BIOPESTICIDES REGISTRATION ACTION DOCUMENT 

Natamycin 

PC Code: 051102 

U.S. Environmental Protection Agency

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

May 14, 2012 
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Biopesticides Registration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY .................................................................................................... 4

II. ACTIVE INGREDIENT OVERVIEW................................................................................. 7

III. REGULATORY BACKGROUND........................................................................................ 7

 

A. Classification.................................................................................................................... 7

 B. Food Clearances/Tolerances......................................................... ....8

IV. RISK ASSESSMENT ............................................................................................................. 8

A. Active Ingredient Characterization Error! Bookmark not defined.Error! Bookmark not defined

B. Human Health Assessment............................................................................................ 8

C. Environmental AssessmentError! Bookmark not defined.Error! Bookmark not defined.

V. ENVIRONMENTAL JUSTICE .Error! Bookmark not defined.Error! Bookmark not defined.

VI. RISK MANAGEMENT AND REGISTRATION DECISIONS ....................................... 14

A. Determination of Eligibility.......................................................................................... 14

B. Regulatory Decision ...................................................................................................... 15

C. Labeling.......................................................................................................................... 15

VII. ACTIONS REQUIRED OF THE REGISTRANT ........................................................... 16

A. Reporting of Adverse Effects and Hypersensitivity Incidents.................................. 16

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONSError! Bookmark not defined.Error! Bookmar

IX. BIBLIOGRAPHY STUDIES SUBMITTED IN SUPPORT OF THESE 

REGISTRATIONS ............................................................................................................... 24

A. Studies Submitted in Support of Natamycin..................................................................

B. EPA Risk Assessment Memoranda.............................................................................. 27

C. References...................................................................................................................... 27
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs

Biopesticides and Pollution Prevention Division

Biochemical Pesticides Branch (BPB)

Cheryl Greene Regulatory Action Leader

Russell Jones, Ph.D. Lead Science Reviewer/Senior Biologist

Linda Hollis Branch Chief

HEALTH CANADA PEST MANAGEMENT REGULATORY AGENCY

Bing Dang Science Coordination Officer

PMRA, Health Canada 

2720 Riverside Drive 

Ottawa, ON K1A 0K9 
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Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY

Natamycin is a new biochemical pesticide active ingredient intended for use as a fungistat to 

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

enclosed mushroom production facilities. Natamycin is a naturally-occurring antimycotic

compound derived from the common soil microorganisms, Streptomyces natalensis, 

Streptomyces lydicus, and Streptomyces chattanoogensis. It is commercially produced by a 

submerged oxygen-based fermentation of Streptomyces natalensis cells which are then lysed by 

increasing the temperature in the fermentation vessel thereby causing the release of Natamycin 

from the cell solids. . Natamycin was originally discovered in Streptomyces natalensis in South 

Africa in the early 1950s, and was subsequently discovered to also occur naturally in North 

America in Streptomyces lydicus, and Streptomyces chattanoogensis. Natamycin has a non-toxic 

mode of action and functions as a fungistat, preventing the germination of fungal spores. It has 

no effects on fungal mycelia. Development of antibiotic resistance to Natamycin has not been 

reported during its entire history of use. 

Natamycin has been used as a food preservative worldwide for over 40 years (WHO TRS 430) 

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 (21CFR172.155) and as an additive to the feed and drinking water of broiler chickens 

to retard the growth of specific molds (21CFR573.685). Natamycin is also FDA approved for 

use as a treatment to suppress fungal eye infections such as blepharitis, conjunctivitis and 

keratitis. On August 17, 2007, the EPA’s Biochemical Classification Committee classified 

Natamycin as a Biochemical Pesticide active ingredient, and -Streptomyces lydicus (the source of 

Natamycin) is currently registered by the Agency under Registration Nos. 73314-1, -2, and -4 as 

a microbial pesticide for greenhouse, nursery, turfgrass, agricultural, and seed treatment uses. 

The Biopesticides and Pollution Prevention Division (BPPD) determined that the 

data/information submitted for product chemistry and Tier I acute toxicity for Natamycin satisfy

the current guideline requirements. Acceptable studies were submitted for the subchronic 90-day

oral (OCSPP 870.3100) and 90-day inhalation (OCSPP 870.3465) data requirements. Those data 

showed no biologically significant changes in the hematology or clinical chemistry profiles of 

the test animals. No 90-Day Dermal (OCSPP 870.3250) or 90-Day Inhalation (OCSPP 

870.3465) studies were submitted and none are required since products containing Natamycin 

will only be applied in irrigation water to mushrooms growing in enclosed facilities. Based on 

this application method, the Agency does not anticipate any repeated dermal exposure to 

Natamycin. 

In lieu of a Guideline study the applicant developed a science based rationale in support of 

Prenatal Developmental Toxicity ((OCSPP 870.3700) for Natamycin. The rationale was 

supported with information and data obtained from the open technical literature. The rationale 

relies primarily on a comprehensive review of Natamycin by the European Food Safety 

Authority (EFSA, 2009) and its associated citations. By way of the EFSA review of Natamycin 

(aka Pimaricin), the rationale demonstrated that Natamycin is poorly absorbed by mammals and 
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that it does not pose any dietary concerns based on current usage. The Agency concurs with this 

conclusion based on per capita consumption of all mushroom commodities in the United States 

(USDA/ERS, 2010), dietary intake from treated, unwashed mushrooms is conservatively 

estimated to be no more than 0.00030 mg a.i./kg bw/person/day. This value is well below any

known acute oral, subchronic and chronic dietary, reproductive, and developmental endpoints for 

Natamycin by many orders of magnitude. In addition, the estimated dietary intake from 

unwashed, treated mushrooms also is well below the Acceptable Dietary Intake (ADI) of 0.3 

established by Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2001& 2006) 

and an ADI of 0.1 established European Food Safety Authority (EFSA, 2009). The information 

submitted by the registrant, along with open technical literature also support the Tolerance 

Exemption Petition submitted for Natamycin. 

Tier I studies were not submitted for non-target organisms and environmental fate data 

requirements (OCSPP 850.1010 to 850.4450) for Natamycin and such studies are not required. 

Based on its use pattern and use instructions as a fungistat intended solely for use in indoor, 

enclosed mushroom production facilities, Natamycin exposure to non-target organisms is not 

expected. Further, EPA has determined that Natamycin will have "No Effect" on any currently

listed threatened or endangered species or any designated critical habitat based on its use pattern 

and use instructions and the fact that Natamycin is intended solely for indoor use in enclosed 

mushroom production facilities. 

Based on the acute toxicity data for Natamycin, the active ingredient is toxicity category III. 

EPA has not identified any toxic endpoints for nontarget mammals, birds, plants, aquatic, or soil 

organisms. EPA has no concerns for any nontarget organisms exposed to Natamycin when used 

in accordance with approved label directions. Given that Natamycin has very low toxicity and 

presents little, if any, risk to nontarget organisms, EPA has concluded that it is in the best 

interests of the public to issue the registration for the Natamycin TGAI (EPA File Symbol No. 

87485-1) and the end-use product Natamycin L (EPA File Symbol No. 87485-2), which contain 

this new active ingredient, Natamycin. 

The Agency has reviewed the data/information in support of the requirements for granting 

registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act 

(FIFRA) and determined that the data/information submitted adequately satisfy current 

guideline requirements (see 40 CFR Subpart U § 158.2000). 

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for 

the public to participate on major registration decisions before they occur. According to this 

policy, EPA provides a public comment period prior to making a registration decision for the 

following types of applications: new active ingredients, first food use, first outdoor use, first 

residential use; and any registration decisions for which the Agency believes there may be 

substantial public interest. 

Consistent with the policy of making registration actions more transparent, Natamycin was 

subject to a 30 day comment period as a “new active ingredient”. The notice for this comment 

period included the draft Biopesticides Registration Action Document (BRAD) and draft product 

labels for the technical grade active ingredient, Natamycin TGAI and the EP, Natamycin L. 
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which contain this new active ingredient, Natamycin. The docket identification (ID) number is 

EPA-HQ-OPP-2010-0685. The Agency believes that based on the risk assessment and 

information submitted in support of the registration of the EP containing Natamycin, it is in the 

best interests of the public to issue the registration for Natamycin L. The basis for this decision 

can be found in the risk assessment for Natamycin, which is characterized in this BRAD. 
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II. ACTIVE INGREDIENT OVERVIEW

 Common Name: Natamycin 

 Chemical Name: IUPAC Chemical Name: 

(1R,3S,5R,7R,8E,12R,14E,16E,18E,20E,22R,24S,25R,26S)-22-[(3-

amino-3,6-dideoxy-β-D-mannopyranosyl)oxy]-1,3,26-trihydroxy12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.05,7]octacosa8,14,16,18,20-pentaene-25-carboxylic acid

Trade & Other Names: Natamycin L

Pimaricin

Tennectin

Delvocid

CAS Registry Number: 7681-93-8

OPP Chemical Code: 051102 

Type of Pesticide: Fungistat

III. REGULATORY BACKGROUND

On May 20, 2010, EPA received an application filed by Keller and Heckman, 1001 G Street, 

N.W., Suite 500 West, Washington, D.C.20001 on behalf of DSM Food Specialties B.V., 

Alexander Fleminglaan 1, Delft, The Netherlands 2613AX to register the products Natamycin 

TGAI (EPA File Symbol No. 87485-1), and Natamycin L (EPA File Symbol No. 87485-2)

containing the new biochemical active ingredient Natamycin. The application was submitted to 

both the U.S. Environmental Protection Agency (EPA) and The Health Canada Pest 

Management Regulatory Agency (PMRA) along with a request for a North American Free Trade 

Agreement (NAFTA) Joint Review of the applications1. Concurrent with these applications,

DSM filed a petition for a tolerance exemption for residues of Natamycin on mushrooms when 

used as a fungistat in enclosed mushroom producing facilities. No comments were received 

following publication of the notice. On November 24, 2010, EPA published in the Federal 

Register (76 FR 22067) a Notice of Receipt (NOR) announcing receipt of the applications and 

on April 20, 2011 EPA published in the Federal Register (76 FR 22067) a Notice of Filing 

(NOF) announcing receipt of the petition. 

A. Classification 

 

1

See http://www.epa.gov/oppfead1/international/naftatwg/guidance/jointreview-biope.pdf.
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Natamycin was classified as a Biochemical Pesticide by the Agency’s Classification Committee 

on August 17, 2007. The Classification Committee confirmed its nontoxic mode of action, its 

natural occurrence in the environment, and its history of exposure to humans and the 

environment without known toxicity. 

B. Food Clearance/Tolerances 

Natamycin is intended for use as a fungistat only on mushrooms grown in enclosed mushroom 

growing facilities. The Agency considers this use to be a food use. On April 20, 2011 the

Agency issued a notice in the federal register (76 FR 22067) of the filing of a petition by DSM 

for the exemption of residues of on mushrooms. 

IV. RISK ASSESSMENT

A. Active Ingredient Characterization 

Natamycin is a biochemical active ingredient intended for use as a fungistat to be in enclosed 

mushroom production facilities for the control of fungi and mold on mushrooms. It is derived 

from the common soil microorganism, Streptomyces natalensis and is commercially produced by 

submerged aerobic fermentation by Streptomyces natalensis, Streptomyces lydicus, and

Streptomyces chattanoogensis. Fermentation is conducted for several days, and the antibiotic is 

isolated either by broth extraction or by extraction of the mycelium. Dried Natamycin recovered 

from the fermentation broth is white to cream-colored and has little or no odor or taste; in the 

crystalline form it is very stable. During the extraction procedure the Natamycin is dissolved and 

filtered through a membrane. The membrane is not permeable to the organism and the 

concentration of the extraction is high enough to kill the organism. None of the microorganism 

that is used to produce Natamycin is viable at the end of this process. 

All product chemistry and composition data requirements for Natamycin have been satisfied.

The information submitted to support the product chemistry and composition data requirements 

for Natamycin are summarized in Tables 1 and 2 in Appendix A. 

 

 B. Human Health Assessment

1. Toxicology 

For acute toxicity data requirements, toxicity categories are assigned based on the hazard(s) 

identified from studies and/or information on file with the Agency. The active ingredient is 

classified into Toxicity Category I, II, III or IV where Toxicity Category I indicates the highest 

toxicity and Toxicity Category IV indicates the lowest toxicity. 

Adequate mammalian toxicology data/information is available to support registration o 

Natamycin. All toxicology data requirements for Natamycin have been satisfied.
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a. Acute Toxicity

Acute toxicity testing is required to 1) determine systemic toxicity from acute exposure via the 

dermal, inhalation and oral routes, 2) determine irritant effects from exposure to the eyes, and 3) 

determine the potential for skin sensitization (allergic contact dermatitis). 

Tier I acute toxicity studies submitted and reviewed showed that Natamycin is Toxicity Category

III for acute oral toxicity and Toxicity Category IV for acute dermal toxicity, acute inhalation 

toxicity, primary eye irritation, and primary dermal irritation. Natamycin is not a sensitizer. 

Natamycin is not a mutagen and is not cytotoxic. 

For more information regarding acute toxicity data requirements, refer to Table 3 in Appendix A. 

b. Subchronic Toxicity 

Subchronic data are required to determine a no-observed-effect-level (NOEL) and any toxic 

effects associated with repeated or continuous exposure to a test substance for a period of ninety 

days. Subchronic (90-day) dermal toxicity and Subchronic inhalation studies were not 

submitted, but are not required based on a lack of repeated exposure to workers and applicators 

via these two routes of exposure. 

A 90-day oral (OCSPP 870.3100) and 90-day inhalation (OCSPP 870.3465) study was 

submitted and is acceptable based on the data demonstrating that no biologically significant 

changes in the hematology or clinical chemistry profiles were observed. The Agency concurs 

with the findings.

For more information regarding the subchronic data requirements, refer to Table 3 in Appendix

A. 

c. Developmental Toxicity and Mutagenicity 

In lieu of a Guideline study the applicant developed a science based rationale in support of 

Developmental Toxicity ((OCSPP 870.3700) for Natamycin. The rationale was supported with 

information and data obtained from the open technical literature. The rationale relies primarily

on a comprehensive review of Natamycin by the European Food Safety Authority (EFSA, 2009) 

and its associated citations. By way of the EFSA review of Natamycin (aka Pimaricin), the 

rationale demonstrated that Natamycin is poorly absorbed by mammals and that it does not pose 

any dietary concerns based on current usage. The Agency concurs with this conclusion based on 

per capita consumption of all mushroom commodities in the United States (USDA/ERS, 2010), 

dietary intake from treated, unwashed mushrooms is conservatively estimated to be no more than 

0.00030 mg a.i./kg bw/person/day. This value is well below any known acute oral, subchronic 

and chronic dietary, reproductive, and developmental endpoints for Natamycin by many orders 

of magnitude. In addition, the estimated dietary intake from unwashed, treated mushrooms also 

is well below the Acceptable Dietary Intake (ADI) of 0.3 established by Joint FAO/WHO Expert 
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Committee on Food Additives (JECFA, 2001& 2006) and an ADI of 0.1 established European 

Food Safety Authority (EFSA, 2009). The information submitted by the registrant, along with 

open technical literature also support the Tolerance Exemption Petition submitted for Natamycin. 

For more information regarding developmental toxicity and Mutagenicity data requirements, 

refer to Table 3 in Appendix A. 

 d. Tier II and Tier III (40 CFR § 158.2050)

No Tier II and Tier III studies were required, based on a lack of acute toxicity in the Tier I 

studies and a lack of exposure relative to Natamycin’s use pattern as a fungistat to control mold 

on mushrooms in enclosed mushroom producing facilities. 

c. Effects on the Endocrine System

As required under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), EPA has 

developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain 

substances (including pesticide active and other ingredients) may have an effect in humans or 

wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine 

effects as the Administrator may designate.” The EDSP employs a two-tiered approach to 

making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found 

to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage 

of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on 

the available data. Tier 2 testing is designed to identify any adverse endocrine-related effects 

caused by the substance, and establish a quantitative relationship between the dose and the E, A, 

or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors.

Natamycin is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA section 408(p), EPA must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP orders/data call-ins for all 

pesticide active ingredients. For further information on the status of the EDSP, the policies and 

procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please 

visit our website: http://www.epa.gov/endo/.
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2. Dose Response Assessment 

No definitive toxicological endpoints were identified for Natamycin and no effects were 

observed at maximum hazard doses.

3. Dietary Exposure and Risk Characterization

Dietary exposure to Natamycin is expected to be minimal. Natamycin is a fungistat that has a 

long history of use in food for the prevention of spoilage. The active ingredient was 

demonstrated to be minimally toxic in OCSPP Guideline studies using the TGAI (see Appendix 

A, Table 4). 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). 

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. 

Acute and Chronic Dietary Exposure and Risks for Sensitive Subpopulations, Particularly 

Infants and Children

Based on the minimal toxicity of Natamycin demonstrated in laboratory testing of the TGAI (see 

Table 4), the anticipated minimal dietary exposure, and the mode of action of Natamycin as a 

fungistat, acute and chronic dietary risks for sensitive subpopulations are not anticipated. 

4. Drinking Water Exposure Risk Characterization

Based on the intended use sites (enclosed mushroom production facilities) and use directions 

(steam sterilization of compost and casing prior to disposal outside of the mushroom growth 

facility), it is highly unlikely that residues of Natamycin will enter any sources of drinking water. 

However, in the unlikely event that Natamycin residues escape from its indoor application site 

(completely enclosed mushroom houses), its concentration in surface waters would never exceed 

30-50 ppm due to its low solubility in water; up to 50 ppm @ 20-25°C and pH 5-7.5; and at t 

<pH2 or >pH 10 it completely degrades (USEPA, 2011). Natamycin is extremely sensitive to 

UV light and is completely degraded by UV within 24 hours of exposure in aqueous solution 

(Koontz et. al., 2003). Even assuming that no environmental degradation takes place, should 

Natamycin be ingested via drinking water, gastric juices typically found in the human stomach 

will completely degrade Natamycin within 24 hrs (JECFA, 2006). Finally, the non-definitive 

endpoints for acute oral toxicity (>1820 ppm) and subchronic oral toxicity (>500 ppm in the diet) 

(USEPA, 2011) are approximately 36X and 10X greater than the highest measured solubility of 

Natamycin in water. For these reasons, the Agency believes that there are no concerns for 

exposure of humans to Natamycin in drinking water.
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5. Occupational, Residential, School and Day Care Exposure and Risk 

Characterization 

Based on use sites (enclosed mushroom production facilities) and use directions (steam 

sterilization of compost and casing prior to disposal outside of the mushroom growth facility), no 

Residential, School, or Day-Care exposure is expected. 

a. Occupational Exposure and Risk Characterization 

Occupational exposure to mixer/loader/applicators is expected to be minimal, but can be 

mitigated with appropriate Personal Protective Equipment (PPE). See Discussion of Human 

Activities below. 

b. Residential, School and Day Care Exposure and Risk Characterization 

A residential, school and day care exposure assessment was not conducted for Natamycin. 

However, based on use sites of products containing Natamycin (enclosed mushroom production 

facilities) and use directions (steam sterilization of compost and casing prior to disposal outside 

of the mushroom growth facility), no Residential, School, or Day-Care exposure is expected. 

6. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and 

Inhalation 

Based on the mode of action of the active ingredient as a fungistat, no aggregate exposure is 

anticipated.

7. Cumulative Effects 

Based on the mode of action of the active ingredient as a fungistat, minimal dietary exposure 

(see Dietary Exposure and Risk Characterization above) and rapid degradation and excretion 

from animal systems (EFSA, 2009), no cumulative exposure is anticipated. 

Pursuant to FFDCA section 408(b)(2)(D)(v), EPA has considered available information 

concerning the cumulative effects of Natamycin residues and other substances that have a 

common mechanism of toxicity. These considerations include the potential for cumulative 

effects on infants and children of Natamycin residues and other substances with a common 

mechanism of toxicity. Because Natamycin has a long history of dietary consumption without 

incident, and because the available data show a lack of acute toxicity in the Tier I studies as well 

as a lack of exposure relative to Natamycin’s use pattern as a fungistat to control mold on 

mushrooms in enclosed mushroom producing facilities, the Agency concludes that Natamycin 

does not share a common mechanism of toxicity and that there are no potential cumulative 

effects arising from incidental exposures to Natamycin residues in or on food commodities. 
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8. Risk Characterization

The Agency considered human exposure to Natamycin in light of the standard for registration in 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the relevant safety factors 

in FFDCA. A determination has been made that no unreasonable adverse effects to the U.S. 

population in general, and to infants and children in particular, will result from the use of 

Natamycin when label instructions are followed. 

C. ENVIRONMENTAL ASSESSMENT 

1. Ecological Hazards

Tier I studies were not submitted but are not required. However, based on its use pattern and use 

instructions as a fungistat intended solely for use in indoor, enclosed mushroom production 

facilities, exposure to non-target organisms is not expected. Additionally, based on its use 

pattern and use instructions, EPA has determined that Natamycin will have "No Effect" on any 

currently listed threatened or endangered species or any designated critical habitat. 

For more information regarding nontarget organism toxicity data requirements, please refer to 

Table 4 in Appendix A. 

2. Environmental Fate and Ground Water Data

Environmental fate and groundwater data are not required at this time because the results of the 

nontarget organism toxicity assessment (Tier I data requirements) did not trigger these Tier II 

data requirements. 

3. Endangered Species Assessment

The Agency has not conducted a risk assessment that supports a complete endangered species 

determination. The ecological risk assessment planned during registration review will allow the 

Agency to determine whether Natamycin use has “no effect” or “may effect” federally listed 

threatened or endangered species (listed species) or their designated critical habitats. When an 

assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical 

habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine 

Fisheries Services (the Services) as appropriate. 

D. EFFICACY DATA 

Product performance data must be developed for all pesticides to ensure that pesticide products 

will perform as intended and that unnecessary pesticide exposure to the environment will not 

occur as a result of the use of ineffective products. The Agency reserves the right to require on a 

case-by- case basis, submission of efficacy data for any pesticide product registered or proposed 

for registration that are intended to be used to control a pest of significance public health 

importance and a public health pest as defined in FIFRA section 28(d) and section 2(nn). For 

further guidance on product performance requirement, refer to Pesticide Registration Notice (PR) 
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Notices 96-7, 2002-1 and Explanation of Statutory Framework for Risk-Benefit Balancing for 

Public Health Pesticides (http://www.epa.gov/PR _Notices/pr1996-7.pdf) 

(http://www.ea.gov/PR_Notices/pr2002-1.pdf) and (http://www.epa.gov/pesticides/health/riskbenefit.htm).

The EPs submitted with this new active ingredient did not list pests of significance public health 

importance or a public health pest as defined in FIFRA section 28(d) and section 2(nn). 

Therefore, the Agency does not require product performance for Natamycin under the proposed 

uses. However, these data are required by Canada/PMRA and was submitted and reviewed by 

Canada/PMRA as part of the joint review of the active ingredient. We are reporting the results of 

that review below.

Canada/PMRA Review 

Natamycin has proven to be an extremely effective in food preservation because its mode of 

action is to stop the growth of molds and yeasts before damage begins. Curative fungicidal 

treatments cannot always negate the harmful effects that a growing mycelium leaves behind. In 

addition, fungi can produce dangerous mycotoxins, some of which are even carcinogenic, that 

can cause health problems. Removing the fungi has no effect on mycotoxins once they are 

embedded. Natamycin is able to protect food products against mold growth for long periods of 

time due to its stability and crystalline form. It has a low level of solubility in water (~50 ppm) 

and in organic materials. Specifically, Natamycin can reduce the development of Verticillium 

disease - a use for which this active ingredient is being registered - of the commercial mushroom. 

As a fungistat to control Verticillium disease, the best control was noted when 2 mL (form) per 

sq m were applied. There appears to be little difference between 2 applications (pinning and 

casing) or 4 applications (pinning, casing, between 1st and 2nd breaks and between 2nd and 3rd

breaks). All product performance data required by Canada/PMRA for registration of Natamycin 

have been satisfied.

V. Environmental Justice

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have

atypical, unusually high exposure to Natamycin, compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

VI. Risk Management and Registration Decision

A. Determination of Eligibility

Section 3(c)(5) of FIFRA provides for the registration of new active ingredients if it is 

determined that (A) its composition is such as to warrant the proposed claims for it; (B) its 

labeling and other materials required to be submitted comply with the requirements of FIFRA; 
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(C) it will perform its intended function without unreasonable adverse effects on the 

environment; and (D) when used in accordance with widespread and commonly recognized 

practice, it will not generally cause unreasonable adverse effects on the environment. 

The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by 

the science assessments supporting products containing Natamycin. Such products are not 

expected to cause unreasonable adverse effects and are likely to provide protection as claimed 

when used according to label instructions. Therefore, EPA concludes that Natamycin is eligible 

for registration for the labeled uses.

B. Regulatory Decision

On October 1, 2009, the EPA announced a new policy to provide a more meaningful opportunity

for the public to participate in major registration decisions before they occur. According to this 

policy, EPA intends to provide a public comment period prior to making a registration decision 

for, at minimum, the following types of applications: new active ingredients; first food uses; first 

outdoor uses; first residential uses; or any other registration actions for which EPA believes there 

may be significant public interest. Accordingly, this pesticide was subjected to a 30-day

comment period as a new active ingredient with outdoor uses. 

The Agency believes that the data submitted fulfill the requirements of registration for products 

containing Natamycin for use as a fungistat for use on mushrooms in enclosed mushroom

production facilities. Acute toxicity data for Natamycin demonstrate that it is toxicity category

III and IV for all routes of exposure. (No toxicological endpoints were established.) Data confirm 

that Natamycin does not demonstrate subchronic or developmental toxicity, and it is not 

mutagenic or genotoxic. EPA has no concerns for any nontarget organisms exposed to 

Natamycin in accordance with its approved uses. EPA has not identified any toxic endpoints for 

nontarget mammals, birds, plants, aquatic, or soil organisms. Nor are there any anticipated 

concerns for any threatened and endangered species. Given the nontoxic character of Natamycin

and because all applicable data requirements have been fulfilled, EPA supports its registration 

under FIFRA section 3(c)(5). 

C. Labeling

Before releasing pesticide products containing Natamycin for shipment, the applicant is required 

to provide appropriate labels. Such labeling for the technical grade active ingredient (TGAI) 

must include personal protection equipment (PPE) requirements as follows: 

“Mixer/loader/applicators are required to wear the following Personal Protection Equipment 

(PPE):

eye protection

long pants

long-sleeved shirt

 closed shoes

 gloves 
Natamycin Page 16 

Biopesticides Registration Action Document

VII. ACTIONS REQUIRED OF THE REGISTRANT

The Agency evaluated the data submitted in connection with the initial registration of Natamycin

and determined that these data fulfill current registration guideline requirements. No additional 

data are required to be submitted to the Agency at this time. Additional data may be required for 

new uses and/or changes to existing uses. 

Notwithstanding the information stated in the previous paragraph, it should be clearly understood 

that certain, specific data are required to be reported to the Agency as a requirement for 

maintaining the Federal registration for a pesticide product. A brief summary of these types of 

data are listed below. 

A. Reporting of Adverse Effects and Hypersensitivity Incidents

Reports of all incidents of adverse effects to the environment must be submitted to the Agency

under the provisions stated in FIFRA section 6(a)(2).

Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents) 

must be reported to the Agency under the provisions of 40 CFR § 158.2050(e).
Natamycin Page 17 

Biopesticides Registration Action Document

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

ADI average daily intake

BPB Biochemical Pesticides Branch

BRAD Biopesticides Registration Action Document

CA chromosomal aberrations

CAS Chemical Abstracts Service

CFR Code of Federal Regulations

EDSP Endocrine Disruptor Screening Program

EP End-use Product

EPA United States Environmental Protection Agency (Agency)

FDA United States Food and Drug Administration 

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FR Federal Register

g gram

g/mL gram per milliliter

Hg mercury

HSDB Hazardous Substances Data Bank

LC50 median lethal concentration. A statistically derived concentration of a 

substance that can be expected to cause death in 50% of test animals. It is 

usually expressed as the weight of substance per weight or volume of water, 

air or feed (e.g., mg/L, mg/kg, or ppm).

LD50 median lethal dose. A statistically derived single dose that can be expected 

to cause death in 50% of the test animals when administered by the route 

indicated (oral, dermal, or inhalation). It is expressed as a weight of 

substance per unit weight of animal (e.g., mg/kg).

LOC level of concern

LOEL lowest observed effect level

μg microgram

μm micrometer

MRID No. Master Record Identification Number

mg/kg milligram per kilogram

mg/L milligram per liter

mg/ml milligram per milliliter

ml milliliter

mm millimeter

MP Manufacturing-use Product

nm nanometer

NOAEL no observed adverse effect level

NOEC no observed effect concentration

NOEL no observed effect level

OCSPP Office of Chemical Safety and Pollution Prevention

OPP Office of Pesticide Programs

Pa pascal

PC Code Pesticide Chemical Code
Natamycin Page 18 

Biopesticides Registration Action Document

ppb parts per billion

PPE personal protective equipment

ppm parts per million

RQ risk quotient

SCE sister chromatid exchange
Natamycin Page 19 

Biopesticides Registration Action Document

IX. Appendix A. Data Requirements (40 CFR Part 158-Subpart U) 

*NOTE: Master Record Identification (MRID) numbers listed in the following tables are 

representative of supporting data/information for the original registration of the product 

containing this active ingredient. Subsequent to this registration, there may be additional MRIDs 

that support registration of other products containing this active ingredient. 

TABLE 1. Product Chemistry Data Requirements for Natamycin Technical (40 CFR § 

158.2030)

OSCPP 

Guideline No. Study Results MRID No.

880.1100

880.1200

880.1400

Product identity;

Manufacturing process;

Discussion of formation 

of impurities

Submitted data satisfy

the requirements for 

product identity, 

manufacturing process, 

and discussion of 

formation of impurities. 

48105401

48105501

47206713

47760931

830.1700 Analysis of samples Submitted data satisfy

the requirements for 

analysis of samples. 

48105502

830.1750 Certification of limits Limits listed in the 

confidential statement of 

formula are acceptable 

48105402

830.1800 Analytical method Acceptable 48105403

TABLE 2. Physical and Chemical Properties of Natamycin Technical (40 CFR § 158.2030)

OCSPP 

Guideline 

No. 

Property Description of Results 

MRID

830.6302 Color Colourless 48105503

830.6303 Physical State Viscous liquid 48105503

830.6304 Odor Odorless 48105503

830.6313

Stability to Normal 

and Elevated 

Temperatures, 

Metals and Metal 

Ions

Natamycin was found stable at 

54°C for 14 days. Storage 

stability studies supporting 

pharmaceutical uses found 

acceptable stability in tests of 2 

to 5 years in duration.

Natamycin is degraded by 

contact with most metals and 

metal ions. However, the product 

is never packaged in metal 

48105504
Natamycin Page 20 

Biopesticides Registration Action Document

TABLE 2. Physical and Chemical Properties of Natamycin Technical (40 CFR § 158.2030)

OCSPP 

Guideline 

No. 

Property Description of Results 

MRID

containers.

830.6315 Flammability Does not contain any flammable 

components. Consists of ~ 80% 

water.

48105503

830.6317 Storage Stability The product is stable when 

stored for 12 and 18 months in 

HDPE plastic bottles at 25oC. 

8105405

48439301

48544501

830.6320 Corrosion 

Characteristics

The product is not corrosive. 48105405

48439301

48544501

830.7000 pH 6.5 (1% aqueous solution)

6.5 (1% aqueous solution). May

vary between 5 to 7.5

48105503?

830.7100 Viscosity ~2200 mPa.s, Brookfield Test 

Method:

RPM-20, Axe=3, T=20°C.

48105503

830.7220 Boiling Point/Range N/A The product is a solid. 48105503

830.7300 Density Loose bulk density 0.3 g/mL

Tapped bulk density 0.59 g/mL

830.7560

830.7570

Octanol/water 

partition coefficient 

(Kow) 

Log Kow = – 3.67 48105503

830.7840 Water Solubility 30-50 ppm @ 20-25°C and pH 

5-

7.5; very soluble at pH ≥ 10 or

pH ≤ 2 but rapidly degrades.

8105503

830.7950 Vapor Pressure NA The product is a solid 48105503

Formulation Type Suspension (SU) 48105501

Container Material 

and Description

HDPE plastic bucket, jerry can, 

drum or jumbo container (5 to 

1000 Litres)

48105501

830.7000 pH 6.5 (1% aqueous solution)

6.5 (1% aqueous solution). May

vary between 5 to 7.5

48105503

830.6314 Oxidizing or 

Reducing Action

Not applicable. Does not contain 

oxidizing or reducing chemicals.

48105503

830.6316 Explodability Not applicable. Does not contain 

any substance capable of 

48105503
Natamycin Page 21 

Biopesticides Registration Action Document

TABLE 2. Physical and Chemical Properties of Natamycin Technical (40 CFR § 158.2030)

OCSPP 

Guideline 

No. 

Property Description of Results 

MRID

exploding.

830.6319 Miscibility Not formulated to be mixed with 

petroleum solvents.

48105503

830.6321 Dielectric 

Breakdown Voltage

Not applicable. Not intended to 

be used around electrical 

equipment.

48105503

1 A = Acceptable; N = Unacceptable (see Deficiency); N/A = Not applicable.

2

For example, “brown” for 830.6302; “1.021” for 830.7300.

3.There was a slight shift in the retention time (close to a minute) for the active ingredient based 

on the chromatograms provided for the 18-month storage stability study. The applicant provided 

a rationale indicating that there was a change in the column packing material (new batch). The 

applicant provided additional chromatograms for the controls (standard sample) for the 6- and 

18-month to confirm the slight shift in the retention times for the active. The rationale is 

accepted.

; 

Table 4. Acute Toxicity Data for the Technical Grade Active Ingredient Product, Natamycin 

TGAI (91.02% a.i.); 

EPA File Symbol No. 87485-R

Study Type/OCSPP Guideline LD50/LC50/Results Toxicity 

Category

MRID

Acute Oral Toxicity/OCSPP 870.1100 >2000 mg/kg

(>1820 mg a.i./kg)

ACCEPTABLE

III 48105505

Acute Dermal Toxicity/OCSPP 

870.1200

>5050 mg/kg

(>4696.5 mg 

a.i./kg)

ACCEPTABLE

IV 48105506

Acute Inhalation Toxicity/OCSPP 

870.1300

>2.39 mg/L

(2.18 mg a.i./L)

IV 48105507
Natamycin Page 22 

Biopesticides Registration Action Document

Table 4. Acute Toxicity Data for the Technical Grade Active Ingredient Product, Natamycin 

TGAI (91.02% a.i.); 

EPA File Symbol No. 87485-R

Study Type/OCSPP Guideline LD50/LC50/Results Toxicity 

Category

MRID

ACCEPTABLE

Primary Eye Irritation/OCSPP 

870.2400

No corneal or 

positive irritation 

effects at 24-hr 

post instillation

ACCEPTABLE

IV 48105508

Primary Dermal Irritation/OCSPP 

870.2500

PII = 0.1

ACCEPTABLE IV 48105509

Skin Sensitization-LLNA/OCSPP 

870.2600

LLNA SI <3

ACCEPTABLE1 Not a sensitizer 48105510

TABLE 3a. Natamycin residues in mushrooms from the first break (MRID 48105408)

Treatment Treatment date Sampling 

date

Tray no. Residue (mg/kg)

Delvocid

2 mL/m2

At casing, January 26

At pinning, February 2

February 11 29 0.0590

29 0.0890

30 0.0267

30 0.0285

31 0.0287

31 0.0178

32 0.0180

32 0.0192

1 0.0230

1 0.0221

2 0.0369

2 <0.01

3 0.0271

3 0.0344

4 0.0340

4 0.0274

Untreated 

control

NA February 11 9 <0.01

9 <0.01

10 <0.01

10 <0.01
Natamycin Page 23 

Biopesticides Registration Action Document

TABLE 3b. Natamycin residues in washed and unwashed mushrooms from the second and 

third breaks (treated three or four times, respectively) MRID 48105408

Treatment Treatment date Sampling 

date

Tray 

no.

Residue 

(mg/kg)

Delvocid

2 mL/m2, 

unwashed

At casing, January 26

At pinning, February 2

Between breaks 1 & 2, 

February 13

February 17 1 0.2370

1 0.1420

At casing, January 26

At pinning, February 2

Between breaks 1 & 2, 

February 13

Between breaks 2 & 3, 

February 20

February 25 1 0.0407

1 0.1452

Delvocid

2 mL/m2, washed

At casing, January 26

At pinning, February 2

Between breaks 1 & 2, 

February 13

February 17 1 <0.01

1 0.0755

At casing, January 26

At pinning, February 2

Between breaks 1 & 2, 

February 13

Between breaks 2 & 3, 

February 20

February 25 1 0.0123

1 0.0220

Untreated control NA February 17 10 <0.01

February 25 10 <0.01
Natamycin Page 24 

Biopesticides Registration Action Document

X. BIBLIOGRAPHY 

MRID Citation Reference

59399 American Cyanamid Company (1959) Antibiotic A-5283, Myprozine: Acute 

Toxicity to Rats; Subacute Toxicity to Rats and Dogs: Re- port No. 59-4. 

(Unpublished study received on unknown date un- der unknown admin. no.; 

CDL:223651-A) 

59400 American Cyanamid Company (1963) Pimaricin (Myprozine^(R)I): Report on TwoYear Toxicity Studies. Summary of studies 223651-C through 223651-H. 

(Unpublished study received on unknown date under unknown admin. no.; 

CDL:223651-B) 

59401 American Cyanamid Company (1963) Pimaricin: Two-Year Feeding to Dogs: Report 

No. 63-6. (Unpublished study received on unknown date under unknown admin. no.; 

CDL:223651-C) 

59402 American Cyanamid Company (1963) Pimaricin: Two-Year Feeding to Rats: Report 

No. 63-7. (Unpublished study, including report no. 63-8, received on unknown date 

under unknown admin. no.; CDL: 223651-D) 

59403 Levinskas, G.J.; Bushey, C.; Kunde, M.L.; et al. (1963) Pimaricin: Successive 

Generation Studies: Report No. 63-9. (Unpublished study received on unknown date 

under unknown admin. no.; submit- ted by American Cyanamid Co., Princeton, N.J.; 

CDL:223651-E) 

59404 Shirk, R.J.; Lovesky, R.L. (1963) A Gross Examination of the Fecal Flora of Rats 

Sustained for Two Years on Diets Containing from 0 to 1000 ppm. Pimaricin: Report 

FS 3. Progress rept., Jun 21, 1962 to Aug 1, 1962. (Unpublished study received on 

unknown date under unknown admin. no.; submitted by American Cyanamid Co., 

Princeton, N.J.; CDL:223651-F) 

59405 Shirk, R.J. (1963) The Fecal Excretion and Non-absorption of Pimaricin in Animals: 

Report FS 3. Progress rept. (Unpublished study received on unknown date under 

unknown admin. no.; submit- ted by American Cyanamid Co., Princeton, N.J.; 

CDL:223651-G) 

48105400 DSM Food Specialties B.V. (2010) Submission of Product Chemistry, Residue, 

Toxicity, and Exposure and Risk Data in Support of the Application for Registration 

of Natamycin L and the Petition for Tolerance of Natamycin for Use on Mushrooms. 

Transmittal of 11 Studies.

48105401 van der Lee, J.; Jovanovich, A. (2010) Natamycin L: Product Identity, Composition, 

and Formulation. Unpublished study prepared by Keller and Heckman LLP. 48 p.

48105402 van der Lee, J.; Jovanovich, A. (2010) Natamycin L: Certified Limits. Unpublished 

study prepared by Keller and Heckman LLP. 9 p.

48105403 van Hilten, P. (2010) Natamycin L: Enforcement Analytical Method. Unpublished 
Natamycin Page 25 

Biopesticides Registration Action Document

MRID Citation Reference

study prepared by Keller and Heckman LLP. 18 p.

48105404 van der Lee, J.; Jovanovich, A. (2010) Natamycin L: Summary of Physical/Chemical 

Properties and Self-Certification. Unpublished study prepared by Keller and 

Heckman LLP. 32 p.

48105405 van der Lee, J.; Jovanovich, A. (2011)(Sic) Natamycin L: Interim Report for Storage 

Stability and Corrosion Characteristics. Project Number: STAB/SLD/09/008. 

Unpublished study prepared by DSM Food Specialties B.V. 24 p.

48105406 Jovanovich, A. (2010) Residue Data: Chemical Identity and Directions for Use for 

Natamycin L. Unpublished study prepared by Keller and Heckman LLP. 9 p.

48105407 Marin, J. (2010) Development and Validation of an Analytical Method for the 

Determination of Natamycin in Mushrooms and Mushroom Compost, Casing and 

Casing plus Innoculum. Project Number: 1869W. Unpublished study prepared by

PTRL West, Inc. 73 p.

48105408 Marin, J. (2009) Magnitude of the Residue of Natamycin in Mushrooms. Project 

Number: 1915W. Unpublished study prepared by PTRL West, Inc. 165 p.

48105409 Wilms, L.; Jovanovich, A. (2010) Natamycin L: Request for Waiver of 5 Acute 

Toxicity Tests. Unpublished study prepared by Keller and Heckman LLP. 16 p.

48105410 Kuhn, J. (2009) Natamycin Liquid Formulation: Acute Eye Irritation Study in 

Rabbits: Final Report. Project Number: 12753/09. Unpublished study prepared by

Stillmeadow, Inc. 20 p.

48105411 Wach, M. (2010) Natamycin L: Descriptions of Human Activity for Natamycin L. 

Unpublished study prepared by Keller and Heckman LLP. 10 p.

48105500 DSM Food Specialties B. V. (2010) Submission of Product Chemistry and Toxicity

Data in Support of the Application for Registration of Natamycin TGAI and the 

Petition for Tolerance of Natamycin for Use on Mushroom. Transmittal of 14 

Studies.

48105501 Zuur, P.; Hee, P.; Roghoenath, D.; et al. (2010) Natamycin TGAI: Product Identity, 

Composition, and Production. Unpublished study prepared by Keller and Heckman 

LLP. 252 p.

48105502 Zeeman, M.; Boogers, I.; Van der Lee, J.; et al. (2010) Natamycin TGAI: Preliminary

Analysis and Certified Limits. Unpublished study prepared by Keller and Heckman 

LLP. 140 p.

48105503 Van der Lee, J.; Jovanovich, A. (2010) Natamycin TGAI: Physical and Chemical 

Properties. Unpublished study prepared by Keller and Heckman LLP. 9 p.

48105504 Van der Lee, J.; Jovanovich, A. (2010) Stability to Normal and Elevated 

Temperatures, Metals, and Metals Ions. Unpublished study prepared by Keller and 

Heckman LLP. 27 p.
Natamycin Page 26 

Biopesticides Registration Action Document

MRID Citation Reference

48105505 Kuhn, J. (2008) Natamycin TGAI: Acute Oral Toxicity Study (UDP) in Rats: Final 

Report. Project Number: 11403/07. Unpublished study prepared by Stillmeadow, Inc. 

12 p.

48105506 Kuhn, J. (2008) Natamycin TGAI: Acute Dermal Toxicity Study in Rat: Final 

Report. Project Number: 11404/07. Unpublished study prepared by Stillmeadow, Inc. 

13 p.

48105507 Crutchfield, V. (2008) Natamycin TGAI: Acute Inhalation Toxicity Study in Rats: 

Final Report. Project Number: 11405/07. Unpublished study prepared by

Stillmeadow, Inc. 19 p.

48105508 Kuhn, J. (2008) Natamycin TGAI: Acute Eye Irritation Study in Rabbits: Final 

Report. Project Number: 11406/07. Unpublished study prepared by Stillmeadow, Inc. 

18 p.

48105509 Kuhn, J. (2008) Natamycin TGAI: Acute Dermal Irritation Study in Rabbits: Final 

Report. Project Number: 11407/07. Unpublished study prepared by Stillmeadow, Inc. 

13 p.

48105510 Kuhn, J. (2008) Natamycin TGAI: Skin Sensitization: Local Lymph Node Assay in 

Mice: Final Report. Project Number: 11408/07. Unpublished study prepared by

Stillmeadow, Inc. 13 p.

48105511 Otterdijk, F. (2003) Natamycin TGAI: 90 Day Oral Toxicity Study with Natamycin 

in the Rat. Project Number: NOTOX/PROJECT/339323, 002019. Unpublished study

prepared by Notox B.V. 220 p.

48105512 Knickerbocker, M. (1979) Natamycin TGAI: Teratologic Evaluation of Pimaricin in 

Dutch-Belted Rabbits. Project Number: 5906. Unpublished study prepared by Food 

& Drug Research Laboratories, Inc. 290 p.

48105513 Verspeek, C. (2002) Natamycin TGAI: Evaluation of the Mutagenic Activity of 

Natamycin in the Salmonella typhimurium Reverse Mutation Assay and the 

Escherichia coli Reverse Mutation Assay (with Independent Rat). Project Number: 

NOTOX/PROJECT/339345. Unpublished study prepared by Notox B.V. 29 p.

48105514 Meerts, I. (2002) Natamycin TGAI: Evaluation of the Ability of Natamycin to Induce 

Chromosome Aberrations in Cultured Peripheral Human Lymphocytes. Project 

Number: NOTOX/PROJECT/339356. Unpublished study prepared by Notox B.V. 28 

p.

48439300 DSM Food Specialties (2011) Submission of Product Chemistry Data in Support of 

the Application for Registration of Natamycin L. Transmittal of 1 Study.

48439301 van der Lee, J.; Jovanovich, A. (2011) 12-Month Interim Report for Storage Stability

and Corrosion Characteristics: Natamycin L. Project Number: STAB/SLD/09/008. 

Unpublished study prepared by DSM Food Specialties B.V. 38 p.
Natamycin Page 27 

Biopesticides Registration Action Document

MRID Citation Reference

48544501 van der Lee, J.; Jovanovich, A. (2011) 18-Month Final Report for Storage Stability

and Corrosion Characteristics: Natamycin L. Project Number: STAB/SLD/09/008. 

Unpublished study prepared by DSM Food Specialties B.V. 41p.

48593401 Cox, G.; Bailey, D. (1973) Natamycin TGAI Rat Development Toxicity Study. 

Project Number: 1052. Unpublished study prepared by Food & Drug Research 

Laboratories, Inc. 495p.

48613501 Thate, C.; Jovanovich, A. (2011) Natamycin TGAI: Request for Waiver of 

Teratology Study Data Requirement. Unpublished study prepared by Keller and 

Heckman LLP and DSM Food Specialities. 177p.

B. EPA Risk Assessment Memoranda

U.S. EPA. 2010- Jones, Russell, Science Review in Support of Natamycin Technical, Containing 

91.02% Natamycin as Its Active Ingredient. Memorandum dated 10/15/2010 

2011a. Jones, Russell, Science Review in Support of Natamycin Technical, Containing 91.02% 

Natamycin as Its Active Ingredient. Memorandum dated 04/04/2011

U.S. EPA. 2011b. Jones, Russell, Science Review in Support of Natamycin Technical, 

Containing 91.02% Natamycin as Its Active Ingredient. Memorandum dated 07/11/2011.

U.S. EPA. 2011c. Jones, Russell, Science Review in Support of Natamycin Technical, 

Containing 91.02% Natamycin as Its Active Ingredient. Memorandum dated 12/13/2011 

06/16/2011.

C. References

Joint FAO/WHO Expert Committee on Food Additives (JECFA). 2001. Safety Evaluation of 

Certain Food Additives and Contaminants. Natamycin (Pimaricin). WHO Food Additives 

Series: 48 http://www.inchem.org/documents/jecfa/jecmono/v48je06.htm

Joint FAO/WHO Expert Committee on Food Additives (JECFA). 2006. Summary and 

Conclusions. Sixty-Seventh Meeting. Rome, 20-29 June 2006. 

ftp://ftp.fao.org/ag/agn/jecfa/jecfa67_final.pdf (Accessed 04/04/2011)

European Food Safety Authority (EFSA). 2009. Scientific opinion on the use of Natamycin (E 

235) as a food additive. EFSA Panel of Food Additives and Nutrient Sources added to Food 

(ANS). EFSA Journal 7(12):1412, 25 p. http://www.efsa.europa.eu/en/efsajournal/doc/1412.pdf

(Accessed 04/04/2011)
Natamycin Page 28 

Biopesticides Registration Action Document

USDA/ERS. 2010. Mushrooms: Supply and Utilization and Per Capita Consumption. 

February 2010 Update. www.ers.usda.gov/data/foodconsumption/spreadsheets/mushroom.xls

(Accessed 04/04/2011). 

World Health Organization (WHO). 2009. The WHO Recommended Classification of 

Pesticides by Hazard and Guidelines to Classification. 

Joint FAO/WHO Expert Committee on Food Additives (JECFA). 1968, 1976, 2002, 2006, and 

2007. See EFSA 2009 for specific reference citations.

European Food Safety Authority (EFSA). 2009. Scientific opinion on the use of Natamycin (E 

235) as a food additive. EFSA Panel of Food Additives and Nutrient Sources added to Food 

(ANS). EFSA Journal 7(12):1412, 25 p. http://www.efsa.europa.eu/en/efsajournal/doc/1412.pdf

(Accessed 04/04/2011)

USDA/ERS. 2010. Mushrooms: Supply and Utilization and Per Capita Consumption. 

February 2010 Update. www.ers.usda.gov/data/foodconsumption/spreadsheets/mushroom.xls

(Accessed 04/04/2011). 

REFERENCES CITED BY EFSA (2009).

Blankwater, Y. J. and W. Hespe. 1979. Autoradiographic and bioautographic study of the 

distribution of oral Natamycin in the rat. Unpublished report No. 20.502, dated 8 May 1979 

from Gist-Brocdades NV, Delft.

Cox, G. E., D. E. Bailey, and K. Morgareidge. 1973. Multigeneration studies in rats with 

Delvocid brand of Pimaricin. Unpublished report No. 1-1052 submitted to WHO by Food and 

Drug Research Laboratories, Inc.

Hespe, W. and A. M. Meier. 1980. Studies involving in regard to the resorption of radioactivity 

following the oral administration of 14C-pimaricin, applied on cheese, in comparison to other 

oral forms of administration. Unpublished report No. 20.532, dated 4 February 1980, submitted 

to WHO by Gist-Brocades NV, Haarlem. 

Hutchinson, E. B., W. E. Ribelin, and G. J. Levinskas. 1966. Report on acid-degraded 

Pimaricin: Ninety-eight day repeated feeding to rats. Unpublished report submitted to WHO by

American Cyanamid Co., Central Medical Department. 

Levinskas, G. J., C. B. Shaffer, C. Bushey, M. L. Kunde, D. W. Stackhouse, L. B. Vidone, B. 

Javier, and E. Monell. 1963. Two year feeding study in rats. Unpublished report from the 

Central Medical department. Submitted to WHO by American Cyanamid Co.

Levinskas, G. J., W. E. Ribelin, and C. B. Shaffer. 1966. Acute and chronic toxicity of 

Pimaricin. Toxicology and Applied Pharmacology 8: 97-109. 

Morgenstern, A. P. and G. J. A. M. Muskens. 1976. Further data on the toxicity of the 

decomposition products of Pimaricin. Unpublished report Gist-Brocades NV, Delft, 4 pages. 
Natamycin Page 29 

Biopesticides Registration Action Document

Pacifici, G. M. and R. Nottoli. 1995. Placental transfer of drugs administered to the mother. 

Clinical Pharmacokinetics 28(3): 235-269. 

Van Ecken, C. J., R. D. R. Birtwhistle, and M. J. e. Aboulwafa-wan Velthoven. 1984. Three 

months study in dogs of the toxicity of Natamycin by addition to the food. Unpublished report

12.401, 24 October 1984. Submitted to WHO by Gist-Brocades Research and Development. 

