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Karl Fent - One of the best experts on this subject based on the ideXlab platform.
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effects of triphenyltin and other Organotins on hepatic monooxygenase system in fish
Comparative Biochemistry and Physiology Part C: Pharmacology Toxicology and Endocrinology, 1998Co-Authors: Karl Fent, Bruce R Woodin, John J StegemanAbstract:The interaction of the organotin fungicide triphenyltin chloride (TPT) with fish microsomal monooxygenase systems has been studied in vitro and in vivo in the marine fish scup (Stenotomus chrysops). In vitro incubation of fish liver microsomes with TPT resulted in the conversion of about 40% of the native total spectral P450 to P420. In addition, a strong concentration-related inhibition of ethoxyresorufin O-deethylase (EROD) activity was observed, with a complete loss at 1.0 mM TPT. Pentoxyresorufin-O-dealkylase (PROD) activity was inhibited only at the highest concentration tested. This suggests either some specificity for the EROD catalyst CYP1A1, or a loss of reductant NADPH cytochrome c reductase as the cause. Further in vitro incubations showed that NADPH, but not NADH, cytochrome c reductase was strongly inhibited at 100 microM TPT and higher. To further investigate this effect, fish were injected with single doses of 5, 25 and 50 microM TPT (1.9, 9.6 and 19.3 mg kg-1 TPT), and 24 and 48 h later, hepatic microsomes were analyzed for total P450 content, EROD activity, NAD(P)H cytochrome c reductase, and the content of three CYP forms. EROD activity tended to be decreased in TPT-treated scup, with the response being stronger after 48 than 24 h. No significant conversion of spectrally determined P450 to cytochrome P420 was found, and cytochrome b5 was not affected. However, both NAD(P)H cytochrome c reductases were significantly inhibited at all concentrations. Immunoblot analysis showed reduction of CYP1A1 content at all doses, being significant at 25 mM after 48 h, but no decrease in CYP3A-like protein, the dominant catalyst of testosterone 6 beta-hydroxylation, nor CYP2B-like protein, the major contributor to indicates significant effects of TPT at high concentrations on fish hepatic CYP1A1 protein, EROD activity and the reductases. TPT seems to act more specifically on CYP1A1 than on other CYP forms. These findings combined with those of our previous studies (Bruschweiler BJ, Wurgler FE, Fent K. Environ Toxicol Chem 1996;15:827-735; Fent K, Bucheli TD. Aquat Toxicol 1994;28:107-126; Fent K, Stegeman JJ. Aquat Toxicol 1991;20:159-168; Fent K, Stegeman JJ. Aquat Toxicol 1993;24:219-240) indicate a general degenerative effect of Organotins on the fish microsomal monooxygenase system, although some differences are seen between the Organotins, and between species. We conclude that these effects of Organotins have consequences for use of CYP1A as a biomarker and endocrine disruption.
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organotin compounds in municipal wastewater and sewage sludge contamination fate in treatment process and ecotoxicological consequences
Science of The Total Environment, 1996Co-Authors: Karl FentAbstract:Abstract Organotin compounds find various applications in industry and agriculture, which may lead to contamination of municipal wastewater and sewage sludge. Here, an overview on the contamination of these media is given, and the behavior of Organotins in the treatment process is described. In raw municipal wastewater of the city of Zurich, Switzerland, mono- (MBT), di- (DBT) and tributyltin (TBT) were detected in the range of 140–560, 130–1030, and 60–220 ng/l, respectively. These compounds were primarily associated with suspended particulates, and transferred from wastewater to the sludge in the primary clarifier of the treatment plant. Both aerobic and anaerobic degradation were found to be insignificant. This has also been shown by a laboratory-scale sludge treatment system. After secondary and tertiary treatment, organotin concentrations were in the range of
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inhibition of cytochrome p4501a by Organotins in fish hepatoma cells plhc 1
Environmental Toxicology and Chemistry, 1996Co-Authors: Beat Johannes Bruschweiler, Friedrich E Wurgler, Karl FentAbstract:Inhibitory effects of several organotin compounds on cytochrome P4501A (CYP1A) induction response and enzyme activity have been analyzed in fish hepatoma cells (PLHC-1). In a first set of experiments, cells were exposed for 3 d to 3-methylcholanthrene (3-MC), an inducer of CYP1A. Simultaneously, series of dilutions of the widely used organotin compounds triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were added to the cells. Relative CYP1A protein contents were measured in an enzyme-linked immunosorbent assay (ELISA), CYP1A activities in the ethoxyresorufin-O-deethylase (EROD) assay, and cytotoxicity in the neutral red (NR) assay. Induction of CYP1A protein and activity was found in the presence of low concentrations of Organotins and 3-MC. The three assays did not show significant differences in sensitivity for TBT and TPT. Concentrations that reduced control values by 50% (EC50) were between 1.6·10−7 M and 3.5·10−7 M, which emphasizes the high cytotoxicity of both compounds. In contrast, DBT led to inhibition of EROD activity at significantly lower concentrations (1.2·10−6 M) than loss of CYP1A protein in the ELISA (9.0·10−6 M) and cytotoxicity in the NR assay (8.7·10−6 M). In a second set of experiments, reduction of CYP1A activity was also obtained after sequential exposure to 3-MC and Organotins. In a third set of experiments, lysates of CYP1A-induced cells were exposed to Organotins. Organotins caused a 50% inhibition of EROD activity at significantly higher concentrations (namely at 4.7·10−5 M and 6.7·10−5 M for TBT and DBT, respectively, and at 1.1·10−3 M for MBT) than in the first set of experiments. For TBT, a noncompetitive inhibitory mechanism on CYP1A enzyme activity has been found. The experiments in this study demonstrate inhibitory capacities of TBT and TPT, but also of DBT and MBT, on the CYP1A system in fish cells. The results lead to the conclusion that the effect is mainly caused by direct inhibition of enzyme activity, not by inhibition of CYP1A protein synthesis. The induction of CYP1A protein and activity in the presence of both an inducer (3-MC) and a low concentration of inhibitors (Organotins) indicates that Organotins do not interfere with the Ah receptor binding, but act at the CYP1A protein level.
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cytotoxicity in vitro of organotin compounds to fish hepatoma cells plhc 1 poeciliopsis lucida
Aquatic Toxicology, 1995Co-Authors: Beat Johannes Bruschweiler, Friedrich E Wurgler, Karl FentAbstract:Abstract Cytotoxicity in vitro to fish hepatoma cells PLHC-1 has been analyzed for a series of 21 organotin compounds consisting of all degrees of alkylation and arylation. The sensitivity of the neutral red (NR) assay and the tetrazolium salt reduction (MTT) assay was similar for most of the organotin compounds. Cytotoxic effects were found at concentrations between 10 −8 M and 10 −2 M. For various trisubstituted organotin compounds, including tributyltin and triphenyltin, which are used in antifouling paints and as pesticides, respectively, cytotoxic concentrations in the range of 10 −8 M to 10 −6 M were observed. Based on the concentration reducing NR uptake by 50% (NR 50 ), the sequence of Cytotoxicity amongst butyltins was tributyltin ⪢ bis(tributyl)-tin ⪢ dibutyltin ⪢ tetrabutyltin ⪢ butyltin ⪢ tin(IV). Tributyltin induced effects on cell functions quickly, as a reduction in NR uptake by 30% was recorded after 30 min exposure to 4 · 10 −7 M. The ranking order in Cytotoxicity in the MTT assay of phenylated Organotins was triphenyltin ⪢ diphenyltin ⪢ phenyltin ⪢ tin(IV). Cytotoxic concentrations of tributyltin and triphenyltin measured in the bromodeoxyuridine (BrdU) assay and with the crystal violet (CV) staining method do not differ significantly from those determined in the NR and MTT assay. Tri-and disubstituted organotin compounds exhibit a significant correlation between the noctanol/water partition coefficient (logK ow ) and the NR 50 ( n = 10, r = 0.86, P = 0.001) and the MTT 50 values ( n = 11, r = 0.85, P = 0.001), respectively. In addition, good qualitative correlations between in vitro Cytotoxicity data and in vivo fish toxicity data were found (for NR assay n = 8, r = 0.86, P = 0.001; for MTT assay n = 9, r = 0.80, P = 0.001). he results indicate that the in vitro Cytotoxicity assays using PLHC-1 cells are useful tools for the estimation of the acute toxicity to fish of Organotins and possibly other compounds.
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occurrence of Organotins in municipal wastewater and sewage sludge and behavior in a treatment plant
Environmental Science & Technology, 1991Co-Authors: Karl Fent, Markus D MuellerAbstract:THe behavior of selected organotin species in a wastewater treatment plant of Zurich, Switzerland, was studied. In untreated wastewater, monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) were detected in the range of 136-564, 127-1,026, and 64-217 ng/L, respectively, of which 81-92% were associated with suspended solids. During treatment, the fraction of Organotins in the particulate phase decreased with decreasing suspended solids concentration. All organotin species monitored were found to be efficiently removed from wastewater, mainly by sedimentation in the primary clarifier. In the secondary effluent, levels of different Organotins were in the range of 7-47 ng/L. These compounds were transferred into sewage sludge, indicating that the most important process for the elimination of Organotins was adsorption into sludge. Residues of MBT, DBT, and TBT in digested sludges were in the range of 0.10-0.97, 0.41-1.24, and 0.28-1.51 mg/kg (dry weight), respectively.
Kenneth M.y. Leung - One of the best experts on this subject based on the ideXlab platform.
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Long-Term Spatio-Temporal Trends of Organotin Contaminations in the Marine Environment of Hong Kong
PLOS ONE, 2016Co-Authors: Kevin K.y. Ho, Guang-jie Zhou, Elvis Genbo Xu, Xinhong Wang, Kenneth M.y. LeungAbstract:Hong Kong imposed a partial restriction on application of organotin-based antifouling paints in 1992. Since September 2008, the International Maritime Organization prohibited the use of such antifouling systems on all sea-going vessels globally. Therefore, it is anticipated a gradual reduction of organotin contamination in Hong Kong’s marine waters. Using the rock shell Reishia clavigera as a biomonitor, we evaluated the organotin contamination along Hong Kong’s coastal waters over the past two decades (1990–2015). In 2010 and 2015, adult R. clavigera were examined for imposex status and analysed for tissue concentrations of six Organotins. We consistently found 100% imposex incidence in female R. clavigera across all sites. Tissue triphenyltin (TPT) concentrations were high in most samples. A probabilistic risk assessment showed that there were over 69% of chance that local R. clavigera would be at risk due to exposure to phenyltins. Comparing with those of previous surveys (2004–2010), both imposex levels and tissue concentrations of Organotins did not decline, while the ecological risks due to exposure to Organotins were increasing. We also observed high concentrations of monobutyltin and TPT in seawater and sediment from locations with intense shipping activities and from stormwater or sewage discharge. Overall, Organotins are still prevalent in Hong Kong’s marine waters showing that the global convention alone may be inadequate in reducing organotin contamination in a busy international port like Hong Kong. Appropriate management actions should be taken to control the use and release of Organotins in Hong Kong and South China.
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long term temporal trends 1992 2008 of imposex status associated with organotin contamination in the dogwhelk nucella lapillus along the icelandic coast
Marine Pollution Bulletin, 2011Co-Authors: Lovisa O Guðmundsdottir, James Lam, Jorundur Svavarsson, Kenneth M.y. LeungAbstract:Abstract Using the dogwhelk Nucella lapillus as a biomonitor, we evaluated the organotin contamination along the Icelandic coast over nearly two decades. In 2008, adult dogwhelks collected from 30 locations were examined for imposex status. In 2009, tissue concentrations of six organotin species in dogwhelks from 16 of the 30 locations were analysed using gas chromatography–mass spectrometry. Tributyltin was the most predominant residue ranging from 2.07 to 70.38 μg kg −1 dw, while triphenyltin was also detected at concentrations up to 22.79 μg kg −1 dw. Higher total organotin concentrations and imposex indices were observed at locations near large harbours (Reykjavik and Hafnarfjorður). By comparing the current imposex results with those of previous surveys (1992–2003), we found that recovery was slow near the large harbours, but more apparent near the smaller harbours. We also observed a notable increase in imposex at several northwest sites implying incessant input of Organotins.
Lidia Regoli - One of the best experts on this subject based on the ideXlab platform.
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Organotins in zebra mussels dreissena polymorpha and sediments of the quebec city harbour area of the st lawrence river
Aquatic Toxicology, 2001Co-Authors: Lidia Regoli, Hing Man Chan, Yves De Lafontaine, Igor MikaelianAbstract:Abstract Toxic antifouling agents such as tributyltin (TBT) and triphenyltin (TPT) have been released in aquatic ecosystems through the use of antifouling paint applied to ship hulls, pleasure crafts and fish nets and these compounds can bioaccumulate in aquatic organisms. The purpose of this study was 1) to assess the extent of the distribution of Organotins from a contaminated marina to the St. Lawrence River system by measuring organotin concentrations in zebra mussels ( Dreissena polymorpha ) and in sediments collected from 9 sites along the St. Lawrence River near Quebec City in July 1998, and 2) to examine the histopathological condition of zebra mussel tissues from these sites. TBT concentrations in zebra mussels were between 37 and 1078 ng Sn g −1 wet weight, with the highest value found in the Bassin Louise marina. Elevated concentrations were also found in two other marinas. The concentrations decreased sharply to background levels just outside the marinas. All butyltins were detected in all sediments analysed, with highest values found in the Bassin Louise marina. Phenyltins were detected in three of the nine sites in low concentrations ( −1 ) in zebra mussels. There was a significant correlation between TBT in sediments and mussels. Gonadal development of zebra mussels varied largely between sites, and was negatively associated to TBT levels in mussel tissue. This study shows that TBT contamination remains a problem in localised freshwater sectors of the St. Lawrence River.
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Organotins in zebra mussels dreissena polymorpha from the saint lawrence river
Journal of Great Lakes Research, 1999Co-Authors: Lidia Regoli, Hing Man Chan, Yves De LafontaineAbstract:Toxic antifouling compounds such as Organotins have been released in the aquatic ecosystems throughout the world and can be bioaccumulating in biota. The purpose of this study was to assess the use of zebra mussels (Dreissena polymorpha) as a biomonitor for investigating the geographical variations of organotin bioavailability along the St. Lawrence River. The presence of Organotins (tributyltins (TBT) and triphenyltins (TPT)) and their degradation products were measured in the soft tissues of zebra mussels collected from 11 sites along the St. Lawrence River (between Cornwall and Ile d’Orleans) in June 1996. TBT and TPT were generally low (< 0.001 to 0.030 μg/g wet weight) and were similar to those reported in Kingston Harbour, Ontario in Canada and Nieuwkoop and Brielse meer in the Netherlands. The highest concentration of TBT (1.44 μg/g wet weight) was found in mussels from Bassin Louise, a marina in Quebec City. This suggests that zebra mussels are effive biomonitors of organotin compounds and that residual levels in the sediment, or illegal use of antifouling paints still remain problematic in localized sectors of the river. A more detailed study on the availability of TBT in marinas and harbors along the freshwater part of the St. Lawrence River is recommended.
Alex Odermatt - One of the best experts on this subject based on the ideXlab platform.
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tributyltin and triphenyltin induce 11β hydroxysteroid dehydrogenase 2 expression and activity through activation of retinoid x receptor α
Toxicology Letters, 2020Co-Authors: Silvia G Inderbinen, Roger T Engeli, Simona R Rohrer, Erminio Di Renzo, Leonie Aengenheister, Tina Buerkithurnherr, Alex OdermattAbstract:Exposure to the environmental pollutants Organotins is of toxicological concern for the marine ecosystem and sensitive human populations, including pregnant women and their unborn children. Using a placenta cell model, we investigated whether Organotins at nanomolar concentrations affect the expression and activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 11β-HSD2 represents a placental barrier controlling access of maternal glucocorticoids to the fetus. The Organotins tributyltin (TBT) and triphenyltin (TPT) induced 11β-HSD2 expression and activity in JEG-3 placenta cells, an effect confirmed at the mRNA level in primary human trophoblast cells. Inhibition/knock-down of retinoid X receptor alpha (RXRα) in JEG-3 cells reduced the effect of Organotins on 11β-HSD2 activity, mRNA and protein levels, revealing involvement of RXRα. Experiments using RNA and protein synthesis inhibitors indicated that the effect of Organotins on 11β-HSD2 expression was direct and caused by increased transcription. Induction of placental 11β-HSD2 activity by TBT, TPT and other endocrine disrupting chemicals acting as RXRα agonists may affect placental barrier function by altering the expression of glucocorticoid-dependent genes and resulting in decreased availability of active glucocorticoids for the fetus, disturbing development and increasing the risk for metabolic and cardiovascular complications in later life.
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Organotins disrupt the 11β hydroxysteroid dehydrogenase type 2 dependent local inactivation of glucocorticoids
Environmental Health Perspectives, 2005Co-Authors: Atanas G Atanasov, Lyubomir G Nashev, Steven Tam, Michael E Baker, Alex OdermattAbstract:Organotins, important environmental pollutants widely used in agricultural and industrial applications, accumulate in the food chain and induce imposex in several marine species as well as neurotoxic and immunotoxic effects in higher animals. Reduced birth weight and thymus involution, observed upon exposure to Organotins, can also be caused by excessive glucocorticoid levels. We now demonstrate that Organotins efficiently inhibit 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting active 11beta-hydroxyglucocorticoids into inactive 11-ketoglucocorticoids, but not 11beta-HSD1, which catalyzes the reverse reaction. Di- and tributyltin as well as di- and triphenyltin inhibited recombinant and endogenous 11beta-HSD2 in lysates and intact cells with IC50 values between 500 nM and 3 microM. Dithiothreitol protected 11beta-HSD2 from organotin-dependent inhibition, indicating that Organotins act by binding to one or more cysteines. Mutational analysis and 3-D structural modeling revealed several important interactions of cysteines in 11beta-HSD2. Cys90, Cys228, and Cys264 were essential for enzymatic stability and catalytic activity, suggesting that disruption of such interactions by Organotins leads to inhibition of 11beta-HSD2. Enhanced glucocorticoid concentrations due to disruption of 11beta-HSD2 function may contribute to the observed organotin-dependent toxicity in some glucocorticoid-sensitive tissues such as thymus and placenta.
Marcos Antonio Fernandez - One of the best experts on this subject based on the ideXlab platform.
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Organotins a review of their reproductive toxicity biochemistry and environmental fate
Reproductive Toxicology, 2013Co-Authors: Jones Bernardes Graceli, Gabriela C Sena, Pedro Francisco Iguatemy Lopes, Gabriela Carvalho Zamprogno, Mercia Barcellos Da Costa, Ana F L Godoi, Dayana Moscardi Dos Santos, Mary Rosa Rodrigues De Marchi, Marcos Antonio FernandezAbstract:Abstract The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to Organotins. Organotins are pollutants that are used as biocides in antifouling paints. They produce endocrine-disrupting effects in mollusks, such as imposex. In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen. The adverse effects that appear in rodents have raised concerns about Organotins’ potential health risk to humans in relation to organotin exposure. At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity. For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta. With these risks in mind, it is important to improve our knowledge of Organotins’ effects on environmental health.
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an easy non destructive probabilistic method to evaluate the imposex response of gastropod populations
Marine Environmental Research, 2007Co-Authors: Marcos Antonio Fernandez, Fernanda Pinheiro, Juliana P Quadros, Edmundo CamilloAbstract:Endocrine disruption in marine populations is a growing concern. One of the best documented examples is imposex, the development of male characteristics in female gastropods, including the development of a penis and/or vas deferens, by exposure to Organotins, mainly tributyltin. This syndrome has been an effective and widely used biomarker of organic tin contamination for almost 20 years. However, established imposex evaluation protocols sacrifice all the animals and repeated assessments can result in depletion of populations. To preserve animal lives as much as possible and to have a fast screening of areas subjected to organotin impacts, a non-destructive approach was tested. This approach uses reversible narcotization and a statistical criterion to evaluate the extent of imposex in the populations, instead of imposex indexes, which are based on evaluation of sacrificed, fixed animals. The data consist of two categories: males plus masculinized females in one category and normal females in another. The probability is then calculated that this sample could have been drawn from a normal population. This new method was tested in two contrasting areas of Brazil and with two different species, and the results compared to the conventional evaluation. Narcotization was completely reversed with a survival rate of 98%. Impacted sites could be identified with this technique in the same way as with the conventional one. The only limitation was that female sterility could not be verified. This disadvantage could well be compensated by the minimal mortality in the studied populations.