Tributyltin Chloride Research Articles

Determination of tributyltin and 4-hydroxybutyldibutyltin chlorides in seawater by liquid chromatography with atmospheric pressure chemical ionization-mass spectrometry

A liquid chromatographic method is described for the simultaneous determination of tributyltin (TBT) and the hydroxylated intermediate 4-hydroxybutyldibutyltin (OHBuDBT). Separation was achieved in reverse phase mode on a cyanopropyl-bonded silica column under a gradient elution. Various organic solvents and additives were tested and the optimum composition of the mobile phase contained methanol, water, formic acid and tropolone as a complexing agent. Butyltin compounds were detected with an ion trap mass spectrometer interfaced to a liquid chromatograph with an atmospheric pressure chemical ionization source (LC–APCI-MS). Identification and fragmentation pattern of OHBuDBT chloride in full scan MS and MS/MS are reported for the first time using LC–APCI-MS. Gas chromatography–mass spectrometry (GC–MS) spectrum of the same compound is also reported for the first time for comparison purpose. This method allowed limits of detection (LOD) of 35 and 26 ng mL −1 for TBT and OHBuDBT, respectively, based on successive injections of 10 μL of blank seawater extract. A liquid–liquid extraction procedure using n-hexane–ethyl acetate was developed for the simultaneous analysis of TBT and OHBuDBT chlorides in natural seawater and allowed average recoveries from 72 to 96% for the two compounds at three different spiking levels.

Down-Regulation ofmdr1bmRNA Expression in the Kidneys of Mice Following Maternal Exposure to Tributyltin Chloride

We investigated the change in renal mdr1b mRNA expression in offspring exposed to tributyltin chloride (TBTC) via the placenta and lactation or via lactation, using the real-time reverse transcription-polymerase chain reaction. Pregnant ICR mice were given water containing TBTC (0, 15, and 50 microg/ml) ad libitum from the start of pregnancy to weaning or from parturition to weaning. Exposure via the placenta and lactation significantly reduced the renal mdr1b level in offspring. Exposure to TBTC through the mother might impair the exclusion system of toxic compounds in offspring.

Effects of sublethal levels of tributyltin chloride on a new toxicity test organism, Liza saliens (osteichthyes, mugilidae): a histological study

AbstractThe histopathological effects of 10−7 and 10−9 M tributyltin(IV)chloride,TBTCl, solutions on different Liza saliens organs have been studied by light microscope. The fish were sacrificed after 3–4 h incubation in 10−7 M TBTCl solution or after 15 days incubation in 10−9 M solution. The observed histopathological changes were dose‐ and time‐dependent. The 10−7 M TBTCl concentration resulted in major damage to the gill epithelium, indicating that TBTCl primarily interfered with the respiration, osmoregulation, acid balance and nitrogenous waste excretion processes. After incubation in 10−9 M TBTCl solution the fish lived 20 or more days, but many of the organs were altered. Thymus atrophy, reduced spleen and altered head kidney were observed. These histological results indicated that TBTCl interfered with organ immunodefense and altered main metabolic pathways in Liza saliens. The presence of melano‐macrophage centers, only in TBT‐treated liver and spleen, can be considered a tool to facilitate, with other biomarkers, the detection of alterations by toxicants. Regarding the pancreas activity in 10−7 M solutions, it has been noted that, in the exocrine cells, very few zymogen granules were still present and the Langerhans islets were more altered. In 10−9M solution the exocrine pancreatic cells had no granules and the islet cells presented degenerative alterations. In addition, TBTCl, which altered the pancreas and gonad morphology, could again be considered an endocrine disrupter even if biochemical data are still necessary. Finally, the Liza saliens juveniles could be considered an interesting biological model for experiments with contaminants, due to their ease of adaptation to experimental conditions and food chain position. Copyright © 2005 John Wiley & Sons, Ltd.

Can mono- or di-butyltin chlorides produce tributyltin chloride at elevated temperatures? Implications for applications in chemical vapour deposition

The thermolysis of the butyltin chlorides at 200–300 °C in the liquid phase has been investigated by 1H, 13C, and 119Sn NMR spectroscopy. The stabilities follow the order: Bu 2SnCl 2 > Bu 3SnCl > BuSnCl 3. Only tributyltin chloride showed any evidence of redistribution, giving dibutyltin dichloride, together with metallic tin, butane, and but-1-ene, which would be formed by decomposition of tetrabutyltin. Dibutyltin dichloride decomposed to give mainly butane with no other apparent liquid organotin compound. Butyltin trichloride gave butane, some butene, and metallic tin, and showed no evidence of forming tributyltin chloride by the redistribution reaction, which would have environmental implications for its use in the CVD coating of glass.

Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling

Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

Endocrine-disrupting chemicals (EDC) are ubiquitous in environment and may have various undesirable effects on human health. In the present study, we have shown that some EDC [benzophenone, p-octylphenol, and tributyltin chloride (TBT)] promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4+ T cells primed with anti-CD3 and splenic antigen-presenting cells (APC). The effect was indicated to be indirect via suppression of IL-12 production and augmentation of IL-10 production of APC, which are critical for the Th1 and Th2 development, respectively. Such modulation of cytokine production by EDC was associated with reduction of intracellular glutathione levels in APC. IL-10 deprivation or the addition of N-acetylcysteine, which replenishes intracellular glutathione level during priming, cancelled the effect of EDC on the promotion of Th2 polarization. Oral administration of TBT, which most effectively promoted Th2 polarization in vitro, exacerbated airway inflammation in a murine model of allergic asthma with concomitant enhancement of Th2-type immunity. Collectively these results suggest that EDC such as benzophenone, p-octylphenol, and TBT promote Th2 polarization indirectly via the depletion of glutathione in APC and subsequent modulation of IL-10 and IL-12 production that might result in the exacerbation of allergic diseases.

1‐Bromo‐1‐lithioethene: A Practical Reagent in Organic Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates

Dietary and xenobiotic compounds can disrupt endocrine signaling, particularly of steroid receptors and sexual differentiation. Evidence is also mounting that implicates environmental agents in the growing epidemic of obesity. Despite a long-standing interest in such compounds, their identity has remained elusive. Here we show that the persistent and ubiquitous environmental contaminant, tributyltin chloride (TBT), induces the differentiation of adipocytes in vitro and increases adipose mass in vivo. TBT is a dual, nanomolar affinity ligand for both the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor gamma (PPARgamma). TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumulation in adipose depots, liver, and testis of neonate mice and results in increased epididymal adipose mass in adults. In the amphibian Xenopus laevis, ectopic adipocytes form in and around gonadal tissues after organotin, RXR, or PPARgamma ligand exposure. TBT represents, to our knowledge, the first example of an environmental endocrine disrupter that promotes adipogenesis through RXR and PPARgamma activation. Developmental or chronic lifetime exposure to organotins may therefore act as a chemical stressor for obesity and related disorders.

The Influence of Tributyltin Chloride and Polychlorinated Biphenyls on Swimming Behavior, Body Growth, Reproduction, and Activity of Biotransformation Enzymes in Daphnia magna

ABSTRACT Exposure to tributyltin chloride (TBT) at 7.1 μg L−1 or polychlorinated biphenyls (PCB) at 1.5 μg L−1 significantly affected Daphnia magna causing rapid decreases in mean swimming activity and a change in the preferred swimming depth. Lower exposure concentrations (0.1 μg L−1 TBT or 0.1 μg L−1 PCB) did not significantly alter swimming behavior. Exposure to medium and high TBT concentrations (0.1 μg L−1 and 7.1 μg L−1) caused a decrease in body growth and decreased the number of newborn daphnids. PCB exposure at 1.5 μg L−1 and 12 μg L−1 did not affect reproduction or body growth of the animals. The lowest exposure levels (0.1 μg L−1 PCB or 0.02 μg L−1 TBT) did not alter any behavioral or ecophysiological parameter of the daphnids. Exposure to PCB as high as 15 μg L−1 or TBT as high as 6.6 μg L−1 had no effect on daphnid glutathione-S-transferase and glutathione-peroxidase activity.

Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.

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 (Pb 2+), 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 μg g −1), Pb 2+ (21 μg g −1), and TBT (0.3 μg 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 Pb 2+ 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.

1P533 Mechanism of Inhibition of the V-type Molecular Motor by Tributyltin Chloride(26. Single molecule biophysics,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

1P533 Mechanism of Inhibition of the V-type Molecular Motor by Tributyltin Chloride(26. Single molecule biophysics,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

Microbial transformation of tributyltin chloride by Pseudomonas aeruginosa strain USS25 NCIM‐5224

AbstractA bacterial isolate capable of utilizing tributyltin chloride (TBTC) as sole source of carbon was isolated from marine water samples. The isolate, producing a soluble green pigment, was identified as Pseudomonas aeruginosa strain USS25 NCIM‐5224. The isolate showed maximum growth with 2 mM of TBTC in mineral salt medium. Time course results showed complete elimination of TBTC after 75 days of incubation. During the growth on TBTC, a product (280 mg) was found to accumulate, which was extracted with chloroform and detected on thin‐layer chromatography. Based on the IR, NMR spectra and GC‐MS analysis, the isolated product was identified as monobutyltin dichloro hydride. Copyright © 2005 John Wiley & Sons, Ltd.

1-Bromo-1-lithioethene: A Practical Reagent in Organic Synthesis

[reaction: see text] A reliable preparative scale synthesis of 1-bromo-1-lithioethene is reported. This reagent undergoes clean 1,2-addition with a range of aldehydes and ketones at -110 degrees C to afford the corresponding 2-bromo-1-alken-3-ols in moderate to excellent yield. Trapping with other electrophiles (acylsilanes, chlorosilanes, tributyltin chloride, iodine) cleanly provides practically useful yields of various 1-substituted 1-bromoethene products. Unexpectedly high diastereoselectivities were observed during the addition of 1-bromo-1-lithioethene to alpha-siloxy aldehydes (typically 10:1, Felkin-Ahn control) and protected ketopyranose and ketofuranose sugars (> or = 10:1, addition from the less-hindered face). The title organolithium reagent possesses relatively low basicity at low temperature, and is compatible with a variety of common protecting groups. We believe that these unusual properties of 1-bromo-1-lithioethene may originate from the specific crystalline structure of the reagent in which lithium is coordinatively saturated and thus unavailable for chelation.

Effect of tributyltin compound onN-methyl-D-aspartate (NMDA) receptors in brain of preweanling mice

The aim of this study was to investigate the effect of tributyltin (TBT) compound onN-methyl-D: -aspartate (NMDA) receptors in the brains of preweanling mice. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, and 50 ppm in water. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. Mouse brain membranes were prepared from cerebral cortices, and the specific binding of [(3)H]MK-801 to an NMDA receptor was determined by radioligand binding assay. The mean body weight of preweanling mice of the 50 ppm dose group decreased by 17-25% (p<0.01) at 1, 2 and 3 weeks of age, compared with that of preweanling mice of the corresponding control group. The [(3)H]MK-801 binding level significantly decreased (p<0.05) in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group. The exposure to TBT via placenta and dam's milk seriously affected not only the growth of preweanling mice, but also the F1 cerebral NMDA receptors involved in memory and learning.

Butyltin accumulation in the marine clam Mya arenaria: An evaluation of its suitability for monitoring butyltin pollution

The use of Mya arenaria as a new sensitive biomonitor of butyltins pollution in the oceanic system was investigated. Field survey indicated that much higher levels of butyltin compounds were found in M. arenaria compared with the other species investigated. Using Mytilus edulis as a control organism, a 28 days exposure of tributyltin chloride (TBT) to M. arenaria for accumulation and subsequent 28 days breeding in clean seawater for elimination were conducted under laboratory conditions in order to confirm its high accumulation ability and characterize its kinetic behavior to TBT. Bioconcentration factor (BCF) of M. arenaria ranged from 15 538 to 91 800 after 28 days exposure. The rapid uptake and low rate to eliminate TBT of M. arenaria displayed first-order kinetics. M. arenaria shows potential as a new bioindicator to monitor TBT pollution in marine environment.

Fluorinated Stannanes. Part 2. The Stereospecific Synthesis of Fluorinated Stannanes via a Barbier‐Type Reaction Between Fluorinated Halides and Tributyltin Chloride Mediated by Zinc or Cadmium.

Abstract Fluorinated stannanes are valuable synthons in synthetic organofluorine chemistry. Fluorinated vinyl, alkyl and aryl halides reacted efficiently with tri- n -butyltin chloride in the presence of zinc or cadmium to yield the corresponding stannanes in good yields. In some cases, yield of the stannanes showed a dramatic improvement over the transmetalation method. In all other cases, comparable yields were obtained.

Synthesis and Characterization of O-Alkyl, O-Cycloalkyl and O-Aryl Trithiophosphato Derivatives of Trimethyl Tin(IV) Chloride and Tributyl Tin(IV) Chloride

Trimethyltin(IV)trithiophosphates[(RO)P(S)S2][Sn(Me)3]2 and tributyl tin(IV)trithiophosphates [(RO)P(S)S2][Sn(Bu)3]2 (R=CH3, –C2H5, –C3H7, –C3H7 iso –C4Hn 9, –C4H9 iso, –C4H5 scc, –C5H11 iso C6H11, –C6H5) were prepared in methanolic solution of R3SnCl and dipotassium salt of trithiophosphates in 2:1 molar ratio. These newly synthesised derivatives have been characterized by elemental analysis, molecular weight measurements, IR, 13C, 31P, and 119Sn,NMR spectral studies. Coordination number of four suggested for tin(IV) in these derivatives.

Acceleration of tributyltin chloride (TBT) degradation in liquid cultures of the filamentous fungus Cunninghamella elegans

In this study, we have examined the effects of synthetic medium ingredients and culture incubation conditions on growth and tributyltin chloride (TBT) degradation activity of the fungus Cunninghamella elegans. The best efficiency of TBT conversion to less toxic derivatives: dibutyltin and monobutyltin was noticed on media which contained glucose, NH 4Cl, K 2HPO 4 and MgSO 4. Next, the constructed M3 medium (with the above components) ensured vigorous growth of C. elegans and allowed the reduction of 80% of the initial TBT content (10 mg l −1), after 3 d of biodegradation. The further acceleration of the biocide utilization by C. elegans was achieved by additional oxygen supply (pO 2 ⩾ 20%) to the growing fungus (89% after 2 d of incubation in the BioFlo II bioreactor). The efficient xenobiotic biodegradation was related to the intensity of fungal growth. The obtained results suggest a cometabolic nature of TBT utilization by C. elegans.

Trialkyltin Compounds Bind Retinoid X Receptor to Alter Human Placental Endocrine Functions

Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple roles in mammalian development and homeostasis. We previously reported that, in human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide, which are typical environmental contaminants and cause masculinization in female mollusks, are potent stimulators of human chorionic gonadotropin production and aromatase activity, which play key endocrine functions in maintaining pregnancy and fetal development. However, the molecular mechanism through which these compounds stimulate these endocrine functions remains unclear. Our current study shows that trialkyltin compounds, including tributyltin chloride and triphenyltin hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand-binding domain of RXR with high affinity and function as transcriptional activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of trialkyltins is RXR specific and does not activate the retinoic acid receptor pathway. In addition, trialkyltins activate RXR to stimulate the expression of a luciferase reporter gene containing the human placental promoter I.1 sequence of aromatase, suggesting that trialkyltins stimulate human placental endocrine functions through RXR-dependent signaling pathways. Therefore, our results suggest that activation of RXR may be a novel mechanism by which trialkyltins alter human endocrine functions.