- Arsenic trioxide
Arsenic trioxide Identifiers CAS number PubChem ChemSpider UNII EC number DrugBank KEGG ChEMBL RTECS number CG3325000 ATC code L01 Jmol-3D images Image 1 Properties Molecular formula As2O3 Molar mass 197.841 g/mol Appearance White solid Density 3.74 g/cm3 Melting point
Solubility in water 20 g/L (25 °C)
Solubility soluble in dilute acids and alkalies, practically insoluble in organic solvents  Acidity (pKa) 9.2 Structure Crystal structure cubic (α)<180°C
monoclinic (β) >180°C
Molecular shape See text Dipole moment Zero Thermochemistry Std enthalpy of
o298 −657.4 kJ/mol Standard molar
o298 ? J.K−1.mol−1 Pharmacology Protein binding 75% bound Hazards MSDS External MSDS EU classification Very toxic (T+)
Carc. Cat. 1
Dangerous for the
R-phrases , , ,
S-phrases , , ,
NFPA 704 LD50 14.6 mg/kg (rat, oral) Related compounds Other anions Arsenic trisulfide Other cations Phosphorus trioxide
Related compounds Arsenic pentoxide
Supplementary data page Structure and
n, εr, etc. Thermodynamic
Solid, liquid, gas
Spectral data UV, IR, NMR, MS (what is: /?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Arsenic trioxide is the inorganic compound with the formula As2O3. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually. Many applications are controversial given the high toxicity of arsenic compounds.
Preparation and properties
Arsenic trioxide can be generated via many routine processing of arsenic compounds including the oxidation (combustion) of arsenic and arsenic-containing minerals in air. Illustrative is the roasting of orpiment, a typical arsenic sulfide ore.
- 2 As2S3 + 9 O2 → 2 As2O3 + 6 SO2
Most arsenic oxide is, however, obtained as a volatile by-product of the processing of other ores. For example, arsenopyrite, a common impurity in gold- and copper-containing ores, liberates arsenic trioxide upon heating in air. The processing of such minerals has led to numerous cases of poisonings. Only in China are arsenic ores intentionally mined.
Arsenic trioxide is an amphoteric oxide, and its aqueous solutions are weakly acidic. Thus, it dissolves readily in alkaline solutions to give arsenites. It is less soluble in acids, although it will dissolve in hydrochloric acid, giving chloro compounds, ultimately arsenic trichloride with concentrated acid. Only with strong oxidizing agents such as ozone, hydrogen peroxide, and nitric acid does it give arsenic pentoxide, As2O5. Reduction gives elemental arsenic or arsine (AsH3) depending on conditions. In this regard, arsenic trioxide differs from phosphorus trioxide which readily combusts to phosphorus pentoxide.
In the liquid and in the gas phase below 800 °C, arsenic trioxide has the formula As4O6 and is isostructural with P4O6. Above 800 °C As4O6 significantly dissociated into molecular As2O3, which adopts the same structure as N2O3. Three forms (polymorphs) are known in the solid state: cubic As4O6, containing molecular As4O6, and two related polymeric forms. The polymers, which both crystallized as monoclinic crystals, feature sheets of pyramidal AsO3 units that share O atoms.
Large scale applications include its use as a precursor to forestry products, in colorless glass production, and in electronics. Being the main compound of arsenic, the trioxide is the precursor to elemental arsenic, arsenic alloys, and arsenide semiconductors. Organoarsenic compounds, e.g. feed additives (Roxarsone) and pharmaceuticals (Neosalvarsan), are derived from arsenic trioxide. Bulk arsenic-based compounds sodium arsenite and sodium cacodylate are derived from the trioxide.
A variety of applications exploit arsenic's toxicity, including the use of the oxide as a wood preservative. Copper arsenates, which are derived from arsenic trioxide, are used on a large scale as a wood preservative in the US and Malaysia, but such materials are banned in many parts of the world. This practice remains controversial. In combination with copper(II) acetate arsenic trioxide gives the vibrant pigment known as paris green used both in paints and as a rodenticide. This application has been discontinued.
Despite the well known toxicity of arsenic, arsenic trioxide has long been of biomedical interest, dating to traditional Chinese medicine, where it is known as Pi Shuang and is still used to treat cancer and other conditions, and to homeopathy, where it is called arsenicum album. Some discredited patent medicines, e.g., Fowler's solution, contained derivatives of arsenic oxide. Arsenic trioxide under the trade name Trisenox (manufacturer: Cephalon) is a chemotheraputic agent of idiopathic function used to treat leukemia that is unresponsive to "first line" agents. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant risks. Use as a cytostatic in the treatment of refractory promyelocytic (M3) subtype of acute myeloid leukemia. The combination therapy of arsenic trioxide and all-trans retinoic acid (ATRA) has been approved by the U.S. Food and Drug Administration (FDA) for treatment of certain leukemias. University of Hong Kong developed a liquid form of arsenic trioxide that can be administered orally.
Arsenic trioxide also appears to be a promising therapeutic agent for autoimmune diseases.
Arsenic trioxide in combination with ascorbic acid and buthionine sulfoxide decrease intracellular glutathione to a greater extent, and render malignant cells more sensitive to apoptosis. Arsenic trioxide induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that this combination may be selectively toxic to some malignant cells. 
Two minerals are known to possess the As2O3 chemical formula: arsenolite(regular) and claudetite (monoclinic). Both are relatively rare secondary minerals found in oxidation zones of As-rich ore deposits (these are often Co-, Ni-, Ag- and U-bearing, too).
Arsenic trioxide is readily absorbed by the digestive system: toxic effects are also well known upon inhalation or upon skin contact. Elimination is rapid at first (half-life of 1–2 days), by methylation to monomethylarsonic acid and dimethylarsonic acid, and excretion in the urine, but a certain amount (30–40% in the case of repeated exposure) is incorporated into the bones, muscles, skin, hair and nails (all tissues rich in keratin) and eliminated over a period of weeks or months.
The first symptoms of acute arsenic poisoning by ingestion are digestive problems: vomiting, abdominal pains, diarrhea often accompanied by bleeding. Sub-lethal doses can lead to convulsions, cardiovascular problems, inflammation of the liver and kidneys and abnormalities in the coagulation of the blood. These are followed by the appearance of characteristic white lines (Mees stripes) on the nails and by hair loss. Lower doses lead to liver and kidney problems and to changes in the pigmentation of the skin. Even dilute solutions of arsenic trioxide are dangerous on contact with the eyes.
Chronic arsenic poisoning is known as arsenicosis. This disorder affects workers in smelters, in populations whose drinking water contains high levels of arsenic (0.3–0.4 ppm), and in patients treated for long periods with arsenic-based pharmaceuticals. Similarly, studies on workers exposed in copper foundries in the U.S., Japan and Sweden indicate a risk of lung cancer 6–10 times higher for the most exposed workers compared with the general population. Long-term ingestion of arsenic trioxide either in drinking water or as a medical treatment can lead to skin cancer. Reproductive problems (high incidence of miscarriage, low birth weight, congenital deformations) have also been indicated in one study of women exposed to arsenic trioxide dust as employees or neighbours of a copper foundry.
In Austria there lived the so called "arsenic eaters of Styria", who ingested doses far beyond the lethal dose of arsenic trioxide without any apparent harm. Arsenic is thought to enable strenuous work at high altitudes, e.g. in the Alps.
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- Case Studies in Environmental Medicine: Arsenic Toxicity
- IARC Monograph – Arsenic and Arsenic Compounds
- International Chemical Safety Card 0378
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- NTP Report on Carcinogens – Inorganic Arsenic Compounds
- Use of Arsenic Trioxide in Multiple Myeloma Treatment
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- Institute of Chemistry Austria, speciallised on arsenic and various arsenic compounds
Intracellular chemotherapeutic agents/antineoplastic agents (L01) SPs/MIs
(M phase)Block microtubule assemblyBlock microtubule disassembly
inhibitorIIICrosslinking of DNA
(CCNS)Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine
Photosensitizers/PDT OtherOther/ungroupedAmsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)
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