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| 3. |
- Bjermo, Helena, et al.
(författare)
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Serum levels of brominated flame retardants (BFRs : PBDE, HBCD) and influence of dietary factors in a population-based study on Swedish adults
- 2017
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 167, s. 485-491
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins.
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- Cantillana, Tatiana, et al.
(författare)
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(2S)-1,1-Dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane
- 2009
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Ingår i: Acta Crystallographica Section E. - 1600-5368. ; 65, s. OO297-U1934
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Tidskriftsartikel (refereegranskat)abstract
- The title compound, C14H10Cl4, is easily crystallized while the other enantiomorph only forms an oil upon crystallization attempts. The title compound has a considerably higher density, rho similar or equal to 1.562 Mg m(-3) compared to the racemic substance, rho similar or equal to 1.514 Mg m(-3). This is supported by the fact there are two intermolecular halogen-halogen contacts in the title compound compared with only one the racemic compound. The dihedral angle between the two phenyl rings is 76.83 (5)degrees
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| 7. |
- Cantillana, Tatiana, et al.
(författare)
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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-DDEs
- 2009
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Ingår i: Chemosphere. - Oxford : PERGAMON-ELSEVIER SCIENCE LTD. - 0045-6535 .- 1879-1298. ; 76:6, s. 805-810
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Tidskriftsartikel (refereegranskat)abstract
- 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%.
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| 8. |
- Cantillana, Tatiana, 1969-
(författare)
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Toxicologically important DDT metabolites : Synthesis, enantioselective analysis and kinetics
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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- Carlsson, Carina, et al.
(författare)
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Olfactory mucosal toxicity screening and multivariate QSAR modeling for chlorinated benzene derivatives
- 2004
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 78:12, s. 706-715
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Tidskriftsartikel (refereegranskat)abstract
- The olfactory mucosa (OM) is an important target for metabolism-dependent toxicity of drugs and chemicals. Several OM toxicants share a 2,6-dichlorinated benzene structure. The herbicides dichlobenil (2,6-dichlorobenzonitrile) and chlorthiamide (2,6-dichlorothiobenzamide) and the environmental dichlobenil metabolite 2,6-dichlorobenzamide all induce toxicity in the OM following covalent binding in the Bowmans glands. In addition, we have shown that 2,6-dichlorophenyl methylsulfone targets the Bowmans glands and is probably the most potent OM toxicant so far described. These findings suggest that the 2,6-positioning of chlorines in combination with an electron-withdrawing group in the primary position of the benzene ring is an arrangement that facilitates OM toxicity. This study examined the physicochemical characteristics of the 2,6-dichlorinated OM toxicants. A number of 2,6-dichlorinated benzene derivatives with various types of substituents in primary position were tested for OM toxicity in mice. In addition, some other 2,6- and 2,5-substituted benzene derivatives were examined. Two novel OM toxicants, 2,6-dichlorobenzaldehyde oxime and 2,6-dichloronitrobenzene, were identified. By the use of partial least squares projection to latent structures with discriminant analysis (PLS-DA) a preliminary quantitative structure-activity relationship (QSAR) model was built also using reported OM toxicity data. Physicochemical properties positively correlated with olfactory mucosal toxicity were identified as molecular dipolar momentum and the electronic properties of the substituent. Inversely correlated descriptors were variables describing the hydrophobicity, electronic properties of the molecule such as electron affinity and the electronic charge on the primary carbon. In conclusion, this preliminary PLS-DA model shows that a 2,6-dichlorinated benzene derivative with a large, polar, and strong electron-withdrawing substituent in the primary position has the potential of being a potent OM toxicant in mice.
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