Nitrosamines, selective

The nitrosamines are insoluble in water, and the lower members are liquid at ordinary temperatures. The separation of an oily liquid when an aqueous solution of an amine salt is treated with sodium nitrite is therefore strong evidence that the amine is secondary. Diphenylnitrosoamine is selected as a preparation because it is a crystalline substance and is thus easier to manipulate on a small scale than one of the lower liquid members. For this preparation, a fairly pure (and therefore almost colourless) sample of diphenyl-amine should be used. Technical diphenylamine, which is almost black in colour, should not be employed. 

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. 

We have developed a quantitative structure-activity model for the variations in potency among the nitrosamines and, more recently, a related model for the variation in target organ for a smaller set of nitrosamines. We are currently developing a model for interspecies variation in susceptibility toward carcinogenic nitrosamines. The model for organ selectivity requires terms for the parent nitrosamine as well as for the hypothesized metabolites while the model for potency variations contains terms only for the unmetabolized parent compound. 

A Structure-Selectivity Model. Nitrosamines are usually highly sensitive towards one or a few target organs some examples are listed in Table III. A casual examination of the structures... 

The experimental conditions and products observed at selected times in the UDMH + O3 experiments are shown in Table I. In general, the nitrosamine yields ranged from -60% when the reaction was carried out in a slight excess of UDMH to -100% when O3 was in excess. The HCHO, H2O2, and HONO yields were -13%,... 

These studies led to some important insights regarding the pathways by which nitrosamine contamination can occur in pesticides, many of which have been described in the literature since the problem was discovered. Let us look at selected papers which have provided this information so we can understand the mechanisms involved, and then at some of the strategies for contamination control which have grown out of these principles. 

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. 

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. 

It is clear that neither NMEA nor NDPA is appropriate for an internal standard in NDMA determination if criteria are interpreted strictly, but both compounds have been used for this purpose. Addition of a nitrosamine, not normally present in the sample, is helpful in detecting any gross errors in the procedure, but the addition should not be considered to be internal standardization. Utilization of NMEA or NDPA to indicate recovery of NDMA can lead to significant errors. In most reports of the application of these "internal standards", recovery of all nitrosamines was close to 100%. Under these conditions, any added compound would appear to be a good internal standard, but none is necessary. NDMA is a particularly difficult compound for use of internal standardization because of its anomalous distribution behavior. I mass j ectrometry is employed for quantitative determination, H- or N-labeled NDMA could be added as internal standard. Because the labeled material would coelute from GC columns with the unlabeled NDMA, this approach is unworkable when GC-TEA is employed or when high resolution MS selected ion monitoring is used with the equipment described above. 

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. 

The literature has numerous citations on both the prevention and destruction of nitrosamines. Techniques, such as the use of scavengers or selective reactions, may be applied to commercial pesticide products. 

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. 

If the selected reaction for nitrosamine is rigidly controlled, the principal product is not modified or... 

The NO + 03 chemiluminescent reaction [Reactions (1-3)] is utilized in two commercially available GC detectors, the TEA detector, manufactured by Thermal Electric Corporation (Saddle Brook, NJ), and two nitrogen-selective detectors, manufactured by Thermal Electric Corporation and Antek Instruments, respectively. The TEA detector provides a highly sensitive and selective means of analyzing samples for A-nitrosamines, many of which are known carcinogens. These compounds can be found in such diverse matrices as foods, cosmetics, tobacco products, and environmental samples of soil and water. The TEA detector can also be used to quantify nitroaromatics. This class of compounds includes many explosives and various reactive intermediates used in the chemical industry [121]. Several nitroaromatics are known carcinogens, and are found as environmental contaminants. They have been repeatedly identified in organic aerosol particles, formed from the reaction of polycyclic aromatic hydrocarbons with atmospheric nitric acid at the particle surface [122-124], The TEA detector is extremely selective, which aids analyses in complex matrices, but also severely limits the number of potential applications for the detector [125-127],... 

Most of the C-diazeniumdiolates are not NO donors since they hydrolyze to produce nitrous oxide directly [174]. However, it has been found that carefully selected compounds can serve as NO donors under physiological conditions via alternative reaction pathways. Many cupferron analogs release NO via enzymatic oxidation [175] as do Oi-alkylated diazeniumdiolates [176]. Several novel types of NO-releasing N-hydroxy-N-nitrosamines have been prepared. These new preparative methods have been described in earlier sections. The precursors are enamines (Scheme 3.10), phenolates (Scheme 3.12), nitriles, and N-hydroxyguanidines (Scheme 3.9). 

Sodium iodide in trifluroacetic anhydride reacts with nitrosamines and releases iodine. This was used for selective detection of nitrosamines after TLC separation602,603. 

Burton HR, Dye NK, Bush LP (1992) Distribution of tobacco constituents in tobacco leaf tissue, 1, Tobacco-specific nitrosamines, nitrate, nitrite and alkaloids, J Agric Food Chem 40 1050-1055 Burton HR, Dye NK, Bush LP (1994) Relationship between tobacco-specific nitrosamines and nitrite from different air cured tobacco varieties, J Agric Food Chem 42 2007-2011 Calafat AM, Polzin GM, Saylor J, Richter P, Ashley DL, Watson CH (2004) Determination of tar, nicotine, and carbon monoxide yields in the mainstream smoke of selected international cigarettes, Tob Control 13 45-51... 

GC/MS(/MS) is also popular for quantifying DBFs. Selected ion monitoring (SIM) or multiple reaction monitoring (MRM) mode are used with GC/MS and GC/ MS/MS, respectively, to maximize the sensitivity and provide low detection limits. Some EFA Methods utilize GC/MS, including EFA Method 524.2, which uses GC/ EI-MS for THM analysis [155], and EFA Method 521, which uses for GC/CI-MS/ MS for nitrosamine analysis [55]. In addition, many priority unregulated DBFs have been measured using GC/MS in a U.S. Nationwide Occurrence Study [11,12]. 

V-Nitrosodiethanolamine has been found in many complex matrices such as cutting and grinding fluids and cosmetics. Analysis for V-nitrosodiethanolamine is complicated by the matrix and a clean-up technique with derivatization is typically required before quantitation of the analyte to achieve adequate sensitivity and selectivity. Ammonium sulfamate may be added to the sample to prevent the artifactual formation ofV-nitrosamines. Derivatives of V-nitrosodiethanolamine have been prepared by acylation, trifluoroacylation, trimethylsilylation and methylation. The derivatives have been analysed by gas chromatography using flame ionization and mass spectro-metric detectors (Occupational Safety and Health Administration, 1990). 

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