Preview

Hygiene and Sanitation

Advanced search
Open Access Open Access  Restricted Access Subscription Access

Hygienic assessment of the impact of N-nitrosamines in their total intake into the body of young children

https://doi.org/10.47470/0016-9900-2025-104-6-755-760

EDN: bwhyfh

Abstract

Introduction. N-nitrosamines are priority potentially hazardous contaminants occurring in some food products; they pose a considerable threat for health in infants and toddlers. The valid standards substantiated per levels of carcinogenic risk regulate contents of two such compounds. However, it is necessary to accomplish complex assessment of impacts exerted by all identified N-nitrosamines at lower doses considering their non-carcinogenic effects. This will provide a more comprehensive approach to assessing risks associated with their intake with food products.

The aim of the study was to assess the impact of N-nitrosamines at their total intake with canned meat in infants and toddlers.

Materials and methods. The study involved Wistar rats (aged 4–8 weeks). The experiment animals were divided into a control group (standard fodder) and two test groups (canned meat). We estimated biochemical blood indices (AST, ALT, GGT, bilirubin, alkaline phosphatase) and histological state of the liver, dose-dependent effects. Statistical analysis included the Mann – Whitney U-test and regression analysis.

Results. After a 28-day experiment, levels of biochemical indices turned out to be significantly higher in the test groups against the control (p < 0.05). Regression analysis confirmed an association between levels of exposure to N-nitrosamines and elevated levels of biomarkers of effect (R2 for GGT = 0.725, p < 0.000001). Histology of the liver found a growing number of Kupffer cells (p < 0.05), which are markers of inflammatory response. We established model parameters for describing a relationship between likelihood of increased markers of the effect and the total dose of N-nitrosamines. Tolerable daily intake (TDI) was determined based on the study findings; it was equal to 0.00175 µg/kg of body weight, ensuring safety, taking into account the carcinogenic risk criterion.

Limitations. The obtained results are applicable exclusively to canned meat for infants and toddlers and cannot be extrapolated onto other food products or age groups.

Conclusion. The experiment results obtained by using markers of effects were also confirmed by histological studies. This indicates that the established regression parameters and TDI can be employed in quantification of health risks for infants and toddlers considering non-carcinogenic effects.

Compliance with ethical standards. The study was approved by the local ethics committee of the Rospotrebnadzor’s (Meeting Report No. 2 dated February 20, 2018) and conducted in conformity with the conventional research principles stated in the WMA Declaration of Helsinki (as of edited in 2013).

Contribution:
Suvorov D.V. – concept and design of the study, collection of literature data, statistical analysis, writing text;
Zaitseva N.V., Shur P.Z., Zemlyanova M.A. – concept of the study, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: April 3, 2025 / Revised: May 19, 2025 / Accepted: June 26, 2025 / Published: July 31, 2025

About the Authors

Dmitri V. Suvorov
Federal Scientific Center for Medical and Preventive Health Risk Management Technologies
Russian Federation

A researcher in health risk analysis department of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: suvorov@fcrisk.ru



Nina V. Zaitseva
Federal Scientific Center for Medical and Preventive Health Risk Management Technologies
Russian Federation

DSc (Medicine), professor, Academician of the RAS, Scientific Head of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: znv@fcrisk.ru



Pavel Z. Shur
Federal Scientific Center for Medical and Preventive Health Risk Management Technologies
Russian Federation

DSc (Medicine), Chief researcher – secretary of the Academic Council of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: shur@fcrisk.ru



Marina A. Zemlyanova
Federal Scientific Center for Medical and Preventive Health Risk Management Technologies
Russian Federation

DSc (Medicine), assistant professor, head of Department of Biochemical and Cytogenetic Diagnostics of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation

e-mail: zem@fcrisk.ru



References

1. Suvorov D.V., Zaitseva N.V., Shur P.Z., Zelenkin S.E., Ngoc N.T.H., Thanh T.T. Health risk assessment associated with priority potentially hazardous chemical compounds detected in canned meat and meat-and-vegetable food for infants. Voprosy pitaniya. 2023; 92(4): 38–48. https://doi.org/10.33029/0042-8833-2023-92-4-38-48 https://elibrary.ru/dqdufj (in Russian)

2. Berezhanskaya S.B., Lukyanova E.A., Kaushanskaya E.Ya., Ishchenko E.V. Dynamics of morphofunctional disorders of the liver in children with perinatal hypoxia during the first year of life. Pediatriya im. G.N. Speranskogo. 2013; 92(2): 52–6. https://elibrary.ru/qikjzb (in Russian)

3. Zobnin Yu.V. Toxic injury of the liver in children. Sibirskii meditsinskii zhurnal (Irkutsk). 2017; 151(4): 37–53. https://elibrary.ru/waoyot (in Russian)

4. Schrenk D., Bignami M., Bodin L., Chipman J.K., del Mazo J., Hogstrand C., et al. Scientific Opinion on the risk assessment of N-nitrosamines in food. EFSA Journal. 2023; 21(3): 7884. https://doi.org/10.2903/j.efsa.2023.7884

5. European Food Safety Authority. Nitrosamines in food raise a health concern; 2023. Available at: https://efsa.europa.eu/en/news/nitrosamines-food-raise-health-concern

6. Liu W., Huang J., Yan Z., Lin Y., Huang G., Chen X., et al. Association of N-nitrosodimethylamine exposure with cognitive impairment based on the clues of mice and humans. Front. Aging Neurosci. 2023; 15: 1137164. https://doi.org/10.3389/fnagi.2023.1137164

7. Maslovskaya A.A. Specific features of energy metabolism in child. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2006; (1): 25–8. https://elibrary.ru/qbfivd (in Russian)

8. ATSDR. Toxicological profile for N-nitrosodimethylamine. Atlanta; 2023.

9. George J., Ramesh Rao K., Stern R., Chandrakasan G. Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen. Toxicology. 2001; 156(2–3): 129–38. https://doi.org/10.1016/s0300-483x(00)00352-8

10. Patterson J., Boateng J., Walker L.T., Verghese M. Cytotoxic effects of multiple n-nitrosamines in human liver cell line Hep2G: possible mechanisms of action. J. Pharmacol. Toxicol. 2012; 7(3): 114–27.

11. Boyev V.M. Methodology for integrated assessment of anthropogenic and socioeconomic factors in the formation of a human health risk. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2009; (4): 4–8. https://elibrary.ru/kwuenz (in Russian)

12. Zhang H., Lu L., Zhao C., Liu Q., Zhou Q., Zhang Y., et al. Lipid metabolism disorders contribute to hepatotoxicity of ICR mice induced by nitrosamines exposure. Environ. Int. 2022; 167: 107423. https://doi.org/10.1016/j.envint.2022.107423

13. U.S. Food and Drug Administration. Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs). Guidance for Industry; 2023.

14. Zaitseva N.V., Tran Cao Son, Bui Cao Tien, Ulanova T.S., Nurislamova T.V., Maltseva O.A. Comparative assessment of n-nitrosamines’ contamination of baby’s canned meat with vegetables and cereals by various methods in Russia and Vietnam. Voprosy pitaniya. 2019; 88(5): 93–102. https://doi.org/10.24411/0042-8833-2019-10058 https://elibrary.ru/lqnhya (in Russian)

15. Zaitseva N.V., Ulanova T.S., Nurislamova T.V., Popova N.A., Maltseva O.A. Identification and chromate-mass-spectrometry quantification of toxic chemicals (n-nitrosamines, phthalates) in baby foods. Voprosy pitaniya. 2022; 91(3): 107–14. https://doi.org/10.33029/0042-8833-2022-91-3-107-114 https://elibrary.ru/twnmod (in Russian)

16. More S.J., Bampidis V., Benford D., Bragard C., Halldorsson T.I., Hernández-Jerez A.F., et al. Guidance on the use of the benchmark dose approach in risk assessment. EFSA Journal. 2022; 20(10): e07584. https://doi.org/10.2903/j.efsa.2022.7584

17. Suvorov D.V., Shur P.Z., Zelenkin S.E. On the issue of determining tolerable daily intake of total n-nitrosamines for toddlers. Analiz riska zdorov’yu. 2024; (4): 72–80. https://doi.org/10.21668/health.risk/2024.4.07 https://elibrary.ru/yuejfa (in Russian)

18. Koterov A.N., Ushenkova L.N., Zubenkova E.S., Wainson A.A., Biryukov A.P. The relationship between the age of the based laboratory animals (mice, rats, hamsters and dogs) and the age of human: actuality for the age-related radiosensitivity problem and the analysis of published data. Meditsinskaya radiologiya i radiatsionnaya bezopasnost’. 2018; 63(1): 5–27. https://doi.org/10.12737/article_5a82e4a3908213.56647014 https://elibrary.ru/ytgihj (in Russian)

19. Shur P.Z., Suvorov D.V., Zemlyanova M.A., Nurislamova T.V. Experimental study of the toxicity of n-nitrosoamines when entering with food products for infants. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2020; 99(8): 848–53. https://doi.org/10.47470/0016-9900-2020-99-8-848-853 https://elibrary.ru/tdtcpj (in Russian)

20. Usunomena U., Joshua A.A., Okugbo O.T., Evuen U.F., Osibemhe M., Okolie N.P. N-nitrosodimethylamine (NDMA), liver function enzymes, renal function parameters and oxidative stress parameters: a review. Br. J. Pharmacol. Toxicol. 2012; 3(4): 165–76.

21. Lathouri M., Korre A., Dusinska M., Durucan S. Human Health Hazard Assessment Strategy for Amine Emissions Around PCC Facilities. Deliverable D3.3. Trondheim: SCOPE; 2022.

22. Roszczenko A., Jablonski J., Moniuszko-Jakoniuk J. Effect of N-nitrosodimethylamine (NDMA) on activity of selected enzymes in blood serum of the rat. Med. Pr. 1996; 47(1): 49–53.

23. Moniuszko-Jakoniuk J., Roszczenko A., Dzieciol J. Influence of low concentrations of N-nitrosodimethylamine on the iron level and histopathological picture of rats liver, spleen and bone marrow. Acta Pol. Toxicol. 1999; 7(2): 179–86.

24. Tsyrkunov V.M., Andreev V.P., Kravchuk R.I., Prokopchik N.I. Clinical cytology of liver: Cupffer’s cells. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2017; 15(4): 419–31. https://doi.org/10.25298/2221-8785-2017-15-4-419-431 https://elibrary.ru/zrktdz (in Russian)

25. Wheeler M.D. Endotoxin and Kupffer cell activation in alcoholic liver disease. Alcohol Res. Health. 2003; 27(4): 300–6.

26. Dixon L.J., Barnes M., Tang H., Pritchard M.T., Nagy L.E. Kupffer cells in the liver. Compr. Physiol. 2013; 3(2): 785–97. https://doi.org/10.1002/cphy.c120026

27. Kolios G., Valatas V., Kouroumalis E. Role of Kupffer cells in the pathogenesis of liver disease. World J. Gastroenterol. 2006; 12(46): 7413–20. https://doi.org/10.3748/wjg.v12.i46.7413

28. Seki E., Schwabe R.F. Hepatic inflammation and fibrosis: Functional links and key pathways. Hepatology. 2015; 61(3): 1066–79. https://doi.org/10.1002/hep.27332


Review

For citations:


Suvorov D.V., Zaitseva N.V., Shur P.Z., Zemlyanova M.A. Hygienic assessment of the impact of N-nitrosamines in their total intake into the body of young children. Hygiene and Sanitation. 2025;104(6):755-760. (In Russ.) https://doi.org/10.47470/0016-9900-2025-104-6-755-760. EDN: bwhyfh

Views: 26


ISSN 0016-9900 (Print)
ISSN 2412-0650 (Online)