Tmic
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Record Information
Version2.0
Creation Date2009-06-19 21:58:30 UTC
Update Date2014-12-24 20:23:29 UTC
Accession NumberT3D1249
Identification
Common NameBis(tributyltin) oxide
ClassSmall Molecule
DescriptionBis(tributyltin) oxide is an organotin compound. Tributyltins are the main active ingredients in certain biocides used to control a broad spectrum of organisms, and are also used in wood preservation, marine paints (as antifouling pesticides), and textiles and industrial water systems (as antifungal agents). They also considered moderately to highly persistent organic pollutants and are especially hazardous to marine ecosystems. The main toxic component of tributyltins is tin. Tin is a chemical element with the symbol Sn and atomic number 50. It is a natural component of the earth's crust and is obtained chiefly from the mineral cassiterite, where it occurs as tin dioxide. (4, 6, 5)
Compound Type
  • Household Toxin
  • Industrial/Workplace Toxin
  • Organic Compound
  • Organometallic
  • Pesticide
  • Pollutant
  • Synthetic Compound
  • Tin Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,1,1,3,3,3-Hexabutyldistannoxane
Bis(tri-n-butyl tin)oxide
Bis(tri-n-butyltin) oxide
Bis(tri-n-butyltin)oxide
Bis(tributyl tin)oxide
Bis(tributyloxide) of tin
Bis(tributylstannium) oxide
Bis(tributylstannyl)oxide
Bis(tributyltin)oxide
Bis[tri-n-butyltin(IV)]oxide
Hexabutyl distannoxane
Hexabutylditin
Oxybis(tributylstannane)
Oxybis(tributyltin)
Oxybis[tributyltin]
Oxyde de tributyletain
Stannane, tri-n-butyl-, oxide
TBTO
Tin, bis(tributyl)-, oxide
Tri-n-butyltin oxide
Tributyltin oxide
Tributyltin(IV) oxide
Chemical FormulaC24H54OSn2
Average Molecular Mass596.100 g/mol
Monoisotopic Mass598.222 g/mol
CAS Registry Number56-35-9
IUPAC Nametributyl[(tributylstannyl)oxy]stannane
Traditional Namebiomet
SMILESCCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC
InChI IdentifierInChI=1S/6C4H9.O.2Sn/c6*1-3-4-2;;;/h6*1,3-4H2,2H3;;;
InChI KeyInChIKey=APQHKWPGGHMYKJ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as trialkyltins. These are triorganotin compounds where the tin atom is linked to exactly three alkyl groups.
KingdomOrganic compounds
Super ClassOrganometallic compounds
ClassOrgano-post-transition metal compounds
Sub ClassOrganotin compounds
Direct ParentTrialkyltins
Alternative Parents
Substituents
  • Trialkyltin
  • Organic metal salt
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic tin salt
  • Organic salt
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceYellow oil.
Experimental Properties
PropertyValue
Melting Point-45°C
Boiling PointNot Available
Solubility0.0195 mg/mL [BLUNDEN,SJ et al. (1984)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0011 g/LALOGPS
logP9.72ALOGPS
logP8.06ChemAxon
logS-5.7ALOGPS
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 ŲChemAxon
Rotatable Bond Count20ChemAxon
Refractivity119.11 m³·mol⁻¹ChemAxon
Polarizability54.75 ųChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot AvailableView in JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot AvailableView in JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot AvailableView in JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot AvailableView in JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot AvailableView in JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot AvailableView in JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-003i-2595760000-a99a23a527886cf4753eView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral (5) ; inhalation (5) ; dermal (5)
Mechanism of ToxicityOrganotin compounds produce neurotoxic and immunotoxic effects. Organotins may directly activate glial cells contributing to neuronal cell degeneration by local release of pro-inflammatory cytokines, tumor necrosis factor-_, and/or interleukins. They may also induce apoptosis by direct action on neuronal cells. Organotin compounds stimulate the neuronal release of and/or decrease of neuronal cell uptake of neurotransmitters in brain tissue, including aspartate, GABA, glutamate, norepinephrine, and serotonin. This may be either a contributing factor to or result of the neuronal cell loss. The immunotoxic effects of organotins are characterized by thymic atrophy caused by the suppression of proliferation of immature thymocytes and apoptosis of mature thymocytes. Organotin compounds are believed to exert these effects by suppressing DNA and protein synthesis, inducing the expression of genes involved in apoptosis (such as nur77), and disrupting the regulation of intracellular calcium levels, giving rise to the uncontrolled production of reactive oxygen species, release of cytochrome c to the cytosol, and the proteolytic and nucleolytic cascade of apoptosis. The suppression of proliferation of immature thymocytes further results in the suppression of T-cell-mediated immune responses. Organotins are also endocrine disruptors and are believed to contribute to obesity by inappropriate receptor activation, leading to adipocyte differentiation. Inorganic tin triggers eryptosis, contributing to tin-induced anemia. (5, 1, 2)
MetabolismThough tin metal is very poorly absorbed, tin compounds may be absorbed via oral, inhalation, or dermal routes, with organotin compounds being much more readily absorbed than inorganic tin compounds. Tin may enter the bloodstream and bind to hemoglobin, where it is distributed and accumulates mainly in the kidney, liver, lung, and bone. Organotin compounds may undergo dealkylation, hydroxylation, dearylation, and oxidation catalyzed by cytochrome P-450 enzymes in the liver. The alkyl products of dealkylation are conjugated with glutathione and further metabolized to mercapturic acid derivatives. Tin and its metabolites are excreted mainly in the urine and feces. (5)
Toxicity ValuesLD50: 7210 ug/kg (Intraperitoneal, Rat) (3) LD50: 11 700 mg/kg (Subcutaneous, Rat) (3) LD50: 55 mg/kg (Oral, Mouse) (3) LD50: 6 mg/kg (Intravenous, Mouse) (3) LD50: 900 mg/kg (Dermal, Rabbit) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesTributyltins are the main active ingredients in certain biocides used to control a broad spectrum of organisms, and are also used in wood preservation, marine paints (as antifouling pesticides), and textiles and industrial water systems (as antifungal agents). (4)
Minimum Risk LevelNot Available
Health EffectsBreathing or swallowing, or skin contact with organotins, can interfere with the way the brain and nervous system work, causing death in severe cases. Organic tin compounds may also damage the immune and reproductive system. (4, 5)
SymptomsInorganic or organic tin compounds placed on the skin or in the eyes can produce skin and eye irritation. (5)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID16682746
ChEMBL IDNot Available
ChemSpider ID10218152
KEGG IDC18149
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDC005961
Stitch IDBis(tributyltin) oxide
PDB IDNot Available
ACToR ID167
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1249.pdf
General References
  1. Nguyen TT, Foller M, Lang F: Tin triggers suicidal death of erythrocytes. J Appl Toxicol. 2009 Jan;29(1):79-83. doi: 10.1002/jat.1390. [18937211 ]
  2. Grun F, Blumberg B: Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006 Jun;147(6 Suppl):S50-5. Epub 2006 May 11. [16690801 ]
  3. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  4. Wikipedia. Tributyltin. Last Updated 31 May 2009. [Link]
  5. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for tin. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  6. Wikipedia. Tin. Last Updated 28 May 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Grun F, Blumberg B: Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006 Jun;147(6 Suppl):S50-5. Epub 2006 May 11. [16690801 ]
General Function:
Threonine-type endopeptidase activity
Specific Function:
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This unit is responsible of the chymotrypsin-like activity of the proteasome and is one of the principal target of the proteasome inhibitor bortezomib. May catalyze basal processing of intracellular antigens. Plays a role in the protection against oxidative damage through the Nrf2-ARE pathway (By similarity).
Gene Name:
PSMB5
Uniprot ID:
P28074
Molecular Weight:
28480.01 Da
References
  1. Shi G, Chen D, Zhai G, Chen MS, Cui QC, Zhou Q, He B, Dou QP, Jiang G: The proteasome is a molecular target of environmental toxic organotins. Environ Health Perspect. 2009 Mar;117(3):379-86. doi: 10.1289/ehp.11865. Epub 2008 Oct 23. [19337512 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
References
  1. Grun F, Blumberg B: Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006 Jun;147(6 Suppl):S50-5. Epub 2006 May 11. [16690801 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50488.63 Da
References
  1. Grun F, Blumberg B: Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006 Jun;147(6 Suppl):S50-5. Epub 2006 May 11. [16690801 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
References
  1. Grun F, Blumberg B: Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006 Jun;147(6 Suppl):S50-5. Epub 2006 May 11. [16690801 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Gene Name:
TXNRD1
Uniprot ID:
Q16881
Molecular Weight:
70905.58 Da
References
  1. Bragadin M, Scutari G, Folda A, Bindoli A, Rigobello MP: Effect of metal complexes on thioredoxin reductase and the regulation of mitochondrial permeability conditions. Ann N Y Acad Sci. 2004 Dec;1030:348-54. [15659816 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
Gene Name:
TXNRD2
Uniprot ID:
Q9NNW7
Molecular Weight:
56506.275 Da
References
  1. Bragadin M, Scutari G, Folda A, Bindoli A, Rigobello MP: Effect of metal complexes on thioredoxin reductase and the regulation of mitochondrial permeability conditions. Ann N Y Acad Sci. 2004 Dec;1030:348-54. [15659816 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity).
Gene Name:
TXNRD3
Uniprot ID:
Q86VQ6
Molecular Weight:
70682.52 Da
References
  1. Bragadin M, Scutari G, Folda A, Bindoli A, Rigobello MP: Effect of metal complexes on thioredoxin reductase and the regulation of mitochondrial permeability conditions. Ann N Y Acad Sci. 2004 Dec;1030:348-54. [15659816 ]