Rule2023-09486
Ledprona (CAS# 2433753-68-3) for Use in or on Potato; Temporary Exemption From the Requirement of a Tolerance
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
May 4, 2023
Effective
May 4, 2023
Issuing agencies
Environmental Protection Agency
Abstract
This regulation establishes a temporary exemption from the requirement of a tolerance for residues of Ledprona (CAS# 2433753-68-3) in or on potatoes when used in accordance with the terms of Experimental Use Permit (EUP) No. 94614-EUP-1. GreenLight Bioscience, Inc. submitted a petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA) for a temporary exemption from the requirement of a tolerance for residues of Ledprona on all raw agricultural products and food products. After reviewing the petition and supporting data, the Agency has limited the temporary tolerance exemption to residues of Ledprona on potatoes only. This regulation eliminates the need to establish a maximum permissible level for residues of Ledprona in or on potatoes. This temporary tolerance exemption expires on April 30, 2025.
Full Text
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<title>Federal Register, Volume 88 Issue 86 (Thursday, May 4, 2023)</title>
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[Federal Register Volume 88, Number 86 (Thursday, May 4, 2023)]
[Rules and Regulations]
[Pages 28427-28430]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-09486]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2022-0932; FRL-10947-01-OCSPP]
Ledprona (CAS# 2433753-68-3) for Use in or on Potato; 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 Ledprona (CAS# 2433753-68-3)
in or on potatoes when used in accordance with the terms of
Experimental Use Permit (EUP) No. 94614-EUP-1. GreenLight Bioscience,
Inc. submitted a petition to EPA under the Federal Food, Drug, and
Cosmetic Act (FFDCA) for a temporary exemption from the requirement of
a tolerance for residues of Ledprona on all raw agricultural products
and food products. After reviewing the petition and supporting data,
the Agency has limited the temporary tolerance exemption to residues of
Ledprona on potatoes only. This regulation eliminates the need to
establish a maximum permissible level for residues of Ledprona in or on
potatoes. This temporary tolerance exemption expires on April 30, 2025.
DATES: This regulation is effective May 4, 2023. Objections and
requests for hearings must be received on or before July 3, 2023, 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-20-2022-0932, is available at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> 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, and the telephone number for the OPP Docket is (202) 566-
1744. Please review the visitor instructions and additional information
about the docket available at <a href="https://www.epa.gov/dockets">https://www.epa.gov/dockets</a>.
FOR FURTHER INFORMATION CONTACT: Frank Ellis, Biopesticides and
Pollution Prevention Division (7511M), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington,
DC 20460-0001; main telephone number: (703) 328-3074; email address:
<a href="/cdn-cgi/l/email-protection#3e7c6e6e7a786c70514a575d5b4d7e5b4e5f10595148"><span class="__cf_email__" data-cfemail="7e3c2e2e3a382c30110a171d1b0d3e1b0e1f50191108">[email protected]</span></a>.
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
[[Page 28428]]
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:
<bullet> Crop production (NAICS code 111).
<bullet> Animal production (NAICS code 112).
<bullet> Food manufacturing (NAICS code 311).
<bullet> 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 Office of the Federal Register's e-CFR site at
<a href="https://www.ecfr.gov/current/title-40">https://www.ecfr.gov/current/title-40</a>.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a(g), 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-2022-0932 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 3, 2023. 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-20-2022-0932, by one
of the following methods:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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.
<bullet> Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW, Washington, DC
20460-0001.
<bullet> Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at <a href="https://www.epa.gov/dockets/where-send-comments-epa-dockets">https://www.epa.gov/dockets/where-send-comments-epa-dockets</a>.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at <a href="https://www.epa.gov/dockets">https://www.epa.gov/dockets</a>.
II. Background
In the Federal Register of January 3, 2023 (88 FR 38) (FRL-9410-08-
OCSPP), 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 (2G9024) by GreenLight Bioscience, Inc., 200 Boston Ave.,
Suite 1000, Medford, MA 02155. The petitioner requested that 40 CFR
part 180 be amended by establishing a temporary exemption from the
requirement of a tolerance for residues of Ledprona on all raw
agricultural products and food products. That document referenced a
summary of the petition prepared by the petitioner GreenLight
Biosciences, Inc., which is available in the docket at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. There were no comments received in response to the
notice of filing.
Based upon review of the petition and associated data and in
accordance with its authority under FFDCA section 408(d)(4)(A)(i) and
(r), EPA is establishing a temporary exemption from the requirement of
a tolerance for residues of Ledprona in or on potatoes only when used
in accordance with the terms of Experimental Use Permit No. 94614-EUP-
1. The EUP is authorized for testing on potatoes only; therefore, the
Agency has limited the temporary tolerance to potatoes alone.
III. Final Rule
A. EPA's Safety Determination
Section 408(r) of FFDCA authorizes EPA to establish a temporary
exemption from the requirement of a tolerance for residues covered by
an experimental use permit issued under the Federal Insecticide,
Fungicide, and Rodenticide Act. That section states that the provisions
of section 408(c)(2) of FFDCA apply to exemptions issued under FFDCA
section 408(r). 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 or tolerance
exemption 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 EPA consider ``available information
concerning the cumulative effects of [a particular pesticide's] . . .
residues and other substances that have a common mechanism of
toxicity.''
EPA evaluated the available toxicity and exposure data for Ledprona
and considered its validity, completeness, and reliability, as well as
the relationship of this information to human risk. In summary, dietary
risk from the use of Ledprona is considered negligible because dietary
exposure to residues of Ledprona in or on food or feed is expected to
be negligible and no adverse effects were observed in toxicity testing.
A full summary of the data upon which EPA relied and its risk
assessments based on that data can be found within the document
entitled, ``Human health and product characterization for the
Experimental Use Permit application for Calantha<SUP>TM</SUP>,
containing 0.8% of the new active ingredient `Ledprona' dsRNA for use
on potatoes and associated petition to establish a temporary tolerance
exemption'' (Human Health Risk Assessment). This document, as well as
other relevant information, is available in the docket for this action
as described under ADDRESSES.
Available data have demonstrated that, with regard to humans,
Ledprona presents no adverse effects of concern and exposure to the
active ingredient will be insignificant. Ledprona consists of double-
stranded ribonucleic acid (dsRNA) that induces mortality of the
Colorado potato beetle (Leptinotarsa decemlineata) via a gene silencing
mode of action. When dsRNA is applied, it causes the inhibition (or
silencing) of the gene product, messenger RNA
[[Page 28429]]
(mRNA), preventing the translation of the mRNA to proteins. Ledprona
dsRNA is targets the Proteasome subunit beta type-5 (PSMB5) mRNA
sequence in the Colorado potato beetle. PSMB5 mRNA encodes a protein
that regulates proper folding of other proteins in the Colorado potato
beetle. Once Ledprona is ingested by the Colorado potato beetle, over
time the lack of PSMB5 mRNA leads to the reduction of the PSMB5 protein
and ultimately causes mortality.
Dietary exposure to Ledprona through residues of the active
ingredient in or on food or feed as well as in drinking water is
expected to be negligible. As detailed in the Human Health Risk
Assessment, dietary exposure to Ledprona is anticipated to be limited
for the following reasons: (1) The EUP is limited to foliar application
on potatoes. Underground tubers would not be directly exposed to
Ledprona, so consumption of residues on potatoes is expected to be
limited; (2) Once applied, Ledprona is expected to undergo rapid
degradation due to microbial activity; (3) Submitted data show that
Ledprona rapidly degrades in the mammalian gut; and (4) Mammals possess
physiological barriers (i.e., nucleases in saliva and gastrointestinal
tract, acidic conditions in the stomach, presence of multiple membrane
barriers) that prevent uptake of dsRNA. Ledprona is expected to degrade
within 20-25 hours after application at the EUP label rates in
microbially rich environments (e.g., soil) Further, Ledprona rapidly
degrades in simulated gastric fluids (within 10 minutes in simulated
intestinal fluid and within 20 minutes in simulated gastric fluid) and
degrades at similar rates as RNA extracted from plants. This
information allows EPA to rely on a well-established history of
exposure to RNA molecules via food. These data indicate that dietary
exposure from the use of this active ingredient is considered
negligible.
In addition to the lack of exposure described above, submitted
acute oral toxicity studies demonstrated a lack of hazard of Ledprona
to the mammalian surrogate species, rats, in vivo. A bioinformatic
analysis was conducted to evaluate the likelihood of off-target effects
of the Ledprona dsRNA in humans in silico, by computer analysis of
Ledprona RNA segments. The analysis represents the potential for
Ledprona dsRNA 21-mers (21 nucleotide segments) to match RNA segments
in the human transcriptome (i.e., the set of all human RNA transcripts,
including coding and non-coding). The analysis identified three
Ledprona 21-mers which display the potential to match and subsequently
silence target mRNAs in silico. The three 21-mers are predicted to
overlap with non-coding RNAs. However, the analysis assumes that the
21-mers identified would be capable of bypassing physiological barriers
to access the cell nucleus in sufficient quantities. As described
above, submitted data show that Ledprona rapidly degrades in the
mammalian gut, and the physiological barriers present in mammals (i.e.,
nucleases in saliva and gastrointestinal tract, acidic conditions in
the stomach, presence of multiple membrane barriers) impede the uptake
of dsRNA, therefore negating any silencing potential of the 21-mer
partial matches via the oral route of exposure.
The potential for residential exposure is highly unlikely because
there are no residential uses proposed for the EUP under which Ledprona
would be applied. Non-occupational exposure is unlikely because
applications will occur in experimental plots generally not accessible
to bystanders. However, should bystander exposure occur post-
application (i.e., contact with treated foliage), adverse effects are
not expected since Ledprona is non-toxic through the dermal route of
exposure.
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.'' No risk of cumulative toxicity/effects
from Ledprona have been identified as no toxicity has been shown for
Ledprona in the submitted studies. Therefore, EPA has not assumed that
Ledprona has a common mechanism of toxicity with other substances.
Although FFDCA section 408(b)(2)(C) provides for an additional
tenfold margin of safety for infants and children in the case of
threshold effects, EPA has determined that there are no such effects
due to the lack of toxicity of Ledprona. As a result, an additional
margin of safety for the protection of infants and children is
unnecessary.
Based upon its evaluation, EPA concludes that there is reasonable
certainty that no harm will result to the U.S. population, including
infants and children, from aggregate exposure to residues of Ledprona
in or on potatoes. This includes all anticipated dietary exposures for
which there is reliable information. The Agency has arrived at this
conclusion based on the rapid degradation of the active ingredient in
environmental and biological conditions, mammalian physiological
barriers limiting the uptake of dsRNA, and the lack of effects observed
in toxicity testing.
B. Analytical Enforcement Methodology
EPA has determined that 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.
C. Conclusion
Based upon its evaluation in the Human Health Risk Assessment, 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 residues of Ledprona in or on potatoes. Therefore, a
temporary exemption from the requirement of a tolerance is established
for residues of Ledprona in or on potatoes when used in accordance with
the terms of Experimental Use Permit No. 94614-EUP-1.
IV. Statutory and Executive Order Reviews
This action establishes a tolerance exemption 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.
[[Page 28430]]
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).
V. 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: May 1, 2023.
Frank Ellis,
Acting Director, Biopesticides and Pollution Prevention Division,
Office of Pesticide Programs.
Therefore, for the reasons stated in the preamble, EPA is amending
40 CFR part 180 as follows:
PART 180--TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES
IN FOOD
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. 180.1403 to subpart D to read as follows:
Sec. 180.1403 Ledprona; temporary exemption from the requirement of a
tolerance.
A temporary exemption from the requirement of a tolerance is
established for residues of Ledprona in or on potato when used in
accordance with the terms of Experimental Use Permit No. 94614-EUP-1.
This temporary exemption from the requirement of a tolerance expires on
April 30, 2025.
[FR Doc. 2023-09486 Filed 5-3-23; 8:45 am]
BILLING CODE 6560-50-P
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