diethylnitrosamine

ジエチルニトロソアミン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/15 19:50:52」(JST)

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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[edit]

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

Occurrences[edit]

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 nitroso reaction ^[3] (not to be confused with the Liebermann's reaction).

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. ^[5]

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.)^[6]

Cancer[edit]

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.^[7]

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.^[7]

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.^[8]

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

Examples of nitrosamines[edit]

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^[9]	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^[10]^[11]^[12]	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[edit]

^ 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.
^ Vogel A I, Practical Organic Chemistry, 3rd Ed. Impression 1962 p. 649
^ Vogel A I, Practical Organic Chemistry, 3rd Ed. Impression 1962 p. 1074
^ http://lpi.oregonstate.edu/f-w00/nitrosamine.html
^ 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". Missing or empty |url= (help)
^ 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[edit]

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

English Journal

Mechanistic study on liver tumor promoting effects of flutamide in rats.

Tawfeeq MM, Hayashi H, Shimamoto K, Suzuki K, Shibutani M, Inokuma H, Mitsumori K.SourceLaboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Archives of toxicology.Arch Toxicol.2012 Mar;86(3):497-507. Epub 2011 Nov 11.
Flutamide (FLU), a nonsteroidal anti-androgen, is used for the treatment of prostate cancer but is also a cytochrome P450 (CYP) 1A inducer. Some CYP1A inducers are known to exert hepatocellular tumor-promoting activities in rodents, and reactive oxygen species (ROS) produced by CYP1A1 induction via
PMID 22076107

Quantitative analysis of the growth kinetics of chemically induced mouse liver tumors by magnetic resonance imaging.

Schmid A, Rignall B, Pichler BJ, Schwarz M.SourceLaboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Röntgenweg 13, 72076 Tübingen, Germany.
Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2012 Mar;126(1):52-9. Epub 2012 Jan 24.
Noninvasive methods for the early detection of tumor onset and progression in rodent liver would be of high value for pharmaceutical and chemical industry and would, at the same time, foster one of the 3 Rs (replacement, reduction, refinement) by reducing the number of animals in the bioassay. We ha
PMID 22273797

Japanese Journal

Effect of buprenorphine on genotoxicity evaluation of chemicals by the rat liver micronucleus test with partial hepatectomy

, , [他],
The Journal of Toxicological Sciences 40(1), 109-114, 2015
… The effects of the analgesic, buprenorphine, on the genotoxicity evaluation of structural chromosome aberration inducers (cyclophosphamide, diethylnitrosamine and 1,2-dimethylhydrazine) and numerical chromosome aberration inducers (colchicine and carbendazim) were examined. …
NAID 130004904027

ラット肝化学発癌過程におけるcyclophilin B の発現変化

細井一広,照井一史,中川潤一,下山律子,津山博匡,板垣史郎,土田成紀,早狩誠
弘前医学 65(2-4), 164-172, 2014-09-30
… 法にて発現誘導したラット肝前がん病変でのcyclophilin B（CyPB）の発現変化についてCyPB に対するペプチド抗体を用いて解析した．Diethylnitrosamine（DEN）を腹腔内投与後，2-acetylamino-fluorene（FAA）を経口投与し部分切除を行った群において，部分切除3 週より特異的な腫瘍マーカーであるGST-P の強力な発現誘導が認められ，前がん病変の形成を確認した．抗N末端抗体は正常ラットおよび化学発癌を施行した肝臓および …
NAID 120005496549

Modifying effects of liver tumor promotion in rats subjected to co-administration of indole-3-carbinol and phenobarbital

, , , , , , , ,
The Journal of Toxicological Sciences 39(1), 129-140, 2014
… Six-week-old male F344 rats received a single intraperitoneal injection of N-diethylnitrosamine for initiation treatment. …
NAID 130004447105

Related Pictures

[1] 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.

[2] 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.

[3] Vogel A I, Practical Organic Chemistry, 3rd Ed. Impression 1962 p. 649

[4] Vogel A I, Practical Organic Chemistry, 3rd Ed. Impression 1962 p. 1074

[5] ttp://lpi.oregonstate.edu/f-w00/nitrosamine.html

[6] 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.

[nitrocancer-7] "Nitrosamines and Cancer". Missing or empty |url= (help)

[8] 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.

[9] 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

[10] [ NIH Substance Profile]

[11] [ Spectrum; Chemical Fact Sheet]

[12] [ Safety data for N-nitrosodiethylamine]

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