NISIN

CAS Number: 1414-45-5
 Synonyms: Nisin A; Nisin Z; E234; Antibiotic 62-62RD; Diplococcin; Lactococcus lactis subsp. lactis fermentate; Nisaplin; Delvo® Nisit
Physical Properties:
Appearance: Off-white to light brown powder or concentrate.
Solubility: Sparingly soluble in water (approx. 3–5 g/L at pH 2.5); solubility decreases sharply at neutral pH; insoluble in organic solvents.
Molecular weight: 3354 Da (Nisin A; 34 amino acid lantibiotic).
Isoelectric point: pI ≈ 9.5 (cationic).
Stability: Stable at low pH (2–4); unstable at neutral/alkaline pH (degrades rapidly above pH 7). Heat-stable: withstands pasteurization (71°C for 15 min) and even autoclaving (121°C for 15 min) at acidic pH.
Activity units: 1 mg pure nisin = 40,000 International Units (IU) measured against Micrococcus luteus.
Odor: Slight sulfurous (due to lanthionine rings).
Applications:
Dairy products: Processed cheese, cheese spreads, cottage cheese, cream cheese, mascarpone (prevents late blowing by Clostridium tyrobutyricum and spoilage by Bacillus stearothermophilus).
Canned foods: Canned vegetables, soups, and sauces (inhibits thermophilic spoilage organisms).
Meat and poultry: Cooked sausages, hot dogs, luncheon meats, and paté (reduces Listeria monocytogenes and Lactobacillus).
Beverages: Fruit juices, beers, and wine (controls lactic acid bacteria spoilage).
Egg products: Liquid egg white (pasteurization enhancement).
Medical and dental: Topical formulations for treating Clostridium difficile-associated diarrhea, Helicobacter pylori infections, and oral hygiene products (mouthwash, toothpaste) for caries prevention.
Animal feed: As a growth promoter and preservative in silage and pet food.
Food packaging: Incorporated into antimicrobial films and coatings (e.g., polyethylene films).
Description:
 Nisin (E234) is a heat-stable, polycyclic antibacterial peptide produced by the fermentation of Lactococcus lactis subsp. lactis (a Gram-positive bacterium traditionally used in cheesemaking). It is classified as a Class I bacteriocin or "lantibiotic" due to the presence of unusual amino acids – lanthionine (Lan) and methyllanthionine (MeLan) – forming thioether cross-linked rings. These rings provide remarkable heat and acid stability. The mechanism of action involves binding to lipid II, the essential carrier molecule for peptidoglycan synthesis in bacterial cell walls. After binding, nisin inserts into the cytoplasmic membrane, creating transient pores that cause rapid efflux of ions (K⁺, phosphate, ATP) and small metabolites, leading to dissipation of the proton motive force and cell death. Nisin is effective primarily against Gram-positive bacteria, including spore-formers (Bacillus, Clostridium), lactic acid bacteria, and pathogens such as Listeria monocytogenes, Staphylococcus aureus, and Streptococcus mutans. It is generally ineffective against Gram-negative bacteria (due to the protective outer membrane) unless combined with chelators (e.g., EDTA) or physical disruption (e.g., mild heat, high pressure). Unlike conventional chemical preservatives, nisin is digested in the human gastrointestinal tract by proteases (trypsin, chymotrypsin) into amino acids, with no systemic absorption or toxicity. JECFA has established an ADI of "not specified" (the safest category). Nisin has been approved globally for over 50 years (first in the UK in 1957, then US FDA in 1988). It does not contribute to cross-resistance with therapeutic antibiotics because its mechanism (lipid II binding) differs from vancomycin (which also binds lipid II but at a different site). However, resistance can develop slowly via alterations in cell wall thickness, lipid II modifications (e.g., D-alanylation of teichoic acids), or proteolytic degradation (nisinase). In processed cheese, nisin allows reduction of thermal processing intensity (lower time/temperature) while preventing spoilage, thus improving texture and flavor. It is often synergized with sodium chloride (salt) and low pH for enhanced activity. Nisin Z (a natural variant with asparagine instead of histidine at position 27) has better diffusion properties and solubility at neutral pH, expanding its potential use to beverages and salad dressings.

SAFETY INFORMATION ABOUT NISIN

First aid measures:
Description of first aid measures:
General advice:
Consult a physician. 
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
 
If inhaled:
If breathed in, move person into fresh air. 
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately. 
Wash off with soap and plenty of water.
Consult a physician.
 
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
 
If swallowed:
Do NOT induce vomiting. 
Never give anything by mouth to an unconscious person. 
Rinse mouth with water. 
Consult a physician.
 
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
 
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. 
 
Avoid breathing vapours, mist or gas. 
Evacuate personnel to safe areas.
 
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste. 
Keep in suitable, closed containers for disposal.
 
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
 
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place. 
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
 
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
 
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles. 
Faceshield (8-inch minimum). 
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
 
Skin protection:
Handle with gloves. 
Gloves must be inspected prior to use. 
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product. 
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. 
Wash and dry hands.
 
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
 
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. 
 
If the respirator is the sole means of protection, use a full-face supplied air respirator. 
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions. 
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
 
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company. 
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product