Nitrosamine amounts

By using modem production methods it is possible to reduce the amounts of 1,4-dioxane to a level that is barely detectable with the best current analytical methods. Free ethylene oxide is now below detectable levels. Furthermore, volatile and nonvolatile nitrosamines ( NDELA ) both seem to be below detection limits of ppb in the alkanolamide-based sulfosuccinates. A good overview of modern analytical methods for the detection of 1,4-dioxane and ethylene oxide as well as nitrosamines and formaldehyde is given in Ref. 60. 

The first ten years of nitrosamine research, particularly with respect to carcinogenesis, were summarized in an admirable review by Magee and Barnes (J ). Since that time an enormous amount of work has been carried out on those substances. Some of this work up to 1974 was reviewed by Magee, Montesano and Preussmann (4. Recently, Lai and Arcos ( 5 provided a useful synopsis of contemporary work on the bioactivation of some selected dialkyInitrosamines. 

Dark Decay of UDMH in the Presence of NO, When 1.3 ppm of UDMH in air was reacted in the dark with an approximately equal amount of NO, 0.25 ppm of UDMH was consumed and formation of -0.16 ppm HONO and -0.07 ppm N2O was observed after -3 hours. Throughout the reaction, a broad infrared absorption at -988 cm" corresponding to an unidentified product(s), progressively grew in intensity. The residual infrared spectrum of the unknown product(s) is shown in Figure 2a. It is possible that a very small amount (50.03 ppm) of N-nitrosodimethylamine could also have been formed but the interference by the absorptions of the unknown product(s) made nitrosamine (as well as nitramine) detection difficult. No significant increase in NH3 levels was observed, in contrast to the UDMH dark decay in the absence of NO. Approximately 70% of the UDMH remained at the end of the 3-hour reaction period this corresponds to a half-life of -9 hours which is essentially the same decay rate as that observed in the absence of NO. 

Nitrite concentration The kinetics of N-nitrosamine formation in vitro has been studied at length (, ) and, in moderately acidic media, the reaction rate is directly proportional to the concentration of the free amine (non-protonated) and to the square of the concentration of the undissociated nitrous acid. Therefore, it is not surprising that the amount of nitrite permitted in bacon has received considerable attention. Although, there have been suggestions that it is the initial and not the residual nitrite that influences N-nitrosamine formation in bacon (41), recent evidence seems to indicate that the lowest residual nitrite gives the least probability of N-nitrosamines... 

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... 

Excluding tobacco and tobacco smoke (lf f3), the largest known human exposure to N-nitrosamines is in the industrial sector (4). The area or process air samples containing the largest amount of nitrosamines are in a tire factory, NMOR at the 250 yg/m level (5, a leather tannery, NDMA at the 47 ]xg/wr level (jy, and a rocket fuel factory, NDMA at the 36 yg/m level (7). 

Effect of decreasing amounts of accelerators on nitrosamine and nitrosatable amine content in nipple rubber... 

Amount of accelerator Nitrosamine in extract Nitrosatable amine in extract... 

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. 

The first step in the analysis is extraction of the tobacco with buffer solution (pH 4.5) containing 20 mM ascorbic acid. The nitrosamines are then concentrated by partition with dichloromethane, and a chromatographic clean-up on alumina. In the final step, the concentrate is analyzed by GC-TEA and confirmation of the nitrosamines is obtained by GC-MS (O. If isolated amounts of the nitrosamines are below levels needed for GC-MS confirmation, we employ confirmatory techniques proposed by Krull et a. ( 5). 

In recent years greater attention has been given to nitrogen containing pesticides and the possibility of their nitrosation in soil. The N-nitrosamines that form may arise from the parent pesticide or from a pesticide metabolite. The reaction calls for favourable pH conditions (pH 3-4) and excess nitrite. Under field conditions, the nitrosable residues are usually present in traces and only small quantities of these will actually be nitrosated in soils. However, the possibility exists that the small amounts of N-nitrosamines could be assimilated by plants. 

Figure 1 shows narrow range high resolution scans of the molecular ion region of NDMA, recorded near the maximum of the GC peaks, present in one of the beer samples prepared in the AOAC collaborative study. The peak at m/z 74.0480 represents approximately 0.15 ng of NDMA injected on the column, corresponding to a concentration of 0.6 yg/kg of beer. Use of high resolution MS permitted confirmation of the identity and amount of nitrosamine without additional cleanup of the concentrate prepared by the AOAC method. Sample quantity requirements were comparable to those of the TEA. 

Available detection and confirmation methods are adequate for establishing identity and amounts of nitrosamines in most environmental and biological samples. The validity of analytical results, especially at levels in the part-per-billion and lower range, depends upon the experience and skill of the analyst in preventing or detecting contamination or artifactual formation of nitrosamines. 

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. 

Temperature Nitrosamine Level Treatment Time Amount of Acid ... 

The amount of acid required for nitrosamine destruction is dependent on the level of the nitrosamine impurity, the dinitroaniline being treated, the organic solvent used, temperature, and time. Each reactive mixture was appropriately worked up to a final isolate of the product. Some typical results are shown in Table 1. 

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]. 

Microorganisms have been shown to catalyze the formation of nitrosamines from secondary amines in the presence of nitrite (26). The amount of nitrosamine formed, however, increased as the basicity of the parent amine decreased, presumably due to the increase in the amount of unprotonated amine present (27). This reaction is especially important with respect to metalworking fluids since water-based fluids are inevitably contaminated by microbes and fungi. Microbes are thought to catalyze nitrosamine formation by lowering the pH of the medium or catalysis by one or more unidentified metabolic products. 

The massive contamination of NDE1A in alkaline synthetic fluids (3%) found by Fan et al Q) cannot be explained by known nitrosation kinetics of di- or triethanolamine. Instead, more powerful nitrosation routes, possibly involving nitrogen oxide (N0X) derivatives (e.g., N02> N O t) may be responsible for the amounts of NDE1A in these products (34). In fact, a nitrite-free commercial concentrate was shown to accumulate NDE1A up to about 10 0 days at which time the levels dropped dramatically (19). Inhibition of N0X contaminants may be an effective route to the inhibition of nitrosamine formation in metalworking fluids. 

Experiment.—In order to show that this formation of aromatic nitrosamines is reversible, boil a small amount of the pure compound just prepared in xylene and hold a piece of moist potassium iodide-starch paper over the mouth of the tube. 

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