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.2 It is found in nature as the minerals arsenolite, cubic and claudetite, monoclinic.
In the liquid and in the gas phase below 800 °C it is As4O6, (isostructural with P4O6).3 Above 800°C partial dissociation occurs to give molecular As2O3 with the N2O3 structure.3 In the solid state there are three forms, a cubic form which contains molecular As4O6 and two related monoclinic forms that contain layers of pyramidal AsO3 units sharing O atoms.3
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.4
Arsenic trioxide is also used to treat leukemia in patients who have not responded to other medications5
In Austria there lived the so called "arsenic eaters", who ingested doses far beyond the lethal dose of arsenic trioxide without any apparent harm. They thought that they would become more powerful for their strenuous work in the Alps. 678
Arsenic trioxide was mixed with copper(II) acetate to form the extremely toxic but exceedingly vibrant pigment known as paris green for its use as a rodenticide in the paris subways.
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 combination therapy of arsenic trioxide and all-trans retinoic acid (ATRA) could clearly improve survival rates.
The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.12
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.
Natural occurrence
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).
Bibliography
Institut national de recherche et de sécurité (INRS), Fiche toxicologique nº 89 : Trioxyde de diarsenic, 1989.
^ abc Egon Wiberg, Arnold Frederick Holleman (2001) Inorganic Chemistry, Elsevier ISBN 0123526515
^ .Steven L. Soignet et al. (2001). "United States Multicenter Study of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia". Journal of Clinical Oncology19 (18): 3852–3860.
^ .Antman, K. H. (2001). "Introduction: The history of arsenic trioxide in cancer therapy". Oncologist6(Suppl. 2) (1–2): 2006.
^ "Stanton v Benzler 9716830". U.S. 9th Circuit Court of Appeals (1998-06-17). Retrieved on 2008-06-09. "(...) convicted by a jury of first degree murder for poisoning her ex-husband. Her ex-husband's body was found with traces of arsenic trioxide in it."
^ ab Emsley, John (2006). "Arsenic", The Elements of Murder: A History of Poison. Oxford University Press, 93 –197. ISBN 9780192806000.
^ 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.