BIOPESTICIDES REGISTRATION ACTION DOCUMENT



# Tagetes Oil

PC Code : 176602

U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division

February 21 , 201 2Tagetes Oil Page 2 of 22 Biopesticides Registration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY:

................................ ................................ ................................ . 5

II. ACTIVE INGREDIENT OV ERVIEW

................................ ................................ .............. 7

II I. REGULATORY BACKGROUND

................................ ................................ .................... 7

A. Classification

................................ ................................ ................................ ........................ 7

B. Food Clearanc es/Tolerances

................................ ................................ ............................... 7

IV. RISK ASSESSMENT

................................ ................................ ................................ ......... 8

A. Active Ingredient Characterization

................................ ................................ .................... 8

B. Human Health Assessment

................................ ................................ ................................ .. 8

1. Toxicology

................................ ................................ ................................ ................................ ...................... 8

2. Dose Response Assessment

................................ ................................ ................................ ......................... 11

4. O ccupational, Residential, School and Day Care Exposure and Risk Characterization

...................... 11

5. Aggregate Exposure from Multiple Routes Inclu ding Dermal, Oral, and Inhalation

........................... 12

6. Cumulative Effects

................................ ................................ ................................ ................................ ...... 12

7. Risk Characterization

................................ ................................ ................................ ................................ . 12

C. E NVIRONMENTAL ASSESSMENT

................................ ................................ .............. 12

1. Ecological Hazards

................................ ................................ ................................ ................................ ...... 12

2. Environmental Fate and Ground Water Data

................................ ................................ .......................... 13

3. Ecological Exposure and Risk Characterization

................................ ................................ ...................... 13

4

. Endangered Species Assesment

................................ ................................ ................................ .................. 13

D. EFFICACY DATA

................................ ................................ ................................ ............ 13

V. RISK MANAGEMENT DECI SION

................................ ................................ ................. 14

A. Determination of Eligibility for Registration

................................ ................................ .. 14

B. Regulatory Decision

................................ ................................ ................................ ........... 14

VI. ACTIONS REQUIRED BY REGISTRANTS

................................ ................................ . 15

A. R eporting of Adverse Effects

................................ ................................ ............................ 15

B. Reporting of Hypersensitivity Incidents

................................ ................................ .......... 15

VII. APPENDIX A. Data Requirements (40 CFR Part 158)

................................ ................. 15

VIII. APPENDIX B. P roduct S pecific I nformation

. ................................ ................................ 19Tagetes Oil Page 3 of 22 Biopesticides Registration Action Document

IX. APPENDIX C . R eferences

. ................................ ................................ ................................ 19Tagetes Oil Page 4 of 22 Biopesticides Registration Action Document



### BIOPESTICIDES REGISTRATION ACTION DOCUMENT (BRAD) TEAM



## Branch Chief Linda A. Hollis, M.S.

Product Chemistry/ Human Health Effects/Nontarget Organisms Angela L. Gonzales, Biologist

Regulatory Action Leader Colin G. Walsh, M.S., BiologistTagetes Oil Page 5 of 22 Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY:

Tagetes o il is a new biochemical pesticide active ingredient intended for use as an insecticide/acaricide for the control of mites, whiteflies, aphids, thrips, mealybugs, scales, and pyslla on a variety of food crops. The active ingredient is extracted from the flo wering herb, Tagetes minuta (Muster John Henry or Mexican Marigold). The major constituents of the identified components of tagetes oil are terpenes, which are found in a variety of essential oils. Tagetes oil, as Tagetes patula L.

, T. erecta L. , or T. minuta L . ( T. glandulifera Schrank)

, is approved by the U.S. Food and Drug Administration (FDA) for use in food as a natural flavoring substance and natural adjuvant (in the oil form only) under 21 CFR 172.510. Tagetes oil is also

used in some cosmetics in cluding shampoos, soaps and lotions (EWG, 2010).

The Biopesticides and Pollution Prevention Division (BPPD) determined that the

data/information submitted for p roduct c hemistry and Tier I a cute t oxicity for tagetes oil satisf y the current guideline requi rements. Acceptable scientific rationales were submit ted for the subchronic [90

- day oral (OCSPP 870.3100) and 90

- day inhalation (OCSPP 870.3465) ], developmental (OCSPP 870.3700), and mutagenicity data requirements [in vitro mammalian cell assay (OCSPP 870. 5300 and 5375)] in lieu of data. BPPD determined that the rationale s submitted w ere acceptable based on tagetes oil ’s toxicological and exposure profile s . S ignificant exposure to humans is not anticipated for tagetes oil based on low application rates, appropriate Personal Protective Equipment (PPE) requirements on the product label, and rapid degradation in

the environment. BPPD granted a waiver from conducting a 90

- day dermal study (OCSPP 870.3250) based on the rapid vol atilization of the active ingredient and because p rolonged dermal exposure is not expected ( the product is not purposely applied to the skin and handlers/applicators are required to wear appropriate PPE ) . BPPD received data for the mutagencity data require ment [ A mes test (OCSPP 870.5100)] , which indicated that tagetes oil was not mutagenic with or without metabolic activation. Although the data requirements were satisfied for the new active ingredient, tagetes oil, BPPD notes that s hould future intended end

use product ( EP ) applications result in different anticipated exposures to humans, the se data requirements may need to be re addressed.

F or n on t arget o rganisms and e nvironmental f ate data requirements (O CS PP 850. 1010 to 850.4450), the applicant either sub mitt ed acceptable data/information for the EP s or the data were waived because the guideline study was not applicable. BPPD granted a request to bridge

the data from the EP s to the active ingredient, tagetes oil, because the applicant indicated that the active ingredients in the EP s act synergistically; thus

, the combination of these chemicals is more potent as an insecticide than each active ingredient alone. Therefore, the toxicological profile of

the EP s is more relevant to the risk assessment than the toxicological profile of tagetes oil alone.

Based on th e nontarget organism data from the EP s , which indicated that the EP s w ere practically nontoxic

, and the screening level risk assessment, the Agency determined that registered use of tagetes oil in the EPs should not result in adverse effects to birds, fish, aquatic invertebrates, plants

, or nontarget insects.

Based on the a cute t oxicity data for tagetes oil , the active ingredient is toxicity category III. EPA has not identified any toxic endpoints for nontarget mammals, birds, plants, aquatic, or soil organisms. EPA has no concerns for any nontarget organisms exposed to tagetes oil when usedTagetes Oil Page 6 of 22 Biopesticides Registration Action Document

in accordance with approved label directions. Given that tagetes oil has very low toxicity and presents litt le, if any

, risk to nontarget organisms, EPA has concluded that it is in the best interests of the public to issue the registration for the EPs, Bug Oil Food Use (EPA File Symbol

No. 85937

- E) and Bug Oil Ornamental (EPA File Symbol No. 85937

- R) , which cont ain this new active ingredient, tagetes oil.

BPPD has reviewed the data/information in support of the requirements for granting registration under Section 3(c)(5) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). It has

been determined that the data/information submitted adequately satisfy current guideline requirements (please refer to 40 CFR Subpart U § 158.2000)

.

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for the public to participate on major registrati on decisions before they occur. According to this policy, EPA provide s a public comment period prior to making a registration decision for the following types of applications: new active ingredients, first food use, first outdoor use, first residential use; and any registration decisions for which the Agency believes there may be substantial public interest.

Consistent with the policy of making registration actions more transparent, tagetes oil is subject to a 30 day comment period as a “ new active ingredient”. The notice for this comment period

include s the draft Biopesticides Registration Action Document ( BRAD) and draft product label s for the EPs, Bug Oil Food Use and Bug Oil Food Ornamental, which contain this new active ingredient, ta getes oil. The docket identification ( ID ) number is EPA

- HQ

- OPP

- 20 09

- 0822 . The Agency believes that based on the risk assessment and information submitted in support of the registration of the EPs containing tagetes oil , it is in the best interests of the p ublic to issue the registration for Bug Oil Food Use and Bug Oil Food Ornamental. The basis for this decision can

be found in the risk assessment for tagetes oil , which is characterized in this BRAD.Tagetes Oil Page 7 of 22 Biopesticides Registration Action Document

II. ACTIVE INGREDIENT OVERVIEW

Common Name: Tagetes Oil

Chemical Names: N/A

Trade & Other Names: Marigold Oil

CAS Registry Number: 8016

- 84

- 0

OPP Chemical Code: 176602

Type of Pesticide: Biochemical Pesticide ( Insecticide/Acaricide )

III. REGULATORY BACKGROUND

On September 18 , 20 09 , EPA received an application filed by Exponent, 1150 Connecticut Avenue, NW, Suite 1100

, Washington, DC 20036

, on behalf of Plant Impact plc, 12 South Preston Office Village, Cuerd e n Way, Bamber Bridge, Preston, PR5 6BL, United Kingdom, to register the product s, Bug Oil Food Use (EPA File Symbol No. 85937

- E) and Bug Oil Ornamental (EPA File Symbol No. 85937

- R) co ntaining the new biochemical active ingredient, tagetes oil, and the currently regist ered active ingredients, canola oil, thyme oil, and wintergreen

oil. A notice of receipt (NOR) of this application, allowing for a 30

- day comment period, was published in the Federal Register o n December 16, 2009 (7 4 FR 666 39 )

. No comments were

received following this publication

.

A. Classification

On July 6, 2006, the biochemical classification committee determined that tagetes oil is marigold oil, which was previously classified as a biochemical in 1997 due to its nontoxic mode of action, natural occurrence in the environment, and history of exposure to humans and the environment demonstrating minimal toxicity. Tag etes oil is derived from Tagetes spp. (marigolds), specifically, African marigold ( Tagetes erecta ) and Aztec marigold ( Tagetes minuta ). The mode of action is repellency by tagetes oil alone and suffocation by tagetes oil in conjunction with the

other acti ves in the proposed EPs , canola oil, thyme oil, and wintergreen oil.

B. F ood Clearances/Tolerances

The applicant filed a petition (PP 9F7619) proposing to establish an exemption from the requirement of a tolerance for residues of tagetes oil in or on all food commodities. A notice of filing (NOF)

, allowing for a 30

- day comment period, was published in the Federal Register on December 16, 2009 (74 FR 66644) . No comments were received following this publication

. EPA determined during the review of the pe tition that the active ingredient, tagetes oil, is an edible oil and is exempt from the requirement of a tolerance as a minimal risk active ingredient under 40Tagetes Oil Page 8 of 22 Biopesticides Registration Action Document

CFR 180.950(c). The petition (PP 9F7619) filed by the applicant is no longer applicable to this new active ingredient, tagetes oil.

IV. RISK ASSESSMENT

A. Active Ingredient Characterization

Tagetes Oil is a new biochemical pesticide active ingredient intended for use as an insecticide/acaricide for the control of mites, whiteflies, aphids, thrips, mealybugs, scales, and pyslla on a variety of food crops. The active ingredient is extracted from the flowering herb, Tagetes minuta (Muster John Henry or Mexican Marigold). There are many species within the Tagetes genus. The herb is non

- native to the United States, but is found in California, Hawaii,

and in most o f the states on the east coast (USDA Plants Database, 2010). It has a widespread geographic distribution

, but is prevalent in subtropical and tropical climates. The major constituents of the identified components of tagetes oil are terpenes, which are foun d in a variety

of essential oils.

Tagetes oil, as Tagetes patula L.

, T. erecta L. , or T. minuta L . ( T. glandulifera Schrank) is approved by the U.S. Food and Drug Administration (FDA) for use in food as a natural flavoring substance and natural adjuvan t (in the oil form only) under 21 CFR 172.510. Reported uses of tagetes oil as a food additive are in alcoholic beverages, nonalcoholic beverages, baked goods, chewing gum, condiments (e.g., relishes), frozen dairy, gelatins (e.g., puddings), hard candy, a nd soft candy (Burdock, 2005). Tagetes oil is also used in some cosmetics including shampoos, soaps and lotions (EWG, 2010).

Descriptions of the product formulation and production process, formation of impurities, and physical and chemical characteristic s were examined by BPPD and found to be acceptable in meeting current guideline standards

.

All product chemistry data requirements for registration of tagetes oil have been satisfied.

For more information regarding product chemistry data requirements, refer to Tables 1 and 2 in Appendix A

.

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 Cat egory I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxicity

.

Adequate mammalian toxicology data /information is available to support registration of tagetes
oil. All toxicology data requirements for tagetes oil have been satisfied.Tagetes Oil Page 9 of 22 Biopesticides Registration Action Document

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 fo r skin sensitization (allergic contact dermatitis).

Tier I acute toxicity studies submitted and reviewed showed that tagetes oil is a toxicity category

III ( slightly toxic ) compound via acute dermal route of exposure , based on testing at a limit dose

of 2000 mg a.i./kg in rat s, and is moderately irritating to the skin based on the results of a primary dermal irritation study in rabbits. Tagetes oil falls in Toxicity Category I V (not toxic) for

acute oral toxicity, acu te inhalation toxicity, and primary eye irritation

. Tagetes oil is minimally irritating in the eye and is not a dermal sensitizer.

For more information regarding acute toxicity data requirements, refer to Table 3 in Appendix A

.

b. Subchronic Toxicit y

Subchronic data are required to determine a no

- observed

- effect

- level (NOEL) and any toxic effects associated with repeated or continuous exposure to a te st substance for a period of ninety days

.

Rationale was submitted for the subchronic [90

- day oral (O CS PP 870.3100) and 90

- day inhalation (O CS PP 870.3465) ] in lieu of data. BPPD determined that the rationale submitted was acceptable based on the EPs toxicological and exposure profile

, summarized below.

i. Tagetes oil is an edible oil and is exempt from the requirement of a tolerance as a minimal risk active ingredient under 40 CFR 180.950(c)

. ii. Tagetes oil is an edible oil and is already consumed in the human diet as it is used as a food additive and FDA has approved the use of the oil (in oil form only) with no

limitations as a food additive under 21 CFR 172.510.

ii i

. Significant exposure to humans is not anticipated based on low application rates and rapid degradation in the environment.

iv

. Significant repeat exposure of tagetes oil to humans as a gas, vapor, or aerosol is not anticipated based on the use pattern.

A waiver requested for the subchronic [90

- day dermal (O CS PP 870.325 0)] was granted by BPPD, based on the EPs toxicological and exposure profile , summarized below.

i. Pr olonged dermal exposure is not expected because the product is not purposely applied to the skin and handlers/applicators are required to wear appropriate PPE.

ii. Tagetes oil is expected to volatilize rapidly after application.

For more information regar ding the subchronic data requirements, refer to Table 3 in Appendix

A.Tagetes Oil Page 10 of 22 Biopesticides Registration Action Document

c. Developmental Toxicity and Mutagenicity

A r ationale for lack of toxicity was submitted for the developmental toxicity data requirement (OCSPP 870.3700 ) in lieu of data. BPPD determined that the rationale submitted was acceptable

based on the EPs toxicological and exposure profile , summarized below.

i. Tagetes oil is an edible oil and is exempt from the requirement of a tolerance as a

minimal risk acti ve ingredient under 40 CFR 180.950(c).

ii. Tagetes oil is an edible oil and is already consumed in the human diet as it is used as a food additive and FDA has approved the use of the oil (in oil form only) with no

limitations as a food additive under 21 C FR 172.510.

iii. Significant exposure to female humans is not anticipated based on low application rates, appropriate PPE requirements on the label, and rapid degradation in the environment.

T he t ier I mutagenicity study [Ames test (OCSPP 870.5100)] submitted and reviewed showed that tagetes oil concentrations of up to 5,000 ug/plate were not mutagenic with or without metabolic activation. Rationale was submitted for the Tier I mutagenicity data requirement [ in vitro mammalian cell assay (OCSPP 870.5300 and 5375)] in lieu of data. BPPD determined that the rationale submitted was acceptable based on the EPs toxicological and exposure profile

, summarized below.

i. Tagetes oil is an edible oil and is exempt fr om the requirement of a tolerance as a minimal risk active ingredient under 40 CFR 180.950(c).

ii. Tagetes oil is an edible oil and is already consumed in the human diet as it is used as a food additive and FDA has approved the use of the oil (in oil form only) with no

limitations as a food additive under 21 CFR 172.510.

iii. Significant exposure to humans is not anticipated based on low application rates, appropriate PPE requirements on the label, and rapid degradation in the environment.

For more in formation regarding developmental and mutagenicity data requirements, refer to Table 3 in Appendix A

.

d. Tier II/Tier III

The data requirement s were not required due to the nature of the active ingredient and its

intended uses in potential new EP products ( insect icides and acaricides ).

e. Effects on the Endocrine System

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an eff ect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily requiredTagetes Oil Page 11 of 22 Biopesticides Registration Action Document

determinations. Tier 1 consists of a battery of 11 screening ass ays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal sys tems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and nine i nert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and water, residential activity, and certain post

- application agricultural scenarios.

This list should not be construed as a lis t of known or likely endocrine disruptors.

Tagetes oil is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA section 408(p) the Agency must screen all pesticide chemicals. Accordingly, E PA anticipates issuing future EDSP test orders/data call

- ins for all pesticide active ingredients.

For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening batt ery, please visit our website: http://www.epa.gov/endo/.

2. Dose Response Assessment

Because n o toxicolog ical endpoints were identified for this active ingredient

, a dose respon se assessment was not required.

3. Drinking Water Exposure and Risk Characterization

No significant exposure via drinking water is expected when tagetes oil is used according to the product label directions

. The active ingredient biodegrades rapidly in the environment (59% volatilization in 48 hours), is applied at low application rates and is not directly applied to water; therefore, residues of tagetes oil are unlikely to accumulate in drinking water. In the unlikely event that exposure via drinking water d oes occur, the health risk would be expected to be minimal based on the low acute oral toxicity of tagetes oil and the fact that t agetes oil is an edible oil and is exempt from the requirement of a toleranc e as a minimal risk active ingredient under 40 CFR 180.950(c).

4. Occupational, Residential, School and Day Care Exposure and Risk Characterization

a. Occupational Exposure and Risk Characterization

An occupational exposure assessment was not conducted for tagetes oil, and is not required. Appropriate PPE requirements on the label will mitigate any potential exposure to applica tors
and/or handlers. Additionally, no relevant toxicological e ndpoints have been identified. Based onTagetes Oil Page 12 of 22 Biopesticides Registration Action Document

the data and information available to the Agency, anticipated exposure is not likely to result in

unreasonable risk to humans.

b. Residential, School and Day Care Exposure and Risk Characterization

Exposure to tagetes oil will be minimal in residential, school, and day care areas, as the product containing this active ingredient is intended for use on horticultural and agricultural crops.

5

. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation

There is reasonable certainty that no harm to the U.S. population will result from aggregate

exposure to tagetes oil . This includes all exposures for which there is reliable information. The Agency arrived at this conclusion based on the lack of toxicity of this active ingredient and the already widespread exposure without any reported adverse effects on human health. The risks from aggregate exposure via oral, dermal and inhalation exposure are a compilation of three low

risk exposur e scenarios and are negligible.

6

. Cumulative Effects

Pursuant to FFDCA section 408(b)(2)(D)(v), EPA has considered available information concerning the cumulative effects of tagetes oil residues and other substances that have a

common mechanism of toxic ity. No toxicological endpoints have been established for exposure to tagetes oil; therefore, cumulative effects with other substances that share a common mechanism of toxicity are not expected.

7. Risk Characterization

The Agency considered human exposure to tagetes oil in light of the relevant safety factors in FQPA and FIFRA. A determination has been made that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will result from the use of tagetes oil when label instructions are followed.

C. ENVIRONMENTAL ASSESSMENT

1. Ecological Hazards

Adequate non target toxicology data /information is available to support registration of tagetes oil with the submission of nontarget toxicology data on the EP s

. All nontarget toxicology data requirements for tagetes oil have been satisfied.

The EP s are practically nontoxic to birds, fish and aquatic invertebrates and is not phytotoxic.

The EPs are prac tically nontoxic via exposure through contact to nontarget insects.

For more information regarding nontarget organism toxicity data requirements, refer to Table 4 in Appendix A

.Tagetes Oil Page 13 of 22 Biopesticides Registration Action Document

2. Environmental Fate and Ground Water Data

Environmental fate and groundwater data are not required at this time because the results of the nontarget organism toxicity assessment (Tier I data requirements) did not trigger these Tier II data requirements.

3. Ecological Exposure and Risk Character ization

Toxicity studies have not been submitted for tagetes oil. A lack of toxicity r ationale and data on the proposed EP s ha ve been submitted to fulfill these data requirements. According to the applicant , the active ingredients act synergistically; thus

, the combination of these chemicals is more potent as an insecticide than each ingredient alone. Therefore, the toxicological profile of

the EP s are germane to the risk assessment rather than the toxicological profile of tagetes oil alone. For registr ation of the proposed EP s , the Agency has bridged the nontarget organism toxicology data from the EP s to th e active ingredient , tagetes oil. The product is a contact insecticide that operates through a physical mode of action. The product is practically no ntoxic to birds, fish and aquatic invertebrates and is not phytotoxic; toxic endpoints have not been identified for these species. The product is practically nontoxic via exposure through contact to nontarget insects. Based on the data submitted, the Agenc y has indicated in its review that the product may be moderately toxic via oral exposure to nontarget insects; however, no mortality was observed at the highest dose tested in the study. Additionally, significant oral exposure is not anticipated as the pr oduct is a contact insecticide and is expected to degrade rapidly in the environment. Toxic endpoints have not been identified for nontarget insects via the oral or contact route of exposure. The results of the submitted studies and screening

- level risk

as sessment indicate that use of the product according to label instructions should not result in adverse effects to birds, fish, aquatic invertebrates, plants or nontarget insects.

4. Endangered Species Assessment

The Agency has not conducted a risk assessment that supports a complete endangered species

det ermination. The ecological risk assessment planned during registration review will allow the Agency to determine whether tagetes oil’s use has “no effect” or “may effect” federally listed

threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Ser vice and/or National Marine Fisheries Services (the Services) as appropriate.

D. EFFICACY DATA

Product performance data must be developed for all pesticides to ensure that pesticide products will perform as intended and that unnecessary pesticide ex posure to the environment will not occur as a result of the use of ineffective products. The Agency reserves the right to require on a

case

- by

- case basis, submission of efficacy data for any pesticide product registered or proposed for registration that a re intended to be used to control a pest of significance public health importance and a public health pest as defined in FIFRA section 28(d) and section 2(nn). For further guidance on product performance requirement, refer to Pesticide Registration Notice (PR)Tagetes Oil Page 14 of 22 Biopesticides Registration Action Document

Notices 96

- 7, 2002

- 1 and Explanation of Statutory Framework for Risk

- Benefit Balancing for

Public Health Pesticides ( http://www.epa.gov/PR _Notices/pr1996

- 7.pdf ) ( http://www.ea.gov/PR_Notices/pr2002

- 1.pdf ) and ( http://www.epa.gov/pesticides/health/risk

benefit.htm ).

The EPs submitted with this n ew active ingredient did not list pests of significance public health importance or a public health pest as defined in FIFRA section 28(d) and section 2(nn). Therefore, product performance (efficacy) was not evaluated.

V. Risk Management Decision

A. Determination of Eligibility for Registration

Section 3(c)(5) of FIFRA provides for the registration of a new active ingredient if it is

determined that : (A) its composition warrant s proposed claims; (B) its labeling and other materials comply with the r equirements of FIFRA; (C) it will perform its intended function without unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice

, it will not generally cause unreasonable adverse

effe cts on the environment.

The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by

the science assessments supporting products containing the technical grade active ingredient

, tagetes oil . Such products are not expected to cau se unreasonable adverse effects

. Therefore, tagetes oil as a technical grade active ingredient is eligible for registration for the labeled uses.

B. Regulatory Decision

The data submitted fulfill the registration requirements of tagetes oil for use as an insect icide and

acaricide

. Refer to Appendix B for product

- specific information.

Conditional/Unconditional Registration

All data requirements are fulfilled, and EPA determined that an unconditional registration of tagetes oil 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

— with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. At this time

, EPA does not believe that use of tagetes oil pesticide products will cause harm or a disproportionate impact on at

- risk communities. For additional information regarding

environmen tal justice issues, please visit EPA’s website at http://www.epa.gov/compliance/environmentaljustice/index.html

.Tagetes Oil Page 15 of 22 Biopesticides Registration Action Document

V I

. ACTIONS REQUIRED BY REGISTRANTS

EPA evaluated all data subm itted in connection with the registration of the tagetes oil pesticide products and determined that these data are sufficient to satisfy current registration data requirements. At this time, n o additional data must be submi tted to EPA for these particular products. For new uses and/or changes to existing uses, EPA may require additional data.

Notwithstanding the information stated in the previous paragraph, it should be clearly understood that certain specific data are required to be reported to EPA as a requirement for maintaining the Federal registration for a pesticide product. A brief summa ry of these types of data are listed

below.

A. R eporting of Adverse Effects

Pursuant to FIFRA section 6(a)(2), r eports of all incidents of adverse effects to the environment

must be submitted to EPA

.

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 CFR Part 158.2050(d).

VI I

. Appendix A. Data Requirements (40 CFR Part 158

- Subpart U)

*NOTE: Master Record Identification (MRID) numbers listed in the following tables are representative of supporting data/information 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.

TABLE 1

. Product Chemistry Data Requirements for Tagetes Oil (40 CFR § 158.2030)

OPPTS G uideline N o

. Study R esults MRID

830.1550

to
830.1670 Product identity; Manufacturing process;

Discussion of formation of unintentional ingredients Acceptable; Confidential Business Information (CBI) 47868201

830.1700 Analysis of samples Acceptable; CBI

830.1750 Certification of limits Limits listed in the CSF are adequate / acceptable. 47868201

830.1800 Analytical method Acceptable; CBITagetes Oil Page 16 of 22 Biopesticides Registration Action Document

TABLE 2

. Physical and Chemical Properties of Tagetes Oil (40 CFR § 158.2030)

OPPTS Guideline No. Property Description of Result MRID

830.6302 Color Yellow to orange 47868202

830.6303 Physical State Liquid 47868202

830.6304 Odor Bright, diffusive, fruity

- floral 47868202

830.6313 Stability to Normal and Elevated Temperatures, Metals and Metal

Ions Stable under normal and elevated temperatures for 14 days. No evidence of instability under contact with metals and

metal ions for 14 days at ambient and

el evated temperatures. Some color and physical state changes to the metal ions were observed during the study. 48649812

830.6315 Flammability Flashpoint = 63 °C

43 °C 47868203

47868202

830.6317 Storage Stability Not required for TGAI.

830.6319 Miscibility Not applicable, the product is not to be mixed with petroleum solvents.

830.6320 Corrosion Characteristics Not required for TGAI.

830.7000 pH 3.79 (neat oil) 4.43 (1% dilution) 47868203

830.7050 UV/Visible light absorption UV profiles are similar under all pH conditions. No significant molar absorbance (ε) at the wavelength range of

290

- 750 nm.

Neutral pH: ε = 44.52, 45.98 at wavelength 237 nm Basic pH: ε = 40.13, 44.80 at wavelength 237 nm Acidic pH: ε = 45.38, 47.81 at wavelength 237 nm 48649806

830.7100 Viscosity 1.5

- 4.05 mPa at shear rates of 5

- 200 rpm

at 20 °C 47868202

830.7200 Melting Point/Range Not applicable, the product is a liquid.

830.7220 Boiling Point/Range 190 °C 47868202

830.7300 Density Specific gravity = 0.870 at 20°C 47868202

830.7370 Dissociation Constant in Water Does not dissociate in water. 47730401

47730409

830.7550

830.7560

830.7570 Partition Coefficient (n

- Octanol/Water) Values estimated using KOWWIN version 1.68 (US EPA) were submitted for the major components of tagetes oil, as the oil itself is not amenable to testing.

Limonene: Log K

ow = 4.83 Ocimene: Log K

ow = 4.80 Dihydrotagetone Log K

ow = 2.92 Linalool Log K

ow = 3.38 48649 802

830.7840 Water Solubility Insoluble 47868202

830.7950 Vapor Pressure Approximately 59% volatilization (measured via weight loss) in 48 hours in laboratory study

. 48329208Tagetes Oil Page 17 of 22 Biopesticides Registration Action Document

Table 3. Mammalian Toxicology Data Requirements for Tagetes Oil (40 CFR § 158.2050)

Study/OPPTS Guideline No. Results Toxicity Category/Description MRID

Acute oral toxicity (rat) (870.1100) LD 50 >5,000 mg/kg (females) IV 47868213

Acute dermal toxicity (ra ts ) (870.1200) LD 50 > 2000 mg/kg for males, females, and for

both sexes combined III 47868214

Acute inhalation toxicity (870.1300) LC 50 > 5.20 mg/L IV 48329203

Primary eye irritation (870.2400) Minimally irritating: positive conjunctival irritation and moderate reddening of sclerae were noted on 3/3 rabbits one hour post

instillation with clearance by 24 hours. IV 47868215

Primary dermal irritation ( rabbit ) (870.2500) Moderately irritating: well defined erythema on 3/3 rabbits one hour after patch removal with clearance on one rabbit by day 7, with reduction to very slight erythema on the second rabbit by 72 hours and clearance by day 7, and with reduction to very sligh t erythema on the third rabbit by day 7 and clearance by day 10. Very slight edema on 3/3 rabbits one hour after patch removal with clearance by 24 hours. Scaling on all rabbits on day 7 with clearance on two rabbits by day 14 and persistence on one rabbit through day

14. III 47868216

Dermal sensitization ( guinea pig ) (870.2600) Not a sensitizer. No positive signs of reactivity at 24 and 48 hours after challenge in

test and naïve control animals after three consecutive weekly inductions. 47868217

90

- Day oral toxicity (870.3100) Rationale was provided in lieu of a 90

- day oral study. Tagetes oil is exempt from the requirement of a tolerance as a minimal risk active ingredient under 40 CFR 158.950(c). Significant exposure is not expected based on low application rates and rapid degradation in the environment. Tagetes oil is an edible oil and is already consumed in the human diet as

it is used as a food additive in alcoholic beverages, baked goods, condi ments, frozen dairy, gelatins, puddings, candy, and nonalcoholic beverages. 48339002

90

- Day dermal toxicity (870.3250) Waived: prolonged dermal exposure not anticipated based on use pattern, volatility (anticipated volatility

- vapor pressure data

must be submitted) of active ingredient and appropriate PPE requirements on label.

90

- Day inhalation toxicity (870.3465) Rationale was provided in lieu of a 90

- day inhalation study. Significant repeat exposure to humans to tagetes oil as a gas, vapor or aerosol is not anticipated based in the use

pattern . Additionally, significant exposure is not expected based on low application rates and rapid degradation in the environment. 48339002Tagetes Oil Page 18 of 22 Biopesticides Registration Action Document

Table 3. Mammalian Toxicology Data Requirements for Tagetes Oil (40 CFR § 158.2050)

Study/OPPTS Guideline No. Results Toxicity Category/Description MRID

Mutagenicity (Ames) (870.5100, 5300 and 5375) Not mutagenic with or without metabolic

activation in Salmonella typhimurium strains TA 98, TA 1537, TA 100, TA 1535 and

Escherichia coli strain Wp2uvrA.

Rationale was provided in lieu of an in vitro mammalian cell assay. Significant exposure to humans is not anticipated based on low application rates, appropriate PPE requirements on the label, and rapid degradation in the environment. Additionally, humans are already exposed to tagetes oil in

the di et, as it is an edible oil and is used as a food additive in alcoholic beverages, baked goods, condiments, frozen dairy, gelatins, puddings, candy, and nonalcoholic beverages. 48329205

Developmental toxicity (870. 3700 ) Rationale was provided in lieu of a developmental study. Significant exposure to female humans is not anticipated based on low application rates, appropriate PPE requirements on the label, and rapid degradation in the environment. Humans are also already exposed to tagetes oil, as it is an

edible oil and is used as a food additive in alcoholic beverages, baked goods, condiments, frozen dairy, gelatins, puddings, candy, and nonalcoholic beverages. 48339002

Table 4: Nontarget Organism Toxicity Data Requirements for Bug Oil Food Use (40 CFR § 158.2060)

Study/ OCSPP Guideline No. Results Toxicity Category/Description MRID

Avian acute oral toxicity Colinus virginianus (850.2100) LD 50 > 10,000mg/kg NOEL = 10,000 mg/kg Practically non

- toxic 1 47868219

Avian dietary toxicity Colinus virginianus (850.2200) NOEL = 12,945 mg/kg bw

- day (50,000 ppm) Practically non

- toxic 1 47868220

Aquatic invertebrate acute toxicity Daphnia magna (850.1010) EC 50 > 1000 mg/L Practically non

- toxic 1 47868223

Freshwater fish LC 50 Oncorhynchus mykiss (850.1075) LC 50 > 1000 mg/L Practically non

- toxic 1 47868222

Non

- target plant studies (850.4000

- 4800, as applicable) Adequate information to support data requirement: non

- phytotoxic to a variety of ornamental and edible plants including tomato, chrysanthemum, lemon, zucchini, lantana, pansy and impatiens in efficacy trials. Not phytotoxic 1 47868237

Non

- target insect testing (880.4350) Apis millifera (honeybee): oral LD 50 > 9.4 μ g a.i./bee.

Apis millifera (honeybee): contact LD 50 >
12.01 μ g a.i./bee.

Coccinella septempunctata (ladybird beetle) : mortality: 12.5% and 20.0% at 2 L/ha and 4 Moderately toxic to honeybees 1 47868224

47868225

47868226Tagetes Oil Page 19 of 22 Biopesticides Registration Action Document

Table 4: Nontarget Organism Toxicity Data Requirements for Bug Oil Food Use (40 CFR § 158.2060)

Study/ OCSPP Guideline No. Results Toxicity Category/Description MRID

L/ha, respectively; reproduction: decrease in viable eggs/female/day at 2 L/ha and increase in viable eggs/female/day at 4 L/ha.

Aphidus rhopalosipi (parasitic wasp) : mortality: 80.0% and 95.0% at 2 L/ha and 4 L/ha, respectively at 48

- hours.

Aphidus rhopalosipi (parasitic wasp) : 48

- hour

LR 50 > 64 L/ha, NOER ≥ 64 L/ha (mortality and reproduction), LOER > 64 L/ha (mortality and reproducti on ).

Typhlodromus pyri (parasitic mite): mortality: 98.0% and 99.0% at 2 L/ha and 4 L/ha, respectively after 7 days.

Typhlodromus pyri (parasitic mite): 7

- day

LR 50 > 64 L/ha, NOER

= 32 L/ha (mortality), LOER = 64 L/ha (mortality), NOER > 4 L/ha (repr oduction), LOER = 4 L/ha (reproduction). 47828227

47868228

47868229

47868230

Algal Toxicity (850.5400) Pseudokirchneriella subcapitata : 96

- hour EbC50 (biomass), ErC50 (growth rate), and EyC50 (yield) > 1000 mg/L, NOEC = 1000 mg/L 47868231

1 Studies were c onducted using the proposed EP. Request to bridge data from EP to tagetes oil is acceptable.

2 Studies were conducted at application rates well below the recommended application rates on the proposed EP label (maximum rate on label = 41 L/ha)

.

VIII. Appendix B.

For product specific information, please refer to http://www.epa.gov/pesticides/pestlabels

.

IX

. A ppendix C.

REFERENCES

Burdock, GA. (2005). Fenaroli’s handbook of flavor ingredients; ada pted from the Italian language works of Giovanni Fenaroli, 5 th edition. Boca Raton, Fl: CRC Press.

Environmental Working Group (EWG) Database. 2010. Products Containing Tagetes

Oil. http://www.cosmeticsdatabase.com

.

USDA Plants Database. 2010. Tagetes minuta . U.S. Department of Agriculture Natural

Resources Conservation Service. http://plants.usda.gov/java/profile?symbol=TAMI3 June 29,

2010.Tagetes Oil Page 20 of 22 Biopesticides Registration Action Document

REVIEWS AND OTHER REFERENCES

U.S. EPA. 2010. Mem orandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Food Use containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its active ingredient s. U.S. Environmental Protection Agency Office of Pesticide Programs. August 25, 2010

.

U.S. EPA. 2010. Memorandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Ornamental containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its activ e ingredient s. U.S. Environmental Protection Agency Office of Pesticide Programs. August 25, 2010

.

U.S. EPA. 2010. Memorandum from Angela L. Gonzales to Colin G. Walsh. Tolerance Exemption Petition Review in Support of Tagetes Oil. U.S. Environmental Prot ection Agency Office of Pesticide Programs. August 25, 2010

.

U.S. EPA. 2011. Memorandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Food Use containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its active ingredient s

. U.S. Environmental Protection Agency Office of Pesticide Programs. June 23, 2011

.

U.S. EPA. 2011. Memorandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Ornamental containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its active ingredient s

. U.S. Environmental Protection Agency Office of Pesticide Programs. June 23, 2011

.

U.S. EPA. 2012. Mem orandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Food Use containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its active ingredient s

. U.S. Environmental Protection Agency Office of Pesticide Programs. January 18 , 201 2

.

U.S. EPA. 2012. Memorandum from Angela L. Gonzales to Colin G. Walsh. Science Review In Support of the Registration of Bug Oil Ornamental containing Canola Oil, Tagetes Oil, Thyme Oil and Wintergreen Oil as its activ e ingredient s

. U.S. Environmental Protection Agency Office of Pesticide Programs. January 18, 2012

.

X. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

a.i. a ctive i ngredient

BPPD Biopesticides and Pollution Prevention Division

BRAD Biopesticide Registration Action Document

bw body weight

CBI Confidential Business Information

CFR Code of Federal RegulationsTagetes Oil Page 21 of 22 Biopesticides Registration Action Document

cm 3 cubic centimeter

CSF Confidential Statement of Formula

°C degrees Celsius

EC 50 median effective concentration. A statistically derived single concentration in environmental medium that can be expected to cause an effect in 50% of the test animals when administrated by the route indicated (inhalation). It is expressed as a concentration in air or water (e.g. mg/L).

EDSP Endocrine Disruptor Screen ing Program

EDSTAC Endocrine Disruptor Screening and Testing Advisory Committee

EP end

- use product

EPA Environmental Protection Agency (the “Agency”)

FDA Food and Drug Administration

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fun gicide, and Rodenticide Act FQPA Food Quality Protection Act

FR Federal Register

g gram ha hectare kg kilogram

Kow octanol

- water partition coefficient

L liter

LC 50 median lethal concentration. A statistically derived single concentratio n in air or water that can be expected to cause death in 50% of the test animals when administrated by the route indicated (inhalation and environment ). It is expressed as a concentration in air or water (e.g. mg/L)

. LD 50 median lethal dose. A statisticall y derived single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral and dermal). It is expressed as a weight of substance per unit weight of animal (e.g., mg/kg).

MRID No. Master Record Identification Number

mg milligram

mPa millipascal

mL milliliter

MP manufacturing

- use product

N/A not applicable

NE “No Effect”

NIOSH National Institute for Occupational Safety and Health

nm nanometer
NOEL no

- observed

- effect

- level

NOF notice of filing

NOR notice of receipt

OPP Office of Pesticide Programs

O CSPP Office of Chemical Safety and Pollution Prevention

pa pascal

PPE personal protective equipmentTagetes Oil Page 22 of 22 Biopesticides Registration Action Document

PR Notice Pesticide Registration Notice

TGAI technical grade of the active ingredient

ug microgram

USDA United States Department of Agriculture

UV ultra

- violet