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[Federal Register Volume 77, Number 97 (Friday, May 18, 2012)]
[Rules and Regulations]
[Pages 29543-29548]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-12105]

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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.

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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

[[Page 29544]]

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

[[Page 29545]]

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 no-observed-adverse-effect-level 
(NOAEL) and the lowest-observed-adverse-effect-level (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 
[deg]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

[[Page 29546]]

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 non-occupational 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 [deg]C and pH 5-7.5; and 
at 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.

[[Page 29547]]

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 
non-occupational 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 acid-degraded 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 Gist-
Brocdades NV, Delft.
8. Hespe, W. and A. M. Meier. 1980. Studies involving 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.
9. 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.
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 
Non-

[[Page 29548]]

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 
Non-Target 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]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. Section 180.1315 is added to subpart D to read as follows:

Sec.  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
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