Nitrosamine specific

Volatile nitroso compounds were determined in hams processed in elastic rubber nettings by SPE and GC-CLD577. By a similar method A-n i tro sodi ben zy lamine (278b), a semivolatile nitrosamine, was determined in these products by SPE followed by GC interfaced to a nitrosamine-specific TEA-CLD detector the coefficient of variation was 10.6% at the 2.1 ppb level578. The nitrosamines detected in ham most likely originate from the amine precursors in rubber and from the nitrite commonly used in the meat curing process. 

Because N-nitroso compounds can have such a wide variety of physical and chemical properties, and because they can be formed from a wide variety of precursors. analysis at the trace level is difficult. The most widely used technique is the use of a nitrosamine specific detector, called a TEA, which can be interfaced to either a gas chromatograph (GC) or a high pressure liquid chromatograph (HPLC) (31,32). General screening procedures which have been designed to detect all N-nitroso compounds have been developed (33,34). Structural confirmation of N-nitroso compounds is gen-... 

Note NNK3 = 4(methylmtrosamino)-l-(3-pyridl)-l-butanone, a nitrosamine specific to tobacco smoke. 

Emissions of nitrosamines (specifically, iV-nitrosamines) arouse particular concern owing to associated cancer risks." All secondary amines are potential precursors to N-nitrosamines and it will be apparent from considerations of the reactions both prior to cure and accompanying cure (e.g. eqns (24), (27)) that amines may be commonly encountered in vulcanized mixes and the vapours from them. Some of the amines already encountered in emissions from rubber are listed in Table 8. It should be made clear from the outset that not all the amines listed are secondary, and that primary amines are not direct precursors to AT-nitrosamines. Considerable attention has been focused on iV-nitrosamine formation within the rubber industry, and various monitoring exercises have detected such nitrosamines in both vapours and solvent extracts.In one study airborne concentrations in excess of 1 mg/m were found for dimethylnitrosamine (A/ -nitrosodimethylamine), and as high as 4-6mg/m for N-nitrosomorpholine." However, the amine is only one-half of the equation and effort has also been directed to establishing the identity... 

Confirmation of the identities of nitrosamines generally is accompHshed by gas chromatography—mass spectrometry (gc/ms) (46,87). High resolution gc/ms, as well as gc/ms in various single-ion modes, can be used as specific detectors, especially when screening for particular nitrosamines (87) (see Analytical LffiTHODS Trace and residue analysis). 

There is insufficient evidence to unequivocally link nitrosamine exposure to elevated risk for human cancer (159). There are, however, a number of specific cases, especially with respect to the tobacco-related nitrosamines, in which exposure to V/-nitroso compounds is of concern. The strongest evidence in this context is probably that relating to oral cancer rates among habitual users of smokeless tobacco (snuff). Oral cancer rates among this group are significantly elevated over those of nonusers, and /V-nitrosonornicotine, and 4-(methylnitrosamino)-l-(3-pyridinyl)-l-butanone [64091 -91 both of... 

Modem legislation puts much emphasis on the prevention of the formation of carcinogenic secondary nitrosamines as by-products of sulfur vulcanization. This requites the choice of specific accelerators. 

Actually the evidence by no means requires this mechanism since there is no reason why the nitrosamine itself should not act as a primary nitrosating agent (thus allowing cross-nitrosation) and there was no rate data available to support the idea of specific catalysis by hydrochloric acid. 

Cyclic nitrosamines are among the most potent and environmentally significant nitrosamine carcinogens. Like the acyclic nitrosamines, metabolism is necessary for their carcinogenicity. Elucidation of the specific metabolic pathways of cyclic nitrosamine activation and detoxification is a challenging problem, and considerable progress has been achieved in recent years. In this chapter, we will review metabolic studies on N-nitrosopyrrolidine (NPYR), N -nitrosonornicotine (NNN), N-nitrosopiperidine (NPIP), N-nitrosohexamethyleneimine (NHEX), N-nitrosomorpholine (NMOR),... 

Dark Decay of UDMH in Air, UDMH was observed to undergo a gradual dark decay in the 30,000-liter Teflon chamber at a rate which depended on humidity. Specifically, at 41 C and 4% RH the observed UDMH half-life was " 9 hours (initial UDMH 4.4 ppm) and at 40 C and 15% RH, the half-life was -6 hours (initial UDMH 2.5 ppm). The only observed product of the UDMH dark decay was NH3, which accounted for only -5-10% of the UDMH lost. In particular, no nitrosamine, nitramine, or hydrazone were observed. Formaldehyde dimethyIhydrazone was observed in previous studies which employed higher UDMH concentrations and reaction vessels with relatively high surface/volume ratios (, ) ... 

The data in Table I are also significant in terms of the type of analysis to determine the presence of NDMA. In all cases analysis was done using gas chromatography coupled with a Thermal Energy Analyzer, a sensitive, relatively specific nitrosamine detector (12). Further, in six of the studies, the presence of NDMA in several samples was confirmed by gas chromatography-mass spectrometry (GC-MS). The mass spectral data firmly established the presence of NDMA in the beer samples. 

N-Nitrosamines are formed during processing and smoking of tobacco products. Proteins, agricultural chemicals and alkaloids in tobacco products serve as major precursors for volatile, nonvolatile, and tobacco-specific nitrosamines (Figure 1). In this review we will summarize the progress achieved in respect to tobacco nitrosamines since the last ACS symposium in Boston in June of 1978 (J ). Additional papers will review the metabolism of cyclic N-nitrosamines, including that of N -nitrosonornicotine 1) and the correlation between tobacco and alcohol consumption and cancer of the upper alimentary tract (J ). 

Nonvolatile Nitrosamines In Tobacco. A method which we developed several years ago for the analysis of tobacco-specific nitrosamines (TSNA 31) involves extraction of tobacco with buffered ascorbic acid TpH 4.5) followed by partition with ethyl acetate, chromatographic clean-up on silica gel, and analysis by HPLC-TEA (Figure 9). Results obtained with this method for a large spectrum of tobacco products (Table IV), strongly support the concept that the levels of nitrate and alkaloids, and especially the methods for curing and fermentation, determine the yields of TSNA in tobacco products. Recent and as yet preliminary data from snuff analyses indicate that aerobic bacteria play a role in the formation of TSNA during air curing and fermentation. 

Nonvolatile Nitrosamines In Saliva. In vitro experiments had indicated that the tobacco-specific nitrosamines are formed also during snuff dipping (26). Therefore, we analyzed the saliva of snuff dippers and tobacco chewers. A comparison of the results demonstrated the presence of TSNA in saliva at a wide range of concentrations (Table Vl), which could be ascribed to differences in the product, but also to differences in the manner of chewing, and, lastly, to individual factors in each person s saliva. 

Tobacco Specific N-Nitrosamines Snuff Dipper Saliva Collected (ng/g)... 

Saliva of 3 non-snufMipping women (controls) was free of nicotine and tobacco-specific N-nitrosamines. 

Figure 10, Tobacco specific nitrosamines as a function of puff volume (other smoking conditions were kept constant puff duration, 2 s puff frequency, once a minute and butt length, 23 mm).

Nonvolatile Nitrosamines In Tobacco Smoke. Although there are more than 10 million exsmokers in the U.S.A., 53 million adults continue to smoke cigarettes and an additional 10 million still smoke cigars or pipes (39). The cigarette smokers are exposed to about 10 ng of volatile nitrosamines, 20-40 ng of NDELA and, most importantly, to 1-10 pg of tobacco specific N-nitros-amines with each cigarette smoked (Table IV). Similar quantities of the TSNA are found in sidestream smoke. The quantities of TSNA in the smoke are dependent on nitrate, nitrite, tobacco alkaloids and on NNN, NNK and NAT in the tobacco itself (31)>... 

Tobacco Specific N-Nitrosamines Occurrence, Carcinogenicity and Metabolism", ACS Symp. Ser, 1979, 101, 125-152,... 

Hoffmann, D. Adams, J.D. Carcinogenic Tobacco Specific N-Nitrosamines in Snuff and in the Saliva of Snuff Dippers. Submitted. 

Yet, except for specific cases of acute poisoning (2,10, 11), and thus mostly of liver damage, there appears to be no reliably documented evidence that there are any cases of human cancer which can be unambiguously associated with an antecedent exposure to nitrosamines In the Western world (12). 

On the other hand, as discussed at this meeting by Hoffmann et al. (13,14), there are certain tobacco-specific nitrosamines such as nltrosonornlcotlne which form a substantial part of the... 

Reliable analytical methods are available for determination of many volatile nitrosamines at concentrations of 0.1 to 10 ppb in a variety of environmental and biological samples. Most methods employ distillation, extraction, an optional cleanup step, concentration, and final separation by gas chromatography (GC). Use of the highly specific Thermal Energy Analyzer (TEA) as a GC detector affords simplification of sample handling and cleanup without sacrifice of selectivity or sensitivity. Mass spectrometry (MS) is usually employed to confirm the identity of nitrosamines. Utilization of the mass spectrometer s capability to provide quantitative data affords additional confirmatory evidence and quantitative confirmation should be a required criterion of environmental sample analysis. Artifactual formation of nitrosamines continues to be a problem, especially at low levels (0.1 to 1 ppb), and precautions must be taken, such as addition of sulfamic acid or other nitrosation inhibitors. The efficacy of measures for prevention of artifactual nitrosamine formation should be evaluated in each type of sample examined. 

Radioisotope-labeled nitrosamines have proven valuable in development of analytical methods and for demonstrating efficiency of recovery of nitrosamines from tobacco products and smoke (37-39). The very high specific activity required for low part-per-billion determinations has discouraged most analysts from using this approach. Unless a radiochromatographic detector with adequate sensitivity is available, samples must be counted independently of the final chromatographic determination, and one of the advantages of internal standardization, correction for variation in volume injected, is lost. 

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