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The enzyme [[thioredoxin reductase]] has recently been identified as a target for arsenic trioxide.<ref name="pmid17640917">{{cite journal |author=Lu J, Chew EH, Holmgren A |title=Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=30 |pages=12288-93 |year=2007 |pmid=17640917 |doi=10.1073/pnas.0701549104}}</ref> |
The enzyme [[thioredoxin reductase]] has recently been identified as a target for arsenic trioxide.<ref name="pmid17640917">{{cite journal |author=Lu J, Chew EH, Holmgren A |title=Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=30 |pages=12288-93 |year=2007 |pmid=17640917 |doi=10.1073/pnas.0701549104}}</ref> |
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Arsenic trioxide is also a very commonly used [[homeopathic medicine]]. Called by its Latin name, [[Arsenicum album]], there is numerous human clinical and animal trials that shows therapeutic effects from homeopathic doses of this substance.<ref>Khuda-Bukhsh, AR, Pathak, S, Guha, B. Can Homeopathic Arsenic Remedy Combat Arsenic Poisoning in Humans Exposed to Groundwater Arsenic Contamination?: A Preliminary Report on First Human Trial, eCAM, doi:10.1093/ecam/neh124</ref>, <ref>Belon P, Banerjee A, Karmakar SR, Biswas SJ, Choudhury SC, Banerjee P, Das JK, Pathak S, Guha B, Paul S, Bhattacharjee N, Khuda-Bukhsh AR. Homeopathic remedy for arsenic toxicity?: Evidence-based findings from a randomized placebo-controlled double blind human trial. Sci Total Environ. 2007 Jul 10. [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17628642&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum]</ref>, <ref>Mallick, P, Chakrabarti (Mallick), J, Bibhas, G, Khuda-Bukhsh, AR. Ameliorating Effect of Microdoses of a Potentized Homeopathic Durg, Arsencium Album, on Arsenic-Induced Toxicity in Mice. BMC Complementary and Alternative Medicine, 2003,3:7.</ref> |
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==Toxicology== |
==Toxicology== |
Revision as of 18:13, 25 January 2008
File:Arsenic trioxide.png | |
Clinical data | |
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ATC code | |
Pharmacokinetic data | |
Protein binding | 75% bound |
Identifiers | |
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CAS Number | |
DrugBank | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.014.075 |
Chemical and physical data | |
Formula | As2O3 |
Molar mass | 197.841 g/mol g·mol−1 |
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]
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]
Arsenic trioxide is also a very commonly used homeopathic medicine. Called by its Latin name, Arsenicum album, there is numerous human clinical and animal trials that shows therapeutic effects from homeopathic doses of this substance.[3], [4], [5]
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
- ^ "Giant Mine - Northwest Territories Region - Indian and Northern Affairs Canada". Retrieved 2007-08-28.
- ^ 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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Khuda-Bukhsh, AR, Pathak, S, Guha, B. Can Homeopathic Arsenic Remedy Combat Arsenic Poisoning in Humans Exposed to Groundwater Arsenic Contamination?: A Preliminary Report on First Human Trial, eCAM, doi:10.1093/ecam/neh124
- ^ Belon P, Banerjee A, Karmakar SR, Biswas SJ, Choudhury SC, Banerjee P, Das JK, Pathak S, Guha B, Paul S, Bhattacharjee N, Khuda-Bukhsh AR. Homeopathic remedy for arsenic toxicity?: Evidence-based findings from a randomized placebo-controlled double blind human trial. Sci Total Environ. 2007 Jul 10. [1]
- ^ Mallick, P, Chakrabarti (Mallick), J, Bibhas, G, Khuda-Bukhsh, AR. Ameliorating Effect of Microdoses of a Potentized Homeopathic Durg, Arsencium Album, on Arsenic-Induced Toxicity in Mice. BMC Complementary and Alternative Medicine, 2003,3:7.
External links
- - Solubility of As2O3 in water as function of temperature
- Case Studies in Environmental Medicine: Arsenic Toxicity
- IARC Monograph – Arsenic and Arsenic Compounds
- International Chemical Safety Card 0378
- NIOSH Pocket Guide to Chemical Hazards
- NTP Report on Carcinogens – Inorganic Arsenic Compounds
- Use of Arsenic Trioxide in Multiple Myeloma Treatment
- The use of Arsenic trioxide in medicine.
- Institut national de recherche et de sécurité (1989). "Trioxyde d'arsenic." Fiche toxicologique n° 89. Paris:INRS. (in French)