Tmic
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Record Information
Version2.0
Creation Date2009-03-06 18:57:58 UTC
Update Date2014-12-24 20:20:56 UTC
Accession NumberT3D0038
Identification
Common NameDisulfoton
ClassSmall Molecule
DescriptionDisulfoton is a manufactured organophosphate used as a pesticide. It is used mainly in agriculture to protect field and vegetable crops. (3)
Compound Type
  • Ester
  • Ether
  • Household Toxin
  • Organic Compound
  • Organophosphate
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Di-syston
Disipton
Disulfoton mixture
Disyston FE-10
Disystox
Dithiodemeton
Dithiosystox
Dution
Ekatin TD
Ekatine
Ethyl thiometon
Ethylthiodemeton
Ethylthiometon
Ethylthiometon b
Glebofos
Insyst-d
O,O-Diaethyl-S-(2-aethylthio-aethyl)-dithiophosphat
O,O-diethyl 2-(ethylthio)ethyl dithiophosphate
O,O-Diethyl 2-ethylthioethyl phosphorodithioate
O,O-Diethyl S-(2-(ethylthio)ethyl) dithiophosphate
O,O-Diethyl S-(2-(ethylthio)ethyl)phosphorodithioate
O,O-Diethyl S-(2-eththioethyl) phosphorodithioate
O,O-Diethyl S-(2-eththioethyl) thiothionophosphate
O,O-Diethyl S-(2-ethylmercaptoethyl) dithiophosphate
O,O-Diethyl S-2-(ethylthio)ethyl phosphorodithioate
O,O-Diethyl S-[2-(ethylsulfanyl)ethyl] dithiophosphate
O,O-Diethyl S-[2-(Ethylthio)ethyl] dithiophosphate
O,O-Diethyl S-[2-(ethylthio)ethyl] phosphorodithioate
O,o-diethyl-s-ethylmercapto-ethyl dithiophosphate
O,O-Ethyl S-2(ethylthio)ethyl phosphorodithioate
S-[2-(ethylsulfanyl)ethyl] O,O-dimethyl dithiophosphate
Solvigran
Solvirex
Thiodemeton
Thiodemetron
Chemical FormulaC8H19O2PS3
Average Molecular Mass274.404 g/mol
Monoisotopic Mass274.028 g/mol
CAS Registry Number298-04-4
IUPAC NameO,O-diethyl {[2-(ethylsulfanyl)ethyl]sulfanyl}phosphonothioate
Traditional NameO,O-diethyl [2-(ethylsulfanyl)ethyl]sulfanylphosphonothioate
SMILESCCOP(=S)(OCC)SCCSCC
InChI IdentifierInChI=1S/C8H19O2PS3/c1-4-9-11(12,10-5-2)14-8-7-13-6-3/h4-8H2,1-3H3
InChI KeyInChIKey=DOFZAZXDOSGAJZ-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
AppearanceColorless (pure) or dark yellow (technical grade) oil.
Experimental Properties
PropertyValue
Melting Point-25°C
Boiling PointNot Available
Solubility0.0163 mg/mL at 20 °C [BOWMAN,BT & SANS,WW (1983A)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0092 g/LALOGPS
logP4.11ALOGPS
logP3.03ChemAxon
logS-4.5ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area18.46 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity74.12 m³·mol⁻¹ChemAxon
Polarizability29.47 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-9720000000-8bca5c80358331bf4e35View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01p9-9110000000-7495c438425dc6f45bd4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-63ab2f848de48c719200View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-8790000000-84a300807312877e3e26View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-9550000000-f4d95badb9b9d9a3c055View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0gwb-5930000000-a170a87f479eadd5c40eView in MoNA
MSMass Spectrum (Electron Ionization)splash10-002r-9200000000-18197bdfeb7682331a47View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral (3) ; inhalation (3) ; dermal (3)
Mechanism of ToxicityDisulfoton 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: 25 mg/kg (Dermal, Rat) (2) LD50: 6.8 mg/kg (Oral, Rat) (2) LD50: 9.4 mg/kg (Intraperitoneal, Rat) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesDisulfoton is used mainly in agriculture to protect field and vegetable crops, as well as some fruit and nut crops. It may also be used in smaller quantities on home and garden plants and for mosquito control in swamps. (3)
Minimum Risk LevelAcute Inhalation: 0.006 mg/m3 (4) Intermediate Inhalation: 0.0002 mg/m3 (4) Acute Oral: 0.001 mg/kg/day (4) Intermediate Oral: 0.00009 mg/kg/day (4) Chronic Oral: 0.00006 mg/kg/day (4)
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.
SymptomsDepending on the amount of disulfoton that enters the body, effects on the nervous system, such as narrowing of the pupils, vomiting, diarrhea, drooling, difficulty in breathing, tremors, convulsions, and even death may occur. Skin contact with disulfoton may cause weakness and fatigue. (3)
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 ID3118
ChEMBL IDCHEMBL1332314
ChemSpider ID3006
KEGG IDC18400
UniProt IDNot Available
OMIM ID
ChEBI ID38661
BioCyc IDNot Available
CTD IDD004222
Stitch IDDisulfoton
PDB IDNot Available
ACToR ID1916
Wikipedia LinkDisulfoton
References
Synthesis ReferenceNot Available
MSDST3D0038.pdf
General References
  1. Usmani KA, Karoly ED, Hodgson E, Rose RL: In vitro sulfoxidation of thioether compounds by human cytochrome P450 and flavin-containing monooxygenase isoforms with particular reference to the CYP2C subfamily. Drug Metab Dispos. 2004 Mar;32(3):333-9. [14977868 ]
  2. American Conference of Governmental Industrial Hygienists (2001). Documentation of Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2001. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
  3. ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for disulfoton. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  4. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  5. International Programme on Chemical Safety (IPCS) INCHEM (1988). Pesticide Document for Disulfoton. [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. ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for disulfoton. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_IL1a_downBioSeek
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:
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_TGFb1_downBioSeek
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.93 uMCLZD_CYP2B6_6CellzDirect
AC504.52 uMCLZD_CYP2B6_24CellzDirect
AC509.48 uMCLZD_CYP2B6_48CellzDirect
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.59 uMCLZD_UGT1A1_24CellzDirect
AC504.63 uMCLZD_UGT1A1_48CellzDirect
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.34 uMCLZD_CYP2C9_48CellzDirect
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 ]