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

Research output: Contribution to journalEditorial (Lead article)Contributedpeer-review


  • Gerhard Eisenbrand - (Author)
  • Matthias Baum - , Solenis Germany Industries GmbH (Author)
  • Alexander T. Cartus - , Chemservice S.A. (Author)
  • Patrick Diel - , German Sport University Cologne (Author)
  • Karl Heinz Engel - , Technical University of Munich (Author)
  • Barbara Engeli - , Federal Food Safety and Veterinary Office (Author)
  • Bernd Epe - , Johannes Gutenberg University Mainz (Author)
  • Tilman Grune - , German Institute of Human Nutrition Potsdam-Rehbruecke (Author)
  • Sabine Guth - , Dortmund University of Technology (Author)
  • Dirk Haller - , Technical University of Munich (Author)
  • Volker Heinz - , German Institute of Food Technology (DIL e.V.) (Author)
  • Michael Hellwig - , Chair of Special Food Chemistry, Institute of Food Chemistry, Technical University of Braunschweig (Author)
  • Jan G. Hengstler - , Dortmund University of Technology (Author)
  • Thomas Henle - , Chair of Food Chemistry (Author)
  • Hans Ulrich Humpf - , University of Münster (Author)
  • Henry Jäger - , University of Natural Resources and Life Sciences, Vienna (Author)
  • Hans Georg Joost - , German Institute of Human Nutrition Potsdam-Rehbruecke (Author)
  • Sabine Kulling - , Max Rubner Institut (Author)
  • Dirk W. Lachenmeier - , Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe (Author)
  • Alfonso Lampen - , Federal Institute for Risk Assessment (Author)
  • Marcel Leist - , University of Konstanz (Author)
  • Angela Mally - , University of Würzburg (Author)
  • Doris Marko - , University of Vienna (Author)
  • Ute Nöthlings - , University of Bonn (Author)
  • Elke Röhrdanz - , Federal Institute for Drugs and Medical Devices (BfArM) (Author)
  • Angelika Roth - , Dortmund University of Technology (Author)
  • Joachim Spranger - , Charité – Universitätsmedizin Berlin (Author)
  • Richard Stadler - , Nestle (Author)
  • Stefan Vieths - , Paul-Ehrlich-Institut (Author)
  • Wim Wätjen - , Martin Luther University Halle-Wittenberg (Author)
  • Pablo Steinberg - , Max Rubner Institut (Author)


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/NOx, 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.


Original languageEnglish
Pages (from-to)1905-1914
Number of pages10
JournalArchives of toxicology
Issue number96(6)
Publication statusPublished - May 2022

External IDs

PubMed 35504979
ORCID /0000-0001-8528-6893/work/142256518



  • Acetaldehyde, Combination effects, N-nitroso compounds, Nitrate, Nitrite, Upper gastrointestinal tract, Nitrates/metabolism, Acetaldehyde/metabolism, Humans, Saliva/metabolism, Upper Gastrointestinal Tract/metabolism, Nitroso Compounds/metabolism, Nitrites/metabolism