Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis

Gerhard Eisenbrand¹, Matthias Baum², Alexander T Cartus³, Patrick Diel⁴, Karl-Heinz Engel⁵, Barbara Engeli⁶, Bernd Epe⁷, Tilman Grune⁸, Sabine Guth⁹, Dirk Haller^{10

11}, Volker Heinz¹², Michael Hellwig¹³, Jan G Hengstler⁹, Thomas Henle¹⁴, Hans-Ulrich Humpf¹⁵, Henry Jäger¹⁶, Hans-Georg Joost¹⁷, Sabine Kulling¹⁸, Dirk W Lachenmeier¹⁹, Alfonso Lampen²⁰, Marcel Leist²¹, Angela Mally²², Doris Marko²³, Ute Nöthlings²⁴, Elke Röhrdanz²⁵, Angelika Roth⁹, Joachim Spranger²⁶, Richard Stadler²⁷, Stefan Vieths²⁸, Wim Wätjen²⁹, Pablo Steinberg³⁰

Affiliations

¹ , Kühler Grund 48/1, 69126, Heidelberg, Germany. geisenbra@gmail.com.
² Solenis Germany Industries GmbH, Fütingsweg 20, 47805, Krefeld, Germany.
³ Chemservice S.A., 13, Fausermillen, 6689, Mertert, Luxembourg.
⁴ Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.
⁵ Chair of General Food Technology, Technical University of Munich, Maximus-von-Imhof-Forum 2, 85354, Freising, Germany.
⁶ Risk Assessment Division, Federal Food Safety and Veterinary Office (FSVO), Schwarzenburgstrasse 155, 3003, Bern, Switzerland.
⁷ Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany.
⁸ Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
⁹ Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.
¹⁰ ZIEL, Institute for Food and Health, Technical University of Munich, 85354, Freising, Germany.
¹¹ Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Str. 2, 85354, Freising, Germany.
¹² German Institute of Food Technologies (DIL), Prof.-von-Klitzing-Str. 7, 49610, Quakenbrück, Germany.
¹³ Institute of Food Chemistry, Technical University of Braunschweig, Schleinitzstr. 20, 38106, Braunschweig, Germany.
¹⁴ Department of Food Chemistry, TU Dresden, Bergstrasse 66, 01069, Dresden, Germany.
¹⁵ Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 45, 48149, Münster, Germany.
¹⁶ Institute of Food Technology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190, Vienna, Austria.
¹⁷ Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
¹⁸ Department of Safety and Quality of Fruit and Vegetables, Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany.
¹⁹ Chemisches und Veterinäruntersuchungsamt Karlsruhe, Weißenburger Straße 3, 76187, Karlsruhe, Germany.
²⁰ Risk Assessment Strategies, Bundesinstitut für Risikobewertung (BfR), Max-Dohrn-Straße 8-10, Berlin, Germany.
²¹ In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Box 657, 78457, Konstanz, Germany.
²² Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany.
²³ Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
²⁴ Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms University Bonn, Friedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany.
²⁵ Unit Reproductive and Genetic Toxicology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, 53175, Bonn, Germany.
²⁶ Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203, Berlin, Germany.
²⁷ Institute of Food Safety and Analytic Sciences, Nestlé Research Centre, Route du Jorat 57, 1000, Lausanne 26, Switzerland.
²⁸ Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
²⁹ Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.
³⁰ Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany. pablo.steinberg@mri.bund.de.

PMID: 35504979
DOI: 10.1007/s00204-022-03296-0

Editorial

Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis

Gerhard Eisenbrand et al. Arch Toxicol. 2022 Jun.

. 2022 Jun;96(6):1905-1914.

doi: 10.1007/s00204-022-03296-0. Epub 2022 May 4.

Authors

Affiliations

¹ , Kühler Grund 48/1, 69126, Heidelberg, Germany. geisenbra@gmail.com.
² Solenis Germany Industries GmbH, Fütingsweg 20, 47805, Krefeld, Germany.
³ Chemservice S.A., 13, Fausermillen, 6689, Mertert, Luxembourg.
⁴ Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.
⁵ Chair of General Food Technology, Technical University of Munich, Maximus-von-Imhof-Forum 2, 85354, Freising, Germany.
⁶ Risk Assessment Division, Federal Food Safety and Veterinary Office (FSVO), Schwarzenburgstrasse 155, 3003, Bern, Switzerland.
⁷ Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany.
⁸ Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
⁹ Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.
¹⁰ ZIEL, Institute for Food and Health, Technical University of Munich, 85354, Freising, Germany.
¹¹ Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Str. 2, 85354, Freising, Germany.
¹² German Institute of Food Technologies (DIL), Prof.-von-Klitzing-Str. 7, 49610, Quakenbrück, Germany.
¹³ Institute of Food Chemistry, Technical University of Braunschweig, Schleinitzstr. 20, 38106, Braunschweig, Germany.
¹⁴ Department of Food Chemistry, TU Dresden, Bergstrasse 66, 01069, Dresden, Germany.
¹⁵ Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 45, 48149, Münster, Germany.
¹⁶ Institute of Food Technology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190, Vienna, Austria.
¹⁷ Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
¹⁸ Department of Safety and Quality of Fruit and Vegetables, Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany.
¹⁹ Chemisches und Veterinäruntersuchungsamt Karlsruhe, Weißenburger Straße 3, 76187, Karlsruhe, Germany.
²⁰ Risk Assessment Strategies, Bundesinstitut für Risikobewertung (BfR), Max-Dohrn-Straße 8-10, Berlin, Germany.
²¹ In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Box 657, 78457, Konstanz, Germany.
²² Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany.
²³ Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
²⁴ Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms University Bonn, Friedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany.
²⁵ Unit Reproductive and Genetic Toxicology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, 53175, Bonn, Germany.
²⁶ Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203, Berlin, Germany.
²⁷ Institute of Food Safety and Analytic Sciences, Nestlé Research Centre, Route du Jorat 57, 1000, Lausanne 26, Switzerland.
²⁸ Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
²⁹ Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.
³⁰ Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany. pablo.steinberg@mri.bund.de.

PMID: 35504979
DOI: 10.1007/s00204-022-03296-0

Abstract

Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Salivary excretion may also occur with certain drug molecules and food constituents and their metabolites. Therefore, putative combination effects in the oral cavity and the upper digestive tract may occur, but this has remained largely unexplored up to now. In this Guest Editorial, published evidence on exposure levels and biokinetics of nitrate/nitrite/NO_x, NOC and acetaldehyde in the organism is reviewed and knowledge gaps concerning combination effects are identified. Research is suggested to be initiated to study the related unresolved issues.

Keywords: Acetaldehyde; Combination effects; N-nitroso compounds; Nitrate; Nitrite; Upper gastrointestinal tract.

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References

1. Bellander T (1990) Nitrosation of piperazine after oral intake or inhalation exposure. In: Eisenbrand G, Bozler G, von Nicolai H (eds) The significance of N-nitrosation of drugs: series drug development and evaluation, vol 16. Gustav Fischer Verlag, Stuttgart, pp 213–232
1. Bellander T, Osterdahl BG, Hagmar L (1985) Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine. Toxicol Appl Pharmacol 80:193–198. https://doi.org/10.1016/0041-008x(85)90075-4 - DOI - PubMed
1. BfR (2010) Gesundheitliche Bewertung von Acetaldehyd in alkoholischen Getränken. https://www.bfr.bund.de/cm/343/gesundheitliche_bewertung_von_acetaldehyd... . Accessed 19 Feb 2022
1. Bulay O, Mirvish SS, Garcia H, Pelfrene AF, Gold B, Eagen M (1979) Carcinogenicity test of six nitrosamides and a nitrosocyanamide administered orally to rats. J Natl Cancer Inst 62:1523–1528 - PubMed
1. Burdock GA (2004) Fenaroli’s handbook of flavour ingredients. CRC Press, Boca Raton - DOI

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Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis

Affiliations

Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis

Authors

Affiliations

Abstract

References

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Grants and funding

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