SAFROLE--PROHIBITED

General Information

From www.fda.gov

2D Structure
CID	5144
IUPAC Name	5-prop-2-enyl-1,3-benzodioxole
InChI	InChI=1S/C10H10O2/c1-2-3-8-4-5-9-10(6-8)12-7-11-9/h2,4-6H,1,3,7H2
InChI Key	ZMQAAUBTXCXRIC-UHFFFAOYSA-N
Canonical SMILES	C=CCC1=CC2=C(C=C1)OCO2
Molecular Formula	C10H10O2
Wikipedia	safrole

From Pubchem

Property Name	Property Value
Molecular Weight	162.188
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Complexity	167.0
CACTVS Substructure Key Fingerprint	A A A D c c B w M A A A A A A A A A A A A A A A A A A A A S A A A A A w A A A A A A A A A E g B A A A A G g A A A A A A D A S A m A M w D o A A B A C A A i B C A A A C C A A g I A A I i A A G i I g d J i K E M R q g M C I k w B E O q A e A w L A O I A A B A A A A Q A B A A A I A A A C A A A A A A A A A A A = =
Topological Polar Surface Area	18.5
Monoisotopic Mass	162.068
Exact Mass	162.068
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	12
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9846
Human Intestinal Absorption	HIA+	0.9951
Caco-2 Permeability	Caco2+	0.6278
P-glycoprotein Substrate	Non-substrate	0.7829
P-glycoprotein Inhibitor	Non-inhibitor	0.7386
P-glycoprotein Inhibitor	Non-inhibitor	0.5800
Renal Organic Cation Transporter	Non-inhibitor	0.8177
Distribution
Subcellular localization	Mitochondria	0.4824
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8814
CYP450 2D6 Substrate	Non-substrate	0.8577
CYP450 3A4 Substrate	Non-substrate	0.7118
CYP450 1A2 Inhibitor	Inhibitor	0.8554
CYP450 2C9 Inhibitor	Non-inhibitor	0.6333
CYP450 2D6 Inhibitor	Inhibitor	0.5435
CYP450 2C19 Inhibitor	Inhibitor	0.6493
CYP450 3A4 Inhibitor	Non-inhibitor	0.6972
CYP Inhibitory Promiscuity	High CYP Inhibitory Promiscuity	0.7769
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9024
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9577
AMES Toxicity	Non AMES toxic	0.9132
Carcinogens	Non-carcinogens	0.8641
Fish Toxicity	High FHMT	0.9255
Tetrahymena Pyriformis Toxicity	High TPT	0.9883
Honey Bee Toxicity	High HBT	0.7790
Biodegradation	Ready biodegradable	0.6285
Acute Oral Toxicity	III	0.8274
Carcinogenicity (Three-class)	Warning	0.5214

From admetSAR

Model	Value	Unit
Absorption
Aqueous solubility	-2.5001	LogS
Caco-2 Permeability	1.5491	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.9517	LD50, mol/kg
Fish Toxicity	0.9028	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.6903	pIGC50, ug/L

From admetSAR

Route of Exposure
Mechanism of Toxicity
Metabolism
Toxicity Values
Lethal Dose
Carcinogenicity (IARC Classification)	2B, possibly carcinogenic to humans.
Minimum Risk Level
Health Effects
Treatment
Reference	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 ] 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 ] 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 ]

From T3DB

Kingdom	Organic compounds
Superclass	Organoheterocyclic compounds
Class	Benzodioxoles
Subclass	Not available
Intermediate Tree Nodes	Not available
Direct Parent	Benzodioxoles
Alternative Parents	Acetals Oxacyclic compounds Hydrocarbon derivatives
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Benzodioxole - Benzenoid - Oxacycle - Acetal - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Aromatic heteropolycyclic compound
Description	This compound 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.

From ClassyFire

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

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 ]

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

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 ]

From T3DB