Editing Nitrite (section)

==Uses==
===Chemical precursor===
[[Azo dye]]s and other colorants are prepared by the process called [[Diazonium compound#Preparation|diazotization]], which requires nitrite.<ref name=Ullmann/>

=== Nitrite in food preservation and biochemistry ===
{{See also|Warmed-over flavor|Sodium nitrite#Food additive and preservative}}
The addition of [[Nitrite#Nitrite in food preservation and biochemistry|nitrites]] and [[nitrates]] to processed meats such as ham, bacon, and sausages speeds up the [[Curing (food preservation)|curing]] of meat and also impart an attractive colour.<ref name="Wilson">{{cite news 
 |last=Wilson
 |first=Bee
 |date=2018-03-01
 |title=Yes, bacon really is killing us
 |url=https://www.theguardian.com/news/2018/mar/01/bacon-cancer-processed-meats-nitrates-nitrites-sausages
 |url-status=live
 |work=The Guardian
 |location=London
 |language=en-GB
 |issn=0261-3077
 |archiveurl=https://web.archive.org/web/20210210183650/https://www.theguardian.com/news/2018/mar/01/bacon-cancer-processed-meats-nitrates-nitrites-sausages
 |archivedate=2021-02-10
 |access-date=2021-02-14
 |quote=In trade journals of the 1960s, the firms who sold nitrite powders to ham-makers spoke quite openly about how the main advantage was to increase profit margins by speeding up production.}}</ref>

The academic and industrial consensus is that nitrites also reduces growth and toxin production of ''[[Clostridium botulinum]]''.<ref>{{cite journal | vauthors = Christiansen LN, Johnston RW, Kautter DA, Howard JW, Aunan WJ | title = Effect of nitrite and nitrate on toxin production by Clostridium botulinum and on nitrosamine formation in perishable canned comminuted cured meat | journal = Applied Microbiology | volume = 25 | issue = 3 | pages = 357–62 | date = March 1973 | pmid = 4572891 | pmc = 380811 | doi = 10.1128/AEM.25.3.357-362.1973 }}</ref><ref>{{Cite journal |last1=Lee |first1=Soomin |last2=Lee |first2=Heeyoung |last3=Kim |first3=Sejeong |last4=Lee |first4=Jeeyeon |last5=Ha |first5=Jimyeong |last6=Choi |first6=Yukyung |last7=Oh |first7=Hyemin |last8=Choi |first8=Kyoung-Hee |last9=Yoon |first9=Yohan |date=August 2018 |title=Microbiological safety of processed meat products formulated with low nitrite concentration — A review |journal=Asian-Australasian Journal of Animal Sciences |volume=31 |issue=8 |pages=1073–1077 |doi=10.5713/ajas.17.0675 |issn=1011-2367 |pmc=6043430 |pmid=29531192}}</ref><ref>{{cite journal |last1=Sindelar |first1=Jeffrey J. |last2=Milkowski |first2=Andrew L. |title=Human safety controversies surrounding nitrate and nitrite in the diet |journal=Nitric Oxide |date=May 2012 |volume=26 |issue=4 |pages=259–266 |doi=10.1016/j.niox.2012.03.011}}</ref>
On the other hand, a 2018 study (full text not available) by the British Meat Producers Association determined that legally permitted levels of nitrite do not affect the growth of ''C. botulinum''.<ref>{{cite news 
 |last=Doward
 |first=Jamie
 |date=2019-03-23
 |title=Revealed: no need to add cancer-risk nitrites to ham
 |url=https://www.theguardian.com/food/2019/mar/23/nitrites-ham-bacon-cancer-risk-additives-meat-industry-confidential--report
 |url-status=live
 |work=The Observer
 |location=London
 |archiveurl=https://web.archive.org/web/20210126134441/https://www.theguardian.com/food/2019/mar/23/nitrites-ham-bacon-cancer-risk-additives-meat-industry-confidential--report
 |archivedate=2021-01-26
 |access-date=2021-02-14
 |quote=The results show that there is no change in levels of inoculated ''C. botulinum'' over the curing process, which implies that the action of nitrite during curing is not toxic to ''C. botulinum'' spores at levels of 150ppm [parts per million] ingoing nitrite and below.}}</ref> In the U.S., meat cannot be labeled as "cured" without the addition of nitrite.<ref>{{Cite book|title=Food Safety and Toxicity |first=John |last=De Vries|publisher=CRC Press |year=1997|isbn=978-0-8493-9488-1|page=70}}</ref><ref>[https://web.archive.org/web/20090617075537/http://www.meatami.com/ht/a/GetDocumentAction/i/44170 sodium nitrite and nitrate facts] Accessed 12 Dec 2014</ref><ref name="CMSFB">{{cite book | url=https://books.google.com/books?id=5IS2n8MBpf8C&pg=PA78 | title=Compendium of the Microbiological Spoilage of Foods and Beverages | pages=78| isbn=9781441908261 | last1=Doyle | first1=Michael P. | last2=Sperber | first2=William H. | date=23 September 2009 | publisher=Springer }}</ref> In some countries, cured-meat products are manufactured without [[nitrate]] or nitrite, and without nitrite from vegetable sources. [[Parma ham]], produced without nitrite since 1993, was reported in 2018 to have caused no cases of botulism. This is because the interior of the muscle is sterile and the surface is exposed to oxygen.<ref name=Wilson/> Other manufacture processes do not assure these conditions, and reduction of nitrite results in toxin production.<ref>{{cite journal |last1=Lebrun |first1=S. |last2=Van Nieuwenhuysen |first2=T. |last3=Crèvecoeur |first3=S. |last4=Vanleyssem |first4=R. |last5=Thimister |first5=J. |last6=Denayer |first6=S. |last7=Jeuge |first7=S. |last8=Daube |first8=G. |last9=Clinquart |first9=A. |last10=Fremaux |first10=B. |title=Influence of reduced levels or suppression of sodium nitrite on the outgrowth and toxinogenesis of psychrotrophic Clostridium botulinum Group II type B in cooked ham |journal=International Journal of Food Microbiology |date=December 2020 |volume=334 |pages=108853 |doi=10.1016/j.ijfoodmicro.2020.108853}}</ref>

In mice, food rich in nitrites together with unsaturated fats can prevent [[hypertension]] by forming nitro fatty acids that inhibit soluble [[epoxide hydrolase]], which is one explanation for the apparent health effect of the [[Mediterranean diet]].<ref>{{Cite journal | doi = 10.1073/pnas.1402965111| title = Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase| journal = Proceedings of the National Academy of Sciences| volume = 111| issue = 22| pages = 8167–72| year = 2014| last1 = Charles | first1 = R. L.| last2 = Rudyk | first2 = O.| last3 = Prysyazhna | first3 = O.| last4 = Kamynina | first4 = A.| last5 = Yang | first5 = J.| last6 = Morisseau | first6 = C.| last7 = Hammock | first7 = B. D.| last8 = Freeman | first8 = B. A.| last9 = Eaton | first9 = P. | pmid=24843165 | pmc=4050620
| bibcode = 2014PNAS..111.8167C| doi-access = free}}</ref> Adding nitrites to meat has been shown to generate known [[carcinogen]]s; the [[World Health Organization]] (WHO) advises that eating {{convert|50|g|abbr=on}} of nitrite processed meat a day would raise the risk of getting [[bowel cancer]] by 18% over a lifetime.<ref name=Wilson/>

The recommended maximum limits by the World Health Organization in [[drinking water]] are 3&nbsp;mg&nbsp;L<sup>−1</sup> and 50&nbsp;mg&nbsp;L<sup>−1</sup> for nitrite and [[nitrate]] ions, respectively.<ref name="ReferenceB">{{Cite journal | doi = 10.1016/j.jhazmat.2016.11.055| pmid = 27894754| title = Composite of Cu metal nanoparticles—multiwall carbon nanotubes—reduced graphene oxide as a novel and high performance platform of the electrochemical sensor for simultaneous determination of nitrite and nitrate| journal = Journal of Hazardous Materials| volume = 324| issue = Pt B| pages = 762–772| year = 2017| last1 = Bagheri | first1 = H.| last2 = Hajian | first2 = A.| last3 = Rezaei | first3 = M.| last4 = Shirzadmehr | first4 = A.| bibcode = 2017JHzM..324..762B}}</ref> Ingesting too much nitrite and/or nitrate through well water is suspected to cause [[methemoglobinemia]].<ref>{{Cite journal |display-authors=6 |vauthors=Powlson DS, Addiscott TM, Benjamin N, Cassman KG, de Kok TM, van Grinsven H, L'Hirondel JL, Avery AA, van Kessel C |year=2008 |title=When does nitrate become a risk for humans? |url=https://digitalcommons.unl.edu/agronomyfacpub/102 |journal=Journal of Environmental Quality |volume=37 |issue=2 |pages=291–295 |bibcode=2008JEnvQ..37..291P |doi=10.2134/jeq2007.0177 |pmid=18268290 |s2cid=14097832|url-access=subscription }}</ref>

95% of the nitrite ingested in modern diets comes from bacterial conversion of nitrates naturally found in vegetables.<ref>{{Cite web |title=Is celery juice a viable alternative to nitrites in cured meats? |url=https://www.mcgill.ca/oss/article/food/celery-juice-viable-alternative-nitrites-cured-meats |access-date=2022-09-14 |website=Office for Science and Society |language=en}}</ref> However, potentially cancer-causing nitroso compounds are not made in the pH-neutral colon. They are mostly made in the acidic stomach.<ref>{{cite journal | pmid = 7285009 | volume=41 | issue=10 | title=Absence of volatile nitrosamines in human feces |date=October 1981 | journal=Cancer Res. | pages=3992–4 | last1 = Lee | first1 = L | last2 = Archer | first2 = MC | last3 = Bruce | first3 = WR}}</ref><ref>{{cite journal | doi = 10.1016/j.freeradbiomed.2007.03.011 | pmid = 17761300 | volume=43 | issue=7 | title=Diet-induced endogenous formation of nitroso compounds in the GI tract |date=October 2007 | journal=Free Radic. Biol. Med. | pages=1040–7 | last1 = Kuhnle | first1 = GG | last2 = Story | first2 = GW | last3 = Reda | first3 = T |display-authors=etal }}</ref>

====Curing of meat====
Nitrite reacts with the meat's [[myoglobin]] by attaching to the heme iron atom, forming reddish-brown nitrosomyoglobin and the characteristic pink "fresh" color of nitrosohemochrome or nitrosyl-heme upon cooking.<ref name=ind>{{cite journal |last1=Pappenberger |first1=Günter |last2=Hohmann |first2=Hans-Peter |title=Industrial Production of l-Ascorbic Acid (Vitamin C) and d-Isoascorbic Acid |journal=Biotechnology of Food and Feed Additives |series=Advances in Biochemical Engineering/Biotechnology |date=2013 |volume=143 |pages=143–188 |doi=10.1007/10_2013_243|pmid=24258144 |isbn=978-3-662-43760-5 }}</ref> In the US, nitrite has been formally used since 1925. According to scientists working for the industry group [[American Meat Institute]], this use of nitrite started in the [[Middle Ages]].<ref>{{Cite journal|last1=Binkerd|first1=E. F.|last2=Kolari|first2=O. E.|date=1975-01-01|title=The history and use of nitrate and nitrite in the curing of meat|journal=Food and Cosmetics Toxicology|volume=13|issue=6|pages=655–661|doi=10.1016/0015-6264(75)90157-1|issn=0015-6264|pmid=1107192}}</ref> Historians and [[epidemiology|epidemiologist]]s argue that the widespread use of nitrite in meat-curing is closely linked to the development of industrial meat-processing.<ref>{{cite book |last=Coudray |first=Guillaume |year=2017 |title=Cochonneries: Comment la charcuterie est devenue un poison |language=fr |location=Paris |publisher=La Découverte |pages=40–70 |isbn=978-2-7071-9358-2}}</ref><ref>{{Cite journal|last=Lauer|first=Klaus|date=1991-01-01|title=The history of nitrite in human nutrition: A contribution from German cookery books|url=https://www.jclinepi.com/article/0895-4356(91)90037-A/abstract|journal=Journal of Clinical Epidemiology|language=en|volume=44|issue=3|pages=261–264|doi=10.1016/0895-4356(91)90037-A|issn=0895-4356|pmid=1999685|url-access=subscription}}</ref> French investigative journalist {{interlanguage link|Guillaume Coudray|fr}} asserts that the meat industry chooses to cure its meats with nitrite even though it is established that this chemical gives rise to cancer-causing [[nitroso]]-compounds.<ref>{{cite web |url=https://www.corporatecrimereporter.com/news/200/guillaume-coudray-on-the-nitro-meat-cancer-connection/ |title=Guillaume Coudray on the Nitro Meat Cancer Connection |author=<!--Editor byline, no author name given.--> |date=14 April 2021 |website=Corporate Crime Reporter |access-date=2024-10-13}}</ref> Some traditional and artisanal producers avoid nitrites.

{{see also|Nitrosamine formation during digestion}}
Addition of [[ascorbic acid]], [[erythorbic acid]], or one of their salts enhance the binding of nitrite to the iron atom in myoglobin.<ref name=ind/> These chemicals also reduce the formation of nitrosamine in the stomach, but only when the fat content of a meal is less than 10%, beyond which they instead increase the formation of nitrosamine.<ref>{{cite journal |pmid=17785370 |pmc=2095705 |year=2007 |last1=Combet |first1=E. |title=Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed ''N''-nitrosation |journal=Gut |volume=56 |issue=12 |pages=1678–1684 |last2=Paterson |first2=S |last3=Iijima |first3=K |last4=Winter |first4=J |last5=Mullen |first5=W |last6=Crozier |first6=A |last7=Preston |first7=T |last8=McColl |first8=K. E. |doi=10.1136/gut.2007.128587}}</ref><ref>{{cite journal |pmid=20026204 |year=2010 |last1=Combet |first1=E |title=Dietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids |journal=Free Radical Biology and Medicine |volume=48 |issue=6 |pages=763–771 |last2=El Mesmari |first2=A |last3=Preston |first3=T |last4=Crozier |first4=A |last5=McColl |first5=K. E. |doi=10.1016/j.freeradbiomed.2009.12.011}}</ref>

=== Antidote for cyanide poisoning===
Nitrites in the form of [[sodium nitrite]] and [[amyl nitrite]] are components of many [[cyanide]] [[antidote]] kits.<ref>{{Cite journal |last1=Meillier |first1=Andrew |last2=Heller |first2=Cara |date=2015 |title=Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event |journal=Case Reports in Medicine |volume=2015 |pages=217951 |doi=10.1155/2015/217951 |issn=1687-9627 |pmc=4620268 |pmid=26543483|doi-access=free }}</ref> Both of these compounds bind to [[hemoglobin]] and oxidize the Fe<sup>2+</sup> ions to Fe<sup>3+</sup> ions forming [[methemoglobin]]. Methemoglobin, in turn, binds to cyanide (CN), creating cyanmethemoglobin, effectively removing cyanide from the [[complex IV]] of the [[electron transport chain]] (ETC) in [[Mitochondrion|mitochondria]], which is the primary site of disruption caused by cyanide. Another mechanism by which nitrites help treat cyanide toxicity is the generation of [[nitric oxide]] (NO). NO displaces the CN from the [[cytochrome c oxidase]] (ETC complex IV), making it available for methemoglobin to bind.<ref>{{Cite journal |last1=Bebarta |first1=Vikhyat S. |last2=Brittain |first2=Matthew |last3=Chan |first3=Adriano |last4=Garrett |first4=Norma |last5=Yoon |first5=David |last6=Burney |first6=Tanya |last7=Mukai |first7=David |last8=Babin |first8=Michael |last9=Pilz |first9=Renate B. |last10=Mahon |first10=Sari B. |last11=Brenner |first11=Matthew |title=Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning when Administered by Intramuscular Injection |date=June 2017 |journal=Annals of Emergency Medicine |volume=69 |issue=6 |pages=718–725.e4 |doi=10.1016/j.annemergmed.2016.09.034 |issn=0196-0644 |pmc=5446299 |pmid=28041825}}</ref>