General Information

Mainterm1,4-DIOXANE
CAS Reg.No.(or other ID)123-91-1
Regnum 175.105

From www.fda.gov

Computed Descriptors

Download SDF
2D Structure
CID31275
IUPAC Name1,4-dioxane
InChIInChI=1S/C4H8O2/c1-2-6-4-3-5-1/h1-4H2
InChI KeyRYHBNJHYFVUHQT-UHFFFAOYSA-N
Canonical SMILESC1COCCO1
Molecular FormulaC4H8O2
Wikipediadioxane

From Pubchem


Computed Properties

Property Name Property Value
Molecular Weight88.106
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count0
Complexity26.5
CACTVS Substructure Key Fingerprint A A A D c c B g M A A A A A A A A A A A A A A A A A A A A A A A A A A k A A A A A A A A A A A A A A A A G g A A A A A A A A C g g A I A A A A A B A A A A A A A A A A A A A A A A A A A A A A A A A A B A A A A A A A C A A A A A A A C A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area18.5
Monoisotopic Mass88.052
Exact Mass88.052
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count6
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem


Food Additives Biosynthesis/Degradation


ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9762
Human Intestinal AbsorptionHIA+0.9846
Caco-2 PermeabilityCaco2+0.6406
P-glycoprotein SubstrateNon-substrate0.7055
P-glycoprotein InhibitorNon-inhibitor0.9338
Non-inhibitor0.9807
Renal Organic Cation TransporterNon-inhibitor0.7580
Distribution
Subcellular localizationMitochondria0.5943
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8964
CYP450 2D6 SubstrateNon-substrate0.8272
CYP450 3A4 SubstrateNon-substrate0.7651
CYP450 1A2 InhibitorNon-inhibitor0.8674
CYP450 2C9 InhibitorNon-inhibitor0.8987
CYP450 2D6 InhibitorNon-inhibitor0.9587
CYP450 2C19 InhibitorNon-inhibitor0.8661
CYP450 3A4 InhibitorNon-inhibitor0.9820
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9459
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.7094
Non-inhibitor0.9431
AMES ToxicityNon AMES toxic0.9133
CarcinogensNon-carcinogens0.8754
Fish ToxicityLow FHMT0.9669
Tetrahymena Pyriformis ToxicityHigh TPT0.5096
Honey Bee ToxicityHigh HBT0.5908
BiodegradationNot ready biodegradable0.7770
Acute Oral ToxicityIII0.8787
Carcinogenicity (Three-class)Warning0.5245

From admetSAR


ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility-0.3519LogS
Caco-2 Permeability1.6250LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity1.3531LD50, mol/kg
Fish Toxicity3.8877pLC50, mg/L
Tetrahymena Pyriformis Toxicity-1.0830pIGC50, ug/L

From admetSAR


Toxicity Profile

Route of ExposureOral ; inhalation ; dermal
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.
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.
Toxicity ValuesLD50: 1550 mg/kg (Intravenous, Rabbit) LD50: 4350 mg/kg (Subcutaneous, Mouse) LD50: >8300 mg/kg (Dermal, Rabbit) LD50: 2100 mg/kg (Oral, Dog) LD50: 799 mg/kg (Intraperitoneal, Rat) LC50: 46 g/m3 over 2 hours (Inhalation, Rat)
Lethal Dose470 ppm for an adult human.
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans.
Minimum Risk LevelNone
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. (L1189)
TreatmentNone
Reference
  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 ]

From T3DB


Taxonomic Classification

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassDioxanes
Subclass1,4-dioxanes
Intermediate Tree NodesNot available
Direct Parent1,4-dioxanes
Alternative Parents
Molecular FrameworkAliphatic heteromonocyclic compounds
SubstituentsPara-dioxane - Oxacycle - Ether - Dialkyl ether - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aliphatic heteromonocyclic compound
DescriptionThis compound 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.

From ClassyFire


Targets

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. 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 ]
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. 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 ]
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. 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 ]
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 ]

From T3DB