Tmic
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Record Information
Version1.0
Creation Date2009-03-06 18:58:19 UTC
Update Date2016-11-09 01:08:11 UTC
Accession NumberCHEM000196
Identification
Common NameArsenic trioxide
ClassSmall Molecule
DescriptionArsenic trioxide is a chemotheraputic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents. It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant health risks. The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.
Contaminant Sources
  • Clean Air Act Chemicals
  • HMDB Contaminants - Urine
  • HPV EPA Chemicals
  • IARC Carcinogens Group 1
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Antineoplastic Agent
  • Arsenic Compound
  • Drug
  • Homeopathic Agent
  • Inorganic Compound
  • Metabolite
  • Metalloid
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
Arseni trioxydumHMDB
Arsenic oxidearsenous trioxideHMDB
Arsenious acidHMDB
Arsenious trioxideHMDB
ArsentrioxideHMDB
TrixenoxHMDB
Arsenic(III) oxideHMDB
Arsenous anhydrideHMDB
Diarsenic trioxideHMDB
NaonobinHMDB
Chemical FormulaAs2O3
Average Molecular Mass197.841 g/mol
Monoisotopic Mass197.828 g/mol
CAS Registry Number1327-53-3
IUPAC Namebicyclo[1.1.1]diarsoxane
Traditional Namearsenic trioxide
SMILESO1[As]2O[As]1O2
InChI IdentifierInChI=1S/As2O3/c3-1-4-2(3)5-1
InChI KeyGOLCXWYRSKYTSP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as miscellaneous arsenites. These are inorganic compounds in which the largest metallic oxoanion is arsenite, to which either no atom or a non metal atom is bonded.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassMiscellaneous mixed metal/non-metals
Sub ClassMiscellaneous metallic oxoanionic compounds
Direct ParentMiscellaneous arsenites
Alternative Parents
Substituents
  • Arsenite
  • Trivalent inorganic arsenic compound
  • Inorganic salt
  • Inorganic metalloid salt
  • Inorganic arsenic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point465°C
Boiling PointNot Available
Solubility1.7E+004 mg/L (at 16°C)
Predicted Properties
PropertyValueSource
logP2.31ChemAxon
pKa (Strongest Basic)-5.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.69 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity4.05 m³·mol⁻¹ChemAxon
Polarizability7.14 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-0002-0900000000-14fe3cc303b049cb7cedView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-6c867befd4a45c267fb2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0900000000-6c867befd4a45c267fb2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-0900000000-6c867befd4a45c267fb2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0900000000-1b8349532ab21b78bc14View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0900000000-1b8349532ab21b78bc14View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-0900000000-1b8349532ab21b78bc14View in MoNA
Toxicity Profile
Route of ExposureOral (8) ; inhalation (8) ; dermal (8)
Mechanism of ToxicityThe mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis. Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carginogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (5, 3)
MetabolismArsenic is mainly absorbed by inhalation or ingestion, and to a lesser extent by dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (9) The metabolism of arsenic trioxide involves reduction of pentavalent arsenic to trivalent arsenic by arsenate reductase and methylation of trivalent arsenic to monomethylarsonic acid and monomethylarsonic acid to dimethylarsinic acid by methyltransferases. The main site of methylation reactions appears to be the liver. Arsenic is stored mainly in liver, kidney, heart, lung, hair and nails. Route of Elimination: Trivalent arsenic is mostly methylated in humans and excreted in urine.
Toxicity ValuesLD50: 871 mg/kg (Intraperitoneal, Rat) (6) LD50: 31 500 ug/kg (Oral, Mouse) (6) LD50: 9800 ug/kg (Subcutaneous, Mouse) (6) LD50: 10 700 ug/kg (Intravenous, Mouse) (6)
Lethal Dose200 mg for an adult human. (7)
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (12)
Uses/SourcesArsenic trioxide is a byproduct of certain kinds of ore processing. It is the starting point for the manufacture of many arsenic-based products, including pesticides, pharamaceuticals, alloys, and semiconductors. It is also used as a wood preservative and decolorizing agent. (13) It is also use for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Minimum Risk LevelAcute Oral: 0.005 mg/kg/day (11) Chronic Oral: 0.0003 mg/kg/day (11) Chronic Inhalation: 0.01 mg/m3 (11)
Health EffectsArsenic poisoning can lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. Arsenic is also a known carcinogen, especially in skin, liver, bladder and lung cancers. (5, 9)
SymptomsSymptoms of overdose include convulsions, muscle weakness and confusion. Exposure to lower levels of arsenic can cause nausea and vomiting, decreased production of red and white blood cells, abnormal heart rhythm, and damage to blood vessels.
TreatmentArsenic poisoning can be treated by chelation therapy, using chelating agents such as dimercaprol, EDTA or DMSA. Charcoal tablets may also be used for less severe cases. In addition, maintaining a diet high in sulfur helps eliminate arsenic from the body. (9)
Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB0015300
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkArsenic trioxide
Chemspider ID452539
ChEBI IDNot Available
PubChem Compound ID518740
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSLink
General References
1. Lu J, Chew EH, Holmgren A: Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12288-93. Epub 2007 Jul 18.