Document ID: EPA-HQ-OPP-2005-0483-0001
Agency: epa
Document Type: Rule
Title: Thymol; Exemption from the Requirement of a Tolerance
Posted Date: 2006-01-18T16:19:03Z

[Federal Register: January 18, 2006 (Volume 71, Number 11)]
[Rules and Regulations]               
[Page 2889-2895]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18ja06-8]                         

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0483; FRL-7754-9]

 
Thymol; 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 the thymol (5-methyl-2-isopropyl-1-
phenol) on honey, honeycomb, and honeycomb with honey when applied/used 
as treatment to decrease the incidence of Varroa mite infestation in 
the honey bee. Vita (Europe) Limited, c/o Landis International Limited, 
submitted a petition to EPA under the Federal Food, Drug, and Cosmetic 
Act (FFDCA), as amended by the Food Quality Protection Act of 1996 
(FQPA), requesting an exemption from the requirement of a tolerance. 
This regulation eliminates the need to establish a maximum permissible 
level for residues of thymol (5-methyl-2-isopropyl-1-phenol).

DATES: This regulation is effective January 18, 2006. Objections and 
requests for hearings must be received on or before March 20, 2006.

ADDRESSES: To submit a written objection or hearing request follow the 
detailed instructions as provided in Unit X. of the SUPPLEMENTARY 
INFORMATION. EPA has established a docket for this action under Docket 
identification (ID) number EPA-HQ-OPP-2005-0483. All documents in the 
docket are listed on the http://www.regulations.gov web site. (EDOCKET, EPA's 

electronic public docket and comment system was replaced on November 
25, 2005, by an enhanced Federal-wide electronic docket management and 
comment system located at http://www.regulations.gov/. Follow the on-

line instructions.) Although listed in the index, some information is 
not publicly available, i.e., CBI or other information whose disclosure 
is restricted by statute. Certain other material, such as copyrighted 
material, is not placed on the Internet and will be publicly available 
only in hard copy form. Publicly available docket materials are 
available either electronically in EDOCKET or in hard copy at the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall 2, 1801 S. Bell St., Arlington, VA. This docket 
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The docket telephone number is (703) 305-
5805.

FOR FURTHER INFORMATION CONTACT: Andrew Bryceland, Biopesticides and 
Pollution Prevention Division (7511C), Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-6928; e-mail address:bryceland.andrew@epa.gov.

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. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Access Electronic Copies of this Document and Other 
Related Information?

    In addition to using EDOCKET (http://www.epa.gov/edocket/), you may 

access this Federal Register document electronically through the EPA 
Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/.
 A frequently updated electronic version of 40 CFR part 180 

is available on E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/. 

To access the OPPTS Harmonized Guidelines referenced in this document 
go directly

[[Page 2890]]

to the guidelines at http://www.epa.gpo/opptsfrs/home/guidelin.htm/.

II. Background and Statutory Findings

    In the Federal Register of April 27, 2005 (70 FR 21773) (FRL-7707-
8), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance 
petition (PP 3F6752) by Vita (Europe) Limited c/o Landis International, 
Inc., P.O. Box 5126, Valdosta, GA 31603-5126. The petition requested 
that 40 CFR part 180 be amended by establishing a temporary exemption 
from the requirement of a tolerance for residues of thymol (5-methyl-2-
isopropyl-1-phenol). This notice included a summary of the petition 
prepared by the petitioner. A public comment has been received 
objecting to ``any tolerance, exemption, or waiver allowing more than 
zero residue of thymol on food.'' This objection was supported by the 
arguments that:
    1. Embryonic chickens have multiple malformations following thymol 
injection into the yolk or air sac, and;
    2. Switzerland has established an Maximum Residue Limit (MRL) of 
0.8 milligram/kilogram (mg/kg). The commenter did not provide a 
specific data citation for either of these arguments.
    The results from the chicken study are of questionable relevance to 
mammals. Currently, EPA does not use chickens (or intrayolk or intra-
airsac exposure routes) as an animal model for developmental toxicity 
because of the differences in developmental physiology and anatomy 
between the two species. Developmental timing, duration, and potential 
environmental effects on developing young are also different in mammals 
and birds, again precluding this model for use in setting developmental 
toxicity endpoints for the regulation of pesticides (Reference 13).
    Developmental malformations have not been found following thymol 
exposure to other mammalian species such as mice, rats, hamsters, and 
rabbits (Environmental Risk Management Agency of New Zealand, 2005). In 
addition, Mortazavi et al. (2003) reported no external tissue 
abnormalities in fetuses following dosing of female rats with an 
infusion of the plant Satureja khuzestanica (which has the components 
thymol and carvacrol).
    Regulatory limits have been set for thymol in other countries. The 
Swiss Federal Department of the Interior has set a tolerance (MRL) 
concentration for thymol in honey as an antiparasitic agent (0.8 mg/kg; 
pharmacological substance active in nutrition or therapeutic 
application; 817.021.23). This tolerance was derived to prevent 
exceedance of the taste threshold for thymol in honey (1.1 - 1.3 mg/kg; 
Bogdanov et al., 1999), not safety. Tolerances set by EPA are based on 
``the reasonable certainty of no harm,'' FFDCA section 
408(c)(2)(A)(ii), and therefore, are not constrained by criteria such 
as taste.
    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 section 408(c)(2)(B), in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take intoaccount the factors set forth in 
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, section 408(b)(2)(D) of FFDCA 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 performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action and considered its validity, completeness, and reliability 
and the relationship of this information to human risk. EPA has also 
considered available information concerning the variability of the 
sensitivities of major identifiable subgroups of consumers, including 
infants and children.
    Thymol is an essential oil that is extracted from thyme and 
mandarine and tangerine oils and is FDA approved when used as a 
synthetic flavoring (21 CFR 172.515), a preservative and indirect food 
additive of adhesives (21 CFR 175.105). Additionally, the source plant 
(thyme), from which thymol is extracted is acknowledged by FDA as 
generally recognized as safe (GRAS) (21 CFR 182.10, 21 CFR 182.20). 
Residues of thymol can be found in other food stuffs either naturally 
such as that found in lime honey or intentionally added to foods such 
as ice cream, non-alcoholic beverages, candy, baked goods, and chewing 
gum. Information from the public literature documents that levels of 
thymol residues in such foods are present at significantly higher 
concentrations than those resulting from pesticidal treatments (Refs. 
1, 3, 14, 15, 16, 17, and 18). End use products containing thymol as 
the active ingredient will be used as a slow release treatment within 
the beehive itself to decrease the incidence of Varroa mite infestation 
in the honey bee.
    Toxicity data requirements were addressed by requests for data 
waivers. The Agency granted data waivers based on publically available 
information/data submitted by the registrant and reviewed by the 
Agency.
    1. Acute oral toxicity waiver (OPPTS 870.1100, 152-10). The waiver 
rationale submitted in support of the acute oral toxicity (870.1100) 
data requirement is based on oral LD50s from the open 
literature and reviewed by the Agency. The oral LD50 of 
thymol has been reported to be 980, 640-1800, and 880 mg/kg in rats, 
mice, and guinea pigs, respectively (Refs. 3 and 5). Thymol occurs in 
various food stuffs and spices from 0.02 mg/kg to 100 mg/kg (Refs. 3, 
14, 15, 16, 17, and 18). The lowest level in which there was an effect 
from thymol was 640 mg/kg (Refs. 3 and 5). The amount in which thymol 
causes an acute effect is approximately 6 times higher than the 100 mg/
kg found in the food stuff with the highest amount of thymol present. 
The information/data described above support the waiver form the data 
requirement for the acute oral toxicity study.
    2. Acute dermal toxicity data waiver (OPPTS 870.1200, 152.11). The 
waiver rationale submitted in support of the acute dermal toxicity data 
requirement is based upon information collected from a report by the 
Environmental Risk Management Agency (ERMA, 2005) of New Zealand and 
Anonymous (2000) which found dermal LD50's for thymol

[[Page 2891]]

greater than 2,000 mg/kg. Thymol occurs in various food stuffs and 
spices from 0.02 mg/kg to 100 mg/kg (Refs. 3, 14, 15, 16, 17, and 18). 
Dermal exposure to thymol already occurs from contact with foodstuffs 
and seasonings containing thymol as it is FDA approved when used as a 
direct food additive and is generally recognized as safe by FDA as a 
spice, natural oil, oleoresin, or natural extract and therefore, any 
additional exposure resulting from dermal contact with thymol will not 
result in any significant exposure. Thymol, when used as a pesticide, 
is to be applied to the inside of beehives. Data from U.S. and European 
field trials demonstrate maximum residue concentrations of 2.59 mg/kg 
thymol in honey (at 30 days following treatment in U.S. trials) and 
4.61 mg/kg thymol in honey (at 2 days following treatment in European 
trials) demonstrate that, following good agricultural practices (as 
specified in the tolerance exemption), the amount of thymol residues 
remaining in the beehive after application will be well below the 
dermal LD50 and within the range of those thymol residues 
already present in food stuffs (MRID No.'s: 460435-10, 11, 12, and 13). 
Based on this information, the Agency therefore concludes that the 
information/data described above support the waiver from the data 
requirement for the acute dermal toxicity study.
    Classification: Acceptable.
    3. Acute inhalation toxicity waiver (OPPTS 870.1300, 152-12). The 
waiver rationale submitted in support of the acute inhalation toxicity 
data requirment is based upon information from the U.S. Food and Drug 
Administration Center for Drug Evaluation and Research (Ref. 19). 
Thymol is added to the anesthetic halothane as a preservative (0.01%) 
and is considered inactive at this concentration (Ref. 19). Halothane 
is used to anesthetize dogs, cats, and other non-food animals for 
periods sometimes exceeding 4 hours (Ref. 19). Anesthetic induction 
concentrations can typically reach approximately 5% (Ref. 19). 
Calculation of the exposure from these factors yields a thymol 
atmospheric concentration of 5 milligram/liter (mg/L). Thymol is for 
application to the inside of beehives. Thymol occurs in various food 
stuffs and spices from 0.02 mg/kg to 100 mg/kg (Refs. 3, 14, 15, 16, 
17, and 18). Inhalation exposure to thymol already occurs from contact 
with foodstuffs and seasonings containing thymol as it is FDA approved 
when used as a direct food additive and is generally recognized as safe 
by FDA as a spice, natural oil, oleoresin, or natural extract and 
therefore, any additional exposure resulting from inhalation contact 
with thymol will not result in any significant exposure The 
information/data described above support the waiver from the data 
requirement for the acute inhalation toxicity study.
    Classification: Acceptable.
    4. Skin hypersensitivity study waiver (OPPTS 870.2600, 152.15). The 
waiver rationale for skin hypersensitivity is based on publically 
available information (Ref. 20). Using quantitative structure activity 
relationships, from the public literature, it was predicted that thymol 
is a dermal sensitizer (Ref. 20). Thymol is for application to the 
inside of beehives. Thymol occurs in various food stuffs and spices 
from 0.02 mg/kg to 100 mg/kg (Refs. 3, 14, 15, 16, 17, and 18). Dermal 
exposure to thymol already occurs from contact with foodstuffs and 
seasonings containing thymol as it is FDA approved when used as a 
direct food additive and is generally recognized as safe by FDA as a 
spice, natural oil, oleoresin, or natural extract and therefore, any 
additional exposure resulting from dermal contact with thymol will not 
result in any significant exposure. The information/data described 
above support the waiver from the data requirement for the skin 
hypersensitivity study.
    Classification: Acceptable.
    The information/data described above support the waiver from the 
data requirement for the skin hypersensitivity study. However, the 
registrant is obliged under the Federal Insecticide, Fungicide, and 
Rodenticide Act (FIFRA) section 6(a)(2) to notify the Agency in the 
events of such incidents.
    Classification: Acceptable.
    5. Genotoxicity and mutagenicity study waivers, Master Record 
Identification Numbers (MRIDs) 46282801 and 46282802 (OPPTS 870.2300, 
870.5195; 152-17, and 152.19). Genotoxicity and mutagenicity studies 
submitted on September 18th of 2003 (MRIDs 462828-01 and -02), 
presumably as waiver rationales for genotoxicity (870.5000) and other 
peer-reviewed publications retrieved by EPA (Refs. 3, 6, 7, 8, 9, 10, 
and 11), were used to support the waivers from the data requirements. 
These data demonstrate that thymol is not genotoxic and/or mutagenic. 
The information/data described above support the waivers from the data 
requirements for the genotoxicity and mutagenicity studies.
    Classification: Acceptable.
    6. Immune response study waiver (OPPTS 870.3550, 152.18). The 
waiver rationale for immune response (870.3550) is based upon 
information presented in a peer-reviewed publication (Ref. 21). No 
effects were shown in this data (Ref. 21). The information/data 
described above support the waiver form the data requirement for the 
acute inhalation toxicity study.
    Classification: Acceptable.

IV. Aggregate Exposures

    In examining aggregate exposure, section 408 of FFDCA directs EPA 
to consider available information concerning exposures from the 
pesticide residue in food and all other non-occupational exposures, 
including drinking water from ground water or surface water and 
exposure through pesticide use in gardens, lawns, or buildings 
(residential and other indoor uses).

A. Dietary Exposure

    1. Food. Thymol is already found naturally in food stuffs such lime 
honey and cooking herbs and/or food stuffs derived from cranberry and 
mandarin and tangerine oils. Thymol is also added to food stuffs 
commonly consumed by humans such as ice cream, non-alcoholic beverages, 
candy, baked goods, and chewing gum. It is FDA approved when used as a 
synthetic flavoring, (21 CFR 172.515), a preservative and indirect food 
additive of adhesives (21 CFR 175.105) and the source plant (thyme), 
from which thymol is extracted is acknowledged by FDA as generally 
recognized as safe (GRAS) (21 CFR 182.10, 21 CFR 182.20). The 
information and/or data reviewed in support of this tolerance exemption 
demonstrate that the levels of thymol already present in foods or 
intentionally added to food stuffs will at concentrations significantly 
higher that those levels expected from the use of thymol as a 
pesticidal product. Because thymol is already present, either naturally 
or intentionally added to various food stuffs, there is a great 
likelihood of exposure to thymol for most, if not all individuals, 
including infants and children. Even if there is a significant increase 
in exposure to thymol due to it's use as a pesticide, the acute 
toxicity information from the public literature demonstrating 
relatively low mammalian toxicity indicate that any possible risk 
associated with acute exposures by the oral route would below to non-
existent.
    2. Drinking water exposure. No exposure to thymol residues in 
drinking water is expected since the use of this product is limited to 
application within the hive box in which the product is contained in a 
dispenser tray, where the

[[Page 2892]]

product is rapidly volatilized or redistributed. Because thymol has 
relatively low toxicity, has been approved for food use by FDA as a 
direct food additive and is generally recognized as safe by FDA, even 
if exposure through drinking water were to occur, the exposure would be 
far less than the exposure that humans already get from consumption of 
thymol thru the diet and therefore, no risk is anticipated.

B. Other Non-Occupational Exposure

    The potential for non dietary exposure to residues of thymol for 
the general population, including infants and children, is unlikely 
because the uses are limited to application to certain agricultural 
crops within the hive box containing the bees and there is no honey 
present in the bee hive. Thymol is consumed by humans thru the diet and 
for this reason, from a dietary exposure standpoint, has been 
determined to have relatively low toxicity. Therefore, while the 
likelihood of exposure exists for most if not all individuals, any 
increased exposure due to the proposed product would not add any 
significant risks.
    1. Dermal exposure. Dermal exposure to thymol already occurs from 
contact with foodstuffs and seasonings containing thymol as it is FDA 
approved when used as a direct food additive and is generally 
recognized as safe by FDA as a spice, natural oil, oleoresin, or 
natural extract and therefore, any additional exposure resulting from 
dermal contact with thymol will not result in any significant risk.
    2. Inhalation exposure. Inhalation exposure to thymol already 
occurs from contact with foodstuffs and seasonings containing thymol as 
it is FDA approved when used as a direct food additive and is generally 
recognized as safe by FDA as a spice, natural oil, oleoresin, or 
natural extract and therefore, any additional exposure resulting from 
dermal contact with thymol will not result in any significant risk.

V. Cumulative Effects

    Thymol has a novel mode of cellular action (GABAA receptor, sodium, 
potassium, and calcium channel modulator) compared to other currently 
registered active ingredients (Ref. 1). In addition, there is no 
indication that toxic effects of thymol would be cumulative (Ref. 1). 
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 does not have, at this time, available data to determine 
whether thymol has a common mechanism of toxicity with other 
substances. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, EPA 
has not made a common mechanism of toxicity finding as to thymol and 
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 not assumed that thymol has 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 the policy statements released by EPA's Office of 
Pesticide Programs concerning common mechanism determinations and 
procedures for cumulating effects from substances found to have a 
common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/
.

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

    1. U.S. population. The Agency has determined that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to residues of thymol to the U.S. population. This includes all 
anticipated dietary exposures and other non-occupational exposures for 
which there is reliable information. The Agency arrived at this 
conclusion based on the relatively low levels of mammalian dietary 
toxicity associated with thymol, its FDA approval as a direct food 
additive, a preservative and indirect food additive of adhesives and 
GRAS listing as a spice, natural oil, oleoresin, or natural extract and 
information and/or data which demonstrate that the U.S. population is 
potentially exposed to 938 times more thymol from the consumption of 
foodstuff such as ice cream, cola beverages and candy, to which thymol 
is intentionally added, than from thymol consumed in honey (Refs. 22, 
23, and MRID 46043510). These data indicate that thymol residues found 
in food and foodstuffs exist at significantly higher concentrations 
that those residues levels resulting from the use of thymol as a 
pesticide. For these reasons, the Agency has determined that thymol 
residues in honey will not pose any significant dietary risk under 
reasonable foreseeable circumstances residue.
    2. Infants and children. FFDCA section 408 provides that EPA shall 
apply an additional tenfold margin of exposure (safety) for infants and 
children in the case of threshold effects to account for prenatal and 
postnatal toxicity and the completeness of the data base unless the EPA 
determines that a different margin of exposure (safety) will be safe 
for infants and children. Based on all the reliable available 
information the Agency reviewed on thymol, the Agency concludes that 
there are no residual uncertainties for prenatal/postnatal toxicity 
resulting from thymol and that thymol has relatively low toxicity to 
mammals from a dietary standpoint, including infants and children thus, 
there are no threshold effects of concern and an additional margin of 
safety is not necessary to protect infants and children.

VII. Other Considerations

A. Endocrine Disruptors

    No studies illustrating thymol-induced immune and endocrine 
toxicity were submitted by the registrant.
    EPA is required under FFDCA, as amended by FQPA, to develop a 
screening program to determine whether certain substances (including 
all pesticide active and other ingredients) ``may have an effect in 
humans that is similar to an effect produced by a naturally occurring 
estrogen, or other such endocrine effects as the Administrator may 
designate.'' Following the recommendations of its Endocrine Disruptor 
Screening and Testing Advisory Committee (EDSTAC), EPA determined that 
there were scientific bases for including, as part of the program, the 
androgen and thyroid hormone systems, in addition to the estrogen 
hormone system. EPA also adopted EDSTAC's recommendation that the 
Program include evaluations of potential effects in wildlife. For 
pesticide chemicals, EPA will use Federal Insecticide, Fungicide and 
Rodenticide Act (FIFRA) and, to the extent that effects in wildlife may 
help determine whether a substance may have an effect in humans, FFDCA 
has authority to require the wildlife evaluations. As the science 
develops and resources allow, screening of additional hormone systems 
may be added to the Endocrine Disruptor Screening Program (EDSP). When 
the appropriate screening and/or testing protocols being considered 
under the Agency's EDSP have been developed, thymol may be subjected to 
additional screening and/or testing to better characterize effects 
related to endocrine

[[Page 2893]]

disruption. Based on available data, no endocrine system-related 
effects have been identified with consumption of thymol. Information 
submitted from the public literature and reviewed by the Agency 
however, describe immunological endpoints in relation to short-term and 
chronic dosing. No effects were seen in the thymus, spleen, lymph 
nodes, white cell counts, red cell counts, hemoglobin counts, or 
hematocrits following the dosing of rats with 1,000 or 10,000 mg/kg of 
food grade thymol for 19 weeks. (MRID 46282803; Ref. 21). This 
information does not however, provide evidence to suggest that thymol 
affects the immune system, functions in a manner similar to any known 
hormone, or that it acts as an endocrine disruptor.

B. Analytical Method(s)

    An analytical method for measuring thymol in honey and beeswax was 
submitted and reviewed by the Agency and found to be acceptable.

C. Codex Maximum Residue Level

    The are no CODEX maximum residues levels for thymol.

VIII. Conclusions

    Based on the information/data submitted and other information 
available to the Agency, there is a reasonable certainty that no harm 
will result from aggregate exposure to residues of thymol to the U.S. 
population, including infants and children, under reasonable 
foreseeable circumstances, when the biochemical pesticide is used in 
accordance with the product label directions. This includes all 
anticipated dietary exposures and all other non-occupational exposures 
for which there is reliable information. The Agency has arrived at this 
conclusion based on the information/data submitted (and publically 
available) demonstrating relatively low toxicity of thymol. As a 
result, EPA is establishing an exemption from the tolerance 
requirements pursuant to FFDCA 408(c) and (d) for residues of thymol in 
or on honey, honeycomb and honeycomb with honey.

IX. References

    1. 12/7/05 Agency review memorandum; From Dr. Kent Carlson, 
Biologist; Through Dr. Russell Jones, Senior Biologist; To Andrew 
Bryceland, Regulatory Action Leader; Subject: Addendum to the 7/19/05 
Agency review memorandum and Review of Response to Deficiency Letter, 
Waiver Rationales, and Product Chemistry.
    2. 7/19/05 Agency review memorandum; From Dr. Kent Carlson, 
Biologist; Through Dr. Russell Jones, Senior Biologist; To Andrew 
Bryceland, Regulatory Action Leader; Review of Response to Deficiency 
Letter, Waiver Rationales, and Product Chemistry.
    3. Environmental Risk Management Authority (ERMA). 2005. Form HS1, 
Application for approval to import or manufacture any hazardous 
substance for release (for APILIFE VAR). http://www.ermanz.govt.nz.

    4. Mortazavi, S.H.R., Ebrahimi, M., Salehnia, A., and M. Abdollahi. 
2003. Effects of satureja khuzestanica on reproduction potency of 
female rats. Neurotoxicology and Teratology. 25. 381-397.
    5. Sax, N.I., 1984. Dangerous properties of industrial materials. 
6th edition. New York, NY. Van Nostrand Reinhold. p2580.
    6. Anonymous. 2000. Thymol. Toxikologische Bewertung. Heidleberg, 
Berufsgenossenschaft der chemischen Industrie Vol:259 (2000) 38p.
    7. Azizan, A. and R.D. Blevins. 1995. Mutagenicity and 
antimutagenicity testing of six chemicals associated with the pungent 
properties of specific spices as revealed by the Ames Salmonella/
microsomal assay. Arch. Environ. Contam. Toxicol. 28: 248-258.
    8. Stammati, A., Bonsi, P., Zucco, F., Moezelaar, R., Alakomi, H.-
L., and A. von Wright. 1999. Toxicity of selected plant volatiles in 
microbial and mammalian short-term assays. Food and Chemical 
Toxicology. 37: 813-823.
    9. Zani, F., Massimo, G., Benvenuti, S., Bianchi, A., Albasini, A., 
Melegari, M., Vampa, G., Bellotti, A., and P. Mazza. 1990. Studies on 
the genotoxic properties of essential oils with Bacillus subtilis rec-
assay and Salmonella/microsome reversion assay. Planta Med. 57:237-241.
    10. Tsutsui, T., Suzuki, N., Kobayashi, Y., Suzuki, H., Fukuda, S., 
and H. Maizumi. 1987. Assessment of the carcinogenic hazard of 27 
substances used in dental practices. Japanese Journal of Pharmacology. 
43 (suppl). 132P.
    11. Grant, W.F. 1982. Chromosome aberration assays in Allium. A 
report of the U.S. Environmental Protection Agency Gene-Tox program. 
Mutat. Res. 99(3). 273-291.
    12. Environmental Protection Agency. 2001. Risk assessment guidance 
for superfund volume I: Human health evaluation manual (Part E, 
Supplemental Guidance for Dermal Risk Assessment) Interim. EPA/540/R/
99/005, OSWER 9285.7-02EP, PB99-963312.
    13. EPA Health Effects Guidelines (OPPTS.7300, Prenatal development 
toxicity study, pg.1 (e)(1)).
    14. FR Notice 7308-1, Vol.68, No. 109, Friday June 6, 2003.
    15. Fenaroli's Handbook of Flavoring ingredients. Vol 2. Edited, 
translated and revised by T.E. Furia and Bellanca. 2\nd\ edition. 
Cleeland: The Chemical Rubber Co., 1975., p536.
    16. De Vincenzi, M., Maialetti, F., and M. Di Pasquale. 1991. 
Monographs on botanical flavoring substances used in food; Part 1. 
Fitoterapia. 62(1). 47-63.
    17. Piasenzotto, L., Gracco, L., Conte, L.S., and S. Bodenov. 2002. 
Application of solid phase microextraction to evaluate traces of thymol 
in honey. Apidologie. 33. 545-552.
    18. Council of Europe. 2000. Council of Europe Publishing, F-67075 
Strousburg Cedex, Koelblin-Fortuna-Dick, p. 85.
    19. Food and Drug Administration, April 10, 1997, NADA, Freedom of 
Information Summary, p3.
    20. Hostynek, J.J. and P.S. Magee. 1997. Fragrance allergens: 
Classification and ranking by QSAR. Toxicology In Vitro. 11. 377-384.
    21. Hagan, E.C., Hansen, W.H., Fitzhugh, O.G., Jenner, P.M., Jones, 
W.I., Taylor, J.M., Long, E.L., Nelson, A.A., and J.B. Brouwer. 1967. 
Food flavourings and compounds of related structure. II. Subacute and 
Chronic Toxocity. Fd. Cosmet. Toxicol. 5. 141-157.
    22. USEPA NCEA-ORD. 1997. Exposure Factors Handbook, Chapter 7 Body 
Weight Studies, at http://cfpub.epa.gov/ncea/cfm/ 

recordisplay.cfm?deid= 12464CFID=17826586 &CFTOKEN=20588395.
    23. Food and Drug Administration. FDA Total Diet Study. 1990. FDA 
Total Diet Study. 2003. TDS Diets, Version 1 (1990 food list + 1987-88 
NFCS data), at http://www.cfsan.fda.gov/~comm/tds-hist.html#fca.

X. Objections and Hearing Requests

    Under section 408(g) of FFDCA, as amended by the FQPA, any person 
may file an objection to any aspect of this regulation and may also 
request a hearing on those objections. The EPA procedural regulations 
which govern the submission of objections and requests for hearings 
appear in 40 CFR part 178. Although the procedures in those regulations 
require some modification to reflect the amendments made to FFDCA by 
the FQPA, EPA will continue to use those procedures, with appropriate 
adjustments, until the necessary modifications can be made. The new 
section 408(g) of FFDCA provides essentially the same process for 
persons to ``object '' to a regulation setting an exemption from the 
requirement of a

[[Page 2894]]

tolerance issued by EPA under new section 408(d) of FFDCA, as was 
provided in the old sections 408 and 409 of FFDCA. However, the period 
for filing objections is now 60 days, rather than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number EPA-HQ-OPP-2005-0483 in the subject line on 
the first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before March 20, 
2006.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900L), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Suite 350, 1099 14\th\ St., NW., 
Washington, DC 20005. The Office of the Hearing Clerk is open from 8 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
telephone number for the Office of the Hearing Clerk is (202) 564-6255.
    2. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit IX.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in ADDRESSES. Mail your 
copies, identified by docket ID number EPA-HQ-OPP-2005-0483, to: Public 
Information and Records Integrity Branch, Information Technology and 
Resource Management Division (7502C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. In person or by courier, bring a copy to the 
location of the PIRIB described in ADDRESSES. You may also send an 
electronic copy of your request via e-mail to: opp-docket@epa.gov. 
Please use an ASCII file format and avoid the use of special characters 
and any form of encryption. Copies of electronic objections and hearing 
requests will also be accepted on disks in WordPerfect 6.1/8.0 or ASCII 
file format. Do not include any CBI in your electronic copy. You may 
also submit an electronic copy of your request at many Federal 
Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

XI. Statutory and Executive Order Reviews

    This final rule establishes an exemption from the tolerance 
requirement under section 408(d) of FFDCA 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 rule has been exempted from review under Executive 
Order 12866 due to its lack of significance, this rule is not subject 
to Executive Order 13211, Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, 
May 22, 2001). This final rule does not contain any information 
collections subject to OMB approval under the Paperwork Reduction Act 
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or 
contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). 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); 
or OMB review or any Agency action under Executive Order 13045, 
entitled Protection of Children from Environmental Health Risks and 
Safety Risks (62 FR 19885, April 23, 1997). 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 of 1995 (NTTAA), 
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of FFDCA, 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. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of FFDCA. For these same reasons, the Agency has 
determined that this rule does not have any ``tribal implications'' as 
described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
Order to include regulations

[[Page 2895]]

that have ``substantial direct effects on one or more Indian tribes, on 
the relationship between the Federal Government and the Indian tribes, 
or on the distribution of power and responsibilities between the 
Federal Government and Indian tribes.'' This rule will not have 
substantial direct effects on tribal governments, on the relationship 
between the Federal Government and Indian tribes, or on the 
distribution of power and responsibilities between the Federal 
Government and Indian tribes, as specified in Executive Order 13175. 
Thus, Executive Order 13175 does not apply to this rule.

XII. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. 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 this final rule in the Federal Register. This final 
rule 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: December 30, 2005.
James Jones,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--AMENDED

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. Section 180.1240 is amended by redesignating the existing text as 
paragraph (a) and adding a new paragraph (b) to read as follows:

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

* * * * *
    (b) An exemption from the requirement of tolerance is established 
for residues of Thymol (5-methyl-2-isopropyl-1-phenol in or on honey, 
honeycomb, and honeycomb with honey when used in accordance with good 
agricultural practices.

[FR Doc. 06-436 Filed 1-17-06; 8:45 am]

BILLING CODE 6560-50-S