T3DB: Benfluralin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (8)XML

Targets (8)

Record Information

Version

2.0

Creation Date

2013-04-25 07:56:50 UTC

Update Date

2014-12-24 20:26:32 UTC

Accession Number

T3D3796

Identification

Common Name

Benfluralin

Class

Small Molecule

Description

Benfluralin is an herbicide of the dinitroaniline class. It is used to control grasses and other weeds. Annual use in the United States was approximately 700,000 pounds in 2004.

Compound Type

Amine
Herbicide
Organic Compound
Organofluoride
Pesticide
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
Benalan
Benefex
Benefin
Benephin
Benfluraline
Bethrodine
Binnell
Blulan
Bonalan
Carpidor
Flubalex
N-Butyl N-ethyl-2,6-dinitro-4-(trifluoromethyl)benzeneamine
N-Butyl-2,6-dinitro-N-ethyl-4-trifluoromethylaniline
N-Butyl-N-ethyl-2,6-dinitro-4-(trifluoromethyl)aniline

Chemical Formula

C₁₃H₁₆F₃N₃O₄

Average Molecular Mass

335.279 g/mol

Monoisotopic Mass

335.109 g/mol

CAS Registry Number

1861-40-1

IUPAC Name

N-butyl-N-ethyl-2,6-dinitro-4-(trifluoromethyl)aniline

Traditional Name

benefin

SMILES

CCCCN(CC)C1=C(C=C(C=C1[N+]([O-])=O)C(F)(F)F)[N+]([O-])=O

InChI Identifier

InChI=1S/C13H16F3N3O4/c1-3-5-6-17(4-2)12-10(18(20)21)7-9(13(14,15)16)8-11(12)19(22)23/h7-8H,3-6H2,1-2H3

InChI Key

InChIKey=SMDHCQAYESWHAE-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as dinitroanilines. These are organic compounds containing an aniline moiety, which is substituted at 2 positions by a nitro group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Aniline and substituted anilines

Direct Parent

Dinitroanilines

Alternative Parents

Substituents

Dinitroaniline
Trifluoromethylbenzene
Nitrobenzene
Nitroaromatic compound
Tertiary aliphatic/aromatic amine
Dialkylarylamine
C-nitro compound
Tertiary amine
Organic nitro compound
Organic oxoazanium
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Allyl-type 1,3-dipolar organic compound
Alkyl fluoride
Organic zwitterion
Hydrocarbon derivative
Organic oxide
Organonitrogen compound
Organofluoride
Organopnictogen compound
Organohalogen compound
Organic oxygen compound
Organic nitrogen compound
Amine
Alkyl halide
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

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

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	65.0°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00034 g/L	ALOGPS
logP	5.18	ALOGPS
logP	4.52	ChemAxon
logS	-6	ALOGPS
pKa (Strongest Basic)	-1.1	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	94.88 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	79.73 m³·mol⁻¹	ChemAxon
Polarizability	28.77 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0adi-4189000000-455a47c7acbdb603b982	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-1009000000-059ed03818ef425cb302	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-06vi-3019000000-2d0b0fea633d7772646a	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4l-9000000000-3ff165b76f5154399619	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-0009000000-e9e44e7c0e33354b601d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-1009000000-571f5778b80506bfeec9	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9043000000-023c514bbf6ee9857aab	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is a man-made compound that is used as a pesticide.

Minimum Risk Level

Not Available

Health Effects

Benfluralin has shown to be toxic to the kidneys, liver and thyroid in long-term animal studies.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

2319

ChEMBL ID

CHEMBL1256668

ChemSpider ID

2229

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

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

T3D3796.pdf

General References

EPA - Benfluralin [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Interstitial collagenase

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	4.44 uM	BSK_hDFCGF_MMP1_up	BioSeek

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 ]

Target Details

2. Bile salt sulfotransferase

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.11 uM	CLZD_SULT2A1_24	CellzDirect
AC50	4.60 uM	CLZD_SULT2A1_48	CellzDirect

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 ]

Target Details

3. Cytochrome P450 1A2

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	5.64 uM	CLZD_CYP1A2_24	CellzDirect

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 ]

Target Details

4. Cytochrome P450 1A1

General Function:: Vitamin d 24-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.
Gene Name:: CYP1A1
Uniprot ID:: P04798
Molecular Weight:: 58164.815 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	6.48 uM	CLZD_CYP1A1_24	CellzDirect
AC50	7.68 uM	CLZD_CYP1A1_48	CellzDirect

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 ]

Target Details

5. Cytochrome P450 3A4

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	7.39 uM	CLZD_CYP3A4_6	CellzDirect

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 ]

Target Details

6. Cytochrome P450 2B6

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.05 uM	CLZD_CYP2B6_6	CellzDirect
AC50	8.59 uM	CLZD_CYP2B6_24	CellzDirect
AC50	9.13 uM	CLZD_CYP2B6_48	CellzDirect

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 ]

Target Details

7. Estrogen receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.00 uM	OT_ERa_EREGFP_0120	Odyssey Thera

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 ]

Target Details

8. UDP-glucuronosyltransferase 1-1

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.08 uM	CLZD_UGT1A1_24	CellzDirect
AC50	9.44 uM	CLZD_UGT1A1_48	CellzDirect

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 ]

Benfluralin (T3D3796)

Structure for T3D3796: Benfluralin

Targets

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