BIOPESTICIDES REGISTRATION ACTION DOCUMENT Tagetes Oil PC Code : 176602 U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division March 22, 2012 ------- Tagetes Oil Page 2 of 22 Biopesticides Registration Action Document TABLE OF CONTENTS I. EXECUTIVE SUMMARY: 5 II. ACTIVE INGREDIENT OVERVIEW 7 III. REGULATORY BACKGROUND 7 A. Classification 7 B. Food Clearances/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. Occupational, Residential, School and Day Care Exposure and Risk Characterization 11 5. Aggregate Exposure from Multiple Routes Including Dermal, Oral, and Inhalation 12 6. Cumulative Effects 12 7. Risk Characterization 12 C. ENVIRONMENTAL 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 DECISION 14 A. Determination of Eligibility for Registration 14 B. Regulatory Decision 14 VI. ACTIONS REQUIRED BY REGISTRANTS 15 A. Reporting of Adverse Effects 15 B. Reporting of Hypersensitivity Incidents 15 VII. APPENDIX A. Data Requirements (40 CFR Part 158) 15 VIII. APPENDIX B. Product Specific Information 19 ------- Tagetes Oil Page 3 of 22 Biopesticides Registration Action Document IX. APPENDIX C. References. ------- Tagetes 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., Biologist ------- Tagetes Oil Page 5 of 22 Biopesticides Registration Action Document I. EXECUTIVE SUMMARY: 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). The major constituents of the identified components of tagetes oil are terpenes, which are found in a variety of essential oils. Tagetes oil, as TagetespatulaL., T. erectaL., 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 including shampoos, soaps and lotions (EWG, 2010). The Biopesticides and Pollution Prevention Division (BPPD) determined that the data/information submitted for product chemistry and Tier I acute toxicity for tagetes oil satisfy the current guideline requirements. Acceptable scientific rationales were submitted 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 rationales submitted were acceptable based on tagetes oil's toxicological and exposure profiles. Significant 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 volatilization of the active ingredient and because prolonged 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 requirement [Ames 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 should future intended end- use product (EP) applications result in different anticipated exposures to humans, these data requirements may need to be readdressed. For nontarget organisms and environmental fate data requirements (OCSPP 850.1010 to 850.4450), the applicant either submitted acceptable data/information for the EPs or the data were waived because the guideline study was not applicable. BPPD granted a request to bridge the data from the EPs to the active ingredient, tagetes oil, because the applicant indicated that the active ingredients in the EPs 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 EPs is more relevant to the risk assessment than the toxicological profile of tagetes oil alone. Based on the nontarget organism data from the EPs, which indicated that the EPs were 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 acute toxicity 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 used ------- Tagetes 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 little, 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 contain 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 registration decisions before they occur. According to this policy, EPA provides 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 was subject to a 30 day comment period as a "new active ingredient". The notice for this comment period included the draft Biopesticides Registration Action Document (BRAD) and draft product labels for the EPs, Bug Oil Food Use and Bug Oil Food Ornamental, which contain this new active ingredient, tagetes oil. The docket identification (ID) number is EPA-HQ-OPP-2009- 0822. The Agency did not receive any comments on the registration of tagetes oil. Therefore, the Agency is issuing the registration for this active ingredient. 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 public 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, 2009, EPA received an application filed by Exponent, 1150 Connecticut Avenue, NW, Suite 1100, Washington, DC 20036, on behalf of Plant Impact pic, 12 South Preston Office Village, Cuerden Way, Bamber Bridge, Preston, PR5 6BL, United Kingdom, to register the products, Bug Oil Food Use (EPA File Symbol No. 85937-E) and Bug Oil Ornamental (EPA File Symbol No. 85937-R) containing the new biochemical active ingredient, tagetes oil, and the currently registered 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 on December 16, 2009 (74 FR 66639). 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. Tagetes oil is derived from Tagetes spp. (marigolds), specifically, African marigold (Tagetes erectci) 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 actives in the proposed EPs, canola oil, thyme oil, and wintergreen oil. B. Food 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. The Agency determined during the review of the petition 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 40 CFR 180.950(c). Therefore, the petition (PP 9F7619) filed by the applicant is no longer ------- Tagetes Oil Page 8 of 22 Biopesticides Registration Action Document applicable, nor needed, for this new active ingredient, tagetes oil, and has been withdrawn by the Agency. 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 of 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 found in a variety of essential oils. Tagetes oil, as TagetespatulaL., T. erectaL., or T. minutaL. (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. 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, and 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 characteristics 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 Category 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 for 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 rats, 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 IV (not toxic) for acute oral toxicity, acute 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 Toxicity Subchronic data are required to determine a no-observed-effect-level (NOEL) and any toxic effects associated with repeated or continuous exposure to a test substance for a period of ninety days. Rationale was submitted for the subchronic [90-day oral (OCSPP 870.3100) and 90-day inhalation (OCSPP 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. iii. 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 (OCSPP 870.3250)] was granted by BPPD, based on the EPs toxicological and exposure profile, summarized below. i. Prolonged 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 regarding 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 rationale 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 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 female humans is not anticipated based on low application rates, appropriate PPE requirements on the label, and rapid degradation in the environment. The tier 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 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. 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 information regarding developmental and mutagenicity data requirements, refer to Table 3 in Appendix A. d. Tier II/Tier III The data requirements were not required due to the nature of the active ingredient and its intended uses in potential new EP products (insecticides 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 effect 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 required ------- Tagetes Oil Page 11 of 22 Biopesticides Registration Action Document determinations. Tier 1 consists of a battery of 11 screening assays 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 systems 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 inert 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 list 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, EPA 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 battery, please visit our website: http://www.epa.gov/endo/. 2. Dose Response Assessment Because no toxicological endpoints were identified for this active ingredient, a dose response 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 does occur, the health risk would be expected to be minimal based on the low acute oral toxicity of tagetes oil and the fact that 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). 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 applicators and/or handlers. Additionally, no relevant toxicological endpoints have been identified. Based on ------- Tagetes 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 exposure 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 toxicity. 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 nontarget toxicology data/information is available to support registration of tagetes oil with the submission of nontarget toxicology data on the EPs. All nontarget toxicology data requirements for tagetes oil have been satisfied. The EPs are practically nontoxic to birds, fish and aquatic invertebrates and is not phytotoxic. The EPs are practically 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 Characterization Toxicity studies have not been submitted for tagetes oil. A lack of toxicity rationale and data on the proposed EPs have 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 EPs are germane to the risk assessment rather than the toxicological profile of tagetes oil alone. For registration of the proposed EPs, the Agency has bridged the nontarget organism toxicology data from the EPs to the active ingredient, tagetes oil. The product is a contact insecticide that operates through a physical mode of action. The product is practically nontoxic 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 Agency 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 product 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 assessment 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 determination. 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 Service 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 exposure 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 are 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/prl996-7.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 new 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 warrants proposed claims; (B) its labeling and other materials comply with the requirements 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 effects 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 cause 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 insecticide 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 environmental justice issues, please visit EPA's website at http: ic ii'ic. epa. gov/comyliance/environmentaliustice/index. html. ------- Tagetes Oil Page 15 of 22 Biopesticides Registration Action Document VI. ACTIONS REQUIRED BY REGISTRANTS EPA evaluated all data submitted 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, no additional data must be submitted 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 summary of these types of data are listed below. A. Reporting of Adverse Effects Pursuant to FIFRA section 6(a)(2), reports of all incidents of adverse effects to the environment must be submitted to EPA. B. Reporting ofHypersensitivity 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). VII. 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 Guideline No. Study Results 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; CBI ------- Tagetes 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 elevated 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 UV profiles are similar under all pH conditions. No significant molar absorbance (e) at the wavelength range of 290-750 nm. 830.7050 UV/Visible light absorption Neutral pH: s = 44.52,45.98 at wavelength 237 nm Basic pH: s = 40.13,44.80 at wavelength 237 nm Acidic pH: s = 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 Kow = 4.83 Ocimene: Log Kow = 4.80 Dihydrotagetone Log Kow = 2.92 Linalool Log Kow =3.38 48649802 830.7840 Water Solubility Insoluble 47868202 830.7950 Vapor Pressure Approximately 59% volatilization (measured via weight loss) in 48 hours in laboratory study. 48329208 ------- Tagetes 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) LD50 >5,000 mg/kg (females) IV 47868213 Acute dermal toxicity (rats) (870.1200) LD50 >2000 mg/kg for males, females, and for both sexes combined III 47868214 Acute inhalation toxicity (870.1300) LC50 > 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 slight 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 naive 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, condiments, 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. 48339002 ------- Tagetes 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 diet, 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) LD50 > 10,000mg/kg NOEL = 10,000 mg/kg Practically non-toxic1 47868219 Avian dietary toxicity Colinus virginianus (850.2200) NOEL = 12,945 mg/kg bw-day (50,000 ppm) Practically non-toxic1 47868220 Aquatic invertebrate acute toxicity Daphnia magna (850.1010) EC50> 1000 mg/L Practically non-toxic1 47868223 Freshwater fish LC50 Oncorhynchus mykiss (850.1075) LC50> 1000 mg/L Practically non-toxic1 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 phytotoxic1 47868237 Non-target insect testing (880.4350) Apis millifera (honeybee): oral LD50 > 9.4 fig a.i./bee. Apis millifera (honeybee): contact LD™ > 12.01 \ig a.i./bee. Coccinella septempunctata (ladybird beetle): mortality: 12.5% and 20.0% at 2 L/ha and 4 Moderately toxic to honeybees1 47868224 47868225 47868226 ------- Tagetes 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. 47828227 Aphidus rhopalosipi (parasitic wasp): 48-hour LR50 > 64 L/ha, NOER > 64 L/ha (mortality and reproduction), LOER > 64 L/ha (mortality and reproduction). 47868228 Typhlodromuspyri (parasitic mite): mortality: 98.0%) and 99.0%o at 2 L/ha and 4 L/ha, respectively after 7 days. 47868229 Typhlodromus pyri (parasitic mite): 7-day LR50 > 64 L/ha, NOER = 32 L/ha (mortality), LOER = 64 L/ha (mortality), NOER > 4 L/ha (reproduction), LOER = 4 L/ha (reproduction). 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 Studies were conducted 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. Appendix C. REFERENCES Burdock, GA. (2005). Fenaroli's handbook of flavor ingredients; adapted from the Italian language works of Giovanni Fenaroli, 5th 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/iava/profile?svmbol=TAMI3 June 29, 2010. ------- Tagetes Oil Page 20 of 22 Biopesticides Registration Action Document REVIEWS AND OTHER REFERENCES U.S. EPA. 2010. 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 ingredients. 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 active ingredients. 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 Protection 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 ingredients. 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 ingredients. U.S. Environmental Protection Agency Office of Pesticide Programs. June 23, 2011. U.S. EPA. 2012. 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 ingredients. U.S. Environmental Protection Agency Office of Pesticide Programs. January 18, 2012. 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 active ingredients. U.S. Environmental Protection Agency Office of Pesticide Programs. January 18, 2012. X. GLOSSARY OF ACRONYMS AND ABBREVIATIONS a.i. active ingredient BPPD Biopesticides and Pollution Prevention Division BRAD Biopesticide Registration Action Document bw body weight CBI Confidential Business Information CFR Code of Federal Regulations ------- Tagetes Oil Page 21 of 22 Biopesticides Registration Action Document cm CSF °C EC50 EDSP EDSTAC EP EPA FDA FFDCA FIFRA FQPA FR g ha kg Kow L LC50 LD 50 MRID No. mg mPa mL MP N/A NE NIOSH nm NOEL NOF NOR OPP OCSPP pa PPE cubic centimeter Confidential Statement of Formula degrees Celsius 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). Endocrine Disruptor Screening Program Endocrine Disruptor Screening and Testing Advisory Committee end-use product Environmental Protection Agency (the "Agency") Food and Drug Administration Federal Food, Drug, and Cosmetic Act Federal Insecticide, Fungicide, and Rodenticide Act Food Quality Protection Act Federal Register gram hectare kilogram octanol-water partition coefficient liter median lethal concentration. A statistically derived single concentration 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). median lethal dose. A statistically 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). Master Record Identification Number milligram millipascal milliliter manufacturing-use product not applicable "No Effect" National Institute for Occupational Safety and Health nanometer no-ob served-effect-1 evel notice of filing notice of receipt Office of Pesticide Programs Office of Chemical Safety and Pollution Prevention pascal personal protective equipment ------- Tagetes Oil Page 22 of 22 Biopesticides Registration Action Document PR Notice Pesticide Registration Notice TGAI technical grade of the active ingredient ug microgram USD A United States Department of Agriculture UV ultra-violet ------- |