Distribution of Seven N-Nitrosamines in Food

  • Park, Jong-eun (Department of Food and Nutrition, Seoul National University) ;
  • Seo, Jung-eun (Department of Food and Nutrition, Seoul National University) ;
  • Lee, Jee-yeon (Bureau of Health Industry Policy, Korea Health Industry Development Institute) ;
  • Kwon, Hoonjeong (Department of Food and Nutrition, Seoul National University)
  • Received : 2015.08.25
  • Accepted : 2015.09.16
  • Published : 2015.09.30


N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated. However, the benefit of nitrite in food supply could not be ignored and the risk-benefit analysis has become a key issue in the use of the additive. For a risk analysis, an accurate estimation of the hazardous material is necessary; therefore, analytical methods for nitrosamines have continuously evolved from the 1950s. Solid supported liquid-liquid extraction and solid phase extractions have replaced the distillation for the clean-up steps, and tandem mass spectrometry is employed for higher selectivity and sensitivity. In the present study, for a better estimation of N-nitrosamine intake, the total diet study samples were prepared for the N-nitrosamines analysis. In order to obtain the most sensitive results, a partial preparation procedure was developed and modified for different food matrices. Among seven N-nitrosamines (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosomorpholine) analyzed in the present study, N-nitrosodiethylamine has shown the highest detection rate in agricultural foods, while N-nitrosodimethylamine has appeared most frequently in livestock and fishery food products. The concentration of N-nitrosodimethylamine was the highest in seasoning.


Supported by : Ministry of Food and Drug Safety


  1. Scanlan, R.A. and Issenberg, P. (1975) N-nitrosamines in foods. CRC Crit. Rev. Food Sci. Nutr., 5, 357-402.
  2. Cho, I. and Bratzler, L. (1970) Effect of sodium nitrite on flavor of cured pork. J. Food Sci., 35, 668-670.
  3. Walker, R. (1990) Nitrates, nitrites and N-nitrosocompounds: a review of the occurrence in food and diet and the toxicological implications. Food Addit. Contam., 7, 717-768.
  4. Rostkowska, K., Zwierz, K., Rozanski, A., Moniuszko-Jako-niuk, J. and Roszczenko, A. (1998) Formation and metabolism of N-Nitrosamines. Pol. J. Environ. Stud., 7, 321-325.
  5. Gray, J.I. and Dugan, L.R. Jr. (1975) Inhibition of N-nitrosamine formation in model food systems. J. Food Sci., 40, 981-984.
  6. Douglass, M.L., Kabacoff, B.L., Anderson, G.A. and Cheng, M.C. (1978) The chemistry of nitrosamine formation, inhibition and destruction. J. Soc. Cosmet. Chem., 29, 581-606.
  7. Mirvish, S.S., Wallcave, L., Eagen, M. and Shubik, P. (1972) Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science, 177, 65-68.
  8. Sen, N.P., Smith, D.C. and Schwinghamer, L. (1969) Formation of N-nitrosamines from secondary amines and nitrite in human and animal gastric juice. Food Cosmet. Toxicol., 7, 301-307.
  9. O'Brien, T.J., Lukes, B.K. and Scanlan, R.A. (1980) Control of N-nitrosodimethylamine in malt through the use of liquid/ gaseous sulfur dioxide. MBAA TQ, 17, 196-200.
  10. Smith, N.A. (1994) Cambridge prize lecture nitrate reduction and N-nitrosamines in brewing. J. Inst. Brew., 100, 347-355.
  11. Mah, J.H., No, H.K., Kim, Y.J. and Hwang, H.J. (2004) Determination of biogenic amines in kimchi, Korean traditional fermented vegetable products. Food Sci. Biotechnol., 6, 826-829.
  12. Choi, J. and Valentine, R.L. (2002) Formation of N-nitrosodimethylamine (NDMA) from reaction of monochloramine: a new disinfection by-product. Water Res., 36, 817-824.
  13. Walters, C.L., Downes, M.J., Edwards, M.W. and Smith, P.L. (1978) Determination of a non-volatile N-nitrosamine on a food matrix. Analyst, 103, 1127-1133.
  14. International Agency for Research on Cancer. (2014) Agents classified by the IARC monographs. IARC, 1-111, pp. 1-35.
  15. Li, L., Wang, P., Xu, X. and Zhou, G. (2012) Influence of various cooking methods on the concentrations of volatile Nnitrosamines and biogenic amines in dry-cured sausages. J. Food Sci., 77, C560-C565.
  16. Pensabene, J.W., Fiddler, W., Gates, R.A., Fagan, J.C. and Wasserman, A.E. (1974) Effect of frying and other cooking conditions on nitrosopyrrolidine formation in bacon. J. Food Sci., 39, 314-316.
  17. Mottram, D.S., Patterson, R.L., Edwards, R.A. and Gough, T.A. (1977) The preferential formation of volatile N-nitrosamines in the fat of fried bacon. J. Sci. Food Agric., 28, 1025-1029.
  18. Fiddler, W., Pensabene, J.W., Kushnir, I. and Piotrowski, E.G. (1973) Effect of frankfurter cure ingredients on N-nitrosodimethylamine formation in a model system. J. Food Sci., 38, 714-715.
  19. Seo, J.E., Park, J.E., Lee, J.Y. and Kwon, H. (2015) Determination of seven N-nitrosamines in agricultural food matrices using GC-PCI-MS/MS. Food Anal. Methods, submitted.
  20. Raoul, S., Gremaud, E., Biaudet, H. and Turesky, R.J. (1997) Rapid solid-phase extraction method for the detection of volatile nitrosamines in food. J. Agric. Food Chem., 45, 4706-4713.
  21. Myeong, S.W. (2011) Study on guideline development for method validation. KFDA final report project No. 11182KFDA673. Accessed November 30, 2011.
  22. Kim, B.Y. and Yoon, S. (2003) Analysis of nitrate contents of Korean common foods. Food Sci. Biotechnol., 32, 779-784.
  23. Kim, K.R., Shin, J.H., Lee, S.J., Kang, H.H., Kim, H.S. and Sung, N.J. (2002) The formation of N-nitrosamine in kimchi and salt-fermented fish under simulated gastric digestion. J. Food Hyg. Saf., 17, 94-100.
  24. KFDA. (2009) Study on establishment of specification and analytical method for nitrosamines in rubber food contact materials. KFDA final report project No. 09071KFDA008. Accessed December 31, 2009.
  25. Hedler, L., Schurr, C. and Marquardt, P. (1979) Determination of volatile N-nitroso compounds in various samples of edible vegetable oils and margarine (commercially available products). J. Am. Oil Chem. Soc., 56, 681-684.
  26. Yurchenko, S. and Molder, U. (2005) The determination of polycyclic aromatic hydrocarbons in smoked fish by gas chromatography mass spectrometry with positive-ion chemical ionization. J. Food Compos. Anal., 18, 857-869.
  27. Kim, K.R., Lee, S.J., Shin, J.H., Seo, J.K., Shon, M.Y. and Sung, N.J. (2002) The formation of N-nitrosamine in soy sauce, soybean paste and beer under simulated gastric digestion. J. Korean Soc. Food Sci. Nutr., 31, 378-383.
  28. Jo, C.H., Park, H.R., Kim, D.S., Lee, K.H. and Kim, M.H. (2010) Exposure assessment of N-nitrosamines in foods. Food Sci. Biotechnol., 5, 541-548.
  29. Sen, N.P. and Seaman, S. (1981) Investigation into the possible presence of volatile N-nitrosamines in cooking oils, margarine, and butter. J. Agric. Food Chem., 29, 787-789.
  30. Mavelle, T., Bouchikhi, B. and Debry, G. (1991) The occurrence of volatile N-nitrosamines in French foodstuffs. Food Chem., 42, 321-338.
  31. Okafor, P.N. and Nwogbo, E. (2005) Determination of nitrate, nitrite, N-nitrosamines, cyanide and ascorbic acid contents of fruit juices marketed in Nigeria. Afr. J. Biotechnol., 4, 1105-1108.
  32. Zou, X., Li, J., Lu, S., Song, X., Wang, X., Guo, L., Li, J. and Ye, J. (1992) Volatile N-nitrosamines in salted fish samples from high-and low-risk areas for NPC in China. Chin. Med. Sci. J., 7, 201-204.
  33. Oliveira, C.P., Gloria, M.B.A., Barbour, J.F. and Scanlan, R.A. (1995) Nitrate, nitrite, and volatile nitrosamines in whey-containing food products. J. Agric. Food Chem., 43, 967-969.
  34. Scanlan, R.A., Barbour, J.F., Hotchkiss, J.H. and Libbey, L.M. (1980) N-nitrosodimethylamine in beer. Food Cosmet. Toxicol., 18, 27-29.

Cited by

  1. Influence of diet on the gut microbiome and implications for human health vol.15, pp.1, 2017,
  2. Health and Safety Considerations of Fermented Sausages vol.2017, pp.1745-4557, 2017,
  3. Inhibitory effects on N-nitrosodimethylamine formation by decrease of salted-fermented fish products and increase of condiments in kimchi vol.26, pp.5, 2017,
  4. -Nitrosodiethylamine-Induced Liver Injury in Mice by Utilizing the Method of Metabonomics vol.65, pp.9, 2017,
  5. -nitrosodimethylamine on the iNOS-dependent NO production in human neutrophils. Role of NF-κB pp.1366-5928, 2017,
  6. Simultaneous determination of sodium saccharin, aspartame, acesulfame-K and sucralose in food consumed in Korea using high-performance liquid chromatography and evaporative light-scattering detection pp.1944-0057, 2017,
  7. Effects of Amount and Type of Jeotgal, a Traditional Korean Salted and Fermented Seafood, on N-Nitrosodimethylamine Formation during Storage of Kimchi vol.45, pp.9, 2016,
  8. Elucidation of Dishes High in <i>N</i>-nitrosamines Using Total Diet Study Data vol.33, pp.5, 2018,
  9. Controversy on the correlation of red and processed meat consumption with colorectal cancer risk: an Asian perspective pp.1549-7852, 2018,
  10. Nitrate and Nitrite in Health and Disease vol.9, pp.5, 2018,
  11. Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats pp.10956670, 2019,