NATAMYCIN

CAS Number: 7681-93-8 (also 1396-30-1 for natamycin hydrate)
 Synonyms: Pimaricin; E235; Natacyn; Delvocid; Delvopos; Antibiotic E-235; Tennecetin; Pimaricin (former name)
Physical Properties:
Appearance: White to cream-colored crystalline powder (almost odorless and tasteless).
Solubility: Very slightly soluble in water (approx. 0.04–0.10 g/L at 25°C); slightly soluble in methanol, dimethyl sulfoxide (DMSO); practically insoluble in ethanol, most organic solvents.
Melting point: 290°C (with decomposition).
Spectroscopic feature: Strong UV absorption at 303 nm (conjugated tetraene chromophore).
Stability: Unstable to light (photolabile; degrades rapidly under UV or sunlight), heat (decomposes above 100°C), and oxidizing agents. Stable at pH 3–9 in the dark.
Partition coefficient (log P): 1.3 (moderately lipophilic).
Molecular weight: 665.73 g/mol (anhydrous).
Applications:
Cheese (surface treatment): Soft cheeses (Camembert, Brie, Gouda, Edam, Havarti, Roquefort, Blue cheese) – sprayed as aqueous suspension or incorporated into the cheese coating/plastic wrap to prevent surface mold growth.
Dry and fermented sausages: Salami, chorizo, pepperoni – surface treatment via dipping or spraying.
Bakery products: Cakes, pastries, bread, tortillas, and pita bread (surface spray or dough addition) to prevent mold during storage.
Yogurt and sour cream: Surface treatment of containers or direct addition.
Fruit juices and beverages: Apple cider, orange juice, grape juice (post-bottling addition in some countries).
Meat and poultry: Cooked ham, turkey breast, and deli meats (surface treatment).
Pharmaceuticals: Ophthalmic suspension (Natacyn® 5%) for treating fungal keratitis (Aspergillus, Fusarium, Candida); topical antifungal for cutaneous infections.
Medical devices: Coating of catheters and contact lenses to prevent fungal colonization.
Agriculture: Post-harvest dip for fruits (citrus, apples, pears, strawberries) to control rot.
Animal feed: Silage preservative.
Description:
 Natamycin (E235) is a naturally occurring polyene macrolide antifungal compound produced by fermentation of Streptomyces natalensis (also S. chattanoogensis, S. gilvosporeus). It belongs to the tetraene subgroup (four conjugated double bonds in the macrolide ring) and is structurally distinct from nystatin (tetraene) and amphotericin B (heptaene). The mechanism of action involves selective, high-affinity binding to ergosterol – the principal sterol in fungal cell membranes. Unlike nystatin and amphotericin B (which form large pores leading to cell lysis), natamycin acts primarily as a fungistatic agent: it binds to ergosterol and disrupts membrane fluidity, inhibits ergosterol biosynthesis, and blocks membrane transport systems without causing immediate leakage. This prevents fungal growth and sporulation without killing the cells rapidly, making it ideally suited for surface preservation where fungal contamination occurs from the environment during ripening (e.g., cheese caves). Natamycin is remarkably specific for fungi (yeasts and molds); it shows negligible activity against bacteria (Gram-positive and Gram-negative) and is inactive against viruses, protozoa, and mammalian cells (mammalian membranes contain cholesterol instead of ergosterol, to which natamycin binds with much lower affinity). This selective toxicity explains its excellent safety profile. Toxicologically, natamycin is poorly absorbed from the gastrointestinal tract (<1% absorption), and any absorbed fraction is rapidly metabolized by the liver and excreted in feces. No systemic toxicity, genotoxicity, carcinogenicity, or reproductive toxicity has been observed at dietary exposure levels. JECFA has set an ADI of 0.3 mg/kg bw/day (very safe). The primary limitation of natamycin is photodegradation: exposure to sunlight or UV light causes isomerization and oxidation of the conjugated tetraene chromophore, turning the solution yellow/brown and inactivating the compound. Therefore, in cheese production, it is applied only to surfaces that are not exposed to light (wrapped in opaque film). Natamycin does not penetrate deeply into food; it remains on the surface, where >90% of contamination occurs. This surface-only action is beneficial because it preserves natural microbial flora (e.g., bacterial starter cultures, cheese rind microflora) while eliminating spoilage fungi. In the US, natamycin is approved as a direct food additive (21 CFR 172.155) only for cheese (including processed cheese) and for treating meats and poultry (as a secondary additive). The EU permits E235 in all surface treatment applications. Unlike sorbic acid or propionates, natamycin is effective at very low concentrations (1–10 ppm) and does not alter the taste, odor, color, or texture of the product. Resistance is rare due to the essentiality of ergosterol for fungal survival; mutations in ergosterol synthesis are often lethal or severely reduce viability. However, some resistance mechanisms have been reported (e.g., overexpression of efflux pumps, altered sterol composition). Natamycin is also used in ophthalmology as a first-line treatment for fungal keratitis – a severe corneal infection often following plant matter injury. The success of topical natamycin underscores its safety and efficacy.

SAFETY INFORMATION ABOUT NATAMYCIN

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