Toxicity Of Organotin Compounds Research Articles

Trimethyltin chloride exposure induces apoptosis and necrosis and impairs islet function through autophagic interference

Trimethyltin chloride (TMT) is a highly toxic organotin compound often used in plastic heat stabilizers, chemical pesticides, and wood preservatives. TMT accumulates mainly through the environment and food chain. Exposure to organotin compounds is associated with disorders of glucolipid metabolism and obesity. The mechanism by which TMT damages pancreatic tissue is unclear. For this purpose, a subacute exposure model of TMT was designed for this experiment to study the mechanism of damage by TMT on islet. The fasting blood glucose and blood lipid content of mice exposed to TMT were significantly increased. Histopathological and ultrastructural observation and analysis showed that the TMT-exposed group had inflammatory cell infiltration and necrosis. Then, mouse pancreatic islet tumour cells (MIN-6) were treated with TMT. Autophagy levels were detected by fluorescence microscopy. Real-time quantitative polymerase chain reaction and Western blotting were used for verification. A large amount of autophagy occurred at a low concentration of TMT but stagnated at a high concentration. Excessive autophagy activates apoptosis when exposed to low levels of TMT. With the increase in TMT concentration, the expression of necrosis-related genes increased. Taken together, different concentrations of TMT induced apoptosis and necrosis through autophagy disturbance. TMT impairs pancreatic (islet β cell) function.

Tin-Free Synthesis of 2,2′-Biphenyl Gold(III) Complexes Using Dibenzosilol

Gold(III) complexes with dianionic 2,2′-biphenyl ligands stand out for their oxophilic Lewis acid character in combination with a stable and well-defined square planar geometry. They have been demonstrated to be unique and efficient chiral (pre)catalysts. Furthermore, their chemical and physical properties make them interesting for stoichiometric studies as well as organic electronics. These complexes are commonly prepared by transmetallating the bph ligand from undesirable and potentially toxic organotin compounds onto gold salts, making their synthesis problematic for health and the environment. Here, we present a tin-free synthesis using stable and nontoxic dibenzosilol as a transmetallating agent, accessing the same range of gold complexes as the dibenzostannanol-based synthesis. Furthermore, we confirm that corresponding isonitrile gold(III) complexes can be transformed into carbene gold(III) complexes by the nucleophilic attack of amines, opening up the route to new gold(III) catalyst design strategies.

Biological Evaluation of Triorganotin Derivatives as Potential Anticancer Agents.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF3) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF3. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF3, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF3 might be the prototype of a family of potential anticancer agents.

Organotin contamination in seafood from the Yucatán Peninsula, Mexico: Is there a potential risk for the health of consumers?

Since seafood is considered an important source of organotin compounds (OTCs), the present study assessed the potential risk to human health of ingesting butyltins (BTs) and phenyltins (PhTs) along with this type of food. Seafood samples were collected at five fishing sites in the Yucatán Peninsula (Mexico) during February and March 2018. In general, organotins were detected in all samples, suggesting a widespread occurrence of these compounds in the investigated region. The average concentration of total organotins in the muscle of demersal fish (Lutjanus synagris, Lutjanus campechanus, Calamus pennatula, Haemulon plumierii, Rhomboplites aurorubens), pelagic fish (Euthynnus alletteratus, and Opisthonema oglinum), gastropods (Melongena bispinosa and Strombus pugilis), oyster (Crassostrea virginica) and shrimp (Penaeus duorarum) was 146.7 ± 76.2, 93.1 ± 92.6, 61.0 ± 53.0, 76.7 ± 2.6, and 28.8 ± 2.7 ng Sn g−1 dry weight, respectively. Overall, MPhT among PhTs was the dominant compound in fish, while TBT among BTs was the dominant compound in shellfish. Regarding the toxic OTCs, TBT followed by DBT were the predominant compounds in all seafood species, while TPhT was below the quantification limit in most samples. The estimated daily intake values were lower than the tolerable daily intake (TDI) for the sum of organotins established by the European Food Safety Authority (EFSA). Furthermore, the hazard quotients (HQ) and hazard indices (HI) values were all lower than 1, suggesting that daily exposure to these levels of organotins is unlikely to cause any harm to the human health of seafood consumers at the Yucatán Peninsula. Thus, consumers may not be at risk through the inclusion of these investigated seafood species in their normal diet. However, due to the increasing coastal urbanization, maritime activities, and the likely illegal use of tin-based paints in Mexico, additional monitoring is needed to assess organotin levels in other regions along the Mexican coastal zone and using other seafood species.

Modified, optimized method of determination of Tributyltin (TBT) contamination in coastal water, sediment and biota in Sri Lanka

Tributyltin (TBT) is a toxic organotin compound that belongs to the group of Persistent Organic Pollutants (POPs) and it is documented to cause severe sexual disorders development in aquatic fauna. According to the present study, The TBT concentration in coastal water ranged from 303 ± 7.4 ngL−1 to 25 ± 4.2 ngL−1 wherein sediment was from 107 ± 4.1 ngKg−1 to 17 ± 1.4 ngKg−1. TBT in Perna viridis was found to range from 4 ± 1.2 ngKg−1 to 42 ± 2.2 ngKg−1 wet weight and in ascending order of the body weight. The highest TBT level in water and sediment was found in the Colombo port where the highest level of TBT in P. viridis (42 ± 2.2 ngKg−1) was recorded from the Dikkowita fishery harbor. A positive correlation between the number of male P. viridis and TBT level (p < 0.05) suggests possible reproductive impairment in aquatic animals exposed continuously to a high concentration of TBT.

The Evidence of Imposex in Turbo sp. from Ujungpiring Waters of Jepara

Imposex is an endocrine disruption syndrome, in which females of marine gastropods develop sexual characteristics of males (penis and/or vas deferens). This syndrome is caused by tributyltin (TBT) or triphenyltin (TPT), toxic organotin compounds found in naval paints used as antifouling system in boats and artificial structures. The main objective of this study was to assess the incidence and severity of imposex in Turbosp.A hundred individus of Turbo sp was collected from Ujung Piring waters of Jepara, and observed for their sex and imposex. The results showed that the ratio male and female was 1.13 : 1, and the frequency of imposex females was 64.58%. The relative penis size were longer in imposex female than in male. The possibility of pollution was clearly shown from high evidence of imposex female.

Tin-Free Direct C-H Arylation Polymerization for High Photovoltaic Efficiency Conjugated Copolymers.

A new and highly regioselective direct C-H arylation polymerization (DARP) methodology enables the reproducible and sustainable synthesis of high-performance π-conjugated photovoltaic copolymers. Unlike traditional Stille polycondensation methods for producing photovoltaic copolymers, this DARP protocol eliminates the need for environmentally harmful, toxic organotin compounds. This DARP protocol employs low loadings of commercially available catalyst components, Pd2(dba)3·CHCl3 (0.5 mol%) and P(2-MeOPh)3 (2 mol%), sterically tuned carboxylic acid additives, and an environmentally friendly solvent, 2-methyltetrahydrofuran. Using this DARP protocol, several representative copolymers are synthesized in excellent yields and high molecular masses. The DARP-derived copolymers are benchmarked versus Stille-derived counterparts by close comparison of optical, NMR spectroscopic, and electrochemical properties, all of which indicate great chemical similarity and no significant detectable structural defects in the DARP copolymers. The DARP- and Stille-derived copolymer and fullerene blend microstructural properties and morphologies are characterized with AFM, TEM, and XRD and are found to be virtually indistinguishable. Likewise, the charge generation, recombination, and transport characteristics of the fullerene blend films are found to be identical. For the first time, polymer solar cells fabricated using DARP-derived copolymers exhibit solar cell performances rivalling or exceeding those achieved with Stille-derived materials. For the DARP copolymer PBDTT-FTTE, the power conversion efficiency of 8.4% is a record for a DARP copolymer.

Trimethyltin-induced hippocampal neurodegeneration: A mechanism-based review.

Trimethyltin (TMT), a toxic organotin compound, induces neurodegeneration selectively involving the limbic system and especially prominent in the hippocampus. Neurodegeneration-associated behavioral abnormalities, such as hyperactivity, aggression, cognitive deficits, and epileptic seizures, occur in both exposed humans and experimental animal models. Previously, TMT had been used generally in industry and agriculture, but the use of TMT has been limited because of its dangers to people. TMT has also been used to make a promising in vivo rodent model of neurodegeneration because of its region-specific characteristics. Several studies have demonstrated that TMT-treated animal models of epileptic seizures can be used as tools for researching hippocampus-specific neurotoxicity as well as the molecular mechanisms leading to hippocampal neurodegeneration. This review summarizes the in vivo and in vitro underlying mechanisms of TMT-induced hippocampal neurodegeneration (oxidative stress, inflammatory responses, and neuronal death/survival). Thus, the present review may be helpful to provide general insights into TMT-induced neurodegeneration and approaches to therapeutic interventions for neurodegenerative diseases, including temporal lobe epilepsy.

Adsorption and degradation processes of tributyltin and trimethyltin in landfill leachates treated with iron nanoparticles

Biotic and abiotic degradation of toxic organotin compounds (OTCs) in landfill leachates is usually not complete. In this work adsorption and degradation processes of tributyltin (TBT) and trimethyltin (TMeT) in leachate sample treated with different iron nanoparticles (FeNPs): Fe0 (nZVI), FeO and Fe3O4 were investigated to find conditions for their efficient removal. One sample aliquot was kept untreated (pH 8), while to the others (pH 8) FeNPs dispersed with tetramethyl ammonium hydroxide (TMAH) or by mixing were added and samples shaken under aerated conditions for 7 days. The same experiments were done in leachates in which the pH was adjusted to 3 with citric acid. Size distribution of TBT and TMeT between particles >5µm, 0.45–5µm, 2.5–0.45µm, and <2.5nm was determined by sequential filtration and their concentrations in a given fraction by gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS). Results revealed that most of the TBT or TMeT was present in fractions with particles >2.5 or <2.5nm, respectively. At pH 8 adsorption of TBT to FeNPs prevailed, while at pH 3, the Fenton reaction provoked degradation of TBT by hydroxyl radicals. TBT was the most effectively removed (96%) when sequential treatment of leachate with nZVI (dispersed by mixing) was applied first at pH 8, followed by nZVI treatment of the aqueous phase, previously acidified to pH 3 with citric acid. Such treatment less effectively removed TMeT (about 40%). It was proven that TMAH provoked methylation of tin, so mixing was recommended for dispersion of nZVI.

Insights into the Organocatalyzed Synthesis of Urethanes in Supercritical Carbon Dioxide: An In Situ FTIR Spectroscopic Kinetic Study

AbstractThe kinetics of urethane (carbamate) formation in supercritical CO2 (scCO2) has been studied by in situ FTIR spectroscopy by using the reaction between n‐butanol and toluene‐2,4‐diisocyanate as a model for the synthesis of polyurethanes. We have evaluated the efficiency of different organocatalysts for this transformation to eliminate the need for potentially toxic organotin compounds. Bicyclic guanidines and amidines (7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene) lead to a significant acceleration of the reaction rate, but we found that their activity in scCO2 is reduced compared to reactions in conventional media because of the formation of guanidinium or amidinium alkylcarbonate salts. In scCO2, these catalysts are also sensitive to the presence of water and can lead to the formation of allophanate or isocyanurate byproducts. On the other hand, we have shown that catalysis with amine N‐oxides (N‐methylmorpholine‐N‐oxide) is suited to the scCO2 medium.

Ranking of (neuro)developmental toxicity of organotin compounds in zebrafish relative to their in vivo potencies

Ranking of (neuro)developmental toxicity of organotin compounds in zebrafish relative to their in vivo potencies

Toxicity and speciation analysis of organotin compounds

The use of antifouling paints in shipbuilding has led to a significant concentration of organotin compounds in the marine environment. Antifouling paints have become the main source of tributyltin and triphenyltin derivatives loaded into the sea. The toxicity of organotin compounds has been of great concern. High concentrations of organotin compounds are associated with growth abnormalities in mussels and oysters and have also resulted to the decline in their abundance. High concentration of organotin compounds have also been found in the tissues of marine mammals and its presence has been linked to mass mortalities of marine mammals. It causes imposex and calcification anomalities in mollusks. Seafood is thought to be a possible source of organotin compounds in human. Therefore, to evaluate the environmental distribution and fate of these compounds and to determine the effectives of legal provisions adopted by a number of countries, a variety of analytical methods have been developed for the speciation of organotin compounds in the environment. A detailed review of the toxicity and chemical speciation of organotin compounds is given.

Triphenyltin induced growth inhibition and antioxidative responses in the green microalga Scenedesmus quadricauda

The toxicity of organotin compounds in the environment is closely related to their uptake by microorganisms and delivery through the food chain. The population at low trophic levels like microalgae plays an important role in this aspect. In this study, the toxic effects of triphenyltin (TPT) on Scenedesmus quadricauda were assessed at the population, cellular and subcellular levels. The alga was exposed to TPT of up to 64 μg l(-1) (nearly lethal concentration), but the algal growth was inhibited significantly when TPT was elevated to 8 μg l(-1). This growth inhibition was correlated to the presence of oxidative stress as evidenced by the accumulation of malondialdehyde (MDA) and confirmed by fluorescent probing of the intracellular reactive oxygen species (ROS) levels. The imbalanced activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) may lead to an accumulation of intracellular H(2)O(2), which can initiate an oxidative damage to cell components and cause growth inhibition and finally cell death. The detachment of plasma membrane from cell wall, the structural change of chloroplasts as well as the increased number and size of starch granules together with electron-dense deposits in chloroplasts were noticed through electron microscopic examination. It was suggested that mitochondria, chloroplasts and protoplasm might be the direct targets of TPT toxicity. This study confirmed that TPT poisoning on phytoplankton can happen at very low concentrations. There existed different defense mechanisms e.g., antioxidant enzyme activation, starch accumulation and possibly metal sequestration in algal species as the means to resist TPT toxicity.

Royal Jelly Facilitates Restoration of the Cognitive Ability in Trimethyltin‐Intoxicated Mice

Trimethyltin (TMT) is a toxic organotin compound that induces acute neuronal death selectively in the hippocampal dentate gyrus (DG) followed by cognition impairment; however the TMT-injured hippocampal DG itself is reported to regenerate the neuronal cell layer through rapid enhancement of neurogenesis. Neural stem/progenitor cells (NS/NPCs) are present in the adult hippocampal DG, and generate neurons that can function for the cognition ability. Therefore, we investigated whether royal jelly (RJ) stimulates the regenerating processes of the TMT-injured hippocampal DG, and found that orally administered RJ significantly increased the number of DG granule cells and simultaneously improved the cognitive impairment. Furthermore, we have already shown that RJ facilitates neurogenesis of cultured NS/NPCs. These present results, taken together with previous observations, suggest that the orally administered RJ may be a promising avenue for ameliorating neuronal function by regenerating hippocampal granule cells that function in the cognition process.

ChemInform Abstract: Toxicity of Butyltin, Phenyltin, and Inorganic Tin Compounds to Sulfate-Reducing Bacteria Isolated from Anoxic Marine Sediments.

The toxicity of butyltin, phenyltin and inorganic tin compounds to three pure strains of sulfate-reducing bacteria (SRB), isolated from a tributyltin (TBT)-polluted sediment, was determined. The isolated strains were identified as belonging to the genus Desulfovibrio. A new toxicological index (GR25) was developed to assay the toxicity of organotin compounds. Deleterious effects on suspended anaerobic cell cultures were observed for concentrations ranging between 500 and 600 µM for tin tetrachloride, 55 and 260 µM for triorganotins, 30 and 90 µM for diorganotins, and 1 and 6 µM for mono-organotins. Whereas the number of substituents influenced the toxicity of organotins, the type of substituent (butyl or phenyl) proved to have little or no impact. Trisubstituted compounds (tributyl- and triphenyl-tin) were less toxic to these strains of SRB than the monosubstituted forms (monobutyl- and monophenyl-tin). This is the opposite trend to that currently reported for aerobic organisms. Under the given anoxic conditions, the toxicity of organotin compounds obtained yielded a significant negative correlation with the total surface area (TSA) of the tested molecules. Comparison of the TBT toxicity data observed for different microbial groups suggests that the tolerance of bacteria to organotin compounds might be related to organotin–cell wall interactions as well as to aerobic or anaerobic metabolise pathways. Copyright © 2000 John Wiley & Sons, Ltd.

Protein Baggage: Toxicity of Organotin Tied to Proteasome Interference

Vol. 117, No. 3 EnvironewsOpen AccessProtein Baggage: Toxicity of Organotin Tied to Proteasome Interference M. Nathaniel Mead M. Nathaniel Mead Search for more papers by this author Published:1 March 2009https://doi.org/10.1289/ehp.117-a116bCited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Organotins have been widely used as agricultural pesticides, anti-fungal agents, polyvinyl chloride stabilizers, industrial catalysts, and antifouling additives in boat paints. These tin-based chemicals, which have been detected in various environmental media, are lipophilic and thus capable of becoming increasingly concentrated as they pass up the food chain. A new study suggests that the toxic effects of organotins on living cells are mediated in part by inhibiting the function of the proteasome, a molecular structure that degrades unneeded or damaged proteins [EHP 117:379–386; Shi et al.].In eukaryotic organisms (animals, plants, fungi, algae, and plankton), more than 80% of intracellular proteins are degraded through the proteasome-mediated pathway. By interfering with proteasome function, organotins enable proteins to accumulate inappropriately. Because normal immune function and many cellular processes depend on the proteasome pathway, the organotin–proteasome interaction could help explain some of the adverse health effects of organotins—notably endocrine disruption, infertility, and immune dysfunction—that have been observed in wildlife and in animal studies. In addition, human exposure to organotins has been proposed as a possible risk factor for cancer (by inhibiting the cytotoxic function of natural killer cells), neurotoxicity, obesity, allergies, asthma, and altered reproductive development.The researchers provide several lines of evidence suggesting that triphenyltin (TPT), a common organotin, binds to and blocks the activity of the proteasome by irreversibly inhibiting its protein-degrading activity. TPT was shown to have greater potency in this regard than seven other organotins examined by the authors. The investigators deduced that the tin present in TPT interacts with the N-terminal threonine of the proteasomal β5 subunit, possibly providing a specific target for organotins. Organotins have long been known to induce necrosis; the authors propose this may occur through caspase-dependent, DNA damage–independent cell death. In addition, the researchers assert that organotins most likely kill cells via a p53-independent pathway.The new findings suggest that other previously identified potential targets of organotins, such as the transcription factor NFκB and the pro-apoptotic protein Bax, might be downstream of proteasome inhibition. The investigators further posit that inhibition of aromatase activity observed in organotin-exposed humans and animals—an effect linked to altered reproductive development—may be due to proteasome inhibition because such inhibition causes up-regulation of factors that suppress transcription of the hCYP19/aromatase gene.FiguresReferencesRelatedDetailsCited By Pagliarani A, Nesci S and Ventrella V (2013) Toxicity of organotin compounds: Shared and unshared biochemical targets and mechanisms in animal cells, Toxicology in Vitro, 10.1016/j.tiv.2012.12.002, 27:2, (978-990), Online publication date: 1-Mar-2013. Vol. 117, No. 3 March 2009Metrics About Article Metrics Publication History Originally published1 March 2009Published in print1 March 2009 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats

Rutin is a flavonoid with various biological activities that are beneficial to human health. Trimethyltin is a toxic organotin compound, and rats injected with trimethyltin serve as a useful in vivo model for studying spatial memory impairment and neurodegeneration in the hippocampus. The protective effect of rutin against the trimethyltin-induced spatial memory impairment and hippocampal neuron damage in rats was examined. Peroral administration of a single dose of trimethyltin (8.5 mg/kg) induced spatial memory loss and the extensive loss of CA3 pyramidal neurons in hippocampi, as indicated by the results of a Morris water maze task and histologic examination, respectively. Prolonged supplementation of rutin significantly reversed the trimethyltin-induced spatial memory impairment and the damage to pyramidal neurons in the hippocampal CA3b region, indicating an antioxidative effect of rutin. These results suggest that rutin in the diet may provide a protective effect against spatial memory impairment accompanied by hippocampal pyramidal neuron loss.

In(III)-Catalyzed Radical Addition of Alkyl and Aryl Iodides to Acrylates

The utility of radical reactions in organic synthesis is rapidly growing. The formation of the radical from a corresponding alkyl or aryl iodide can be easily achieved using a catalytic amount of indium(III) in the presence of a silane like PhSiH3. Such a radical can be trapped by an electron-deficient alkene, thus providing an elegant method for a new C-C bond formation of a quite broad scope, applicability, and excellent tolerance to functional groups, replacing the classical method using toxic organotin compounds.

Effects of Toxic Organotin Compounds on Bacteria Investigated by Micro‐Raman Spectroscopy

Within the framework of the detection of toxic substances using specific bacteria, the effect of the toxic chemical compound tributyltin chloride (TBT) on the bacterium Escherichia coli TBT3 was investigated using a noninvasive approach based on micro‐Raman spectroscopy. Various cellular densities with optical density (OD) ranging from 1 to 4 and harvested at different growth phases were induced for 1 h with different TBT concentrations: 1, 3, 5, and 10 µM. As an original contribution, the Raman results show that, in these conditions, the vibrational signatures of bacteria were affected by the presence of the toxic TBT compound, mainly in the signal characteristics from carbohydrates and lipids. Hierarchical cluster analysis (HCA) carried out on the Raman data in these regions makes it possible to classify the spectra in three groups according to the TBT concentration, confirming the progressive influence of the chemical pollutant on the bacterium. This work shows the potentiality for the Raman technique on this subject, even though a low detection threshold corresponding with a concentration of 1 µM of TBT was established.

Fate and Toxicity of Organotin Compounds in the Marine Environment

Fate and Toxicity of Organotin Compounds in the Marine Environment