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M Tysklind

Publications and source records attributed to M Tysklind.

14 recordsLinked to original sources
PubMed2004

An overview of OSPAR priority compounds and selection of a representative training set.

The aim of our study was to chemically characterize a set of priority substances in order to systematically select a representative set of heterogeneous substances for experimental studies of their persistence, bioaccumulation and toxicity (PBT). By including structurally diverse compounds in a PBT-screening protocol, structure-based knowledge would be achieved as a basis for more detailed studies of specific compounds from certain regions of the chemical domain. Initially compounds on the Draft Preliminary List of Substances of Possible Concern presented by the Oslo & Paris Commission (OSPAR) were subjected to broad chemical characterization using Principal Component Analysis (PCA). Molecular weight and seven physico-chemical descriptors collected from the literature, five calculated properties and 25 constitutional descriptors were used in this characterization. The OSPAR list represents a broad spectrum of substances, and thus provides a good basis for selecting heterogeneous substances. D-optimal design was applied to the first four principal components derived in the PCA. In total, 19 structurally diverse substances were chosen as representatives of the chemical domain including 353 substances.

Hazardous Substances↗
PubMed2001

Effect of polychlorinated biphenyls on the uptake of dopamine into rat brain synaptic vesicles: a structure-activity study.

PCBs are neurotoxic compounds that have a known effect on the dopaminergic system in the brain. In a previous work it was established that PCBs are potent inhibitors of the uptake of dopamine into rat brain synaptic vesicles. In this work we further investigated the vesicular dopamine uptake in response to different PCBs to explore the structure-activity relationship involved in this effect. Twenty PCB congeners were selected, based on multivariate chemical characterization, to cover the chemical variation within tetra- to hepta-chlorinated PCBs. PCBs of large structural variation were tested and the general finding was that only the ortho-substituted PCBs inhibited the dopamine uptake. The most active congeners were the penta- and hexa-chlorinated PCBs. Furthermore, the uptake was correlated with parameters describing the absolute hardness, the octanol-water partition coefficient, and the Henry's law constant. These parameters are correlated to the number of chlorine atoms in ortho positions and to the size of the molecule. Notably the most active PCBs are highly prevalent in the environment and are disposed to bioaccumulate in wildlife. Thus, these neurotoxic effects should be included in the risk assessment of PCBs.

Animals↗
PubMed2001

Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and arctic char after three different routes of exposure.

The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

Administration, Oral↗
PubMed2001

Dietary uptake and elimination of selected polychlorinated biphenyl congeners and hexachlorobenzene in earthworms.

Earthworms (Eisenia foetida) were given food contaminated with hexachlorobenzene (HxCBz) and 20 tetra- to heptachlorinated biphenyls (PCBs). The PCBs were selected to cover a wide range of physicochemical properties. The uptake efficiencies, uptake rate constants, and elimination rate constants in worms varied between the 20 PCBs. The uptake efficiencies were between 10 and 68%. The PCBs that were eliminated fastest contained few chlorine atoms, had more polar characteristics, and were sterically hindered. Slowest was the elimination for less polar PCBs with six or seven chlorine atoms such as the non-ortho-substituted PCB 169. Elimination half-lives varied between 6 and 25 d. The biomagnification factors (BMFs) for the PCBs and HxCBz averaged 0.1 based on lipids and 0.04 based on wet (worms) and dry (food) weight. Worm cocoons were analyzed for PCBs for the first time. The PCB pattern in the cocoons differed from the adult worms by the comparatively higher load of non-ortho PCBs. By studying congeners covering a large range of PCB physicochemical characteristics, their fate within the environmental and the factors influencing biological responses can be better understood.

Animals↗
PubMed2000

Activation of respiratory burst in human granulocytes by polychlorinated biphenyls: A structure-activity study.

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 x 10(-20) m(2). 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.

Environmental Pollutants↗
PubMed2000

Pressurised liquid extraction of polycyclic aromatic hydrocarbons from contaminated soils.

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.

Chromatography, Liquid↗
PubMed2000

Impact of polychlorinated naphthalenes (PCNs) in juvenile Baltic salmon, Salmo salar: evaluation of estrogenic effects, development, and CYP1A induction.

Juvenile Baltic salmon, Salmo salar, were fed commercial salmon food contaminated with different concentrations of polychlorinated naphthalenes (PCNs; 0.1, 1, 2, or 10 microg PCN/g food). Among other effects, possible estrogenic impact caused by PCNs were evaluated. Fish were therefore fed a diet contaminated with 17beta-estradiol (E2; 0.94 or 9.4 microg E2/g food), as a positive control. After 8, 13, 17, and 41 weeks, sampling took place. Growth, liver somatic index (LSI), EROD activity, and vitellogenin content in blood plasma were measured along with morphological studies of gonads and chemical analyses to determine the effects caused by PCNs. Exposure to PCNs did not seem to have any effects on body weight gain, since the group fed the high dose followed the growth in the control group during the entirely experimental period. After 41 weeks of exposure the groups fed 2 and 10 microg PCN/g food had significantly lower LSIs compared with the control, indicating liver toxic effects of PCNs. Furthermore, a dose-dependent induction of EROD activity was found. At week 41, the control group had an activity of 4.9 +/- 4.8 pmol/mg prot/min, whereas it was between 69 +/- 21 and 720 +/- 370 pmol/mg prot/min in the exposed groups, respectively. Examination of gonadal morphology showed that PCNs also had negative effects on ovaries in Baltic salmon, including delayed development. The distribution between females and males, gonadal morphology, and vitellogenin content in blood plasma did, however, indicate that PCNs are not capable of causing effects similar to E2 or xenoestrogens. Exposure to both of the concentrations of E2 resulted in decreased body weight gain, increased LSI, and feminization of the gonads. E2 did, however, not induce any EROD activity.

Animals↗
PubMed2000

Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs.

Hepatocytes cultures prepared from castrated pig hepatocytes (Great Yorkshire x Dutch 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.

Animals↗
PubMed1999

Structure-dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of cynomolgus monkeys (Macaca fascicularis).

Until now structure-activity relationships (SARs) for in vitro or in vivo CYP1A induction by polychlorinated biphenyls (PCBs) have only been determined in rodents and birds. This study describes the first development of such a SAR in a primate species by using hepatocyte cultures of cynomolgus monkey (Macaca fascicularis). Hepatocyte cultures of primate species might be a more suitable model for humans than those of rodents. For 20 PCBs, the in vitro induction of CYP1A activity was determined by measuring dealkylation of either methoxyresorufin or ethoxyresorufin. Selection of PCBs was based on multivariate physical-chemical characterization of all tetra- through heptachlorinated congeners. The non-ortho-substituted congeners were found to be the most potent inducers, followed by the mono-ortho-substituted PCBs. Multiple-ortho-substituted congeners, with more than five chlorine atoms, were inducers of CYP1A activity in monkey hepatocytes as well, with EC50 values approximately 10,000 times higher than 3,3',4,4',5 PeCB (PCB 126), the most potent congener. Using partial least-squares (PLS) modeling, predictions of CYP1A activity were established for all other tetra- to hepta-substituted congeners. Several congeners, which are abundant in the (a)biotic environment, were predicted to have CYP1A activity in cynomolgus monkey hepatocytes. Because induction of CYP1A activity is generally used as an early and sensitive biomarker for the Ah-receptor-mediated potential of a chemical, further studies are recommended to determine the possible risks of these multiple-ortho PCBs to humans.

Animals↗
PubMed1999

Assessment of PCBs and hydroxylated PCBs as potential xenoestrogens: In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes.

In the present study, four structurally diverse polychlorinated biphenyls (PCBs) were chosen from a set of 20 PCBs selected to represent the 154 tetra- through hepta-chlorinated biphenyls. The purpose was to determine estrogenic activities of the chosen PCBs and five of their hydroxylated derivatives (OH-PCBs). A human breast cancer cell line (MCF-7) and primary cultures of rainbow trout (Oncorhyncus mykiss) hepatocytes were used to determine estrogenic effects. The PCBs 2,2',4,6,6'-pentachlorobiphenyl (104) and 2,2',3, 4', 5,6,6'-heptachlorobiphenyl (188), and the hydroxylated PCBs 2,2', 4',6'-tetrachloro-4-biphenylol (4'-50), 2',4', 6'-trichloro-4-biphenylol (4'-30), 2',3,5, 5'-tetrachloro-4-biphenylol (4'-72), 2',3,3',5', 6'-pentachloro-4-biphenylol (4'-112), and 2',3,4',5, 6'-pentachloro-4-biphenylol (4'-121) significantly increased MCF-7 cell proliferation. The coaddition of hydroxytamoxifen, an estrogen antagonist, inhibited increased cell proliferation. The activity of the hydroxylated PCBs 4'-50 and 4'-30 was significantly higher at all nominal concentrations tested as compared to the corresponding PCB, viz., PCB 104. The hydroxylated PCBs 4'-50, 4'-30, 4'-72 and 4'-112 induced vitellogenin synthesis in rainbow trout hepatocytes. Significant differences were found in the MCF-7 system between the parent PCB and its hydroxylated derivative, viz., for 4'-50/4'-30 and 104, and in the rainbow trout hepatocyte assay between 4'-112 and 112, respectively. No activity was observed for PCB 58 in any of the two assays in the present study. Even though cells from two different species (human and fish) are used in the present study, the results obtained by the two methods agree fairly well. In both studies the hydroxylated PCBs were more active than the PCBs, and 4'-30 was the most active compound second only to 17beta-estradiol. http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p145.html

Animals↗
PubMed1998

The impact on reproduction of an orally administered mixture of selected PCBs in zebrafish (Danio rerio).

Zebrafish (Danio rerio) were orally exposed to a mixture of 20 PCBs in three different dose levels (0.008, 0.08, and 0.4 microg of each congener per gram of freeze-dried chironomids). Generally, the PCBs accumulated in a dose-related manner. After 13 weeks of exposure body, liver, and ovary weights, as well as the liver and ovary somatic index, were significantly lower in exposed groups. In addition, the PCB mixture was an effective inducer of hepatic EROD activity. The reproduction study performed with exposed females and unexposed males after 9 weeks revealed that median survival time for larvae was only 7.7 days in the high-dose group as compared with 14 days in controls. Furthermore, egg production was reduced in all three groups exposed. No differences in hatching frequency or median hatching time were recorded. Histologically, females in both the intermediate and high-dose groups contained a reduced number of mature oocytes. The present study demonstrates that the potency of the mixture of selected PCBs induces hepatic EROD activity and has a clearly negative effect on zebrafish reproduction.

Administration, Oral↗
PubMed1998

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Animals↗
PubMed1994

A toxic equivalency factor scale for polychlorinated dibenzofurans.

The ethoxyresorufin O-deethylase (EROD) induction of 20 polychlorinated dibenzofurans (PCDFs) was examined in the H4IIE rat hepatoma cell bioassay. The selection of the compounds tested was based on a multivariate chemical characterization laying the groundwork for covering the whole chemical series of PCDFs. The EROD induction potency was found to vary in ED50 values from 25 to 100,000,000 pg/mg, i.e., nearly seven orders of magnitude. The response of the bioassay was calibrated against the 2,3,7,8-tetrachlorodibenzo-p-dioxin, enabling the corresponding toxic equivalency factors (TEFs) to be calculated. In order to establish a quantitative structure-activity relationship (QSAR) for the TEF values, 37 physicochemical descriptor variables were used to chemically characterize the 87 tetra- to octachlorinated PCDFs. Using partial least-squares modeling on a training set of 10 congeners, a QSAR model with sound predictive power was obtained. The QSAR model was validated with a validation set of additional 10 congeners. The predicted TEFs indicate that a large number of congeners are potent EROD inducers.

Animals↗