Nitrosamines Subject

The trialkyltrlazenes are essentially protected diazo-nlum ions. They decompose cleanly and quantitatively to the dlazonlum ions and the corresponding amines over a wide pH range (M). Good kinetic data were obtained over the range of pH 6.9 - 8.3. In more acid solutions, the reactions are too rapid to measure by conventional kinetics. The decomposition reaction is subject to general acid catalysis. Thus, the trialkyltrlazenes will be a useful tool for the study of the reactive intermediates produced by the metabolism of dialkyl-nitrosamines. 

The literature concerning mechanisms of nitrosamine formation in general has been the subject of several excellent reviews, e.g. that of Douglass al. (9). However, the basic principles of nitrosamine formation wTll Fe briefly stated here by way of introduction. 

N-Nitrosamines in Cured Meats Other Than Bacon. The presence of N-nitrosamines in cured meats other than bacon has been the subject of several recent surveys (19,58,59). In general, the majority of the positive samples contained extremely low levels of N-nitrosamine, usually less than I yg/kg (19,58). This low level could, in part, be attributed to the discontinuation of the use of nitrite-spice premixes in the mid-l970 s (l 9). In the Holland study (59), the predominant N-nitrosamines detected were NDMA and N-nitrosomorpholine (NMOR) and, generally, values of 4 yg/kg were obtained for each N-nitrosamine. More correctly, these are presumptive N-nitrsoamine levels since mass spectral confirmation of their identities was not achieved. 

Dinitroaniline herbicides have an unusual property of serving both as an amine contributor and nitrosating agent. The phenomenon (Grove, 1979) was observed when solid or liquid dinitroanilines are subjected to heat. For exan le, when trifluralin is heated to 70 0, N-nitrosodipropylamine (NDPA) is formed. Figure 1 shows the accumulation of NDPA with time. Increased nitrosamine formation is a function of temperature and time. 

Strategies used for the synthesis of polyazapolycyclic-caged nitramines and nitrosamines are the subject of an excellent review by A. T. Nielsen. Nielsen identified three routes to such compounds "... 

Although N-nitrosamines (l) have been known since the nineteenth century, it was not until quite recently that they became the subject of intensive investigations. This renewed interest was spurred in large part by the report of Magee and Barnes ( ) on the carcinogenicity of these compounds. Since then, research into the chemistry and biological properties of N-nitrosamines has accelerated. This brief survey is intended to serve both as a summary of some of the frontiers in this area and as an introduction to the chemistry of N-nitrosamines discussed in the remaining chapters of this Volume. 

Like nitro and azo groups, the nitrosamine moiety is subject to reduction by Fe° and is present in some important environmental contaminants. One such contaminant is A-nitrosodimethylamine (NDMA), which is reduced by Fe° via a complex mechanism that gives the following overall reaction [114,115] ... 

Lu SH, Yang WX, Guo LP, et al. 1987. Determination of N-nitrosamines in gastric juice and urine and a comparison of endogenous formation of N-nitrosoproline and its inhibition in subjects from high-and low-risk areas for oesophageal cancer. lARC Sci Publ 84 538-543. 

RDX is a widely used military explosive. It is a synthetic compound and is not known to exist in nature. Effluents and emissions from Army ammunition plants are responsible for the release of RDX into the environment. When released to the atmosphere, RDX may be removed by reaction with photochemically generated hydroxyl radicals (half-life =1.5 hours). When released to water, RDX is subject to photolysis (half-life = 9-13 hours). Photoproducts include formaldehyde and nitrosamines. 

The U.S. Surgeon General [see p. 200 in (4010)], on the subject of A-nitrosamines in tobacco smoke, stated There is lack of direct evidence that these compounds are also human carcinogens. This was also the view of Magee, who first demonstrated the tumorigenicity of A-nitrosamines in... 

In another example, Schobert et al. [67] address the nitrosamine problem. In view of the health relevance of the subject, their study is quoted verbatim for the most part (cited in a somewhat shortened form in Rothemeyer [7]. 

N-nitrosamines generated at low levels from secondary amines liberated from some of the accelerators can cause health concerns and have been subject to regulation. Volatile N-nitrosamines are quantified using GC with a thermal energy analyzer. 

Fig. 7 Molecules of N-methylated 1,8-diaminonaphthalenes (a), glycine (b), uracil (c), and a-hydroxy-N-nitrosamine (d) subjected to theoretical investigations.

It is clear, therefore, that on balance, it is preferable to allow the use of nitrites to continue until the effects of the consumption of the very small quantities of nitrosamines by human beings, referred to above, are known. Nitrite use should be subject to a number of changes which can be implemented now without much difficulty ... 

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