Origin and occurrence of NDMA in food drinks and cigarette smoke

High concentrations of nitrosamines were widely reported in foods in the 1970s, particularly in cured meats and fish, cheese, beer, and dried milk [41]. Since NDMA is a potent liver carcinogen, this was good reason for concern. Subsequently, the mechanisms for NDMA formation in these foods were determined. Those are nitrosation of naturally occurring amine by sodium nitrite (a preservative added to fish, meat, and cheese), or by gaseous nitrogen oxides (formed during flue drying of milk and malt used in brewing). Once the routes to NDMA formation in food were understood, steps were taken to reduce its presence. Consequently, the NDMA levels reported in these foodstuff; has been significantly reduced. As an example, Table 3 compares early reports of NDMA concentrations in food with those measured more recently. Reports from the 1990s to 2000s show more than an order of magnitude less NDMA than studies from the 1970s to 1980s. Preparation methods are important, for example, cooking meat at high temperatures (frying or baking) gives a significant increase in NDMA [43].

Synergistic effects of dietary components may increase the likelihood of tumors arising from NDMA. Alcohol and diets rich in fats have been shown to increase the occurrence of liver tumors in laboratory animals fed NDMA [53,54]. Furthermore, cadmium in the diet has been shown to promote NDMA carcinogenesis [55].

Many studies indicate that endogenous NDMA formation from amines and nitrites/nitrates in the stomach is important, and the contribution of endogenous NDMA formation was estimated to be significant by Fristachi and Rice [5]. This occurs because nitrates are reduced to nitrites in the oral

Table 3 Concentrations of NDMA reported in foods

Product

Unit

Year

NDMA concentration

Reference

Range

Mean

Cured fish

ng/g

1971

nd to 26

[42]

2001-

2005

0.541.99

[43]

Cured

ng/g

1975

nd to 35

[44]

meat

2004

7.3 7 0.93

[45]

Bacon

ng/g

1973

nd to 30

[46]

1993-

-1994

nd to 3

[47]

Cheese

ng/g

1978

nd to 68

[48]

1995

nd to 0.84

0.28

[47, 49]

Dried milk

ng/g

1981

0.45 to 4.2

1.697 0.17

[50]

1995

nd to 0.18

[51]

Beer

ng/L

1978-

-1979

nd to 78,000

[52]

2000-

-2006

nd to 660

[52]

cavity, and many amines in foods are rapidly nitrosated in the presence of nitrite under the acidic conditions pertaining to the stomach. Nitrosamines can also form through bacterial nitrosation of amines. However, it is very difficult to accurately estimate endogenous NDMA formation. This has consequences on the intake of nitrites and nitrates in drinking water also, for which health effects are currently unknown.

In vitro experiments frequently use excessively high nitrite concentrations, making extrapolation to realistic physiological concentrations complicated. Investigation of the endogenous NDMA formation in vivo is particularly difficult due to its rapid metabolism. Furthermore, coingestion of foods rich in some antioxidants, such as strawberries, garlic, and green tea, significantly inhibit nitrosation under gastric conditions [56,57]. For example, human excretion of NDMA was 26 times lower following green tea ingestion. These factors make predicting endogenous formation of NDMA in humans difficult, and we will not address it further herein.

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