Related Nitrosamines

LABORATORY CHEMICAL SAFETY SUMMARY DIETHYLNITROSAMINE (AND RELATED NITROSAMINES)  

Substance Diethyinitrosamine (and related nitrosamines) (N-nitrosodiethylamine N-ethyl-N-nitrosoethananime) CAS 55-18-5 

Physical Properties Yellow liquid bp 177 °C Soluble in water 

Major Hazards Probable human carcinogen (OSHA select carcinogen ) other nitrosamines should also he regarded as carcinogenic. 

Flammability and Explosibility Volatilization during combustion produces hazardous vapors. Combustion products contain nitrogen oxides. 

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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... 

Tobacco Habits Other than Smoking Betel-Quid and Areca-Nut Chewing and Some Related Nitrosamines... 

Aminotriazoles are comparable to aromatic amines of the benzene series. Their alkylation and acylation in competition against nuclear nitrogen and functions containing O or S has been mentioned and some reactions of diazo compounds and related nitrosamines have been considered as examples of nucleophilic attack on a nuclear C atom. 

F. P. Guengerich, and T. Shimada (1992). Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of A-nitrosodi-alkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis 13, 1789-1794. 

Tobacco habits other than smoking betel-quid and areca-nut chewing and some related nitrosamines ... 

In the LiAllLj reduction of the nitroso derivative of 53 (see Scheme 13) and related nitrosamines, an induction period may occur. The out-of-control refluxing and frothing that have resulted can be controlled by using oversized glassware and cautiously warming the mixture to reflux. 

R. N. Loeppky and C. J. Michejda, eds., Nitrosamines and Related N-Nitroso Compounds, American Chemical Society, Washington, D.C., 1994. 

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). 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

The related sydnone imine hydrochloride 147 has also been isolated in low yield by treating N-nitroso-A -diphenylphosphinylmethylglycinonitrile 146 with anhydrous HQ and ether at low temperature (2), in a manner similar to that described previously for other nitrosamines of aminoacetonitrile (80). 

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. 

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. 

Our approach is to examine small, closely-related series of nitrosamines and to develop structure-activity models based on molecular descriptors which are explicitly meaningful with respect to the organic chemistry and biochemistry of the compounds. The forms of these models can then often be interpreted in terms of the mechanisms through which these compounds exert their carcinogenic effects. 

There appears now to be ample evidence that the variations in carcinogenicity among the nitrosamines are systematically and rationally related to structure and that several Indices of carcinogenic potency can be used as indices of biological response for the generation of quantitative structure-activity models (11-17). 

Carcinogenicity of NDELA. Our special interest in NDELA as a constituent of tobacco products and as an environmental agent relates to the observation that this nitrosamine induces carcinoma of the liver as well as of the kidney in rats (21,22) and carcinoma of the nasal cavity and papillomas of the trachea in hamsters (23). Recently, Lijinsky reported that NDELA admini-... 

Mende, P., Preussmann, R., Spiegelhalder, B., Nitrosamide formation from foodstuffs, in ACS Symp. Ser. 553, Nitrosamines and related N-Nitroso- compounds, 314, 1994. (CA121 156110p)... 

Occupational health and safety in the rubber industry is discussed with reference to UK, US and European legislation. The review covers both natural and synthetic rubber industries. The first section outlines the laws affecting health and safety in the industry and the remainder presents specific health and safety issues of interest to employers and employees. Industrial safety is examined with reference to equipment, fire and explosions, solvents, epidemiology, NR latex allergy, skin irritations and dermatitis, dust and fume control, work-related musculoskeletal disorders, nitrosamines, 1,3-butadiene, and handling of rubber chemicals. 484 refs. 

Consideration is given to the toxicity of nitrosamines formed during rubber vulcanisation in the presence of certain accelerators, the mechanisms by which they are formed, and French, German and European Union regulations relating to nitrosamines in the workplace atmosphere and in rubber products. Methods used in the sampling and analysis of nitrosamines are also described. 6 refs. 

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