Arsenic trioxide

Arsenic trioxide is the most important commercial compound of arsenic, and the main starting material for arsenic chemistry. It is the highly toxic byproduct of certain kinds of ore processing, for example gold mining.^[1]

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Preparation

• Burning arsenic in air.
• Hydrolysis of arsenic trichloride.
• Roasting of arsenide minerals. (Main industrial route)

Chemical properties

Arsenic trioxide is an amphoteric oxide which shows a marked preponderance for its acidic properties. It dissolves readily in alkaline solutions to give arsenites. It is much less soluble in acids, but will dissolve in hydrochloric acid to give arsenic trichloride or related species. It reacts with oxidizing agents such as ozone, hydrogen peroxide and nitric acid to give arsenic pentoxide, As₂O₅: the reaction with hydrogen peroxide can be explosive. It is also readily reduced to arsenic, and arsine (AsH₃) may also be formed.

Molecular structure

Tetrahedral molecules, As₄O₆, in α-form and in liquid and gas phases.

Uses

• Starting point for the manufacture of arsenic-based pesticides .(sodium arsenite, sodium arsenate, sodium cacodylate).
• Starting point for the manufacture of certain arsenic-based pharamaceuticals (Neosalvarsan) and veterinary products.
• Decolorizing agent for glasses and enamels.
• Preservative for wood.
• Hydrogen recombination poison for metallurgical studies.
• Starting point for the preparation of elemental arsenic, arsenic alloys and arsenide semiconductors.
• Use as a cytostatic in the treatment of refractory promyelocytic (M3) subtype of acute myeloid leukemia. The drug is available as Trisenox® ampules; each containing 10mg to be diluted for i.v. infusion.
• Arsenic trioxide is also used to treat leukemia in patients who have not responded to other medications.

Medical applications

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 trisulfide induces cancer cells to undergo apoptosis. Due to the toxic nature of arsenic, this drug carries significant risks.

The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.^[2]

Toxicology

See also: arsenicosis.

Arsenic trioxide is readily absorbed by the digestive system: toxic effects are also well known after inhalation of the dust or fumes and after skin contact. Elimination is rapid at first (half-life of 1–2 days), by methylation to cacodylic 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.

Cases of acute arsenic poisoning are known after inhalation and after skin contact with arsenic trioxide. The first signs are severe irritation, either of the respiratory tract or of the exposed skin, followed by longer term neurological problems. Even dilute solutions of arsenic trioxide are dangerous on contact with the eyes.

Chronic arsenic poisoning is known as arsenicosis: it is found after professional exposure (for example, in metal 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.

Arsenic trioxide has been shown to be a human carcinogen. 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.

Bibliography

• Institut national de recherche et de sécurité (INRS), Fiche toxicologique nº 89 : Trioxyde de diarsenic, 1989.
• AFHS Database on use as a cytostatic

References

1. ^ Giant Mine - Northwest Territories Region - Indian and Northern Affairs Canada. Retrieved on 2007-08-28.
2. ^ Lu J, Chew EH, Holmgren A (2007). "Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide". Proc. Natl. Acad. Sci. U.S.A. 104 (30): 12288-93. doi:10.1073/pnas.0701549104. PMID 17640917.