| 1. |
- 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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| 2. |
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| 3. |
- Lundstedt, Staffan, et al.
(författare)
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Pressurised liquid extraction of polycyclic aromatic hydrocarbons from contaminated soils
- 2000
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Ingår i: Journal of Chromatography A. ; 883:1-2, s. 151-62
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Tidskriftsartikel (refereegranskat)abstract
- The reliability and efficiency of the pressurised liquid extraction technique (PLE) for extracting polycyclic aromatic hydrocarbons (PAHs) from contaminated soil has been investigated. Experimental design was used to study the influence of seven extraction variables (sample load, solvents used, solvent ratios, pressure, temperature, extraction time, and rinse volume). The results show that large sample loads in combination with small solvent volumes may result in low extraction efficiency. They also indicate that the recovery of low-molecular-mass PAHs is reduced by low extraction temperatures. The exact settings of the other variables are, however, less significant for the extraction efficiency. Repeated extractions at optimised settings of the tested variables show that PLE is an exhaustive extraction technique that generally results in high yields. In addition, extraction of a certified reference material (CRM 103-100) revealed that the method is both accurate and precise. Another finding was that adding the internal standard on top of the soil in the extraction cell causes considerable over-estimation of the concentrations when large samples are extracted with small solvent volumes. This is because the PLE-cell resembles a chromatographic column, so compounds added to the top of the soil layer have a longer distance to travel through the soil compared to the average distance of the native compounds, which are distributed evenly throughout the column. We therefore recommend that the internal standard should be added to the extract immediately after the extraction or, alternatively, carefully mixed with the sample prior to extraction.
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| 4. |
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| 7. |
- Van der Burght, A S A M, et al.
(författare)
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Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs
- 2000
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Ingår i: Chemosphere. ; 41:10, s. 1697-1708
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocytes cultures prepared from castrated pig hepatocytes (Great YorkshirexDutch Landrace), as a model for human liver, were used to study the effect of twenty polychlorinated biphenyls (PCBs) on CYP1A activity, measured as the dealkylation of either ethoxyresorufin or methoxyresorufin. The selection of the PCBs was based on their differences in physico-chemical properties. The non-ortho and mono-ortho substituted PCBs were the most potent CYP1A inducers in pig hepatocytes. In addition, several multiple-ortho substituted congeners, with five or more chlorine atoms, were inducers of CYP1A activity as well. Their relative effect potencies (REP) were proximately 10,000 times lower than the most potent congener, 3,3',4,4',5 PeCB (PCB#126). Using partial least-squares (PLS) modeling, predictions of CYP1A activity could be made for all tetra to hepta substituted congeners. Several multiple-ortho substituted PCBs, which are highly abundant in the biotic and abiotic environment, have been found to induce CYP1A activity in pig hepatocytes. Because induction of CYP1A activity is used as biomarker for Ah-receptor mediated responses, it is suggested to include these congeners in future risk assessment.
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| 8. |
- Voiea, Ø A, et al.
(författare)
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Activation of Respiratory Burst in Human Granulocytes by Polychlorinated Biphenyls : A Structure–Activity Study
- 2000
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 167:2, s. 118-24
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory burst in human granulocytes activated by 33 different congeners of polychlorinated biphenyls (PCBs) was measured as luminol-amplified chemoluminescence. The selection of 20 (training set) compounds was based on multivariate chemical characterization, laying the groundwork for covering the whole chemical series of tetra- through hepta-chlorinated PCBs. In addition 6 congeners were used as a validation set, and 7 were mono- to tri-chlorinated congeners representing low-chlorinated compounds not covered by the training set. Only ortho-substituted biphenyls activate respiratory burst. There is a correlation between activated respiratory burst and the total surface area of congeners up to 230 × 10−20 m2. Congeners of larger size show a reduced activity. There is also a correlation between respiratory burst activity and the number of ortho-substituents. Furthermore, there is also a correlation with parameters that describe absolute hardness of the molecule and respiratory burst activity. Congeners with a 2,4,6-substitution on one biphenyl ring are optimal activators. In conclusion, all three factors, size, rotation, and electronic properties, which are not independent of each other, are important for the activity of the PCBs.
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| 9. |
- Westerlund, L, et al.
(författare)
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Early life-stage mortality in zebrafish (Danio rerio) following maternal exposure to polychlorinated biphenyls and estrogen
- 2000
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268. ; 19:6, s. 1582-8
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, specific polychlorinated biphenyl (PCB) congeners were examined far embryo and early life stage mortality in zebrafish (Danio rerio). A set of eight PCBs and two hydroxylated PCBs and 17 beta-estradiol were tested. Of the compounds tested, 4'-OH-PCB30 (hydroxylated polychlorinated biphenyl) and PCB 104 were found to be highly toxic to embryos following maternal exposure and transfer to the oocyte. It was also observed that 17 beta-estradiol exposure resulted in a high incidence of embryo mortality. Analysis of estrogen receptor levels during embryonic development showed increased mRNA (ribonucleic acid) levels from the 1K stage to 50% epiboly. Following injection of the different compounds, the estrogen receptor mRNA levels were also analyzed in adult male fish to determine if there was a correlation between embryo mortality and estrogenicity of the studied PCBs. The two PCBs that were highly embryo toxic were observed to be estrogenic.
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| 10. |
- Wiberg, Karin, et al.
(författare)
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The Enantioselective Bioaccumulation of Chiral Chlordane and -HCH Contaminants in the Polar Bear Food Chain
- 2000
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 34:13, s. 2668-74
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Tidskriftsartikel (refereegranskat)abstract
- The enantiomer ratios (ERs) of -HCH and chlordane related compounds (CHLs) were examined in the polar bear food chain (arctic cod-ringed seal-polar bear), using chiral gas chromatography-mass spectrometry (GC-MS). The cod showed near-racemic mixtures (ER = 1) for most of the compounds. In contrast, ERs in ringed seal and polar bear were frequently nonracemic (ER 1), due to enantiomer-specific biotransformation. As (+)--HCH was transferred up the food chain, it became more abundant relative to (-)--HCH. For the CHLs, there was no uniform trend for the ER changes and the increasing trophic level. Apparent chiral biomagnification factors (BFs) were calculated and up to a 20-fold difference in the BF between enantiomers was found. Analysis of chiral BFs relative to CB-153 indicated that oxychlordane was formed by ringed seal and metabolized by polar bears. However, the ERs did not change significantly as a result of these biotransformations. Multivariate statistical methods revealed the clustering of sample categories and were used to investigate the relationships between the ERs, chemical residue concentrations, and biological data. ERs were important variables for the sample groupings and for the class separation of male/female seals and fat/liver tissues. The variance in the cytochrome P450 CYP2B protein content of bear liver could be explained by the variances in chemical residue data. In this analysis the ERs were of secondary importance. The ERs of some highly recalcitrant CHLs in polar bear adipose showed linear relationships with the age of the bears.
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