Nitrosamines

Nitrosamines.—Secondary amines are well known to give nitrosamines on treatment with nitrosyl chloride, but yields are variable addition of pyridine makes 

Henning, F. Lehr, and D. Seebach, Helo. Chim. Acta, 1976, 59, 2213. 

Yamashita, Y. Watanabe, T. Mitsudo, and Y. Takegami, Tetrahedron Letters, 1976, 1585. M. Yamashita, K. Mizushima, Y. Watanabe, T. Mitsudo, and Y. Takegami, y.C.i. Chem. Comm., 1976, 670. 

Thiopivaloyl has been found to be as effective as Mnitroso in promoting quantitative metallations to give stable derivatives of type (18), suitable as amino-methylation agents. 

Aliphatic and aromatic nitrosamines can be separated on silica gel G layers. Preussmann et al. [19, 32, 33] use appropriately modified solvents for TLC of the various nitrosamine classes  

Symmetrical dialkyl-nitrosamines Methyl alkyl nitrosamines Cyclic nitrosamines Aryl-alkyl and diaryl nitrosamines 

Detection, Violet spots are obtained with the diphenylamine-palladium chloride reagent (No. 84). The limit of detection is about 1.2 [xg for volatile nitrosamines and 0.5 (xg for solids. Detection with the sulphanilic acid-a-naphthylamine reagent (No. 239) is still more sensitive aliphatic nitrosamines yield a red-violet colour and aromatic nitrosamines, green to blue (0.2—0.5 xg detected). Yasuda [50] has separated 20 different N-nitroso- and nitro-diphenylamines, using two-dimensional TLC he utilised the results in the analysis of explosives (see p. 672, Fig. 188). 

Solvents A n-Butanol-water-formic acid (60 + 35 + 16) (upper layer) B n-Butanol-water-acetic acid (66 + 17 + 17) C n-Butanol-water-acetic acid (40 + 60 + 10) (upper phase). 

Sttblivan and Brady [37] have likewise used alumina G layers for separating betaine, choline and muscarine with the solvent methanol-carbon tetrachloride-acetic acid (70 + 30 + 2.5) the IlR/-values were 57, 77 and 87 respectively. Tyihak [46], however, works on silica gel G layers, using methanol-water (50 + 50) hi /-values 6 for choline and 45 for betaine. 

Basak et al. correlated information- or complexity-based parameters with mutagenic potency of nitrosamines  

Not only does the question of the content of nitrite or nitrate in pickle-cured meat arise, but also whether nitrosamines are formed and to what extent they occur in meat (cf. 9.8). 

In general, nitrosamines arise only in very low concentrations. Since some of these compounds are a great health hazard, they should be detectable below 0.1 ppm in food for human consumption. The same procedures are available for identifying volatile nitrosamines which have been described earlier for the analysis of aroma constituents (cf. 5.2). However, precautions should be taken during the isolation step. Isolation of nitrosamines should not proceed at low pH since an acid medium in the presence of residual meat nitrites promotes further de novo synthesis of nitrosamines. Since the isolated fraction of neutral volatile confounds, which also includes nitrosamines, is highly conplex in composition, reliable nitrosamines identification by gas chromatographic retention data is not possible. Additional mass spectrometric data are needed to verify the chemical structure. 

Bailey, A. J. (Ed.) Recent advances in the chemistry of meat. The Royal Society of Chemistry, Burlington House London. 1984 

Blander, J., Eyring, G., Richter, B. Wiirzen. In Ullmemns Encyktofradie der technischen Chemie, 4. edn., vol. 24, p. 507, Verlag Chemie Weinheim. 1983 

Grosch, W. Quantification of character-impact odour compounds of roasted beef Z. Lebensm. Unters. Forsch. 196,417 (1993) 

One difficulty in studying the photooxidation of amines is the rapid reaction in the dark with nitrous acid to form nitrosamines (Hanst et al., 1977 Pitts et al., 1978)  

As discussed in Chapter 7.B.3, N02 undergoes a surface reaction with water, which is perhaps enhanced at the air-water interface, forming HONO  

in the course of preparing reactant mixtures for photooxidation studies under typical atmospheric conditions where both N02 and water vapor are present, it is essentially impossible to avoid the production of some HONO, and in the case of studies of amine reactions, some nitrosamines. However, this too is quite relevant, since nitrosamines are carcinogenic in experimental animals. In addition, there are a number of sources that emit nitrosamines directly into the air, 

The major atmospheric fate of the A-nitrosamines such as A-nitrosodimethylamine is photolysis (Tuazon et al., 1984)  

The dimethylamino radical then reacts as described earlier. 

Trimethylenetrinitrosamine (TMTN) 1,3,5-trinitrosohexahydro-sym-triazine, 1,3,5-trinitroso-l,3,5-triazacyclohexane (I) and dinitrosopentamethylenetetramine (DNPT) or l,5-endomethylene-3,7-dinitro-l,3,5,7-tetrazacyclo-octane or 3,5-dinitroso-l,3,5,7-tetrazabicyclo [3,3,1] nonane (II) 

Trimethylenetrinitrosamine (I) was first described in 1881 by F. Mayer [75] who suggested the structure (I). Duden and Scharff [76], Bachmann and Deno [77], and Aubertein [78] gave detailed descriptions of its preparation and chemical properties. Finally, Ficheroulle and Kovache [79] worked out the mechanism of its production on a semi-commercial scale. 

Dinitrosopentamethylenetetramine (II) was first obtained by Griess and Harrow [80]. Formulae of these two substances (I) and (II) were proposed by Cambier and Brochet [81] and Duden and Scharff [76], 

The yield of both reactions is 65-70%. According to Aubertein [78] substance (I) may be prepared in a yield 84% of theoretical. 

The explosive properties of this compound (I) may be of particular interest. 

T0138 Calgon Carbon Corporation, Perox-Pure 

T0144 Carus Chemical Company, CAIROX Potassium Permanganate 

T0641 Radian International, L.L.C., Aquadetox/Soil Vapor Extraction (SVE) T0817 T-Thermal Company, Submerged Quench Incineration 

See individual entries for N-Nitrosodimethylamine, N-Nitroso-N-ethylurea, and N-Nitroso-N-methylurea. 

These compounds are suspected of causing cancers of the lung, nasal sinuses, brain, esophagus, stomach, liver, bladder, and kidney.1 

Wear nitrile rubber gloves, protective laboratory coat, self-contained breathing apparatus, eye protection, and protective shoes. 

On skin. Wash with strong soap solution immediately. Rinse well. 

Contaminated gloves, clothing, and shoes. Remove and clean at once or destroy by burning. 

Nitrosoamines (Fig. 7.8) are the most dangerous EDCs, showing several mutagenic and carcinogenic properties [75]. 

A -Nitrosamines, according to the directive of the Polish Ministry of Health and Social Security, as well as EU directive 93/11/EEC [76, 77], are rated as carcinogenic or probably carcinogenic compounds [78]. 

Every year, over 50 million tons of waste containing nitro-related compounds is created aU over the world. Nitrocompounds are formed by nitration of not only amines, but also amides, urea, guanidines, carbamates, cyanides, and sulfonamides. Because of their chemical properties they are divided easily into hydrolyzable N-nitrosamides and relatively stable N-nitrosamines. Nitrosamines are stable compounds that slowly decompose when exposed to light or in acidic aqueous solutions. 

Large amounts of nitrosamines leak into the environment from the pharmaceutical and food industries, plastics industry, textile industry, waste transport (motor vehicles), industrial effluents (dyes, lubricants, mbber), and the production of solvents. Fuel manufacturing plants and oil refineries are also important emitters of nitrosamines, as well as landfills and fossil fuel combustion processes (to produce heat and power). These compounds naturally penetrate the environment through animal droppings. 

N-Nitroso compounds were detected in low concentrations in air, water, and food, particularly meat products to which nitrate(III) had been added and certain fish products. NDMA was detected in urban air samples. The presence of N-nitroso 

Reaction of the acylarylnitrosamine, PhN(N0)C(0)Me with phosgene, formed in situ from oxidation of CCljBr, gave [PhN JCl, COj and MeC(0) j0 as the reaction products (see Fig. 10.4) [318]. 

Mills and Alexander [78] have discussed the factors affecting the formation of dimethyinitrosamine in samples of water and soil. 

Other applications of gas chromatography to the determination of nitrosamines in non saline waters are reviewed in Table 15.9. 

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The nitrosamines are insoluble in water, and the lower members are liquid at ordinary temperatures. The separation of an oily liquid when an aqueous solution of an amine salt is treated with sodium nitrite is therefore strong evidence that the amine is secondary. Diphenylnitrosoamine is selected as a preparation because it is a crystalline substance and is thus easier to manipulate on a small scale than one of the lower liquid members. For this preparation, a fairly pure (and therefore almost colourless) sample of diphenyl-amine should be used. Technical diphenylamine, which is almost black in colour, should not be employed. 

Reaction of Diphenylnitrosoamine. Carry out Liebermann s Nitroso Reaction as described for phenol (p. 340), but use about 0 05 g. of the nitrosamine instead of the one crystal of sodium nitrite, and finally add only 3-4 drops of sulphuric acid. The deep greenish-blue colour is obtained, becoming red on dilution and reverting to blue on being made alkaline. 

Note. The nitrosamines in Class (ii) do not give the Liebermann reaction. 

N-Nitrosodiethylamine. Add 36-5 g. (51-5 ml.) of diethylamine slowly to the calculated quantity of carefully standardised 5A-hydra chloric acid cooled in ice (1). Introduce the solution of the hydi ochloride into a solution of 39 g. of sodium nitrite (assumed to be of 90 per cent, purity) in 45 ml. of water contained in a 250 ml. distilling flask. Distil the mixture rapidly to dryness. Separate the yellow upper layer of the nitrosamine from the distillate saturate the aqueous layer with soUd potassium carbonate and remove the nitroso compound which separates and add it to the main product. Dry over anhydrous potassium carbonate and distil. Collect the diethylnitrosamine at 172-173-5°, The yield is 41 g. 

Reduction of a nitrosamine to a secondary amine. Proceed as for a nitro compound. Determine the solubility of the residue after evaporation of the ether and also its behaviour towards benzenesulphonyl (or p-toluenesulphonyl) chloride. 

N Nitroso amines are more often called nitrosamines and because many of them are potent carcinogens they have been the object of much investigation We encounter nitrosamines m the environment on a daily basis A few of these all of which are known carcinogens are... 

Nitrosamines are formed whenever nitrosating agents come m contact with secondary amines Indeed more nitrosamines are probably synthesized within our body than enter it... 

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