Document ID: EPA-HQ-OPP-2014-0834-0004
Agency: epa
Document Type: Rule
Title: Tolerance Requirements; Exemptions: Defensin Proteins derived from spinach in Citrus Plants
Posted Date: 2015-05-06T04:00Z

[Federal Register Volume 80, Number 87 (Wednesday, May 6, 2015)]
[Rules and Regulations]
[Pages 25943-25946]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-10486]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 174

[EPA-HQ-OPP-2014-0834; FRL-9926-99]

Defensin Proteins (SoD2 and SoD7) Derived From Spinach (Spinacia 
oleracea L.) in Citrus Plants; Temporary Exemption From the Requirement 
of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a temporary exemption from the 
requirement of a tolerance for residues of SoD2 and SoD7, two defensin 
proteins derived from spinach (Spinacia oleracea L.), in or on citrus 
when used as plant-incorporated protectants (PIPs) in accordance with 
the terms of Experimental Use Permit (EUP) No. 88232-EUP-1. Southern 
Gardens Citrus submitted a petition to EPA under the Federal Food, 
Drug, and Cosmetic Act (FFDCA), requesting the temporary tolerance 
exemption. This regulation eliminates the need to establish a maximum 
permissible level for residues of SoD2 and SoD7 in or on citrus. The 
temporary tolerance exemption expires on April 18, 2018.

DATES: This regulation is effective May 6, 2015. Objections and 
requests for hearings must be received on or before July 6, 2015, 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-2014-0834, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., 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: Robert McNally, Biopesticides and 
Pollution Prevention Division (7511P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200

[[Page 25944]]

Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone 
number: (703) 305-7090; email address: BPPDFRNotices@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. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

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 Publishing Office's e-CFR site at 
http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

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-2014-0834 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 6, 2015. 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 (excluding any Confidential Business Information (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 the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2014-0834, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.html.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Background and Statutory Framework

    In the Federal Register of January 28, 2015 (80 FR 4525) (FRL-9921-
55), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 
petition (PP 4F8289) by Southern Gardens Citrus, 1820 Country Road 833, 
Clewiston, FL 33440. The petition requested that 40 CFR part 174 be 
amended by establishing a temporary exemption from the requirement of a 
tolerance for residues of spinach defensin (SoD2 and SoD7) proteins in 
or on citrus. That document referenced a summary of the petition 
prepared by the petitioner Southern Gardens Citrus, which is available 
in the docket, http://www.regulations.gov. A comment was received on 
the notice of filing. EPA's response to this comment is discussed in 
Unit VII.C.
    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 FFDCA section 408(c)(2)(B), in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take into account the factors set forth in 
FFDCA section 408(b)(2)(C), 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, FFDCA section 408(b)(2)(D) 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 FFDCA section 408(b)(2)(D), 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.
    Diverse defensin proteins are expressed by most eukaryotic species 
to combat various bacterial and fungal organisms. Homologous proteins 
have also diverged in evolution to provide functions related to plant 
stresses such as heat and drought.
    There is a long history of mammalian consumption of the entire 
spinach plant (both raw and cooked) as food, without causing any known 
deleterious human health effects or any evidence of toxicity. Spinach 
plant leaves have long been part of the human diet and there have been 
no findings that indicate toxicity or allergenicity of spinach 
proteins. Spinach is commonly regarded as a ``super food'' that serves 
as an excellent source of vitamins, minerals, and antioxidants. Recent 
U.S. consumption statistics indicate that, on average, 2 lbs. of 
spinach are consumed per person per year in the United States. 
``Spinach Profile,'' Agricultural Marketing Resource Center (June 2013) 
(http://www.agmrc.org/commodities_products/vegetables/spinach-profile/
). Similarly, citrus whole fruits and juices have been an important 
part of the

[[Page 25945]]

American and international diets for centuries. ``History of Citrus,'' 
All Foods Natural (2013) (available online at: http://www.allfoodnatural.com/article/history-of-citrus.html). Available 
studies demonstrate that spinach defensin 2 (SoD2) and spinach defensin 
7 (SoD7) proteins have very low oral toxicity. In an acute oral 
toxicity study conducted with a single dose of 5,000 milligram/kilogram 
(mg/kg) of microbial-produced SoD2 protein, no evidence of toxic or 
adverse effects was observed. Due to the high similarity between SoD2 
and SoD7, the toxicity assessment is applicable to both proteins.
    In an in vitro study, microbial-produced SoD2 and SoD7 proteins 
were rapidly and extensively hydrolyzed in stimulated gastric and 
intestinal conditions in the presence of pepsin (at pH 1.2) and 
pancreatin, respectively. Both microbial-produced SoD2 and SoD7 
proteins demonstrated half-lives of approximately five minutes when 
subjected to pepsin digest, and both proteins were completely 
proteolyzed to amino acids and small peptide fragments in less than one 
minute in the presence of 0.15 milligram/liter (mg/ml) pancreatin. 
These results indicate that both the SoD2 and SoD7 proteins are highly 
susceptible to degradation in conditions similar to the human digestive 
tract.
    A literature search was performed to identify any published studies 
that might implicate these spinach proteins as allergens. No scientific 
references were found to suggest possible allergenicity associated with 
these spinach proteins. Sequence comparisons were made between the 
novel proteins from spinach, SoD2 and SoD7, against those of known and 
putative allergens using FASTA3 to search the AllergenOnline.org 
database using full-length matches, sliding window of 80 amino acids 
and finally 8-mer identity searches. In addition, the sequences were 
searched against the National Center for Biotechnology Information 
(NCBI) Protein database without keyword limits to identify highly 
related proteins and with the keyword limit of allergen, to find any 
high scoring identity matches to proteins annotated as allergens, as a 
check on the AllergenOnline.org data. No significant sequence matches 
were found between either SoD2 or SoD7 and any allergens. Thus there 
are no potential safety concerns related to allergenicity that would 
require further testing.

IV. Aggregate Exposures

    In examining aggregate exposure, FFDCA section 408 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).
    The Agency has considered available information on the aggregate 
exposure levels of consumers (and major identifiable subgroups of 
consumers) to the pesticide chemical residue and to other related 
substances. These considerations include dietary exposure under the 
tolerance exemption and all other tolerances or exemptions in effect 
for the plant-incorporated protectant chemical residue, and exposure 
from non-occupational sources. The Agency anticipates that there may be 
dietary exposure to the pesticide from the consumption of citrus 
products. In addition, people have a long history of consumption of 
spinach and will continue to be exposed to defensin proteins through 
consumption of spinach. Since the PIP is integrated into the plants 
genome, the Agency has concluded, based upon previous science reviews, 
that residues in drinking water will be extremely low or non-existent. 
Non-occupational exposure via the skin or inhalation is not likely 
since the plant-incorporated protectant is contained within plant 
cells, which essentially eliminates these exposure routes or reduces 
these exposure routes to negligible. In any event, there are no non-
dietary non-occupational uses of SoD2 and SoD7 as it is only used in 
agricultural settings.

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.''
    Since SoD2 and SoD7 proteins do not act through a toxic mode of 
action nor do the SoD2 and SoD7 proteins appear to produce a toxic 
metabolite produced by other substances, the proteins do not have a 
common mechanism of toxicity with other substances; therefore, the 
requirements of section 408(b)(2)(D)(v) do not apply.

VI. Determination of Safety for U.S. Population, Infants and Children

    FFDCA section 408(b)(2)(C) provides that, in considering the 
establishment of a tolerance or tolerance exemption for a pesticide 
chemical residue, 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 exposure (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 exposure (safety) will 
be safe for infants and children. This additional margin of exposure 
(safety) is commonly referred to as the Food Quality Protection Act 
Safety Factor (FQPA SF). 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 information discussed in Unit III., EPA concludes that 
there are no threshold effects of concern to infants, children, or 
adults from exposure to the spinach defensin proteins SoD2 and SoD7. As 
a result, EPA concludes that no additional margin of exposure (safety) 
is necessary to protect infants and children and that not adding any 
additional margin of exposure (safety) will be safe for infants and 
children.
    Therefore, based on the discussion in Units III and IV, 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 spinach defensin proteins SoD2 and SoD7 in 
citrus, when it is used as a plant-incorporated protectant. Such 
exposure includes all anticipated dietary exposures and all other 
exposures for which there is reliable information. The Agency has 
arrived at this conclusion based on a lack of toxicity and 
allergenicity of the SoD2 and SoD7 proteins.

VII. Other Considerations

A. Endocrine Disruptors

    The pesticidal active ingredient is a protein, derived from a 
source that is not known to exert an influence on the endocrine system. 
Therefore, the Agency is not requiring information on the endocrine 
effects of the plant-incorporated protectant at this time.

[[Page 25946]]

B. Analytical Enforcement Methodology

    A standard operating procedure for an enzyme-linked immunosorbent 
assay for the detection and quantification of spinach defensin proteins 
SoD2 and SoD7 in citrus plant tissue has been judged useful for its 
intended purpose.

C. Response to Comments

    EPA received one comment relevant to this petition. The comment 
supports this tolerance exemption and therefore warrants no response.

VIII. Conclusion

    The Agency concludes that there is a reasonable certainty that no 
harm will result to the U.S. population, including infants and 
children, from aggregate exposure residues of spinach defensin SoD2 and 
SoD7 proteins in or on citrus. This includes all anticipated dietary 
exposures and all other exposures for which there is reliable 
information. The Agency has arrived at this conclusion because, as 
discussed previously no toxicity to mammals has been observed, nor is 
there any indication of allergenicity potential for the plant-
incorporated protectant.
    Therefore, an exemption is established for residues of spinach 
defensin SoD2 and SoD7 proteins in or on citrus when the protein is 
used as a PIP in citrus plants.

IX. Statutory and Executive Order Reviews

    This action establishes a temporary exemption from the requirement 
of a tolerance under FFDCA section 408(d) 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 action has been exempted from review 
under Executive Order 12866, this action 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 action 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 FFDCA section 408(d), such as the 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 action 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 FFDCA section 408(n)(4). 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 action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    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 (NTTAA) (15 U.S.C. 272 note).

X. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
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 
the rule in the Federal Register. This action is not a ``major rule'' 
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 174

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: April 28, 2015.
Robert McNally,
Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 174--[AMENDED]

0
1. The authority citation for part 174 continues to read as follows:

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

0
2. Add Sec.  174.535 to subpart W to read as follows:

Sec.  174.535  Spinach Defensin proteins; temporary exemption from the 
requirement of a tolerance.

    (a) Residues of the defensin protein SoD2 derived from spinach 
(Spinacia oleracea L.) in or on citrus food commodities are temporarily 
exempt from the requirement of a tolerance when used as a plant-
incorporated protectant in citrus plants in accordance with the terms 
of Experimental Use Permit No. 88232-EUP-1. This temporary exemption 
from the requirement of a tolerance expires on April 18, 2018.
    (b) Residues of the defensin protein SoD7 derived from spinach 
(Spinacia oleracea L.) in or on citrus food commodities are temporarily 
exempt from the requirement of a tolerance when used as a plant-
incorporated protectant in citrus plants in accordance with the terms 
of Experimental Use Permit No. 88232-EUP-1. This temporary exemption 
from the requirement of a tolerance expires on April 18, 2018.

[FR Doc. 2015-10486 Filed 5-5-15; 8:45 am]
 BILLING CODE 6560-50-P