
[Federal Register Volume 88, Number 152 (Wednesday, August 9, 2023)]
[Rules and Regulations]
[Pages 53806-53809]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-17019]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2021-0226; FRL-11264-01-OCSPP]


Flg22-Bt Peptide; 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 Flg22-Bt Peptide in or on all food 
commodities when used as a plant regulator and inducer of local and 
systemic resistance in accordance with label directions and good 
agricultural practices. Elemental Enzymes Ag & Turf, LLC submitted a 
petition, pursuant to section 408(d) of the Federal Food, Drug, and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), requesting an exemption from 
the requirement of a tolerance for the biochemical pesticide Flg22-Bt 
Peptide. This regulation eliminates the need to establish a maximum 
permissible level for residues of Flg22-Bt Peptide under FFDCA when 
used in accordance with this exemption.

DATES: This regulation is effective August 9, 2023. Objections and 
requests for hearings must be received on or before October 10, 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-2021-0226, 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 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: Chris Pfeifer, Biopesticides and 
Pollution Prevention Division (7511P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington, 
DC 20460-0001; main telephone number: (202) 566-1599; 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, greenhouse owner, 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 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-2021-0226 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 10, 2023. Addresses for mail and hand delivery of objections 
and hearing requests are provided in 40 CFR 178.25(b).

[[Page 53807]]

    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-2021-0226 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 and Statutory Findings

    In the Federal Register of April 22, 2021 (86 FR 21317) (FRL-10022-
59), 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 0F8889) by Elemental Enzymes Ag & Turf, LLC, 1685 Galt 
Industrial Blvd. Saint Louis, MO 63132. The petition requested that 40 
CFR part 180 be amended to establish an exemption from the requirement 
of a tolerance for residues of Flg22-Bt Peptide, when used as a plant 
regulator and an inducer of local and systemic resistance in accordance 
with label directions and good agricultural practices. That document 
referenced a summary of the petition prepared by Elemental Enzymes Ag & 
Turf, LLC, which is available in the docket at https://www.regulations.gov. No comments were received on the notice of filing.

III. Aggregate Risk Assessment and Determination of Safety

    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 establishes exemptions from the requirement of a tolerance only 
in those cases where it can be clearly demonstrated that the risks from 
aggregate exposure to pesticide chemical residues under reasonably 
foreseeable circumstances will pose no harm to human health. If EPA is 
able to determine that a tolerance is not necessary to ensure that 
there is a reasonable certainty that no harm will result from aggregate 
exposure to the pesticide chemical residue, an exemption from the 
requirement of a tolerance may be established.
    Consistent with FFDCA section 408(c)(2)(A), and the factors 
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available 
scientific data and other relevant information in support of this 
action. EPA has sufficient data to assess the hazards of and to make a 
determination on aggregate exposure to Flg22-Bt Peptide, including 
exposure resulting from the exemption established by this action. EPA's 
assessment of exposures and risks associated with Flg22-Bt Peptide 
follows.

A. Toxicological Profile

    Flg22-Bt Peptide is a synthetically produced and purified peptide 
containing 22 amino acids. The amino acid sequence is naturally 
occurring and is derived from the Bacillus thuringiensis flagellin 
protein. Bacillus thuringiensis is a ubiquitous soil-dwelling bacterium 
and is a common active ingredient in microbial pesticide products. 
Mode-of-action claims for the active ingredient include activation of 
multiple plant defense mechanisms, promotion of plant growth and 
increased vigor. With regard to activation of plant defenses, it is 
proposed that the active ingredient activates plant cell-surface 
receptor Flagellin-Sensing 2, which results in the initiation of 
various intra- and extra-cellular responses that ultimately inhibit 
pathogen growth.
    As an active ingredient in pesticidal end-use products (EPs), 
Flg22-Bt Peptide is intended to be applied as part of a solution, 
primarily as a spray applied to crops, but also as a commercial seed 
treatment and an injection for trees. Potential exposures to the 
biochemical active ingredient Flg22-Bt Peptide are not expected to 
result in any risks of toxicological concern. The active ingredient is 
naturally occurring and is derived from the Bacillus thuringiensis 
flagellin Deleprotein to which humans are already exposed. (Flagellin 
is the major structural protein of the flagella of Gram-negative 
bacteria, including Bacillus thuringiensis, and these microbes are 
ubiquitous in the environment.) Flg22-Bt Peptide is not expected to 
pose a risk through any pathways for the following reasons. (1) Flg22-
Bt Peptide degrades in the gastrointestinal tract as it is digested by 
the common digestive enzyme Pepsin. (2) This peptide sequence is 
dissimilar to any allergenic peptide sequences. As such, the potential 
for any allergenicity is negligible. (3) Negligible potential for 
allergenicity notwithstanding, Flg22-Bt Peptide is rapidly degraded 
under simulated mammalian gastric conditions and will not persist long 
enough under these conditions to induce an allergic response. (4) 
Flg22-Bt Peptide degrades rapidly in the environment and is not 
anticipated to be present in any concentration outside potential 
naturally occurring background levels. (5) No toxicological endpoints 
have been identified for Flg22-Bt Peptide. All the data submitted in 
support of the registration of this peptide confirm its low toxicity 
profile.
    With regard to the overall toxicological profile, Flg22-Bt Peptide 
is of low toxicity. Acute toxicity data indicate that Flg22-Bt Peptide 
is Toxicity Category IV for acute oral toxicity, acute dermal toxicity, 
dermal irritation, and eye irritation, and Toxicity Category III for 
acute inhalation toxicity. The available data also suggest it is not a 
skin sensitizer. Guideline

[[Page 53808]]

studies were submitted for all the acute toxicity data requirements.
    All subchronic data requirements for the active ingredient Flg22-Bt 
Peptide (90-day oral toxicity, 90-day dermal toxicity and 90-day 
inhalation toxicity) were satisfied with acceptable waiver rationales, 
based on low toxicity and low exposure. The 90-day oral toxicity 
rationale provided the following points of support: (1) Flg22-Bt 
Peptide is of low acute oral toxicity (Toxicity Category IV); (2) based 
on an acceptable in vitro digestion study using simulated gastric 
fluid, Flg22-Bt Peptide is anticipated to be rapidly and completely 
degraded in the gastrointestinal tract; (3) a search of in silico 
databases revealed no similarity in sequence between the Flg22-Bt 
Peptide and any known protein toxins, indicating low toxicity through 
its structural relationships; (4) Flg22-Bt Peptide is naturally 
occurring and is derived from the Bacillus thuringiensis flagellin 
protein to which humans are regularly exposed.; and (5) dietary 
exposure is expected to be negligible based on low application rates 
(e.g., maximum rate of 0.00052 lb AI/acre for foliar applications) and 
rapid degradation in the environment. The 90-day dermal toxicity data 
requirement was also addressed with an acceptable rationale that 
contained the same information provided to address the 90-day oral 
toxicity requirement combined with the following additional 
information: (1) the active ingredient is of low acute dermal toxicity 
(Toxicity Category IV), is only slightly irritating to the skin 
(Toxicity Category IV), and is not a skin sensitizer; and (2) 
significant repeat dermal exposure is not anticipated as the proposed 
end-use products containing this peptide will not be directly applied 
to the skin and will be applied in low concentrations (0.002-0.012%, by 
weight) at low application rates. As a final limitation to dermal 
exposure, personal protective equipment (PPE) required for pesticides 
using Flg22-Bt Peptide (i.e., long-sleeved shirt and long pants, shoes 
plus socks, and waterproof gloves) will mitigate dermal exposure to 
pesticide applicators and other handlers. The 90-day inhalation 
toxicity data requirement was also addressed with an acceptable 
rationale that contained the same information used to address the 90-
day oral toxicity requirement combined with the following additional 
information: (1) Flg22-Bt Peptide is of low acute inhalation toxicity; 
(2) because Flg22-Bt Peptide is of low acute toxicity for all paths of 
exposure, there is minimal concern for localized or portal-of-entry 
inhalation effects; (3) significant repeat inhalation exposure is not 
anticipated as the proposed end-use products will be applied at low 
concentrations of active ingredient (0.002-0.012%, by weight) and at 
low application rates; and (4) based on its physical and chemical 
properties, such as low vapor pressure and high water solubility, 
inhalation exposure due to volatilization is not expected for Flg22-Bt 
Peptide.
    The data requirements for developmental toxicity were also 
satisfied with the submission of an acceptable rationale, which was 
nearly identical to that submitted to satisfy the subchronic toxicity 
data requirements. For details of that rationale, refer to the points 
of support in the preceding paragraph. In short, Flg-22 Bt Peptide is 
of low toxicity and significant exposure from use as a pesticide is not 
anticipated and, as such, is not expected to pose any risks with regard 
to developmental toxicity.
    As for the mutagenicity data requirements, those were satisfied 
through the submission of guideline studies. There were no indications 
of genotoxicity or mutagenicity in the submitted guideline in vitro 
studies. Specifically, there was no evidence of induced mutant colonies 
over background with or without metabolic activation in the reverse 
gene mutation assay in bacteria; and there was no evidence of inducted 
mutant colonies over background with or without metabolic activation in 
the mammalian forward gene mutation assay in Chinese hamster ovary 
cells. All submitted data indicate that Flg22-Bt Peptide is non-
genotoxic and non-mutagenic.

B. Toxicological Points of Departure/Levels of Concern

    No toxicological endpoints have been identified for Flg22-Bt 
Peptide. The active ingredient is of low toxicity, and significant 
exposure is not expected based on the low application rates and rapid 
degradation in the environment.

C. Exposure Assessment

    1. Dietary exposure from food, feed uses, and drinking water. As 
part of its qualitative risk assessment for Flg22-Bt Peptide, the 
Agency considered the potential for dietary exposure to residues of the 
chemical. EPA concludes that dietary (food and drinking water) 
exposures are possible, but they are expected to be negligible based on 
low application rates and rapid degradation in the environment and are 
not anticipated in any concentration outside potential naturally 
occurring background levels. Moreover, no toxicological endpoint of 
concern was identified for Flg22-Bt Peptide; and therefore, a 
quantitative assessment of dietary exposure is not necessary. Dietary 
risk is not of a concern.
    2. Non-dietary exposure. The term ``residential exposure'' is used 
in this document to refer to non-occupational, non-dietary exposure 
(e.g., textiles (clothing and diapers), carpets, swimming pools, and 
hard surface disinfection on walls, floors, tables). There are 
currently no proposed residential uses for this active ingredient, 
although there is a potential for residential post-application exposure 
from pesticide applications to turf. However, no risks of concern have 
been identified for this turf application due to the low toxicity of 
the Flg22-Bt Peptide and negligible exposure based on low application 
rates and rapid degradation in the environment. Therefore, a 
quantitative assessment of residential exposure is not necessary.
    3. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.'' EPA has not found that 
Flg22-Bt Peptide shares a common mechanism of toxicity with any other 
substances, and it does not appear to produce a toxic metabolite 
produced by other substances. For the purposes of this tolerance 
action, therefore, EPA has assumed Flg22-Bt Peptide does not have a 
common mechanism of toxicity with other substances. For information 
regarding EPA's efforts to determine which chemicals have a common 
mechanism of toxicity and to evaluate the cumulative effects of such 
chemicals, see EPA's website at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

D. Safety Factor for Infants and Children

    FFDCA Section 408(b)(2)(C) provides that EPA shall retain an 
additional tenfold (10X) margin of 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 based on reliable data that a different margin of 
safety will be safe for infants and children. This additional margin of 
safety is commonly referred to as the Food Quality Protection Act 
(FQPA) safety factor. In applying this provision, EPA

[[Page 53809]]

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. An FQPA safety factor is not required at this time 
for Flg22-Bt Peptide because no toxicological endpoints have been 
established and the qualitative risk assessment has concluded that 
Flg22-BT Peptide is of low toxicity and that no significant exposures 
are expected.

E. Aggregate Risk

    In accordance with the FFDCA, OPP must consider and aggregate (add) 
pesticide exposures and risks from three major sources: food, drinking 
water, and residential exposures. In an aggregate assessment, exposures 
from relevant sources that have the same toxicological endpoints are 
added together and compared to quantitative estimates of hazard, or the 
risks themselves can be aggregated. When aggregating exposures and 
risks from various sources, EPA considers both the route and duration 
of exposure. A qualitative aggregate risk assessment has been conducted 
for the proposed use of Flg22-Bt Peptide based on the lack of 
identified endpoints in the toxicological database and minimal exposure 
to the active ingredient. No risks of concern have been identified.
    A full explanation of the data upon which EPA relied and its risk 
assessment based on those data can be found within the April 7, 2023, 
document entitled ``Product Chemistry Review and Human Health 
Assessment for a FIFRA Section 3 Registration of Flg22-BtPeptide 
Technical, Containing 70% Flg22-Bt Peptide as the Active Ingredient.'' 
This document, as well as other relevant information, is available in 
the docket for this action as described under ADDRESSES.

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

    Based on the Agency's 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 
Flg22-Bt Peptide.

V. Other Considerations

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.

VI. Conclusion

    Therefore, EPA is establishing an exemption from the requirement of 
a tolerance for residues of Flg22-BtPeptide in or on all food 
commodities when used as a plant regulator and inducer of local and 
systemic resistance in accordance with label directions and good 
agricultural practices.

VII. 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).

VIII. 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 3, 2023.
Edward Messina,
Director, Office of Pesticide Programs.

    Therefore, for the reasons stated in the preamble, EPA is amending 
40 CFR chapter I 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.  180.1405 to subpart D to read as follows:


Sec.  180.1405  Flg22-Bt Peptide; exemption from the requirement of a 
tolerance.

    An exemption from the requirement of a tolerance is established for 
residues of Flg22-Bt Peptide in or on all food commodities when used as 
a plant regulator and inducer of local and systemic resistance in 
accordance with label directions and good agricultural practices.

[FR Doc. 2023-17019 Filed 8-8-23; 8:45 am]
BILLING CODE 6560-50-P


