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- Andersson, Patrik, et al.
(författare)
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Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species : ranking scales and species differences
- 2000
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 19:5, s. 1454-1463
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Tidskriftsartikel (refereegranskat)abstract
- Cytochrome P4501A–induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure-activity relationships have been established, including 52 physi-cochemical parameters and different measures of the dose-response curves. Relative effect potencies are predicted for the 154 tetra-to hepta-PCBs and reported for the most potent congeners according to both EC50 and maximal response values. Important physicochemical parameters of the PCBs as related to the modeled activity are parts of their ultraviolet absorption spectra, the Henry's law constant, the ionization potential, and the octanol-water partition coefficient. Interspecies differences were found in terms of varied sensitivity to different structural subgroups of the compounds. The chicken hepatocyte assay showed the most specific structure-activity relationship, with high activity for the non-ortho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the principal induction potency, is presented for the 41 most potent PCBs. These responses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.
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- Bergknut, Magnus, et al.
(författare)
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Assessment of the availability of polycyclic aromatic hydrocarbons from gasworks soil using different extraction solvents and techniques
- 2004
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 23:8, s. 1861-1866
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to assess the availability of polycyclic aromatic hydrocarbons (PAHs) present at a gasworks site to different soil remediation techniques. The study examined the effect on PAH availability of using different organic solvents, the degree of pretreatment, and the extraction time. In total, 25 PAHs (with two to six fused rings) and five carbonyl derivatives were measured. The results indicated that the PAHs and their derivatives were bound loosely to the surface of the studied soil and that there were no significant kinetic boundaries associated with the extraction of the PAHs. Furthermore, it was concluded that the studied soil was not suitable for bioremediation, as the concentration of PAHs with low molecular weight were limited. However, pressurized liquid extraction (PLE) with methanol as the solvent extracted 97% of all PAHs and PAH-derivatives, indicating that extraction may be effective as part of a soil remediation technique for old gasworks soils.
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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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