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ABSTRACT: Er zijn nog steeds PCB's aanwezig in het ecosysteem (water en land). Als palingen 6000 km migreren, zullen ze hun vetreserves aanspreken en komen er giftige PCB's vrij in het lichaam. Daarnaast kan de embryonale ontwikkeling nadelig beïnvloed worden door ophoping van PCB's in dooiermateriaal. Palingen afkomstig uit de Italiaanse lagunes werden met een placebo (geen PCB's) in de buikholte ingespoten of met een mengsel van PCB's. Tijdens het zwemmen werd het zuurstofverbruik gemeten met zuurstofelectrodes. Tevens werd de PCB belasting gemeten. Na 800 km trad er een hoge mortaliteit op in de PCB groep en werden de dieren bemonsterd
Aquacultuur 20 (2005) 3.
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ABSTRACT: Breast cancer cells show overexpression of estrogen receptor (ER) relative to ERß compared to normal breast tissues. This observation has lead to the hypothesis that ERß may modulate the proliferative effect of ER. This study investigated how variable cellular expression ratios of the ER and ERß modulate the effects on cell proliferation induced by ER or ERß agonists, respectively. Using human osteosarcoma (U2OS) ER or ERß reporter cells, propyl-pyrazole-triol (PPT) was shown to be a selective ER and diarylpropionitrile (DPN) a preferential ERß modulator. The effects of these selective estrogen receptor modulators (SERMs) and of the model compound E2 on the proliferation of T47D human breast cancer cells with tetracycline-dependent expression of ERß (T47D-ERß) were characterized. E2-induced cell proliferation of cells in which ERß expression was inhibited was similar to that of the T47D wild-type cells, whereas this E2-induced cell proliferation was no longer observed when ERß expression in the T47D-ERß cells was increased. In the T47D-ERß cell line, DPN also appeared to be able to suppress cell proliferation when levels of ERß expression were high. In the T47D-ERß cell line, PPT was unable to suppress cell proliferation at all ratios of ER/ERß expression, reflecting its ability to activate only ER and not ERß. It is concluded that effects of estrogen-like compounds on cell proliferation are dependent on the actual ER/ERß expression levels in these cells or tissues and the potential of the estrogen agonists to activate ER and/or ERß.
Toxicological sciences 105 (2008) 2.
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A.J. Murk, Berg,
J.H.J,
van den,
M. Fellinger,
M.J.C. Rozemeijer,
C. Swennen,
P. Duiven,
J.P. Boon,
A. Brouwer,
J.H. Koeman
Environ. Pollut. 86 (1994) 21-30.
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Environmental Toxicology and Pharmacology 10 (2001). - ISSN 1382-6689.
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Chemosphere 75 (2009) 11.
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Environmental Toxicology and Pharmacology 8 (1999).
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Science of the Total Environment 262 (2000).
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Environmental Pollution 72 (1991) 57-67.
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In: Congress Proceedings/Society of Environmental Toxicology and Chemistry, Charlotte, NC, USA, November 1998. - [S.l.] : [s.n.], 1998.
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M.J.C. Rozemeijer,
J.P. Boon,
P. Duiven,
Meer,
Sant,
J.S.J,
van de,
C. Swennen,
A.J. Murk, Berg,
J.H.J,
van den,
M. Fellinger,
A. Brouwer,
J.H. Koeman
Marine Envir. Res. 34 (1992) 207-213.
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Mutation Research 552 (2004) 1-2.
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ABSTRACT: Amphibian metamorphosis assays are used to evaluate potential effects of endocrine disrupting compounds on the thyroid hormone axis. In this study, Xenopus laevis tadpoles are kept in a solution of 0.2% thiourea (TU) to arrest and synchronise them in their development. The advantage of this synchronized amphibian metamorphosis assays is that synchronised tadpoles are available at any time to start metamorphosis experiments, and experimental groups are much more homogenous at the start of experimental exposure compared with groups selected from an untreated pool of animals. The water volume per animal was kept constant throughout the experimental period to overcome the influence of declining numbers of animals per aquarium due to metamorphosis and mortality on the density dependent development of the remaining tadpoles. Clophen A50 (a technical PCB mixture), the single congener 3,3¿,4,4¿-tetrachlorobiphenyl (PCB 77) and apolar sediment extracts that were previously tested positive in the T-Screen, an in vitro proliferation assay for thyroid hormone disruption, were tested in the Synchronized Amphibian Metamorphosis Assay. Endpoints studied were mortality, malformations, body weight, and percentage of metamorphosed froglets at the end of the 60-day experimental period, percentage of tadpoles in different developmental stages, and developmental stage-dependent awarded penalty points. Dietary exposure to Clophen A50 (0.2¿50 mg/kg food) resulted in a significant increased percentage of tadpoles that did not pass metamorphosis at concentrations higher than 2 mg/kg food. Time until metamorphosis in those animals that were able to metamorphose after the 60-days experimental period was significantly decreased. Dietary exposure to PCB 77, a congener that can be readily metabolised, did not result in significant effects in any exposure group (2¿500 ¿g/kg food). Apolar sediment extracts from two of the three sites that are contaminated with a wide variety of chemicals significantly decreased the percentage of metamorphosed animals and significantly increased the number of tadpoles that remained in early and late metamorphic stages. These effects already occurred when the extracts where diluted more than 1000 times (on an organic carbon base) compared to environmental concentrations. The rank of potency was comparable to results obtained with the T-screen. This suggests the presence of thyroid hormone disrupting compounds in the aquatic environment and possible effects of such compounds on animal development in the wild.
Chemosphere 70 (2007) 1.
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Weert,
J.P.A,
Cal,
de la, Berg,
J.H.J,
van den,
A.J. Murk,
A.A.M. Langenhoff,
H.H.M. Rijnaarts,
J.T.C. Grotenhuis
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ABSTRACT: The surfactant nonylphenol (NP) is an endocrine-disrupting compound that is widely spread throughout the environment. Although environmental risk assessments are based on total NP concentrations, only the bioavailable fraction posses an environmental risk. The present study describes the bioavailability and biodegradability of NP over time in contaminated river sediment of a tributary of the Ebro River in Spain. The bioavailable fraction was collected with Tenax TA® beads, and biodegradation was determined in aerobic batch experiments. The presence of NP was analyzed chemically using gas chromatography¿mass spectrometry and indirectly as estrogenic potency using an in vitro reporter gene assay (ER¿-luc assay). Of the total extractable NP in the sediment, 95% ± 1.5% (mean ± standard error) desorbed quickly into the water phase. By aerobic biodegradation, the total extractable NP concentration and the estrogenic activity were reduced by 97% ±0.5% and 94% ± 2%, respectively. The easily biodegradable fraction equals the potential bioavailable fraction. Only 43 to 86% of the estrogenic activity in the total extractable fraction, as detected in the ER¿-luc assay, could be explained by the present NP concentration. This indicates that other estrogenic compounds were present and that their bioavailability and aerobic degradation were similar to that of NP. Therefore, we propose to use NP as an indicator compound to monitor estrogenicity of this Ebro River sediment. To what extent this conclusion holds for other river sediments depends on the composition of the contaminants and/or the nature of these sediments and requires further testing
Environmental Toxicology and Chemistry 27 (2008) 4.
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Veld,
M.G.R,
ter,
E. Zawadzka, Berg,
J.H.J,
van den,
Saag,
P.T,
I.M.C.M. Rietjens,
A.J. Murk
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ABSTRACT: The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8 h after dosing the ER-luc male mice intraperitoneally (IP) or 14 h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1 mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50 mg/kg bw), dichlorodiphenyldichloroethylene (p,p¿-DDE; at 5 and 25 mg/kg bw), quercetin (at 1.66 and 16.6 mg/kg bw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100 mg/kg bw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50 mg/kg bw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 104 times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high
Chemico-Biological Interactions 174 (2008) 2.
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ABSTRACT: Quantitative structure¿activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemicals (REACH). The objective of the present study was to generate in vitro acute toxicity data that could be used to develop a QSAR model to describe acute in vivo toxicity of chlorinated alkanes. Cytotoxicity of a series of chlorinated alkanes to Chinese hamster ovary (CHO) cells was observed at concentrations similar to those that have been shown previously to be toxic to fish. Strong correlations exist between the acute in vitro toxicity of the chlorinated alkanes and (i) hydrophobicity [modeled by the calculated log Kow (octanol¿water partition coefficient); r2 = 0.883 and rint2 = 0.854] and (ii) in vivo acute toxicity to fish (r2 = 0.758). A QSAR model has been developed to predict in vivo acute toxicity to fish, based on the in vitro data and even on in silico log Kow data only. The developed QSAR model is applicable to chlorinated alkanes with up to 10 carbon atoms, up to eight chlorine atoms, and log Kow values lying within the range from 1.71 to 5.70. Out of the 100204 compounds on the European Inventory of Existing Chemicals (EINECS), our QSAR model covers 77 (0.1%) of them. Our findings demonstrate that in vitro experiments and even in silico calculations can replace animal experiments in the prediction of the acute toxicity of chlorinated alkanes.
Chemical Research in Toxicology 21 (2008) 3.
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ABSTRACT: In the prolonged-FETAX (prolonged-Frog Embryo Teratogenic Assay-Xenopus) tadpoles are allowed to develop until metamorphosis after an initial 4 day early life-stage exposure (FETAX). PCB 77 (3,4,3¿,4¿-tetrachlorobiphenyl) and sediment extracts were used in the presented experiments. Concentrations of PCB 77 (0.03 nM = 8.55 ng/L; 3 nM = 855 ng/L; 300 nM = 85.5 ¿g/L, 30,000 nM = 8.55 mg/L) were derived on the basis of dioxin-like toxic equivalency concentrations known to be present in pore-water. The results were compared to those obtained with the standard FETAX. In the prolonged-FETAX the percentage of animals passing metamorphosis within 115 days was significantly decreased in the groups exposed to 300 or 30,000 nM PCB 77. Significantly increased percentages of tadpoles were halted in thyroid hormone dependent early metamorphic NF stages ¿ 55 (3 nM PCB 77) and metamorphic stages 56¿60 tadpoles (300 nM PCB 77 and 30,000 nM PCB 77). Non-polar sediment extracts from two contaminated Dutch sites significantly decreased, and one significantly increased the percentage of animals that passed metamorphosis. These results were in accordance with earlier in vitro results in a thyroid hormone dependent assay and strongly suggest the presence of thyroid hormone disrupting compounds in the aquatic environment. In the classical FETAX neither PCB 77 nor non-polar sediment extracts induced any effects. The results of the present study indicate that the prolonged-FETAX is an important in vivo tool in addition to the in vitro T-screen to assess long-term effects of early life-stage exposure to environmentally relevant concentrations of (mixtures of) compounds and that affect thyroid hormone dependent physiology.
Science of the Total Environment 381 (2007) 1-3.
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ABSTRACT: A risk assessment was made for a carnivorous and a herbivorous food chain in a heavily polluted natural estuary (Biesbosch), by determining the most critical pollutants and the food chain most at risk. Exposure of food chains to metals, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) was assessed by analyzing dietary concentrations, internal concentrations, and biomarkers of exposure. Common shrew (Sorex araneus) and bank vole (Clethrionomys glareolus) were selected as representative small mammal species for the carnivorous and herbivorous food chain, respectively, and earthworms (Lumbricus rubellus) and snails (Cepaea nemoralis) as representative prey species for the carnivorous food chain. Metals contributed most to the total risk for small mammals and earthworms. PCBs, but not PAHs, contributed to the overall risk for S. araneus at regularly flooded locations. The carnivorous food chain appeared most at risk given the higher exposure levels and bioaccumulating potency found for contaminants in S. araneus.
Environmental Pollution 144 (2006) 2.
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Ginneken,
A. Palstra,
M. Nieveen, Berg,
J.H.J,
van den,
G Flik,
F.A. Spanings,
P. Niemantsverdriet,
Thillart,
A.J. Murk
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ABSTRACT: Organochlorine compounds were widely used after the Second World War because they were cheap to produce and useful for many purposes, such as in agriculture for insecticides, in public health to control disease insect vectors and in industry (Pelletier et al. 2002). It is estimated that 16¿30% of the 1 million tons of PCBs produced are still present in aquatic and terrestrial ecosystems (Borlakoglu and Haegele 1991). In spite of discharge restrictions, the concentrations of PCBs and chemically similar compounds in natural environments will likely remain elevated because of atmospheric transport and the internal cycling of contaminants already present in ecosystems. So, when not retrieved or destroyed, the rest of the PCBs will be released into the environment and eventually reach the oceans (Klamer et al. 1991). PCBs encompass a class of chlorinated compounds that includes up to 209 variations, or congeners, with different physical and chemical characteristics. They are ubiquitous environmental contaminants with specific modes of action (Safe 1984, 1990) and exposure to each of the congeners is associated with different levels of risk for harmful effects. Technical mixtures of PCBs, referred to by the trade names such as Aroclor, Phenoclor and Kanechlor, have been widely used for a variety of industrial purposes: hydraulic fluids in mining activities, plasticisers, fluid-filled capacitors and transformers, heat transfer fluids and paints. There are no known natural sources of PCBs. Most PCBs are oily liquids whose colour darkens and viscosity increases with rising chlorine content. PCBs with fewer chlorine atoms are more soluble, more amenable to chemical and biological degradation, and less persistent in the environment than those PCBs with more chlorine atoms bound to the biphenyl core (Safe 1984) (Fig. 15.1).
Spawning migration of the European Eel: Reproduction index, a useful tool for conservation management.
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Toxicological Sciences 48 (1999).
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ABSTRACT: This study describes biomarker effects in small mammals exposed to traffic emissions. Animals were collected at 10-50 m (site 1), 150-200 m (site 2), and 5 km (site 3) from a very busy highway (A2). To distinguish between routes of exposure, strictly carnivorous common shrews (Sorex araneus) and predominantly herbivorous bank voles (Clethrionomys glareolus) were collected. As a measure of exposure to polycyclic aromatic hydrocarbons (PAHs), aromatic DNA adduct levels were determined by 32P-postlabeling techniques in tissue from heart, lung, and liver. Lead (Pb), cadmium (Cd), and copper (Cu) levels were analyzed in kidney as a measure of exposure to heavy metals. EROD and PROD activity and retinoid levels were determined in liver as effect biomarkers for exposure to PAHs and polyhalogenated aromatic hydrocarbons (PHAHs). Relatively high Cd levels in S. araneus and in particular elevated DNA adduct levels in C. glareolus indicated that small mammals at site 3 were exposed to more compounds than at sites 1 and 2 (3 S 1 > 2). The latter effect is probably due to an incidental and actual input of airborne pollutants that is deposited on plant surfaces. By consumption of above-ground vegetation, voles are chronically exposed to this pollution. Relatively high background input of PAHs probably hinders that the traffic-related gradient of airborne PAH concentrations found in an earlier study is reflected in DNA adduct levels in small mammals in the present study. Moreover, historical biomarkers for exposure to traffic emissions, such as increased kidney Pb levels, increased hepatic EROD activity, and disturbed hepatic vitamin A homeostasis are no longer applicable to indicate differences in exposure. This is a result of the ban on addition of Pb and chlorinated scavengers to gasoline and of cleaner combustion techniques, which were enforced by law over the past decade. Finally, it is advisable to use only juvenile small mammals for in situ monitoring of diffuse pollution because DNA adduct levels increased with age.
Archives of Environmental Contamination and Toxicology 43 (2002) 3. - ISSN 0090-4341.
