Thymol; Exemption From the Requirement of a Tolerance, 54623-54626 [2022-19294]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 87, Number 172 (Wednesday, September 7, 2022)]
[Rules and Regulations]
[Pages 54623-54626]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-19294]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2018-0520; FRL-10188-01-OCSPP]


Thymol; Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes an exemption from the requirement 
of a tolerance for residues of thymol (5-methyl-2-isopropyl-1-phenol) 
in or on all food commodities when used in accordance with good 
agricultural practices. Sci Reg, Inc., on behalf of Eden Research PLC, 
6 Priory Ct., Priory Court Business Park, Poulton, Cirencester, GL7 
5JB, United Kingdom, 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 thymol when used 
in accordance with this exemption.

DATES: This regulation is effective September 7, 2022. Objections and 
requests for hearings must be received on or before November 7, 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-2018-0520, 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).

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-2018-0520 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 7, 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-2018-0520 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.

[[Page 54624]]

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 (PP 8F8680) 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 thymol 
(5-methyl-2-isopropyl-1-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 thymol including exposure 
resulting from the exemption established by this action. EPA's 
assessment of exposures and risks associated with thymol follows.

IV. Toxicological Profile

    Thymol is a constituent of oil of thyme, a naturally occurring 
mixture of compounds in the plant, Thymus vulgaris. Thymol has long 
been a regular part of the human diet and is listed as an approved food 
additive by FDA (21 CFR 172.515). Thymol has a long history of safe use 
as a direct food additive. Additionally, the source plant (thyme), from 
which thymol is extracted, is acknowledged by FDA as generally 
recognized as safe (GRAS) (21 CFR 182.10 and 182.20).
    In conducting its hazard assessment for thymol, EPA relied on data 
from the open scientific literature which includes a combined repeated 
dose oral toxicity study with the reproduction/developmental toxicity 
screening test, genotoxicity studies, and a 6-month inhalation study. 
In these data, no adverse effects were seen at the highest dose tested 
of 200 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 thymol such as its low toxicity; rapid degradation into the 
environment; and natural occurrence and widespread use in foods that 
are commonly consumed and a part of the human diet, EPA would not 
expect to see adverse effects at higher doses.
    Regarding the overall acute toxicological profile of thymol, the 
active ingredient is of minimal toxicity. Thymol is of low acute oral 
toxicity (Toxicity Category III), inhalation toxicity (Toxicity 
Category IV) and dermal toxicity (Toxicity Category III). It is 
corrosive to the skin and eye (Toxicity Category I) and may or may not 
be a dermal sensitizer (inconclusive).
    With regard to subchronic oral, dermal and inhalation toxicity, EPA 
granted waivers for these data requirements based on a weight of the 
evidence approach (WOE). Specific to the 90-day oral toxicity, as 
stated in section IV. of this document, thymol has a documented and 
long history of use as a direct food additive as a flavoring agent and 
preservative. Moreover, thymol is commonly consumed as it is used in 
ice cream, non-alcoholic beverages, candy, baked goods, chewing gum, 
lime blossom honey and pesto sauce. In a thymol report from the 
European Medicines Evaluation Agency, the Committee of Experts on 
Flavoring Substances of the Council of Europe established an upper 
limit of 50 mg/kg in food and 10 mg/kg in beverages.
    Regarding the 90-day dermal toxicity, thymol is a constituent of 
oil of thyme, a naturally occurring mixture in the plant Thymus 
vulgaris (thyme). It is currently used in cosmetics and human medicine. 
For example, oil of thyme and thymol have been proposed for use as a 
skin penetration enhancer for transdermal drug delivery. In addition, 
all dermal margins of exposure (MOEs) were well above the Agency's 
Level of Concern (LOC) of 100. MOE's for occupational handler exposure 
range from 980 to 22,000.
    In terms of the 90 day-inhalation toxicity, thymol has low 
inhalation toxicity. In human medicine, it is administered via 
inhalation to treat a range of infections in the upper respiratory 
tract and is added to the anesthetic halothane as a preservative and is 
inhaled by patients undergoing surgery. Furthermore, the MOEs 
calculated using a POD of 200 mg/kg/day were significantly above 10X 
the LOC of 100 for inhalation exposure scenarios, ranging from 370,000 
to 8,000,000.
    EPA granted a waiver for the developmental data requirement due to 
thymol's long history of exposure to the human population without 
apparent toxic effects. It has long been a part of the human diet and 
is recognized as a GRAS essential oil by FDA (21 CFR 182.20). 
Furthermore, in a reproductive safety assessment, no adverse effects 
were seen up to a dose of 1,875 mg/kg, the highest dose tested.
    In terms of mutagenicity, the active ingredient was determined to 
be non-mutagenic, and no adverse effects were identified relative to 
either

[[Page 54625]]

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 thymol hazard and exposure data. This WOE approach 
includes the following rationale:
    1. Exposure from all routes and in all scenarios of thymol is 
considered to be negligible due to the following reasons: (a) Thymol is 
moderately volatile with a vapor pressure of 3.4 Pa @25oC; 
volatilization from both moist and dry soil surfaces is expected due to 
thymol's Henry's Law Constant of 4.44 x 10-3 atm/m3/mol and vapor 
pressure; thymol 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 3.6 hours; (b) In a 
batch system using an activated sludge inoculum, thymol was found to be 
94.8% readily biodegradable with a degradation rate of 15.6 mg COD/g-
hr.
    2. Thymol is naturally occurring and has long been part of the 
normal human diet. It is currently FDA-approved for use as a synthetic 
flavoring (21 CFR 172.515), a preservative, a direct food additive, and 
an indirect food additive in adhesives (21 CFR 175.105).
    3. Thymol demonstrates low toxicity throughout its toxicity 
database. No adverse effects were observed to highest dose tested (200 
mg/kg/day) in thymol's toxicity database. The database includes a 
combined repeated dose oral toxicity study with the reproduction/
developmental toxicity screening test, several genotoxicity studies, 
and a 6-month inhalation study. Data from the open literature indicates 
that thymol is rapidly metabolized as well as rapidly excreted. Thus, 
high levels of thymol would likely not be found present in the body 
after 24 hours, with the majority of thymol and related metabolites 
being eliminated through the urine after 6 hours.
    4. Pesticidal use of thymol is unlikely to contribute significantly 
to overall human exposure for the following reasons: (a) Thymol is 
naturally-occuring, and thus humans have had a long history of exposure 
to it. (b) It is FDA-approved for use as direct food additive. (c) 
Thymol is currently used in foods, cosmetics, and human medicine. (d) 
Dietary exposure is expected to be low based on thymol's physical/
chemical properties (readily biodegradable, non-persistent). (e) 
Limited thymol residue data is available on honey, however 
extrapolating from this information, thymol residues on grapevine and 
other food crops would not be significantly greater and therefore not 
contribute significantly to the overall dietary exposure of thymol.

A. Toxicological Points of Departure/Levels of Concern

    Based on the toxicological profile, EPA did not identify any 
toxicological endpoints of concern for assessing risk for this 
chemical.

B. Exposure Assessment

    1. Dietary exposure from food, feed uses, and drinking water. 
Thymol naturally occurs in foods, is widely used as a food additive, 
and is consumed by humans through the diet. As part of its qualitative 
risk assessment for thymol, the Agency considered the potential for any 
additional dietary exposure to residues of thymol from its proposed use 
as a fungicide and nematicide on agricultural use sites. EPA concludes 
that such dietary (food and drinking water) exposures are likely to be 
negligible, due to the short half-life and biodegradable nature of 
thymol. 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. 
Currently, thymol is not registered for any pesticidal uses that would 
result in residential exposure. Residential exposure may occur from 
non-pesticidal uses such as essential oils, household cleaning 
products, and mouthwash. 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 thymol shares a 
common mechanism of toxicity with any other substances, and thymol does 
not appear to produce a toxic metabolite produced by other substances. 
For the purposes of this tolerance action, therefore, EPA has assumed 
thymol 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. EPA has determined that a qualitative risk assessment rather 
than a quantitative risk assessment would be most appropriate for the 
proposed use based on the toxicity profile of this active ingredient 
along with a long history of human exposure of thymol. For this reason, 
a FQPA safety factor is not required at this time.

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 thymol. This conclusion is based on the minimal toxicity of 
thymol, long history of human exposure to thymol, and expected rapid 
degradation of thymol 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 Thymol Technical, 
containing 99.34%% Thymol as its Active Ingredient, Mevalone, 
containing 6.42% Thymol, as an Active Ingredient, and Cedroz, 
Containing 11.9% Thymol as its Active Ingredient. Tolerance Exemption 
Petition for Thymol''. This document, as well as other relevant 
information, is available in the docket for this action as described 
under ADDRESSES.

[[Page 54626]]

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 
thymol. Therefore, the establishment of an exemption from the 
requirement of a tolerance for residues of thymol (5-methyl-2-
isopropyl-1-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. Conclusion

    Therefore, an exemption from the requirement of a tolerance is 
established for residues of thymol (5-methyl-2-isopropyl-1-phenol) in 
or on all food commodities when used in accordance with good 
agricultural practices.
    In addition, as a housekeeping measure, EPA is removing time-
limited exemptions from the requirement of a tolerance for residues of 
thymol on honey and honeycomb in connection with use of the pesticide 
under section 18 emergency exemptions granted by the EPA. These 
exemptions expired on June 30, 2007.

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 1, 2022.
Charles Smith,
Director, Biopesticides and Pollution Prevention Division, 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. Amend Sec.  180.1240 by revising paragraph (a) to read as follows:


Sec.  180.1240   Thymol; exemption from the requirement of a tolerance.

    (a) An exemption from the requirement of a tolerance is established 
for thymol (5-methyl-2-isopropyl-1-phenol) in or on all food 
commodities when used in accordance with good agricultural practices.
* * * * *
[FR Doc. 2022-19294 Filed 9-6-22; 8:45 am]
BILLING CODE 6560-50-P