関: nitrosodimethylamine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/17 07:23:29」(JST)

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Not to be confused with MDMA or NMDA.

N-Nitrosodimethylamine (NDMA), also known as dimethylnitrosamine (DMN), 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.^[1] The EPA has not yet set a regulatory maximum contaminant level (MCL) for drinking water. At high doses, it is a "potent hepatotoxin that can cause fibrosis of the liver" in rats.^[2] The induction of liver tumors in rats after chronic exposure to low doses is well documented.^[3] Its toxic effects on humans are inferred from animal experiments but not well-established experimentally.

NDMA appears to have a very strong affinity as a poison for the liver and at least one case of poisoning in humans is reported. NDMA is water-soluble, colorless, and has at best a weak taste and odor. In the incident reported by New Yorker writer Berton Roueché, a jealous former boyfriend spiked lemonade with NDMA, which he had acquired while working at a cancer research center. At the time of writing, this substance was in common use in the laboratory to induce cancer in mice for study. The incident resulted in the death of an 11-month-old male child and a 30-year old man from, ultimately, massive liver damage. In the victims, NDMA produced very characteristic lesions in the liver, rapidly declining platelet count, and highly elevated SGOT levels. Other symptoms included headache, fever, vomiting, abdominal pain, scattered intradermal hemorrhage, lethargy, nausea, and diarrhea.^[4]

NDMA is an industrial by-product or waste product of several industrial processes. It first came to attention as a groundwater contaminant in California in 1998 and 1999 at several sites that produced rocket fuel. Manufacturing of unsymmetrical dimethylhydrazine (UDMH), which is a component of rocket fuel that requires NDMA for its synthesis, proved to be the culprit in these cases. Of more general concern, water treatment via chlorination or chloramination of organic nitrogen-containing wastewater can lead to the production of NDMA at potentially harmful levels. Further, NDMA can form or be leached during treatment of water by anion exchange resins.^[5] Finally, NDMA is found at low levels in numerous items of human consumption including cured meat, fish, beer, and tobacco smoke ^[5] It is, however, unlikely to bioaccumulate.

NDMA's contamination of drinking water is of particular concern due to the minute concentrations at which it is harmful, the difficulty in detecting it at these concentrations, and to the difficulty in removing it from drinking water. It does not readily biodegrade, adsorb, or volatilize. As such, it cannot be removed by activated carbon and travels easily through soils. Relatively high levels of UV radiation in the 200 to 260 nm breaks the N-N bond and can thus be used to degrade NDMA. Additionally, reverse osmosis is able to remove approximately 50% of NDMA.^[6]

References

^ Andrzejewski, P.; Kasprzyk-Hordern, B.; Nawrocki, J. (2005). "The hazard of N-nitrosodimethylamine (NDMA) formation during water disinfection with strong oxidants". Desalination 176 (1–3): 37–45. doi:10.1016/j.desal.2004.11.009.
^ George, J.; Rao, K. R.; Stern, R.; Chandrakasan, G. (2001). "Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen". Toxicology 156 (2–3): 129–138. doi:10.1016/S0300-483X(00)00352-8. PMID 11164615.
^ Peto, R.; Gray, R.; Brantom, P.; Grasso, P. (1991). "Dose and Time Relationships for Tumor Induction in the Liver and Esophagus of 4080 Inbred Rats by Chronic Ingestion of N-Nitrosodiethylamine or N-Nitrosodimethylamine" (pdf). Cancer Research 51 (23 Part 2): 6452–6469. PMID 1933907. http://cancerres.aacrjournals.org/content/51/23_Part_2/6452.full.pdf.
^ Roueche, Betron (January 25, 1982). "Annals of Medicine - The Prognosis for this Patient is Horrible". The New Yorker: 57–71.
^ ^a ^b Najm, I.; Trussell, R. R. (2001). "NDMA Formation in Water and Wastewater". Journal American Water Works Association 93 (2): 92–99. ISSN 0003-150X. http://apps.awwa.org/WaterLibrary/showabstract.aspx?an=JAW_0053373.
^ Mitch, W. A.; Sharp, J. O.; Trussell, R. R.; Valentine, R. L.; Alvarez-Cohen, L.; Sedlak, D. L. (2003). "N-Nitrosodimethylamine (NDMA) as a Drinking Water Contaminant: A Review". Environmental Engineering Science 20 (5): 389–404. doi:10.1089/109287503768335896.

External links

Nitrosodimethylamine (NDMA) Information
Method Development for the Determination of N-Nitrosodimethylamine (NDMA) in Drinking Water
SFPUC NDMA White Paper
Public Health Statement for n-Nitrosodimethylamine
Toxicological Profile for n-Nitrosodimethylamine CAS# 62-75-9

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1. 肝細胞移植 hepatocyte transplantation
2. 肝線維症の新しい治療法 emerging therapies for hepatic fibrosis

English Journal

Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats.

Elshazly SM1, Mahmoud AA.Author information 1Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.AbstractHepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic effect of hesperidin (100 or 200 mg/kg, a flavanone glycoside with potent anti-inflammatory and antioxidant activities) against liver fibrosis in rats compared to silymarin (100 mg/kg). Liver fibrosis was induced in rats using dimethylnitrosamine (10 mg/kg/day, i.p.) three times per week on alternating days for 4 weeks. After 28 days, tissue and blood samples were collected to assess the protective effect of hesperidin. Dimethylnitrosamine caused liver fibrosis as evidenced by the elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, as well as hepatic malondialdehyde content, gene expression of inducible nitric oxide synthase, α-smooth muscle actin and caspase-3. In addition, dimethylnitrosamine caused a reduction in serum total protein, albumin and hepatic glutathione content. Treatment with hesperidin (100 or 200 mg/kg) successfully ameliorated the deleterious effects of dimethylnitrosamine on all tested parameters. Our study indicates a novel protective effect of hesperidin against dimethylnitrosamine-induced liver fibrosis. Interestingly, the protection evoked by hesperidin (200 mg/kg) was superior to that of the standard silymarin.
Naunyn-Schmiedeberg's archives of pharmacology.Naunyn Schmiedebergs Arch Pharmacol.2014 Mar 14. [Epub ahead of print]
Hepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic
PMID 24627177

Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats.

Qian H, Shi J, Fan TT, Lv J, Chen SW, Song CY, Zheng ZW, Xie WF, Chen YX.Author information Hui Qian, Jian Shi, Ting-Ting Fan, Si-Wen Chen, Chun-Yan Song, Wei-Fen Xie, Yue-Xiang Chen, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.AbstractAIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.
World journal of gastroenterology : WJG.World J Gastroenterol.2014 Feb 21;20(7):1822-32. doi: 10.3748/wjg.v20.i7.1822.
AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.METHODS: Sophocarpine was injected intraperitoneally in two distinct rat hepatic fibrosis models induced either by dimethylnitrosamine or bile duct ligation. Masson's trichrome staining, Si
PMID 24587659

Inhibitory potency of 4-carbon alkanes and alkenes toward CYP2E1 activity.

Hartman JH1, Miller GP1, Boysen G2.Author information 1Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.2Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 820. Little Rock, AR 72205, Unites States; The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: gboysen@uams.edu.AbstractCYP2E1 has been implicated in the bioactivation of many small molecules into reactive metabolites which form adducts with proteins and DNA, and thus a better understanding of the molecular determinants of its selectivity are critical for accurate toxicological predictions. In this study, we determined the potency of inhibition of human CYP2E1 for various 4-carbon alkanes, alkenes and alcohols. In addition, known CYP2E1 substrates and inhibitors including 4-methylpyrazole, aniline, and dimethylnitrosamine were included to determine their relative potencies. Of the 1,3-butadiene-derived metabolites studied, 3,4-epoxy-1-butene was the strongest inhibitor with an IC50 of 110μM compared to 1700μM and 6600μM for 1,2-butenediol and 1,2:3,4-diepoxybutane, respectively. Compared to known inhibitors, inhibitory potency of 3,4-epoxy-1-butene is between 4-methylpyrazole (IC50=1.8μM) and dimethylnitrosamine (IC50=230μM). All three butadiene metabolites inhibit CYP2E1 activity through a simple competitive mechanism. Among the 4-carbon compounds studied, the presence and location of polar groups seems to influence inhibitory potency. To further examine this notion, the investigation was extended to include structurally and chemically similar analogues, including propylene oxide and various butane alcohols. Those results demonstrated preferential recognition of CYP2E1 toward the type and location of polar and hydrophobic structural elements. Taken together, CYP2E1 metabolism may be modified in vivo by exposure to 4-carbon compounds, such as drugs, and nutritional constituents, a finding that highlights the complexity of exposure to mixtures.
Toxicology.Toxicology.2014 Apr 6;318:51-8. doi: 10.1016/j.tox.2014.02.003. Epub 2014 Feb 18.
CYP2E1 has been implicated in the bioactivation of many small molecules into reactive metabolites which form adducts with proteins and DNA, and thus a better understanding of the molecular determinants of its selectivity are critical for accurate toxicological predictions. In this study, we determin
PMID 24561005

Japanese Journal

Traditional Herbal Medicine for the Control of Tropical Diseases

,
Tropical Medicine and Health 42(2SUPPLEMENT), S3-S13, 2014
… Preliminary investigation has demonstrated its promising anti-CCA activity both in vitro and animal (Opisthorchis viverrini/dimethylnitrosamine-induced CCA in hamsters and CCA—xenografted nude mice) models with high selectivity index comparing with the standard drug, 5-fluorouracil. …
NAID 130004463465

Metabolomic Profiling for Identification of Potential Biomarkers in the Protective Effects of Modified Sinisan against Liver Injury in Dimethylnitrosamine Treated Rats

, , [他], , , , ,
Biological and Pharmaceutical Bulletin 36(11), 1700-1707, 2013
… This paper was designed to explore the effects and potential mechanisms of MSNS against dimethylnitrosamine-induced liver injury. …
NAID 130003382028

Suppression by Fucoidan of Liver Fibrogenesis via the TGF-β/Smad Pathway in Protecting against Oxidative Stress

, , [他], , , ,
Bioscience, biotechnology, and biochemistry 75(5), 833-840, 2011-05-23
… We investigated the protective effect of fucoidan on dimethylnitrosamine-induced liver fibrogenesis in rats and its mechanism. …
NAID 10028272223

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リンク元	「ジメチルニトロソアミン」「nitrosodimethylamine」

「ジメチルニトロソアミン」

N-Nitrosodimethylamine
Identifiers
CAS number	62-75-9
PubChem	6124
ChemSpider	5894
EC number	200-549-8
KEGG	C14704
MeSH	Dimethylnitrosamine
ChEBI	CHEBI:35807
ChEMBL	CHEMBL117311
RTECS number	IQ0525000
Jmol-3D images	Image 1; Image 2
	SMILES C[n](C):n:[o] CN(C)N=O ;
	InChI InChI=1S/C2H6N2O/c1-4(2)3-5/h1-2H3 ; Key: UMFJAHHVKNCGLG-UHFFFAOYSA-N ;
Properties
Molecular formula	C2H6N2O
Molar mass	74.08 g mol−1
Appearance	Yellow, transparent liquid
Density	1.005 g mL−1
Boiling point	153 °C, 426.2 K, 307 °F
Solubility in water	290 mg mL−1 (at 20 °C)
log P	−0.496
Vapor pressure	700 Pa (at 20 °C)
Refractive index (nD)	1.437
Thermochemistry
Std enthalpy of; combustion ΔcHo298	1.65 MJ mol−1
Hazards
GHS pictograms
GHS signal word	DANGER
GHS hazard statements	H301, H330, H350, H372, H411
GHS precautionary statements	P260, P273, P284, P301+310, P310
EU Index	612-077-00-3
EU classification	T+ N
R-phrases	R45, R25, R26, R48/25, R51/53
S-phrases	S45
Flash point	61.0 °C
LD50	37.0 mg kg−1 (oral, rat)
Related compounds
Related amines	Dimethylamine; Trimethylamine; Diethylamine; Triethylamine; Diisopropylamine; Dimethylaminopropylamine; Diethylenetriamine; N,N-Diisopropylethylamine; Triisopropylamine; Tris(2-aminoethyl)amine; Mechlorethamine; HN1 (nitrogen mustard); HN3 (nitrogen mustard);
Related compounds	Unsymmetrical dimethylhydrazine; Biguanide; Dithiobiuret;
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

　　[★]

英: dimethylnitrosamine
関: ニトロソジメチルアミン

「nitrosodimethylamine」

　　[★]

ニトロソジメチルアミン

関: dimethylnitrosamine

[Andrzejewski2005-1] Andrzejewski, P.; Kasprzyk-Hordern, B.; Nawrocki, J. (2005). "The hazard of N-nitrosodimethylamine (NDMA) formation during water disinfection with strong oxidants". Desalination 176 (1–3): 37–45. doi:10.1016/j.desal.2004.11.009.

[george2001-2] George, J.; Rao, K. R.; Stern, R.; Chandrakasan, G. (2001). "Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen". Toxicology 156 (2–3): 129–138. doi:10.1016/S0300-483X(00)00352-8. PMID 11164615.

[peto-3] Peto, R.; Gray, R.; Brantom, P.; Grasso, P. (1991). "Dose and Time Relationships for Tumor Induction in the Liver and Esophagus of 4080 Inbred Rats by Chronic Ingestion of N-Nitrosodiethylamine or N-Nitrosodimethylamine" (pdf). Cancer Research 51 (23 Part 2): 6452–6469. PMID 1933907. http://cancerres.aacrjournals.org/content/51/23_Part_2/6452.full.pdf.

[HorribleProg-4] Roueche, Betron (January 25, 1982). "Annals of Medicine - The Prognosis for this Patient is Horrible". The New Yorker: 57–71.

[najm2001-5] Najm, I.; Trussell, R. R. (2001). "NDMA Formation in Water and Wastewater". Journal American Water Works Association 93 (2): 92–99. ISSN 0003-150X. http://apps.awwa.org/WaterLibrary/showabstract.aspx?an=JAW_0053373.

[mitch2003-6] Mitch, W. A.; Sharp, J. O.; Trussell, R. R.; Valentine, R. L.; Alvarez-Cohen, L.; Sedlak, D. L. (2003). "N-Nitrosodimethylamine (NDMA) as a Drinking Water Contaminant: A Review". Environmental Engineering Science 20 (5): 389–404. doi:10.1089/109287503768335896.

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dimethylnitrosamine