{{Chembox | verifiedrevid = 444387517 | ImageFileL1 = Roxarsone.png | ImageClassL1 = skin-invert-image | ImageFileL1_Ref = {{chemboximage|correct|??}} | ImageSizeL1 = 121 | ImageAltL1 = Skeletal formula of roxarsone | ImageFileR1 = Roxarsone-3D-spacefill.png | ImageClassR1 = bg-transparent | ImageSizeR1 = 130 | ImageAltR1 = Space-filling model of the roxarsone molecule | ImageName = Kekulé, skeletal formula of 4-hydroxy-3-nitrobenzenearsonic acid | PIN = (4-Hydroxy-3-nitrophenyl)arsonic acid | OtherNames = |Section1={{Chembox Identifiers | CASNo_Ref = {{cascite|correct|??}} | CASNo = 121-19-7 | PubChem = 5104 | ChemSpiderID = 4925 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | EINECS = 204-453-7 | ChEMBL = 1321154 | UNNumber = 3465 | KEGG = D05771 | KEGG_Ref = {{keggcite|correct|kegg}} | MeSHName = Roxarsone | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 35817 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = H5GU9YQL7L | RTECS = CY5250000 | Beilstein = 1976533 | Gmelin = 1221211 | SMILES = Oc1ccc(cc1[N+](=O)[O-])[As](O)(O)=O | SMILES1 = OC1=CC=C(C=C1[N+]([O-])=O)[As](O)(O)=O | StdInChI = 1S/C6H6AsNO6/c9-6-2-1-4(7(10,11)12)3-5(6)8(13)14/h1-3,9H,(H2,10,11,12) | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | InChI = 1/C6H6AsNO6/c9-6-2-1-4(7(10,11)12)3-5(6)8(13)14/h1-3,9H,(H2,10,11,12) | StdInChIKey = XMVJITFPVVRMHC-UHFFFAOYSA-N | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | InChIKey = XMVJITFPVVRMHC-UHFFFAOYAF }} |Section2={{Chembox Properties | Formula = {{Chem|C|6|AsNH|6|O|6}} | MolarMass = 263.0365 g mol<sup>−1</sup> | MeltingPt = > | MeltingPtC = 300 }} |Section3={{Chembox Hazards | GHSPictograms = {{GHS skull and crossbones}} {{GHS environment}} | GHSSignalWord = '''DANGER''' | HPhrases = {{H-phrases|301|331|410}} | PPhrases = {{P-phrases|261|273|301+310|311|501}} }} }}
'''Roxarsone''' is an organoarsenic compound that has been used in poultry production and to a lesser extent in pig production as a feed additive to increase weight gain, for greater feed efficiency, to improve pigmentation, and as a coccidiostat.<ref name=FDA>{{cite news | author = U.S. Food and Drug Administration | url = https://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm258313.htm | archive-url = https://web.archive.org/web/20110612145259/http://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm258313.htm | url-status = dead | archive-date = June 12, 2011 | title = Questions and Answers Regarding 3-Nitro (Roxarsone) | date = June 8, 2011}}</ref><ref name="NYT2011">{{cite web | last1=Harris | first1=Gardiner | last2=Grady | first2=Denise | title=Pfizer Suspends Sales of Chicken Drug | website=The New York Times | date=9 June 2011 | url=https://www.nytimes.com/2011/06/09/business/09arsenic.html | access-date=19 October 2018}}</ref> Until June 2011, it was approved for use in the United States, Canada, Australia, and 12 other countries.<ref name="NYT2011"></ref> It is no longer approved for use in most jurisdictions.<ref name=FCT>{{cite journal |last1=Baynes |first1=Ronald E. |last2=Dedonder |first2=Keith D. |last3=Kissell |first3=Lindsey W. |last4=Mzyk |first4=Danielle A. |last5=Marmulak |first5=Tara |last6=Smith |first6=Geoffrey |last7=Tell |first7=Lisa A. |last8=Gehring |first8=Ronette |last9=Davis |first9=Jennifer L. |last10=Riviere |first10=Jim E. |title=Health concerns and management of select veterinary drug residues |journal=Food and Chemical Toxicology |volume=88 |pages=112–122 |year=2016 |doi=10.1016/j.fct.2015.12.020 |url=https://doi.org/10.1016/j.fct.2015.12.020|doi-access=free }}</ref>
Roxarsone has been banned in the European Union since 1999.<ref name="MJ">{{cite web| url=https://www.motherjones.com/tom-philpott/2011/06/arsenic-chicken-fda-roxarsone-pfizer| title=Some Arsenic With That Supermarket Chicken?| first=Tom| last=Philpott| website=Mother Jones| date=11 June 2011| access-date=19 October 2018}}</ref> Its use in the United States was voluntarily ended by the manufacturers in June 2011, and it has been illegal since 2013.<ref name="withdrawn"/><ref>{{Cite news|url=https://www.chickencheck.in/faq/arsenic-chicken/|title=Arsenic in Chicken: Does chicken meat contain arsenic?|date=21 July 2017|work=Chicken Check In|access-date=20 March 2018|language=en-US}}</ref> Its use was suspended in Malaysia in June 2011.<ref name="Malaysia">{{cite web | title=Malaysian Pharmaceutical Society | website=Malaysian Pharmaceutical Society | url=http://www.mps.org.my/newsmaster.cfm?&menuid=36&action=view&retrieveid=3448 | access-date=19 October 2018}}</ref> It was banned in Canada in August 2011.<ref name="Canada">{{cite news | title=Sales halted after arsenic found in chicken drug | website=The Globe and Mail | date=3 May 2018 | url=https://www.theglobeandmail.com/life/health-and-fitness/sales-halted-after-arsenic-found-in-chicken-drug/article591962/ | access-date=19 October 2018}}</ref> In Australia, its use was discontinued in 2012.<ref>{{cite web| url=https://www.chicken.org.au/wp-content/uploads/2018/05/New_ACMF_Position-Statement_Roxarsone_180222F-3.pdf| title=Roxarsone not used in the Australian chicken industry| publisher=Australian Meat Chicken Federation| date=24 May 2018| access-date=19 October 2018}}</ref>
==Production and applications== Roxarsone is a derivative of phenylarsonic acid (C<sub>6</sub>H<sub>5</sub>As(O)(OH)<sub>2</sub>). It was first reported in a 1923 British patent that described the nitration and diazotization of arsanilic acid.<ref>GB 226255 19230718</ref> When blended with calcite powder, it is used in poultry feed premixes in some parts of the world. Where available, it can be purchased in 5%, 20% and 50% concentrations.{{cn|date=December 2022}}
Roxarsone was marketed as '''3-Nitro''' by Zoetis, a former subsidiary of Pfizer now a publicly traded company. In 2006, approximately one million kilograms of roxarsone were produced in the U.S.<ref>{{cite news | author = Hileman, B. | url = http://pubs.acs.org/cen/government/85/8515gov2.html | title = Arsenic in Chicken Production | publisher = Chemical and Engineering News | date = April 9, 2007 | pages = 34–35}}</ref>
==Marketing approval in the United States== Roxarsone is one of four arsenical animal drugs that had been approved by the U.S. Food and Drug Administration (FDA) for use in poultry and swine, along with nitarsone, arsanilic acid, and carbarsone.<ref name=FDA /> In September 2013, the FDA announced that Zoetis and Fleming Laboratories would voluntarily withdraw current roxarsone, arsanilic acid, and carbarsone approvals, leaving only nitarsone approvals in place.<ref name="withdrawn">{{cite news | author = U.S. Food and Drug Administration | url = https://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm370568.htm | archive-url = https://web.archive.org/web/20131022074630/http://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm370568.htm | url-status = dead | archive-date = October 22, 2013 | title = FDA Response to Citizen Petition on Arsenic-based Animal Drugs | date = September 20, 2011}}</ref> In 2015, the FDA withdrew the approval of using nitarsone in animal feeds. The ban came into effect at the end of 2015.<ref name="nitarsone">{{cite news | author = U.S. Food and Drug Administration | url =https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm440668.htm | archive-url =https://web.archive.org/web/20150404001249/http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm440668.htm | url-status =dead | archive-date =April 4, 2015 | title =FDA Announces Pending Withdrawal of Approval of Nitarsone | date = April 1, 2015}}</ref>
==Controversy== Roxarsone has attracted attention as a source of arsenic contamination of poultry and other foods.<ref>{{cite news | author = Institute for Agriculture and Trade Policy | url = http://www.iatp.org/documents/playing-chicken-avoiding-arsenic-in-your-meat | title = Playing Chicken: Avoiding Arsenic in Your Meat | date = April 4, 2006}}</ref><ref>{{cite news | author = Consumer Reports | url = http://www.consumerreports.org/cro/magazine/2012/11/arsenic-in-your-food/index.htm | title = Arsenic in your food | date = November 2012}}</ref> In June 2011, the manufacturers suspended sales of roxarsone in the U.S. and Canada in response to a study by the Food and Drug Administration (FDA) that found that roxarsone use was associated with elevated levels of inorganic arsenic in chicken livers.<ref name=FDA2>{{cite news | author = U.S. Food and Drug Administration | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm258342.htm | archive-url = https://web.archive.org/web/20110611010155/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm258342.htm | url-status = dead | archive-date = June 11, 2011 | title = FDA: Pfizer will voluntarily suspend sale of animal drug 3-Nitro | date = June 8, 2011}}</ref><ref name="AGCanada">{{cite web | author=AGCanada | title=Poultry antibiotic pulled in Canada | website=AGCanada | date=7 July 2011 | url=https://www.agcanada.com/daily/poultry-antibiotic-pulled-in-canada | access-date=19 October 2018}}</ref><ref>{{cite news | author = Cevallos, M. | url = http://www.latimes.com/health/boostershots/la-heb-arsenic-chicken-pfizer-20110608,0,6568583.story | title = Arsenic-containing drug in chicken feed to be pulled from U.S | newspaper = LA Times | date = June 9, 2011}}</ref> An FDA press release stated that the findings raised "concerns of a very low but completely avoidable exposure to a carcinogen."<ref name=FDA2 />
A 2013 market basket study conducted in the United States linked the use of roxarsone and other arsenical feed additives to increased levels of inorganic arsenic in chicken breast meat.<ref name="Basket">{{cite journal |author1=KE Nachman |author2=PA Baron |author3=G Raber |author4=KA Francesconi |author5=A Navas-Acien |author6=DC Love | title = Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample | journal = Environmental Health Perspectives | year = 2013 | doi = 10.1289/ehp.1206245 |pmid=23694900 |pmc=3701911 | url = http://ehp.niehs.nih.gov/wp-content/uploads/121/5/ehp.1206245.pdf | archive-url = https://web.archive.org/web/20130810224715/http://ehp.niehs.nih.gov/wp-content/uploads/121/5/ehp.1206245.pdf | url-status = dead | archive-date = August 10, 2013 | volume=121 |issue=7 | pages=818–824|bibcode=2013EnvHP.121..818N }}</ref><ref name="NYT2013">{{cite news | author = Sabrina Tavernise | url = https://www.nytimes.com/2013/05/11/health/study-finds-an-increase-in-arsenic-levels-in-chicken.html | title = Study Finds an Increase in Arsenic Levels in Chicken | work = New York Times | date = May 11, 2013}}</ref> The study was performed on chickens raised prior to the voluntary withdrawal of roxarsone from the market by its manufacturer.<ref name="Basket"></ref><ref name="NYT2013"></ref> Breast meat from chickens exposed to arsenical feed additives contained inorganic arsenic at the level of about two parts per billion.<ref name="Basket"></ref><ref name="NYT2013"></ref> Breast meat from chickens raised in farms with a policy not to use arsenical feed additives contained inorganic arsenic at the level of 0.7 parts per billion.<ref name="Basket"></ref> Organic chickens are not exposed to arsenical feed additives and contained about half a part per billion.<ref name="Basket"></ref><ref name="NYT2013"></ref>
Federal standards at the time permitted concentrations of 500 parts per billion of total arsenic, but were established before 1963 and did not differentiate between organic arsenic and its highly toxic inorganic variety.<ref name="Basket"></ref><ref name="NYT2013"></ref> In February 2011 the FDA's Center for Veterinary Medicine recommended inorganic arsenic in chicken not exceed 1 part per billion, then revised the statement to remove language suggesting a safe concentration, noting: "any new animal drug that contributes to the overall inorganic arsenic burden is of potential concern."<ref name="Basket"></ref><ref>{{cite web |author=U.S. Food and Drug Administration |title=Final Report on Study 275.30: Arsenic Species in Broilers Treated with Roxarsone (PDF) |publisher=U.S. Food and Drug Administration |date=April 2011 |url=http://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/UCM257545.pdf |archive-url=https://web.archive.org/web/20110618061932/http://www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/UCM257545.pdf |archive-date=June 18, 2011 |url-status=dead |access-date=July 3, 2025}}</ref>
==References== {{reflist}}
==Further reading== * {{cite journal |author1=J. R. Garbarino |author2=A. J. Bednar |author3=D. W. Rutherford |author4=R. S. Beyer |author5=R. L. Wershaw |name-list-style=amp | title = Environmental Fate of Roxarsone in Poultry Litter. I. Degradation of Roxarsone during Composting | journal = Environ. Sci. Technol. | year = 2003 | volume = 37 | issue = 8 | pages = 1509–1514 | doi = 10.1021/es026219q | pmid = 12731831|bibcode=2003EnST...37.1509G }} * {{cite journal |author1=Chiou P. W.-S. |author2=Chen K.-L. |author3=Yu B. | title = Effects of roxarsone on performance, toxicity, tissue accumulation and residue of eggs and excreta in laying | journal = Journal of the Science of Food and Agriculture | year = 1997 | volume = 74 | issue = 2 | pages = 229–236 | doi = 10.1002/(SICI)1097-0010(199706)74:2<229::AID-JSFA793>3.0.CO;2-F}} * {{cite conference |author1=R. L. Wershaw |author2=J. R. Garbarino |author3=M. R. Burkhardt |name-list-style=amp | title = Roxarsone in Natural Water Systems | conference = Effects of Confined Animal Feeding Operations (CAFOs) on Hydrologic Resources and the Environment | date = 1999 | location=Fort Collins, Colorado |publisher=U.S. Geological Survey | url = https://water.usgs.gov/owq/AFO/proceedings/afo/pdf/Wershaw.pdf |accessdate=2020-06-06}} * {{cite journal |author1=KB Kerr |author2=JR Narveson |author3=FA Lux | title = Toxicity of an organic arsenical, 3-nitro-4-hydroxyphenylarsonic acid. Residues in chicken tissues | journal = Journal of Agricultural and Food Chemistry | year = 1969 | volume = 17 | pages = 1400 | doi =10.1021/jf60166a021 | issue = 6|bibcode=1969JAFC...17.1400K }}
==External links== * [https://www.npr.org/blogs/health/2010/11/24/131566322/no-arsenic-in-pardoned-turkeys-but-it-might-be-in-yours No Arsenic In Pardoned Turkeys, But It Might Be In Yours] at NPR
Category:Arsonic acids Category:Antiprotozoal agents Category:Veterinary drugs Category:Food safety Category:Medicated feed Category:Nitrophenol derivatives