BIOPESTICIDES REGISTRATION ACTION DOCUMENT
/-Carvone
U.S. Environmental Protection Agency
Office of Pesticide Programs
Biopesticides and Pollution Prevention Division
(Last updated August 31, 2009)
This document is for informational purposes only and is representative of the Agency's justification in
registering products containing this active ingredient. This is not a legal document.
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TABLE OF CONTENTS
I. EXECUTIVE SUMMARY 5
II. ACTIVE INGREDIENT OVERVIEW 6
III. REGULATORY BACKGROUND 6
A. Food Clearances/Tolerances 6
IV. RISK ASSESSMENT 6
A. Active Ingredient Characterization 6
B. Human Health Assessment 7
1. Toxicology 7
a. Acute Toxicity 8
b. Subchronic Toxicity 8
c. Developmental Toxicity and Mutagenicity 9
d. Effects on the Endocrine System 9
2. Dose Response Assessment 10
3. Drinking Water Exposure and Risk Characterization 10
4. Occupational, Residential, School and Day Care Exposure and Risk Characterization ..10
a. Occupational Exposure and Risk Characterization 10
b. Residential, School and Day Care Exposure and Risk Characterization 10
5. Risk Characterization 10
C. ENVIRONMENTAL ASSESSMENT 10
1. Ecological Hazards 10
2. Environmental Fate and Ground Water Data 11
3. Ecological Exposure and Risk Characterization 11
4. Endangered Species Assessment 11
V. Risk Management Decision 11
A. Determination of Eligibility for Registration 11
B. Regulatory Decision 11
1. Conditional/Unconditional Registration 12
C. Environmental Justice 12
VI. ACTIONS REQUIRED BY REGISTRANTS 12
A. Reporting of Adverse Effects 12
B. Reporting of Hypersensitivity Incidents 12
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VII. Appendix A. Data Requirements (40 C.F.R. Part 158-SubpartU) 12
VIII. Appendix B. Product Specific Information 15
IX. Appendix C. References 16
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM
Office of Pesticide Programs:
Biopesticides and Pollution Prevention Division
Biochemical Pesticides Branch (BPB)
Linda A. Hollis Chief
Colin Walsh Regulatory Action Leader
Mike Rexrode Biologist, Acute Toxicology
Jacob Moore Chemist
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I. EXECUTIVE SUMMARY
/-Carvone, which is the fragrance of mint, comprises 50-65% of the essential oil from the
spearmint plant (Mentha spicatd). It can also be made synthetically from d-limonene. /-Carvone
has a long history of use as a flavoring in a variety of foods and beverages, as well as in
toothpaste and mouth wash. It is also used as a fragrance in personal care products, and in
consumer products such as air fresheners. The technical grade active ingredient (TGAI) is
identified as Bedoukian L-Carvone and is intended for use in the manufacture of an area
repellent for mosquitoes and biting flies.
The Tier I toxicology data suggest that /-Carvone is acutely non toxic (Toxicology Category IV)
and has very low acute dermal and inhalation concerns (Toxicology Category III). This
compound is a mild-slight dermal sensitizer, and a negative mutagen. L-Carvone has been used
as a fragrance for personal care products and flavoring in various foods (safe exposure limits
have already been established). There is no evidence of inhalation toxicity (Toxicology Category
IV) and primary eye irritation cleared in seven days (Toxicology Category III). Therefore, the
information submitted is sufficient to justify the requested waivers for Acute Oral Toxicity,
Acute Inhalation, Acute Dermal Toxicity, Primary Eye Irritation, Primary Dermal Irritation,
Dermal Sensitization, Hypersensitivity, Prenatal Development, Bacterial Reverse Mutation
Testing, In vitro Mammalian Cell Assay and the 90-Day Inhalation Toxicity. Since this is a
manufacturing use registration, all Tier I Ecotoxicity data requirements per 40 C.F.R. 158.2060
have also been waived at this time. The registrant, however, should be reminded that this
requirement will be reexamined upon application of an end use product. The Agency has
determined that use of the technical grade of/-Carvone will have No Adverse Effects (NAE) on
threatened and/or endangered species.
The registrant has noted that /-Carvone is to be used in an end use product in order to repel
mosquitoes and other biting insects. Since this is a public health issue, the registrant must submit
an appropriate efficacy study for Agency review upon registration request for the end use
product.
To mitigate any risk for handlers of the TGAI, the Agency will require the appropriate signal
word and precautionary statements on the product label. Residential, school, or day care
exposure to /-Carvone is unlikely due to the expected use pattern. Should an exposure occur, the
health risk is expected to be minimal, based on the low acute toxicity and the history of safe use
of/-Carvone in foods, beverages, and consumer products. No significant exposure via drinking
water is expected when /-Carvone is used according to the product label directions. In the
unlikely event that exposure via drinking water does occur, the health risk is expected to be
minimal, based on the low acute toxicity of/-Carvone and its long history of safe use as a
flavoring ingredient in foods and beverages. BPPD has determined that no unreasonable adverse
effects to the U.S. population will result from the use of/-Carvone when label directions are
followed.
The Biopesticides and Pollution Prevention Division (BPPD) has reviewed data requirements for
granting registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide
Act (FIFRA), and has determined that the data/information submitted for Tier I Acute Toxicity
and Product Chemistry adequately satisfy current guideline requirements (refer to 40 C.F.R.
SubpartU§ 158.2000).
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II. ACTIVE INGREDIENT OVERVIEW
Common Name: /-Carvone
Chemical Names: 2-Cyclohexen-l-one, 2-methyl-5-(l-methylethenyl)-, (5R)-
2-Cyclohexen-l-one, 2-methyl-5-(l-methylethenyl)-, (R)- (9CI)
2-Cyclohexen-l-one, 2-methyl-5-(l-methylethenyl)-, (theta)-
(-)-Carvone
(R)-Carvone
L(-)-Carvone
p-Mentha-6,8-dien-2-one, (-)-
p-Mentha-6,8-dien-2-one, (R)-(-)-
1-p-Mentha-1 (6),8-dien-2-one
l-l-Methyl-4-isopropenyl-6-cyclohexen-2-one
Trade & Other Names: Bedoukian L-Carvone
CAS Registry Number: 6485-40-1
OPP Chemical Code: 079500
Type of Pesticide: Biochemical pesticide (Insect Repellent)
Application rates and methods vary depending on the product. For specific information
regarding the product^ refer to Appendix B.
III. REGULATORY BACKGROUND
On July 15, 2008, the Agency received an application filed by Bedoukian Research, Inc. 21
Finance Dr., Danbury, CT 06810 (submitted by Keller and Heckman LLP, 1001 G Street, N.W.,
Suite 500 West, Washington, DC 20001) to register the product Bedoukian /-Carvone
containing the new biochemical active ingredient /-Carvone at 99.5%. A notice of receipt of this
application was published in the Federal Register March 4, 2009 (74 FR Number 41 Page 9396).
A. Food Clearances/Tolerances
Currently, this active ingredient is not registered for use on food or feed commodities. A
tolerance or exemption from the requirement of a tolerance is not relevant.
IV. RISK ASSESSMENT
A. Active Ingredient Characterization
The active ingredient /-Carvone is the fragrance of mint, and comprises 50-65% of the essential
oil from the spearmint plant (Mentha spicatd). It can also be made synthetically from d-
limonene. Both the natural and synthetic forms of/-Carvone are used as flavorings in a variety of
foods, including candies, chewing gum, beverages, and baked goods, and are also used to flavor
toothpaste and mouthwash. Additionally, /-Carvone is used as a fragrance in personal care
products such as soaps, cosmetics, and perfumes, and in consumer products such as air
fresheners.
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The technical grade active ingredient (TGAI) is identified on the proposed product label as
Bedoukian L-Carvone. The description of the production process, including the formation of
impurities, was examined by the Agency and found to be acceptable in meeting current guideline
standards. The analytical method used to determine the content of the active ingredient is also
acceptable. Physical and chemical properties were submitted for the TGAI and are adequate.
Refer to Table 1 in Appendix A for a summary of product chemistry data requirements. Refer to
Table 2 in Appendix A for the summary of physical and chemical characteristics for /-Carvone.
All product chemistry data requirements for registration of/-Carvone have been satisfied.
B. Human Health Assessment
1. Toxicology
For acute toxicity data requirements, toxicity categories are assigned based on the hazard(s)
identified from studies and/or information on file with the Agency. The active ingredient is
classified into Toxicity Category I, II, III or IV where Toxicity Category I represents the highest
toxicity and Toxicity Category IV indicates the lowest toxicity. For more information, refer to
http://www.epa.gov/pesticides/pestlabels/.
The registrant requested waivers for the Tier I mammalian toxicity studies (Table 3) based on the
historically safe use of/-Carvone as a flavoring and fragrance agent, and the availability of
previously-generated toxicity data for /-Carvone or surrogate compounds in the open literature.
The Agency has reviewed the information submitted to support the mammalian toxicity data
waivers and found it to be adequate to support registration of 1-Carvone.
Adequate mammalian toxicology data/information is available to support registration of/-
Carvone. All toxicology data requirements for /-Carvone have been satisfied.
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a. Acute Toxicity
Acute toxicity testing is required to 1) determine systemic toxicity from acute exposure via the
dermal, inhalation and oral routes, 2) determine irritant effects from exposure to the eyes and 3)
determine the potential for skin sensitization (allergic contact dermatitis). The registrant
requested waivers for conducting acute toxicity testing, based on the history of safe use in food,
fragrances, and other consumer products, and the availability of sufficient acute toxicity data for
/-Carvone or surrogate compounds in the public literature.
In an acute oral toxicity study with rats, the LD50 (the dose required to kill half the members of
the tested population) for /-Carvone administered orally by gavage was 5.4 grams/kilogram of
body weight (mg/kg bw) (Quest International, 1986a).
In an acute dermal toxicity study with the surrogate chemical d-Carvone, the acute dermal LD50
in rabbits was 3,860 mg/kg bw (Opdyke, 1978).
Carvone has been used extensively as a fragrance in consumer and personal care products,
resulting in much higher exposures than those that would likely result from the use of products
containing /-Carvone as an area insect repellent, with no evidence of inhalation toxicity.
In studies to determine irritant/corrosive effects on the eyes of mammals (Quest International,
1986b, 1986c), /-Carvone was instilled into the eye of New Zealand white rabbits. Three rabbits
treated with 10% test material in Tween 80 had a slight transient conjunctivitis, with unaffected
corneas, resolving within 24 hours. One rabbit treated with 50% test material in Tween 80
showed loss of an extensive area of corneal epithelium, with moderate corneal swelling and iritis.
Conjunctivitis was slight, but lasted eight days. A persistent pannus developed. One rabbit
treated with undiluted test material showed superficial corneal effects with slight conjunctivitis,
healing by day four.
/-Carvone was not found to be a dermal irritant in guinea pigs treated with 10%, 20%, or 50% /-
Carvone in acetone/polyethylene glycol for 24 hours (Quest International, 1983). In humans, /-
Carvone was not an irritant when applied at a concentration of 2.25% in 1:3 ethanol:diethyl
phthalate for 24 hours, which was repeated nine times at 24-hour intervals (Harrison and Spey,
2000).
In a dermal sensitization test with guinea pigs, /-Carvone produced sensitization at a challenge
concentration of 1% following an intradermal induction using 10% /-Carvone (Kozuka, 1996). In
a patch test, human subjects were induced with 0.3 mL of/-Carvone nine times over three weeks
(Harrison and Spey, 2007). A challenge with 2.25% (2657 jig/cm2) Carvone did not produce
sensitization in any of the 99 subjects.
For more information regarding the acute toxicity data requirements, refer to Table 3 in
Appendix A.
b. Subchronic Toxicity
Subchronic data is required to determine a no-observed-effect-level (NOEL) and toxic effects (if
any) associated with repeated or continuous exposure to a test substance for a period of 90 days.
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The registrant requested waivers for conducting a 90-Day Inhalation Toxicity study, based on the
history of safe use. Carvone has been used extensively as a fragrance in consumer and personal
care products, resulting in much higher exposures than those anticipated to result from the use of
/-Carvone as an area insect repellent, with no evidence of inhalation toxicity.
For more information regarding the subchronic data requirements, refer to Table 3 in Appendix
A.
c. Developmental Toxicity and Mutagenicity
The registrant requested waivers for Developmental Toxicity and Mutagenicity testing, based on
the history of safe use in food, fragrances, and other consumer products, and the availability of
sufficient mutagenicity data for /-Carvone or surrogate compounds in the public literature.
Carvone has a long history of use as a flavoring in foods. Based on current levels of per capita
intake in the US (9900 ng/day), the World Health Organization (WHO) has concluded that there
is no safety concern for Carvone (WHO, 1999). Furthermore, the level of exposure to pregnant
women based on the proposed use pattern as an area insect repellent would be negligible.
Carvone and surrogate compounds have tested negative in a variety of gene mutation studies
(Florin et al., 1980; Mortelmans et al., 1986; National Toxicology Program (NTP), 1990;
Rockwell, 1979; Matsui et al., 1989). Equivocal results were found in a sister chromatid
exchange study and a chromosomal aberration study with Chinese hamster ovary cells (NTP,
1990), but WHO did not consider this to be an issue in its assessment of/-Carvone as a safe food
additive (WHO, 1999).
For more information regarding these data requirements, refer to Table 3 in Appendix A.
d. Effects on the Endocrine System
EPA is required under the Federal Food, Drug, and Cosmetics Act (FFDCA), as amended by the
Food Quality Protection Act (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 Disrupter Screening and Testing Advisory Committee (EDSTAC), EPA determined
that there was scientific basis 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, the Agency will use FIFRA and, to the extent that effects in wildlife may
help determine whether a substance may have an effect in humans, FFDCA authority to require
the wildlife evaluations. As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disrupter Screening Program (EDSP).
The Agency is not requiring information on the endocrine effects of/-Carvone at this time. The
Agency has considered, among other relevant factors, available information concerning whether
the active ingredient may have an effect on humans similar to an effect produced by naturally
occurring estrogen or other endocrine effects. There is no known metabolite that acts as an
endocrine disrupter produced by this active ingredient. Based on the low potential exposure level
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associated with the proposed use, the Agency expects no incremental adverse effects to the
endocrine or immune systems.
2. Dose Response Assessment
No toxicological endpoints were identified; therefore, a dose response assessment was not
required.
3. Drinking Water Exposure and Risk Characterization
No significant exposure via drinking water is expected when /-Carvone is used according to the
product label directions. The TGAI is intended for use in the manufacture of an area repellent for
mosquitoes and other biting flies. End use products using the TGAI will be placed in stations that
release small amounts of/-Carvone over the area, and it is unlikely to accumulate in drinking
water. In the unlikely event that exposure via drinking water did occur, the health risk would be
expected to be minimal, based on the low acute and dermal toxicity of/-Carvone and its long
history of safe use as a flavoring ingredient in foods and beverages.
4. Occupational, Residential, School and Day Care Exposure and Risk Characterization
a. Occupational Exposure and Risk Characterization
The potential for oral, dermal, eye and inhalation exposure to /-Carvone exists for handlers. The
Agency will require the appropriate signal word and precautionary statements on the product
label to mitigate any risk from exposure via these routes. Due to the low acute oral and acute
dermal toxicity and history of safe use in foods, beverages, and consumer products, worker
exposure data are not required.
b. Residential, School and Day Care Exposure and Risk Characterization
Residential, school, or day care exposure to /-Carvone is expected to be minimal since products
containing /-Carvone will release the TGAI in low amounts. The health risks are expected to be
minimal based on the low acute oral and acute dermal toxicity and the history of safe uses in
foods, beverages and other consumer products.
5. Risk Characterization
Human exposure to /-Carvone in light of the relevant safety factors in FQPA and FIFRA were
not considered for this active ingredient since /-Carvone is intended for formulation into end use
products with non food use patterns.
C. ENVIRONMENTAL ASSESSMENT
1. Ecological Hazards
Adequate non-target toxicology information is available to support registration of/-Carvone. All
non-target toxicology data requirements for /-Carvone have been satisfied.
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Ecological effects data requirements for /-Carvone were satisfied by the submitted data waiver
requests. Based on the waiver rationales, the Agency concluded that exposure and risk from the
manufacturing use product is not expected to pose a threat to non-target organisms.
For more information regarding the non-target toxicity data requirements, refer to Table 4 in
Appendix A.
2. Environmental Fate and Ground Water Data
The need for environmental fate and groundwater data was not triggered because results of the
acute toxicity studies did not trigger any additional Tier I studies.
3. Ecological Exposure and Risk Characterization
Based on the rationales submitted in the data waiver requests, the proposed use of/-Carvone as a
manufacturing use product is not expected to result in exposure or risk to non-target organisms.
4. Endangered Species Assessment
Based on the information presented above, the Agency has determined that registered use of/-
Carvone as an active ingredient will have No Adverse Effects (NAE) on threatened and/or
endangered species. When the product is used according to label use directions, there are no
concerns for any non-target organisms.
V. Risk Management Decision
A. Determination of Eligibility for Registration
Section 3(c)(5) of FIFRA provides for the registration of/-Carvone if it is determined that (A) /-
Carvone's composition is such as to warrant the proposed claims for it; (B) /-Carvone's labeling
and other materials required to be submitted comply with the requirements of FIFRA; (C) /-
Carvone will perform its intended function without unreasonable adverse effects on the
environment; and (D) when used in accordance with widespread and commonly recognized
practice /-Carvone will not generally cause unreasonable adverse effects on the environment.
The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by
the science assessments supporting products containing /-Carvone. Such products are not
expected to cause unreasonable adverse effects, and are likely to provide protection as claimed
when used according to label instructions. Therefore, /-Carvone is eligible for registration for the
labeled uses.
B. Regulatory Decision
The data submitted fulfill the requirements of registration for use of/-Carvone in the
manufacture of area insect repellents to repel mosquitoes and other biting flies. Refer to
Appendix B for product-specific information.
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1. Conditional/Unconditional Registration
All data requirements are fulfilled and EPA has determined that unconditional registration of /-
Carvone is appropriate.
C. Environmental Justice
EPA seeks to achieve environmental justice - the fair treatment and meaningful involvement of
all people, regardless of race, color, national origin, or income - in the development,
implementation, and enforcement of environmental laws, regulations, and policies. At this time
EPA does not believe that use of pesticide products containing /-Carvone will cause harm or a
disproportionate impact on at-risk communities.
For additional information regarding environmental justice issues, please visit EPA 's website at:
http://www.epa.gov/compliance/environmentaljustice/index.html.
VI. ACTIONS REQUIRED BY REGISTRANTS
The Agency evaluated all of the data submitted in connection with the initial registration of /-
Carvone and determined that these data are sufficient to satisfy current registration data
requirements. No additional data are required to be submitted to the Agency at this time. For
new uses and/or changes to existing uses, additional data may be required.
Not withstanding the information stated in the previous paragraph, it should be clearly
understood that certain, specific, data are required to be reported to the Agency as a requirement
for maintaining the Federal registration for a pesticide product. A brief summary of these types
of data are listed below.
A. Reporting of Adverse Effects
Reports of all incidents of adverse effects to the environment must be submitted to the Agency
under the provisions stated in FIFRA, Section 6(a)(2).
B. Reporting of Hypersensitivity Incidents
Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents)
must be reported to the Agency under the provisions of 40 C.F.R. Part 158.2050(d).
VII. Appendix A. Data Requirements (40 C.F.R. Part 158-Subpart U)
*NOTE: MRID numbers listed in the following tables are representative of supporting data for
the original registration of the product containing this active ingredient. Subsequent to this
registration, there may be additional MRIDs that support registration of other products
containing this active ingredient.
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TABLE 1. Product Chemistry Data Requirements for /-Carvone (40 C.F.R. § 158.2030)
OPPTS Guideline No.
830.1550
to
830.1670
830.1700
830.1750
830.1800
Study
Product identity;
Manufacturing process;
Discussion of formation of
unintentional ingredients
Analysis of samples
Certification of limits
Analytical method
Results (below are example results)
Submitted data satisfy the requirements
for product identity, manufacturing
process, and discussion of formation of
impurities.
Submitted data satisfy the requirements
for analysis of samples.
Limits listed in the CSF are adequate /
acceptable.
Acceptable.
MRID
47546101
47546102
47546102
47515503
TABLE 2. Physical and Chemical Properties of /-Carvone (40 C.F.R § 158.2030)
OPPTS Guideline
No.
830.6302
830.6303
830.6304
830.6313
830.6314
830.6315
830.6316
830.6317
830.6319
830.6320
830.7000
830.7100
830.7200
830.7220
830.7300
830.7520
830.7550
830.7560
830.7570
830.7840
830.7950
Property
Color
Physical State
Odor
Stability to Normal and Elevated
Temperatures, Metals and Metal Ions
Oxidation/Reduction:
Chemical Incompatibility
Flammability
Explodability
Storage Stability
Miscibility
Corrosion Characteristics
pH
Viscosity
Melting Point/Range
Boiling Point/Range
Density
Particle Size, Fiber Length and
Diameter Distribution
Partition Coefficient (n-
Octanol/Water)
Water Solubility
Vapor Pressure
Description of Result
Colorless to light yellow
Liquid @ room temperature
Spearmint
Stable
Not required
200°F
Not required
Store in glass, plastic, plastic-
lined or coated containers, not
metal. Do not store in iron.
Guideline study in progress;
initiated 7/2 1/2008.
Not applicable, product is only
marginally soluble in water.
Guideline study in progress;
initiated 7/2 1/2008.
Not applicable, product is only
marginally soluble in water.
2.72 Centistokes
<25°C (experimental)
9.86°C (EPA EPISuite, QSAR)
228.5°C (experimental)
224.23°C (EPA EPISuite, QSAR)
0.960 @25°C
7.4 Ib/gal @ 25°C
Not applicable, the product is a
liquid
<3.0
Marginally soluble (367.1 mg/L)
0.1mmHg@25°C
(experimental)
0.13 mmHg @ 25°C (EPA
EPISuite, QSAR)
MRID
47515504
47515504
47515504
47515504
47515504
47515504
47515506
47515504
47515504
47515504
47515504
47515504
47515504
47515504
47515504
47515504
47515504
47515504
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Table 3. Human Toxicology Data Requirements for /-Carvone (40 C.F.R § 158.2050)
Study/OPPTS Guideline No.
Acute oral toxicity (rat)
(870.1100)
Acute dermal toxicity (rat)
(870.1200)
Acute inhalation toxicity (rat)
(870.1300)
Primary eye irritation (rabbit)
(870.2400)
Primary dermal irritation (rabbit)
(870.2500)
Dermal sensitization (guinea pig)
(870.2600)
Hypersensitivity incidents
(885.3400)
90-Day inhalation toxicity
(870.3465)
Mutagenicity
(870.5100, 5300 and 5375)
Developmental toxicity
(870.3700)
Results
LD50 > 5400 mg/kg
Data waiver acceptable
LD50 = 3,860 mg/kg
Data waiver acceptable
No evidence of inhalation toxicity
Data waiver acceptable
Corneal irritation clearing within 7 days
Data waiver acceptable
Mild or slight
Data waiver acceptable
Data waiver acceptable
Data waiver acceptable
Data waiver acceptable
Data waiver acceptable
Data waiver acceptable
Toxicity
C atego ry/Des cription
IV
III
IV
III
IV
Produced
sensitization
effects
Potential for
sensitization
No safety concern
Negative
No safety concern
MRID
Quest
International
(1986)
47515505
Opdyke,
(1978)
47515505
Heuberger,
(2001)
47515505
Quest
International,
(1986)
47515505
Quest
International
(1985)
47515505
47515505
47515505
47515505
47515505
47515505
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TABLE 4. Non-Target Organism Toxicity Requirements for /-Carvone (40 C.F.R. § 158.2060)
Study/OPPTS Guideline No.
Avian acute oral toxicity
Colinus virginianus
(850.2100)
Avian oral toxicity
Colinus virginianus
(850.2200)
Avian dietary toxicity
Anas platyrhynchos
(850.2200)
Aquatic invertebrate acute toxicity
(Daphnia magna)
(850.1010)
Freshwater fish LC50
(Oncorhynchus mykiss)
(850.1075)
Non-target plant studies
(850.4000-4800, as applicable)
Non-target insect testing
(880.4350)
Results
Data waiver request submitted.
Data waiver request submitted.
Data waiver request submitted.
Data waiver request submitted.
Data waiver request submitted.
Data waiver request submitted.
Data waiver request submitted.
Toxicity
Category /Description
MRID
47515505
47515505
47515505
47515505
47515505
47515505
47515505
VIII. Appendix B.
For product specific information, please refer to http://www.epa.gov/pesticides/pestlabels
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IX. Appendix C.
REFERENCES
Florin, I, L. Rutberg, M. Curvall, et al. 1980. Screening of Tobacco Smoke Constituents for
Mutagenicity Testing Using the Ames Test. Toxicology 15:219-232.
Harrison, L.B., and D.R. Spey. 2000. Repeated Insult Patch Test with laevo-Carvone.
Unpublished Report 52896, Research Institute for Fragrance Materials, Inc.
Kozuka, T., H. Hayashi, H. Hiroyama et al. 1996. Allergenicity of Fragrance Materials:
Collaborative Study of the Second Research Group of the Japanese Society for Cutaneous
Health. Environmental Dermatology 3(4):326-335.
Matsui, S., R. Yamamoto, and H. Yamada. 1989. The Bacillus subtilis/microsome rec-assay for
the Detection of DNA Damaging Substances Which May Occur in Chlorinated and Ozonated
Waters. Water Sci. Technol. 21:875-887.
Mortelmans, K. S. Haworth, T. Lawlor, et al. 1986. Salmonella Mutagenicity Tests: II. Results
from the Testing of 270 Chemicals. Envrion. Mutag. 8:1-119.
National Toxicology Program. 1990. Toxicology and Carcinogenesis Studies of d-Carvone in
B6C3F1 Mice (Gavage Studies) (NTP TR 381). Department of Health and Human Services,
Research Triangle Park, North Carolina.
Opdyke, D.L.J. 1978. Fragrance Raw Materials Monographs. d-Carvone. Food Cosmet. Toxicol.
16, Suppl. 1:673-674.
Quest International. 1983. Guinea Pig Skin Sensitization Test with laevo-Carvone. Unpublished
Report.
Quest International. 1986a. Acute Oral Toxicity to Rats of laevo-Carvone. Unpublished Report.
Quest International. 1986b. Rabbit Eye Irritation Test with laevo-Carvone. Unpublished Report.
Quest International. 1986c. Rabbit Eye Irritation Test with laevo-Carvone. Unpublished Report.
Rockwell, P., and I. Raw. 1979. A Mutagenic Screening of Various Herbs, Spices, and Food
Additives. Nutrition and Cancer 1(4): 10-15.
World Health Organization (WHO). 1999. International Programme on Chemical Safety. Safety
Evaluation of Certain Food Additives. WHO Food Additive Series 42.
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