Nitrosamines, Nitrosamides

Nitrosamines and nitrosamides are powerful carcinogens. They are obtained from secondary 

Calf-liver sausage, finely grained Salted herring filet 154 27.4 1.0-405.0 19 5.4 1.9-12.3 

Nitrosamine formation is also possible from primary amines  

smoked and pickled with nitrites or nitrates NDMA 4-26 

Cheese (Danish, Blue, Gouda, Tilsiter, goatmilk cheese) NDMA 1-4 

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Using this approach, methods were established for the degradation of selected compounds in the following seven classes of chemical carcinogens aflatoxins, nitrosamines, nitrosamides, polycyclic aromatic hydrocarbons, hydrazines, haloethers and aromatic amines. A first study was also set up to investigate methods of degradation of some antineoplastic agents,... 

When phenolics are added to nitrosation mixtures, C-nitroso derivatives could be formed. The question must be raised as to their genotoxic or carcinogenic properties. It would be an act of folly to use phenolics as inhibitors of mutagenic nitrosamines, nitrosamides or nitrosoalkylureas and, in the course of this process, create equally or even more active C-nitroso phenolics. Only scanty information is available on this issue. The mutagenicity of p-nitrosophenol is higher than that of phenol in the S, typhi-... 

Bologna sausage orange dietary fiber avoiding the formation of nitrosamines nitrosamides 2009... 

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

Decomposition studies confirmed that N-nitrosamides are much less stable than volatile N-nitrosamines such as NPYR and NDMA (79). Thermal studies utilizing heating conditions commonly encountered in the cooking of bacon and pork roasts indicated that N nitrosomethylpropionamide (NOMP) was degraded to the extent of 74-97% compared to 3-14% for NPYR and NDMA (Table V). It was tentatively concluded that the major... 

The class of Il-nitroso compounds (l e , nitrosamines and nitrosamides) is currently considered a unique group that includes members with remarkable carcinogenic properties. Because of their potency and almost ubiquitous presence in... 

An attempt to estimate human daily impact of N nitroso compounds is shown in Table I. The apparent intake from food of preformed nitrosamines is comparatively low, at least in these surveys of a Western diet in England (3). The Intake directly to the respiratory tract from smoking could be somewhat larger. However, if the blood levels reported are confirmed as correct, then inputs of up to 700 meg per day of at least N nitrosodimethylamine (NDMA) may be calculated, based on pharmacokinetic considerations of data obtained in animals and extrapolated to man. It should be emphasized that no information is available at present on nitrosamide intake or in vivo formation, largely because of analytical limitations. 

Mirvish (53,54) discovered that vitamin C could inhibit ni-trosation reactions. The purely chemical interaction of ascorbic acid with nitrite has been studied for theoretical reasons and because of its importance in the preservation of foods. This interaction has received increased attention for minimizing the presence of nitrosamines and nitrosamides in the environment, and especially in foods. We have studied the relationship in gastric carcinogenesis between high levels of nitrite, including pickling, and of vitamin C as a protective and inhibiting element. 

Mende, P., Preussmann, R., Spiegelhalder, B., Nitrosamide formation from foodstuffs, in ACS Symp. Ser. 553, Nitrosamines and related N-Nitroso- compounds, 314, 1994. (CA121 156110p)... 

N-Nitrosamines have been shown to be inhibitors of cysteine-containing enzymes. For example, dephostatin and other N-methyl-N-nitrosoanilines (1) were found to be inhibitors of the protein tyrosin phosphatases, papain and caspase [90,91]. Inhibition results from the S-nitrosation of the critical cysteine residues in the active sites of the enzymes by the nitrosamines. Compounds 6 and 7 have been found to inhibit thrombus formation in arterioles and venules of rats [92], while N-nitrosamide 9 exhibited vasodilation and mutagenicity as a result of NO release [93]. 

Various nonvolatile nitrosamines were analyzed using HPLC-UV photolysis-CLD. This was applied for determination of V-nitrosamides in dried squid589 and N-nitrosodiphenylamine (278c) in treated apples590. 

Nitrosamines, which are the amides of nitrous acid, are more stable and are derived from secondary amines with nitrous acid. iV-nitrosamides are substances which have a carbonyl group attached to a nitrogen-bearing NO group, e.g. iV-nitrosamides, iV-nitrosocarbamates and /V-nitrosoLireas see Figure 10. 

NOC constitute a large category of genotoxic chemical carcinogens occurring in human diet and are known to induce cancer in experimental animals. Nitrosamines are generally found in foods since they are more stable than nitrosamides. Some NOC precursors do not act directly but must be converted to other nitrosation species. 

Concurrent with our investigation on nitrosamine photochemistry (11), we also initiated an investigation of the ground and excited state chemistry of nitrosamides because of a wide discrepancy in the chemical behavior of these two classes of nitroso compounds. For nitrosamines, the presence of extensive delocalization of the unshared electron pair and the tt electrons of the N=0 group as in VI and VII has been well supported by i) n.m.r. evidence of the restricted rotation about the N-N bond (12), ii) electron diffraction analysis revealing the rather short N-N bond... 

X) for VIII (13) y iii) theoretical calculations indicating unusually high contributions of the polar resonance form VII (15) and iv) association with a proton or metal ion at the nitroso oxygen, the site of the highest electron density (14). The structure of nitrosamines is more realistically represented by the resonance hybrid VIII which explains the extraordinary stability of nitrosamines towards acids and bases in contrast to the lability of nitrosamides I under dilute acidic and basic conditions. ... 

Nitrosamides and nitrosamines exhibit considerably different reaction patterns when thermolysed or photolysed. The differences are discussed in relation to the ground state electronic configurations of these two classes of nitroso compounds. At -150 ,... 

Broadly, NOC are divided into two groups (a) /V-nitrosamines and (b) N-nitrosamides. In jV-nitrosamines, the two remaining substituent groups on the >N—N=0 atom can be either alkyl or aryl, or they can form the part of a heterocyclic ring (as in N-nitrosopyrrolidine). On the other hand, in N-nitrosamides, more correctly called N-acyl-N-nitroso compounds, one of these... 

Recent advances in chromatography have made it possible to employ microbore HPLC for the determination of NOC. Its main advantage is that it uses a very low mobile-phase flow (20-100 /rl/min). This might make the TEA compatible with a reversed-phase system. Massey et al. (73), in fact, have successfully used reversed-phase chromatography for the HPLC-TEA determination of V-nitroso-V, 7V -di methylpiperazinium iodide. A 500-mm X 1-mm microbore ODS column and a mobile phase consisting of 0.1 M ammonium heptane-sulfonate in methanol water (70 30) (flow rate 20 /zl/min) was used for the HPLC separation. In another study, Riihl and Reusch (74) used a microbore Spherisorb 3 SW column for HPLC-TEA determination of volatile V-nitrosamines. The mobile phase was a mixture of 2-propanol and n-hexane (2.5 97.5). Further application of such techniques for the determination of various polar NOC, especially A-nitrosamides, in foods is desirable. 

Ar-Nitroso compounds. All nitrosamines [R -N(NO)-R] and nitrosamides [R -N(NO)COR] should be regarded as potentially powerful carcinogens, since most compounds of these types have been shown to possess high activity in experimental animals. The following are some of the more likely to be encountered in the laboratory. 

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