Reduction of nitrosamines

We recently completed a new survey of 25 beers representing the same labels from similar markets in Oregon and found a mean value of 0.2 ppb, which is more than an order of magnitude lower than the original mean value. The reduction is a direct result of measures taken by the industry to reduce nitrosamine levels in beer. Reduction of nitrosamine levels in beer will be further discussed in the final section of this paper. 

Eizember (1978) and Eizember et al (1979 and 1980) investigated other contingencies for the additional reduction of nitrosamine impurities in a wide variety of dinitroaniline analogs. Trifluralin is chosen as being typical of the dinitroanilines. 

N,N-dialkylhydrazines 93, prepared either by reduction of nitrosamines 91 or by Hofmann degradation of ureas 92 [84] are cyanomethylated with aldehydes and... 

The production of hydrazine and hydrazones by reduction of nitrosamines is another route for NOC production. Piperazine also leads to production of NOC and its use as an antihelminthic has decreased considerably in most developed countries, though not in the case of developing countries due to its low cost. 

The secondary amine and nitrous oxide are the only isolated products from reduction of nitrosamines in alkaline solution [117]. 

The reduction of nitrosamines to hydrazino compounds is accomplished by lithium aluminum hydride 5-(a-methylhydrazino)-3-phenyl-l,2,4-thiadiazole has been obtained in 65% yield by this method.170... 

Fig. 31. Relation of half-wave potentials (at pH 11) for the oxidation of cyclic -phenylenediamines to half-wave potentials in 0.1 M NaOH for the reduction of nitrosamines derived from the same cyclic amines...

These compounds are prepared in part by methods similar to those for amines in addition, specific methods are employed including the reduction of diazonium compounds, reduction of azo compounds, and reduction of nitrosamines leading to sym or unsym-substituted hydrazines. 

Challis BC, Trew DF, Guthrie WG, Roper DV. Reduction of nitrosamines in cosmetic products. Int J Cosmet Sci 1995 17 119-131. 

Reduction. Carboxylic acids can be reduced satisfactorily to primary alcohols by a slight excess of TiC14 and NaBH4 in the molar ratio 1 3. A molar ratio of 1 2 is the optimum for reduction of amides, lactams, and sulfoxides.1 The 1 2 system is also effective for reduction of nitrosamines, R R2N—NO, to secondary amines.2... 

Table 2. Reduction of nitrosamines amine oxide production...

Asymmetrically disubstituted hydrazines can be obtained by reduction of nitrosamines. Singly substituted hydrazines can be prepared, in principle, analogously through the intermediacy of alkylnitrosoureas. These reductions are usually carried out by zinc in acetic acid if mineral acid is used the nitroso group is split off. The method goes back to work by Emil Fischer.124... 

Sodium amalgam,135 aluminum in weakly alkaline aqueous suspension,136 and sodium in alcohol or liquid ammonia130 have also been used for reduction of nitrosamines. 

Hecht, S.S. and A.R. Tricker Nitrosamines derived from nicotine and other tobacco alkaloids Chapter 11 in Analytical determination of nicotine and related compounds and their metabohtes, edited by J.W. Gorrod and P. lacob III, Elsevier, New York NY (1999) 421 88. Hecht, S.S., T.C. Tso, and D. Hoffmann Approaches to the reduction of nitrosamines and aromatic amines in Modifying the risk for the smoker. Proc. 3rd World Conf. on Smoking and Health, edited by E.L. Wynder, D. Hoffmann, and G.B. Gori, 1975, DHEW Publ. No. (NIH) 76-1221 (1976) 535-545. 

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-Nitrosamines, formed principally from the reaction of naturally occurring secondary amines with nitrites that may be added to foods or produced by bacterial reduction of nitrates, have been identified in many food systems including cured meat products, nonfat dried milk, dried malt and beer. In addition, the presence of less volatile and non-volatile N-nitroso compounds or their precursors in foods have been suggested from a number of model system studies. 

Indeed, given an improperly designed or understood system, a blocking agent, like ascorbic acid, could be catalytic toward nitrosamine formation. For example, if the source of nitrosatlng agent is nitrite ion and the susceptible amine is in the lipid phase, conceivably ascorbic acid could cause the rapid reduction of nitrite ion to nitric oxide which could migrate to the lipid phase. Subsequent oxidation of NO to NO in the lipid phase could cause nitrosation. 

The complex pattern of human exposure to environmental N-nitroso compounds is summarized. Recent results are given in three areas, where a significant reduction of human exposure has been achieved after elucidation of its causes 1, N-Nitrosodimethylamine in beer. 2, Volatile N-nitrosamines in baby nipples and pacifiers and 3. occupational exposure in the rubber industry. 

In other working areas the reduction of airborne nitrosamines is possible, too. In a special curing process using a nitrite-nitrate salt bath for tube... 

In Tobacco. At the time of harvesting, fresh tobacco leaves do not contain measurable amounts of nitrosamines (<5 ppb). However, these compounds are formed during curing, aging and fermentation. Their concentrations depend primarily on the content of proteins, alkaloids, agricultural chemicals and nitrate in the tobacco, as well as on the processing conditions which lead to the reduction of the nitrates. 

Scavengers Inhibit nitrosamine formation by competing with the amine for the nltrosatlng agent. Ascorbic acid Is a typical exan le of the competition by rapid reduction of the nltrosatlng agent as shown. 

Chemically, nitrosamines are considered to be quite stable compounds and are difficult to destroy cmce they are formed. Reducing or destroying preformed nitrosamines in pesticides offers special challenge, as they occur in trace amounts which require specific selective treatment without effecting the composition of the principal product. Experimental laboratory work revealed that reactions suitable for mass quantities of reactants, that is neat samples, are not necessarily analagous to micro reactions for the reduction of a given trace nitrosamine contaminant or impurity. 

Aromatic nitro and nitroso compounds are easily reduced at carbon and mercury electrodes. Other nitro compounds such as nitrate esters, nitramines, and nitrosamines are also typically easily reduced. The complete reduction of a nitro compound consists of three two-electron steps (nitro-nitroso-hydroxylamine-amine). Since most organic oxidations are only two-electron processes, higher sensitivity is typically found for nitro compounds. Several LCEC based determination of nitro compounds have been reported... 

Ascorbic acid has been found to be the most effective and useful inhibitor of amine nitrosation [23]. Ascorbic acid inhibits the formation of DMN from oxytetracycline and nitrite, and also from aminophenazone (aminopyrine) and nitrite. Tannins are present in a variety of foods, competing with secondary amines for nitrite and thus leading to a reduction in the amount of nitrosamine formed [24]. 

The syntheses of N-hydroxy-N-nitrosamines are usually carried out by the nitrosation of the corresponding N-hydroxyamines (Scheme 3.8) [123, 124]. N-Hydroxyamines are readily obtained by the reduction of the corresponding nitro-compounds. The most efficient methods are neutral or basic reactions. Recent applications of this method have resulted in the preparation of a variety of cupferron derivatives (Scheme 3.8) via nitrosation of phenylhydroxylamine with amyl nitrite/ammonia [125] or methyl nitrite/ammonia [126]. Behrend and Konig have shown that the organic... 

Chemical complexes of various transition metals have been shown to promote N-nitrosation (28). These metal complexes include ferrocyanide, ferricyanide, cupric ion, molybate ion, cobalt species, and mercuric acetate. All of the reactions are thought to proceed by oxidation-reduction mechanisms. However, such promotion may not be characteristic of transition metal complexes in general, since ferricyanide ion has been shown to promote nitrosation in metalworking fluids, whereas ferric EDTA does not (2 0). Since the metalworking operation generates metal chips and fines which build up in the fluids, this reaction could be of significance in the promotion of nitrosamine formation in water-based metalworking fluids. 

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