame retardants with very similar molecular structures showing three different packing patterns have been studied. The crystal structure of 2,2',6,6'-tetrachloro-4,4'-propane-2,2-diyldiphenol, C15H12Cl4O2, can be described as a packing of sheets. The packing shows a very short intermolecular ClCl contact distance of 3.094  (2)  Å between pairs of molecules inside each sheet. The crystal structure of 2,2',6-tribromo-4,4'-propane-2,2-diyldiphenol, C15H13Br3O2, can be described as a packing of doubly stranded helical square tubes. These square helices are interconnected through BrBr contacts between different helices. Finally, a previously known structure, 2,2',6,6'-tetrabromo-4,4'-propane-2,2-diyldiphenol [Simonov, Cheban, Rotaru & Bels'skii (1986). Kristallografiya, 31, 397-399], C15H12Br4O2, which is the most commonly used flame retardant and which has twofold rotational symmetry, has been refined in the correct absolute configuration. The structure shows large differences from the chloro analogue with regard to packing, van der Waals distances and hydrogen-bond distances.

  • 34.
    Eriksson, Johan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi, Avdelningen för strukturkemi.
    Jakobsson, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi, Avdelningen för strukturkemi.
    Decabromodiphenyl ether1999Inngår i: Acta crystallographica Section C, ISSN 0108-2701, Vol. 55, nr 12, s. 2169-2171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bis(pentabromophenyl) ether, C12Br100, shows strangedifferences in the endocyclic angles between the twodifferent rings, although they are both substituted inthe same manner. Several short van der Waals contact distances give clues to the anomalous endocyclic anglesand some hints to the formation of decompositionproducts. We suggest that the intermolecular Br...Brcontacts contribute to the distortions of the ring systems.Usually distortions of this kind would be explained fromhighly anisotropic TLS behaviour, but the data from thetitle compound do not show any conclusive TLS effects.

  • 35.
    Eriksson, Johan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Green, Nicholas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Marsh, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Photochemical decomposition of fifteen polybrominated diphenyl ether congeners in methanol/water2004Inngår i: Environmental Science & Technology, ISSN 1520-5851, Vol. 38, nr 11, s. 3119-3125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Among all brominated flame retardants in use, the polybrominated diphenyl ethers (PBDEs) have been identified as being of particular environmental concern due to their global distribution and bioaccumulating properties, as observed in humans and wildlife worldwide. Still there is a need for more data on the basic characteristics of PBDEs to better understand and describe their environmental fate. Hence, the aim of this study was to investigate the photochemical degradation of PBDEs with different degrees of bromination. The photochemical degradation of 15 individual PBDEs substituted with 4−10 bromine atoms was studied in methanol/water (8:2) by UV light in the sunlight region. Nine of these were also studied in pure methanol, and four of the nine PBDEs were studied in tetrahydrofuran. The photochemical reaction rate decreased with decreasing number of bromine substituents in the molecule but also in some cases influenced by the PBDE substitution pattern. The reaction rate was dependent on the solvent in such a way that the reaction rate in a methanol/water solution was consistently around 1.7 times lower than in pure methanol and 2−3 times lower than in THF. The UV degradation half-life of decaBDE (T1/2 = 0.5 h) was more than 500 times shorter than the environmentally abundant congener 2,2‘,4,4‘-tetraBDE (T1/2 = 12 d) in methanol/water. The quantum yields in the methanol/water solution ranged from 0.1 to 0.3. The photochemical reaction of decaBDE is a consecutive debromination from ten- down to six-bromine-substituted PBDEs. Products with less than six bromines were tentatively identified as brominated dibenzofurans and traces of what was indicated as methoxylated brominated dibenzofurans.

  • 36.
    Eriksson, Johan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Marsh, G
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Å
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi, Avdelningen för strukturkemi.
    3,4,5,6-Tetrabromo phenyl-2,3,4,5,6-pentabromo phenyl ether, C12HBr9O, 2,4,5,6-tetrabromo phenyl-2,3,4,5,6-pentabromo phenyl ether, C12HBr9O and 2,3,5,6-tetrabromo phenyl-2,3,4,5,6-pentabromo phenyl ether, C12HBr9O2004Manuskript (preprint) (Annet (populærvitenskap, debatt, mm))
  • 37. Eriksson, Johan
    et al.
    Rahm, Sara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Green, Nicholas
    Bergman, Åke
    Jakobsson, Eva
    Photochemical transformations of tetrabromobisphenol A and related phenols in water2004Inngår i: Chemosphere, ISSN 0045-6535, Vol. 54, nr 1, s. 117-126Artikkel i tidsskrift (Fagfellevurdert)
  • 38.
    Eriksson, Johan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Rahm, Sara
    Stockholms universitet, Stockholm Resilience Centre, Centrum för tvärvetenskaplig miljöforskning (CTM). Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Green, Nicholas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Bergman, Åke
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Jakobsson, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Photochemical transformations of tetrabromobisphenol A and related phenols in water2004Inngår i: Chemosphere, ISSN 0045-6535, Vol. 54, nr 1, s. 117-126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    romobisphenolA (TBBPA), tribromobisphenol A (TriBBPA), tetrachlorobisphenol A (TCBPA), 2,4-dichlorophenolat various pHs as well as 2-chlorophenol, 2-bromophenol, 3,4-dichlorophenol and bisphenol A at pH 11. The absorbancespectra of the compounds and the emission spectra of the light-source were determined and used to calculatedisappearance quantum yields of the photochemical reactions that were taking place. No major differences between thedisappearance quantum yields of TBBPA and TCBPA were observed at pH 10, while the disappearance quantum yieldof TriBBPA was approximately two times higher. The rate of decomposition of TBBPA was six times higher at pH 8than at pH 6. Identification of the degradation products of TBBPA and TriBBPA, by GC–MS analysis and bycomparison to synthesised reference compounds, indicated that TBBPA and TriBBPA decompose via differentmechanisms. Three isopropylphenol derivatives; 4-isopropyl-2,6-dibromophenol, 4-isopropylene-2,6-dibromophenoland 4-(2-hydroxyisopropyl)-2,6-dibromophenol, were identified as major degradation products of TBBPA while themajor degradation product of TriBBPA was tentatively identified as 2-(2,4-cyclopentadienyl)-2-(3,5-dibromo-4-hydroxyphenyl)propane.

  • 39.
    Eriksson, Sune
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Acrylamide in food products: Identification, formation and analytical methodology2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The aim of this thesis was to verify the indicated occurrence of acrylamide formation in heating of food, to identify factors affecting the formation, and to identify important sources of acrylamide exposure from food. As a prerequisite for the studies, gas- and liquid-chromatographic methods with mass spectrometric detection were developed for the analysis of acrylamide in food. The developed methods showed a high correlation coefficient (0.99), high sensitivity and reproducibility. Acrylamide was demonstrated to occur in heated food products, with unexpectedly high levels in potato products (up to mg/kg level in potato crisps) and in beetroot. The identity of acrylamide was confirmed by the developed methods.

    With potato as a food model, different factors affecting the acrylamide formation were tested. It was shown that the addition of asparagine and fructose, as well as heating temperature and time had a large impact on the formation. Other factors affecting the acrylamide content were pH, addition of other amino acids apart from asparagine, protein and other reducing sugars. No significant effects were observed from addition of neither antioxidant nor radical initiators. It was discovered that acrylamide could be formed during heating of biological materials similar to food, also at temperatures below 100 ˚C. Furthermore, it was demonstrated that a fraction of acrylamide evaporates during heating, similar to conditions for cooking in household kitchens, and during dry matter determinations in laboratories (65-130 ˚C). This constitutes an earlier unobserved source of exposure to acrylamide.

    The method for extraction of food was studied with regard to yield of acrylamide. It was shown that the yield at pH ≥12 increases 3 - 4 times compared to normal water extraction for some foods products. Extraction at acidic pH or with enzymatic treatment was also tested, showing no effect on yield.

    In a study with mice the bioaviability of acrylamide extracted with the normal water extration and at alkaline pH was compared. It was shown that the extra acrylamide released at alkaline pH gave insignificant contributions to the in vivo dose, measured by hemoglobin adducts.

  • 40.
    Eriksson, Sune
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Karlsson, Patrik
    Alternative extraction techniques for analysis of acrylamide in food: Influence of pH and digestive enzymes2006Inngår i: Journal of food science and technology, ISSN 0022-1155, E-ISSN 0975-8402, Vol. 39, nr 4, s. 393-399Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acrylamide in food is normally measured as “water-soluble free acrylamide”. However, it is shown that the technique of extraction, according to the method for extraction of dietary fibres or at high pH can affect the results. This has to be accounted for, particularly in the assessment of exposure and in studies of bioavailability and, in the long term, health risk assessment.

  • 41.
    Eriksson, Sune
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Karlsson, Patrik
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Measurement of evaporated acrylamide during heat treatment of food and other biological materials2007Inngår i: LWT – Food Science and Technology, ISSN 0023-6438, Vol. 40, nr 7, s. 706-712Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is established that acrylamide could be formed during heating of food products. In the present work we have studied whether the formed acrylamide could evaporate from food at elevated temperatures used in cooking (>160 °C) or used in determination of dry matter in laboratory analysis (ca. 105 °C). It was demonstrated that acrylamide evaporates from food samples during both cooking and temperatures used for drying. Up to ca. 4 μg/m3 could be measured above the fry pan during frying of potato. In parallel we have also studied whether acrylamide could be formed and evaporate during the elevated temperatures of 65–130 °C used for dry matter determinations in other types of samples containing biological material, like agricultural and environmental samples. It was found that acrylamide is formed during conditions for drying of soil, sediment and silage samples, as well as cereals, animal feed, etc. After drying, levels of acrylamide up to about 100 μg/kg were found, e.g. in samples of sediment and sludge. The measurements showed in the food, agricultural and environmental samples tested a minor fraction, roughly estimated to be 0.15–7.2% of the formed acrylamide evaporates at the used elevated temperatures.

  • 42. Eriksson, Sune
    et al.
    Karlsson, Patrik
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Measurement of evaporated acrylamide during heat treatment of food and other biological materials2007Inngår i: LWT - Food Science and Technology, Vol. 40, nr 4, s. 706-712Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    It is established that acrylamide could be formed during heating of food products. In the present work we have studied whether the formed acrylamide could evaporate from food at elevated temperatures used in cooking (>160 °C) or used in determination of dry matter in laboratory analysis (ca. 105 °C). It was demonstrated that acrylamide evaporates from food samples during both cooking and temperatures used for drying. Up to ca. 4 μg/m3 could be measured above the fry pan during frying of potato. In parallel we have also studied whether acrylamide could be formed and evaporate during the elevated temperatures of 65–130 °C used for dry matter determinations in other types of samples containing biological material, like agricultural and environmental samples. It was found that acrylamide is formed during conditions for drying of soil, sediment and silage samples, as well as cereals, animal feed, etc. After drying, levels of acrylamide up to about 100 μg/kg were found, e.g. in samples of sediment and sludge. The measurements showed in the food, agricultural and environmental samples tested a minor fraction, roughly estimated to be 0.15–7.2% of the formed acrylamide evaporates at the used elevated temperatures.

  • 43.
    Fred, Charlotta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Methods for measurement of reactive metabolites as a basis for cancer risk assessment: Application to 1,3-butadiene and isoprene2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    1,3-Butadiene is a general air pollutant associated with combustion of organic matter and is also an extensively used monomer in polymer production. The cancer risk estimation of 1,3-butadiene is encumbered with large uncertainties. Extrapolation from tumour frequencies in long-term animal tests has led to a relatively high figure for the risk associated with 1,3-butadiene exposure. This is mainly based on observations of very high tumour incidences in butadiene-exposed mice, which in this respect are about 100 times more sensitive than rats. It has been hypothesized that a high cancer risk from 1,3-butadiene could be associated with its metabolism to the bifunctional 1,2:3,4-diepoxybutane (DEB) which, in comparison with monofunctional epoxides, 1,2-epoxy-3-butene (EB) and 1,2-epoxy-3,4-butanediol (EBdiol), is a highly effective mutagen, i.e. cancer initiator. Measurement of in vivo doses of DEB is therefore essential for the risk assessment of 1,3-butadiene. Reaction products with hemoglobin offer a possibility of measuring reactive metabolites in vivo. Hemoglobin adducts from EBdiol have in this study been measured with available methods, which are, however, not applicable to the bifunctional DEB, and method development was therefore needed.

    This work presents a procedure for measurement of a specific, ring-closed adduct, Pyr-Val, formed from the reaction of DEB with N-terminal valines in hemoglobin. It is based on LC-ESI-MS/MS analysis of the Pyr-modified N-terminal peptides enriched after trypsin digestion of globin. Mouse and rat could be compared regarding the metabolism of EB, DEB and EBdiol. From the data it was concluded that, in 1,3-butadiene exposure, about 60 times higher levels of DEB are formed in mice compared to rats. Estimates of in vivo doses in published cancer tests showed that carcinogenesis in mice is mainly due to DEB, whereas in rat, and possibly man, the monofunctional EBdiol is the predominant causative factor. Preliminarily, the cancer risk assessed from these data is compatible with the epidemiology-based risk estimate of US EPA.

    Due to the structural similarity with 1,3-butadiene, certain parallel studies of isoprene (2-methyl-1,3-butadiene) metabolism were initiated. Isoprene is the major endogenously produced hydrocarbon in humans and mammals and shows a similar difference in sensitivity between species for tumour development as 1,3-butadiene. In mice treated with the isoprene monoepoxide, 1,2-epoxy-2-methyl-3-butene (IMO), an in vivo formation of the corresponding diepoxide, 1,2:3,4-diepoxy-2-methyl-butane (IDO), was demonstrated. The in vivo dose of IDO formed from IMO was about half of that of DEB formed from EB. In the analysis of bone marrow erythrocytes an increased frequency of micronuclei, induced by treatment with EB or IMO, showed correlation with the in vivo doses of the respective diepoxides.

    With the ambition to reduce animal experiments a general procedure has been developed for trapping reactive metabolites in in vitro test systems, with the specific aim to study differences between species in metabolism of 1,3-butadiene. Vitamin B12 in its reduced form [Cbl(I)] has been used for instant trapping of 1,3-butadiene metabolites formed in S9-mixture. LC-ESI-MS/MS is then used for quantification of the formed alkyl-Cbls. The method has been applied to the epoxide metabolites of 1,3-butadiene, which all form specific alkyl-Cbls in the reaction with Cbl(I)

  • 44.
    Fred, Charlotta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Cantillana, Tatiana
    Henderson, Alistair
    Golding, Bernard T.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Adducts to N-terminal valines in hemoglobin from isoprene di-epoxide, a metabolite of isoprene2004Inngår i: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 18, nr 18, s. 2177-2184Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Isoprene (2-methylbuta-1,3-diene) is a multi-site carcinogen in rodents. To evaluate the role of the diepoxide metabolite (1,2:3,4-diepoxy-2-methylbutane) in carcinogenesis, measurements of in vivo doses of the diepoxide are needed. The in vivo dose may be inferred from levels of reaction products with hemoglobin (Hb adducts). This report presents in vitro studies of the adduct formation by the diepoxide of isoprene with valinamide and oligopeptides as model compounds of N-terminal valines in hemoglobin (Hb). In the reaction with valinamide it was shown that isoprene diepoxide forms as the main product a ring-closed adduct, which is a pyrrolidine derivative [N,N-(2,3-dihydroxy-2-methyl-1,4-butadiyl)valinamide, MPyr-Val]. The analysis was performed by gas chromatography/mass spectrometry (GC/MS) (EI and PICI) after acetylation. The ring-closed adduct was also identified by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) as the main product in the reaction between isoprene diepoxide and standard hepta- or (2H8)octapeptides, corresponding to the N-terminal peptides of the α-chains in mouse and rat Hb. These peptides, alkylated with isoprene diepoxide, to be used as internal standards and calibration standards for quantification of MPyr-adduct levels in vitro and in vivo, were analyzed with respect to the degree of MPyr-alkylation by two independent methods, amino acid analysis and HPLC-UV; similar results were obtained using these methods. A method for measurement of Hb adducts as modified peptides, used earlier to measure a similar adduct to N-terminal valines in Hb from the diepoxide of 1,3-butadiene, has in the present work been tested for application to isoprene diepoxide. The method is based on tryptic degradation of globin and LC/ESI-MS analysis of N-terminal Pyr-heptapeptides of the Hb α-chain enriched by HPLC. MPyr-adduct levels in isoprene diepoxide alkylated hemolysate from mouse erythrocytes incubated with different concentrations of isoprene diepoxide (2 and 10 mM) for 1 h were quantified. The adduct level was about 50 nmol/g α-chain Hb per mM × h. From the adduct levels the rate constant of isoprene diepoxide for reaction with N-terminal valine was calculated to be about 1.6 times faster than for diepoxybutane

  • 45.
    Fred, Charlotta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Grawé, Jan
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Hemoglobin adducts and micronuclei in rodents after treatment with isoprene monoxide or butadiene monoxide2005Inngår i: Mutation Research, ISSN 1383-5742, E-ISSN 1388-2139, Vol. 585, nr 1-2, s. 21-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    1,3-Butadiene and isoprene (2-methyl-1,3-butadiene) are chemically related substances that are carcinogenic to rodents. The overall aim of this work is to elucidate the role of the genotoxic action of diepoxide metabolites in the carcinogenesis of the dialkenes. In vivo doses of the diepoxide metabolites were measured through reaction products with hemoglobin (Hb adducts) in studies of induced micronuclei (MN) in rodents. In the reaction with N-terminal valine in Hb, diepoxybutane and isoprenediepoxide form ring-closed adducts, pyrrolidines [N,N-(2,3-dihydroxy-1,4-butadiyl)valine and N,N-(2,3-dihydroxy-2-methyl-1,4-butadiyl)valine, respectively]. The method applied for Hb-adduct measurement is based on tryptic degradation of the protein and liquid chromatography electrospray ionisation tandem mass spectrometry (LC–ESI-MS/MS) analysis. Mice were given single i.p. injections of the monoepoxides of butadiene and isoprene, 1,2-epoxy-3-butene or 1,2-epoxy-2-methyl-3-butene, respectively. Rats were treated in the same way with 1,2-epoxy-3-butene. In mice pyrrolidine adduct levels increased with increasing administered doses of the monoepoxides. The in vivo dose of diepoxybutane was on average twice as high (0.29 ± 0.059 mMh) as the in vivo dose of isoprenediepoxide (0.15 ± 0.053 mMh) per administered dose (mmol/kg body weight) of the monoepoxides. In mice the genotoxic effects of the two monoepoxides, measured as the increase in the frequencies of micronuclei (MN), were approximately linearly correlated to the in vivo doses of the diepoxides (except at the highest dose of diepoxybutane). In rats the pyrrolidine-adduct levels from diepoxybutane were below the limit of quantification at all administered doses of 1,2-epoxy-3-butene and no significant increase was observed in the frequency of MN. Measurement of the ring-closed adducts to N-termini in Hb by the applied method permits analysis of in vivo doses of diepoxybutane and isoprenediepoxide, which may be further used for the elucidation of the mechanisms of carcinogenesis of butadiene and isoprene.

  • 46.
    Fred, Charlotta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Haglund, Johanna
    Alsberg, Thomas
    Rydberg, Per
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Minten, Johanna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Characterization of alkyl-cobalamins formed in trapping of epoxide metabolites of 1,3-butadiene2004Inngår i: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 27, nr 7-8, s. 607-612Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analytical methods facilitating studies of electrophilically reactive and genotoxic compounds in vitro and in vivo are needed. The strong nucleophile, cob(I)alamin, formed by reduction of Vitamin B12 [cob(III)alamin], may be used for trapping and analysis of 1,2-epoxides and other electrophiles. In the present study, cob(I)alamin is evaluated as an analytical tool for 1,2-epoxide metabolites (oxiranes) of 1,3-butadiene. Products of reaction of cob(I)alamin with 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EBdiol) have been analyzed by reversed phase high performance liquid chromatography (HPLC) coupled on-line to electrospray ionization mass spectrometry (ESI-MS) and ultraviolet diode array detection (UV-DAD). It was shown that a specific alkyl-Cbl complex is formed for each metabolite and that it was possible to discriminate between the products by HPLC-UV and by LC-MS. Quantification of DEB with the method by use of another 1,2-epoxide as an internal standard was successfully performed. The possibility of using cob(I)alamin for trapping and analysis of the three oxirane metabolites of 1,3-butadiene will facilitate quantitative comparisons of species in vitro with regard to metabolism of 1,3-butadiene.

  • 47.
    Fred, Charlotta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Kautiainen, Antti
    Athanassiadis, Ioannis
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för miljökemi.
    Hemoglobin adduct levels in rat and mouse treated with 1,2:3,4-diepoxybutane2004Inngår i: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 17, nr 6, s. 785-794Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For cancer risk assessment of 1,3-butadiene from rodent cancer test data, the in vivo doses of formed 1,2:3,4-diepoxybutane (DEB) should be known. In vivo doses of DEB were measured through a specific reaction product with hemoglobin (Hb), a ring-closed adduct, N,N-(2,3-dihydroxy-1,4-butadiyl)valine (Pyr-Val), to N-terminal valines. An analytical method based on tryptic digestion of Hb and quantification of Pyr-modified heptapeptides by LC-MS/MS has been further developed and applied in vivo to DEB-treated rats. Furthermore, N-(2,3,4-trihydroxybutyl)valine adducts (THB-Val) to the N-terminal valine in Hb were measured in rats and mice treated with DEB and in a complementary experiment with 1,2-epoxy-3,4-butanediol (EBdiol), using a modified Edman degradation method and GC-MS/MS. In vitro reactions of hemolysate with DEB and EBdiol were used to measure reaction rates for adduct formation needed for calculation of doses and rates elimination in vivo. The results showed that the level of the Pyr-Val adduct per administered dose of DEB was approximately the same in rats as had earlier been observed in mice [Kautiainen et al. (2000) Rapid Commun. Mass Spectrom. 14, 1848−1853]. Levels of the THB-Val adduct after DEB treatment were 3−4 times higher in rat than in mouse, probably reflecting an enhanced hydrolysis of DEB to EBdiol catalyzed by epoxide hydrolase. After EBdiol treatment, the THB-Val adduct levels were about the same in rat and mouse. Calculations from in vitro data show that the Pyr-Val adduct is a relevant monitor for the in vivo dose of DEB and that THB-Val primarily reflects doses to EBdiol. The calculated rates of formation of adducts and rates of elimination agree with expectations. Procedures for quantification of Hb adducts as modified peptides as well as preparation and characterization of peptide standards have been evaluated.

  • 48. Fred, Charlotta
    et al.
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Granath, Fredrik
    Evaluation of cancer tests of 1,3-butadiene using internal dose, genotoxic potency, and a multiplicative risk model.2008Inngår i: Cancer Res, ISSN 1538-7445, Vol. 68, nr 19, s. 8014-21Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted quantitatively on the basis of the concentration over time in blood (AUC) of the epoxide metabolites, their mutagenic potency, and a multiplicative cancer risk model, which has earlier been used for ionizing radiation. Published data on hemoglobin adduct levels from inhalation experiments with BD were used for the estimation of the AUC of the epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were then weighed together to a total genotoxic dose, by using the relative genotoxic potency of the respective epoxide inferred from in vitro hprt mutation assays using EB as standard. The tumor incidences predicted with the risk model on the basis of the total genotoxic dose correlated well with the earlier observed tumor incidences in the cancer tests. The total genotoxic dose that leads to a doubling of the tumor incidences was estimated to be the same in both species, 9 to 10 mmol/Lxh EB-equivalents. The study validates the applicability of the multiplicative cancer risk model to genotoxic chemicals. Furthermore, according to this evaluation, different epoxide metabolites are predominating cancer-initiating agents in the cancer tests with BD, the diepoxide in the mouse, and the monoepoxides in the rat.

  • 49.
    Fängström, B
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Athanasiadou, M
    Grandjean, P
    Weihe, P
    Bergman, Å
    Hydroxylated PCB Metabolites and PCBs in Serum from Pregnant Faroese Women2002Inngår i: Environ. Health Perspect., ISSN 0091-6765, Vol. 110, nr 9, s. 895-899Artikkel i tidsskrift (Fagfellevurdert)
  • 50.
    Fängström, B
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
    Hovander, L
    Bignert, A
    Athanassiadis, I
    Linderholm, L
    Grandjean, P
    Weihe, P
    Bergman, Å
    Assessment of PBDEs, PCBs and OH-PCBs in Faroese mothers 1994 and their children seven years laterManuskript (Annet vitenskapelig)
1234 1 - 50 of 178
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf