Basic Info

Common NameClofentezine(F05044)
2D Structure
Description

Clofentezine is an acaricide used for the residual control of mites. It acts primarily as an ovicide, with some activity on early motile stages. Used on a wide range of crops – apples, pears, stone fruit, nuts, ornamentals, almonds etc. The main toxicological effects seen in studies in rats and dogs were hepatotoxicity and changes to the thyroid, including follicular hyperplasia. Clofentezine does not pose a high toxicity risk to humans.

FRCD IDF05044
CAS Number74115-24-5
PubChem CID73670
FormulaC14H8Cl2N4
IUPAC Name

3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine

InChI Key

UXADOQPNKNTIHB-UHFFFAOYSA-N

InChI

InChI=1S/C14H8Cl2N4/c15-11-7-3-1-5-9(11)13-17-19-14(20-18-13)10-6-2-4-8-12(10)16/h1-8H

Canonical SMILES

C1=CC=C(C(=C1)C2=NN=C(N=N2)C3=CC=CC=C3Cl)Cl

Isomeric SMILES

C1=CC=C(C(=C1)C2=NN=C(N=N2)C3=CC=CC=C3Cl)Cl

Synonyms
        
            Clofentezine
        
            3,6-Bis(2-chlorophenyl)-1,2,4,5-tetrazine
        
            74115-24-5
        
            Apollo
        
            Bisclofentazin
        
            Bisclofentazine
        
            Acaristop
        
            Panatac
        
            Apollo (pesticide)
        
            Apollo 50W
        
Classifies
                

                  
                    Pesticide
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassBenzenoids
ClassBenzene and substituted derivatives
SubclassHalobenzenes
Intermediate Tree NodesNot available
Direct ParentChlorobenzenes
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsChlorobenzene - Tetrazine - Aryl halide - Aryl chloride - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety.

Properties

Property NameProperty Value
Molecular Weight303.146
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count4
Rotatable Bond Count2
Complexity280
Monoisotopic Mass302.013
Exact Mass302.013
XLogP3.2
Formal Charge0
Heavy Atom Count20
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9792
Human Intestinal AbsorptionHIA+1.0000
Caco-2 PermeabilityCaco2+0.7596
P-glycoprotein SubstrateNon-substrate0.7476
P-glycoprotein InhibitorNon-inhibitor0.8738
Non-inhibitor0.9932
Renal Organic Cation TransporterNon-inhibitor0.7969
Distribution
Subcellular localizationMitochondria0.8115
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8275
CYP450 2D6 SubstrateNon-substrate0.8728
CYP450 3A4 SubstrateNon-substrate0.6396
CYP450 1A2 InhibitorInhibitor0.8946
CYP450 2C9 InhibitorNon-inhibitor0.5770
CYP450 2D6 InhibitorNon-inhibitor0.9478
CYP450 2C19 InhibitorNon-inhibitor0.7154
CYP450 3A4 InhibitorNon-inhibitor0.8782
CYP Inhibitory PromiscuityHigh CYP Inhibitory Promiscuity0.5000
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9530
Non-inhibitor0.9084
AMES ToxicityNon AMES toxic0.7322
CarcinogensNon-carcinogens0.8487
Fish ToxicityHigh FHMT0.9338
Tetrahymena Pyriformis ToxicityHigh TPT0.9651
Honey Bee ToxicityLow HBT0.8111
BiodegradationNot ready biodegradable1.0000
Acute Oral ToxicityIII0.7901
Carcinogenicity (Three-class)Non-required0.6738

Model Value Unit
Absorption
Aqueous solubility-2.6834LogS
Caco-2 Permeability2.0108LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.0076LD50, mol/kg
Fish Toxicity0.8297pLC50, mg/L
Tetrahymena Pyriformis Toxicity1.3172pIGC50, ug/L

MRLs

FoodProduct CodeCountryMRLsApplication DateNotes
Others (2)0251990European Union0.02*25/06/2015
Others (2)0631990European Union0.05*25/06/2015
Sugar beet roots0900010European Union0.02*25/06/2015
Citrus fruits0110000European Union0.525/06/2015
Others (2)0154990European Union0.02*25/06/2015
Oranges (Bergamots, Bitter oranges/sour oranges, Blood oranges, Cara caras, Chinottos, Trifoliate oranges, Other hybrids of Citrus sinensis, not elsewhere mentioned,)0110020European Union0.525/06/2015
Lemons (Buddha's hands/Buddha's fingers, Citrons,)0110030European Union0.525/06/2015
Limes (Indian sweet limes/Palestine sweet limes, Kaffir limes, Sweet limes/mosambis, Tahiti limes, Limequats,)0110040European Union0.525/06/2015
Mandarins (Calamondins, Clementines, Cleopatra mandarins, Minneolas, Satsumas/clausellinas, Tangerines/dancy mandarins, Tangors, Other hybrids of Citrus reticulata, not elsewhere mentioned,)0110050European Union0.525/06/2015
Others (2)0110990European Union0.525/06/2015
Tree nuts0120000European Union0.05*25/06/2015
Almonds (Apricot kernels, Bitter almonds, Canarium nuts/galip nuts, Pili nuts, Okari nuts,)0120010European Union0.05*25/06/2015
Brazil nuts0120020European Union0.05*25/06/2015
Cashew nuts0120030European Union0.05*25/06/2015
Chestnuts0120040European Union0.05*25/06/2015
Coconuts (Areca nuts/betel nuts,)0120050European Union0.05*25/06/2015
Hazelnuts/cobnuts (Acorns, Filberts,)0120060European Union0.05*25/06/2015
Macadamias0120070European Union0.05*25/06/2015
Pecans (Hickory nuts,)0120080European Union0.05*25/06/2015
Pistachios0120100European Union0.05*25/06/2015

References

TitleJournalDatePubmed ID
Risk Assessment of Florists Exposed to Pesticide Residues through Handling of Flowers and Preparing Bouquets.Int J Environ Res Public Health2017 May 1328505067
Study on Mobility, Distribution and Rapid Ion Mobility Spectrometry Detection of Seven Pesticide Residues in Cucumber, Apple, and Cherry Tomato.J Agric Food Chem2017 Jan 1127936707
Evaluation of etoxazole against insects and acari in vegetables in China.J Insect Sci201425199415
Resistance to acaricides in Italian strains of Tetranychus urticae: toxicologicaland enzymatic assays.Exp Appl Acarol2012 May22447041
Effects of acaricides, pyrethroids and predator distributions on populations ofTetranychus urticae in apple orchards.Exp Appl Acarol200718008172
Baseline susceptibility and cross resistances of some new acaricides in theEuropean red mite, Panonychus ulmi.Exp Appl Acarol200516323048
An index for selective toxicity of miticides to phytophagous mites and their predators based on orchard trials.Pest Manag Sci2003 Dec14667054
Characterization of resistance to clofentezine in populations of European redmite from orchards in Ontario.Exp Appl Acarol200212593584
[Method-performance studies of notified analytical method for clofentezine].Shokuhin Eiseigaku Zasshi2001 Aug11817146
Relevance of kinetic and metabolic data to the interpretation of toxicologicalfindings.Food Addit Contam19892599154

Targets

General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
References
  1. 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 ]
Gene Name:
CCL2
Uniprot ID:
P13500
Molecular Weight:
11024.87 Da
References
  1. 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:
Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.
Gene Name:
MMP1
Uniprot ID:
P03956
Molecular Weight:
54006.61 Da
References
  1. 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:
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
Gene Name:
MMP9
Uniprot ID:
P14780
Molecular Weight:
78457.51 Da
References
  1. 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:
Urokinase plasminogen activator receptor activity
Specific Function:
Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:
PLAUR
Uniprot ID:
Q03405
Molecular Weight:
36977.62 Da
References
  1. 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:
Sulfotransferase activity
Specific Function:
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.
Gene Name:
SULT2A1
Uniprot ID:
Q06520
Molecular Weight:
33779.57 Da
References
  1. 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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. 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:
Platelet-derived growth factor binding
Specific Function:
Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of GPR56 in the developing brain and binding to GPR56 inhibits neuronal migration and activates the RhoA pathway by coupling GPR56 to GNA13 and possibly GNA12.
Gene Name:
COL3A1
Uniprot ID:
P02461
Molecular Weight:
138564.005 Da
References
  1. 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
  1. 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:
Prostaglandin e receptor activity
Specific Function:
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.
Gene Name:
PTGER2
Uniprot ID:
P43116
Molecular Weight:
39759.945 Da
References
  1. 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:
Vitamin d3 25-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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. 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
  1. 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. 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
  1. 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:
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
  1. 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 binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
References
  1. 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 ]