DIISOBUTYL PHTHALATE
General Information
| Mainterm | DIISOBUTYL PHTHALATE |
| CAS Reg.No.(or other ID) | 84-69-5 |
| Regnum |
175.105 177.1200 |
From www.fda.gov
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 6782 |
| IUPAC Name | bis(2-methylpropyl) benzene-1,2-dicarboxylate |
| InChI | InChI=1S/C16H22O4/c1-11(2)9-19-15(17)13-7-5-6-8-14(13)16(18)20-10-12(3)4/h5-8,11-12H,9-10H2,1-4H3 |
| InChI Key | MGWAVDBGNNKXQV-UHFFFAOYSA-N |
| Canonical SMILES | CC(C)COC(=O)C1=CC=CC=C1C(=O)OCC(C)C |
| Molecular Formula | C16H22O4 |
| Wikipedia | diisobutyl phthalate |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 278.348 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 8 |
| Complexity | 290.0 |
| CACTVS Substructure Key Fingerprint | A A A D c e 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 Q 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 | 278.152 |
| Exact Mass | 278.152 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 20 |
| 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+ | 0.9308 |
| Human Intestinal Absorption | HIA+ | 0.9745 |
| Caco-2 Permeability | Caco2+ | 0.7151 |
| P-glycoprotein Substrate | Non-substrate | 0.6465 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.7684 |
| Non-inhibitor | 0.8162 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8914 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8897 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8206 |
| CYP450 2D6 Substrate | Non-substrate | 0.8820 |
| CYP450 3A4 Substrate | Non-substrate | 0.6097 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.5666 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.6604 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9218 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7906 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8983 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.7003 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9738 |
| Non-inhibitor | 0.9621 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.5391 |
| Fish Toxicity | High FHMT | 0.9862 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9669 |
| Honey Bee Toxicity | High HBT | 0.6573 |
| Biodegradation | Ready biodegradable | 0.6348 |
| Acute Oral Toxicity | IV | 0.7836 |
| Carcinogenicity (Three-class) | Non-required | 0.5420 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.5973 | LogS |
| Caco-2 Permeability | 1.2521 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.2991 | LD50, mol/kg |
| Fish Toxicity | 0.3153 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.0247 | 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: 15000 mg/kg (Oral, Rat) LD50: 10 g/kg (Dermal, Guinea pig) LD50: 3749 mg/kg (Intraperitoneal, Rat) |
| 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 |
|
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 | |
| 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
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
- Gene Name:
- PPARG
- Uniprot ID:
- P37231
- Molecular Weight:
- 57619.58 Da
References
- Pereira-Fernandes A, Demaegdt H, Vandermeiren K, Hectors TL, Jorens PG, Blust R, Vanparys C: Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect. PLoS One. 2013 Oct 14;8(10):e77481. doi: 10.1371/journal.pone.0077481. eCollection 2013. [24155963 ]
- 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
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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity).Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
- Gene Name:
- RORB
- Uniprot ID:
- Q92753
- Molecular Weight:
- 53219.385 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 ]
- General Function:
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
- Gene Name:
- CYP1A2
- Uniprot ID:
- P05177
- Molecular Weight:
- 58293.76 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