
[Federal Register Volume 81, Number 168 (Tuesday, August 30, 2016)]
[Rules and Regulations]
[Pages 59499-59503]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-20547]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2016-0034; FRL-9947-19]


Citrus tristeza Virus Expressing Spinach Defensin Proteins 2, 7, 
and 8; 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 the Citrus tristeza virus 
expressing spinach defensin proteins 2, 7, and 8 alone or in various 
combinations on citrus fruit (Citrus spp., Fortunella spp., Crop Group 
10-10) when applied/used as a microbial pesticide in accordance with 
the terms of Experimental Use Permit (EUP) No. 88232-EUP-2. 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 Citrus tristeza virus expressing 
spinach defensin proteins 2, 7, and 8 alone or in various combinations. 
The temporary tolerance exemption expires on August 31, 2020.

DATES: This regulation is effective August 30, 2016. Objections and 
requests for hearings must be received on or before October 31, 2016, 
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-2016-0034, 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 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 Printing 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-2016-0034 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 
October 31, 2016. 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

[[Page 59500]]

by docket ID number EPA-HQ-OPP-2016-0034, 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 Findings

    In the Federal Register of March 29, 2016 (81 FR 17422) (FRL-9943-
67), 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 5F8418) by Southern Gardens Citrus, 1820 County Road 833, 
Clewiston, FL 33440. The petition requested that 40 CFR part 180 be 
amended by establishing a temporary exemption from the requirement of a 
tolerance for residues of Citrus tristeza virus expressing spinach 
defensin proteins 2, 7, and 8 alone or in various combinations. 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. There were no comments received in response 
to the notice of filing; however, several comments were received in 
response to the notice of issuance for the associated Experimental Use 
Permit No. 88232-EUP-2 that related to food safety and are found in 
Docket ID No. EPA-HQ-OPP-2016-0035. EPA's response to these comments is 
contained in Unit VII.B.
    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.
    The pesticide chemical is Citrus tristeza virus that has been 
genetically altered to express spinach defensin proteins 2 (SoD2), 7 
(SoD7), and 8 (SoD8) to combat Citrus Greening disease. Although EPA 
did not receive data on the altered virus itself, EPA has sufficient 
data to evaluate each component of the pesticide individually--i.e., 
the Citrus tristeza virus and the spinach defensin proteins 2, 7, and 
8. Assessing overall risk based on the virus and spinach defensin 
proteins' individual risks is reasonable because the antimicrobial 
spinach defensin proteins are unlikely to change the host range of the 
plant virus and the plant virus is unlikely to affect the toxicity or 
allergenicity profile of the antimicrobial spinach defensin proteins.
    The U.S. human population has been exposed to the Citrus tristeza 
(C. tristeza) virus in citrus products for at least two decades since 
its discovery as being widespread in the Florida citrus industry in the 
mid-1990s. No adverse effects from this exposure in people have been 
reported. This lack of adverse effects is consistent with the fact that 
C. tristeza is a plant virus, which do not cause disease in humans; 
human intestines commonly harbor plant viruses without any adverse 
effect. (Ref 1).
    Spinach defensin proteins are naturally found in every spinach 
plant, and oral exposure to the spinach plant provides exposure to 
these proteins. There is a long history of mammalian consumption of the 
entire spinach plant (both raw and cooked)--including necessarily--
these defensin proteins, 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.
    Bioinformatic sequence comparisons to assess the toxicity potential 
of spinach defensin proteins 2 (SoD2), 7 (SoD7), and 8 (SoD8) yielded 
no potential significant toxicity matches. Furthermore, literature 
searches did not produce any papers that showed any mammalian toxicity 
associated with spinach or spinach defensins. Available data 
demonstrate that SoD2, SoD7, and SoD8 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. Since SoD 
proteins are consumed in spinach without adverse effect and SoD2, SoD7, 
and SoD8 are similar both functionally in spinach and in regards to 
their amino acid sequence, the results of the acute oral toxicity study 
are applicable to all three proteins.
    Because SoD2, SoD7, and SoD8 are proteins, EPA also evaluated their 
potential for allergenicity. 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 spinach or these spinach 
proteins. Finding no indication that these proteins are derived from a 
known allergenic source, EPA also considered the proteins' 
bioinformatics and resistance to digestibility.
    Searching both the AllergenOnline.org database and the National 
Center for Biotechnology Information (NCBI) Protein database for 
sequence

[[Page 59501]]

similarities to known allergens, no significant sequence matches to 
SoD2, SoD7, and SoD8 were found using a sliding window of 80 amino 
acids.
    In an in vitro study, microbial produced SoD2 and SoD7 proteins 
were rapidly and extensively hydrolyzed in simulated 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.
    An evaluation of the similarities of SoD8 compared to SoD2 and SoD7 
proteins to estimate SoD8 protein digestibility indicates that SoD8 
should be digested very similarly to SoD2 and SoD7. The sequences are 
homologous, but SoD8 is longer on both the beginning and the end of the 
sequence. The proteins were found to be nearly identical in major 
overlapping sequences, while SoD8 has one more pepsin cleavage site 
compared to SoD2 and SoD7 which indicates that it will be even more 
susceptible to digestion.
    Based on the source, bioinformatics, and digestibility of these 
proteins, EPA concludes that these spinach defensin proteins will not 
pose any allergenicity concerns. In sum, EPA concludes that due to the 
lack of toxicity and pathogenicity concerns for C. tristeza and any 
toxicity or allergenicity concerns for the spinach defensin proteins 2, 
7, and 8, the altered C. tristeza virus expressing those spinach 
defensin proteins does not pose any toxicity, pathogenicity, or 
allergenicity concerns. Therefore, EPA did not identify any points of 
departure for regulating exposure, and a qualitative assessment was 
conducted. For further information about EPA's assessment of the Citrus 
tristeza virus that has been genetically altered to express spinach 
defensin proteins 2 (SoD2), 7 (SoD7), and 8 (SoD8), see the C. tristeza 
SoD2, SoD7, and SoD8 Human Health Review March 2016 found in Docket ID 
No. EPA-HQ-OPP-2016-0035.

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 residue from genetically engineered C. tristeza expressing spinach 
defensins SoD2, SoD7, and SoD8, and exposure from non-occupational 
sources.
    The Agency anticipates that there may be dietary exposure to Citrus 
tristeza virus expressing spinach defensin proteins 2, 7, and 8 (either 
alone or in combinations with each other) from the consumption of 
citrus products treated with this pesticide. Significant dietary 
exposure to spinach defensin proteins 2, 7, and 8 (either alone or in 
combinations with each other) from use of this pesticide is not 
expected due to the very low expression of the defensin proteins from 
the C. tristeza vector. Dietary exposure to spinach defensins from 
consumption of treated citrus products containing them will be far 
below the amount consumed from raw and cooked spinach. 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/). EPA 
has also approved another experimental use permit (88232-EUP-1) 
involving use of defensin proteins SoD2 and SoD7, to which people may 
be exposed. 75 kg of SoD proteins were authorized for treatment of 720 
acres in Florida and Texas. May 6, 2015 (80 FR 25943) (FRL-9926-99) and 
August 28, 2015 (80 FR 52270) (FRL-9931-26). In terms of non-pesticidal 
dietary exposure, the U.S. population will continue to be exposed to C. 
tristeza virus through infected citrus plants and will continue to be 
exposed to these spinach defensin proteins through consumption of 
spinach plants.
    Residues in drinking water from use of this pesticide will be 
extremely low or non-existent since the pesticide will be present only 
in the vascular tissue of citrus trees and is applied under the bark, 
and it is highly unlikely that any environmental exposure will occur.
    The Agency does not expect there to be any non-occupational 
exposure to this pesticide chemical residue. Exposure via the skin or 
inhalation is not likely since the viral vector will be phloem limited 
in citrus trees, and very little phloem is present in citrus fruit, 
which essentially eliminates these exposure routes or reduces these 
exposure routes to negligible.

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 EPA consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.''
    Citrus tristeza virus expressing spinach defensin proteins 2, 7, 
and 8 (either alone or in combinations with each other) is not toxic 
and does not have a common mechanism of toxicity with other substances. 
Consequently, section 408(b)(2)(D)(v) does not apply.

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

A. Children's Safety Factor

    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 2, 7, and 8. As a result, EPA 
concludes that no additional margin of exposure (safety) is

[[Page 59502]]

necessary to protect infants and children and that not adding any 
additional margin of exposure (safety) will be safe for infants and 
children.

B. Determination of Safety

    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 C. tristeza virus expressing 
spinach defensin proteins 2, 7, and 8. 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 C. tristeza virus 
expressing spinach defensin proteins 2, 7, and 8.

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 based on the lack of any 
toxicity or allergenicity of the C. tristeza virus expressing spinach 
defensin proteins 2, 7, and 8.

B. Response to Comments

    Five non-governmental organizations opposed the issuance of the 
temporary exemption from the requirement for a tolerance in order to 
prevent the issuance of the related experimental use permit (EUP). 
Their objections on the EUP focused on concerns about the potential for 
environmental impacts as a result of the pesticide spreading beyond the 
field trial boundaries of the EUP. They did not raise any concern about 
the human health or safety of the pesticide itself. Without more, the 
commenters have not provided a basis on which the Agency should 
reconsider issuing this temporary tolerance exemption. The FFDCA 
requires EPA to make a safety finding about the pesticide; the 
statutory scope of that review is focused on human health, not 
environmental, impacts.

VIII. Conclusion

    Therefore, a temporary exemption is established for residues of 
Citrus tristeza virus expressing spinach defensin proteins 2, 7, and 8 
alone or in various combinations on commodities in the fruit, citrus, 
group 10-10, when used in accordance with the Experimental Use Permit 
No. 88232-EUP-2. Because Experimental Use Permit No. 88232-EUP-2 will 
expire on August 31, 2019, EPA is similarly limiting the term of this 
exemption; this temporary exemption from the requirement of a tolerance 
will expire on August 31, 2020.

IX. Reference

    1. U.S. Environmental Protection Agency. Meeting Minutes of the 
FIFRA Scientific Advisory Panel Meeting Held December 6-8, 2005 on 
Plant-Incorporated Protectants Based on Virus Coat Protein Genes: 
Science Issues Associated with the Proposed Rule, http://www.regulations.gov. Docket No. EPA-HQ-OPP-2005-0249-12.

X. Statutory and Executive Order Reviews

    This action establishes an 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).

XI. 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 180

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

    Dated: August 10, 2016.
Robert McNally,
Director, Biopesticides and Pollution Prevention Division, 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. Add Sec.  180.1337 to subpart D to read as follows:


Sec.  180.1337  Citrus tristeza virus expressing spinach defensin 
proteins 2, 7, and 8; exemption from the requirement of a tolerance.

    A temporary exemption from the requirement of a tolerance is 
established for residues of the microbial pesticide Citrus tristeza 
virus expressing spinach defensin proteins 2, 7, and 8 (either alone or 
in combinations with each

[[Page 59503]]

other) in or on the commodities listed in fruit, citrus group 10-10, 
when used in accordance with the terms of Experimental Use Permit No. 
88232-EUP-2. This temporary exemption from the requirement of a 
tolerance expires on August 31, 2020.

[FR Doc. 2016-20547 Filed 8-29-16; 8:45 am]
BILLING CODE 6560-50-P


