Sodium nitrite, with
chemical formulaA chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
NaSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
NNitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere.Many industrially important...
OOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
2, is used as a
color fixativeColour retention agents are food additives that are added to food to prevent the color from changing. Many of them work by absorbing or binding to oxygen before it can damage food...
and
preservativeA preservative is a natural or synthetic chemical that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes.-Preservatives in wood:...
in meats and fish.
When pure, it is a white to slight yellowish crystalline powder. It is very soluble in
waterWater is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...
and is hygroscopic. It is also slowly oxidized by oxygen in the air to
sodium nitrateSodium nitrate is the chemical compound with the formula NaNO
3. This salt, also known as "Chile saltpeter" or "Peru saltpeter" , is a white solid which is very soluble in water...
, NaNO
3. The compound is a strong oxidizing agent.
It is also used in manufacturing
diazoAzo compounds are compounds bearing the functional group R-N=N-R', in which R and R' can be either aryl or alkyl. The N=N group is called an azo group, although the parent compound, HNNH, is called diimide. The more stable derivatives contain two aryl groups...
dyeA dye can generally be described as a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and may require a mordant to improve the fastness of the dye on the fiber....
s, nitroso compounds, and other organic compounds; in dyeing and printing textile fabrics and bleaching fibers; in
photographyPhotography is the process, activity and art of creating still or moving pictures by recording radiation on a sensitive medium, such as a photographic film, or an electronic sensor...
; as a laboratory
reagentA reagent or reactant is a substance or compound consumed during a chemical reaction. Solvents and catalysts, although they are involved in the reaction, are usually not referred to as reactants....
and a
corrosion inhibitorA corrosion inhibitor is a chemical compound that, when added to a fluid or gas, decreases the corrosion rate of a metal or an alloy.The effectiveness, or corrosion inhibition efficiency, of a corrosion inhibitor is a function of many factors like: fluid composition, quantity of water, flow regime......
; in metal coatings for phosphatizing and detinning; and in the manufacture of
rubberNatural rubber is an elastomer that was originally derived from a milky colloidal suspension, or latex, found in the sap of some plants. The purified form of natural rubber is the chemical polyisoprene, which can also be produced synthetically...
chemicals.
Sodium nitrite, with
chemical formulaA chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
NaSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
NNitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere.Many industrially important...
OOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
2, is used as a
color fixativeColour retention agents are food additives that are added to food to prevent the color from changing. Many of them work by absorbing or binding to oxygen before it can damage food...
and
preservativeA preservative is a natural or synthetic chemical that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes.-Preservatives in wood:...
in meats and fish.
When pure, it is a white to slight yellowish crystalline powder. It is very soluble in
waterWater is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...
and is hygroscopic. It is also slowly oxidized by oxygen in the air to
sodium nitrateSodium nitrate is the chemical compound with the formula NaNO
3. This salt, also known as "Chile saltpeter" or "Peru saltpeter" , is a white solid which is very soluble in water...
, NaNO
3. The compound is a strong oxidizing agent.
It is also used in manufacturing
diazoAzo compounds are compounds bearing the functional group R-N=N-R', in which R and R' can be either aryl or alkyl. The N=N group is called an azo group, although the parent compound, HNNH, is called diimide. The more stable derivatives contain two aryl groups...
dyeA dye can generally be described as a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and may require a mordant to improve the fastness of the dye on the fiber....
s, nitroso compounds, and other organic compounds; in dyeing and printing textile fabrics and bleaching fibers; in
photographyPhotography is the process, activity and art of creating still or moving pictures by recording radiation on a sensitive medium, such as a photographic film, or an electronic sensor...
; as a laboratory
reagentA reagent or reactant is a substance or compound consumed during a chemical reaction. Solvents and catalysts, although they are involved in the reaction, are usually not referred to as reactants....
and a
corrosion inhibitorA corrosion inhibitor is a chemical compound that, when added to a fluid or gas, decreases the corrosion rate of a metal or an alloy.The effectiveness, or corrosion inhibition efficiency, of a corrosion inhibitor is a function of many factors like: fluid composition, quantity of water, flow regime......
; in metal coatings for phosphatizing and detinning; and in the manufacture of
rubberNatural rubber is an elastomer that was originally derived from a milky colloidal suspension, or latex, found in the sap of some plants. The purified form of natural rubber is the chemical polyisoprene, which can also be produced synthetically...
chemicals. It may also be used as an
electrolyteIn chemistry, an electrolyte is any substance containing free ions that behaves as an electrically conductive medium, usually when in a solution...
in
electrochemical grindingElectrochemical grinding is grinding with a negatively charged abrasive grinding wheel, an electrolyte fluid, and a positively charged workpiece. Materials removed from the workpiece stay in the electrolyte fluid...
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
bronchodilatorA bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing airway resistance and thereby facilitating airflow. Bronchodilators may be endogenous , or they may be medications administered for the treatment of breathing difficulties...
, and an
antidoteAn antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"....
for
cyanide poisoningCyanide poisoning occurs when a living organism is exposed to cyanide. The cyanide ion, if used as poison, is generally delivered in the form of gaseous hydrogen cyanide or in the form of potassium cyanide or sodium cyanide.-Acute poisoning:...
.
Food additive
As a
food additiveFood additives are substances added to food to preserve flavour or improve its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...
, it serves a dual purpose in the
foodFood is any substance, usually composed of carbohydrates, fats, proteins and water, that can be eaten or drunk by an animal, including humans, for nutrition or pleasure. Items considered food may be sourced from plants, animals or other categories such as fungus or fermented products like alcohol...
industryAn industry is the manufacturing of a good or service within a category. Although industry is a broad term for any kind of economic production, in economics and urban planning industry is a synonym for the secondary sector, which is a type of economic activity involved in the manufacturing of raw...
since it both alters the
colorColor or colour is the visual perceptual property corresponding in humans to the categories called red, yellow, blue and others. Color derives from the spectrum of light interacting in the eye with the spectral sensitivities of the light receptors...
of preserved
fishA fish is any aquatic vertebrate animal that is typically ectothermic , covered with scales, and equipped with two sets of paired fins and several unpaired fins...
and
meatMeat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat, but it may also describe other edible tissues such as organs, livers, skin, brains, bone marrow, kidneys, or lungs...
s and also prevents growth of
Clostridium botulinumClostridium botulinum is a Gram-positive, rod shaped bacterium that produces the neurotoxin botulin, which causes the flaccid muscular paralysis seen in botulism, and is also the main paralytic agent in botox...
, the bacteria which causes
botulismBotulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum...
. 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 numberE numbers are number codes for food additives and are usually found on food labels throughout the European Union. The numbering scheme follows that of the International Numbering System as determined by the Codex Alimentarius committee. Only a subset of the INS additives are approved for use in...
E250.
Potassium nitritePotassium nitrite, with chemical formula 2, is a material which contains potassium and nitrogen.Potassium nitrite should not be confused with potassium nitrate....
(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 LD
50 in rats is 180 mg/kg and its human
LDLoIn toxicology, the LDLo is the lowest dosage per unit of bodyweight of a substance known to have resulted in fatality in a particular animal species...
is 71 mg/kg, meaning a 65 kg person would likely have to consume at least 4.615
gThe gram , ; symbol g, is a unit of mass.Originally defined as "the absolute weight of a volume of pure water equal to the cube of the hundredth part of a metre, and at the temperature of melting ice" , a gram is now defined as one one-thousandth of the SI base unit, the kilogram, or...
to result in toxicity. To prevent toxicity, sodium nitrite sold as a food additive is dyed bright pink to avoid mistaking it for something else.
A principal concern of sodium nitrite is the formation of
carcinogenicA carcinogen is any substance, radionuclide or radiation that is an agent directly involved in the promotion of cancer or in the increase of its propagation. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
nitrosamineNitrosamines are chemical compounds of the chemical structure R
1N-N=O, some of which are carcinogenic.- Food :...
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. In about 1970, it was found that
ascorbic acid (vitamin C)Ascorbic acid is a sugar acid with antioxidant properties. Its appearance is white to light-yellow crystals or powder, and it is water-soluble. One form of ascorbic acid is commonly known as vitamin C. The name is derived from a- and scorbutus , the disease caused by a deficiency of vitamin C...
, an
antioxidantAn antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals, which start chain reactions that damage cells...
, inhibits nitrosamine formation. 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 acidErythorbic acid, formerly known as isoascorbic acid and D-araboascorbic acid, is a stereoisomer of ascorbic acid . It is a vegetable-derived food additive produced from sucrose...
, a cheaper but equally effective isomer of ascorbic acid. Additionally, manufactures may include
alpha-tocopherol (vitamin E)α-Tocopherol is a type of tocopherol with formula C
29H
50O
2. It has E number "E307".α-Tocopherol is a form of vitamin E that is preferentially absorbed and accumulated in humans...
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 acidDehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells and generates the oxidative potential found there. Protein disulfide isomerases are known to reduce DHA back to ascorbic acid, oxidizing their disulfide bonds in the process....
when
oxidizedRedox describes all chemical reactions in which atoms have their oxidation number changed....
, which when in the presence of nitrous anhydride, a potent nitrosating agent formed from sodium nitrate, reduces the nitrous anhydride into the
nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
gas.
Sodium nitrite consumption has also been linked to triggering migraines in individuals who already suffer from them.
A recent study has found a link between frequent ingestion of cured meats and the 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 doesn't 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.
Disease treatment
Recently, sodium nitrite has been found to be an effective means to increase blood flow by dilating
blood vesselThe blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart, the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, acting as a vasodilator. Research is ongoing to investigate its applicability towards treatments for sickle cell anemia, cyanide poisoning,
heart attackMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, is the interruption of blood supply to part of the heart, causing some heart cells to die...
s, brain aneurysms, and
pulmonary hypertensionIn medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
in infants.
Synthetic reagent
Sodium nitrite is used to convert
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s into diazo compounds. The synthetic utility of such a reaction is to render the amino group labile for
nucleophilic substitutionIn organic and inorganic chemistry, nucleophilic substitution is a fundamental class of substitution reaction in which an "electron rich" nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom attached to a group or atom called the leaving group; the...
, as the N
2 group is a better
leaving groupIn chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters,...
.
In the laboratory, sodium nitrite is also used to destroy excess
sodium azideSodium azide is the chemical compound with the formula NaN3. This colourless azide salt is a common reagent in organic synthesis, and it is a component in many car airbag systems.-Structure:...
.
- NaNO2 + H2SO4 → HNO2 + NaHSO4
- 2 NaN3 + 2 HNO2 → 3 N2 + 2 NO + 2 NaOH
Health Concerns
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
cancerCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
. "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 AssociationThe American Dietetic Association is the United States' largest organization of food and nutrition professionals, with nearly 67,000 members. Approximately 75 % of ADA's members are registered dietitians and about 4 % are dietetic technicians, registered...
. "Under certain high-temperature cooking conditions such as grilling, it transforms into a reactive compound that has been shown to promote
cancerCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
."
"[Sodium nitrite] is used to cure and preserve meats but can be toxic in large quantities, due to its property of removing oxygen from the blood. Sodium nitrite is also suspected of playing a role in the development of colon cancer,
migraineMigraine is a neurological syndrome characterized by altered bodily perceptions, severe headaches, and nausea. Physiologically, the migraine headache is a neurological condition more common to women than to men. The word migraine was borrowed from Old French migraigne...
s and chronic obstructive lung disease."
"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 nitrateSodium nitrate is the chemical compound with the formula NaNO
3. This salt, also known as "Chile saltpeter" or "Peru saltpeter" , is a white solid which is very soluble in water...
(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."
"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 nitrate does not cause cancer, although some population studies have found an association between high exposure to nitrate 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."
"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.
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 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.
Mechanism of Action
Carcinogenic nitrosamines are formed when
aminesAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
that occur naturally in food react with sodium nitrite found in cured meat products.
- R2NH (amines) + NaNO2 (sodium nitrite) → R2N-N=O (nitrosamine)
In the presence of acid (such as in the stomach) or heat (such as via cooking), nitrosamines are converted to
diazonium ionsDiazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group with the characteristic structure of R-N2+ X- where R can be any organic residue such alkyl or aryl and X is an inorganic or organic anion such as a halogen...
.
- R2N-N=O (nitrosamine) + (acid or heat) → R-N+-N=O (diazonium ion)
Certain nitrosamines such as
N-nitrosodimethylamineN-Nitrosodimethylamine , also known as dimethylnitrosamine , is a semi-volatile organic chemical that is highly toxic and is a suspected human carcinogen. The US Environmental Protection Agency has determined that the maximum admissible concentration of NDMA in drinking water is 7 ng L−1...
and N-nitrosopyrrolidine form carbocations that react with biological nucleophiles (such as DNA or an enzyme) in the cell.
- R-N+-N=O (diazonium ion) → R+ (carbocation) + N2 (leaving group) + :Nu (biological nucleophiles) → R-Nu
If this
nucleophilic substitutionThe S
N1 reaction is a substitution reaction in organic chemistry. "S
N" stands for nucleophilic substitution and the "1" represents the fact that the rate-determining step is unimolecular...
reaction occurs at a crucial site in a biomolecule, it can disrupt normal cell functioning leading to cancer or
cell deathApoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed cell death involves a series of biochemical events leading to a characteristic cell morphology and death; in more specific terms, a series of biochemical events that lead to a variety of...
.
External links