Vinclozolin
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Basic Info
| Common Name | Vinclozolin(F05154) |
| 2D Structure | |
| Description | Vinclozolin (trade names: Ronilan, Curalan, Vorlan, Touche) is a common dicarboximide fungicide used to control diseases, such as blights, rots and molds in vineyards, and on fruits and vegetables such as raspberries, lettuce, kiwi, snap beans, and onions. It is also used on turf on golf courses. Two common fungi that vinclozolin is used to protect crops against are botrytis cinerea and sclerotinia scleotiorun. First registered in 1981, vinclozolin is widely used but its overall application has declined. As a pesticide, vinclozolin is regulated by the United States Environmental Protection Agency (U.S. EPA). It has gone through a series of tests and regulations in order to evaluate the risks and hazards to the environment and animals. Among the research, a main finding is that vinclozolin has been shown to be an endocrine disruptor with antiandrogenic effects. |
| FRCD ID | F05154 |
| CAS Number | 50471-44-8 |
| PubChem CID | 39676 |
| Formula | C12H9Cl2NO3 |
| IUPAC Name | 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-1,3-oxazolidine-2,4-dione |
| InChI Key | FSCWZHGZWWDELK-UHFFFAOYSA-N |
| InChI | InChI=1S/C12H9Cl2NO3/c1-3-12(2)10(16)15(11(17)18-12)9-5-7(13)4-8(14)6-9/h3-6H,1H2,2H3 |
| Canonical SMILES | CC1(C(=O)N(C(=O)O1)C2=CC(=CC(=C2)Cl)Cl)C=C |
| Isomeric SMILES | CC1(C(=O)N(C(=O)O1)C2=CC(=CC(=C2)Cl)Cl)C=C |
| Synonyms |
VINCLOZOLIN
Vinclozoline
Ronilan
50471-44-8
Ornalin
Vorlan
Vinchlozoline
Vinclozolin [German]
Caswell No. 323C
BAS 352 F
|
| Classifies |
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Halobenzenes |
| Intermediate Tree Nodes | Chlorobenzenes |
| Direct Parent | Dichlorobenzenes |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| Substituents | 1,3-dichlorobenzene - Oxazolidinedione - Aryl chloride - Aryl halide - Oxazolidinone - Dicarboximide - Oxazolidine - Carbamic acid ester - Carbonic acid derivative - Carboxylic acid derivative - Oxacycle - Azacycle - Organoheterocyclic compound - Organonitrogen compound - Organochloride - Organohalogen compound - Organopnictogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxygen compound - Organooxygen compound - Organic oxide - Carbonyl group - Aromatic heteromonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 286.108 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 2 |
| Complexity | 391 |
| Monoisotopic Mass | 284.996 |
| Exact Mass | 284.996 |
| XLogP | 3.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 18 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9810 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.5367 |
| P-glycoprotein Substrate | Non-substrate | 0.8235 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8782 |
| Non-inhibitor | 0.8382 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9480 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4633 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7680 |
| CYP450 2D6 Substrate | Non-substrate | 0.8468 |
| CYP450 3A4 Substrate | Substrate | 0.5665 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.6775 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7081 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8816 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.5520 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7427 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5730 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9852 |
| Non-inhibitor | 0.9220 | |
| AMES Toxicity | Non AMES toxic | 0.7211 |
| Carcinogens | Non-carcinogens | 0.7617 |
| Fish Toxicity | High FHMT | 0.9975 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9760 |
| Honey Bee Toxicity | Low HBT | 0.8173 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | IV | 0.6229 |
| Carcinogenicity (Three-class) | Non-required | 0.4296 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.8676 | LogS |
| Caco-2 Permeability | 1.3800 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.4880 | LD50, mol/kg |
| Fish Toxicity | 0.9122 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.6277 | pIGC50, ug/L |
MRLs
| Food | Product Code | Country | MRLs | Application Date | Notes |
|---|---|---|---|---|---|
| Pig,Fat | Japan | 0.05ppm | |||
| Cattle,Fat | Japan | 0.05ppm | |||
| Beans | New Zealand | 0. 5mg/kg | |||
| Tomato | New Zealand | 3mg/kg | |||
| Kiwi Fruit | New Zealand | 5mg/kg | |||
| Fludioxonil | New Zealand | 5mg/kg | |||
| Other Cucurbits-Edible Peel | Britain | 1mg/kg | |||
| Courgettes | Britain | 1mg/kg | |||
| Gherkins | Britain | 1mg/kg | |||
| Cucumbers | Britain | 1mg/kg | |||
| Other Solanacea | Britain | 3mg/kg | |||
| Okra | Britain | 3mg/kg | |||
| Aubergines | Britain | 3mg/kg | |||
| Chili Peppers | Britain | 3mg/kg | |||
| Peppers | Britain | 3mg/kg | |||
| Tomatoes | Britain | 0.05mg/kg | |||
| Milk & Dairy Produce | Britain | 0.05mg/kg | |||
| Meat, Fat & Preparations Of Meat | Britain | 0.05mg/kg | |||
| Other Cereals Do Not Include Rice | Britain | 0.05mg/kg | |||
| Rice | Britain | 0.05mg/kg |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Analysis of Numerous Androgen Disruptors in Fish by Gas Chromatography TandemMass Spectrometry. | J AOAC Int | 2017 May 1 | 28118568 |
| Investigations on the dose-response relationship of combined exposure to lowdoses of three anti-androgens in Wistar rats. | Arch Toxicol | 2017 Dec | 28879601 |
| Investigations of putative reproductive toxicity of low-dose exposures tovinclozolin in Wistar rats. | Arch Toxicol | 2017 Apr | 27612472 |
| The ability of the YAS and AR CALUX assays to detect the additive effects ofanti-androgenic fungicide mixtures. | Toxicol Lett | 2016 Jan 22 | 26602169 |
| Transcripts of genes encoding reproductive neuroendocrine hormones and androgenreceptor in the brain and testis of goldfish exposed to vinclozolin, flutamide,testosterone, and their combinations. | Fish Physiol Biochem | 2016 Aug | 26899179 |
| Alternations in neuroendocrine and endocrine regulation of reproduction in malegoldfish (Carassius auratus) following an acute and chronic exposure tovinclozolin, in vivo. | Aquat Toxicol | 2014 Oct | 24995616 |
| Perinatal xenohormone exposure impacts sweet preference and submandibulardevelopment in male rats. | Oral Dis | 2013 Nov | 23410115 |
| Genistein and dicarboximide fungicides in infant formulae from the EU market. | Food Chem | 2013 Jan 1 | 23017401 |
| Effect of phenylpyrrole-resistance on fitness parameters and ochratoxin production in Aspergillus carbonarius. | Int J Food Microbiol | 2013 Aug 1 | 23800740 |
| The influence of fining agents on the removal of some pesticides from white wine of Vitis vinifera L. cv. Emir. | Food Chem Toxicol | 2012 Nov | 22939932 |
| Analysis of six fungicides and one acaricide in still and fortified wines usingsolid-phase microextraction-gas chromatography/tandem mass spectrometry. | Food Chem | 2012 May 1 | 26434342 |
| In utero and lactational exposure to low-dose genistein-vinclozolin mixtureaffects the development and growth factor mRNA expression of the submandibularsalivary gland in immature female rats. | Toxicol Pathol | 2012 Jun | 22317923 |
| Antagonistic effects of gestational dietary exposure to low-dose vinclozolin and genistein on rat fetal germ cell development. | Reprod Toxicol | 2011 May | 21172421 |
| Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminantvinclozolin. | Reprod Toxicol | 2011 Jul | 21539910 |
| Assessment of combinations of antiandrogenic compounds vinclozolin and flutamide in a yeast based reporter assay. | Regul Toxicol Pharmacol | 2011 Aug | 21620918 |
| Fate of vinclozolin, thiabendazole and dimethomorph during storage, handling and forcing of chicory. | Pest Manag Sci | 2010 Feb | 19746400 |
| Cell viability and PSA secretion assays in LNCaP cells: a tiered in vitroapproach to screen chemicals with a prostate-mediated effect on male reproductionwithin the ReProTect project. | Reprod Toxicol | 2010 Aug | 20363314 |
| Cumulative effects of in utero administration of mixtures of reproductivetoxicants that disrupt common target tissues via diverse mechanisms of toxicity. | Int J Androl | 2010 Apr | 20487044 |
| Synergistic disruption of external male sex organ development by a mixture offour antiandrogens. | Environ Health Perspect | 2009 Dec | 20049201 |
| Probabilistic cumulative risk assessment of anti-androgenic pesticides in food. | Food Chem Toxicol | 2009 Dec | 19665045 |
Targets
- 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 ]
- 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
- Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R: Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci. 2006 Aug 15;79(12):1160-9. Epub 2006 Mar 27. [16626760 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
- Gene Name:
- NR3C2
- Uniprot ID:
- P08235
- Molecular Weight:
- 107066.575 Da
References
- Molina-Molina JM, Hillenweck A, Jouanin I, Zalko D, Cravedi JP, Fernandez MF, Pillon A, Nicolas JC, Olea N, Balaguer P: Steroid receptor profiling of vinclozolin and its primary metabolites. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):44-54. Epub 2006 Jun 5. [16750840 ]
- General Function:
- Zinc ion binding
- Specific Function:
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
- Gene Name:
- PGR
- Uniprot ID:
- P06401
- Molecular Weight:
- 98979.96 Da
References
- Molina-Molina JM, Hillenweck A, Jouanin I, Zalko D, Cravedi JP, Fernandez MF, Pillon A, Nicolas JC, Olea N, Balaguer P: Steroid receptor profiling of vinclozolin and its primary metabolites. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):44-54. Epub 2006 Jun 5. [16750840 ]
- General Function:
- Cytokine activity
- Specific Function:
- Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
- Gene Name:
- IL1A
- Uniprot ID:
- P01583
- Molecular Weight:
- 30606.29 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:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular Weight:
- 55930.545 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 ]
- General Function:
- Steroid hydroxylase activity
- 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. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular Weight:
- 56277.81 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:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- Sonneveld E, Jansen HJ, Riteco JA, Brouwer A, van der Burg B: Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. Toxicol Sci. 2005 Jan;83(1):136-48. Epub 2004 Oct 13. [15483189 ]
- 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
- Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R: Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci. 2006 Aug 15;79(12):1160-9. Epub 2006 Mar 27. [16626760 ]
- General Function:
- Type iii transforming growth factor beta receptor binding
- Specific Function:
- Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells.
- Gene Name:
- TGFB1
- Uniprot ID:
- P01137
- Molecular Weight:
- 44340.685 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 ]