Nitrosamines sources

The carcinogenicity of nitrosamines has created widespread concern over the safety of food products that are significant sources of nitrates and nitrites. Nitrosamines are readily formed by reaction of secondary amines with nitrites at acid pH, conditions which may occur in the gastrointestinal tract. 

It has been shown in these studies that the principal, and probably only significant source of NDMA, is malt which had been dried by direct-fired drying (21, 73). It is well known that malts kilned by indirect firing have either low or non-detectable levels of NDMA (74). Consequently, changes in malting procedures have been implemented in both the U.S. and Canada which have resulted in marked reductions in N-nitrosamine levels in both malts and beer (70,74). For example, sulfur dioxide or products of sulfur combustion are now used routinely by all maltsters in the U.S. to minimize N-nitrosamine formation (70). The Canadian malting industry, on the other hand, has... 

Results of a systematic study ( ) of food from the German market indicate the average daily intake for male persons amounts to l.l yg for NDMA and 0.1-0.15 yg for NPYR. Approximately 64% of this total daily intake for NDMA is found in beer, while another 10% comes from cured meat products. It is also important to note that food is not only the only source of N-nitrosamine or N-nitrosatable amines to which we are... 

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 most important sources of preformed environmental nitrosamines according to present knowledge, are given in Table I. 

We have previously shown in a survey on the occurence of volatile nitrosamines in commercial food of the German market that beer is the most important source of N-nitrosodimethylamine (NDMA) (Spiegelhalder et al, 1979 Preussmann et al., 1980 Spiegelhalder et al, 1980) The investigation of about 3000 food samples allowed the calculation of an average daily intake of 1.1 /ug NDMA and of 0.1-0.15/ig N-nitrosopyrrolidine (NPYR) for a male adult in the year 1978. For NDMA 64% (= 0.7yug/day) of the total daily intake resulted from the consumption of beer. 

Morristown, NJ) for the ion source. No carrier gas separator was used. For determination of nitrosamines and TBDMS derivatives of hydroxy-nitrosamines, columns and operating conditions were identical to those for GC-TEA analyses For most work, the He flow rate was 15 cc/min and the column effluent was split 1 1 between a flame ionization detector and the mass spectrometer. The stainless steel splitter, solvent vent valve (Carle Instruments, Fullerton, CA), and associated plumbing were... 

Low resolution MS yields specificity comparable to that of high resolution MS, if a relatively pure sample is delivered to the ion source. Either high resolution GC or additional sample purification is required. To obtain sufficient specificity, it is necessary to demonstrate that the intensities of the major peaks in the mass spectrum are in the correct proportions. Usually 10 to 50 ng of sample is required to establish identity unambiguously. Use of preparative GC for purification of nitrosamines detected by the TEA ( ) is readily adaptable to any nitrosamine present in a complex mixture and requires a minimum of analytical method development when new types of samples are examined. 

Prevention of nitrosamine formation in other important commercial dinitroanilines such as trifluralin, benefin, isopropalin, profluralin, ethalfluralin and other tertiary amines is approached first eliminating sources of nitrosating agents from the reaction mixture prior to amination. 

If animal systems are chosen, preparations derived from fish (see, e.g., Kada, 1981) and birds (Parry et al., 1985) have been used. However, by far the most widely used and validated are those derived from rodents, in particular, the rat. Hamsters may be preferred as a source of metabolizing enzymes when particular chemical classes are being screened, for example, aromatic amines, heterocyclic amines, N-nitrosamines and azo dyes (Prival and Mitchell, 1982 Haworth et al., 1983). 

Extensive developments in the preparation of the enantiomers of chiral nitroso and nitro compounds have not appeared since the earlier review1, and thus no additional discussion of the sources of nitroso and nitro compounds is made in this supplement. However, because of the continuing interest in carcinogenic properties of /V-nitrosamines and related compounds24, there has been a number of reports concerning the ECD and VCD of such compounds, and the ECD and VCD of nitrosamines are discussed as derivatives of chiral amines. 

Migration of nitrosamines into consumer products can occur via direct contact of materials such as waxed containers, elastic and rubber etc.81. Morpholine is used extensively as an industrial solvent for wax formulations. The wax formulations are used for coating fruits and vegetables to prevent moisture loss and increase shelf-life of the products. Paper and cardboard packed with morpholine was also found to give rise to NDMA, as these packaging materials were found to be contaminated with NDMA as well. Besides this, rubber products also provided a migratory source for both nitrosamines and nitros-able amine precursors, as trace levels of NDEA and TV-nitrosodibutylamine (NDBA) have been reported in cured meats with amine-based accelerators in the rubber nettings82. 

The contamination in beer with NOC was first reported in Germany in 197987. The contamination of beer occurs during the kilning (drying) process of malt88 and fermentation89, which leads to the occurrence of NDMS and NPYR. The nitrogen oxides were identified as a source of nitrosamine formation in the beer, formed by nitrosation of the alkaloids... 

Miscellaneous. Volatile nitrosamines can escape into the atmosphere from a variety of other sources. Automobile and diesel engine exhausts may contain N-nitroso compounds, including NDMA at trace levels (5). Nitrosodiethanolamine (NDEIA) is a likely air contaminant in machine shops which use cutting and grinding fluids contaminated with high concentrations of NDElA (10). Several herbicides, known to contain appreciable levels of volatile nitrosamines (9), are applied as aqueous sprays it is likely that worker exposure via inhalation may be appreciable. 

Uses/Sources. Research chemical impurity in herbicides treflan, isopropalin, and triflu-ralin contaminant in wastewater from chemical factories and production of cheese and brandy and other liquors. AT-nitrosamines are frequently produced during rubber processing and may be airborne in the workplace. 

The potentially harmful effects of exposure to high concentrations of nitrates in drinking water result from reduction to nitrites, which combine with haemoglobin to form methaemoglobin (blue baby disease). Additionally, nitrosamine formation can cause cancer and hypertension. In nature, high levels of nutrients, such as nitrates, lead to eutrophication of water sources, which in, severe cases, lead to the extermination of the other aquatic life due the decreased levels of oxygen and luminosity. 

Michejda, C. J. Tipton, T. J. Campbell, D. H. Nitrosative dealkylation under oxidative conditions as a possible source of nitrosamines. In Walker, E. A. Bogovski, P. Griciute, L., Eds. "Environmental N-Nitroso Compounds. Analysis and Formation" lARC Scientific Publication No. 

Thus, 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,... 

In 1985, Stuehr and Marietta demonstrated that the macrophage is the major source of N02 and NO, in response to LPS, at least in the mouse. Subsequently, this group showed that addition of LPS and the immune cytokine interferon-y (cytokines are discussed in more detail below) to macrophages results in N-nitrosation of morpholine the N-nitrosamine was not formed by addition of NO2 and morpholine to the macrophages, and the highest levels of N-nitrosamine occurred many hours prior to the peak NO2" formation (Miwa et al., 1987). Thus, treated macrophages are stimulated to produce a reactive precursor to N02 and NO,, which is capable of N-nitrosamine formation. 

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