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Effect of SKF-525A on liver metabolism and hepatotoxicity of tri- and dibutyltin compounds in mice.

The effect of pretreatment with SKF-525A, which inhibits hepatic cytochrome P450 enzymes, on metabolism and hepatotoxicity was examined in mice orally administered tributyltin chloride (TBTC) or dibutyltin dichloride (DBTC) at a dose of 180 mumol/kg. Analysis of butyltin compounds showed that the main metabolites in liver of mice treated with TBTC alone were DBTC (40%) and dibutyl(3-carboxylpropyl)tin chloride (TCOOH; 12-26%), with the levels of other butyltin compounds including TBTC comprising < 12% of total butyltin compounds at 3-24 h following treatment. The pretreatment with SKF-525A resulted in four- to tenfold increased TBTC levels and a significant decrease of debutylated metabolites, particularly DBTC (60 and 37% decrease) at both 3 and 6 h in liver of mice treated with TBTC, leading to complete inhibition of hepatotoxicity at 24 h. At 24 h after TBTC treatment, hepatic levels of TBTC and most of the debutylated metabolites in mice pretreated with SKF-525A did not differ significantly when compared to those in unpretreated mice, resulting in the induction of hepatotoxicity at 48 h, although levels of TCOOH decreased even at 24 h. In the case of DBTC treatment, > 95% of the butyltin compounds were detected as DBTC in liver, and the levels of DBTC inside cells as well as the induction of DBTC hepatotoxicity were unaffected by pretreatment with SKF-525A. These results suggest that debutylated metabolites, in particular DBTC, are the main metabolites of butyltin compounds responsible for the induction of hepatotoxicity following in vivo administration of TBTC. The results also indicate that cytochrome P450 enzymes may play a greater role in the metabolism of TBTC to form DBTC or butyltin trichloride (MBTC) than that of DBTC to form MBTC in liver of mice.

Animals↗

Inhibition of neutrophil chemotaxis by organotin compounds.

Organotin compounds such as Bu2SnCl2, Bu3SnCl and Ph3SnCl suppressed significantly not only chemotactic response of neutrophils to stimulation by the chemoattractant fMet-Leu-Phe but also phospholipase activity in situ as measured by the release of [1-14C] arachidonic acid previously incorporated into phospholipids. Moreover, these suppressions were dose dependent and a parallelism was found between dose-dependent inhibition of chemotaxis and that of arachidonate release. These results suggest that the chemotactic response is controlled by the activation of phospholipase activity in neutrophils, and that the inhibitory effects of these organotin compounds on chemotactic response reflect the blockage of phospholipase activation system regulated by phosphorylation of lipomodulin.

Animals↗

The accumulation of organotins in adult and seed oysters from selected estuaries prior to the introduction of U.K. regulations governing the use of tributyltin-based antifouling paints.

Between April and November, 1985, a study of the levels of organotins in adult and seed Crassostrea gigas grown in the southwest and southeast of England was carried out. This work corresponds with a similar study of organotin water levels (reported separately). The analytical procedure used was directly coupled high performance liquid chromatography-flame atomic absorption spectrometry. Individual adult oysters and groups of 20-40 seed oysters were taken for analysis on a monthly basis. The profiles of tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) are discussed in relation to each other and levels found in the waters. In general, levels of all three organotin species were found to be higher in the seed oysters. Mean levels of TBT reached 3.1 micrograms g-1 in seed oysters from the Exe, Devon, in October, whereas mean levels of DBT and MBT reached 16.1 and 16.7 micrograms g-1 in Teign, Devon, seed oysters in October. Bioconcentration factors of approximately 1000 were found, but seem to be greater when lower levels of TBT were present in the water, perhaps indicating a more 'efficient' removal from the water. The degree of shell thickening was calculated for all oysters submitted for analysis. The highest percentage of adult oysters with severely thickened shells was found at Tollesbury Fleet, where 61% of oysters showed shell thickness index values of six or less. Generally, two peaks in TBT levels in the oysters were observed, in the late spring and early summer: these seem to correlate with peak levels of TBT in the waters immediately preceding these times. A large proportion of the DBT and MBT found in the oysters seems to come from the metabolism of the TBT ingested. It is suggested that high sediment loadings may contribute to the severe deformation of oysters grown at Tollesbury Fleet, but only in the presence of TBT.

Aging↗

Occurrence of butyltin species in sewage and sludge in Canada.

Samples of sewage treatment influent, effluent and sludges collected monthly from five Canadian cities over the period from July 1990 to January 1991 were analysed for butyltin and octyltin species. Monobutyltin was found in all influent samples, but dibutyltin and tributyltin were found only infrequently, and octyltin species were not found at all. In the case of monobutyltin, there was significant reduction in its concentration by degradation and adsorption to sludge during passage through the sewage treatment plant. The average reduction was 40%. The monobutyltin found in the effluent likely came from its use as a poly (vinyl chloride) stabilizer, and from the degradation of tributyltin, which is used as a slimicide. No butyltin or octyltin species was found in five landfill leachate samples in southern Ontario during the same period.

Canada↗

Effect of triorganotin compounds on membrane permeability.

Organotin compounds are widely distributed toxicants. They are membrane-active molecules with broad biological toxicity. In this contribution, we study the effect of triorganotin compounds on membrane permeability using phospholipid model membranes and human erythrocytes. Tribultyltin and triphenyltin are able to induce the release of entrapped carboxyfluorescein from large unilamellar vesicles. The rate of release is similar for phosphatidylcholine and phosphatidylserine systems and the presence of equimolar cholesterol decreases the rate of the process. Release of carboxyfluorescein is almost abolished when a non-diffusible anion like gluconate is present in the external medium, and it is restored by addition of chloride. Tributyltin is able to cause hemolysis of human erythrocytes in a dose-dependent manner. Relative kinetics determination shows that potassium leakage occurs simultaneously with hemoglobin release. Hemolysis is reduced when erythrocytes are suspended in a gluconate medium. These results indicate that triorganotin compounds are able to transport organic anions like carboxyfluorescein across phospholipids bilayers by exchange diffusion with chloride and suggest that anion exchange through erythrocyte membrane could be related to the process of hemolysis.

Fluoresceins↗

Butyltins in water, biofilm, animals and sediments of the west coast of India.

Biofilm, fish, oyster, mussel, clam, surface seawater, suspended particulate matter (SPM), and sediment samples were collected from marine and/or estuarine waters of the west coast of India. These samples were analysed for butyltin derivatives such as dibutyltin (DBT) and tributyltin (TBT). The concentrations DBT plus TBT varied between 2.4 and 8.3, 163 and 363 ng/l, 5 and 2853 ng/g dry wt in the SPM, seawater and sediment samples, respectively, of the Marmugao harbour. The values of DBT plus TBT ranged between 0.60 and 29, 123 and 242 ng/l and 1.4 and 65 ng/g dry wt in SPM, water and sediment samples, respectively, collected from the Mandovi estuary. In the Dona Paula Bay the DBT plus TBT varied from 10 to 89 ng/l in surface seawater, and TBT from 10 to 513 ng/g in biofilm samples. For the coastal sediment samples the concentration of DBT plus TBT ranged between 36 and 133 ng/g dry wt of sediment. For the animal samples the DBT plus TBT ranged between 58 and 825 ng/g dry wt of the tissue. Mussel tissues contained the highest amount of DBT plus TBT (825 ng/g dry wt tissue), whereas highest TBT concentration was recorded in the oyster (732 ng/g dry wt). TBT was generally the most abundant butyltin compound in most of the samples suggesting fresh inputs and/or less degradation of TBT. A wide range of the observed butyltin concentrations suggests the presence of localized areas of contamination. Leaching of tributyltin-containing antifouling paints from the ocean going ships, fishing and recreational boats, barges, and the inputs of TBT from the Goa shipyard and dry dock facility situated in the harbour are the probable sources of the DBT and TBT in the samples of the west coast of India. Higher levels of TBT were observed in biofilm relative to that in the surrounding seawater. When fed on TBT contaminated biofilm of the diatom Navicula subinflata, butyltin concentrations in the clam Paphia malabarica increased over the period of feeding suggesting the importance of biofilm in the transfer of butyltins to higher group of organisms.

Animals↗

Distribution of butyltin and derivatives in oyster shells and trapped sediments of two estuaries in Cantabria (Northern Spain).

Distribution of butyltin compounds (BTs) and derivatives (monobutyltin, MBT; dibutyltin, DBT and tributyltin, TBT) was analysed in Crassostrea gigas oyster shells and the sediments trapped in the shell chambers, from two different estuaries in Cantabria (Northern Spain), with very different environmental conditions, where previous data have not been reported. Inorganic tin analysis in oyster shells was performed in order to study the degradation of BTs. Shell thickening and losses in biological growth are related with the presence of TBT, and were determined using three morphological indexes. Total BTs concentrations, expressed as Sn, ranged from 18.0 ng g(-1) to 176.7 ng g(-1) in sediments, and from 2.4 ng g(-1) to 11.1 ng g(-1) in oyster shells. Total inorganic tin concentrations ranged from 1775.0 ng g(-1) to 4781.3 ng g(-1) in oyster shells. The amount of BTs in oyster shells has been associated with the concentrations in the sediments trapped in the shell chambers. Partition coefficients between oyster sediments and oyster shells show the affinity of BTs by the sediments and the higher inorganic tin in oyster shells does not seem to be related to the BTs pollution.

Animals↗

Butyltins in the sediments of Kochi and Mumbai harbours, west coast of India.

Surface sediment samples were collected from various locations in the Mumbai and Kochi harbours, west coast of India, to assess the presence of butyltin compounds. Tributyltin (TBT) and dibutyltin (DBT) varied from 16 to 16,816 ng/g dry wt. and from undetected to 469 ng/g dry wt., respectively, of the sediment in Kochi harbour. In Mumbai harbour, the values of TBT and DBT ranged between 4.5 and 1193 ng/g dry wt. and from undetected to 131 ng/g dry wt. of the sediments, respectively. The concentrations of both TBT and DBT showed strong seasonal variation probably due to the effect of tides and currents. Nevertheless, the levels of butyltin compounds were generally higher at sites influenced by shipping activities such as navigation, dry dock and ship-building activities. The presence of DBT indicates the abiotic or microbiological degradation of TBT. Compared to TBT, DBT was relatively less abundant, suggesting either fresh inputs of TBT and/or less degradation of TBT. The concentrations of TBT showed significant positive relationships with organic carbon and lipid, implying that both lipophilic and ionic interactions were probably involved in controlling the abundance of TBT at these sediments. The observed levels of butyltin compounds are much higher than those required to induce toxic effects on marine organisms, suggesting that these sediments were contaminated with butyltin compounds.

Carbon↗

Contamination of butyltin compounds in Malaysian marine environments.

Concentration of butyltin compounds (BTs), including tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) and total tin (SigmaSn) were determined in green mussel (Perna viridis), 10 species of muscle fish and sediment from coastal waters of Malaysia. BTs were detected in all these samples ranging from 3.6 to 900 ng/g wet wt., 3.6 to 210 ng/g wet wt., and 18 to 1400 ng/g dry wt. for mussels, fish and sediments, respectively. The concentrations of BTs in several locations of this study were comparable with the reported values from some developed countries and highest among Asian developing nations. Considerable concentration of BTs in several locations might have ecotoxicological consequences and may cause concern to human health. The parent compound TBT was found to be highest than those of its degradation compounds, DBT and MBT, suggesting recent input of TBT to the Malaysian marine environment. Significant positive correlation (Spearman rank correlation: r2=0.82, P<0.0001) was found between BTs and SigmaSn, implying considerable anthropogenic input of butyltin compounds to total tin contamination levels. Enormous boating activities may be a major source of BTs in this country, although aquaculture activities may not be ignored.

Animals↗

Hematological findings in neotropical fish Hoplias malabaricus exposed to subchronic and dietary doses of methylmercury, inorganic lead, and tributyltin chloride.

Hematological indices are gaining general acceptance as valuable tools in monitoring various aspects the health of fish exposed to contaminants. In this work some effects of methyl mercury (MeHg), inorganic lead (Pb2+), and tributyltin (TBT) in a tropical fish species were evaluated by hematological methods after a trophic exposition at a subchronic level. Forty-two mature individuals of the freshwater top predator fish Hoplias malabaricus were exposed to trophic doses (each 5 days) of MeHg (0.075 microg g(-1)), Pb2+ (21 microg g(-1)), and TBT (0.3 microg g(-1)) using young fish Astyanax sp. as prey vehicle. After 14 successive doses over 70 days, blood was sampled from exposed and control groups to evaluate hematological effects of metals on erythrocytes, total leukocytes and differential leukocytes counts, hematocrit, hemoglobin concentration, and red blood cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Transmission electron microscopy and image analysis of erythrocytes were also used to investigate some morphometric parameters. Results show no significant effects in MCH and MCHC for all tested metals, but differences were found in erythrocytes, hemoglobin, hematocrit, MCV, and white blood cells counts. The number of leukocytes was increased in the presence of MeHg, suggesting effects on the immune system. Also the MCV increased in individuals exposed to MeHg. No ultrastructural damages were observed in red blood cells but the image analysis using light microscopy revealed differences in area, elongation, and roundness of erythrocytes from individuals exposed to Pb2+ and TBT but not in the group exposed to MeHg. The present work shows that changes in hematological and blood indices could highlight some barely detectable metal effects in fish after laboratory exposure to contaminated food, but their application in field biomonitoring using H. malabaricus will need more detailed studies and a careful consideration of environmental parameters.

Animals↗

Effects of antifouling biocides to the germination and growth of the marine macroalga, Hormosira banksii (Turner) Desicaine.

The International Maritime Organisation's (IMO) ban on the use of tributyltin in antifouling paints has inevitability increased the use of old fashioned antifoulants and/or the development of new paints containing 'booster biocides'. These newer paints are intended to be environmentally less harmful, however the broader environmental effects of these 'booster biocides' are poorly known. Germination and growth inhibition tests using the marine macroalga, Hormosira banksii (Turner) Desicaine were conducted to evaluate the toxicity of four new antifouling biocides in relation to tributyltin-oxide (TBTO). Each of the biocides significantly inhibited germination and growth of Hormosira banksii spores. Toxicity was in increasing order: diuron < zineb < seanine 211< zinc pyrithione < TBTO. However, the lack of knowledge on partitioning in the environment makes it difficult to make a full assessment on whether the four biocides tested offer an advantage over organotin paints in terms of environmental impact.

Analysis of Variance↗

Organotin compounds alter the physical organization of phosphatidylcholine membranes.

Organotin compounds have a broad range of biological activities and are ubiquitous contaminants in the environment. Their toxicity mainly lies in their action on the membrane. In this contribution we study the interaction of tributyltin and triphenyltin with model membranes composed of phosphatidylcholines of different acyl chain lengths using differential scanning calorimetry, (31)P-nuclear magnetic resonance, X-ray diffraction and infrared spectroscopy. Organotin compounds broaden the main gel to liquid-crystalline phase transition, shift the transition temperature to lower values and induce the appearance of a new peak below the main transition peak. These effects are more pronounced in the case of tributyltin and are quantitatively larger as the phosphatidylcholine acyl chain length decreases. Both tributyltin and triphenyltin increase the enthalpy change of the transition in all the phosphatidylcholine systems studied except in dilauroylphosphatidylcholine. Organotin compounds do not affect the macroscopic bilayer organization of the phospholipid but do affect the degree of hydration of its carbonyl moiety. The above evidence supports the idea that organotin compounds are located in the upper part of the phospholipid palisade near the lipid/water interface.

1,2-Dipalmitoylphosphatidylcholine↗

Organotin compounds promote the formation of non-lamellar phases in phosphatidylethanolamine membranes.

Organotin compounds are important contaminants in the environment. They are membrane active molecules with broad biological toxicity. We have studied the interaction of tri-n-butyltin chloride and tri-n-phenyltin chloride with model membranes composed of different phosphatidylethanolamines using differential scanning calorimetry, X-ray diffraction, 31P-nuclear magnetic resonance and infrared spectroscopy. Organotin compounds laterally segregate in phosphatidylethanolamine membranes without affecting the shape and position of the lamellar gel to lamellar liquid-crystalline phase transition thermogram of the phospholipid. This is in contrast with their reported effect on phosphatidylcholine membranes [Chicano et al. (2001) Biochim. Biophys. Acta 1510, 330-341] and emphasises the importance of the nature of the lipid headgroup in determining how the behaviour of lipid molecules is affected by these toxicants. Interestingly, we have found that organotin compounds disrupt the pattern of hydrogen-bonding in the interfacial region of dielaidoylphosphatidylethanolamine membranes and have the ability to promote the formation of hexagonal H(II) structures in this system. These results open the possibility that some of the specific toxic effects of organotin compounds might be exerted through the alteration of membrane function produced by their interaction with the lipidic component of the membrane.

Calorimetry, Differential Scanning↗

Occurrence and effects of organotins on adult common whelk (Buccinum undatum) (Mollusca, Gastropoda) in harbours and in a simulated dredging situation.

Transplanted common whelk (Buccinum undatum) (Mollusca, Gastropoda) accumulated fairly high levels of organotins (tributyltin (TBT) and triphenyltin (TPT)) during exposure in three harbours with different TBT contamination. This did not though lead to an increase in imposex frequency in the adult females studied. Simulating harbour dredging in an experiment using suspended sediment from one of the harbours only resulted in a low concentration of TBT in the tissues of the common whelk and subsequently no changes in the occurrence and degree of imposex. The common whelk seemed to receive the main part of TBT from the water column and the limited bioaccumulation in the experiment indicates that desorption of TBT from the suspended sediment was slow. After TBT has been totally banned, dredging of contaminated sediments will cause increased exposure of the biota to TBT. Due to slow desorption the increase may however, be slight and temporary to pelagic and epibenthic species unless the settled particles are resuspended.

Animals↗

Assessment of organotin contamination in marine sediments and biota from the Gulf and adjacent region.

Butyltin species were measured in sediments from coastal locations in the Gulf and Gulf of Oman. Both butyltin and phenyltin species were measured in biota samples from four countries in this region. With tributyltin (TBT) concentrations up to 60 ngSng(-1), some sediments could be classified as contaminated (i.e. TBT>1.3 ngSng(-1)), namely Dukhan (Qatar), the BAPCO industrial complex and Askar (Bahrain), and Hilf and the Raysut Port Area (Oman). Higher concentrations of total butyltins were found in oysters relative to fish, but ranging from 6.5 to 488 ngSng(-1) dry weight they are nonetheless relatively low. Diphenyltin and triphenyltin were found in some fish and bivalves from the Gulf, but not in biota from the Gulf of Oman. The environmental levels of organotin species are comparatively low by global standards and pose no immediate public health problems.

Animals↗

Distribution pattern of organotin compounds at different trophic levels of aquatic ecosystems.

Organotin compounds including methyl- and butyltin species were determined in selected aquatic specimens (fish muscles, fish liver, mussels, algae) as well as in sediment and water from the mud flats of the German North Sea and the River Elbe. The concentration of tributyltin (TBT) ranged between 27-202 ng/g (fresh mass) in fish muscles, 54-223 ng/g (fresh mass) in fish liver, 10-25 ng/g (fresh mass) in common mussels and 42-97 ng/g (fresh mass) in bladderwrack. The concentration of total organotin compounds (mono-, di-, and trimethyltin + mono-, di-, and tributyltin) in water samples along the River Elbe up to the Elbe estuary ranged between 30-96 ng/l. Retrospective investigation of butylin compounds in mussel samples from the North Sea was performed by the analysis of cryogenically stored samples from 1985. A comparison of the results with that in muscles from 1993 shows that the total tin content and the TBT content decreased from 1985-1993 by a factor of 3.5 and 6.5, respectively. In addition estimated bioconcentration factors (BCF) for organotin compounds in samples from different trophic levels are presented.

Animals↗

A review of organotin regulatory strategies, pending actions, related costs and benefits.

Achieving consensus on equitable and effective national and global regulation(s) for the use of organotins as biocides in antifouling boat bottom paints has proven to be very complex and difficult for a variety of reasons as discussed in this paper. There appears to be broad agreement among stakeholders about the effectiveness of tributyltin (TBT) in antifouling paints. A draft Assembly Resolution prepared by the Marine Environmental Protection Committee (MEPC) of the International Maritime Organization (IMO) to propose a global ban on the use of organotins in antifouling paints was approved by the IMO at its 21st regular session (November 1999). In approving the Resolution, the Assembly agreed that a legally binding instrument (global convention--an international treaty) be developed by the Marine Environmental Protection Committee that should ensure by 1 January 2003, a ban on the application of tributyltin (TBT)-based antifouling paints; and 1 January 2008 as the last date for having TBT-based antifouling paint on a vessel. The Assembly also agreed that a diplomatic conference be held in 2001 to consider adoption of the international legal instrument. Monitoring, policing, enforcement, fines and record-keeping are yet to be defined. In addition, the MEPC has also proposed that IMO promotes the use of environmentally-safe anti-fouling technologies to replace TBT. Existing national regulations in the US and Europe have: (1) restricted the use of TBT in antifouling boat bottom paints by vessel size (less than 25 m in length), thus eliminating TBT from the smaller and recreational vessels that exist in shallow coastal waters where the impacted oysters species grow; (2) restricted the release rates of TBT from co-polymer paints; and (3) eliminated the use of free TBT in paints. The present movement toward a global ban suggests that the above regulatory approach has not been sufficient in some countries. Advocates of the ban cite international findings of: (1) higher levels of TBT in surface waters of ports and open waters; (2) imposex still occurring and affecting a larger number of snail species; (3) TBT bioaccumulation in selected fisheries; and (4) the availability of 'comparable' alternatives (to TBT) with less environmental impact. The global ban has been absent of a policy debate on the: (1) lack of 'acceptable and approved' alternatives in many nations; (2) appreciation of market forces in nations without TBT regulations; (3) full consideration of the economic benefits from the use of TBT; (4) 'acceptance' of environmental impacts in marinas, ports and harbors; and (5) realization of the 'real' time period required by ships for antifoulant protection (is 5-7 years necessary or desirable?). Estimates of fuel savings range from $500 million to one billion. In assessing the environmental impact from TBT, there are two sources: the shipyard painting vessels and the painted vessel itself. Today vessels can be painted with regulated or banned antifouling materials by boatyards in a country that does not have TBT regulations and subsequently travel in international and regulated national waters and thus bringing the impact back to the country which was trying to prevent it. Worse, local and national regulations for TBT have proven to be the antithesis of the popular environmental cliché--'Think Globally and Act Locally.' Legislative policies enacted by 'regulated' countries to regulate the use of TBT to protect (their) local marine resources have subsequently had far reaching environmental and economic impacts which have in essence transferred TBT contamination to those countries least able to deal with it. Market forces are selective for cheap labor and cheap environments. 'Unregulated' countries have unknowingly accepted the environmental and human health risks to gain the economic benefits from painting TBT on ships. (ABSTRACT TRUNCATED)

Cost-Benefit Analysis↗