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EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION 

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN 

THE FEDERAL REGISTER 

EPA Biopesticides and Pollution Prevention Division contact: [insert name and 

telephone number with area code]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

SUBMISSION: E-mail the completed template to: hollis.linda@epa.gov.

TEMPLATE:

DSM Food Specialties, B.V.

[Insert petition number]

EPA has received a pesticide petition ([insert petition number]) from DSM 

Food Specialties, B.V., PO Box 1, 2600 MA Delft, The Netherlands proposing, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to amend 40 CFR part 180.

(Options (pick one)

1. by establishing a tolerance for residues of NA-Remove

2. to establish an exemption from the requirement of a tolerance for NA-Remove

3. to establish an amendment/expansion of an existing tolerance exemption for the

(Options (pick one)

1. microbial pesticide NA-Remove

2. biochemical pesticide Natamycin

3. plant-pesticide NA-Remove in or on NA-Remove
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Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, DSM Food Specialties, 

B.V. has submitted the following summary of information, data, and arguments in 

support of their pesticide petition. This summary was prepared by DSM Food 

Specialties, B.V. and EPA has not fully evaluated the merits of the pesticide petition. The 

summary may have been edited by EPA if the terminology used was unclear, the 

summary contained extraneous material, or the summary unintentionally made the reader 

conclude that the findings reflected EPA’s position and not the position of the petitioner.

I. DSM Food Specialties, B.V. Petition Summary

[Insert petition number]

A. Product Name and Proposed Use Practices

Natamycin is already approved for use as a fungistat to prevent and control mold 

and yeast spores in the growth media of mushrooms produced in enclosed 

mushroom facilities (EPA Reg. No. 87485-2) and for use on pineapple as a postharvest treatment (EPA Reg. No. 87485-3). Additional uses are being proposed to 

control several postharvest diseases in or on citrus, pome, stone fruit crop groups, 

avocado, kiwi, mango and pomegranates by dip, drench, flood or spray in 

packinghouse facilities. 

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. Natamycin L contains 

10.34% (by wt) Natamycin anhydrous.

2. Magnitude of residues at the time of harvest and method used to determine the 

residue. Not applicable.

3. A statement of why an analytical method of detecting and measuring the levels 

of the pesticide residue are not needed. An analytical method for detecting and measuring 

the levels of pesticide residue for Natamycin is not applicable. It is expected that, when 

used as proposed Natamycin would not result in residues that are of toxicological 

concern.

C. Mammalian Toxicological Profile

The toxicology data indicate that the active ingredient, Natamycin is of low acute

toxicity and is not a developmental toxicant, a mutagen, or toxic via repeat oral exposure.

Acute Toxicity: Acute toxicity studies on Natamycin TGAI (98.17% and 98.27% pure),

confirm a low toxicity profile. The acute toxicity data show nontoxicity for all routes of 

exposure. It can be concluded that any dietary risks associated with Natamycin would 

be negligible. 

1. The acute oral LD50 in rats was greater than 2,000 milligrams per kilogram (mg/kg)
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bodyweight. There were no observed toxicological effects on the test subjects in the acute

oral study submitted (MRID No. 48105505). Natamycin is classified as Toxicity

Category III for acute oral toxicity.

2. The acute dermal LD50 in rats was greater than 5,050 mg/kg body weight (MRID 

48105506). Natamycin is classified as Toxicity Category IV for acute dermal toxicity.

3. The acute inhalation LC50 was greater than 2.39 milligrams per liter (mg/L) in rats

and showed no significant inhalation toxicity (MRID 48105507). Natamycin is

classified as Toxicity Category IV for acute inhalation toxicity.

4. A primary eye irritation study on rabbits indicated that Natamycin is severely

irritating to the eye but with no effects observed at 24 hours after treatment (MRID 

48015508). Natamycin is classified as Toxicity Category IV for primary eye irritation.

5. A skin irritation study on rabbits indicates that Natamycin is slightly irritating (MRID 

48105509). Natamycin is classified as Toxicity Category IV for primary skin irritation.

6. Data indicate that Natamycin is not a dermal sensitizer (MRID 48105510).

Mutagenicity: Two mutagenicity studies, using Natamycin TGAI were performed. These

studies confirm that there are no expected dietary or non-occupational risks of 

mutagenicity with regard to food use of Natamycin.

1. A Bacterial Reverse Gene Mutation Test (MRID No. 48105513) investigating doses 

of test substance up to those that were cytotoxic, both with and without metabolic S9 

activation, found no incidences of a 2-fold or greater increase in the number of

revertants compared to the corresponding solvent control in two independently repeated

experiments. Natamycin is considered to be non-mutagenic under the conditions of this

assay.

2. An in vitro Mammalian Cell Chromosome Aberration Test (MRID No. 48105514) 

tested Natamycin genotoxicity on cultured peripheral human lymphocytes in the

presence and absence of metabolic S9 activation. Natamycin did not induce a

statistically significant or biologically relevant increase in the number of cells with

chromosome aberrations in the absence and in the presence of S9-mix, in two 

independently repeated experiments. In addition, all of the negative, solvent, and

positive controls gave appropriate responses. Natamycin is considered to be nonmutagenic and does not cause chromosome aberrations.

Subchronic Toxicity: In a subchronic oral toxicity study using Natamycin TGAI, doses of 

125 and 500 mg/kg/day showed no treatment related findings. The highest concentration l 

level, 2,000 mg/kg/day, showed reduced weight for both male and female rats (MRID 

48105511). The Agency did not consider the temporary decrease in body weight or food 

intake observed in the 2,000 mg/kg bw/day test group to be an adverse effect, as this is

likely due to the palatability of the food containing this high dose of test substance. The

Agency established the NOAEL (No Observed Adverse Effect Level) for this study as 
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2,000 mg/kg bw/day. A LOAEL (Lowest Observed Adverse Effect Level) was not

identified, suggesting that the test animals could have tolerated a higher dose.

Developmental Toxicity: A developmental toxicity study using Natamycin TGAI (MRID 

48105512) showed no discernable effects on growth, reproduction, teratological or 

mutagenic responses, or on gross and microscopic pathology, at concentration levels 0, 5, 

15 and 50 mg/kg bw/day.

D. Aggregate Exposure

1. Dietary exposure. Dietary exposure from the additional uses of Natamycin L 

being proposed for the control of postharvest fungal diseases on citrus, pome, 

stone fruit crop groups, avocado, kiwi, mango and pomegranates by dip, drench or 

spray in packinghouse facilities is expected to be minimal. 

i. Food. Natamycin has a long history of use. Natamycin has been used as 

a food preservative worldwide for over 50 years and is approved as a food 

additive/preservative by the European Union, the World Health 

Organization and individual countries for use as a fungistat to suppress 

mold on cheese, meats and sausage. In the United States, Natamycin is 

approved by The Food and Drug Administration (FDA) as a direct food 

additive/preservative for the inhibition of mold and yeast on the surface of 

cheeses (21 CFR § 172.155) and as an additive to the feed and drinking 

water of broiler chickens to retard the growth of specific molds (21 CFR § 

573.685). Natamycin is also FDA approved for use as a treatment to 

suppress fungal eye infections such as blepharitis, conjunctivitis, and 

keratitis. Natamycin is already approved for use as a fungistat to prevent 

and control mold and yeast spores in the growth media of mushrooms 

produced in enclosed mushroom facilities (EPA Reg. No. 87485-2) and to 

control fungal growth postharvest on pineapples indoors (EPA Reg. No. 

87485-3).

The results of toxicity testing indicate there is little if any risk to human 

health from exposure to Natamycin. The absence of toxicity in laboratory 

animals demonstrates the lack of toxicological concern for any increase in 

dietary exposure from the use Natamycin L. In a review of toxicological 

literature by the European Food Safety Agency (EFSA, 2009), Natamycin

was shown to be poorly absorbed by gastrointestinal systems of mammals 

and rapidly excreted in the feces (Blankwater and Hespe, 1979; Hespe and 

Meier, 1980; both reviewed and cited in EFSA, 2009). In addition, 

Natamycin is rapidly degraded by stomach acids, with a 1-hour half-life in 

simulated gastric juice (Morgenstern and Muskens, 1976; reviewed and 

cited in EFSA, 2009). In addition, Daamen and van den Berg (1985) and 

Kiermeier and Zierer (1975) demonstrated that Natamycin remained on 

the surface of cheese and only slight amounts penetrated into the cheese. It 

is expected the same thing would occur, when fruit is treated with 

Natamycin postharvest, that Natamycin will remain on the surface of the 
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fruit and very little would penetrate into the fruit and add to the dietary

intake. 

All inert ingredients used in the end-use product, Natamycin L, are 

approved for food use under 40 CFR 180.950 and 40 CFR 180.960; and 

are considered to be Generally Recognized As Safe (GRAS) by FDA.

ii. Drinking water. There are no concerns for exposure of humans to 

Natamycin in drinking water. Based on the additional proposed 

postharvest uses in treatment facilities on citrus fruit, pome fruit, stone 

fruit and cherries it is highly unlikely that residues of Natamycin will enter 

any sources of drinking water. In addition, due to its low solubility in 

water its concentration in surface waters would never exceed 50 ppm. 

Natamycin is also extremely sensitive to UV light and is completely 

degraded by UV within 24 hours of exposure in aqueous solution (Koontz 

et. al., 2003). 

2. Non-dietary exposure. The potential for non-dietary exposure to the general 

population, including infants and children is not expected because Natamycin is 

not approved for residential uses and the use sites are for enclosed mushroom 

production facilities or postharvest treatment facilities.

E. Cumulative Effects

The Food Quality Protection Act of 1996 requires the EPA to consider the 

cumulative effects of chemicals with a common mechanism of toxicity in its 

tolerance assessment decisions. There is no indication that Natamycin has a 

common mechanism of action with other compounds to result in any cumulative 

effects.

F. Safety Determination

1. U.S. population. Toxicity studies have shown that Natamycin is non-toxic to

mammals following acute exposures. These results indicate the product is not of 

toxicological concern for the general population when used as proposed on the label. 

Based on the data available, there is a reasonable certainty of no harm to the

general US population from exposure to Natamycin from the proposed 

additional uses.

2. Infants and children. As mentioned above, it is expected that, when used as

proposed, Natamycin would not result in residues that are of concern for 

potential toxicity. Based on the data provided, there is a reasonable certainty of

no harm for infants and children from exposure to Natamycin from the

proposed additional uses.

G. Effects on the Immune and Endocrine Systems
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To date there is no evidence to suggest that Natamycin functions in a manner 

similar to any known hormone, or that it acts as an endocrine disrupter.

H. Existing Tolerances

Natamycin is exempt from the requirement of a tolerance as stated at 40 CFR § 180.1315:

40 CFR § 180.1315 Natamycin; exemption from the requirement of a tolerance.

An exemption from the requirement of a tolerance is established for residues of 

natamycin in or on mushrooms when applied as a fungistat to prevent the germination of 

fungal spores on mushrooms produced in enclosed mushroom production facilities, and 

in or on pineapples when applied as a fungistat in accordance with label directions and 

good agricultural practices.

I. International Tolerances

There are no current tolerances or tolerance exemptions in place for Natamycin.

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