The safety of Nisin as a natural preservative

As a "safety-grade" natural preservative jointly evaluated by the Food and Agriculture Organization (FAO) and the World Health Organization (WHO), the safety of Nisin has been verified through extensive toxicological studies. Its ADI value (Acceptable Daily Intake) is "unrestricted" (ADI = Not Specified, NS), making it one of the food additives with the highest safety rating.

I. Safety Assessment: From Toxicological Studies to Practical Application Verification

The safety assessment of Nisin focuses on four core dimensions: acute toxicity, long-term toxicity, genotoxicity, and allergenic risk. All studies are based on its application scenario as a food preservative (conventional addition level: 0.01%–0.1%), with key conclusions as follows:

1. Acute Toxicity: Extremely Low Toxicity, High Safety Threshold

Acute toxicity studies tested the median lethal dose (LD₅₀) of Nisin in animal models (e.g., rats, mice) via oral gavage:

The oral LD₅₀ of Nisin in rats is > 5000 mg/kg body weight, and in mice, it is > 10000 mg/kg body weight.

Converted to human dosage, a 60 kg adult would need to ingest more than 30 g of pure Nisin at one time to potentially experience acute toxicity. However, the actual addition of Nisin in food is usually 50–500 mg per kg of food (i.e., an adult ingests less than 0.3 g of Nisin through food daily), which is far below the acute toxicity threshold, eliminating the risk of acute poisoning.

2. Long-Term Toxicity: No Cumulative Toxicity, No Organ Damage

Long-term toxicity studies (lasting 12–24 months) were conducted on animals such as rats and dogs, with daily Nisin administration at 100–1000 mg/kg body weight (equivalent to 100–1000 times the daily intake of humans). The results showed:

No abnormalities were observed in animal weight gain or food intake, and no adverse reactions such as diarrhea or vomiting occurred.

Post-dissection tests of liver and kidney function (transaminases, serum creatinine), blood indicators (complete blood count, blood lipids, blood glucose), and organ pathological sections revealed no damage to organs such as the liver, kidneys, or heart. There was also no evidence that Nisin accumulates in the body (it is mainly degraded by proteases in the intestines and does not enter the bloodstream).

3. Genotoxicity: No Mutagenic or Carcinogenic Risks

Genotoxicity was verified through authoritative methods such as the "AMES test (Salmonella mutagenicity test), chromosome aberration test, and mouse bone marrow micronucleus test":

In the AMES test, Nisin did not induce gene mutations in Salmonella at different concentrations (10–1000 μg/plate).

The chromosome aberration test and micronucleus test showed that Nisin does not cause chromosome breakage or increased micronucleus rate in mammalian cells, confirming no mutagenicity.

A long-term carcinogenicity study (24-month rat test) found no correlation between Nisin and increased tumor incidence, ruling out carcinogenic risks.

4. Allergenic Risk: Extremely Low Allergenicity, Suitable for Special Populations

Nisin is produced by the fermentation of lactic acid bacteria (Streptococcus lactis) and is essentially a polypeptide (composed of 34 amino acids), with an allergenic risk far lower than that of chemical preservatives:

Epidemiological surveys show that the incidence of Nisin allergy in the general population is < 0.01%. Only a very small number of people allergic to lactic acid bacteria may experience mild skin itching or gastrointestinal discomfort, and symptoms resolve spontaneously.

For special populations such as children, pregnant women, and the elderly, FAO/WHO assessments confirm that Nisin’s safety is consistent with that for the general population at conventional addition levels, requiring no additional restrictions on intake.

II. ADI Value Study: Scientific Basis for "Unrestricted" Classification

The ADI value (Acceptable Daily Intake) refers to the maximum daily amount of a food additive allowed per kg of body weight, established by the FAO/WHO Joint Expert Committee on Food Additives (JECFA). Nisin’s ADI value is classified as "unrestricted" (NS, Not Specified), based on two core pieces of evidence:

1. Safe Metabolic Pathway: Complete Degradation in the Intestines, No Residues

As a polypeptide, Nisin is completely degraded into amino acids by proteases in the gastrointestinal tract (e.g., trypsin, pepsin) after entering the human body. This metabolic pathway is consistent with that of dietary proteins—no toxic metabolites are formed in the body, and no burden is imposed on liver or kidney metabolism. This is fundamentally different from chemical preservatives (e.g., sodium benzoate, which requires liver metabolism) and eliminates the risk of "cumulative toxicity," so no specific upper limit for ADI is needed.

2. No Risks from Long-Term Exposure: Extensive Studies Confirm "No Threshold" in Dose-Effect Relationship

During JECFA’s assessment, dose-effect relationship analysis revealed that even long-term daily intake of Nisin far exceeding conventional doses (e.g., 1000 mg per kg of body weight) did not induce any toxic reactions (i.e., "No Observed Adverse Effect Level," NOAEL > 1000 mg/kg body weight). The dose of Nisin ingested by humans through food (usually < 1 mg/kg body weight/day) is far below the NOAEL, with a safety margin (NOAEL/actual intake) exceeding 1000 times. Thus, JECFA concluded that "Nisin does not pose health risks to humans when used appropriately according to production needs," and no ADI limit is required.

III. Safety Control in Practical Applications: Compliance Is Key

Although Nisin has high safety, "compliant use" must be followed in practical applications to ensure safety:

1. Control Addition Levels: Comply with National Standards

China’s National Food Safety Standard for the Use of Food Additives (GB 2760) stipulates that the maximum usage of Nisin in food is 0.2 g/kg (i.e., no more than 200 mg of Nisin per kg of food). This is far below the safety threshold in toxicological studies, so conventional use will not exceed the limit.

2. Avoid Purity Issues: Choose High-Purity Products

Low-purity Nisin products may contain residual fermentation by-products (e.g., lactic acid, small amounts of miscellaneous proteins). While these do not affect safety, they may alter food flavor. It is recommended to select food-grade Nisin with a purity > 95% (e.g., Nisin Type Z, Type A/Z mixture) to minimize impurity interference.

3. Adapt to Food Types: Avoid Degradation Under Extreme Conditions

Nisin is stable under acidic conditions (pH 2.0–6.0) but partially degrades under alkaline conditions (pH > 8.0) or high temperatures (> 121°C). Degradation products are amino acids (non-toxic), but degradation reduces preservative efficacy. The addition level should be adjusted according to food processing conditions (e.g., pH, temperature) rather than increasing the dose to compensate, balancing "efficacy" and "safety."

As a natural preservative, Nisin’s safety has been verified through multiple dimensions, including acute toxicity, long-term toxicity, genotoxicity, and allergenic risk. The "unrestricted" ADI classification is based on its metabolic characteristics of "complete degradation and no cumulative toxicity," making it one of the safest preservatives in the food industry. In practical applications, as long as addition levels are controlled in accordance with national standards and high-purity products are selected, Nisin can be safely used in various foods, including special categories such as children’s food and pregnant women’s food.