umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Selection of polychlorinated biphenyls for use in quantitative structure-activity modelling
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
1995 (English)In: SAR and QSAR in environmental research (Print), ISSN 1062-936X, E-ISSN 1029-046X, Vol. 4, no 1, 11-19 p.Article in journal (Refereed) Published
Abstract [en]

By characterizing the 154 tetra- through heptachlorinated biphenyl (PCB) congeners with a multitude of physico-chemical descriptors, a model representing chemical similarities and differences is achieved. The multivariate characterization of the PCBs was based on 47 physico-chemical descriptor variables, which were summarised by using principal component analysis (PCA). By applying statistical design to the orthogonal scores from the PCA, a 24-factorial design was used to select a set of 16 congeners. In addition, four congeners were added to provide information about the interior region of the chemical domain of PCBs. This set of 20 structurally different congeners is suggested to be used in future quantitative structure-activity relationships (QSARs) for screening of the toxicological and biochemical effects of the PCBs.

Place, publisher, year, edition, pages
1995. Vol. 4, no 1, 11-19 p.
Keyword [en]
polychlorinated biphenyls, multivariate chemical characterisation, PCA, statistical design, QSARs
National Category
Pharmacology and Toxicology
Research subject
Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-3299DOI: 10.1080/10629369508234010OAI: oai:DiVA.org:umu-3299DiVA: diva2:141851
Available from: 2000-05-26 Created: 2000-05-26 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Physico-chemical characteristics and quantitative structure-activity relationships of PCBs
Open this publication in new window or tab >>Physico-chemical characteristics and quantitative structure-activity relationships of PCBs
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The polychlorinated biphenyls (PCBs) comprise a group of 209 congeners varying in the number of chlorine atoms and substitution patterns. These compounds tend to be biomagnified in foodwebs and have been shown to induce an array of effects in exposed organisms. The structural characteristics of the PCBs influence their potency as well as mechanism of action. In order to assess the biological potency of these compounds a multi-step quantitative structure-activity relationship (QSAR) procedure was used in the project described in this thesis.

The ultraviolet absorption (UV) spectra were measured for all 209 PCBs, and digitised for use as physico-chemical descriptors. Interpretations of the spectra using principal component analysis (PCA) showed the number of ortho chlorine atoms and para-para substitution patterns to be significant. Additional physico-chemical descriptors were derived from semi-empirical calculations. These included various molecular energies, the ionisation potential, electron affinity, dipole moments, and the internal barrier of rotation. The internal barrier of rotation was especially useful for describing the conformation of the PCBs on a continuous scale.

In total 52 physico-chemical descriptors were compiled and analysed by PCA for the tetra- to hepta-chlorinated congeners. The structural variation within these compounds was condensed into four principal properties derived from a PCA for use as design variables in a statistical design to select congeners representative for these homologue-groups. The 20 selected PCBs have been applied to study structure-specific biochemical responses in a number of bioassays, and to study the biomagnification of the PCBs in various fish species.

QSARs were established using partial least squares projections to latent structures (PLS) for the PCBs potency to inhibit intercellular communication, activate respiratory burst, inhibit dopamine uptake in synaptic vesicles, compete with estradiol for binding to estrogen receptors, and induce cytochrome P4501A (CYP1A) related activities. By the systematic use of the designed set of PCBs the biological potency was screened over the chemical domain of the class of compounds. Further, sub-regions of highly potent PCBs were identified for each response measured. For risk assessment of the PCBs potency to induce dioxin-like activities the predicted induction potencies (PIPs) were calculated. In addition, two sets of PCBs were presented that specifically represent congeners of environmental relevance in combination with predicted potency to induce estrogenic and CYP1A related activities.

Place, publisher, year, edition, pages
Umeå: Kemi, 2000. 70 p.
Keyword
polychlorinated biphenyls, PCBs, physico-chemical properties, statistical design, multivariate, PCA, PLS, biomagnification, BMF, bioassay, CYP1A, SAR, QSAR, REPs, risk assessment, Chemistry, Kemi
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-17 (URN)91-7191-838-8 (ISBN)
Public defence
2000-05-26
Opponent
Available from: 2000-05-26 Created: 2000-05-26Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Tysklind, MatsAndersson, PatrikHaglund, Peter
By organisation
Department of Chemistry
In the same journal
SAR and QSAR in environmental research (Print)
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 89 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf