Eugenol; Exemption From the Requirement of a Tolerance, 56895-56898 [2022-20041]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 87, Number 179 (Friday, September 16, 2022)]
[Rules and Regulations]
[Pages 56895-56898]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-20041]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2018-0522; FRL-10130-01-OCSPP]


Eugenol; 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 eugenol (2-methoxy-4-(-2-
propenyl)phenol) in or on all food commodities when used in accordance 
with good agricultural practices. SciReg, Inc., on behalf of Eden 
Research PLC, 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 eugenol when used in 
accordance with this exemption.

DATES: This regulation is effective September 16, 2022. Objections and 
requests for hearings must be received on or before November 15, 2022 
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-2018-0522, 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, docket access, visit https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Charles Smith, Biopesticides and 
Pollution Prevention Division (7511P), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington, 
DC 20460-0001; main telephone number: (703) 305-7090; 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 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).

[[Page 56896]]

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-2018-0522 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 
November 15, 2022. 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-2018-0522, 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.
    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 August 24, 2018 (83 FR 42818) (FRL-9982-
37), 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 (PP8F8681) by Eden Research PLC, 6 Priory Ct., Priory Court 
Business Park, Poulton, Cirencester, GL7 5JB, United Kingdom (c/o 
SciReg, Inc., 12733 Director's Loop, Woodbridge, VA 22192). The 
petition requested that 40 CFR part 180 be amended by establishing an 
exemption from the requirement of a tolerance for residues of eugenol 
(2-methoxy-4-(-2-propenyl)phenol) in or on raw agricultural commodities 
and processed foods when used in accordance with good agricultural 
practices. That document referenced a summary of the petition prepared 
by the petitioner Eden Research plc, c/o SciReg Inc., which is 
available in the docket, https://www.regulations.gov. There were no 
substantive comments received in response to 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 for, including exposure resulting 
from the exemption established by this action. EPA's assessment of 
exposures and risks associated with eugenol follows.

IV. Toxicological Profile

    Eugenol is a naturally occurring allyl chain-substituted guaiacol 
and a member of the phenylpropanoid class of chemicals. Eugenol is also 
the main constituent of clove bud oil (80 to 90%) and clove leaf oil 
(82 to 88%), and is also found in cinnamon bark and leaves, Tulsi 
leaves, turmeric, pepper, ginger, oregano and thyme and various other 
herbs. As such, eugenol has long been part of the normal human diet. It 
is currently approved by the U.S. Food and Drug Administration (FDA) 
for use as a food additive and generally recognized as safe (GRAS) by 
the FDA (21 CFR 184.1257).
    In conducting its hazard assessment for eugenol, EPA relied on data 
from the open scientific literature which includes (1) a 19-week 
dietary study in rates, (2) a 13-week dietary study in rates, (3) five 
prenatal developmental toxicity studies, and (4) several mutagenicity 
studies. In these data, no adverse effects were seen at the highest 
dose test of 300 mg/kg/day. For guideline studies, EPA generally 
recommends testing at a limit dose of 1000 mg/kg/day. However, based on 
the data reviewed from the open literature along with a body of 
knowledge regarding eugenol such as its low toxicity; rapid degradation 
into the environment; natural occurrence and widespread use in herbs 
and a part of the human diet; EPA would not expect to see adverse 
effects at higher doses.
    With regard to the overall toxicological profile of eugenol, the 
active ingredient is of minimal toxicity. Where data was not available 
on eugenol for acute inhalation and primary eye irritation toxicity, it 
was provided on isoeugenol. Isoeugenol is structurally and 
physiochemically

[[Page 56897]]

similar to eugenol. Based on data provided for eugenol and isoeugenol, 
eugenol is of low acute oral toxicity (Toxicity Category III) and 
inhalation toxicity (Toxicity Category III). The active ingredient 
shows moderate dermal toxicity (Toxicity Category II). It is a mild eye 
(Toxicity Category III), a severe dermal irritant (Toxicity Category 
II), and a weak dermal sensitizer.
    With regard to subchronic toxicity, developmental toxicity, 
reproductive toxicity and mutagenicity data requirements for the active 
ingredient eugenol, all data requirements were satisfied by a 
combination of guideline and non-guideline studies, data waivers, and 
citations to studies from the Agency database as well as to the open 
literature. For the 90-day oral data requirement, data was provided on 
isoeugenol. There were no adverse subchronic effects for any oral or 
dermal routes of exposure. Regarding subchronic dermal and subchronic 
inhalation, EPA granted waivers for these data requirements based on 
weight of evidence approach (WOE). Specific to subchronic dermal, 
eugenol is the main constituent of clove bud oil and clove leaf oil. It 
is used extensively in dentistry for its analgesic and anti-
inflammatory activities. In addition, the dermal margin of exposure 
(MOE) is based on a 300 mg/kg/day point of departure (POD) range from 
460-33,000. This is well above the Agency's Level of Concern (LOC) of 
100.
    In terms of subchronic inhalation toxicity, eugenol has low 
inhalation toxicity. Eugenol is used in spray perfumes up to a 
concentration of 10%, in air fresheners up to 5%, and oil of clove in 
massage products and perfumes up to 30%. Despite its broad usage in 
cosmetics and air fresheners, no or few adverse incidents have been 
reported. Lastly, the occupational handler inhalation MOEs are more 
than ten times the LOC of 100, ranging from 550,000 to 12,000,000.
    In terms of mutagenicity, the active ingredient was determined to 
be non-mutagenic, and no adverse effects were identified relative to 
either developmental toxicity or reproductive toxicity.
    In conclusion, there were no adverse subchronic effects for any 
oral, dermal, inhalation, or developmental routes of exposure and as 
stated previously, EPA has granted a waiver of these data requirements 
based on a WOE approach for the subchronic toxicity testing considering 
all the available eugenol hazard and exposure data. This WOE approach 
includes the following rationale:
    1. Exposure from all routes and in all scenarios is considered to 
be negligible due to the following reasons: (1) eugenol is moderately 
volatile with a vapor pressure of 2.7 Pa @25oC; volatilization from 
both moist and dry soil surfaces is expected due to thymol's Henry's 
Law Constant of 1.92 x 10-6 atm-cu m/mol and vapor pressure; eugenol is 
expected to exist solely as a vapor in the ambient atmosphere, which 
would be readily degraded in the atmosphere by reaction with 
photochemically-produced hydroxyl radicals; the half-life for this 
reaction in the air is estimated to be 5.9 hours; vapor phase eugenol 
is also degraded in the atmosphere by reaction with ozone, the half-
life for this reaction is estimated to be 23 hours; Eugenol also 
absorbs UV light and therefore is likely susceptible to direct 
photolysis by sunlight; and (2) eugenol is expected to readily 
biodegrade as demonstrated in guideline ready biodegradability studies.
    2. Eugenol is naturally occurring and has long been part of the 
normal human diet. It is currently FDA-approved for use as a food 
additive (21 CFR 175.105). FDA also considers eugenol as GRAS (21 CFR 
184.1257). Eugenol is commonly used in foods, air fresheners, 
cosmetics, and perfumes.
    3. Eugenol demonstrates low toxicity throughout its toxicity 
database. No adverse effects were observed to highest dose tested (300 
mg/kg/day) (exception is one eugenol study with no-observed-adverse-
effect level (NOAEL) of 300 mg/kg/day and lowest-observed-adverse-
effect-level (LOAEL) of 625 mg/kg/day based on decreased body weight) 
in the eugenol toxicity database. The database includes a 19-week 
dietary study in rats, a 13-week dietary study in rats, five prenatal 
developmental toxicity studies, and several genotoxicity studies. Data 
from the open literature indicates that eugenol is rapidly metabolized 
as well as rapidly excreted.

A. Toxicological Points of Departure/Levels of Concern

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

B. Exposure Assessment

    1. Dietary exposure from food, feed uses, and drinking water. 
Eugenol is naturally occurring and has long been part of the normal 
human diet. As part of its qualitative risk assessment for eugenol, the 
Agency considered the potential for any additional dietary exposure to 
residues of eugenol from its proposed use as a fungicide and nematicide 
on agricultural use sites. EPA expects dietary (food and drinking 
water) exposures from the proposed use of eugenol to be negligible due 
to its short half-life and biodegradable nature. A quantitative dietary 
exposure assessment was not conducted since a toxicological endpoint 
for risk assessment was not identified.
    2. Residential exposure. The term ``residential exposure'' is used 
in this document to refer to non-occupational, non-dietary exposure. 
Eugenol is not proposed to be registered for any pesticidal uses that 
would result in residential exposure. Residential exposure may occur 
from non-pesticidal uses such as air fresheners, cosmetics, and 
perfumes. However, a quantitative residential exposure assessment was 
not conducted since a toxicological endpoint for risk assessment was 
not identified.
    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 a tolerance exemption, 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 eugenol shares a 
common mechanism of toxicity with any other substances, and eugenol 
does not appear to produce a toxic metabolite produced by other 
substances. For the purposes of this tolerance action, therefore, EPA 
has assumed eugenol 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.

C. 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 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. The Agency has determined that

[[Page 56898]]

a qualitative risk assessment rather than a quantitative risk 
assessment would be most appropriate for the proposed use based on the 
toxicity profiles of eugenol along with its long history of human 
exposure. For this reason, a FQPA safety factor is not required at this 
time. EPA has concluded there are no toxicological endpoints of concern 
for the U.S. population, including infants and children.

D. Aggregate Risks

    Based on the available data and information, EPA has concluded that 
a qualitative aggregate risk assessment is appropriate to support this 
action, and that risks of concern are not anticipated from aggregate 
exposure to eugenol. This conclusion is based on the low toxicity of 
eugenol, long history of human exposure to eugenol via the normal human 
diet and expected rapid degradation of eugenol in the environment.
    A full explanation of the data upon which EPA relied and its risk 
assessment based on those data can be found in the December 15, 2021, 
document entitled ``Risk Assessment for FIFRA Section 3 Registrations 
of Eugenol Technical Containing 99.62% Eugenol as an Active Ingredient, 
Mevalone, Containing 3.21% Eugenol as an Active Ingredient. Tolerance 
Exemption Petition for Eugenol''. This document, as well as other 
relevant information, is available in the docket for this action as 
described under ADDRESSES.

V. 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 
eugenol. Therefore, the establishment of an exemption from the 
requirement of a tolerance for residues of eugenol (2-methoxy-4-(-2-
propenyl)phenol) in or on all food commodities when used in accordance 
with good agricultural practices is safe under FFDCA section 408.

VI. 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.

VII. Conclusions

    Therefore, an exemption from the requirement of a tolerance is 
established for residues of eugenol (2-methoxy-4-(-2-propenyl)phenol) 
in or on all food commodities when used in accordance with good 
agricultural practices.

VIII. 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 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).

IX. 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: September 12, 2022.
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.  180.1395 to subpart D to read as follows:


Sec.  180.1395  Eugenol; exemption from the requirement of a tolerance.

    An exemption from the requirement of a tolerance is established for 
eugenol (2-methoxy-4-(-2-propenyl)phenol) in or on all food commodities 
when used in accordance with good agricultural practices.

[FR Doc. 2022-20041 Filed 9-15-22; 8:45 am]
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