The genotoxicity and mutagenicity of Nisin

Nisin, a natural food preservative, studies on its genotoxicity and mutagenicity have always been important directions for safety assessment. Based on existing research evidence, it shows low risks in these two aspects, with specific conclusions as follows:

I. Genotoxicity Research

Genotoxicity refers to the ability of chemical substances to directly or indirectly damage DNA, leading to gene mutations or chromosomal structural changes. Studies on Nisin show:

DNA Damage Assays: In vitro cell experiments (e.g., E. coli, mammalian cell lines), Nisin did not exhibit direct DNA damage. Its mechanism primarily inhibits bacteria by disrupting cell membrane integrity, rather than acting on genetic material.

Gene Mutation Detection: Results from the classic Ames test (Salmonella typhimurium reverse mutation assay) showed that Nisin did not induce gene mutations in Salmonella with or without a metabolic activation system (e.g., S9 mixture), indicating it lacks the basic toxicity for mutagenesis.

Chromosomal Aberration Analysis: In in vitro cultured mammalian cells (e.g., Chinese hamster ovary cells, CHO) or in vivo animal experiments (e.g., mouse bone marrow cells), Nisin did not cause chromosomal structural abnormalities or numerical changes, further confirming no significant impact on chromosomal stability.

II. Mutagenicity Research

Mutagenicity focuses on the ability of chemical substances to induce permanent changes in cellular genetic material. Conclusions from Nisin-related studies are as follows:

In Vitro Cell Mutation Assays: Beyond the Ames test, other in vitro models (e.g., mammalian cell HGPRT gene mutation assay) also confirmed that Nisin did not induce gene mutations even at high concentrations (far exceeding food additive dosages), indicating extremely low mutagenic potential.

In Vivo Animal Experiments: Evaluations using in vivo models such as the mouse micronucleus test and dominant lethal test showed Nisin did not cause mutagenic effects in germ or somatic cells. For example, after gavage with high-dose Nisin, the bone marrow micronucleus rate in mice showed no significant difference from the control group, demonstrating no mutagenicity under in vivo metabolic conditions.

Safety of Action Mechanism: Nisin is a natural polypeptide produced by lactic acid bacteria, with a molecular weight of ~3.5 kDa. It is easily degraded into amino acids by proteases in the human digestive tract and cannot enter cell nuclei to act on DNA. Its antibacterial spectrum mainly targets Gram-positive bacteria without damaging the membrane structure of eukaryotic cells (including human cells), which mechanistically reduces genotoxic risks.

III. Safety Assessment and Practical Applications

Based on the above research, institutions such as the Joint Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA) have recognized Nisin as a safe food preservative, setting its acceptable daily intake (ADI) at 0–33,000 IU/kg body weight (calculated by potency units). In the food industry, Nisin is typically used at concentrations of 10–1000 ppm, far lower than experimental doses in toxicity studies. Thus, from the perspectives of genotoxicity and mutagenicity, its application safety has been fully verified.

Studies on Nisin’s genotoxicity and mutagenicity both show no significant damage to genetic material, closely related to its chemical properties as a natural polypeptide, action mechanism, and metabolic characteristics. Existing evidence supports its wide application as a safe food additive, and long-term practical use has not revealed related safety controversies.