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{{Short description|Chemical compound (industrial chemical and medication)}}{{Use dmy dates|date=February 2024}}{{cs1 config |name-list-style=vanc |display-authors=6}}

factoids

Arsenic>As {{Color boxborder=darkgray}} O| pronounce = AR se nik tri OKS id| tradename = Trisenox, othersmonograph|arsenic-trioxide}}| MedlinePlus = a608017| DailyMedID = Arsenic trioxide| pregnancy_AU = X| pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = Intravenous| class = Antineoplastic agent| ATC_prefix = L01| ATC_suffix = XX27| ATC_supplemental = | legal_AU = S4| legal_AU_comment = | legal_BR = | legal_BR_comment =| legal_CA = | legal_CA_comment = | legal_DE = | legal_DE_comment = | legal_NZ = | legal_NZ_comment = | legal_UK = | legal_UK_comment = | legal_US = Rx-only DATE=30 JUNE 2022 ACCESS-DATE=3 FEBRUARY 2024, | legal_EU = Rx-only DATE=10 AUGUST 2010 ACCESS-DATE=3 FEBRUARY 2024, | legal_UN = | legal_UN_comment = | legal_status = | bioavailability = | protein_bound = 75%| metabolism = | metabolites =| onset = | elimination_half-life = | duration_of_action =| excretion = Urine| CAS_number = 1327-53-3correct|CAS}}| PubChem = 261004| IUPHAR_ligand = | DrugBank = DB01169| ChemSpiderID = 452539| UNII = S7V92P67HO| KEGG = C13619| KEGG2 = D02106| ChEBI = | ChEMBL = 1200978| NIAID_ChemDB =| PDB_ligand = sesquioxide,Arseneous oxide,Ratsbane,Arseneous anhydride,White arsenic,Aqua TofaniHTTP://SCIFUN.CHEM.WISC.EDU/CHEMWEEK/ARSENIC/ARSENIC.HTML TITLE = CHEMICAL OF THE WEEK: ARSENIC ACCESS-DATE = 3 AUGUST 2008 ARCHIVE-DATE = 2 AUGUST 2008, dead, | IUPAC_name = Diarsenic trioxide O=3| SMILES = O1[As]3O[As]2O[As](O3)O[As]1O2| StdInChI = 1S/As2O3/c3-1-4-2(3)5-1correct|chemspider}}| StdInChIKey = GOLCXWYRSKYTSP-UHFFFAOYSA-N| density = 3.74| density_notes = | melting_point = 312.2| melting_high = | melting_notes = | boiling_point = 465| boiling_notes = | solubility = 20 g/L (25 Â°C) (see text)| sol_units = | specific_rotation = }}{hide}Chembox| data page pagename = none|Section1={{Chembox Identifiers| EINECS = 215-481-4 |Section7 = {{Chembox HazardsPUBLISHER=AMERICAN ELEMENTS DATE=2021, | GHSPictograms = {{GHS05}} {{GHS06}} {{GHS08}} {{GHS09}}| GHSSignalWord = Danger300350|410}}201260270280303+361+353305+351+338+310363405|501}}| ExternalSDS=american elements SDS }}Arsenic trioxide is an inorganic compound with the formula {{chem|As|2|O|3}}.BOOK, Sun H, Biological Chemistry of Arsenic, Antimony and Bismuth, 2010, John Wiley & Sons, 9780470976227, 295,books.google.com/books?id=nrKXcXQF0QAC&pg=PA295, As an industrial chemical, its major uses include the manufacture of wood preservatives, pesticides, and glass.BOOK, Landner L, Chemicals in the Aquatic Environment: Advanced Hazard Assessment, 2012, Springer Science & Business Media, 9783642613340, 259,books.google.com/books?id=wZb6CAAAQBAJ&dq=Arsenic+trioxide+industrial+chemical&pg=PA259, It is sold under the brand name Trisenox among others when used as a medication to treat a type of cancer known as acute promyelocytic leukemia.WEB, Arsenic Trioxide Monograph for Professionals,www.drugs.com/monograph/arsenic-trioxide.html, Drugs.com, 15 November 2019, For this use it is given by injection into a vein.Common side effects include vomiting, diarrhea, swelling, shortness of breath, and headaches. Severe side effects may include APL differentiation syndrome and heart problems. Use during pregnancy or breastfeeding may harm the baby.BOOK, British national formulary : BNF 76, 2018, Pharmaceutical Press, 9780857113382, 907, 76, WEB, Arsenic trioxide (Trisenox) Use During Pregnancy,www.drugs.com/pregnancy/arsenic-trioxide.html, Drugs.com, 16 November 2019, Its mechanism in treating cancer is not entirely clear.Arsenic trioxide was approved for medical use in the United States in 2000. It is on the World Health Organization’s List of Essential Medicines.BOOK, ((World Health Organization)), The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023), 2023, 10665/371090, World Health Organization, World Health Organization, Geneva, WHO/MHP/HPS/EML/2023.02, free, Approximately 50,000 tonnes are produced a year.{{Ullmann | vauthors = Grund SC, Hanusch K, Wolf HU | title = Arsenic and Arsenic Compounds | doi = 10.1002/14356007.a03_113.pub2 }} Due to its toxicity, a number of countries have regulations around its manufacture and sale.BOOK, Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Chemicals, 2009, United Nations Publications, 9789211302196, 24,books.google.com/books?id=OtVZqdPHsm8C&dq=%22Arsenic+Trioxide%22+industrial+uses&pg=PA24, {{Dead link|date=February 2024 |bot=InternetArchiveBot |fix-attempted=yes }}

Uses

Medical

Arsenic trioxide is indicated in combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia whose acute promyelocytic leukemia is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; and for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose acute promyelocytic leukemia is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.WEB, Drug Approval Package: Trisenox (Arsenic Trioxide) NDA #21-248, U.S. Food and Drug Administration (FDA), 12 July 2001,www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-248_Trisenox.cfm, 3 February 2024, Arsenic trioxide is used to treat a type of cancer known as acute promyelocytic leukemia (APL). It may be used both in cases that are unresponsive to other agents, such as all-trans retinoic acid (ATRA) or as part of the initial treatment of newly diagnosed cases. This initial treatment may include combination therapy of arsenic trioxide with all-trans retinoic acid (ATRA).JOURNAL, Zhu J, Chen Z, Lallemand-Breitenbach V, de Thé H, How acute promyelocytic leukaemia revived arsenic, Nature Reviews. Cancer, 2, 9, 705–713, September 2002, 12209159, 10.1038/nrc887, 2815389, Effectiveness appears similar to Realgar/Indigo naturalis, which can be taken by mouth and is less expensive but is less available.WEB, Howard SC, Proposal for the inclusion of arsenic therapies in the WHO Model List of Essential Medicines for the treatment of acute promyelocytic leukemia.,web.archive.org/web/20220309054858/https://www.who.int/selection_medicines/committees/expert/22/applications/s8.2_arsenic.pdf,www.who.int/selection_medicines/committees/expert/22/applications/s8.2_arsenic.pdf, WHO, 15 November 2019, 9 March 2022, It works by encouraging the proteosome breakdown of retinoic acid receptor alpha, by moving the protein on to the nuclear matrix and increasing ubiquitination.JOURNAL, Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z, de Thé H, Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia, Proceedings of the National Academy of Sciences of the United States of America, 94, 8, 3978–3983, April 1997, 9108090, 10.1073/pnas.94.8.3978, 20553, 1997PNAS...94.3978Z, free, In the 1970s, Chinese researcher Zhang Tingdong and colleagues discovered this use.JOURNAL, Rao Y, Li R, Zhang D, A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered, Science China Life Sciences, 56, 6, 495–502, June 2013, 23645104, 10.1007/s11427-013-4487-z, free, It was approved for leukemia treatment in the United States in 2000.JOURNAL, 10.1016/j.apsb.2011.12.007, Developing new drugs from annals of Chinese medicine, 2012, Bian Z, Chen S, Cheng C, Wang J, Xiao H, Qin H, Acta Pharmaceutica Sinica B, 2, 1–7, free, University of Hong Kong developed a liquid form of arsenic trioxide that can be given by mouth.JOURNAL, Au WY, Kumana CR, Kou M, Mak R, Chan GC, Lam CW, Kwong YL, Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia, Blood, 102, 1, 407–408, July 2003, 12814916, 10.1182/blood-2003-01-0298, free, Organoarsenic compounds, such as feed additives (roxarsone) and medication (neosalvarsan), are derived from arsenic trioxide.{{citation needed|date=July 2020}}

Manufacturing

Industrial uses include usage 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. Bulk arsenic-based compounds sodium arsenite and sodium cacodylate are derived from the trioxide.{{citation needed|date=July 2020}}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 U.S. 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 in paints and as a rodenticide. This application has been discontinued.{{citation needed|date=July 2020}}

Alternative medicine

Despite the well known toxicity of arsenic, arsenic trioxide was used in traditional Chinese medicine, where it is known as pi-shuang ({{zh|c=砒霜|p=pÄ«shuāng|l=arsenic frost}}). In homeopathy, it is called arsenicum album. Some discredited patent medicines, e.g., Fowler’s solution, contained derivatives of arsenic oxide.BOOK, Gibaud S, Jaouen G, Medicinal Organometallic Chemistry, Arsenic-Based Drugs: From Fowler’s Solution to Modern Anticancer Chemotherapy, 2010, 32, 1–20, 10.1007/978-3-642-13185-1_1, Topics in Organometallic Chemistry, 2010moc..book....1G, 978-3-642-13184-4,

Toxicology

{{See also|Arsenic poisoning}}Arsenic trioxide is readily absorbed by the digestive system. Ingestion of as little as 0.1 grams can be fatal.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. Long-term ingestion of arsenic trioxide either in drinking water or as a medical treatment can lead to skin cancer. Reproductive problems (high incidences 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 the U.S., the OSHA 1910.1018 occupational permissible exposure limit for inorganic arsenic compounds in breathing zone air is 0.010 mg/m3.

Production and occurrence

File:St.BlasenArsenikstollen5.jpg|left|thumb|upright|Historic arsenic mine Sankt BlasenSankt BlasenArsenic trioxide can be generated via 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. 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,WEB,nwt-tno.inac-ainc.gc.ca/giant/atg_e.html,nwt-tno.inac-ainc.gc.ca/giant/atg_e.html," title="web.archive.org/web/20060627075016nwt-tno.inac-ainc.gc.ca/giant/atg_e.html,">web.archive.org/web/20060627075016nwt-tno.inac-ainc.gc.ca/giant/atg_e.html, dead, 27 June 2006, Giant Mine – Northwest Territories Region – Indian and Northern Affairs Canada, 28 August 2007, and after the mine is closed, the leftover trioxide waste will present environmental hazard (as was the case with the Giant Mine, for example). Only in China are arsenic ores intentionally mined.In the laboratory, it is prepared by hydrolysis of arsenic trichloride: {{chem|As|2|O|3}} occurs naturally as two minerals, arsenolite (cubic) and claudetite (monoclinic). Both are relatively rare secondary minerals found in oxidation zones of As-rich ore deposits. Sheets of {{chem2|As2O3}} stand for part of structures of the recently discovered minerals lucabindiite, {{chem2|(K,NH4)As4O6(Cl,Br)}},Garavelli et al. 2013,www.minsocam.org/msa/ammin/toc/Abstracts/2013_Abstracts/FM13_Abstracts/Garavelli_p470_13.pdf and its sodium-analogue torrecillasite.Kampf et al. 2013,minmag.geoscienceworld.org/content/78/3/747.abstract

Properties and reactions

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.Greenwood, N. N.; & Earnshaw, A. (1997). Chemistry of the Elements (2nd Edn.), Oxford:Butterworth-Heinemann. {{ISBN|0-7506-3365-4}}.With anhydrous HF and HCl, it gives {{chem2|AsF3}} and the trichloride:Handbook of Preparative Inorganic Chemistry, 2nd Ed. Edited by G. Brauer, Academic Press, 1963, NY. Only with strong oxidizing agents such as ozone, hydrogen peroxide, and nitric acid does it yield arsenic pentoxide, {{chem|As|2|O|5}} or its corresponding acid: In terms of its resistance to oxidation, arsenic trioxide differs from phosphorus trioxide, which readily combusts to phosphorus pentoxide.Reduction gives elemental arsenic or arsine ({{chem|AsH|3}}) depending on conditions: This reaction is used in the Marsh test.

Structure

In the liquid and gas phase below 800 Â°C, arsenic trioxide has the formula {{chem|As|4|O|6}} and is isostructural with {{chem|link=phosphorus trioxide|P|4|O|6}}. Above 800 Â°C {{chem|As|4|O|6}} significantly dissociates into molecular {{chem|As|2|O|3}}, which adopts the same structure as {{chem|link=dinitrogen trioxide|N|2|O|3}}. Three forms (polymorphs) are known in the solid state: a high temperature ( > 110 Â°C) cubic {{chem|As|4|O|6}}, containing molecular {{chem|As|4|O|6}}, and two related polymeric forms.Wells A.F. Structural Inorganic Chemistry. 5th. London, England: Oxford University Press, 1984. Print. {{ISBN|0-19-855370-6}} The polymers, which both crystallize as monoclinic crystals, feature sheets of pyramidal {{chem|AsO|3}} units that share O atoms.BOOK, Holleman AF, Wiberg E, Inorganic Chemistry, Academic Press, San Diego, 2001, 0-12-352651-5, {|align=“center” class=“wikitable”170px) (File:Claudetite-I-layer-3D-balls.png|150px) (File:Claudetite-II-layer-3D-balls.png|220px)arsenolite(cubic)}}{{centerclaudetite II(monoclinic)}}

Society and culture

Environmental effects

Smelting and related ore processing often generate arsenic trioxide, which poses a risk to the environment. For example, the Giant Mine in Canada processed substantial amounts of arsenopyrite-contaminated gold ores.

Arsenic poisoning in literature and society

The poisonous properties of arsenic are the subject of an extensive literature.WEB,caselaw.lp.findlaw.com/scripts/getcase.pl?navby=search&case=/data2/circs/9th/9716830.html&friend=usatoday, Stanton v Benzler 9716830, U.S. 9th Circuit Court of Appeals, 17 June 1998, 9 June 2008, (...) 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., BOOK, The Elements of Murder: A History of Poison, Emsley J, Oxford University Press, 2006, 978-0-19-280600-0, Arsenic, 93–197, BOOK, Flaubert G, Gustave Flaubert, Madame Bovary, 1856, 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.NEWS, Arsenic Eaters, The New York Times, 26 July 1885,www.nytimes.com/1885/07/26/archives/arsenic-eaters.html, JOURNAL, The arsenic eaters of Styria: a different picture of people who were chronically exposed to arsenic, Przygoda G, Feldmann J, Cullen WR, Applied Organometallic Chemistry, 15, 6, 457–462, 2001, 10.1002/aoc.126, BOOK, The Arsenic Century,archive.org/details/arseniccenturyho00whor, limited, Whorton JC, Oxford University Press, 978-0-19-960599-6, 2010, 270–273,

References

{{reflist}}

External links

• Case Studies in Environmental Medicine: Arsenic Toxicity
• WEB, Arsenic and Arsenic Compounds, February 1998, Summaries & Evaluations, International Agency for Research on Cancer (IARC),www.inchem.org/documents/iarc/suppl7/arsenic.html,
• International Chemical Safety Card 0378
• Safety Data Sheet from American Elements
• NIOSH Pocket Guide to Chemical Hazards
• ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s015arse.pdf" title="web.archive.org/web/20051111213656ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s015arse.pdf">NTP Report on Carcinogens – Inorganic Arsenic Compounds
• {{inrs|title=Trioxyde d’arsenic|number=89|year=1989}}

{{Chemotherapeutic agents}}{{Arsenic compounds}}{{Oxides}}{{Authority control}}