Di-n-propyl phthalate (T3D3655)
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| Version | 2.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-12-04 03:38:33 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:26:17 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D3655 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identification | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Di-n-propyl phthalate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Small Molecule | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Di-n-propyl phthalate is a phthalate ester. Phthalate esters are esters of phthalic acid and are mainly used as plasticizers, primarily used to soften polyvinyl chloride. They are found in a number of products, including glues, building materials, personal care products, detergents and surfactants, packaging, children's toys, paints, pharmaceuticals, food products, and textiles. Phthalates are hazardous due to their ability to act as endocrine disruptors. They are being phased out of many products in the United States and European Union due to these health concerns. (3) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Chemical Structure |  | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | C14H18O4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 250.290 g/mol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Mass | 250.121 g/mol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 131-16-8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | 1,2-dipropyl benzene-1,2-dicarboxylate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | dipropyl phthalate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES | CCCOC(=O)C1=CC=CC=C1C(=O)OCCC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/C14H18O4/c1-3-9-17-13(15)11-7-5-6-8-12(11)14(16)18-10-4-2/h5-8H,3-4,9-10H2,1-2H3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=MQHNKCZKNAJROC-UHFFFAOYSA-N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Benzenoids | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Benzene and substituted derivatives | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Benzoic acids and derivatives | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Benzoic acid esters | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Aromatic homomonocyclic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors |
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| Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status | Detected and Not Quantified | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Origin | Exogenous | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biofluid Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Applications | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | Liquid | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Appearance | Colorless liquid. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra |
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| Toxicity Profile | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Oral (3) ; inhalation (3) ; dermal (3) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. (1) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. (2) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | Phthalate esters are mainly used as plasticizers, primarily used to soften polyvinyl chloride. They are found in a number of products, including glues, building materials, personal care products, detergents and surfactants, packaging, children's toys, paints, pharmaceuticals, food products, and textiles. Phthalates are used in a variety of household applications such as shower curtains, vinyl upholstery, adhesives, floor tiles, food containers and wrappers, and cleaning materials. Personal care items containing phthalates include perfume, eye shadow, moisturizer, nail polish, liquid soap, and hair spray. (3) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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’. (1) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | Phthalate esters are endocrine disruptors and can cause a number of developmental malformations termed 'phthalate syndrome'. (1) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treatment | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 8559 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | C14469 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | 33308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | O-ACETYLCARNITINE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General References |
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| Gene Regulation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Up-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Down-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
- Toda C, Okamoto Y, Ueda K, Hashizume K, Itoh K, Kojima N: Unequivocal estrogen receptor-binding affinity of phthalate esters featured with ring hydroxylation and proper alkyl chain size. Arch Biochem Biophys. 2004 Nov 1;431(1):16-21. [15464722 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
References
- Toda C, Okamoto Y, Ueda K, Hashizume K, Itoh K, Kojima N: Unequivocal estrogen receptor-binding affinity of phthalate esters featured with ring hydroxylation and proper alkyl chain size. Arch Biochem Biophys. 2004 Nov 1;431(1):16-21. [15464722 ]
- 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
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.
- Gene Name:
- PPARD
- Uniprot ID:
- Q03181
- Molecular Weight:
- 49902.99 Da
References
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
- 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
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
- Gene Name:
- RXRA
- Uniprot ID:
- P19793
- Molecular Weight:
- 50810.835 Da
References
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
- Gene Name:
- RXRB
- Uniprot ID:
- P28702
- Molecular Weight:
- 56921.38 Da
References
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
- Gene Name:
- RXRG
- Uniprot ID:
- P48443
- Molecular Weight:
- 50870.72 Da
References
- Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [23843199 ]