How Nitrosamines Form: The Chemistry Behind It

By Eben van Tonder, 29 April 25

(Including a tribute to Dr Karl Kißkalt, 1875–1962.  from an actual photo taken in 1955 on the occasion of his 80th birthday. He studied under Prof. Dr Karl Bernhard Lehmann (1858–1940), a leading toxicologist and hygienist, at the University of Würzburg.

Our journey continues into the science and history of nitrosamines and cured meats, based on my larger article “Nitrosamines, Cured Meats, and Human Health: A Critical Review of Risk and Physiology”.

In the first two articles, we explored what amines and nitrosamines are, and how fear about nitrosamines developed. Tonight, we go to the heart of the matter: how exactly nitrosamines are formed. We also celebrate the life and work of Dr Karl Kißkalt, a key figure in the early scientific understanding of curing.

This is part three of our unfolding story.

How Nitrosamines Form

To understand nitrosamine formation, we first recall the role of secondary amines. These are organic compounds with a nitrogen atom attached to two carbon groups. They occur naturally in many foods, including meat, and become reactive when exposed to nitrosating agents, particularly nitrite (NO₂⁻).

Nitrosamines form when nitrite reacts with a secondary amine under specific conditions:

  • Acidic pH (low pH encourages the formation of nitrous acid)
  • Presence of secondary amines
  • Elevated temperatures, especially above 130°C (such as during frying or grilling)

The key chemical step is that nitrite under acidic conditions forms reactive species such as nitrous acid (HNO₂), dinitrogen trioxide (N₂O₃), and nitrosonium ions (NO⁺). These highly reactive intermediates transfer a nitroso group (–NO) to the nitrogen atom in the amine.

The simplified reaction looks like this:

R₂NH (secondary amine) + NO⁺ → R₂N–NO (nitrosamine)

Once formed, nitrosamines are chemically stable. That stability is part of what makes them concerning. Some nitrosamines, such as N-nitrosodimethylamine (NDMA), have shown carcinogenic properties in laboratory animals under specific conditions.

It is important to stress that not all nitrosamines are equally dangerous, and the actual risk depends on structure, dose, and metabolic pathways in the body. Still, the chemistry set off concerns about the safety of fried and grilled cured meats where these reactions could occur.

Tribute to Dr Karl Kißkalt (1875–1962)

Dr Karl Kißkalt was a German physician and hygienist, a title which at the time referred to an expert in public health, bacteriology, food safety, and environmental sanitation.

He studied medicine in Würzburg, Berlin, and Munich. From 1899 to 1901, he served as assistant to Prof. Dr Karl Bernhard Lehmann at the Hygiene Institute in Würzburg. Lehmann was already one of the leading figures in Germany in toxicology and microbiological hygiene.

Together, Kißkalt and Lehmann provided the first clear experimental proof that nitrate (saltpetre), long used by butchers, was not the direct curing agent. Instead, they demonstrated that bacteria in the meat reduced nitrate to nitrite, and that it was this nitrite that produced the pink colour and preservation effect in cured meats.

While Dr Eduard Polenske had earlier speculated that bacteria might play such a role, it was Kißkalt and Lehmann who first provided solid experimental evidence. Their discovery laid the groundwork for all subsequent research into the chemical reactions between nitrite and meat components, including the later discovery of nitrosamine formation.

Kißkalt’s later academic career was distinguished. He became director of the Institute for Hygiene at the University of Munich and served as Rector of the University of Kiel in 1921–22. He remained active in scientific societies and medical research until his death in 1962.

Looking Ahead

In tomorrow’s article, we will explore the actual health risks associated with nitrosamines. How real are the dangers? Are cured meats truly unsafe, or was much of the fear based on misunderstanding and early-stage laboratory science?

I invite you to continue with me as we unfold the full story.

Link to all my work on meat curing and human health. / Link zu all meinen Arbeiten über Fleischpökelung und menschliche Gesundheit.

References

  • Van Tonder, E. (2024). Nitrosamines, Cured Meats, and Human Health – A Critical Review of Risk and Physiology. EarthwormExpress
  • Cassens, R. G. (1997). Residual nitrite in cured meat. Advances in Experimental Medicine and Biology, 433, 95–102
  • Pegg, R. B., & Shahidi, F. (2000). Nitrite Curing of Meat: The N-Nitrosamine Problem and Nitrite Alternatives. Food & Nutrition Press
  • Lehmann, K. B., & Kißkalt, K. (1899). Historical studies on nitrate and nitrite conversion, cited in Van Tonder (2024) and Pegg & Shahidi
  • Wikipedia (de): Karl Kißkalt, Karl Bernhard Lehmann