Nitrosamine volatile

Tobacco smoke and iV-nitrosation are the focus of intense research activity. Workers in the field use the following concepts Tobacco-specific /V-nitrosamines (TSNA) mainstream tobacco smoke (MSTS), smoke inhaled in a puff sidestream tobacco smoke (SSTS), smoke evolved by smoldering cigarettes between puffs nitroso organic compounds (NOC), referring especially to IV-nitrosamines volatile NOC (VNOC) and iV-nitroso amino acids (NAA). 

V-Nitrosamines typically are light yellow volatile soHds or oils. The electron delocalization in the NNO functionaUty sufficiendy restricts rotation around the N—N bond that the E (4) and Z (5) isomers of unsymmetrically substituted examples can often be separated (43). 

A)Ai-dicyclohexyl-2-benzotliiazolesulfenamide (42) [4979-32-2], The cyclohexylamine derivative is preferred over /n/ butylamine [75-64-9] and morpholine sulfenamide analogues because of lower amine volatility and less nitrosamine risk respectively. 

Thiuram Sulfides. These compounds, (8) and (9), are an important class of accelerator. Thiurams are produced by the oxidation of sodium dithiocarbamates. The di- and polysulfides can donate one or more atoms of sulfur from their molecular stmcture for vulcanization. The use of these compounds at relatively high levels with litde or no elemental sulfur provides articles with improved heat resistance. The short-chain (methyl and ethyl) thiurams and dithiocarbamates ate priced 2/kg. Producers have introduced ultra-accelerators based on longer-chain and branched-chain amines that are less volatile and less toxic. This development is also motivated by a desire to rninirnize airborne nitrosamines. 

Retarders were originally arenecarboxylic acids. These acidic materials not only delay the onset of cross-linking but also slow the cross-linking reaction itself. The acidic retarders do not function weU in black-fiUed compounds because of the high pH of furnace blacks. Another type of retarder, A/-nitroso diphenylamine [86-30-6] was used for many years in black-fiUed compounds. This product disappeared when it was recognized that it trans-nitrosated volatile amines to give a several-fold increase in airborne nitrosamines. U.S. production peaked in 1974 at about 1.6 million kg. 

There is an industry trend to supply SBR certifiably free of volatile nitrosamines or nitrosatable compounds. This has generally been accomplished by replacing shortstop systems based on carbamates and hydroxyl amines with products that are not based on secondary amines or are secondary amines of high molecular weight, such as dibenzyldithiocarbamate. A more recendy issued patent for ESBR shortstop is based on isopropyUiydroxylamine, a primary amine that does not form nitrosamine (46). 

The efficient recovery of volatile nitrosamines from frankfurters, followed by gc with chemiluminescence detection, has been described (133). Recoveries ranged from 84.3 to 104.8% for samples spiked at the 20 ppb level. Methods for herbicide residues and other contaminants that may also relate to food have been discussed. Inorganic elements in food can be deterrnined by atomic absorption (AA) methods. These methods have been extensively reviewed. Table 8 Hsts methods for the analysis of elements in foods (134). 

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 symposium upon which this volume is based was organized at a turning point in nitrosamine research. Almost all types of commercial products have been tested for volatile nitrosamines, and there have been a number of outstanding accomplishments of combined university-gov-emment-private industry actions to lower or eliminate volatile nitrosamines in those products found to be contaminated. However, there is still a major gap of knowledge with regard to compounds that are not amenable to analysis by gas chromatography, and this is clearly a frontier of current research. There are also many important questions regarding chemistry, mechanism of action, and relation to human disease whose answers lie in the future of research in this field. 

NPYR occurs in processed meats and, most commonly, in cooked bacon NPYR is one of the principal volatile nitrosamines... 

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. 

N-Nitrosamine inhibitors Ascorbic acid and its derivatives, andDC-tocopherol have been widely studied as inhibitors of the N-nitrosation reactions in bacon (33,48-51). The effect of sodium ascorbate on NPYR formation is variable, complete inhibition is not achieved, and although results indicate lower levels of NPYR in ascorbate-containing bacon, there are examples of increases (52). Recently, it has been concluded (29) that the essential but probably not the only requirement for a potential anti-N-nitrosamine agent in bacon are its (a) ability to trap NO radicals, (b) lipophilicity, (c) non-steam volatility and (d) heat stability up to 174 C (maximum frying temperature). These appear important requirements since the precursors of NPYR have been associated with bacon adipose tissue (15). Consequently, ascorbyl paImitate has been found to be more effective than sodium ascorbate in reducing N-nitrosamine formation (33), while long chain acetals of ascorbic acid, when used at the 500 and lOOO mg/kg levels have been reported to be capable of reducing the formation of N-nitrosamines in the cooked-out fat by 92 and 97%, respectively (49). 

The functions of nitrite and the formation of volatile N-nitrosamines in food systems and their toxicity have been well... 

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 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. 

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. 

A migration test was developed to simulate human exposure patterns. 5 g of rubber material was cut into 1-2 mm stripes and then immersed in 20 ml of standard test solution of artificial saliva (4.2 g NaHC03, 0.2 g K2CO3, 0.5 g NaCl, 0.03 g NaNO, ad 1000 ml with aqua dest.j. After 24 h incubation at 40 C volatile nitrosamines were determined in an aliquot and determined after destination with a standard technique (GC-TEA-method). 

In the last fifteen years there has been considerable interest in the analysis of volatile N-nitrosamines in foods. The primary focus has been on meat cured with nitrite (3 ) although nitrosamines have been shown to occur occasionally in other foods such as fish and cheese (, 3) Recently, attention has been directed to volatile nitrosamines in beer and other alcoholic beverages. The purpose of this paper is to review current information on the presence of nitrosamines in beer, and to discuss work done in our laboratory and elsewhere on the mode of formation of nitrosamines in beer. 

Since the first report of N-nitrosodimethylamine (NDMA) contamination in beer (ij ), there have been a number of surveys on volatile nitrosamine occurrence in beers of different types and origins. The data in Table I includes NDMA analyses on light beers, dark beers, ales, and malt liquors. Table I shows that the... 

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 ). 

Volatile Nitrosamines (ng/cig) NDMA NEMA NDEA8 OTYp"... 

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)>... 

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. 

Reliable methods are available for determination of nitrosamines, especially volatile nitrosamines, in a variety of foods, environmental samples, commercial products, blood and animal tissues. Reviews of these methods are available (1, 2) and descriptions of some state-of-the-art procedures are included in papers on nitrosamine occurrence in this volume. This paper is not intended to be a comprehensive review of historical developments or of the many variations of procedures... 

Major emphasis in studies of N-nitroso compounds in foods has been placed upon volatile nitrosamines, in part because these compounds are relatively easy to isolate from complex matrices by virtue of their volatility. Procedures utilizing atmospheric pressure or vacuum distillation have been used by most investigators, with variations of the method of Fine e al. (2) being among the most popular. This procedure employs vacuum distillation of a mineral oil suspension of the sample with optional addition of water to improve nitrosamine recovery from low moisture content samples (6) The usual approach to prevention of nitrosamine formation during analysis involves adding sulfamic acid or ascorbate to destroy residual nitrite at an early stage of sample preparation. 

In the AOAC procedure, the beer was treated with dilute HCl and sulfamic acid, and the added acid was then neutralized by addition of dilute alkali. Volatile nitrosamines were collected by atmospheric pressure distillation. The distillate was made alkaline and extracted with DCM. The extract was dried and concentrated to 1.0 ml and an aliquot was analyzed by GC-TEA. We used these concentrates, without further cleanup, for evaluating the GCMS high resolution selected ion monitoring procedure. 

Table II. Distribution Ratios of Some Volatile Nitrosamines...

Egan, H. Preussmann, R. Walker, E.A. Castegnaro, M. Wasserman, A.E. Eds. "Environmental Carcinogens Selected Methods of Analysis Vol. 1 - Analysis of Volatile Nitrosamines in Food." lARC Scientific Publications No. 18. International Agency for Research on Cancer Lyon, 1978. Walker, E.A. Griciute, L. Castegnaro, M. Borzsonyi, M., Eds. "N-Nitroso Compounds Analysis Formation and Occurrence" lARC Scientific Publications No. 31. International Agency for Research on Cancer Lyon, 1980. Hedler, L. Schurr, C. Marquadt, P. J. Am. Oil Chem. Soc. 1979, 681-684. 

Other environmental properties of interest are those that govern movement of chemicals, for these properties can influence not only the possibility of human exposure but also the lifetime and fate of the chemical. Clearly, if a nitrosamine is formed in, or introduced into, the soil and stays there, it presents little threat to man, and its lifetime will depend on the chemical or microbiological properties of the soil. If it should move to the surface and volatilize into the atmosphere, on the other hand, there will exist the possibility of human exposure via inhalation and also the possibility of vapor-phase photodecomposition. If a nitrosamine were to leach from soil into water, it could perhaps be consumed in drinking water alternatively, exposure of the aqueous solution to sunlight could provide another opportunity for photodecomposition. 

Volatilization of NDPA, NDEA, NDMA and Ji-nitrosopendime-thalin were examined in a model system. The nitrosamines were either mixed into predetermined depths of the soil or applied to the soil surface (the conditions were chosen to represent those that would be encountered by nitrosamines coapplied with dini-troaniline herbicides). Volatilization of nitrosopendimethalin was extremely slow regardless of application. The volatile nitrosamines, NDPA, NDEA, and NDMA, in contrast, volatilized so rapidly after application to the surface of moist soil that we predicted that a substantial proportion of the nitrosamine thus applied would enter the atmosphere within a few hours. Incorporation of the nitrosamine in the top 7.5 cm of soil (as might be the case when the herbicide was applied and incorporated in a single operation) decreased total volatilization by at least an order of magnitude. 

The presence of volatile nitrosamine impurities in pesticide formulations was an unsuspected phenomenon until the advent of more sensitive and reliable analytical tools for their detection, such as the Thermo Energy Analyzer. 

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