
[Federal Register Volume 88, Number 153 (Thursday, August 10, 2023)]
[Rules and Regulations]
[Pages 54244-54247]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-17135]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2018-0158; FRL-11022-01-OCSPP]


(2S)-5-Oxopyrrolidine-2-carboxylic Acid (L-PCA); 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 (2S)-5-Oxopyrrolidine-2-carboxylic Acid 
(L-PCA) in or on all food commodities when used as a plant growth 
regulator in accordance with label directions and good agricultural 
practices. Exponent, on behalf of Verdesian Life Sciences U.S., LLC, 
submitted a petition, pursuant to the Federal Food, Drug, and Cosmetic 
Act (FFDCA), asking the EPA to amend its regulations to establish an 
exemption from the requirement of a tolerance for residues of the 
pesticide, when used as a plant growth regulator on agricultural crops, 
turf and ornamental plants. Instead, EPA is establishing an exemption 
from the requirement of a tolerance for residues L-PCA in or on all 
food commodities when applied in buffered end-use products and used in 
accordance with label directions and good agricultural practices. This 
regulation eliminates the need to establish a maximum permissible level 
for residues of L-PCA when used in accordance with this exemption.

DATES: This regulation is effective August 10, 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-2018-0158, 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. For the latest 
status information on EPA/DC services and docket access, visit https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Madison Le, 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) 566-1400; 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-2018-0158 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).
    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-2018-0158, by one of 
the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically

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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 May 18, 2018 (83 FR 23247) (FRL-9976-
87), 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 8F8663) by Exponent, on behalf of Verdesian Life Sciences 
U.S., LLC, 1001 Winstead Dr., Suite 480, Cary, NC 27513. The petition 
requested that 40 CFR part 180 be amended to establish an exemption 
from the requirement of a tolerance for residues of L-PCA, when used as 
a plant growth regulator on agricultural crops, turf, and ornamental 
plants, in accordance with label directions and good agricultural 
practices. That document referenced a summary of the petition prepared 
by the petitioner, Verdesian Life Sciences U.S., LLC, which is 
available in docket EPA-HQ-OPP-2018-0158 at https://www.regulations.gov. No substantive comments were received in response 
to this 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 for L-PCA including exposure 
resulting from the exemption established by this action. EPA's 
assessment of exposures and risks associated with L-PCA follows.

A. Toxicological Profile

    L-PCA is derived from L-glutamic acid via an intramolecular 
condensation reaction. L-PCA is naturally found in mammalian tissues. 
L-PCA has a non-toxic mode of action and can effectively enhance 
upregulation of the glutamine synthesis pathway. When applied to 
plants, it has demonstrated effects, such as increased growth, 
increased nodulation, and greater fresh weight. It also has seed 
priming properties. L-PCA has a long history of use in consumer 
products, including dietary supplements and cosmetic products.
    L-PCA can be applied in various forms (free acids or salts), but it 
releases a common moiety that is the pesticidally-active component and 
serves as the basis for risk assessment and tolerance regulation. Since 
L-PCA is a strong acid, buffered solutions will contain some salt form, 
but not enough at any moment in time to be toxicologically relevant.
    In the field, the above rationale continues to apply when active 
ingredient is in solution. If the products dry out on plants and then 
someone touches them, there would likely be some exposure from the salt 
form, however, it will not change the toxicology since it would not 
stay in the salt form once it was solubilized upon ingestion/contact 
with water.
    With regard to the overall toxicological profile, L-PCA is of low 
toxicity. Acute toxicity data indicate that L-PCA is of low acute oral, 
dermal, and inhalation toxicity. However, with its low pH (2), it is 
likely corrosive. The available data suggest it is not a skin 
sensitizer.
    Studies from the open scientific literature on the sodium salt 
analog, Na-PCA, were submitted to satisfy the 90-day oral for L-PCA. 
The Na-PCA toxicity database is considered appropriate for use in L-PCA 
risk assessment when EP formulations are buffered. There is an 
expectation that EP formulations for use as plant growth regulators 
will be buffered because unbuffered solutions will not be effective as 
a plant growth regulator, i.e., unbuffered solutions would likely 
destroy the plant due to the acidity of L-PCA. This is because buffered 
L-PCA behaves similarly to Na-PCA. There is comparable acute toxicity 
between the proposed EP formulations and Na-PCA. Further, both L-PCA 
and Na-PCA are naturally occurring and are products of human 
metabolism. Using a weight of the evidence (WOE) approach, these 
studies allowed EPA to establish a no-observed-adverse-effect-level 
(NOAEL) of 849 mg/kg/day for subchronic oral toxicity for L-PCA in 
buffered end-use products.
    For developmental toxicity, a non-guideline 1-generation 
reproduction toxicity screening study was submitted on Na-PCA in lieu 
of a developmental toxicity study. The study showed no treatment-
related effects on offspring body weights, body weight gains or on 
post-implantation losses, mean litter size, numbers of live and dead 
pups born, sex ratio, or the birth or survival indices. No gross or 
microscopic pathology of the reproductive tract was seen, and 
reproductive performance was not affected by treatment. While this 
study is not a guideline developmental toxicity study, EPA has 
determined that the screening study is acceptable to satisfy the 
prenatal developmental toxicity data at this time for the specified 
products. This decision is based on the fact that no observable 
toxicity was produced at the limit dose

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level in this study and an effect would not be expected from 
structurally related compounds.
    EPA determined that 90-day inhalation toxicity and 90-day dermal 
studies were not required to assess the risks from L-PCA for the 
following reasons: (1) physical and chemical properties of the buffered 
formulations of L-PCA are similar to those of Na-PCA; (2) estimated 
margins of error (MOEs) are more than 10X the level of concern (LOC); 
and (3) no irritation was observed in studies conducted using the 
buffered end-use products.
    The available data indicates that the active ingredient is non-
mutagenic.

B. Toxicological Points of Departure/Levels of Concern

    Based on the toxicological profile, EPA did not identify any 
toxicological endpoints of concern for L-PCA.

C. Exposure Assessment

    1. Dietary exposure from food, feed uses, and drinking water. No 
toxicological endpoint of concern was identified for L-PCA, and 
therefore, a quantitative assessment of dietary exposure is not 
necessary. As part of its qualitative risk assessment for L-PCA, the 
Agency considered the potential for dietary exposure to residues of the 
chemical. EPA concludes that dietary (food and drinking water) 
exposures are possible. However, due to the lack of a toxicological 
endpoint, dietary risk is not of 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, 
therefore a residential exposure assessment 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 L-
PCA 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 L-PCA 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 (SF). In applying this provision, EPA either 
retains the default value of 10X, or uses a different additional safety 
factor when reliable data available to EPA support the choice of a 
different factor. An FQPA safety factor is not required at this time 
for L-PCA because there are no threshold effects; no dietary endpoints 
have been selected based on the lack of human-relevant adverse effects 
at limit doses in the 90-day oral toxicity study and prenatal 
developmental toxicity study.

E. Aggregate Risk

    Based on the available data and information, EPA has concluded that 
a qualitative aggregate risk assessment is appropriate to support the 
pesticidal use of L-PCA in buffered end-use products, and that risks of 
concern are not anticipated from aggregate exposure to the substance in 
this manner. This conclusion is based on the low toxicity of the active 
ingredient and its salts, which release a common moiety that is the 
basis for the risk assessment. Due to the lack of toxicity, EPA 
concludes that there is no aggregate risk from exposure to L-PCA.
    A full explanation of the data upon which EPA relied and its risk 
assessment based on those data can be found within the September 20, 
2022, document entitled ``Product Chemistry Review and Human Health 
Risk Assessment for FIFRA Section 3 Registrations of (2S)-5-
Oxopyrrolidine-2-carboxylic Acid (L-PCA) Technical, containing 99.1% L-
PCA, VLS 2002-03, Containing 25.0% L-PCA and VLS 2002-03-0.10, 
Containing 10.0% L-PCA.'' 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 
L-PCA.

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. Conclusions

    Therefore, EPA is establishing an exemption for residues of L-PCA 
in or on all food commodities when used as a plant growth regulator 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 tolerance 
exemption in this final rule, do not require the issuance of a proposed 
rule, the requirements of the

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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 4, 2023.
Edward Messina,
Director, 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.  180.1404 to subpart D to read as follows:


Sec.  180.1404  (2S)-5-Oxopyrrolidine-2-carboxylic Acid (L-PCA); 
exemption from the requirement of a tolerance.

    An exemption from the requirement of a tolerance is established for 
residues of the pesticide, (2S)-5-Oxopyrrolidine-2-carboxylic Acid (L-
PCA) in or on all food commodities when used as a plant growth 
regulator in accordance with label directions and good agricultural 
practices.

[FR Doc. 2023-17135 Filed 8-9-23; 8:45 am]
BILLING CODE 6560-50-P


