Editing Sodium nitrite (section)

==Toxicity ==
Sodium nitrite is toxic.<ref>{{cite web |title=How toxic is it? |vauthors=Crellin J |url=https://www.ase.org.uk/sites/default/files/chemistry%20PDFs/PDFs/How%20toxic%20is%20it.pdf |access-date=6 February 2022 |website=The Association for Science Educators |orig-date=First published in March 1989, reviewed in 2015}}</ref> The [[median lethal dose|LD<sub>50</sub>]] in rats is 180&nbsp;mg/kg and in humans [[lowest published lethal dose|LD<sub>Lo</sub>]] is 71&nbsp;mg/kg.<ref>{{cite web |title=Safety data for sodium nitrite |archive-url=https://web.archive.org/web/20080410131202/http://msds.chem.ox.ac.uk/SO/sodium_nitrite.html |archive-date=10 April 2008 |url=http://msds.chem.ox.ac.uk/SO/sodium_nitrite.html |work=The Physical and Theoretical Chemistry Laboratory |publisher=[[Oxford University]]}}</ref> The mechanism by which sodium nitrite causes death is [[methemoglobinemia]].<ref>{{cite journal | vauthors = Katabami K, Hayakawa M, Gando S | title = Severe Methemoglobinemia due to Sodium Nitrite Poisoning | journal = Case Reports in Emergency Medicine | volume = 2016 | pages = 9013816 | date = 3 August 2016 | pmid = 27563472 | pmc = 4987464 | doi = 10.1155/2016/9013816 | doi-access = free}}</ref> The oftentimes severe methemoglobinemia found in sodium nitrite poisoning cases results in systemic [[Hypoxia (medical)|hypoxia]], [[metabolic acidosis]], and [[cyanosis]].<ref>{{cite journal | vauthors = Padovano M, Aromatario M, D'Errico S, Concato M, Manetti F, David MC, Scopetti M, Frati P, Fineschi V | title = Sodium Nitrite Intoxication and Death: Summarizing Evidence to Facilitate Diagnosis | journal = International Journal of Environmental Research and Public Health | volume = 19 | issue = 21 | pages = 13996 | date = October 2022 | pmid = 36360874 | pmc = 9654862 | doi = 10.3390/ijerph192113996 | doi-access = free}}</ref> The reported<ref>{{cite web |title=Nitrate and Nitrite Poisoning |url=https://www.poison.org/articles/causes-and-symptoms-of-nitrate-nitrite-poisoning-174 |access-date=4 November 2023 |website=www.poison.org |language=en}}</ref> signs of sodium nitrite poisoning are as follows:
{{Blockquote|text=Symptoms of [nitrite] poisoning can vary depending on the amount and duration of the exposure. Those with very mild methemoglobinemia might not have any symptoms at all, or might appear a little pale and feel tired. Moderate-to-severe poisoning is associated with cyanosis (blueness of the skin), confusion, loss of consciousness, seizures, abnormal heart rhythms, and death.}}
With prompt action, sodium nitrite poisoning is reversible using an antidote, [[methylene blue]].<ref name=":0" /> It has been reported<ref>{{cite journal | vauthors = Hickey TB, MacNeil JA, Hansmeyer C, Pickup MJ | title = Fatal methemoglobinemia: A case series highlighting a new trend in intentional sodium nitrite or sodium nitrate ingestion as a method of suicide | journal = Forensic Science International | volume = 326 | pages = 110907 | date = September 2021 | pmid = 34298207 | doi = 10.1016/j.forsciint.2021.110907}}</ref> that sodium nitrite poisoning can also be detected post-mortem:
{{Blockquote|text=Postmortem detection of [methemoglobinemia] is typically established via screening techniques such as scene evidence suggesting fatal consumption of a toxic salt in addition to the characteristic grey-purple lividity observed upon the body. The diagnosis can be established via postmortem blood testing demonstrating elevated methemoglobin saturation. Additionally, we have confirmed that postmortem MRI in cases of [methemoglobinemia] demonstrates a T1-bright (hyperintense) signal of the blood; both within intracardiac blood on chest MRIs and postmortem blood samples in tubes.}}
Death by sodium nitrite ingestion can happen at lower doses than the previously known [[lowest published lethal dose|LD<sub>Lo</sub>]].<ref>{{cite journal | vauthors = Gowans WJ | title = Fatal methaemoglobinaemia in a dental nurse. A case of sodium nitrite poisoning | journal = The British Journal of General Practice | volume = 40 | issue = 340 | pages = 470–471 | date = November 1990 | pmid = 2271282 | pmc = 1371420}}</ref><ref>{{cite journal | vauthors = Standefer JC, Jones AM, Street E, Inserra R | title = Death associated with nitrite ingestion: report of a case | journal = Journal of Forensic Sciences | volume = 24 | issue = 4 | pages = 768–771 | date = October 1979 | pmid = 541641 | doi = 10.1520/JFS10905J}}</ref> Sodium nitrite has been used for homicide<ref>{{cite news |title=Chinese teacher sentenced to death for poisoning nursery children |url=https://www.bbc.com/news/world-asia-china-54335841 |work=[[BBC News]] |date=29 September 2020}}</ref><ref>{{cite news |title=Teacher in China sentenced to death for poisoning children's porridge |url=https://www.theguardian.com/world/2020/sep/29/teacher-in-china-sentenced-to-death-for-poisoning-childrens-porridge |work=The Guardian |agency=Agence France-Presse in Beijing |date=29 September 2020}}</ref> and suicide.<ref>{{cite news |title='General Hospital' Actress Lindsey Pearlman's Cause of Death Revealed
 |url=https://www.hollywoodreporter.com/news/general-news/lindsey-pearlman-suicide-coroners-office-1235200099/ |work=[[The Hollywood Reporter]] |date=16 August 2022}}</ref><ref>{{cite news |title=Police charge Mississauga man in connection with sale, distribution of sodium nitrite in GTA
 |url=https://toronto.ctvnews.ca/police-charge-mississauga-man-in-connection-with-sale-distribution-of-sodium-nitrite-in-gta-1.6380920 |work=[[CTV News]] |date=3 May 2023}}</ref> To prevent accidental intoxication, sodium nitrite (blended with salt) sold as a food additive in the US is dyed bright pink to avoid mistaking it for plain salt or sugar. In other countries, nitrited curing salt is not dyed but is strictly regulated.<ref>{{cite web|url=https://www.fsai.ie/faq/use_and_removal_of_nitrite.html|title=The Use and Removal of Nitrite in Meat Products &#124; FAQs | work = The Food Safety Authority of Ireland|access-date=10 February 2021|archive-date=27 June 2022|archive-url=https://web.archive.org/web/20220627111348/https://www.fsai.ie/faq/use_and_removal_of_nitrite.html|url-status=dead}}</ref>

=== Occurrence in vegetables ===
Nitrites do not occur naturally in vegetables in significant quantities,<ref name="Dennis & Wilson 2003 Nitrates and Nitrites">{{cite book |doi=10.1016/B0-12-227055-X/00830-0 |chapter=Nitrates and Nitrites |title=Encyclopedia of Food Sciences and Nutrition |year=2003 |vauthors=Dennis MJ, Wilson LA |pages=4136–4141 |isbn=978-0-12-227055-0}}</ref> but deliberate fermentation of [[celery|celery juice]], for instance, with a naturally high level of nitrates, can produce nitrite levels sufficient for commercial meat curing.<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=14 September 2022 |website=Office for Science and Society |language=en}}</ref> Boiling vegetables does not affect nitrite levels.<ref name="Leszczyńska">{{cite journal |vauthors=Leszczyńska T, Filipiak-Florkiewicz A, Cieślik E, Sikora E, Pisulewski PM |date=June 2009|title=Effects of some processing methods on nitrate and nitrite changes in cruciferous vegetables |journal=Journal of Food Composition and Analysis |volume=22 |issue=4 |pages=315–321 |doi=10.1016/j.jfca.2008.10.025}}</ref>

The presence of nitrite in animal tissue is a consequence of metabolism of [[nitric oxide]], an important neurotransmitter.<ref>{{cite journal | vauthors = Meulemans A, Delsenne F | title = Measurement of nitrite and nitrate levels in biological samples by capillary electrophoresis | journal = Journal of Chromatography. B, Biomedical Applications | volume = 660 | issue = 2 | pages = 401–404 | date = October 1994 | pmid = 7866533 | doi = 10.1016/0378-4347(94)00310-6}}</ref> Nitric oxide can be created ''[[wiktionary:de novo|de novo]]'' from [[nitric oxide synthase]] utilizing [[arginine]] or from ingested nitrite.<ref>{{cite journal | vauthors = Southan GJ, Srinivasan A | title = Nitrogen oxides and hydroxyguanidines: formation of donors of nitric and nitrous oxides and possible relevance to nitrous oxide formation by nitric oxide synthase | journal = Nitric Oxide | volume = 2 | issue = 4 | pages = 270–286 | date = August 1998 | pmid = 9851368 | doi = 10.1006/niox.1998.0187}}</ref>

=== Pigs ===
Due to sodium nitrite's high level of toxicity to swine (''Sus scrofa'') it is now being developed in Australia to control feral pigs and [[wild boar]].<ref>{{cite conference |vauthors=Lapidge S, Wishart J, Smith M, Staples L |title=Is America Ready for a Humane Feral Pig Toxicant? |conference=Wildlife Damage Management Conference |date=4 May 2009 |location=Saratoga Springs, NY |url=https://digitalcommons.usu.edu/wdmconference/2009/session2/2/}}</ref><ref>{{cite patent |inventor=Cowled BD, Lapidge SJ, Humphrys S, Staples L |title=Nitrite Salts as Poisons in Baits for Omnivores |country=WO |number=2008/104028 |pubdate=2008 |url=http://www.wipo.int/patentscope/search/en/WO2008104028}}</ref> The sodium nitrite induces [[methemoglobinemia]] in swine, i.e. it reduces the amount of oxygen that is released from hemoglobin, so the animal will feel faint and pass out, and then die in a humane manner after first being rendered unconscious.<ref>{{cite book |vauthors=Porter S, Kuchel T |title=Assessing the humaness and efficacy of a new feral pig bait in domestic pigs. Study PC0409 |year=2010 |publisher=Veterinary Services Division, Institute of Medical and Veterinary Science |location=Canberra, South Australia |page=11 |url=http://www.environment.gov.au/biodiversity/invasive/publications/pubs/pigs-imvs-report.pdf}}</ref> The [[Texas Parks and Wildlife Department]] operates a research facility at [[Kerr Wildlife Management Area]], where they examine feral pig feeding preferences and bait tactics to administer sodium nitrite.<ref>{{cite web |url=https://www.youtube.com/watch?v=GigpxLNbgeg |archive-url=https://ghostarchive.org/varchive/youtube/20211212/GigpxLNbgeg |archive-date=12 December 2021 |url-status=live |title=Hogs Wild – Fighting the Feral Pig Problem | work = Texas Parks and Wildlife |date=21 February 2013|access-date=1 April 2018 |via=[[YouTube]]}}{{cbignore}}</ref>

=== Cancer ===
[[Carcinogenicity]] is the ability or tendency of a chemical to induce tumors, increase their incidence or malignancy, or shorten the time of tumor occurrence.<ref>{{cite web|url=https://www.cancer.org/cancer/cancer-causes/general-info/known-and-probable-human-carcinogens.html|title=Known and Probable Human Carcinogens |website=www.cancer.org |language=en|access-date=28 January 2019}}</ref>

Adding nitrites to meat has been shown to generate known carcinogens such as [[nitrosamine]]s; the [[World Health Organization|World Health Organization (WHO)]] advises that {{convert|50|g|abbr=on}} of "processed meats" a day would raise the risk of getting bowel cancer by 18% over a lifetime, and eating larger amounts raises the risk more. The World Health Organization's review of more than 400 studies concluded, in 2015, that there was sufficient evidence that "processed meats" caused cancer, particularly colon cancer;<ref name="Wilson" /> the WHO's [[International Agency for Research on Cancer|International Agency for Research on Cancer (IARC)]] classified "processed meats" as carcinogenic to humans ([[List of IARC Group 1 carcinogens|Group 1]]); "processed meat" meaning meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavour or improve preservation.).<ref name=Wilson/><ref>{{cite web |title=IARC Monographs evaluate consumption of red meat and processed meat |url=https://www.iarc.who.int/wp-content/uploads/2018/07/pr240_E.pdf |publisher=International Agency for Research on Cancer |date=26 October 2015 |access-date=14 February 2021 |archive-date=18 January 2021 |archive-url=https://web.archive.org/web/20210118044116/https://www.iarc.who.int/wp-content/uploads/2018/07/pr240_E.pdf|quote=Processed meat was classified as carcinogenic to humans (Group 1), based on sufficient evidence in humans that the consumption of processed meat causes colorectal cancer.}}</ref>

Nitrosamines can be formed during the curing process used to preserve meats, when sodium nitrite-treated meat is cooked, and also from the reaction of nitrite with secondary amines under acidic conditions (such as occurs in the human stomach). Dietary sources of nitrosamines include US cured meats preserved with sodium nitrite as well as the dried salted fish eaten in Japan. In the 1920s, a significant change in US meat curing practices resulted in a 69% decrease in average nitrite content. This event preceded the beginning of a dramatic decline in gastric cancer mortality.<ref>{{cite journal | vauthors = Paik DC, Saborio DV, Oropeza R, Freeman HP | title = The epidemiological enigma of gastric cancer rates in the US: was grandmother's sausage the cause? | journal = International Journal of Epidemiology | volume = 30 | issue = 1 | pages = 181–182 | date = February 2001 | pmid = 11171883 | doi = 10.1093/ije/30.1.181 | doi-access = free}}</ref> Around 1970, it was found that [[ascorbic acid]] (vitamin C), an [[antioxidant]], inhibits nitrosamine formation.<ref>{{cite journal | vauthors = Mackerness CW, Leach SA, Thompson MH, Hill MJ | title = The inhibition of bacterially mediated N-nitrosation by vitamin C: relevance to the inhibition of endogenous N-nitrosation in the achlorhydric stomach | journal = Carcinogenesis | volume = 10 | issue = 2 | pages = 397–399 | date = February 1989 | pmid = 2492212 | doi = 10.1093/carcin/10.2.397}}</ref> Consequently, the addition of at least 550 ppm of ascorbic acid is required in meats manufactured in the United States. Manufacturers sometimes instead use [[erythorbic acid]], a cheaper but equally effective [[isomer]] of ascorbic acid. Additionally, manufacturers may include [[Alpha-Tocopherol|α-tocopherol (vitamin E)]] to further inhibit nitrosamine production. α-Tocopherol, ascorbic acid, and erythorbic acid all inhibit nitrosamine production by their oxidation-reduction properties. Ascorbic acid, for example, forms [[dehydroascorbic acid]] when [[redox|oxidized]], which when in the presence of [[nitrosonium]], a potent nitrosating agent formed from sodium nitrite, reduces the nitrosonium into nitric oxide.<ref>{{cite web |url=http://lpi.oregonstate.edu/publications/research-newsletter|title=Research Newsletter |date=1 July 2014|website=Linus Pauling Institute|access-date=1 April 2018}}</ref> The nitrosonium ion formed in acidic nitrite solutions is commonly<ref>{{cite journal | vauthors = Scanlan RA | title = Formation and occurrence of nitrosamines in food | journal = Cancer Research | volume = 43 | issue = 5 Suppl | pages = 2435s–2440s | date = May 1983 | pmid = 6831466 | id = {{NAID|80001710206}}}}</ref><ref>{{cite book |title=Handbook of Food Analysis |edition=Third |year=2015 |vauthors=Nollet LM, Toldrá F |page=290 |publisher=CRC Press |isbn=978-1-4822-9784-3}}{{page needed|date=February 2021}}</ref> mislabeled [[nitrous anhydride]], an unstable nitrogen oxide that cannot exist in vitro.<ref>{{cite book |doi=10.1016/B978-044451721-0/50002-5 |chapter=Reagents effecting nitrosation |title=Nitrosation Reactions and the Chemistry of Nitric Oxide |year=2004 |vauthors=Williams DL |pages=1–34 |isbn=978-0-444-51721-0}}</ref>

Ingesting nitrite under conditions that result in endogenous [[nitrosation]] has been classified as "probably carcinogenic to humans" by [[International Agency for Research on Cancer]] (IARC).<ref name="monographs.iarc.fr">{{cite web|url=http://monographs.iarc.fr/ENG/Classification/latest_classif.php|title=List of classifications, Volumes 1–116 – IARC Monographs on the Evaluation of Carcinogenic Risks to Humans|date=2010|work=International Agency for Research on Cancer (IARC) – World Health Organization (WHO)|access-date=25 September 2016|archive-date=10 June 2017|archive-url=https://web.archive.org/web/20170610015529/http://monographs.iarc.fr/ENG/Classification/latest_classif.php|url-status=dead}}</ref><ref name="ReferenceA">{{cite book |url=http://monographs.iarc.fr/ENG/Monographs/vol94/index.php|title=Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins |volume=94 |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |date=2010 |publisher = International Agency for Research on Cancer (IARC) – World Health Organization (WHO) |access-date=25 September 2016 |isbn=978-92-832-1294-2}}</ref>

Sodium nitrite consumption has also been linked to the triggering of migraines in individuals who already experience them.<ref>{{cite web |url=http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/1998/398_pain.html |title=Heading Off Migraine Pain |publisher=[[U.S. Food and Drug Administration]] |work=FDA Consumer magazine |year=1998}}</ref>

One study has found a correlation between highly frequent ingestion of meats cured with [[curing salt|pink salt]] and the [[chronic obstructive pulmonary disease|COPD]] form of [[lung disease]].<ref>{{cite news | url = http://www.webmd.com/news/20070417/study-copd-cured-meats-may-be-linked | title = Study: Cured Meats, COPD May Be Linked | vauthors = Hitti M | publisher = WebMD Medical News | date = 17 April 2007}}</ref><ref>{{cite journal | vauthors = Jiang R, Paik DC, Hankinson JL, Barr RG | title = Cured meat consumption, lung function, and chronic obstructive pulmonary disease among United States adults | journal = American Journal of Respiratory and Critical Care Medicine | volume = 175 | issue = 8 | pages = 798–804 | date = April 2007 | pmid = 17255565 | pmc = 1899290 | doi = 10.1164/rccm.200607-969OC}}</ref> The study's researchers suggest that the high amount of nitrites in the meats was responsible; however, the team did not prove the nitrite theory. Additionally, the study does not prove that nitrites or cured meat caused higher rates of COPD, merely a link. The researchers did adjust for many of COPD's risk factors, but they commented they cannot rule out all possible unmeasurable causes or risks for COPD.<ref>{{cite news | url = http://www.webmd.com/news/20070417/study-copd-cured-meats-may-be-linked | title = Study: Cured Meats, COPD May Be Linked | vauthors = Hitti M | publisher = WebMD Medical News | date = 17 April 2007}}</ref><ref>{{cite journal | vauthors = Jiang R, Paik DC, Hankinson JL, Barr RG | title = Cured meat consumption, lung function, and chronic obstructive pulmonary disease among United States adults | journal = American Journal of Respiratory and Critical Care Medicine | volume = 175 | issue = 8 | pages = 798–804 | date = April 2007 | pmid = 17255565 | pmc = 1899290 | doi = 10.1164/rccm.200607-969OC}}</ref>