1,4-Dioxane (T3D0210)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-03-06 18:58:17 UTC
Update Date2014-12-24 20:21:20 UTC
Accession NumberT3D0210
Identification
Common Name1,4-Dioxane
ClassSmall Molecule
Description1,4-Dioxane (commonly referred to as simply ‘dioxane’) is used as a solvent in the manufacture of other chemicals and as a laboratory reagent. It is a trace contaminant of some chemicals used in cosmetics, detergents, and shampoos. (7)
Compound Type
  • Cosmetic Toxin
  • Ether
  • Household Toxin
  • Industrial/Workplace Toxin
  • Lachrymator
  • Organic Compound
  • Pollutant
  • Solvent
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1, 4-Diethylene dioxide
1,4 Dioxane
1,4-DIethylene dioxide
1,4-Diethylenedioxide
1,4-Diethyleneoxide
1,4-Dioxacyclohexane
1,4-Dioxan
Di(ethylene oxide)
Diethylene dioxide
Diethylene ether
Diethylene oxide
Dioxan
Dioxan-1,4
Dioxane
Dioxane-1,4
Dioxyethylene ether
Glycol ethylene ether
P-dioxane
Para-dioxane
Tetrahydro-1,4-dioxin
Tetrahydro-p-dioxin
Tetrahydro-para-dioxin
Chemical FormulaC4H8O2
Average Molecular Mass88.105 g/mol
Monoisotopic Mass88.052 g/mol
CAS Registry Number123-91-1
IUPAC Name1,4-dioxane
Traditional Namedioxane
SMILESC1COCCO1
InChI IdentifierInChI=1S/C4H8O2/c1-2-6-4-3-5-1/h1-4H2
InChI KeyInChIKey=RYHBNJHYFVUHQT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,4-dioxanes. These are organic compounds containing 1,4-dioxane, an aliphatic six-member ring with two oxygen atoms in ring positions 1 and 4.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDioxanes
Sub Class1,4-dioxanes
Direct Parent1,4-dioxanes
Alternative Parents
Substituents
  • Para-dioxane
  • Oxacycle
  • Ether
  • Dialkyl ether
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
Appearance1,4-Dioxane is a colorless volatile liquid with a faint pleasant odor and mixes easily with water. (7)
Experimental Properties
PropertyValue
Melting Point11.8°C
Boiling Point101.1 °C
Solubility1000 mg/mL at 20 °C [RIDDICK,JA et al. (1986)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility283 g/LALOGPS
logP-0.23ALOGPS
logP-0.094ChemAxon
logS0.51ALOGPS
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity22.09 m³·mol⁻¹ChemAxon
Polarizability8.97 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0570-9000000000-fdad6aa284c3554c651b2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-056u-9000000000-ecaeff4720923991aaf72021-09-24View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-7416375fa93c0232c2a52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9000000000-cde6a647139e5c454cde2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9000000000-5654a8542422e5b264442016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052o-9000000000-65decf9e96649a33752e2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06rf-9000000000-0632a2171f1de13ca2402021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-06f5fc3dedd188a15fe92021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-a45455298eba19de60ad2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-9000000000-77a0261c34ff328faf532016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-08fu-9000000000-f3d10a4316418b32ed1d2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-9000000000-1cd14a6c0dba761ba7262021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4m-9000000000-633cab61fb801edbb6522021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052g-9000000000-4a133ce242a34983b4d02021-10-12View Spectrum
MSMass Spectrum (Electron Ionization)splash10-004i-9000000000-fabd529b7bd7382fe0952014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 15.09 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-12View Spectrum
Toxicity Profile
Route of ExposureOral (7) ; inhalation (7) ; dermal (7)
Mechanism of ToxicityThough the mechanism of toxicity of 1,4-dioxane has not yet been elucidated, it is known that its carcinogenic effects are caused by a non-genotoxic mechanism that is most likely cytotoxic in nature. (7, 9)
MetabolismExposure to 1,4-dioxane may occur by inhalation, ingestion, and to a lesser extent by dermal contact. 1,4-Dioxane is quickly absorbed and metabolized to beta-hydroxyethoxyacetic acid (HEAA) by mixed-function oxidase enzymes. HEAA can then be converted to 1,4-dioxane-2-one under acidic conditions. Both of these products are rapidly and extensively eliminated in the urine (>95%). Unchanged 1,4-dioxane can also be excreted in the urine and in exhaled air, but mainly after high-dose exposure. (7)
Toxicity ValuesLD50: 1550 mg/kg (Intravenous, Rabbit) (1) LD50: 4350 mg/kg (Subcutaneous, Mouse) (1) LD50: >8300 mg/kg (Dermal, Rabbit) (1) LD50: 2100 mg/kg (Oral, Dog) (1) LD50: 799 mg/kg (Intraperitoneal, Rat) (3) LC50: 46 g/m3 over 2 hours (Inhalation, Rat) (1)
Lethal Dose470 ppm for an adult human. (2)
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (6)
Uses/Sources1,4-Dioxane is primarily used in solvent applications for the manufacturing sector; however, it is also found in fumigants and automotive coolant. 1,4-Dioxane is a byproduct of the ethoxylation process in cosmetics manufacturing, thus many products on the market today contain 1,4-dioxane in very small amounts. However, some cosmetics, detergents, and shampoos may contain 1,4-dioxane at levels higher than recommended by the FDA for other products. 1,4-Dioxane can also be found in tap water, so human exposure to 1,4-dioxane may also occur during activities such as showering, bathing, and laundering. (7, 8)
Minimum Risk LevelNot Available
Health Effects1,4-Dioxane for short period of time cause eye and nose irritation at low levels, and severe kidney and liver effects and possibly death at very high levels. For long-term exposure, studies in animals have shown that breathing vapors of 1,4-dioxane, swallowing liquid 1,4-dioxane or contaminated drinking water, or having skin contact with liquid 1,4-dioxane affects mainly the liver and kidneys. Studies in workers did not indicate whether 1,4-dioxane causes cancer, but animal studies suggest that it is a probable human carcinogen. (7)
Symptoms1,4-Dioxane causes eye and respiratory tract irritation. (8)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03316
HMDB IDNot Available
PubChem Compound ID31275
ChEMBL IDCHEMBL453716
ChemSpider ID29015
KEGG IDC14440
UniProt IDNot Available
OMIM ID
ChEBI ID47032
BioCyc IDNot Available
CTD IDC025223
Stitch ID1,4-Dioxane
PDB IDNot Available
ACToR ID541
Wikipedia Link1,4-Dioxane
References
Synthesis ReferenceNot Available
MSDST3D0210.pdf
General References
  1. Fukuoka T, Johnston DA, Winslow CA, de Groot MJ, Burt C, Hitchcock CA, Filler SG: Genetic basis for differential activities of fluconazole and voriconazole against Candida krusei. Antimicrob Agents Chemother. 2003 Apr;47(4):1213-9. [12654649 ]
  2. Bellamine A, Lepesheva GI, Waterman MR: Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J Lipid Res. 2004 Nov;45(11):2000-7. Epub 2004 Aug 16. [15314102 ]
  3. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  4. European Chemicals Bureau (2000). IUCLID Dataset, 1,4-DIoxane (123-91-1) (2000 CD-ROM edition).
  5. Sullivan JB and Krieger GR (eds) (1999). Clinical Environmental Health and Toxic Exposures. Second edition. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins.
  6. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  7. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for 1,4-dioxane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. Wikipedia. 1,4-Dioxane. Last Updated 26 July 2009. [Link]
  9. Institute for Health and Consumer Protection, ECB (2002). EU Risk Assessment Final Report: 1,4-Dioxane. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Epsin-1
General Function:
Lipid binding
Specific Function:
Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis.
Gene Name:
EPN1
Uniprot ID:
Q9Y6I3
Molecular Weight:
60292.655 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Target Details
2. Transforming growth factor beta-3
General Function:
Type iii transforming growth factor beta receptor binding
Specific Function:
Involved in embryogenesis and cell differentiation.
Gene Name:
TGFB3
Uniprot ID:
P10600
Molecular Weight:
47327.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Target Details
3. Tumor necrosis factor ligand superfamily member 13B
General Function:
Receptor binding
Specific Function:
Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.Isoform 2 seems to inhibit isoform 1 secretion and bioactivity.Isoform 3: Acts as a transcription factor for its own parent gene, in association with NF-kappa-B p50 subunit, at least in autoimmune and proliferative B-cell diseases. The presence of Delta4BAFF is essential for soluble BAFF release by IFNG/IFN-gamma-stimulated monocytes and for B-cell survival. It can directly or indirectly regulate the differential expression of a large number of genes involved in the innate immune response and the regulation of apoptosis.
Gene Name:
TNFSF13B
Uniprot ID:
Q9Y275
Molecular Weight:
31222.48 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
4. Transient receptor potential cation channel subfamily A member 1
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]