Intake nitrosamines

Several aspects of the problem of herbicides being contaminated with nitrosamines, and the resulting inadvertent introduction of nitrosamines into the environment, will be discussed in other papers in this symposium. Unrecognized until less than five years ago, the situation has inspired intense debate and prompted several of the environmental chemistry studies mentioned in this paper. Like the presumed threat from the in vivo nitros-ation of pesticide residues, discussions sometimes lack the type of anticipated dose and effect calculations just mentioned. Unlike the active ingredients, whose benefits can justify residue tolerances and acceptable daily intakes, nitrosamine contaminents afford no known benefits, and the desirability of minimizing their levels is undisputed. 

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

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... 

An attempt to estimate human daily impact of N nitroso compounds is shown in Table I. The apparent intake from food of preformed nitrosamines is comparatively low, at least in these surveys of a Western diet in England (3). The Intake directly to the respiratory tract from smoking could be somewhat larger. However, if the blood levels reported are confirmed as correct, then inputs of up to 700 meg per day of at least N nitrosodimethylamine (NDMA) may be calculated, based on pharmacokinetic considerations of data obtained in animals and extrapolated to man. It should be emphasized that no information is available at present on nitrosamide intake or in vivo formation, largely because of analytical limitations. 

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. 

If the concepts and facts presented in this paper are correct, a major kind of human cancer in many regions of the world, cancer of the stomach, is due to a type of nitroso compound, a nitrosoureido derivative, even though not a nitrosamine It is quite certain that the formation of such compounds can be blocked by vitamin C and vitamin E, as well as by some other substances such as gallates Thus, the primary prevention of cancer caused by nitroso compounds is readily accomplished through an adequate Intake of such harmless inhibitors with every meal from infancy onwards ... 

Vapors horn cooking. About 90% of NDMA and 75% of NPYR formed in cooked bacon is lost through evaporation during frying (44,45). It has been calculated that the airborne nitrosamine levels in a typical kitchen could be as high as 56 ng/m3 of NDMA and 560 ng/m3 of NPYR (16). However, the exposure would be of short duration (<1 hr.) and the total nitrosamine intake would be small. 

ELLEN G, EGMOND E, VAN LOON J W, SAHERTIAN E T and TOLSMA K, Dietary intakes of some essential and non-essential trace elements, nitrate, nitrite and N-nitrosamines by Dutch adults estimated by a 24-hour duplicate portion study , Food Additives and Contaminants, 1990 7 207-22. 

In addition to dietary sources, a significant amount of nitrate is formed endogenously by the metabolism of nitric oxide - 1 mg per kg of body weight per day (about the same as the average dietary intake), increasing 20-fold in response to inflammation and immune stimulation. There is considerable secretion of nitrate in saliva, and up to 20% of this may be reduced to nitrite by oral bacteria. Under the acidic conditions of the stomach, nitrite can react with amines in foods to form carcinogenic N-nitrosamines, although it is not known to what extent this occurs in vivo. 

A number of nitroso compounds, A-nitrosamines among them, are potent carcinogens. The most common carcinogenic nitrosamines, found mainly in protein food, are A-nitroso-dimethylamine (NDMA), A-nitroso-diethylamine (NDEA), A-nitroso-pyrrolidine (N-Pyr), and A-nitroso-piperidine (N-Pip). These compounds supposedly increase the risk of colon, rectum, stomach, pancreas, and bladder cancers. Nitrosamines are most prevalent in cured meats, but have also been detected in smoked fish, soy protein foods dried by direct flame, and food-contact elastic nettings. Dietary surveys indicated weekly mean intakes of these compounds amounting to about 3 pg per person (Anon., 1988 Cassens, 1995). In addition, the precursors of nitrosamines, especially nitrate, are abundant in some leafy and root vegetables (Table 14.1). 

Stephany, R.W. and PL. Schuller Daily dietary intakes of nitrite, nitrate and volatile nitrosamines in the Netherlands using the duplicate sampling technique Oncology 37 (1980) 203-210. 

A179. Walker, E.A., M. Castegnaro, L. Garren, G. Toussaint, 26A197. and B. Kowalski Intake of volatile nitrosamines from consnmption of alcohols J. Natl. Cancer Inst. 63 (1979)... 

No experiments are known as to how far nitrosation of amine drugs can be influenced by CDs. Nitrosamines as reaction products can have carcinogenic effects. The in vivo formation of nitrosamines is theoretically possible with all ccmpcunds containing nitrosatable amino groups if conditions are favourable for such reacticais. Nitrate is a normal constituent of human saliva its concentration depends largely on the nitrate intake in food. 

The nitrosopyrrolidine (1.5 pg/kg) in meat products increases almost ten fold (to 15.4pg/kg) during roasting and frying. An estimate of the average daily intake of nitrosamines ranges from 0.1 pg nitrosodimethylamine and 0.1 pg nitrosopyrrolidine to a total of 1 pg. 

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