Dimethylnitrosamine

Structural formula
General
Surname	Dimethylnitrosamine
other names	Dimethylnitrosoamine N -nitrosodimethylamine N , N -dimethylnitrosamine N -methyl- N -nitrosomethanamine DMN DMNA NDMA
Molecular formula	C 2 H 6 N 2 O
Brief description	yellow liquid with a weak characteristic odor
External identifiers / databases
CAS number 62-75-9 EC number 200-549-8 ECHA InfoCard 100,000,500 PubChem 6124 Wikidata Q409367
properties
Molar mass	74.08 g mol −1
Physical state	liquid
density	1.0048 g cm −3
boiling point	151-153 ° C
Vapor pressure	3.6 mbar (20 ° C)
solubility	easily soluble in water
Refractive index	1.4368 (20 ° C)
safety instructions
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger H and P phrases H: 350-330-301-372-411 P: 201-260-273-284-301 + 310-310
MAK	Switzerland: 0.001 mg m −3
Toxicological data	37 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Dimethylnitrosamine (also known as DMN) is a chemical compound from the group of nitrosamines .

Occurrence

Dimethylnitrosamine is found in foods such as cured meat and alcoholic beverages. It arises in animals when feeding food with nitrite additives. It also occurs as a breakdown product of aminophenazone . In humans, the connection is found in some diseases such as schistosomiasis .

Drinking water ozonation

The ozonization of drinking water in water works , one common method of disinfection or for degradation of chemical (v a drug..) Impurities leads the raw material in the presence dimethylsulfamide , a fungicide - metabolites formed by activated carbon filtration can not be sufficiently eliminated or known methods, to yield of dimethylnitrosamine.

Valsartan contamination

At the beginning of July 2018, a contamination of the active pharmaceutical ingredient valsartan that became known at the Chinese manufacturer Zhejiang Huahai Pharmaceutical and has probably been in existence since 2012 led to numerous drug recalls . At the beginning of August 2018, contamination with DMNA was also found in valsartan batches from the Indian active ingredient manufacturer Hetero Labs Limited and the Chinese manufacturer Zhejiang Tianyu.

→ Main article : Valsartan scandal

Metformin contamination

On December 6, 2019, the Federal Institute for Drugs and Medical Devices (BfArM) informed about traces of N-nitrosodimethylamine (NDMA) in some drugs with the active ingredient metformin. As a result, Streuli Pharma AG from Switzerland, with a letter dated December 11, 2019 and in cooperation with Swissmedic , started a recall campaign for the affected batches down to the retail trade level. As of mid-December 2019, it was not known whether other manufacturers were affected by the contamination.

Extraction and presentation

Dimethylnitrosamine can be obtained by reacting secondary amines with sodium nitrite in the presence of hydrochloric acid .

properties

Dimethylnitrosamine is a yellow liquid with a faint odor and is easily soluble in water. It gradually decomposes when stored (especially when exposed to light) and when heated, producing nitrogen , hydrogen , ethene , methane , dimethylamine and nitrogen oxides .

use

Dimethylnitrosamine can be used to make other chemical compounds (such as daminocide ).

safety instructions

The vapors of dimethylnitrosamine can form an explosive mixture with air ( flash point 61 ° C). In a series of experiments on rodents, oral ingestion of dimethylnitrosamine mainly caused liver tumors and, after inhalation, additional tumors in the lungs and kidneys. The substance was also found to be carcinogenic in numerous other animal species. It was even a carcinogen with diaplacental effect when pregnant rodents were exposed. No valid information is available for humans. However, similarities in the metabolism in tissues of rats and humans have been proven, so that the substance should be regarded as carcinogenic for humans despite the lack of epidemiological data. Oral ingestion of dimethylnitrosamine in large quantities is fatal for humans.

The carcinogenic effect comes about through metabolism , the end product is mutagenic (genotoxic) .

Individual evidence

1. ↑ Hazardous substances database of the University of Hamburg. Accessed on August 12, 2015
2. ↑ ^{a b c d e f g h i} Entry on dimethylnitrosamine in the GESTIS substance database of the IFA , accessed on February 1, 2016(JavaScript required) .
3. ↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-396.
4. ↑ Entry on dimethylnitrosoamine in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
5. ↑ Data sheet N-Nitrosodimethylamine, analytical standard from Sigma-Aldrich , accessed on August 1, 2011 ( PDF ).
6. ↑ Swiss Accident Insurance Fund (Suva): Limit values ​​- current MAK and BAT values (search for 62-75-9 or dimethylnitrosamine ), accessed on November 2, 2015.
7. ↑ Jan Murken: Human Genetics . 2006, ISBN 3-13-139297-5 , pp. 60 ( limited preview in Google Book search).
8. ↑ Heinz Lüllmann, Klaus Mohr, Lutz Hein: Pharmacology and Toxicology . 2010, ISBN 978-3-13-368517-7 ( page 593 in the Google book search).
9. ^ Jan Lehmann: Bladder cancer: New perspectives in diagnosis and treatment . 2004, ISBN 3-540-20504-7 ( page 21 in the Google book search).
10. ↑ S. Hauswirth: Dimethyl sulfamide in groundwater and drinking water - the pollutant of the year? In: Healthcare . tape 70 , no. 3 , 2008, 38, doi : 10.1055 / s-2008-1076545 .
11. ↑ Identification and evaluation of selected drugs and their metabolites (degradation and conversion products) in the water cycle: 3.4.5 N, N-Dimethylnitrosamine-Problematik Umweltbundesamt 2009, p. 23 or 39 (PDF)
12. ↑ tagesschau.de: Active ingredient valsartan: Risk of cancer from antihypertensive drugs. Retrieved on July 22, 2018 (German). 
13. ↑ Valsartan: batch-related recall of valsartan-containing drugs, the active ingredient of which was produced by the Chinese manufacturer Zhejiang Huahai Pharmaceutical, Federal Institute for Drugs and Medical Devices on July 5, 2018, accessed on July 9, 2018.
14. ↑ Recall of pharmaceuticals with active ingredient valsartan from the Chinese manufacturer Zhejiang Huahai Pharmaceutical, Federal Office for Health Safety, AGES Austria on July 5, 2018, accessed on July 10, 2018.
15. ↑ NDMA in Valsartan: Another active ingredient producer affected , online August 10, 2018, accessed August 29, 2018.
16. ↑ Rapid Alert of the BfArM on valsartan , as of August 24, 2018, accessed on August 29, 2018.
17. ↑ Information on medicinal products containing metformin. In: bfarm.de. December 6, 2019, accessed December 23, 2019 . 
18. ↑ Batch recall - Metformin Streuli, film-coated tablets. In: swissmedic.ch. December 16, 2019, accessed December 23, 2019 . 
19. ↑ Celine Müller: Swissmedic / BfArM: Will further metformin recalls follow? In: deutsche-apotheker-zeitung.de . December 18, 2019, accessed December 23, 2019 . 
20. ↑ Paul Margaretha: Chemistry for Medic . 2002, ISBN 3-540-42892-5 ( page 115 in the Google book search).
21. ^ Joint Meeting on Pesticide Residues (JMPR), Monograph for Daminozide , accessed December 9, 2014.
22. ↑ Mona Abdel-Tawab et al. a .: Valsartan: ZL finds NDMA in tablets , issue 30/2018, accessed August 29, 2018.