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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-08-13 19:29:25 UTC
Update Date2020-04-23 20:56:21 UTC
HMDB IDHMDB0004472
Secondary Accession Numbers
  • HMDB0002267
  • HMDB02267
  • HMDB04472
Metabolite Identification
Common NameEucalyptol
DescriptionEucalyptol is an organic compound that is a colourless 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 accidental exposure, 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 flavour (PMID: 12048025 , Fitoterapia. 2002 Jun;73(3):269-75).
Structure
Data?1583864524
Synonyms
ValueSource
1,3,3-TRIMETHYL-2-oxabicyclo[2.2.2]octaneChEBI
1,8-CineolChEBI
1,8-Epoxy-p-menthaneChEBI
1,8-Oxido-p-menthaneChEBI
CajeputolChEBI
CineoleChEBI
ZineolChEBI
EucalyptolChEBI
1,8-CineoleHMDB
1,8-EucalyptolHMDB
2-Oxa-1,3,3-trimethylbicyclo[2.2.2]octaneHMDB
EucaliptolHMDB
EucalyptoleHMDB
EucalytolHMDB
EukalyptolHMDB
p-CineoleHMDB
Chemical FormulaC10H18O
Average Molecular Weight154.2493
Monoisotopic Molecular Weight154.135765198
IUPAC Name(1s,4s)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
Traditional Name1,8-cineole
CAS Registry Number470-82-6
SMILES
C[C@@]12CC[C@@H](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/t8-,10+
InChI KeyWEEGYLXZBRQIMU-WAAGHKOSSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as oxanes. Oxanes 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
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Role

Industrial application:

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 g/LALOGPS
logP3.36ALOGPS
logP2.35ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.86 m³·mol⁻¹ChemAxon
Polarizability18.54 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0f79-3900000000-207d29106cfe3c54c018Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-9500000000-9dc534a13d795eb1b96cSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9000000000-c05885d0e60c65af2adfSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-003u-9000000000-217a9576a252e6456825Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0900000000-87fbd679809c90a3eb19Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0900000000-aa8e8e9cd53dad3b120eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-0900000000-5296316e735fc49999bfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0900000000-99f5c9faaf8cf2b40394Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0900000000-99f5c9faaf8cf2b40394Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0f79-0900000000-da51d6a18dbcbda3b168Spectrum
MSMass Spectrum (Electron Ionization)splash10-0536-9200000000-aa52695ff4a2c1313e0bSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Saliva
Tissue Locations
  • Epidermis
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
SalivaDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified5.13 (2.98-7.36) uMAdult (>18 years old)Both
Eucalyptol exposure
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>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. [PubMed:8866111 ]
Nonalcoholic fatty liver disease
  1. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP: Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2013 Jul;11(7):868-75.e1-3. doi: 10.1016/j.cgh.2013.02.015. Epub 2013 Feb 27. [PubMed:23454028 ]
Associated OMIM IDsNone
DrugBank IDDB03852
Phenol Explorer Compound IDNot Available
FooDB IDFDB014616
KNApSAcK IDC00000136
Chemspider ID21111689
KEGG Compound IDC09844
BioCyc IDCPD-4261
BiGG IDNot Available
Wikipedia LinkEucalyptol
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID27961
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
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. [PubMed:12086718 ]
  2. 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. [PubMed:15477123 ]
  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. [PubMed:16451823 ]
  4. 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. [PubMed:9811155 ]
  5. 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. [PubMed:2133450 ]
  6. 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. [PubMed:11460277 ]
  7. 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. [PubMed:15715982 ]
  8. 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. [PubMed:15653134 ]
  9. 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. [PubMed:7536240 ]
  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. [PubMed: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. [PubMed: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