Rule2023-22199
Ledprona Double-Stranded RNA; 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
October 5, 2023
Effective
October 5, 2023
Issuing agencies
Environmental Protection Agency
Abstract
This regulation establishes an exemption from the requirement of a tolerance for residues of Ledprona double-stranded (ds) RNA in or on potato when used as a foliar-applied insecticide for the selective control of Colorado potato beetle and in accordance with label directions and good agricultural practices. GreenLight Biosciences, Inc. 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 residues of Ledprona dsRNA under FFDCA when used in accordance with this exemption.
Full Text
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<title>Federal Register, Volume 88 Issue 192 (Thursday, October 5, 2023)</title>
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[Federal Register Volume 88, Number 192 (Thursday, October 5, 2023)]
[Rules and Regulations]
[Pages 69039-69043]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-22199]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2021-0269; FRL-10944-01-OCSPP]
Ledprona Double-Stranded RNA; 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 Ledprona double-stranded (ds) RNA in or
on potato when used as a foliar-applied insecticide for the selective
control of Colorado potato beetle and in accordance with label
directions and good agricultural practices. GreenLight Biosciences,
Inc. submitted a petition to EPA under the Federal Food, Drug, and
[[Page 69040]]
Cosmetic Act (FFDCA), requesting an exemption from the requirement of a
tolerance. This regulation eliminates the need to establish a maximum
permissible level for residues of Ledprona dsRNA under FFDCA when used
in accordance with this exemption.
DATES: This regulation is effective October 5, 2023. Objections and
requests for hearings must be received on or before December 4, 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-2021-0269, is available online at
<a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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: Madison Le, 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) 305-7090; email address:
<a href="/cdn-cgi/l/email-protection#622032322624302c0d160b010711220712034c050d14"><span class="__cf_email__" data-cfemail="511301011517031f3e2538323422113421307f363e27">[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 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 Government Printing Office's e-CFR site at <a href="https://www.ecfr.gov/current/title-40">https://www.ecfr.gov/current/title-40</a>. To access the OCSPP test guidelines
referenced in this document electronically, please go to <a href="https://www.epa.gov/ocspp">https://www.epa.gov/ocspp</a> 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(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-2021-0269 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
December 4, 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-2021-0269, 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/contacts.html">https://www.epa.gov/dockets/contacts.html</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 and Statutory Findings
In the Federal Register of June 28, 2021 (86 FR 33922) (FRL-10025-
08), 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 1F8900) by GreenLight Biosciences, Inc., 200 Boston Ave.,
Suite 1000, Medford, MA 02155. The petition requested that 40 CFR part
180 be amended by establishing an exemption from the requirement of a
tolerance for residues of Ledprona dsRNA in or on all agricultural
commodities and food products. That document referenced a summary of
the petition prepared by the petitioner GreenLight Biosciences, Inc.,
which is available in the docket, <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 data supporting the petition and in
accordance with its authority under FFDCA section 408(d)(4)(A)(i), EPA
is establishing a tolerance exemption for residues of Ledprona dsRNA in
or on potato only, rather than all agricultural commodities and food
products as requested. The reasons for this change are explained in
Unit III.C.
In addition, EPA previously established a temporary tolerance
exemption for residues of Ledprona dsRNA in or on potato (40 CFR
180.1403; 88 FR 28427) in conjunction with Experimental Use Permit
(EUP) No. 94614-EUP-1 issued to GreenLight BioSciences, Inc. in May
2023. The temporary tolerance exemption expires on April 30, 2025.
Because this action establishes a permanent tolerance exemption for
residues of Ledprona dsRNA in or on potato, EPA is removing the
temporary tolerance exemption as no longer necessary.
III. Final Rule
A. EPA's Safety Determination
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 it 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) and (D). FFDCA section 408(b)(2)(C) requires
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
[[Page 69041]]
infants and children from aggregate exposure to the pesticide chemical
residue. . . . '' Additionally, FFDCA section 408(b)(2)(D) requires
that the Agency consider factors including ``available information
concerning the cumulative effects of a particular pesticide's
residues'' and ``other substances that have a common mechanism of
toxicity.''
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. A full explanation of the data upon which EPA
relied and its risk assessment based on those data can be found within
the document entitled ``Final human health risk assessment, review of
product characterization and manufacturing process for the new end-use
product, Calantha<SUP>TM</SUP>, containing 0.8% of the new active
ingredient ``Ledprona'' dsRNA'' (Human Health Risk Assessment). This
document, as well as other relevant information, is available in the
docket for this action at docket ID number EPA-HQ-OPP-2021-0269.
Ledprona (CAS# 2433753-68-3) 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 (mRNA), preventing the translation of the
mRNA to proteins. Ledprona dsRNA 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.
Available data and scientific information have demonstrated that,
with regard to humans, Ledprona presents no adverse effects of concern
and exposure to the active ingredient will be insignificant. Dietary
and drinking water exposure resulting from the proposed use is expected
to be minimal due to the following factors: (1) the application rate is
low (0.53 oz/acre/calendar year); (2) residues of Ledprona dsRNA on
food will be limited, as Ledprona dsRNA is a foliar insecticide and is
expected to undergo rapid degradation due to microbes in the
environment once applied; (3) mammals possess physiological barriers to
dsRNA uptake (i.e., nucleases in saliva and the gastrointestinal tract,
acidic conditions in the stomach, and presence of multiple membrane
barriers); and (4) Ledprona dsRNA degrades rapidly in simulated gastric
and intestinal fluids, including when combined with certain tank mix
components (i.e., fungicides and insecticides commonly used on
potatoes). This information allows EPA to rely on a well-established
history of exposure to RNA molecules via food and supports the
conclusion that dietary exposure from the use of the active ingredient
will be negligible.
With respect to dietary and drinking water hazards, submitted data
demonstrate that Ledprona dsRNA is expected to pose minimal hazard.
Ledprona dsRNA was found to have low toxicity via the oral route of
exposure (EPA Toxicity Category IV). In addition, a bioinformatic
analysis was conducted to evaluate the likelihood of off-target effects
of the Ledprona dsRNA in humans in silico (i.e., by computer analysis
of Ledprona RNA segments). This analysis identified two potential human
transcripts as ``off targets.'' However, further analyses of these
transcripts coupled with the specificity of Ledprona dsRNA to its
target indicate that Ledprona is not expected to affect these genes in
vivo, resulting in negligible hazard.
Ledprona is not proposed for residential use and therefore a
residential exposure assessment was not conducted. For non-occupational
exposure, bystander exposure may occur post-application (i.e., contact
with treated foliage or through spray drift of nearby treated areas).
Due to the low application rate coupled with spray drift advisories and
restrictions on product labels, exposure via contact with treated
foliage and spray drift is considered to be negligible. 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 dsRNA has been identified as no toxicity has been shown
for Ledprona dsRNA in the submitted studies. Therefore, EPA has not
assumed that Ledprona dsRNA 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 dsRNA. As a result, an
additional margin of safety for the protection of infants and children
is unnecessary.
Based upon the evaluation described above and in the Human Health
Risk Assessment, 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 dsRNA. This
includes all anticipated dietary exposures and all other 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
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. Revisions to Petitioned-for Tolerance Exemption
The petitioner requested that EPA establish a permanent tolerance
exemption for residues of Ledprona dsRNA in or on all agricultural
commodities and food products. EPA previously established a temporary
tolerance exemption for residues of Ledprona dsRNA in or on potato in
conjunction with EUP No. 94614-EUP-1. The exposure analysis and
evaluation of additional data to establish this permanent tolerance
exemption is based in part upon the specificity of Ledprona dsRNA to
its target organism, the Colorado potato beetle, and the proposed use
of Ledprona dsRNA on potatoes. No other use of Ledprona dsRNA on other
agricultural commodities or food products has been proposed. As a
result, EPA has not assessed whether use of Ledprona dsRNA on
commodities other than potatoes would result in the same dietary
exposures described in the current evaluation. Consequently, the
permanent tolerance exemption for Ledprona dsRNA residues that EPA is
granting in this action varies from what the petitioner sought and is
limited to residues of Ledprona dsRNA in or on potato when used as a
foliar-applied insecticide for the selective control of Colorado potato
beetle and in
[[Page 69042]]
accordance with label directions and good agricultural practices.
D. Conclusion
Based on the conclusions detailed in Unit III.A. and 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
dsRNA. Therefore, an exemption is established for residues of Ledprona
dsRNA in or on potato when used as a foliar-applied insecticide for the
selective control of Colorado potato beetle and in accordance with
label directions and good agricultural practices. In addition, EPA is
replacing the previously established temporary tolerance exemption for
Ledprona dsRNA (40 CFR 180.1403) with this permanent tolerance
exemption.
IX. Statutory and Executive Order Reviews
Additional information about these statutes and Executive Orders
can be found at <a href="https://www.epa.gov/laws-regulations/laws-and-executive-orders#influence">https://www.epa.gov/laws-regulations/laws-and-executive-orders#influence</a>.
A. Executive Orders 12866: Regulatory Planning and Review and 14094:
Modernizing Regulatory Review
This action is exempt from review by the Office of Management and
Budget (OMB) under Executive Orders 12866, October 4, 1993 (58 FR
51735), as amended by Executive Order 14094 (88 FR 21879, April 11,
2023), because it establishes or modifies a pesticide tolerance or a
tolerance exemption under FFDCA section 408, and also applies to
tolerance revocations for which extraordinary circumstances do not
exist.
B. Paperwork Reduction Act (PRA)
This action does not impose an information collection burden under
the PRA, 44 U.S.C. 3501 et seq., because it does not contain any
information collection activities.
C. Regulatory Flexibility Act (RFA)
I certify that this action will not have a significant economic
impact on a substantial number of small entities under the RFA, 5
U.S.C. 601 et seq. In making this determination, EPA concludes that the
impact of concern for this rule is any significant adverse economic
impact on small entities and that the Agency is certifying that this
rule will not have a significant economic impact on a substantial
number of small entities because the rule has no net burden on small
entities subject to the rule.
D. Unfunded Mandates Reform Act (UMRA)
This action does not contain any unfunded mandate as described in
UMRA, 2 U.S.C. 1531-1538, and does not significantly or uniquely affect
small governments. The action imposes no enforceable duty on any state,
local or tribal governments or the private sector.
E. Executive Order 13132: Federalism
This action does not have federalism implications as specified in
Executive Order 13132, August 10, 1999 (64 FR 43255) because it will
not have substantial direct effects on the states, on the relationship
between the national government and the states, or on the distribution
of power and responsibilities among the various levels of government.
F. Executive Order 13175: Consultation and Coordination With Indian
Tribal Governments
This action does not have tribal implications as specified in
Executive Order 13175, November 9, 2000 (65 FR 67249), because it will
not have substantial direct effects on tribal governments, on the
relationship between the Federal government and the Indian tribes, or
on the distribution of power and responsibilities between the Federal
government and Indian tribes.
G. Executive Order 13045: Protection of Children From Environmental
Health Risks and Safety Risks
This action is not subject to Executive Order 13045 (62 FR 19885,
April 23, 1997) because it is not a significant regulatory action under
section 3(f)(1) of Executive Order 12866, and because EPA does not
believe the environmental health or safety risks addressed by this
action present a disproportionate risk to children. However, EPA's
Policy on Children's Health applies to this action.
This rule finalizes a tolerance action under the FFDCA, which
requires 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 . . .'' (FFDCA 408(b)(2)(C)). Consistent with FFDCA
section 408(b)(2)(D), and the factors specified therein, EPA has
reviewed the available scientific data and other relevant information
in support of this final tolerance action.
H. Executive Order 13211: Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution or Use
This action is not subject to Executive Order 13211, May 22, 2001
(66 FR 28355), because it is not a significant regulatory action under
Executive Order 12866.
I. National Technology Transfer Advancement Act (NTTAA)
This action does not involve technical standards under the NTTAA
section 12(d), 15 U.S.C. 272.
J. Executive Order 12898: Federal Actions To Address Environmental
Justice in Minority Populations and Low-Income Populations
Executive Order 12898 (59 FR 7629, February 16, 1994) directs
federal agencies, to the greatest extent practicable and permitted by
law, to make environmental justice part of their mission by identifying
and addressing, as appropriate, disproportionately high and adverse
human health or environmental effects of their programs, policies, and
activities on minority populations (people of color and/or indigenous
peoples) and low-income populations. EPA has considered the safety
risks for the pesticide subject to this rulemaking and in the context
of the tolerance action set out in this rulemaking. EPA believes that
the human health and environmental conditions that exist prior to this
action do not result in disproportionate and adverse effects on people
of color, low-income populations, and/or indigenous peoples.
Furthermore, EPA believes that this action is not likely to result in
new disproportionate and adverse effects on people of color, low-income
populations and/or indigenous peoples.
K. Congressional Review Act (CRA)
This action is subject to the CRA, 5 U.S.C. 801 et seq., and EPA
will submit a rule report to each House of the Congress and to the
Comptroller General of the United States. 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.
[[Page 69043]]
Dated: September 29, 2023.
Edward Messina,
Director, Office of Pesticide Programs.
Therefore, for the reasons stated in the preamble, 40 CFR chapter I
is amended 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. Revise Sec. 180.1403 to subpart D to read as follows:
Sec. 180.1403 Ledprona double-stranded RNA (CAS# 2433753-68-3);
exemption from the requirement of a tolerance.
An exemption from the requirement of a tolerance is established for
residues of Ledprona dsRNA in or on potato when used as a foliar-
applied insecticide for the selective control of Colorado potato beetle
and in accordance with label directions and good agricultural
practices.
[FR Doc. 2023-22199 Filed 10-4-23; 8:45 am]
BILLING CODE 6560-50-P
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