Safety
Natamycin does not have acute toxicity. In animal studies, the lowest LD50 found was 2.5-4.5 g/kg. In rats, the LD50 is ≥2300 mg/kg, and doses of 500 mg/kg/day over 2 years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD50 than natamycin, but in all cases, the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea.No evidence shows natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available. However, some people are allergic to natamycin.The EFSA has concluded that the use of natamycin as a food additive has no relevant risk for the development of resistant fungi. Mechanism of action
Natamycin inhibits the growth of fungi by specifically binding to ergosterol present in fungal cell membranes. Natamycin inhibits amino acid and glucose transport proteins leading to a loss of nutrient transport across the plasma membrane. While this binding is reversible, ergosterol binding acts as a universal mechanism of fungal inhibition, allowing natamycin to act on diverse fungal pathogens from Saccharomyces yeast to Aspergillus moulds. Natamycin is unique amongst related antifungals specifically because it does not directly cause membrane permeabilization.
It can be applied in a variety of ways: as an aqueous suspension (such as mixed into a brine) sprayed on the product or into which the product is dipped, or in powdered form (along with an anticaking agent such as cellulose) sprinkled on or mixed into the product. While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Also, natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cream cheeses, cottage cheese, sour cream, yogurt, shredded cheeses, cheese slices, and packaged salad mixes. One of the reasons for food producers to use natamycin is to replace the artificial preservative sorbic acid.As a food additive, it has E number E235. Throughout the European Union, it is approved only as a surface preservative for certain cheese and dried sausage products. It must not be detectable 5 mm below the rind. While natamycin is approved in different applications at different levels in the world, it is approved in over 150 countries worldwide.The European Food Safety Authority (EFSA) panel took over the responsibilities of providing scientific food safety advice to the EU from the Scientific Committee on Food  in 2002. In 2009, the EFSA considered the proposed use levels of natamycin are safe if it is used for the surface treatment for these cheese and sausage types.