View source for Sodium nitrite

{{multiple issues|cleanup =March 2010|globalize =June 2010|POV =June 2010}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 269311552
| Name = Sodium nitrite
| ImageFile = Sodium nitrite.jpg
|   ImageSize = 200px
|   ImageName = Sodium nitrite
| ImageFileL1 = Sodium-3D.png
|   ImageSizeL1 = 80px
|   ImageNameL1 = The sodium cation
| ImageFileR1 = Nitrite-3D-vdW.png
|   ImageNameR1 = The nitrite anion (space-filling model)
| Section1 = {{Chembox Identifiers
|   CASNo = 7632-00-0
|    CASNo_Ref = {{cascite}}
|   PubChem = 23668193
|   UNNumber = 1500
|   EINECS = 231-555-9
|   RTECS = RA1225000
  }}
| Section2 = {{Chembox Properties
|   Formula = NaNO<sub>2</sub>
|   MolarMass = 68.9953 g/mol
|   Appearance = white solid
|   Density = 2.168 g/cm<sup>3</sup>
|   Solubility = 82 g/100 ml (20 °C)
|   MeltingPt = 271 °C decomp.
  }}
| Section3 = {{Chembox Structure
|   Coordination =
|   CrystalStruct = [[rhombohedral|Trigonal]]
  }}
| Section7 = {{Chembox Hazards
|   ExternalMSDS = [http://ptcl.chem.ox.ac.uk/MSDS/SO/sodium_nitrite.html External MSDS]
|   EUIndex = 007-010-00-4
|   EUClass = Oxidant ('''O''')<br/>Toxic ('''T''')<br/>Dangerous for the environment ('''N''')
|   NFPA-H = 3
|   NFPA-F = 0
|   NFPA-R = 1
|   NFPA-O = OX
|   RPhrases = {{R8}}, {{R25}}, {{R50}}
|   SPhrases = {{S1/2}}, {{S45}}, {{S61}}
|   FlashPt =
|   Autoignition = 489 °C
|   LD50 = 85 mg/kg
  }}
| Section8 = {{Chembox Related
|   OtherAnions = [[Lithium nitrite]]<br/>[[Sodium nitrate]]
|   OtherCations = [[Potassium nitrite]]<br/>[[Ammonium nitrite]]
  }}
}}

'''Sodium nitrite''', with [[chemical formula]] [[Sodium|Na]][[Nitrogen|N]][[Oxygen|O]]<sub>2</sub>, is used as a [[colour retention agent|color fixative]] and [[preservative]] in meats and fish.
When pure, it is a white to slight yellowish crystalline powder. It is very soluble in [[water]] and is [[hygroscopic]]. It is also slowly oxidized by oxygen in the air to [[sodium nitrate]], NaNO<sub>3</sub>. The compound is a strong oxidizing agent.

It is also used in manufacturing [[azo compound|diazo]] [[dye]]s, [[nitroso compound]]s, and other organic compounds; in dyeing and printing textile fabrics and bleaching fibers; in [[photography]]; as a laboratory [[reagent]] and a [[corrosion inhibitor]]; in metal coatings for phosphatizing and detinning; and in the manufacture of [[rubber]] chemicals. It may also be used as an [[electrolyte]] in [[electrochemical grinding]] manufacturing processes, typically diluted to about 10% concentration in water. Sodium nitrite also has been used in human and veterinary medicine as a [[vasodilator]], a [[bronchodilator]], and an [[antidote]] for [[cyanide poisoning]].

==Uses==
===In normal human diet===
Nitrites are a normal part of human diet, found in most vegetables.<ref>{{cite journal | doi = 10.1016/j.jfca.2008.10.025 | title = Effects of some processing methods on nitrate and nitrite changes in cruciferous vegetables | year = 2009 | last1 = Leszczyńska | first1 = Teresa | last2 = Filipiak-Florkiewicz | first2 = Agnieszka | last3 = Cieślik | first3 = Ewa | last4 = Sikora | first4 = ElżBieta | last5 = Pisulewski | first5 = Paweł M. | journal = Journal of Food Composition and Analysis | volume = 22 | pages = 315}}</ref><ref>http://www.wholesomebabyfood.com/nitratearticle.htm</ref><ref name="sciencedirect.com">{{cite journal | doi = 10.1016/B0-12-227055-X/00830-0 | title = Nitrates and Nitrites | year = 2003 | last1 = Dennis | first1 = M J | last2 = Wilson | first2 = L A | pages = 4136}}</ref> Spinach and lettuce can have as high as 2500&nbsp;mg/Kg nitrate, curly kale (302.0&nbsp;mg/kg) and green cauliflower (61.0&nbsp;mg/kg), to a low of 13&nbsp;mg/Kg for asparagus. Nitrite levels in 34 vegetable samples, including different varieties of cabbage, lettuce, spinach, parsley and turnips ranged between 1.1 and 57&nbsp;mg/Kg, e.g. white cauliflower (3.49&nbsp;mg/kg) and green cauliflower (1.47&nbsp;mg/kg).<ref>{{cite journal | doi = 10.1016/j.foodchem.2009.11.030 | title = Contribution of different vegetable types to exogenous nitrate and nitrite exposure | year = 2010 | last1 = Correia | first1 = Manuela | last2 = Barroso | first2 = ÂNgela | last3 = Barroso | first3 = M. FáTima | last4 = Soares | first4 = DéBora | last5 = Oliveira | first5 = M.B.P.P. | last6 = Delerue-Matos | first6 = Cristina | journal = Food Chemistry | volume = 120 | pages = 960}}</ref><ref name =  Leszczyńska>{{cite journal | doi = 10.1016/j.jfca.2008.10.025 | title = Effects of some processing methods on nitrate and nitrite changes in cruciferous vegetables | year = 2009 | last1 = Leszczyńska | first1 = Teresa | last2 = Filipiak-Florkiewicz | first2 = Agnieszka | last3 = Cieślik | first3 = Ewa | last4 = Sikora | first4 = ElżBieta | last5 = Pisulewski | first5 = Paweł M. | journal = Journal of Food Composition and Analysis | volume = 22 | pages = 315 }}</ref> Boiling vegetables lowers nitrate but not nitrite.<ref name =  Leszczyńska/> Fresh meat contains 0.4-0.5&nbsp;mg/Kg nitrite and 4–7&nbsp;mg/Kg of nitrate (10–30&nbsp;mg/Kg nitrate in cured meats).<ref name="sciencedirect.com"/> The presence of nitrite in animal tissue is a consequence of metabolism of [[nitric oxide]], an important neurotransmitter.<ref>{{cite journal | doi = 10.1016/0378-4347(94)00310-6 | title = Measurement of nitrite and nitrate levels in biological samples by capillary electrophoresis | year = 1994 | last1 = Meulemans | first1 = A. | last2 = Delsenne | first2 = F. | journal = Journal of Chromatography B: Biomedical Sciences and Applications | volume = 660 | pages = 401}}</ref> Nitric oxide can be created ''de novo'' from [[nitric oxide synthase]] utilizing [[arginine]] or from ingested [[nitrate]] or [[nitrite]].<ref>{{cite journal | doi = 10.1006/niox.1998.0187 | title = Nitrogen Oxides and Hydroxyguanidines: Formation of Donors of Nitric and Nitrous Oxides and Possible Relevance to Nitrous Oxide Formation by Nitric Oxide Synthase | year = 1998 | last1 = Southan | first1 = G | journal = Nitric Oxide | volume = 2 | pages = 270}}</ref> Most all research on negative effects of Nitrites on humans predates discovery of [[nitric oxide]]'s importance to human metabolism and human endogenous metabolism of nitrite.

===Food additive===
As a [[food additive]], it serves a dual purpose in the [[food]] [[industry]] since it both alters the [[color]] of preserved [[fish]] and [[meat]]s and also prevents growth of ''[[Clostridium botulinum]]'', the [[bacterium]] which causes [[botulism]]. In the European Union it may be used only as a mixture with salt containing at most 0.6% sodium nitrite. It has the [[E number]] E250. [[Potassium nitrite]] (E249) is used in the same way.

While this chemical will prevent the growth of bacteria, it can be toxic in high amounts for animals, including humans. Sodium nitrite's [[median lethal dose|LD<sub>50</sub>]] in rats is 180&nbsp;mg/kg and its human [[lowest published lethal dose|LD<sub>Lo</sub>]] is 71&nbsp;mg/kg, meaning a 65&nbsp;kg person would likely have to consume at least 4.615 [[gram|g]] to result in toxicity.<ref>http://msds.chem.ox.ac.uk/SO/sodium_nitrite.html</ref> To prevent toxicity, sodium nitrite (blended with salt) sold as a food additive is dyed bright pink to avoid mistaking it for plain salt or sugar.

===Medical uses===
Recently, sodium nitrite has been found to be an effective means to increase blood flow by dilating [[blood vessel]]s, acting as a [[vasodilator]]. Research is ongoing to investigate its applicability towards treatments for [[sickle cell anemia]], cyanide poisoning, [[myocardial infarction|heart attack]]s, [[brain aneurysm]]s, and [[pulmonary hypertension]] in infants.<ref>{{cite news | url = http://www.usatoday.com/news/health/2005-09-05-hot-dog-drug_x.htm | author = [[Associated Press]] | title = Hot dog preservative could be disease cure | date = 9/5/2005}}</ref><ref>{{cite news | url = http://www.newscientist.com/article.ns?id=dn8643 | title = Food preservative fights cystic fibrosis complication | date = 27 January 2006 | publisher = NewScientist.com | author = Roxanne Khamsi}}</ref>

An intravenous mixture including sodium nitrite solution has been used as an emergency treatment for cyanide poisoning (see [[Cyanide#Antidote]]).

===Synthetic reagent===
Sodium nitrite is used to convert [[amine]]s into diazo compounds. The synthetic utility of such a reaction is to render the amino group labile for [[nucleophilic substitution]], as the N<sub>2</sub> group is a better [[leaving group]].

In the laboratory, sodium nitrite is also used to destroy excess [[sodium azide]].<ref>{{cite web | url = http://www.ehs.neu.edu/hazardous_waste/fact_sheets/sodium_azide/ | work = Hazardous Waste Management | title = Sodium Azide | month = March | year = 2003 | publisher = [[Northeastern University]]}}</ref><ref>{{cite book | title = Prudent practices in the laboratory: handling and disposal of chemicals | year = 1995 | publisher = [[National Academy Press]] | city = Washington, D.C. | isbn = 0309052297 | url = http://books.nap.edu/openbook.php?record_id=4911&page=165 | author = Committee on Prudent Practices for Handling, Storage, and Disposal of Chemicals in Laboratories, Board on Chemical Sciences and Technology, Commission on Physical Sciences, Mathematics, and Applications, National Research Council.}}</ref>

: NaNO<sub>2</sub> + H<sub>2</sub>SO<sub>4</sub> &rarr;  HNO<sub>2</sub> + NaHSO<sub>4</sub>

: 2 NaN<sub>3</sub> + 2 HNO<sub>2</sub> &rarr; 3 N<sub>2</sub> + 2 NO + 2 NaOH

==Health concerns==

A principal concern about sodium nitrite is the formation of [[carcinogen]]ic [[nitrosamine]]s in meats containing sodium nitrite when exposed to high temperatures. Sodium nitrite's usage is carefully regulated in the production of cured products in the United States, as the concentration in finished products is limited to 200 ppm, and is usually lower. About 1970, it was found that [[ascorbic acid]](vitamin C), an [[antioxidant]], inhibits nitrosamine formation.<ref>{{cite journal | url = http://carcin.oxfordjournals.org/cgi/content/abstract/10/2/397 | 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 | year = 1989 | volume = 10 | issue = 2 | pages = 397–399 | author = C.W. Mackerness, S.A. Leach, M.H. Thompson and M.J. Hill | doi = 10.1093/carcin/10.2.397 | pmid = 2492212}}</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|alpha-tocopherol (vitamin E)]] to further inhibit nitrosamine production. Alpha-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 [[nitrous anhydride]], a potent nitrosating agent formed from sodium nitrate, reduces the nitrous anhydride into the [[nitric oxide]] gas.<ref>http://lpi.oregonstate.edu/f-w00/nitrosamine.html Nitrosamines and Cancer by Richard A. Scanlan, Ph.D.</ref> Note that Nitrous Anhydride does not exist<ref>{{cite journal | doi = 10.1016/B978-044451721-0/50002-5 | title = Reagents effecting nitrosation | year = 2004 | last1 = Williams | first1 = D | pages = 1 }}</ref> in vitro.

Sodium nitrite consumption has also been linked to the triggering migraines in individuals who already suffer from them.<ref>{{cite web | url = http://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>

A recent study has found a link between frequent ingestion of cured meats and the [[chronic obstructive pulmonary disease|COPD]] form of [[lung disease]]. 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 | author = Miranda Hitti | publisher = WebMD Medical News | date = 17 April 2007}}</ref><ref>{{cite journal | doi = 10.1164/rccm.200607-969OC | title = Cured Meat Consumption, Lung Function, and Chronic Obstructive Pulmonary Disease among United States Adults | year = 2007 | last1 = Jiang | first1 = R. | last2 = Paik | first2 = D. C. | last3 = Hankinson | first3 = J. L. | last4 = Barr | first4 = R. G. | journal = American Journal of Respiratory and Critical Care Medicine | volume = 175 | pages = 798}}</ref>

{{Copypaste|date=March 2010}}
Sodium nitrite is commonly added to bacon, ham, hot dogs, luncheon meats, smoked fish, and corned beef to stabilize the red color and add flavor. The preservative prevents growth of bacteria, but studies have linked eating it to various types of [[cancer]]. "This would be at the top of my list of additives to cut from my diet," says Christine Gerbstadt, M.D., M.P.H., R.D., L.D.N., a spokesperson for the [[American Dietetic Association]]. "Under certain high-temperature cooking conditions such as grilling, it transforms into a reactive compound that has been shown to promote [[cancer]]."<ref>http://health.msn.com/nutrition/slideshow.aspx?cp-documentid=100204508</ref>

"The cured meat industry made substantial changes to the manufacturing process in the past 20 years to address some of the concerns about nitrite in cured meats. It has stopped using [[sodium nitrate]] (except for some specialty meats) in major meat processes and reduced the use of nitrite in the processing of cured meats. Residual levels of nitrite found in nitrite-cured meats have decreased in the past 20 years and now average one-tenth of what the regulations actually allow. The industry also has increased the use of two other substances – [[ascorbate]] and [[erythorbate]] – in the curing process, which are known to deplete residual nitrite and inhibit the production of N-nitrosamines." <ref name="medem.com">http://www.medem.com/?q=medlib/article/ZZZ80XEN0IC</ref>{{Dead link|date=March 2010}}

"There...were a number of studies during the 1970s that linked the consumption of nitrite with cancer in laboratory animals or associated the consumption of cured meats with illnesses in children. As a result of some lingering concerns about nitrite safety, the FDA and the USDA commissioned a comprehensive review of sodium nitrite's role as a food additive.  The results were two scientific reports from the National Academy of Sciences (issued in 1981 and 1982). The 1981 report stated that nitrite does not cause cancer, although some population studies have found an association between high exposure to nitrite levels and certain cancers. Also, nitrite does not act directly as a cancer-causing agent in animals. The NAS recommended that both these issues be researched further. The NAS also recommended that people's exposure to both nitrates and nitrites be reduced as much as possible without jeopardizing the protection against botulism." <ref name="medem.com"/>{{Dead link|date=March 2010}}

"Two important actions in the year 2000 have reinforced the message that the use of sodium nitrite in cured meats is safe and is not associated with cancer risk in humans.  The first is a thorough review of the results of sodium nitrite studies by the National Toxicology Program, which undertook the review at the request of the FDA. After carefully considering all the evidence presented, the NTP Board of Scientific Counselors voted unanimously in May 2000 that the evidence showed that sodium nitrite does not cause cancer in male rats, male mice or female rats. While they found "equivocal evidence" in the forestomachs of female mice, the scientists have determined that the finding is not relevant to human health because humans do not have forestomachs. This comprehensive review by NTP shows that sodium nitrite does not cause cancer in laboratory animals, even when they are fed massive doses throughout the animals' lifetime.  The second action occurred in the state of California, where a panel of independent expert toxicologists reviewing almost 100 scientific publications about sodium nitrite voted that the evidence does not show that sodium nitrite causes developmental or reproductive toxicity. If found by the DART committee to be harmful, sodium nitrite would have been listed under the state's Proposition 65 law, which was enacted to protect citizens against known cancer-causing agents and reproductive toxicants.<ref name="medem.com"/>{{Dead link|date=March 2010}}

As of June 2004, the American Medical Association concludes that: "Data are irrefutable that when ingested in high concentrations nitrites can cause [[methemoglobinemia]]. Additionally, certain populations such as infants may be particularly vulnerable. However, the human body can tolerate fairly high levels of methemoglobin before toxemia sets in. Thus, there have been no reports of methemoglobinemia caused by nitrites added intentionally to food, although disease caused by contamination of water and food by sodium nitrite has been reported. USDA regulations do not permit nitrites and nitrates in baby, junior, or toddler foods.  The scientific evidence is clear that [[Nitroso compound|NOCs]] have carcinogenic effects in animal models. Thus, it must be assumed that at the right concentrations, NOCs are likely to be carcinogenic in humans as well. The primary source of NOCs in the human diet is the nitrosation of secondary amines and amides by nitrites present in food. However, epidemiological studies cannot confirm the link between the presence of nitrites (or nitrates) in food and the formation of NOCs and the causation of human cancer. In fact, studies that suggest a link between nitrites in food and cancer have largely been disputed due to these studies’ inability to exclude confounding factors, such as recall bias.  Regardless, the use of nitrites in the preparation and preservation of meats and poultry has been substantially reduced from the time when these studies were first performed. Additionally, the use of erythorbate and/or ascorbate with nitrites has been shown to inhibit the formation of NOCs.  Accordingly, given the current FDA and USDA regulations on the use of nitrites, the risk of developing cancer as a result of consumption of nitrites-containing foods is negligible.<ref>http://www.ama-assn.org/ama/no-index/about-ama/13661.shtml</ref>

===Mechanism of action===
Carcinogenic nitrosamines are formed when [[amine]]s that occur naturally in food react with sodium nitrite found in cured meat products.

:R<sub>2</sub>NH (amines) + NaNO<sub>2</sub> (sodium nitrite) → R<sub>2</sub>N-N=O (nitrosamine)

In the presence of acid (such as in the stomach) or heat (such as via cooking), nitrosamines are converted to [[diazonium compound|diazonium ions]].

:R<sub>2</sub>N-N=O (nitrosamine) + (acid or heat) → R-N<sup>+</sup>-N=O (diazonium ion)

Certain nitrosamines such as [[N-nitrosodimethylamine]]<ref name=najm2001>{{cite journal|title=NDMA Formation in Water and Wastewater|author= Najm, Issam; Trussell, R. Rhodes|journal=Journal AWWA|volume=93|issue=2|date=February 2001|pages=92–99}}</ref> and [[N-nitrosopyrrolidine]]<ref name=bills1973>{{cite journal|title=Potential precursors of N-nitrosopyrrolidine in bacon and other fried foods|author=Donald D. Bills, Kjell I. Hildrum, Richard A. Scanlan, Leonard M. Libbey|journal=J. Agric. Food Chem.|volume=21|issue=5|date=May 1973|pages=876–877|doi=10.1021/jf60189a029|pmid=4739004}}</ref> form carbocations that react with biological nucleophiles (such as DNA or an enzyme) in the cell.

:R-N<sup>+</sup>-N=O (diazonium ion) → R<sup>+</sup> (carbocation) + N<sub>2</sub> (leaving group) + :Nu (biological nucleophiles) → R-Nu

If this [[SN1 reaction|nucleophilic substitution]] reaction occurs at a crucial site in a biomolecule, it can disrupt normal cell functioning leading to cancer or [[apoptosis|cell death]].

==References==
{{reflist|2}}

==External links==
* [http://www.organicconsumers.org/foodsafety/processed100705.cfm Organic Consumers Association: Why Processed Meats Are Dangerous to Your Health]
* [http://www.atsdr.cdc.gov/csem/nitrate/ ATSDR - Case Studies in Environmental Medicine - Nitrate/Nitrite Toxicity] U.S. [[Department of Health and Human Services]] (public domain)
* [http://www.ilo.org/public/english/protection/safework/cis/products/icsc/dtasht/_icsc11/icsc1120.htm International Chemical Safety Card 1120].
* [http://ecb.jrc.it/ European Chemicals Bureau].
* [http://www.uga.edu/nchfp/how/cure_smoke/nitrates_nitrites.html National Center for Home Food Preservation Nitrates and Nitrites].
* [http://ntp-server.niehs.nih.gov/index.cfm?objectid=070B04E4-0E6C-7453-7747FB268B93D146  TR-495: Toxicology and Carcinogenesis Studies of Sodium Nitrite (CAS NO. 7632-00-0) Drinking Water Studies in F344/N Rats and B6C3F<sub>1</sub> Mice].
* [http://www.foxnews.com/story/0,2933,208307,00.html FOX news article concerning carcinogicity and hot dogs]

{{Antidotes}}
{{Sodium compounds}}

[[Category:Sodium compounds]]
[[Category:Nitrites]]
[[Category:Color fixers]]
[[Category:Curing agents]]
[[Category:Corrosion inhibitors]]
[[Category:Food additives]]
[[Category:Garde manger]]
[[Category:Antidotes]]
[[Category:World Health Organization essential medicines]]
[[Category:Oxidizing agents]]

[[ar:نتريت الصوديوم]]
[[bs:Natrijum nitrit]]
[[ca:Nitrit de sodi]]
[[cs:Dusitan sodný]]
[[de:Natriumnitrit]]
[[fr:Nitrite de sodium]]
[[it:Nitrito di sodio]]
[[he:נתרן חנקיתי]]
[[lt:Natrio nitritas]]
[[hu:Nátrium-nitrit]]
[[nl:Natriumnitriet]]
[[ja:亜硝酸ナトリウム]]
[[no:Natriumnitritt]]
[[pl:Azotan(III) sodu]]
[[pt:Nitrito de sódio]]
[[ro:Nitrit de sodiu]]
[[ru:Нитрит натрия]]
[[sr:Natrijum nitrit]]
[[fi:Natriumnitriitti]]
[[sv:Natriumnitrit]]
[[zh:亚硝酸钠]]
[[Category:2Fix]]