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Record Information
Version2.0
Creation Date2009-03-06 18:58:19 UTC
Update Date2014-12-24 20:21:22 UTC
Accession NumberT3D0225
Identification
Common NamePhorate
ClassSmall Molecule
DescriptionPhorate is an organophosphate insecticide and acaricide that controls pests by systemic, contact, and fumigant action. It is used against sucking and chewing insects, leafhoppers, leafminers, mites, some nematodes and rootworms. Phorate is used in pine forests and on root and field crops, including corn, cotton, coffee, some ornamental and herbaceous plants and bulbs. Phorate is extremely toxic; it is a Restricted Use Pesticide (RUP) and is among the most poisonous chemicals commonly used for pest control. (1)
Compound Type
  • Ester
  • Ether
  • Organic Compound
  • Organophosphate
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Aastar
Agrimet
Forate
Geomet
Granutox
O,O-diethyl ethylthiomethyl phosphorodithioate
O,O-diethyl S-(ethylthio)methyl phosphorodithioate
O,O-diethyl S-(ethylthiomethyl) phosphorodithioate
O,O-diethyl s-ethylmercaptomethyl dithiophosphate
O,O-diethyl S-ethylmercaptomethyl dithiophosphonate
O,O-diethyl S-ethylthiomethyl dithiophosphate
O,O-diethyl S-ethylthiomethyl dithiophosphonate
O,O-diethyl s-ethylthiomethyl thiothionophosphate
O,O-diethyl S-[(ethylsulfanyl)methyl] dithiophosphate
O,O-diethyl S-[(ethylsulfanyl)methyl] phosphorodithioate
O,O-diethyl S-[(ethylthio)methyl] phosphorodithioate
O,O-diethyl-S-((ethylthio)methyl)phosphorodithioate
Phoric acid
Phosphorodithioic acid, O,O-diethyl S-((ethylthio)methyl) ester
Rampart
Terrathion
Thimate
Thimenox
Thimet
Timet
Vegfru foratox
Vergfru foratox
Volphor
Chemical FormulaC7H17O2PS3
Average Molecular Mass260.377 g/mol
Monoisotopic Mass260.013 g/mol
CAS Registry Number298-02-2
IUPAC NameO,O-diethyl {[(ethylsulfanyl)methyl]sulfanyl}phosphonothioate
Traditional Namerampart
SMILESCCOP(=S)(OCC)SCSCC
InChI IdentifierInChI=1S/C7H17O2PS3/c1-4-8-10(11,9-5-2)13-7-12-6-3/h4-7H2,1-3H3
InChI KeyInChIKey=BULVZWIRKLYCBC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dithiophosphate o-esters. These are o-ester derivatives of dithiophosphates, with the general structure RSP(O)(O)=S (R = organyl group).
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic dithiophosphoric acids and derivatives
Sub ClassDithiophosphate O-esters
Direct ParentDithiophosphate O-esters
Alternative Parents
Substituents
  • Dithiophosphate o-ester
  • Dithiophosphate s-ester
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Organothiophosphorus compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
AppearancePhorate is a clear pale-yellow liquid with a skunk-like odor. (1)
Experimental Properties
PropertyValue
Melting Point-43.7°C
Boiling Point188 °C at 2 torr 118-120 °C at 0.8 torr
Solubility0.05 mg/mL at 25 °C [MARTIN,H & WORTHING,CR (1977)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.037 g/LALOGPS
logP3.71ALOGPS
logP3.16ChemAxon
logS-3.8ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity68.95 m³·mol⁻¹ChemAxon
Polarizability27.46 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-8690000000-389dad16a59caffc79a8JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0bt9-4930000000-536940f69767dcfa3259JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03fr-9410000000-edd61bd6bf01829ee071JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03fr-9100000000-9231513319c344a8e4a0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1890000000-2773b2f8dd4dd604b399JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06si-7950000000-9aac6c50700b539fd079JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00m0-2910000000-996ded89e76694fe1689JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01t9-9560000000-e1ae6dcd5627a1573a5dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00b9-5900000000-a2feb285263c94a0fdd5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-9000000000-39d4ad61034257710be6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0590000000-176c82bfdacfb604a119JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0zfr-0910000000-53991a594f0917a1db89JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-2910000000-8f1600d8f0b4bb436a5fJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-004i-9200000000-982f1838d1ab58fda966JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral (1) ; inhalation (1) ; dermal. (1)
Mechanism of ToxicityPhorate is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesLD50: 1.0 mg/kg (Oral, Rat) (1) LD50: 3.5 to 6.59 mg/kg (Oral, Mouse) (1) LD50: 20 mg/kg (Oral, Guinea pig) (1) LD50: 5.7 mg/kg (Dermal, Rat) (1) LD50: 5.2 mg/kg (Dermal, Rabbit) (1) LD50: 20-30 mg/kg (Dermal, Guinea pig) (1) LC50: 11 mg/m3 (Inhalation, Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is a man-made compound that is used as a pesticide.
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of acute oral exposure may include blurred vision, headache, inability to concentrate, fatigue, nausea, diarrhea, irregular heart and respiration rates, tremors, excessive sweating, confusion and convulsions. Death can occur at high doses due to respiratory arrest or lung constriction. Symptoms resulting from phorate inhalation or skin contact may occur from a few minutes up to 12 hours after exposure. Workers chronically exposed to organophosphates have shown slow thinking, memory defects, irritability, delayed reaction time, and anxiety. Symptoms included a lowering of the heart rate. (1)
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID4790
ChEMBL IDCHEMBL510014
ChemSpider ID4626
KEGG IDC18690
UniProt IDNot Available
OMIM ID
ChEBI ID38764
BioCyc IDNot Available
CTD IDD010702
Stitch IDPhorate
PDB IDNot Available
ACToR ID7903
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0225.pdf
General References
  1. Extension Toxicology Network (1993). Pesticide Information Profile for Phorate. A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. [Link]
  2. International Programme on Chemical Safety (IPCS) INCHEM (1988). Pesticide Document for Phorate. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Henderson MC, Krueger SK, Siddens LK, Stevens JF, Williams DE: S-oxygenation of the thioether organophosphate insecticides phorate and disulfoton by human lung flavin-containing monooxygenase 2. Biochem Pharmacol. 2004 Sep 1;68(5):959-67. [15294458 ]
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Kashyap SK, Jani JP, Saiyed HN, Gupta SK: Clinical effects and cholinesterase activity changes in workers exposed to Phorate (Thimet). J Environ Sci Health B. 1984 Jun-Jul;19(4-5):479-89. [6470423 ]
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
TypeValueAssay TypeAssay Source
AC503.40 uMNVS_ADME_hCYP1A1Novascreen
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:
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 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. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.01 uMATG_RARa_TRANSAttagene
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:
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.06 uMNVS_ADME_hCYP2C19Novascreen
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 ]