[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 [www.gpo.gov]
[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 
https://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, 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 https://www.epa.gov/dockets.

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: 
[email protected].

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:
     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 Office of the Federal Register's e-CFR site at 
https://www.ecfr.gov/current/title-40.

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:
     Federal eRulemaking Portal: https://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 https://www.epa.gov/dockets/where-send-comments-epa-dockets.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at https://www.epa.gov/dockets.

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 https://www.regulations.gov. 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 CalanthaTM, 
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