You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2006-08-13 19:29:25 UTC
Update Date2016-02-11 01:06:44 UTC
HMDB IDHMDB04472
Secondary Accession Numbers
  • HMDB02267
Metabolite Identification
Common NameEucalyptol
DescriptionEucalyptol is an organic compound which is a colorless liquid. It is a cyclic ether and a monoterpene. Eucalyptol is a natural constituent of a number of aromatic plants and their essential oil fraction. Eucalyptol was given GRAS (Generally Recognized As Safe) status by the Flavor and Extract Manufacturer's Association FEMA, 1965 and is approved by the Food and Drug Administration for food use. 1,8-Dihydroxy-10-carboxy-p-menthane, 2-hydroxy-cineole and 3-hydroxy-cineole are the main metabolites of Eucalyptol. Toxicological data available on eucalyptol are rather limited. Following the accidental exposure of human beings, death was reported in two cases after ingestion of 3.5-5 ml of essential eucalyptus oil, but a number of recoveries have also been described for much higher amounts of oil. In a 1994 report released by five top cigarette companies, eucalyptol was listed as one of the 599 additives to cigarettes. It is added to improve the flavor. (PMID: 12048025 , Fitoterapia. 2002 Jun;73(3):269-75).
Structure
Thumb
Synonyms
ValueSource
1,8-CineolKegg
EucalyptolKegg
CineoleKegg
1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octaneHMDB
1,8-CineoleHMDB
1,8-Epoxy-P-menthaneHMDB
1,8-oxido-P-MenthaneHMDB
2-Oxa-1,3,3-trimethylbicyclo[2.2.2]octaneHMDB
CajeputolHMDB
CINEOLHMDB
CNLHMDB
CucalyptolHMDB
EucalyptoleHMDB
EucapurHMDB
EukalyptolHMDB
Limonene oxideHMDB
P-CineoleHMDB
TerpanHMDB
Zedoary oilHMDB
ZineolHMDB
Chemical FormulaC10H18O
Average Molecular Weight154.2493
Monoisotopic Molecular Weight154.135765198
IUPAC Name1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
Traditional Nameeucalyptol
CAS Registry Number470-82-6
SMILES
CC12CCC(CC1)C(C)(C)O2
InChI Identifier
InChI=1S/C10H18O/c1-9(2)8-4-6-10(3,11-9)7-5-8/h8H,4-7H2,1-3H3
InChI KeyInChIKey=WEEGYLXZBRQIMU-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oxanes. These are compounds containing an oxane (tetrahydropyran) ring, which is a six-member saturated aliphatic heterocycle with one oxygen atom and five carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassOxanes
Sub ClassNot Available
Direct ParentOxanes
Alternative Parents
Substituents
  • Oxane
  • Oxacycle
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
StateLiquid
Experimental Properties
PropertyValueReference
Melting Point1.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.5 mg/mL at 21 °CNot Available
LogP2.74GRIFFIN,S ET AL. (1999)
Predicted Properties
PropertyValueSource
Water Solubility0.022 mg/mLALOGPS
logP3.36ALOGPS
logP2.35ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.86 m3·mol-1ChemAxon
Polarizability18.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-9500000000-9dc534a13d795eb1b96cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9000000000-c05885d0e60c65af2adfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-003u-9000000000-217a9576a252e6456825View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Feces
  • Saliva
Tissue Location
  • Skin
  • Stratum Corneum
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified5.13 (2.98-7.36) uMAdult (>18 years old)Both
Eucalyptol exposure
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Nonalcoholic fatty liver disease (NAFLD)
details
Associated Disorders and Diseases
Disease References
Eucalyptol exposure
  1. Jager W, Nasel B, Nasel C, Binder R, Stimpfl T, Vycudilik W, Buchbauer G: Pharmacokinetic studies of the fragrance compound 1,8-cineol in humans during inhalation. Chem Senses. 1996 Aug;21(4):477-80. [8866111 ]
Associated OMIM IDsNone
DrugBank IDDB03852
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB014616
KNApSAcK IDC00000136
Chemspider ID2656
KEGG Compound IDC09844
BioCyc IDCPD-4261
BiGG IDNot Available
Wikipedia Link1,8-Cineol
NuGOwiki LinkHMDB04472
Metagene LinkHMDB04472
METLIN ID7060
PubChem Compound2758
PDB IDNot Available
ChEBI ID584235
References
Synthesis ReferenceLana, Enio J. Leao; Rocha, Kelly A. da Silva; Kozhevnikov, Ivan V.; Gusevskaya, Elena V. Synthesis of 1,8-cineole and 1,4-cineole by isomerization of a-terpineol catalyzed by heteropoly acid. Journal of Molecular Catalysis A: Chemical (2006), 259(1-2), 99-102.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Giannakou SA, Dallas PP, Rekkas DM, Choulis NH: In vitro evaluation of nimodipine permeation through human epidermis using response surface methodology. Int J Pharm. 2002 Jul 8;241(1):27-34. [12086718 ]
  2. Narishetty ST, Panchagnula R: Effect of L-menthol and 1,8-cineole on phase behavior and molecular organization of SC lipids and skin permeation of zidovudine. J Control Release. 2005 Jan 20;102(1):59-70. [15653134 ]
  3. Lim PF, Liu XY, Kang L, Ho PC, Chan YW, Chan SY: Limonene GP1/PG organogel as a vehicle in transdermal delivery of haloperidol. Int J Pharm. 2006 Mar 27;311(1-2):157-64. Epub 2006 Jan 31. [16451823 ]
  4. Cornwell PA, Barry BW, Stoddart CP, Bouwstra JA: Wide-angle X-ray diffraction of human stratum corneum: effects of hydration and terpene enhancer treatment. J Pharm Pharmacol. 1994 Dec;46(12):938-50. [7536240 ]
  5. Juergens UR, Engelen T, Racke K, Stober M, Gillissen A, Vetter H: Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes. Pulm Pharmacol Ther. 2004;17(5):281-7. [15477123 ]
  6. Moghimi HR, Williams AC, Barry BW: Enhancement by terpenes of 5-fluorouracil permeation through the stratum corneum: model solvent approach. J Pharm Pharmacol. 1998 Sep;50(9):955-64. [9811155 ]
  7. Kato T, Iijima H, Ishihara K, Kaneko T, Hirai K, Naito Y, Okuda K: Antibacterial effects of Listerine on oral bacteria. Bull Tokyo Dent Coll. 1990 Nov;31(4):301-7. [2133450 ]
  8. Harper DS, Brogdon CL, Wu MM, Epelle U: A rapid method for evaluating microbicidal activity of dentifrice formulations against salivary bacteria ex vivo. J Clin Dent. 2000;11(4):89-93. [11460277 ]
  9. Duisken M, Sandner F, Blomeke B, Hollender J: Metabolism of 1,8-cineole by human cytochrome P450 enzymes: identification of a new hydroxylated metabolite. Biochim Biophys Acta. 2005 Apr 15;1722(3):304-11. Epub 2005 Jan 17. [15715982 ]
  10. De Vincenzi M, Silano M, De Vincenzi A, Maialetti F, Scazzocchio B: Constituents of aromatic plants: eucalyptol. Fitoterapia. 2002 Jun;73(3):269-75. [12048025 ]
  11. Bastos VP, Gomes AS, Lima FJ, Brito TS, Soares PM, Pinho JP, Silva CS, Santos AA, Souza MH, Magalhaes PJ: Inhaled 1,8-cineole reduces inflammatory parameters in airways of ovalbumin-challenged Guinea pigs. Basic Clin Pharmacol Toxicol. 2011 Jan;108(1):34-9. doi: 10.1111/j.1742-7843.2010.00622.x. Epub 2010 Aug 16. [20722639 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
Reactions
Eucalyptol + NADPH + Oxygen → 2-exo-hydroxy-1,8-cineole + NADP + Waterdetails