Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/12 03:13:09」(JST)

wiki en

Not to be confused with nitroamine.

Structure of the nitrosamino group

Nitrosamines are chemical compounds of the chemical structure R¹N(-R²)-N=O, most of which are carcinogenic.

Usages

Nitrosamines are used in the manufacture of some cosmetics, pesticides, and in most rubber products.^{[citation needed]}

Occurrences

Nitrosamine occurs in latex products such as balloons,^[1] and in many foods and other consumables. Nitrosamines from condoms are not expected to be of toxicological significance.^[2]

In foods, nitrosamines are produced from nitrites and secondary amines, which often occur in the form of proteins. Their formation can occur only under certain conditions, including strongly acidic conditions such as that of the human stomach. High temperatures, as in frying, can also enhance the formation of nitrosamines. The presence of nitrosamines may be identified by the Liebermann's reaction.^[3]

Under acidic conditions the nitrite forms nitrous acid (HNO₂), which is protonated and splits into the nitrosonium cation N≡O⁺ and water: H₂NO₂⁺ = H₂O + NO⁺. The nitrosonium cation then reacts with an amine to produce nitrosamine.^[4]

These processes lead to significant levels of nitrosamines in many foodstuffs, especially beer, fish, and fish byproducts, and also in meat and cheese products preserved with nitrite pickling salt. The U.S. government established limits on the amount of nitrites used in meat products in order to decrease cancer risk in the population.^{[citation needed]} There are also rules about adding ascorbic acid or related compounds to meat, in order to inhibit nitrosamine formation.^{[citation needed]}

Nitrosamines can also be found in tobacco smoke, American dip snuff, Chewing Tobacco, and to a much lesser degree, snus. (127.9 PPM for American dip snuff compared to 2.8 PPM in Swedish snuff or snus.)^[5]

Tobacco companies have and are working extensively to reduce Nitrosamine levels in the finished products that are sold retail to consumers. Ensuring the seeds used to grow the plants are non-converter seeds and teaching farmers the best practices in the harvesting and drying/curing processes to minimize Nitrosamines are among the things done to reduce these levels. These practices have helped to significantly lower Nitrosamine levels in American moist snuff as well as Swedish snus to levels much lower than the previously reported 127.9 PPM level of moist snuff and 2.8 PPM level of snus.^{[citation needed]}

Cancer

In 1956, two British scientists, John Barnes and Peter Magee, reported that dimethylnitrosamine produced liver tumours in rats. Research was undertaken and approximately 90% of nitrosamine compounds were deemed to be carcinogenic.^[6]

In the 1970s, there was an increased frequency of liver cancer found in Norwegian farm animals. The farm animals had been fed on herring meal, which was preserved using sodium nitrite. The sodium nitrite had reacted with dimethylamine in the fish and produced dimethylnitrosamine.^[6]

Nitrosamines can cause cancers in a wide variety of animal species, a feature that suggests that they may also be carcinogenic in humans. At present, available epidemiological evidence from case-control studies on nitrite and nitrosamine intake supports a positive association with gastric cancer risk. Regarding oesophageal cancer, available evidence supports a positive association between nitrite and nitrosamine intake and GC, between meat and processed meat intake and GC and OC, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.^[7]

Hydrazines derived from these nitrosamines, e.g. UDMH, are also carcinogenic.

Examples of nitrosamines

Main article: Tobacco-specific nitrosamines

Substance Name	CAS #	Synonyms	Molecular Formula	Physical Appearance	Carcinogenicity Category
N-Nitrosonornicotine	16543-55-8	NNN	C₉H₁₁N₃O	Light Yellow Low Melting Solid
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone^[8]	64091-91-4	NNK, 4'-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone	C₁₀H₁₅N₃O₂	Light Yellow Oil
N-Nitrosodimethylamine	62-75-9	Dimethylnitrosamine, N,N-Dimethylnitrosamine, NDMA, DMN	C₂H₆N₂O	Yellow liquid	EPA-B2; IARC-2A; OSHA Carcinogen; TLV-A3
N-Nitrosodiethylamine^[9]^[10]^[11]	55-18-5	diethylnitrosamide, diethylnitrosamine, N,N-diethylnitrosamine, N-ethyl-N-nitrosoethanamine, diethylnitrosamine, DANA, DENA, DEN, NDEA	C₄H₁₀N₂O	Yellow liquid	EPA-B2; IARC-2A
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol	76014-81-8	NNAL
N-Nitrosoanabasine	37620-20-5	NAB	C₁₀H₁₃N₃O	Yellow Oil	IARC-3
N-Nitrosoanatabine	71267-22-6	NAT	C₁₀H₁₁N₃O	Clear Yellow to Orange Oil	IARC-3

References

^ Altkofer, W; Braune, S; Ellendt, K; Kettl-Grömminger, M; Steiner, G (2005). "Migration of nitrosamines from rubber products--are balloons and condoms harmful to the human health?". Molecular nutrition & food research 49 (3): 235–8. doi:10.1002/mnfr.200400050. PMID 15672455.
^ Proksch, E (2001). "Toxicological evaluation of nitrosamines in condoms". International journal of hygiene and environmental health 204 (2–3): 103–10. doi:10.1078/1438-4639-00087. PMID 11759152.
^ Mulliken, Samuel Parsons "A method for the identification of pure organic compounds" John Wiley & Sons; 1916; 327 pages
^ Vogel A I, Practical Organic Chemistry, 3rd Ed. Impression 1962 p. 1074
^ Gregory N. Connolly, and Howard Saxner (August 21, 2001). Informational Update Research on Tobacco Specific Nitrosamines (TSNAs) in Oral Snuff and a Request to Tobacco Manufacturers to Voluntarily Set Tolerance Limits For TSNAs in Oral Snuff.
^ ^a ^b "Nitrosamines and Cancer".
^ Jakszyn, P; Gonzalez, CA (2006). "Nitrosamine and related food intake and gastric and oesophageal cancer risk: A systematic review of the epidemiological evidence". World journal of gastroenterology : WJG 12 (27): 4296–303. PMID 16865769.
^ Hecht, Steven S.; Borukhova, Anna; Carmella, Steven G. "Tobacco specific nitrosamines" Chapter 7; of "Nicotine safety and toxicity" Society for Research on Nicotine and Tobacco; 1998 - 203 pages
^ [ NIH Substance Profile]
^ [ Spectrum; Chemical Fact Sheet]
^ [ Safety data for N-nitrosodiethylamine]

External links

Oregon State University, Linus Pauling Institute article on Nitrosamines and cancer, including info on history of meat laws
Risk factors in Pancreatic Cancer

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 脳腫瘍の危険因子 risk factors for brain tumors
2. 胃癌の危険因子 risk factors for gastric cancer
3. 尿路上皮（移行上皮）膀胱癌の疫学および病因 epidemiology and etiology of urothelial transitional cell carcinoma of the bladder
4. 鼻咽頭癌の疫学、病因、および診断 epidemiology etiology and diagnosis of nasopharyngeal carcinoma
5. 化生（慢性）萎縮性胃炎 metaplastic chronic atrophic gastritis

English Journal

Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers.

Ramírez N1, Ozel MZ1, Lewis AC2, Marcé RM3, Borrull F3, Hamilton JF4.
Environment international.Environ Int.2014 Oct;71:139-47. doi: 10.1016/j.envint.2014.06.012. Epub 2014 Jul 16.
In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncer
PMID 25036615

In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A2 activity.

Vijayaraj P1, Sivaprakasam C1, Varthini LV1, Sarkar M2, Nachiappan V3.
Toxicology in vitro : an international journal published in association with BIBRA.Toxicol In Vitro.2014 Sep;28(6):1097-105. doi: 10.1016/j.tiv.2014.05.001. Epub 2014 May 15.
Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and a
PMID 24835565

Characteristic fragmentation behavior of tobacco-specific N-nitrosamines using electrospray ionization multistage tandem mass spectrometry incorporating deuterium labeling.

Hu AF1, Jiang J, Zhou GJ, Yang J, Xiao WQ, Xu J.
Rapid communications in mass spectrometry : RCM.Rapid Commun Mass Spectrom.2014 Aug 15;28(15):1658-64. doi: 10.1002/rcm.6943.
RATIONALE: Tobacco-specific N-nitrosamines (TSNAs) mainly include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), N-nitrosoanabasine (NAB) and N-nitrosoanatabine (NAT) that are formed from tobacco alkaloids during the curing process and contained in tobacco and toba
PMID 24975245

Japanese Journal

オゾン-セラミック膜を併用した下水再生プロセスにおける副生成物の挙動とリスク評価 (京都大学環境衛生工学研究会第36回シンポジウム講演論文集)

福間泰之,林東範,中田典秀 [他]
環境衛生工学研究 : 京都大学環境衛生工学研究会機関誌 28(3), 67-70, 2014-07
NAID 40020160068

Mutagenicity and NO Formation from UVA Irradiated N-Nitrosoproline, and Characterization of Photoproduct Formed in UVA-irradiated Mixture of N-Nitrosoproline with 2'-Deoxyguanosine in Neutral Solution

Arimoto-Kobayashi Sakae,Machida Masaki,Sano Kayoko [他]
Genes and environment : the official journal of the Japanese Environmental Mutagen Society 36(2), 47-53, 2014-05
NAID 40020073371