Safrole (T3D4212)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-08-29 05:53:23 UTC
Update Date2014-12-24 20:26:42 UTC
Accession NumberT3D4212
Identification
Common NameSafrole
ClassSmall Molecule
DescriptionSafrole is found in anise. Safrole occurs in nutmeg. Banned by FDA for use in food. Safrole is formerly used as a food flavour It is a precursor in the synthesis of the insecticide synergist piperonyl butoxide and the recreational drug MDMA (Ecstacy). Safrole is a natural plant constituent, found in oil of sassafras and certain other essential oils. It is a member of the methylenedioxybenzene group of compounds, many of which (e.g. piperonyl butoxide) are extensively used as insecticide synergists. Safrole is a major source of human exposure to safrole is through consumption of spices, such as nutmeg, cinnamon and black pepper, in which safrole is a constituent. Safrole is also present in root beer, and has been used as an additive in chewing gum, toothpaste, soaps and certain pharmaceutical preparations. Safrole is a weak hepatocarcinogen and it is a matter of considerable interest whether the ally1 moiety or the methylenedioxy group, or both, are involved in the mechanism of its carcinogenesis. Safrole is extensively metabolized, giving rise to a large number of metabolites. Metabolism involves essentially two major routes, oxidation of the ally1 side chain, and oxidation of the methylenedioxy group with subsequent cleavage to form the catechol. Safrole undergoes oxidation of the allylic group to yield the 2, 3-epoxide (safrole epoxide). The dihydrodiol is one of the metabolites of safrole, and presumably arises from the hydration of the 2, 3-epoxide. The principal route of metabolism of safrole is through cleavage of the methylenedioxy group, the major metabolites being allylcatechol and its isomer, propenylcatechol. Eugenol and its isomer I-methoxy- 2-hydroxy-4-allylbenzene have been detected as minor metabolites in the rat, mouse and man. ; Safrole, also known as shikimol, is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil, or synthesized from other related methylenedioxy compounds. It is the principal component of brown camphor oil, and is found in small amounts in a wide variety of plants, where it functions as a natural pesticide. The Ocotea cymbarum[verification needed] oil made of the Ocotea pretiosa[verification needed], a plant growing in Brazil, and sassafras oil made of Sassafras albidum, a tree growing in eastern North America, are the main natural sources for safrole. It has a characteristic candy-shop aroma. Safrole has been shown to exhibit antibiotic and anti-angiogenic functions (1, 2, 3).
Compound Type
  • Cigarette Toxin
  • Food Toxin
  • Insecticide
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Pesticide
  • Plant Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(allyldioxy)benzene methylene ether
(E)5-1-Propenyl]-1,3-benzodioxole
1, 2-(Methylenedioxy)-4-allylbenzene
1,2-Methylenedioxy-4-allyl-Benzene
1-Allyl,3,4-methylenedioxy benzene
3, 4-(Methylenedioxy)allylbenzene
3,4-Methylenedioxy-allybenzene
3,4-Methylenedioxyallylbenzene
3-(3,4-Methylenedioxyphenyl)prop-1-ene
4-Allyl-1, 2-(methylenedioxy)benzene
4-Allyl-1,2-(methylenedioxy)benzene, 8CI
4-Allylpyrocatechol formaldehyde acetal
4-Propenylcatechol methylene ether
5-(2-Propenyl)-1,3-benzodioxole, 9CI
5-Allyl-1,3-benzodioxolerlet DS Base
5-prop-2-enyl-1,3-benzodioxole
Allylcatechol methylene ether
Allyldioxybenzene methylene ether
Allylpyrocatechol methylene ether
M-Allylpyrocatechin methylene ether
Shikimol
Shikomol
Chemical FormulaC10H10O2
Average Molecular Mass162.185 g/mol
Monoisotopic Mass162.068 g/mol
CAS Registry Number94-59-7
IUPAC Name5-(prop-2-en-1-yl)-2H-1,3-benzodioxole
Traditional Namesassafras
SMILESC=CCC1=CC2=C(OCO2)C=C1
InChI IdentifierInChI=1S/C10H10O2/c1-2-3-8-4-5-9-10(6-8)12-7-11-9/h2,4-6H,1,3,7H2
InChI KeyInChIKey=ZMQAAUBTXCXRIC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodioxoles
Sub ClassNot Available
Direct ParentBenzodioxoles
Alternative Parents
Substituents
  • Benzodioxole
  • Benzenoid
  • Oxacycle
  • Acetal
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point11.2°C
Boiling Point232 - 234°C
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.24 g/LALOGPS
logP2.23ALOGPS
logP2.7ChemAxon
logS-2.1ALOGPS
pKa (Strongest Basic)-4.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity46.11 m³·mol⁻¹ChemAxon
Polarizability17.24 ųChemAxon
Number of Rings2ChemAxon
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)splash10-0ik9-3900000000-27e98ee529004a2d8b662017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ik9-6900000000-54b4c1509456711936df2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-6900000000-87b7efd770862a8f97a52017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ik9-5900000000-0e7164aea8e5fa73ab552017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-0900000000-cae3268c72651c72100c2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ik9-3900000000-27e98ee529004a2d8b662018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ik9-6900000000-54b4c1509456711936df2018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-6900000000-87b7efd770862a8f97a52018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ik9-5900000000-0e7164aea8e5fa73ab552018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-03di-0900000000-cae3268c72651c72100c2018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01sa-2900000000-390702c1e607859e47002017-09-01View 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, Positivesplash10-03di-0900000000-ce90b24b2ef83a6092612016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-1900000000-cb602c608751e483efce2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udl-9600000000-85407378b64267759f6d2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0900000000-f5650e9b49b023a3cfd22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0900000000-9dbd39032834251755462016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-02ti-5900000000-4204c0caaf5bb9b5d2582016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-9b0c6d7bc981d77b19272021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03k9-0900000000-01530378eccaf5c845f02021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fvr-9400000000-d251b0867c3f55c2e90e2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0900000000-4d3d221c51bdf4e740a22021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0900000000-3a92a79dc10e1183839f2021-09-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01ot-7900000000-1024f7dba32bfc58ce372021-09-25View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0ik9-4900000000-9558c12b4c5a01a274902014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (5)
Uses/SourcesThis is a natural compound that is used as a pesticide.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB33591
PubChem Compound ID5144
ChEMBL IDCHEMBL242273
ChemSpider ID13848731
KEGG IDC10490
UniProt IDNot Available
OMIM ID
ChEBI ID8994
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkSafrole
References
Synthesis ReferenceNguyen, Duc Tao; Le, Huyen; Pham, Van Tin. Study on the preparation of isosafrol from essential oil of Xa Xi. Tap Chi Duoc Hoc (1998), (1), 9-10.
MSDSLink
General References
  1. Ioannides C, Lum PY, Parke DV: Cytochrome P-448 and the activation of toxic chemicals and carcinogens. Xenobiotica. 1984 Jan-Feb;14(1-2):119-37. [6719936 ]
  2. Hung SL, Chen YL, Chen YT: Effects of safrole on the defensive functions of human neutrophils. J Periodontal Res. 2003 Apr;38(2):130-4. [12608906 ]
  3. Zhao J, Miao J, Zhao B, Zhang S, Yin D: Safrole oxide inhibits angiogenesis by inducing apoptosis. Vascul Pharmacol. 2005 Jun;43(1):69-74. [15936989 ]
  4. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Peroxisome proliferator-activated receptor alpha
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:
PPARA
Uniprot ID:
Q07869
Molecular Weight:
52224.595 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.90 uMNVS_NR_hPPARaNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. Oxysterols receptor LXR-alpha
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:
NR1H3
Uniprot ID:
Q13133
Molecular Weight:
50395.34 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.74 uMATG_LXRa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]