Federal Register / Vol. 77, No. 97 / Friday, May 18, 2012 / Rules and Regulations 29543 

Executive Order 13175 (65 FR 67249, 

November 9, 2000), because it does not 

have substantial direct effects on an 

Indian Tribe. The Catawba Indian 

Nation Reservation is located within the 

South Carolina portion of the bi-state 

Charlotte Area. Pursuant to the Catawba 

Indian Claims Settlement Act, S.C. Code 

Ann. 27–16–120, ‘‘all state and local 

environmental laws and regulations 

apply to the [Catawba Indian Nation] 

and Reservation and are fully 

enforceable by all relevant state and 

local agencies and authorities.’’ EPA 

notes today’s action will not impose 

substantial direct costs on Tribal 

governments or preempt Tribal law. 

The Congressional Review Act, 5 

U.S.C. 801 et seq., as added by the Small 

Business Regulatory Enforcement 

Fairness Act of 1996, generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report, which includes a 

copy of the rule, to each House of the 

Congress and to the Comptroller General 

of the United States. EPA will submit a 

report containing this action and other 

required information to the U.S. Senate, 

the U.S. House of Representatives, and 

the Comptroller General of the United 

States prior to publication of the rule in 

the Federal Register. A major rule 

cannot take effect until 60 days after it 

is published in the Federal Register. 

This action is not a ‘‘major rule’’ as 

defined by 5 U.S.C. 804(2). 

Under section 307(b)(1) of the CAA, 

petitions for judicial review of this 

action must be filed in the United States 

Court of Appeals for the appropriate 

circuit by July 17, 2012. Filing a petition 

for reconsideration by the Administrator 

of this final rule does not affect the 

finality of this action for the purposes of 

judicial review nor does it extend the 

time within which a petition for judicial 

review may be filed, and shall not 

postpone the effectiveness of such rule 

or action. Parties with objections to this 

direct final rule are encouraged to file a 

comment in response to the parallel 

notice of proposed rulemaking for this 

action published in the proposed rules 

section of today’s Federal Register, 

rather than file an immediate petition 

for judicial review of this direct final 

rule, so that EPA can withdraw this 

direct final rule and address the 

comment in the proposed rulemaking. 

This action may not be challenged later 

in proceedings to enforce its 

requirements. See section 307(b)(2). 

List of Subjects in 40 CFR Part 52 

Environmental protection, Air 

pollution control, Incorporation by 

reference, Intergovernmental relations, 

Nitrogen dioxide, Ozone, Reporting and 

recordkeeping requirements, Volatile 

organic compounds. 

Dated: May 8, 2012. 

A. Stanley Meiburg, 

Acting Regional Administrator, Region 4. 

40 CFR part 52 is amended as follows: 

PART 52—[AMENDED] 

■ 1. The authority citation for part 52 

continues to read as follows: 

Authority: 42 U.S.C. 7401 et seq. 

Subpart PP—South Carolina 

■ 2. Section 52.2120(e) is amended by 

adding a new entry for ‘‘South Carolina 

portion of bi-state Charlotte; 1997 8- 

Hour Ozone 2002 Base Year Emissions 

Inventory’’ to the end of the table to 

read as follows: 

§ 52.2120 Identification of plan. 

* * * * * 

(e) 

EPA-APPROVED SOUTH CAROLINA NON-REGULATORY PROVISIONS

Provision 

State 

effective 

date 

EPA approval date Explanation 

*******

South Carolina portion of bi-state Charlotte; 1997 8-Hour Ozone 2002 Base 

Year Emissions Inventory.

04/29/2010 05/18/2012 [Insert citation of publication] Applicable to the 1997 8-hour Ozone 

boundary in York County only (Rock 

Hill-Fort Mill Area Transportation 

Study Metropolitan Planning Organization Area). 

[FR Doc. 2012–12003 Filed 5–17–12; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2010–0727; FRL–9349–2] 

Natamycin; Exemption From the 

Requirement of a Tolerance 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes an 

exemption from the requirement of a 

tolerance for residues of the 

biochemical, natamycin, in or on 

mushrooms when applied as a fungistat 

to prevent the germination of fungal 

spores on mushrooms produced in 

mushroom production facilities. DSM 

Food Specialties B.V. (DSM) submitted 

a petition to EPA under the Federal 

Food, Drug, and Cosmetic Act (FFDCA), 

requesting an exemption from the 

requirement of a tolerance. This 

regulation eliminates the need to 

establish a maximum permissible level 

for such residues of natamycin. 

DATES: This regulation is effective May 

18, 2012. Objections and requests for 

hearings must be received on or before 

July 17, 2012, and must be filed in 

accordance with the instructions 

provided in 40 CFR part 178 (see also 

Unit I.C. of the SUPPLEMENTARY

INFORMATION). 

ADDRESSES: The docket for this action, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2010–0727; 

FRL–9349–2, is available either 

electronically through http://www.

regulations.gov or in hard copy at the 

OPP Docket in the Environmental 

Protection Agency Docket Center (EPA/ 

DC), located in EPA West, Rm. 3334, 

1301 Constitution Ave. NW., 

Washington, DC 20460–0001. The 

Public Reading Room is open from 8:30 

a.m. to 4:30 p.m., Monday through 

Friday, excluding legal holidays. The 

telephone number for the Public 

Reading Room is (202) 566–1744, and 

the telephone number for the OPP 

Docket is (703) 305–5805. Please review 

the visitor instructions and additional 

information about the docket available 

at http://www.epa.gov/dockets. 

FOR FURTHER INFORMATION CONTACT: 

Cheryl Greene, Biopesticides and 


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29544 Federal Register / Vol. 77, No. 97 / Friday, May 18, 2012 / Rules and Regulations 

Pollution Prevention Division (7511P), 

Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave. NW., Washington, 

DC 20460–0001; telephone number: 

(703) 308–0352, email address: greene.

cheryl@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this action apply to me? 

You may be potentially affected by 

this action if you are an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. Potentially 

affected entities may include, but are 

not limited to: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

This listing is not intended to be 

exhaustive, but rather provides a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

B. How can I get electronic access to 

other related information? 

You may access a frequently updated 

electronic version of 40 CFR part 180 

through the Government Printing 

Office’s e-CFR site at http://ecfr.

gpoaccess.gov/cgi/t/text/text-idx?&c=

ecfr&tpl=/ecfrbrowse/Title40/40tab_

02.tpl. To access the harmonized test 

guidelines referenced in this document 

electronically, please go to http://www.

epa.gov/ocspp and select ‘‘Test Methods 

and Guidelines.’’ 

C. How can I file an objection or hearing 

request? 

Under FFDCA section 408(g), 21 

U.S.C. 346a, any person may file an 

objection to any aspect of this regulation 

and may also request a hearing on those 

objections. You must file your objection 

or request a hearing on this regulation 

in accordance with the instructions 

provided in 40 CFR part 178. To ensure 

proper receipt by EPA, you must 

identify docket ID number EPA–HQ– 

OPP–2010–0727 in the subject line on 

the first page of your submission. All 

objections and requests for a hearing 

must be in writing, and must be 

received by the Hearing Clerk on or 

before July 17, 2012. Addresses for mail 

and hand delivery of objections and 

hearing requests are provided in 40 CFR 

178.25(b).

In addition to filing an objection or 

hearing request with the Hearing Clerk 

as described in 40 CFR part 178, please 

submit a copy of the filing that does not 

contain any CBI for inclusion in the 

public docket. Information not marked 

confidential pursuant to 40 CFR part 2 

may be disclosed publicly by EPA 

without prior notice. Submit a copy of 

your non-CBI objection or hearing 

request, identified by docket ID number 

EPA–HQ–OPP–2010–0727, by one of 

the following methods: 

• Federal eRulemaking Portal: 

http://www.regulations.gov. Follow the 

online instructions for submitting 

comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave. NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. Deliveries 

are only accepted during the Docket 

Facility’s normal hours of operation 

(8:30 a.m. to 4 p.m., Monday through 

Friday, excluding legal holidays). 

Special arrangements should be made 

for deliveries of boxed information. The 

Docket Facility telephone number is 

(703) 305–5805. 

II. Background and Statutory Findings 

In the Federal Register of April 20, 

2011, (76 FR 22067) (FRL–8869–7), EPA 

issued a notice pursuant to section 

408(d)(3) of FFDCA, 21 U.S.C. 

346a(d)(3), announcing the notice of 

filing of a pesticide tolerance petition 

(PP 0F7729), by DSM Food Specialties 

B.V. (DSM), Alexander Fleminglaan 1, 

2613 AX Delft, The Netherlands, c/o 

Keller and Heckman, LLP, 1001 G Street 

NW., Washington, DC 20001. The 

petition requested that 40 CFR part 180 

be amended by establishing an 

exemption from the requirement of a 

tolerance for residues of natamycin in or 

on mushrooms when applied as a 

fungistat to mushrooms produced in an 

enclosed mushroom production facility. 

This notice referenced a summary of the 

petition prepared by the petitioner 

which is available in the docket (EPA– 

HQ–OPP–2010–0727) at http:// 

www.regulations.gov. There were no 

comments received in response to the 

notice of filing. 

Section 408(c)(2)(A)(i) of FFDCA 

allows EPA to establish an exemption 

from the requirement for a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the exemption is ‘‘safe.’’ 

Section 408(c)(2)(A)(ii) of FFDCA 

defines ‘‘safe’’ to mean that ‘‘there is a 

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 

occupational exposure. Pursuant to 

section 408(c)(2)(B) of FFDCA, in 

establishing or maintaining in effect an 

exemption from the requirement of a 

tolerance, EPA must take into account 

the factors set forth in section 

408(b)(2)(C) of FFDCA, which require 

EPA to give special consideration to 

exposure of infants and children to the 

pesticide chemical residue in 

establishing a tolerance and to ‘‘ensure 

that there is a reasonable certainty that 

no harm will result to infants and 

children from aggregate exposure to the 

pesticide chemical residue * * *’’ 

Additionally, section 408(b)(2)(D) of 

FFDCA requires that the Agency 

consider ‘‘available information 

concerning the cumulative effects of a 

particular pesticide’s residues’’ and 

‘‘other substances that have a common 

mechanism of toxicity.’’ 

EPA performs a number of analyses to 

determine the risks from aggregate 

exposure to pesticide residues. First, 

EPA determines the toxicity of 

pesticides. Second, EPA examines 

exposure to the pesticide through food, 

drinking water, and through other 

exposures that occur as a result of 

pesticide use in residential settings. 

III. Toxicological Profile 

Consistent with section 408(b)(2)(D) 

of FFDCA, EPA has reviewed the 

available scientific data and other 

relevant information in support of this 

action and considered its validity, 

completeness, and reliability and the 

relationship of this information to 

human risk. EPA has also considered 

available information concerning the 

variability of the sensitivities of major 

identifiable subgroups of consumers, 

including infants and children. 

Natamycin is a naturally occurring 

antimicrobial compound derived from 

the common soil microorganisms, 

Streptomyces natalensis, Streptomyces 

lydicus, and Streptomyces 

chattanoogensis. Natamycin was 

originally discovered in Streptomyces 

natalensis in South Africa in the early 


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1950s, and was subsequently discovered 

to also occur naturally in North America 

in Streptomyces lydicus and 

Streptomyces chattanoogensis. It is 

commercially produced by a submerged 

oxygen-based fermentation of 

Streptomyces natalensis, Streptomyces 

lydicus, or Streptomyces 

chattanoogensis. As a biochemical 

pesticide active ingredient, natamycin is 

intended for use as a fungistat to 

prevent and control the germination of 

mold and yeast spores in the growth 

media of mushrooms produced in 

enclosed mushroom production 

facilities. Natamycin has a non-toxic 

mode of action, has no effects on fungal 

mycelia, and 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 (Ref.1) and is approved as a food 

additive/preservative by the European 

Union, the World Health Organization, 

and individual countries including New 

Zealand and Australia 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 (21CFR 172.155) and 

as an additive to the feed and drinking 

water of broiler chickens to retard the 

growth of specific molds (21CFR 

573.685). Natamycin is also FDA 

approved for use as a treatment to 

suppress fungal eye infections such as 

blepharitis, conjunctivitis, and keratitis. 

EPA has evaluated the available 

toxicity data on natamycin and 

considered their validity, completeness, 

and reliability as well as the 

relationship of the results of the studies 

to human risk. EPA has also considered 

available information concerning the 

variability of the sensitivities of major 

identifiable subgroups of consumers, 

including infants and children, to 

natamycin. Specific information on the 

studies and information received and 

reviewed, the nature of adverse effects 

caused by natamycin as well as the noobserved-adverse-effect-level (NOAEL) 

and the lowest-observed-adverse-effectlevel (LOAEL) from the toxicity studies 

and information are discussed in this 

unit. 

1. Acute toxicity (MRIDs 48105505 

through 48105510). The natamycin 

Technical Grade Active Ingredient 

(TGAI) is classified in 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. 

2. Subchronic toxicity (MRID 

48105511). Subchronic (rat) feeding 

studies demonstrate that the LOAEL 

was 2,000 parts per million (ppm) in the 

diet (204 milligrams/kilogram of body 

weight per day (mg/kg bw/day) for 

males and 238 mg/kg bw/day for 

females) based on significantly lower 

body weight. The NOAEL was 500 ppm 

in the diet (42 mg/kg bw/day for males 

and 48 mg/kg bw/day for females). 

Natamycin is not a mutagen and is not 

cytotoxic. 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. The 

pesticide product is applied in irrigation 

water to mushrooms growing in 

enclosed facilities. There will not be any 

repeated dermal exposure to natamycin 

based on this application method. A 

review of the literature demonstrates 

that natamycin is not a developmental 

or reproductive toxicant at up to 50 mg/ 

kg bw/day in rats and up to 15 mg/kg 

bw/day in rabbits. 

3. Developmental toxicity (MRID 

48613501). In lieu of a study addressing 

prenatal developmental toxicity, 

Guideline Data Requirement (OCSPP 

870.3700), the registrant developed a 

rationale supported with information 

and data obtained from the open 

technical literature to address the data 

requirement (MRID 48613501), which is 

available for review in the docket for 

this tolerance exemption. Based on the 

data, information, and the weight of 

evidence, fetal exposure from oral 

ingestion of natamycin in or on treated 

mushrooms by the mother would likely 

be extremely low. There are no concerns 

for subchronic, chronic, and 

reproductive/developmental toxicity 

resulting from dietary exposure to 

natamycin-treated mushrooms. 

Natamycin is not a subchronic toxicant 

in rats when administered in the diet at 

up to 45 mg/kg bw/day for 96 days, nor 

in dogs at up to 12 mg/kg bw/day for 3 

months (Refs. 2, 3, and 4). Based on a 

lack of observable differences in tumors 

relative to untreated controls, natamycin 

is not a carcinogen in rats or dogs that 

were administered natamycin in the 

daily diet for up to 2 years (Ref. 5). The 

NOAEL for chronic toxicity was 22.4 

mg/kg bw/day in rats and 6.25 mg/kg 

bw/day in dogs, based on reduced body 

weight. Natamycin is not a reproductive 

or developmental toxicant when 

administered to experimental animals at 

≥ 50 mg/kg bw/day in 3-generation and 

2-generation studies with rats (Ref. 6). 

Exposure to dietary natamycin is 

expected to be extremely low. Dietary 

natamycin is rapidly metabolized by 

stomach acids, poorly absorbed by 

mammalian systems; and its degradates 

are rapidly excreted in the feces within 

24 hrs when orally ingested (Refs. 7, 8, 

and 9). Natamycin is a high molecular 

weight compound (666 Daltons) with 

low solubility in water (30–50 ppm at 

20–25 °C) and many organic solvents. 

Chemical compounds having molecular 

weights >600 Daltons are not known to 

diffuse across the placental barrier of 

humans (Ref. 10) and there are no 

known active transport mechanisms for 

natamycin. Further, based on per capita 

consumption of all mushroom 

commodities in the United States (Ref. 

11), dietary intake from treated, 

unwashed mushrooms is conservatively 

estimated to be no more than 0.00030 

milligrams of Active ingredient per 

kilogram of body weight per person per 

day (mg a.i./kg bw/person/day) (Ref.12). 

This value is well below any known 

acute oral, subchronic and chronic 

dietary, reproductive, and 

developmental endpoints for natamycin 

by many orders of magnitude. Likewise, 

the estimated dietary intake from 

unwashed, treated mushrooms also is 

well below the Acceptable Dietary 

Intake (ADI) of 0.3 established by the 

Joint Food Agriculture Organization of 

the United Nations (FAO) and the 

World health Organization Expert 

Committee on Food Additives (JECFA, 

2001 & 2006) and an ADI of 0.1 

established by the European Food Safety 

Authority (Ref. 13). 

4. Other. 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. 

5. Residue analytical method (MRID 

48105407). The registrant developed 

and validated a residue analytical 

method to determine residues of 

natamycin in mushrooms, mushroom 

compost, casing, and casing plus 

inoculum. Samples were extracted in 

methanol, filtered, and then analyzed by 

liquid chromatography with mass 

spectrometry/mass spectrometry 

detection (LC–MS/MS). The analyte was 

quantified by comparison with external 

calibration curve using natamycin 

(88.7% purity). The analytes in 

mushroom samples and casing plus 

inoculum samples were quantified 

using a solvent-based reference standard 

(88.7% natamycin), whereas the 

analytes in compost and casing was 

quantified relative to a matrix-based 

reference standard. Samples were 

fortified with 0.1 or 1.0 mg/kg 

natamycin. Recovery for mushrooms 


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was 89 ± 11%. Overall recovery for 

compost was 84 ± 12%, and for casing 

was 99 ± 16%. Overall recovery for 

casing plus inoculum was 66 ± 8%. The 

limit of quantitation (LOQ) was 0.01 

mg/kg (ppm) for mushrooms and 0.1 

mg/kg for the other matrices. There were 

no interfering substances. The limit of 

detection (LOD) was 0.25 nanograms/ 

milliliter (ng/mL) for the reference 

substances. A copy of the submitted 

Residue Analytical Method (MRID 

48105407) is available for review in the 

docket for this tolerance exemption. 

IV. Aggregate Exposures 

In examining aggregate exposure, 

section 408 of FFDCA directs EPA to 

consider available information 

concerning exposures from the pesticide 

residue in food and all other nonoccupational exposures, including 

drinking water from ground water or 

surface water and exposure through 

pesticide use in gardens, lawns, or 

buildings (residential and other indoor 

uses). 

A. Dietary Exposure 

1. Food exposure. Natamycin is a 

fungistat that has a long history of use 

in food for the prevention of spoilage. In 

evaluating exposure to natamycin, EPA 

considered exposure under the 

submitted tolerance petition for an 

exemption from the requirement of a 

tolerance for natamycin when used to 

control mold spores and fungi in or on 

mushrooms produced in an enclosed 

mushroom production facility. EPA 

assessed dietary exposure from data and 

information submitted by the petitioner, 

as well as publically available literature 

which demonstrates that dietary 

exposure from the use of natamycin as 

a fungistat on mushrooms produced in 

an enclosed mushroom production 

facility is expected to be minimal. Based 

on laboratory testing of the Technical 

Grade Active Ingredient (described 

below), and 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. 

The active ingredient is minimally 

toxic (10.34% of the EP by weight), as 

demonstrated by Tier I Guideline 

toxicity studies. Finally, in connection 

with the proposed use of natamycin as 

a biopesticide intended solely for use in 

enclosed mushroom production 

facilities, all compost and casing used in 

mushroom production will be 

autoclaved prior to being removed from 

the mushroom growing facilities to 

destroy any natamycin residues, thus 

preventing them from entering the 

outdoor environment. Based on the 

mode of action of the active ingredient 

as a fungistat, no aggregate exposure is 

anticipated. 

2. Drinking water exposure. 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 <pH 2 or >pH 10 it 

completely degrades (Ref. 14). 

Natamycin is extremely sensitive to UV 

light and is completely degraded by UV 

within 24 hours of exposure in aqueous 

solution (Ref. 15). Even assuming that 

no environmental degradation takes 

place, gastric juices typically found in 

the human stomach will completely 

degrade natamycin within 24 hrs (Ref. 

16). Finally, the non-definitive 

endpoints for acute oral toxicity (>1820 

ppm) (Ref. 17) and subchronic oral 

toxicity (>500 ppm in the diet) (Ref. 18), 

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. 

V. Cumulative Effects From Substances 

With a Common Mechanism of Toxicity 

Section 408(b)(2)(D)(v) of FFDCA 

requires that, when considering whether 

to establish, modify, or revoke a 

tolerance, the Agency consider 

‘‘available information’’ concerning the 

cumulative effects of a particular 

pesticide’s residues and ‘‘other 

substances that have a common 

mechanism of toxicity.’’ 

EPA has not found natamycin to share 

a common mechanism of toxicity with 

any other substances, and natamycin 

does not appear to produce a toxic 

metabolite produced by other 

substances. For the purposes of this 

tolerance action, therefore, EPA has 

assumed that natamycin does not have 

a common mechanism of toxicity with 

other substances. For information 

regarding EPA’s efforts to determine 

which chemicals have a common 

mechanism of toxicity and to evaluate 

the cumulative effects of such 

chemicals, see EPA’s Web site at 

http://www.epa.gov/pesticides/ 

cumulative. 

VI. Determination of Safety for U.S. 

Population, Infants and Children 

FFDCA section 408(b)(2)(C) provides 

that EPA shall assess the available 

information about consumption patterns 

among infants and children, special 

susceptibility of infants and children to 

pesticide chemical residues and the 

cumulative effects on infants and 

children of the residues and other 

substances with a common mechanism 

of toxicity. In addition, FFDCA section 

408(b)(2)(C) provides that EPA shall 

apply an additional tenfold (10X) 

margin of safety for infants and children 

in the case of threshold effects to 

account for prenatal and postnatal 

toxicity and the completeness of the 

database on toxicity and exposure 

unless EPA determines that a different 

margin of safety will be safe for infants 

and children. This additional margin of 

safety is commonly referred to as the 

FQPA Safety Factor. In applying this 

provision, EPA either retains the default 

value of 10X or uses a different 

additional safety factor when reliable 

data available to EPA support the choice 

of a different factor. 

Based on the acute toxicity and 

pathogenicity data summarized in Unit 

III. EPA concludes that there is a 

reasonable certainty that no harm will 

result to the U.S. population, including 

infants and children, from aggregate 

exposure to the residues of natamycin. 

This includes all anticipated dietary 

exposures and all other exposures for 

which there is reliable information. EPA 

has arrived at this conclusion because 

the data and information available on 

natamycin does not demonstrate toxic, 

pathogenic, and/or infective potential to 

mammals when used as a fungistat to 

prevent the germination of fungal spores 

on mushrooms produced in enclosed 

mushroom production facilities. Thus, 

there are no threshold effects of concern 

and, as a result, an additional margin of 

exposure is not necessary. 

VII. Other Considerations 

A. Analytical Enforcement Methodology 

An analytical method is not required 

for enforcement purposes since the 

Agency is establishing an exemption 

from the requirement of a tolerance 

without any numerical limitation. 

Nonetheless, and as discussed in more 

detail earlier in this final rule, an 

analytical method was submitted with 

the application to register natamycin as 

a new active ingredient. The Agency has 

reviewed the analytical method and 

determined it to be acceptable. 


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B. International Residue Limits 

In making its tolerance decisions, EPA 

seeks to harmonize U.S. tolerances with 

international standards whenever 

possible, consistent with U.S. food 

safety standards and agricultural 

practices. EPA considers the 

international maximum residue limits 

(MRLs) established by the Codex 

Alimentarius Commission (Codex), as 

required by FFDCA section 408(b)(4). 

The Codex Alimentarius is a joint U.N. 

Food and Agriculture Organization/ 

World Health Organization food 

standards program, and it is recognized 

as an international food safety 

standards-setting organization in trade 

agreements to which the United States 

is a party. EPA may establish a tolerance 

that is different from a Codex MRL; 

however, FFDCA section 408(b)(4) 

requires that EPA explain the reasons 

for departing from the Codex level. 

The Codex has not established a MRL 

for natamycin. 

C. Response to Comments 

One anonymous comment was 

received (EPA–HQ–OPP–2010–0685– 

0006) in response to the notice of filing 

for this action. The commenter, who 

focused specifically on the application 

of ‘‘powdered natamycin’’ in cheese 

processing plants (presumably as a 

preservative), expressed the concern 

that natamycin ‘‘is a health hazard’’ and 

further asserted that people at such 

plants have no real protection from 

inhalation or dermal exposures to 

powdered natamycin. In response, the 

Agency notes that under the FFDCA, the 

controlling standard governing EPA’s 

consideration of a petition for a 

tolerance exemption is whether there is 

a reasonable certainty that no harm will 

result from aggregate exposure to 

natamycin, including all anticipated 

dietary exposures and all other nonoccupational exposures for which there 

is reliable information. Worker risk 

issues, therefore, are not relevant in the 

context of the Agency’s assessment of a 

petition for a tolerance exemption under 

the FFDCA. For all the reasons noted in 

this Final Rule, EPA has determined 

that there is a reasonable certainty that 

no harm will result from aggregate 

exposure to residues of natamycin, 

including all anticipated dietary 

exposures and all other (non 

occupational) exposures for which there 

is reliable information. This finding is 

specific to natamycin residues resulting 

in or on mushrooms when natamycin is 

used as a fungistat to prevent the 

germination of fungal spores on 

mushrooms produced in mushroom 

production facilities. Worker risk issues, 

where relevant, were taken into 

consideration in the context of EPA’s 

separate consideration (under FIFRA) of 

the applications for registration of the 

pesticide products containing 

natamycin as a new biochemical active 

ingredient for use on mushrooms in 

enclosed mushroom production 

facilities. Specifically, EPA reviewed, 

among other things, data and 

information (MRIDS 48105505 and 

48105510) submitted specifically to 

address the Agency’s data requirements 

for dermal and inhalation toxicity 

(OCSPP 870.1200; 870.1300, 8703250 

and 870.3465). Based on that review, the 

Agency categorized natamycin as a 

toxicity IV active ingredient Toxicity 

Categories are determined based on 

hazard indicators by considering oral, 

dermal, inhalation and eyes routes of 

exposure. A Toxicity Category IV is 

defined as a pesticide product that is 

non toxic or slightly toxic and not an 

irritant by all routes of and determined 

that natamycin, as formulated in the two 

products (EPA File Symbol 87485–1 and 

87485–2) at issue, is reasonably not 

expected to cause harm when used 

according to product labeling. Finally, 

in light of the commenter’s focus on 

powdered natamycin, it is also worth 

noting that the one end use product that 

EPA is registering does not contain 

powdered natamycin. Instead, it is 

contained in a liquid suspension 

formulation that is directly added to 

irrigation water using standard 

irrigation equipment. In addition, all 

mixers, loaders, applicators and 

handlers will be required through 

instructions on the product label to 

wear personal protective garments 

(protective eyewear, long sleeved shirt, 

long pants and socks and shoes). To be 

clear, though, these separate registration 

decisions under FIFRA are not the focus 

of or at issue in connection with this 

Final Rule granting a tolerance 

exemption under the FFDCA. 

VIII. Conclusions 

Therefore, an exemption from the 

requirement of a tolerance is established 

for residues of natamycin in or on 

mushrooms when used as a fungistat to 

prevent the germination of fungal spores 

on mushrooms produced in enclosed 

mushroom production facilities. 

IX. References 

1. Joint FAO/WHO Expert Committee on 

Food Additives (JECFA). 1968, 1969, 

1976, 2002, 2006, and 2007. See EFSA 

2009 for specific reference citations. 

2. Hutchinson, E. B., W. E. Ribelin, and G. 

J. Levinskas. 1966. Report on aciddegraded pimaricin: Ninety-eight day 

repeated feeding to rats. Unpublished 

report submitted to WHO by American 

Cyanamid Co., Central Medical 

Department. 

3. Levinskas, G. J., W. E. Ribelin, and C. B. 

Shaffer. 1966. Acute and chronic toxicity 

of pimaricin. Toxicology and Applied 

Pharmacology 8: 97–109. 

4. 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. 

5. 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. 

6. 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. 

7. 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 GistBrocdades NV, Delft. 

8. Hespe, W. and A. M. Meier. 1980. Studies 

involving the resorption of radioactivity 

following the oral administration of 14Cpimaricin, 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. 

9. Morgenstern, A. P. and G. J. A. M. 

Muskens. 1976. Further data on the 

toxicity of the decomposition products of 

pimaricin. Unpublished report GistBrocades NV, Delft, 4 pages. 

10. Pacifici, G. M. and R. Nottoli. 1995. 

Placental transfer of drugs administered 

to the mother. Clinical Pharmacokinetics 

28(3). 

11. 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). 

12. USEPA 2011. Memorandum from R.S. 

Jones to C Greene, dated 04/11/2011. 

13. 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). 

14. USEPA. 2011. Science Review in Support 

of the Registration of natamycin TGAI, a 

Technical Grade Active Ingredient 

(TGAI) Product; and Natamycin L, an 

End-Use Product (EP), Respectively 

Containing 91.02% and 10.34% 

natamycin, a New Active Ingredient. 

Hazard Assessment for Tier I Toxicity 

Studies and Waiver Requests, Tier I NonVerDate Mar<15>2010 16:15 May 17, 2012 Jkt 226001 PO 00000 Frm 00011 Fmt 4700 Sfmt 4700 E:\FR\FM\18MYR1.SGM 18MYR1

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29548 Federal Register / Vol. 77, No. 97 / Friday, May 18, 2012 / Rules and Regulations 

Target Organism Waiver Requests, and 

Metabolism/Residue Studies. 

Memorandum from R. S. Jones to C. 

Greene, dated 04/04/2011. 

15. 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). 

16. Koontz, J. L., J. E. Marcy, W. E. Barbeau, 

and S. E. Duncan. 2003. Stability of 

Natamycin and Its Cyclodextrin 

Inclusion Complexes in Aqueous 

Solution. Journal of Agricultural Food 

Chemistry. 51 (24): 7111–7114. 

17. USEPA. 2011. Science Review in Support 

of the Registration of Natamycin TGAI, a 

Technical Grade Active Ingredient 

(TGAI) Product; and Natamycin L, an 

End-Use Product (EP), Respectively 

Containing 91.02% and 10.34% 

Natamycin, a New Active Ingredient. 

Hazard Assessment for Tier I Toxicity 

Studies and Waiver Requests, Tier I NonTarget Organism Waiver Requests, and 

Metabolism/Residue Studies. 

Memorandum from R. S. Jones to C. 

Greene, dated 04/04/2011. 

18. Subchronic (rat) feeding studies 

demonstrate that the No Observable 

Adverse Effect Level NOAEL was 500 

ppm in the diet (42 mg/kg bw/day for 

males and 48 mg/kg bw/day for females) 

(MRID 48105511). 

X. Statutory and Executive Order 

Reviews 

This final rule establishes a tolerance 

exemption under section 408(d) of 

FFDCA in response to a petition 

submitted to the Agency. The Office of 

Management and Budget (OMB) has 

exempted these types of actions from 

review under Executive Order 12866, 

entitled Regulatory Planning and 

Review (58 FR 51735, October 4, 1993). 

Because this final rule has been 

exempted from review under Executive 

Order 12866, this final rule is not 

subject to Executive Order 13211, 

entitled Actions Concerning Regulations 

That Significantly Affect Energy Supply, 

Distribution, or Use (66 FR 28355, May 

22, 2001) or Executive Order 13045, 

entitled Protection of Children from 

Environmental Health Risks and Safety 

Risks (62 FR 19885, April 23, 1997). 

This final rule does not contain any 

information collections subject to OMB 

approval under the Paperwork 

Reduction Act (PRA), 44 U.S.C. 3501 et 

seq., nor does it require any special 

considerations under Executive Order 

12898, entitled Federal Actions to 

Address Environmental Justice in 

Minority Populations and Low-Income 

Populations (59 FR 7629, February 16, 

1994). 

Since tolerances and exemptions that 

are established on the basis of a petition 

under section 408(d) of FFDCA, such as 

the tolerance exemption in this final 

rule, do not require the issuance of a 

proposed rule, the requirements of the 

Regulatory Flexibility Act (RFA) (5 

U.S.C. 601 et seq.) do not apply. 

This final rule directly regulates 

growers, food processors, food handlers, 

and food retailers, not States or tribes, 

nor does this action alter the 

relationships or distribution of power 

and responsibilities established by 

Congress in the preemption provisions 

of section 408(n)(4) of FFDCA. As such, 

the Agency has determined that this 

action will not have a substantial direct 

effect on States or tribal governments, 

on the relationship between the national 

government and the States or tribal 

governments, or on the distribution of 

power and responsibilities among the 

various levels of government or between 

the Federal Government and Indian 

tribes. Thus, the Agency has determined 

that Executive Order 13132, entitled 

Federalism (64 FR 43255, August 10, 

1999) and Executive Order 13175, 

entitled Consultation and Coordination 

with Indian Tribal Governments (65 FR 

67249, November 9, 2000) do not apply 

to this final rule. In addition, this final 

rule does not impose any enforceable 

duty or contain any unfunded mandate 

as described under Title II of the 

Unfunded Mandates Reform Act of 1995 

(UMRA) (Pub. L. 104–4). 

This action does not involve any 

technical standards that would require 

Agency consideration of voluntary 

consensus standards pursuant to section 

12(d) of the National Technology 

Transfer and Advancement Act of 1995 

(NTTAA), Public Law 104–113, section 

12(d) (15 U.S.C. 272 note). 

XI. Congressional Review Act 

The Congressional Review Act, 5 

U.S.C. 801 et seq., generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and to the Comptroller 

General of the United States. EPA will 

submit a report containing this rule and 

other required information to the U.S. 

Senate, the U.S. House of 

Representatives, and the Comptroller 

General of the United States prior to 

publication of this final rule in the 

Federal Register. This final rule is not 

a ‘‘major rule’’ as defined by 5 U.S.C. 

804(2). 

List of Subjects in 40 CFR Part 180 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and recordkeeping 

requirements. 

Dated: May 8, 2012. 

Steven Bradbury, 

Director, Office of Pesticide Programs. 

Therefore, 40 CFR chapter I is 

amended as follows: 

PART 180—[AMENDED] 

■ 1. The authority citation for part 180 

continues to read as follows: 

Authority: 21 U.S.C. 321(q), 346a and 371. 

■ 2. Section 180.1315 is added to 

subpart D to read as follows: 

§ 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. 

[FR Doc. 2012–12105 Filed 5–17–12; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2010–0048; FRL–9347–9] 

Prohydrojasmon; Amendment of 

Temporary Exemption From the 

Requirement of a Tolerance 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation revises the 

temporary exemption from the 

requirement of a tolerance for residues 

of Prohydrojasmon (PDJ), propyl-3-oxo2-pentylcyclo-pentylacetate, by 

including grapes and extending the date 

of expiration of the temporary tolerance 

exemption from August 1, 2012, to 

August 1, 2014, when used as a plant 

growth regulator pre-harvest and in 

accordance with good agricultural 

practices and with the terms of 

Experimental Use Permit (EUP) No. 

62097–EUP–1. Fine Agrochemicals, 

Ltd., submitted a petition to the U.S. 

Environmental Protection Agency (EPA 

or the Agency) under the Federal Food, 

Drug, and Cosmetic Act (FFDCA), 

requesting the amendment to the 

temporary tolerance exemption. 

DATES: This regulation is effective May 

18, 2012. Objections and requests for 

hearings must be received on or before 

July 17, 2012, and must be filed in 

accordance with the instructions 

provided in 40 CFR part 178 (see also 

Unit I.C. of the SUPPLEMENTARY

INFORMATION). 


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