Dimethylamine, nitrosation

A101. Mirvish, S.S. Kinetics of dimethylamine nitrosation in relation to nitrosamine carcinogenesis J. Natl. Cancer Inst. 44 (1970) 633-639. 

We conclude that the major role of bacteria in the nitrosa-tion of dimethylamine is the reduction of nitrate to nitrite and the lowering of the pH of the medium. Furthermore, the complex medium Itself catalyzes nitrosation. The nature of this catalysis is not known, although it could be due to the presence of carbonyl compounds, cysteine, or a variety of other compounds which are known to catalyze nitrosation (17). 

However, at the time the bulk samples were collected, NDMA was present in the air at all test sites in the tannery. The airborne data (see Table III), shows that dimethylamine (DMA) was always present. The amount of airborne NDMA was always approximately equal to 1% of the amount of airborne DMA. The apparent lack of correlation of the NDMA levels with nitrosating capacity is probably due to the relatively small variation in the measured NO levels. 

Spiegelhalder et al. suggested that nitrosation of either dimethylamine or a germination product such as hordenine (Figure 3) by NOx gases in the drying air could lead to NDMA formation in malt (13) Kann and co-workers held that nitrosation of hordenine was the more likely source of NDMA formation in malt... 

Phenols are rather common antimicrobial components of metalworking fluids however, their use in recent years has been declining (36). The inhibition of nitrosation by phenols has recently been reviewed (35). In general, phenolic compounds inhibit nitrosation by reacting with nitrite (phenol reacts with nitrite 10,0 0 0 times faster than with dimethylamine), but the intermediate nitrosophenolis unstable and enhances nitrosation. "The overall effect is dependent on the steady state concentration of the nitrosophenol and the relative degrees of retardation and enhancement exerted by the phenol and the nitrosophenol, respectively ( 35)". 

Soil. After 2 d, degradation yields in an Arkport fine sandy loam (Varna, NY) and sandy soil (Lake George, NY) amended with sewage and nitrite-N were 50 and 20%, respectively. N-Nitrosodimethylamine was identified as the major metabolite (Greene et al., 1981). Mills and Alexander (1976) reported that A-nitrosodimethylamine also formed in soil, municipal sewage, and lake water supplemented with dimethylamine (ppm) and nitrite-N (100 ppm). They found that nitrosation occurred under nonenzymatic conditions at neutral pHs. 

The Smith-Loeppky mechanism [2) convincingly rationalized much of what was known about tertiary amine nitrosations. However, there was some evidence in the literature that there might be more to the mechanistic story. For one thing, it was not clear why the nitrosation of tertiary amines should have a higher pH optimum than that of secondary amines (2). Even more troubling was the somewhat controversial later report by Mai ins (15) that dimethylnitrosamine formed at pH 6 more readily from trimethyl amine than from dimethyl amine. If that report is correct, then free dimethylamine and the corresponding ammonium ion could not be the only kinetically significant intermediates in the trimethyl amine nitrosation. 

A source for the NDMA was not found in this tannery. It was reported that they did use dimethylamine sulfate on an experimental basis and nitrosation of three of the bulk process water samples did result in the formation of 0.0015 to 0.0025 yg/ml of NDMA. We also collected three air samples using acid pH traps and after nitrosating the content, found twice the level of NDMA, thus indicating the presence of the NDMA precursor amine in the air. In a further experiment we sampled air over magnesium silicate coated with morpholine and found that from 3-20% of the 30 yg of morpholine had been converted to N-nitroso morpholine thus indicating an airborne nitrosating agent. 

Among the homologues of hydrazine, asymmetric dimethylhydrazine (CH3)2N- NH2 is important. It is obtained from dimethylamine by nitrosation followed by reduction... 

The irradiation of dimethylamine and nitrite was shown to yield the well-known carcinogenic species nitroso dimethylamine, indicating that carcinogenic compounds may form upon photolysis of nitrite in natural waters [141]. Probably nitrosating agents for amines in irradiated nitrite solution are NO2 and N2O3 [142],... 

An overview of the transformation pathways of various substrates in the presence of nitrate and nitrite under irradiation is reported in Tables 1 and 2, respectively. Quite interestingly, nitrosation intermediates have been detected only in the presence of phenolic compounds, dimethylamine and the herbicide monolinuron [144],... 

Scheme 12 is correct, then the observed overall rate constant should decrease as [added RR NH] is increased. This was found to be so, and was quantitatively in agreement with the rate equation deduced from Scheme 12 (Williams, 1977). Later, direct catalysis of nitrosation of dimethylamine by added thiourea and alkylthioureas was found, which was greater than that produced by thiocyanate ion (Masui et al., 1979). The same effect was noted for the nitrosation of morpholine (Meyer and Williams, 1981). The results are shown graphically in Fig. 3 and include the effects of both Br and SCN" for... 

NDMA is not an industrially or commercially important chemical nevertheless, it can be released into the environment from a wide variety of manmade sources. This is due to the inadvertent formation of NDMA in industrial situations when alkylamines, mainly dimethylamine and trimethylamine, come in contact and react with nitrogen oxides, nitrous acid, or nitrite salts, or when trans-nitrosation via nitro or nitroso compounds occurs. Thus, potential exists for release into the environment from industries such as tanneries, pesticide manufacturing plants, rubber and tire manufacturers, alkylamine manufacture/use sites, fish processing industries, foundries and dye manufacturers. At this time, NDMA has been found in at least 1 out of 1177 hazardous waste sites on the National Priorities List (NPL) in the United States (VIEW Database 1989). 

Nitrosation reaction may also result in the formation of NDMA in the environment. In air, NDMA may form as a product of the nighttime reaction of dimethylamine with NOx. In water and soil, NDMA forms by the reaction of widely-occurring primary, secondary or tertiary amines in the presence of nitrite. 

NDMA has been found in soil at 1-8 ig/kg (dry basis) in Belle and Charleston, WV, New Jersey and New York City (Fine et al. 1977c). It is speculated that occurrence of NDMA in soil may have arisen from (a) absorption of NDMA in air, (b) absorption of dimethylamine from air and its subsequent N-nitrosation, or (c) from pesticide application. 

From their studies with cultures of several microorganisms. Mills and Alexander [45] found that Pseudomonas stutzeri was able to catalyze nitrosation, only when in the growing phase. Although the species was not identified, Ishiwata et al. [46,47] found that bacteria in human saliva formed DMNA from nitrate and dimethylamine. 

Endogenous N-nitrosation may result from cell-mediated reactions, involving alveolar and peritoneal macrophages, bacteria, and yeasts [5,58,59]. In earlier investigation, dimethylamine was used to determine... 

Miscellaneous Reactions. Tetramethylthiourea forms 1 1 adducts with arsenic trihalides and arylarsenic dihalides. The nitrosation of dimethylamine by sodium nitrite at pH 4 is catalysed by thiourea, less efficiently by AW -dimethylthiourea, and more efficiently by tetramethylthiourea. Base-catalysed condensation of thiourea with phthalaldehyde gives A -thiocarbamoyl-l,3-dihydroxyisoindoline (29)... 

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