Sodium Nitrite as Food Additive

Introduction
Sodium nitrite, with a chemical formula of NaNo​2​, is a salt that is usually used to
cure meat products. Sodium nitrite has the characteristics of having a pale yellow color
and crystalline appearance. Due to the similar appearance of sodium nitrite with sugar,
salt and other food ingredients having crystalline appearance, it is often mistaken and thus
can be used in large quantities. Like any other salts, sodium nitrite can also dissolve in
water as it is hygroscopic (Tarte, 2009). However, sodium nitrite is easily oxidized into
sodium nitrate in the presence of air (Toldra, 2015).
Up until now sodium nitrite has long been used as a color enhancer in cured
meats and fishes, also used as a preservative, and antimicrobial agent worldwide. Sodium
nitrite is able to prevent the growth of microorganisms and toxin production of
Clostridium botulinum in cured products. The concentration of sodium nitrite usually
added is around 100 mg/kg to 200 mg/kg in which is able to prevent the growth of various
microorganisms such as ​Achromobacter​, ​Aerobacter​, ​Escherichia,​ ​Flavobacterium​,
Micrococcus and ​Pseudomonas​. ​Staphylococcus aureus can be inhibited with sodium
nitrite especially if the product is vacuum packed. The sodium nitrite will block the
pyruvate metabolism of the ​Staphylococcu​s.
To inhibit the growth of microorganisms, the nitrite hinders the microorganisms
from oxygen uptake, oxidative phosphorylation and active transport dependent on
protons. Other than that, the nitrite also acts as an uncoupler which prevents ATP from
forming and be used by the microorganisms and it also restrains the activities of some
metabolic enzymes. When 156µg of sodium nitrite was added to a perishable canned
cured meat, the first swelling of can was found to be 87 days later compared to when no
sodium nitrite was added (Rahman, 1999). Other functions of sodium nitrite are as an
industrial chemical and therapeutic agent, as stabilizer for meat color, to improve texture
of meat (Madhavi ​et al​., 1996).
The toxicity level of sodium nitrite has been reported to be around 50 mg/kg body
weight for humans. The intoxication of sodium nitrite can cause irritation to the skin
(Toldra, 2015). The average lethal dose of nitrite is around 4 grams and poisoning
symptoms of sodium nitrite can develop within 15-45 minutes of consumption. Sodium
nitrite intoxication is a common cause of severe methemoglobinemia. The dose-response
relationship of sodium nitrite and methemoglobinemia is assumed to be linear. Lethality
of methemoglobinemia is around 60% thus the lethal dose of sodium nitrite for a 60-70
kilogram human being is around 1.5-2.5 grams (Maga and Tu, 1995). According to the
university of West liberty (2010), the use of sodium nitrite may cause mutagenic somatic
cells on mammals. Thus it may cause damage to the blood, cardiovascular system and
smooth muscle. It can also cause adverse reproductive effects; of fertility and fetotoxicity,
and birth defects.
Poisoning cases caused by sodium nitrite are usually an unexpected accident. In
North American and European countries, where foods are usually added with large
amounts of sodium nitrite, many cases of methemoglobinemia caused by accidental
ingestion or inhalation of nitrites have been reported. On the other hand, in Japan few
cases of fatal poisoning by nitrites in food were reported. Consumption of small amounts
of nitrite, as food additives are not linked with poisoning symptoms, whereas acute
exposure to excessive dosage of sodium nitrite may be linked with lethal symptoms such
as methemoglobinemia, a condition where hemoglobin not able to release oxygen
effectively (Nishiguchi ​et al.​ , 2015). Hemoglobin has an auto-oxidized iron process which
cause Ferrous that can bind to oxygen changed into Ferric. Ferric cannot carry oxygen so
the body has its own way to reduce ferric to ferrous using NADH, NADPH and
Cytochrome B5 Reductase. Methemoglobin happened when the ferric concentration in
blood increased because of oxidation of ferrous (Brown and Bowling, 2013). This
condition make the oxygen cannot bind to the hemoglobin and leads to decrease
peripheral oxygen saturation. Although methemoglobin levels above 70% are generally
fatal, patients with methemoglobin levels of up to 94% still have the chance to survive. In
normal physiological state methemoglobin concentration does not exceed 1-2%, levels of
10-20% generally caused cyanosis, levels of 20-50% may cause symptoms such as
respiratory distress, dizziness, headache, and fatigue while levels of 50-70% may cause
loss of consciousness and death (Nishiguchi ​et al.​ , 2015; Katabami ​et al​., 2016).

Current Issues and Discussions

In food products, especially in meat products sodium nitrite is usually added. As
mentioned before, the function in the meat product is as a curing agent. According to
Honikel (2008), the maximum amount of sodium nitrite to be added during manufacturing
is 100 mg/kg and the maximum residual level is 50-175 mg/kg. The lethal oral doses for
human beings is 33-250 mg/kg body weight. The first regulation for the usage of sodium
nitrite in meat was by the Fleischverordnung (meat regulation), limiting the residual
amount to 100 mg sodium nitrite/kg in ready to eat meat products, in raw ham 150
mg/kg. The regulation was then followed by other countries like Europe and Denmark.
European Parliament and Council Directive 95/2/EC on food additive, limits the usage
amount 150 mg nitrite/kg and the residual amount in non-heat treated meat product
should be 50 mg/kg and 100 mg nitrite/kg in all other meat product except bacon 175
mg/kg. For Denmark 150 mg nitrite/ kg is written down in the Danish Regulation. As
time goes, European court must reconsider their past regulation about nitrite as consumer
safety and health concern become more important. In USA, nitrite is labelled a toxic
substance and only may be safely used in or on specified foods.
As published by The Epoch Times in March 2019, nitrites and nitrates are often
used in meat curing processes. In this article, the British Meat Processors Association
stated that the nitrites didn’t destroy ​C.botulinum in meat curing thus the levels of ​C.
botulinum ​contained in the meat remain the same and shows no effectivity when 150 ppm
of sodium nitrites was added. A representative of the parliament then stated that this
chemical should be removed from processed meats immediately. According to both the
National Toxicology Program as part of the U.S. Department of Health and Human
Services and Food Standards Australian and New Zealand (FSANZ), sodium nitrite in
small quantities is safe to be used in food. Although the safety of sodium nitrite in small
quantities is confirmed, however due to the findings that it doesn’t reduce contamination
by ​C. botulinum in meat products, the addition of nitrites in food products will be further
regulated by the FDA especially since traditional processes of meat curing can be used.
As mentioned by the National Toxicology Program and FSANZ that small
quantities of sodium nitrite in small quantities is safe. However, consumption of sodium
nitrites of around 1.5-2.5 grams by an average human being of weight 60-70 kg can cause
methemoglobinemia (Maga and Tu, 1995). Other diseases concerned with the
consumption of sodium nitrite include childhood leukemia and brain cancer. The
International Agency for Research on Cancer also reported that nitrite may be
carcinogenic to humans (Tarte, 2009).
Another case for nitrite poisoning happens in April 2013 on Suzhou City, China.
One male and two females from the same family reported that they suffer from lip
cyanosis, dizziness, tachycardia, nausea, vomiting, unconsciousness and coma. The article
showed that they mistook nitrate as sugar in food preparation and presumed to cook using
nitrate in their dishes which cause three people ill. The family cooked the food using
chicken powder, where after it was investigated, the nitrite content in the chicken powder
sample exceed the national standard for condiments. This case happened due to the
appearance of sodium nitrate that are similar to salt and sugar. The salty taste also
overthrew the family suspicions (Wang ​et al, 2​ 013).
Nishiguchi ​et al​. (2015), reported a 30 year old man, 175 cm tall and 121.0 kg
weighed was found dead due to fatal methemoglobinemia caused by consuming sodium
nitrite. The man was working in the ham-processing factory and had history of mild
depression, diabetes and hypertension. The autopsy was done and the brownish color of
blood was found. The toxicological analysis using colorimetric method revealed that
nitrite and nitrate was found in his heart and femoral blood. Nitrite concentrations were <
0.05 and 0.09 µg/mL and nitrate concentrations were 71.69 and 83.48 µg/mL in the heart
and femoral blood, respectively. Biochemical analysis showed that level of
methemoglobin in the man’s blood reached 83.4%. The median lethal level of oral
sodium nitrite is 71 mg/kg of body weight in human. As mentioned above
Methemoglobin can occur normally by auto-oxidation, however, NADH, NADPH and
cytochrome B5 reductase catalyzed the process of reducing methemoglobin and maintain
it <1% in the normal human body. Although the nitrite and nitrate in the man’s blood was
not reached lethal level, the ingestion of large amount of sodium nitrite causes
methemoglobinemia in a very short time. Therefore, the level of methemoglobin in the
blood is more significant than nitrite and nitrate level (Nishiguchi ​et al.​ , 2015).
As mentioned before, methemoglobinemia is one of the disease that occur due to
high sodium nitrite consumption. Methemoglobinemia is a metabolic disorder in which
hemoglobin is oxidized into methemoglobin (metHB). Methemoglobin are unable to bind
and transport oxygen, which leads to low oxygen supply and can be extremely fatal.
Inhaling and ingesting oxidizing agent such as nitrates are the common cause of this
disease. According to WHO, consuming nitrates orally 0​.4-200 mg/kg body weight are
considered to be toxic and becomes lethal with dose 33-250 mg/kg body weight.
Symptoms starts to show when the ​methemoglobinemia affect 10% of the red blood
cells such as cyanosis, which is a discoloration of the skin to blue or purple due to the low
amount of oxygen saturation in the tissue. Other symptoms such as headaches, dizziness,
panting, tachycardia and general weakness start to show when the cell are affected over
20%. Over 60% serious disease such as loss of consciousness may occur and above 70%
it will become fatal. The antidote to treat the disease is therapeutic protocol of methylene
blue 1% (Matteucci ​et al.,​ 2008)
Another cases of severe methemoglobinemia due to sodium nitrite poisoning was
reported by Katabami (2016), where a 28-year-old man loss consciousness and cyanosis
after ingesting approximately 15 g of sodium nitrite. The blood test revealed that a
methemoglobin level is 92.5%. As mentioned before, methemoglobin level of >70% are
generally fatal and can lead to death. Then, the man immediately given 150 mg methylene
blue (2 mg/kg body weight) intravenously over 5 minutes. After the methylene blue
treatment, he regained consciousness, and his cyanosis resolved within minutes and after
60 minutes his methemoglobin concentration decreased to 19%. From this case, it can be
seen that the initial sign of methemoglobinemia is cyanosis and the antidote is methylene
blue. The dose of using methylene blue for methemoglobinemia level >30% is 1-2 mg/kg
body weight.

Conclusion
To conclude, high doses of sodium nitrite can give several adverse effects to the
human body such as mutagenic somatic cells which can result in damage to the blood,
cardiovascular system and adverse reproductive effects including birth defects. The
intoxication of sodium nitrite is able to cause methemoglobinemia. Moreover,
consumption of sodium nitrite may be carcinogenic to humans. Although the use of
sodium nitrite is still allowed in some countries, it needs to be further regulated for health
concerns.

References

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