DIOCTYL PHTHALATE

General Information

Mainterm	DIOCTYL PHTHALATE
CAS Reg.No.(or other ID)	117-84-0
Regnum	175.105 177.2600 177.1460

From www.fda.gov

Computed Descriptors

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2D Structure
CID	8346
IUPAC Name	dioctyl benzene-1,2-dicarboxylate
InChI	InChI=1S/C24H38O4/c1-3-5-7-9-11-15-19-27-23(25)21-17-13-14-18-22(21)24(26)28-20-16-12-10-8-6-4-2/h13-14,17-18H,3-12,15-16,19-20H2,1-2H3
InChI Key	MQIUGAXCHLFZKX-UHFFFAOYSA-N
Canonical SMILES	CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC
Molecular Formula	C24H38O4
Wikipedia	di-N-octyl phthalate

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	390.564
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	18
Complexity	369.0
CACTVS Substructure Key Fingerprint	A A A D c f B 4 O 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 w A A A A A A A A A A A B A A A A G g A A A A A A D A C g m A I y C I A A B A C I A i D S C A A C A A A k A A A I i A E A C M g I J j K A N R i C M Q A k w A E I q Y f L y K C O g A A A A A A Q A A A A A A A A A C A A A A A A A A A A A A = =
Topological Polar Surface Area	52.6
Monoisotopic Mass	390.277
Exact Mass	390.277
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	28
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

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9455
Human Intestinal Absorption	HIA+	0.9770
Caco-2 Permeability	Caco2+	0.7002
P-glycoprotein Substrate	Substrate	0.5000
P-glycoprotein Inhibitor	Non-inhibitor	0.7542
P-glycoprotein Inhibitor	Non-inhibitor	0.8654
Renal Organic Cation Transporter	Non-inhibitor	0.8266
Distribution
Subcellular localization	Mitochondria	0.8914
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8622
CYP450 2D6 Substrate	Non-substrate	0.8757
CYP450 3A4 Substrate	Non-substrate	0.5960
CYP450 1A2 Inhibitor	Non-inhibitor	0.6448
CYP450 2C9 Inhibitor	Non-inhibitor	0.8318
CYP450 2D6 Inhibitor	Non-inhibitor	0.8275
CYP450 2C19 Inhibitor	Non-inhibitor	0.6765
CYP450 3A4 Inhibitor	Non-inhibitor	0.8309
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.6788
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.8980
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.7517
AMES Toxicity	Non AMES toxic	0.9504
Carcinogens	Non-carcinogens	0.7741
Fish Toxicity	High FHMT	0.9924
Tetrahymena Pyriformis Toxicity	High TPT	0.9999
Honey Bee Toxicity	High HBT	0.5227
Biodegradation	Ready biodegradable	0.7764
Acute Oral Toxicity	IV	0.6802
Carcinogenicity (Three-class)	Warning	0.5091

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-5.7280	LogS
Caco-2 Permeability	0.9491	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.0217	LD50, mol/kg
Fish Toxicity	0.0302	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	1.8389	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Oral ; inhalation ; dermal
Mechanism of Toxicity	Phthalate esters are endocrine disruptors. They decrease foetal testis testosterone production and reduce the expression of steroidogenic genes by decreasing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide 3 (insl3), an important hormone secreted by the Leydig cell necessary for development of the gubernacular ligament. Animal studies have shown that these effects disrupt reproductive development and can cause a number of malformations in affected young.
Metabolism	Phthalate esters are first hydrolyzed to their monoester derivative. Once formed, the monoester derivative can be further hydrolyzed in vivo to phthalic acid or conjugated to glucuronide, both of which can then be excreted. The terminal or next-to-last carbon atom in the monoester can also be oxidized to an alcohol, which can be excreted as is or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and oxidative metabolites are excreted in the urine and faeces.
Toxicity Values	LD50: 13000 mg/kg (Oral, Mouse) LD50: 73 500 mg/kg (Dermal, Guinea pig)
Lethal Dose
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level
Health Effects	Phthalate esters are endocrine disruptors. Animal studies have shown that they disrupt reproductive development and can cause a number of malformations in affected young, such as reduced anogenital distance (AGD), cryptorchidism, hypospadias, and reduced fertility. The combination of effects associated with phthalates is called 'phthalate syndrome’. (A2883)
Treatment
Reference	Wilson VS, Blystone CR, Hotchkiss AK, Rider CV, Gray LE Jr: Diverse mechanisms of anti-androgen action: impact on male rat reproductive tract development. Int J Androl. 2008 Apr;31(2):178-87. doi: 10.1111/j.1365-2605.2007.00861.x.[18315717 ] Wittassek M, Angerer J: Phthalates: metabolism and exposure. Int J Androl. 2008 Apr;31(2):131-8. Epub 2007 Dec 7.[18070048 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Benzenoids
Class	Benzene and substituted derivatives
Subclass	Benzoic acids and derivatives
Intermediate Tree Nodes	Not available
Direct Parent	Benzoic acid esters
Alternative Parents	Carboxylic acid esters Hydrocarbon derivatives Organic oxides Organooxygen compounds Benzoyl derivatives Dicarboxylic acids and derivatives
Molecular Framework	Aromatic homomonocyclic compounds
Substituents	Benzoate ester - Benzoyl - Dicarboxylic acid or derivatives - Carboxylic acid ester - Carboxylic acid derivative - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound
Description	This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.

From ClassyFire

Targets

Target Details

Nuclear receptor subfamily 1 group I member 2

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:: NR1I2
Uniprot ID:: O75469
Molecular Weight:: 49761.245 Da

References

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