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**EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY**  **NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE**  **FEDERAL REGISTER EPA**  **Biopesticides and Pollution Prevention Division contact:**  **[insert name and telephone**  **number with area code] INSTRUCTIONS:**  **Please utilize this outline in preparing the pesticide**  **petition. In cases where the outline element does not apply**  **, please insert “NA**  **- Remove” and**  **maintain the outline. Please do not chang e the margins, font, or format**  **in your pesticide petition**  **. Simply replace the instructions that appear in green**  **, i.e., “ [**  **insert company name**  **] ,” with the information specific to your action.**  **SUBMISSION: Email**  **the completed template to: hollis**  **. linda**  **@epa.gov. TEMPLATE:**  [ Becker Underwood, Inc. ] [Insert petition number is not available (OPP Decision Number D

- 457601) ] EPA has received a pesticide petition ( [insert petition number is not available ] ) from [ Becker Underwood, Inc. ] , [ 801 Day ton Avenue, Ames, IA 50010 ] request ing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 ( Options (pick one) 1. by establishing a tolerance for residues of NA
- Remove 2. to establish an exemption from the requirement of a tolerance for 3. to establish an amendment/expansion of an existing tolerance exemption for the NA
- Remove (Options (pick one) 1. microbial pesticide [ NA
- Remove ] 2. biochemical pesticide [ Methyl jasmonate ] 3. plant

- pesticide [ NA
- Remove ] in or on [ NA
- Remove ].2

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, [ Becker Underwood, Inc. ] has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by [ Becker Underwood, Inc. ] and EPA has not fully

evaluated the merits of the pesticide petition. The summary may have been edited b y EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally

made the reader conclude that the findings reflected EPA’s position and not the position of the petitioner.
I. [ Becker Underwood, Inc. ] Petition Summary [Insert petition number

– not available ] A. Product Name and Proposed Use Practices [1 ) Methy l Jasmonate Technical Grade (TGAI; for manufacturing use onl y) 2) SCI MI TAR (EP; for agricultural use) Methy l jasmonate acts as a plant signaling molecule in stimulating the plant’s own defense s ys tem resulting in enhanced resistance of the plant to attack by insects, fungi, and bacteria. The group of jasmonates is widely distributed in plants and include biologically active intermediates such as methy l jasmonate, as well as other jasmonic acid derivatives sy nthesized in the jasmonic acid biosy nthesis pathway . These chemicals trigger plant responses to biotic and abiotic stresses and regulate such processe s as wound responses clearl y demonstrated in plants like Arabidopsis. Methy l jasmonate is produced in response to stress and serves as a signal, in the form of a chemical vapor, to turn on natural defense mechanisms. Methy l jasmonate signals plants to sy

nthesize proteins that increase their resistance to temperature changes as well as attack b y insects. Furthermore, these proteins can also lead to production of antifungal and/or antibacterial compounds. Jasmonates induce gene expression leading to s yn thesi s of many proteins that increase sy stemic resistance against biotic damage. In conifers, jasmonates act as plant elicitors, which induce a wide range of chemical and anatomical defense reactions. An anal yt ical method for residues is not applicable. It is expect ed that, when used as proposed, methyl jasmonate would not result in residues that are of toxicological concern. Application of methyl jasmonate to seeds through seed treatment, in

- furrow or soil drench applications is not expected to increase the levels of the biochemical in the environment above natural concentrations. The proposed use of SCI MI TAR , the formulated end

- use product containing meth yl jasmonate , is a seed applied bioactive for protection against flea beetles in canola, rapeseed, mustard, safflower, sunflower and camelina
. As such, the proposed use pattern and low application rate s minimize the potential for exposure above the natural background levels of methyl jasmonate
. ]3

B. Product Identity/Chemistry 1. Identity of the pesticide and corresponding residues

. [ Methy l jasmonate CAS No. 1211
- 29
- 6; Cy clopentaneacetic acid, 3

- oxo - 2
- (2

- penten yl )

- , methy l ester ] 2. Magnitude of residues at the time of harvest and method used to determine the residue

. [ NA
- Remove ] 3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. [ An analy tical method for residues of methyl jasmonate is not necessary as this petition requests an exemption from the requirement of a tolerance without numerical limitations **.]** C. Mammalian Toxicological Profile [ Acute Oral Toxicity

(OCSPP 870.1100): Methy l jasmonate was categorized in Toxicity Category I II in an acute oral toxicity study with an estimated rat LD50 of 3129 mg/kg/day

(Kuhn, 2010). In this study on the Technical Grade Active Ingredient ( TGAI) (98.7% meth yl jasmonate), the up

- and

- down procedure was used to identify an oral LD50. Three rats received a dose of 1750 mg/kg, and none died, while three rats that received 5000 mg/kg did die. The study was terminated according to the guideline rules for stopping. Acute Dermal Toxicity

(OCSPP 870.1200): Methyl jasmonate was categorized in Toxicity Category I V in an acute dermal toxicity study with an estimated rat L D50 greater than 5050 mg/kg/day (Kuhn, 2010). In this study on the TGAI (98.7% methy l jasmonate), five male and five female rats received a dermal dose of 5050 mg/kg of the undiluted test article, and the area of application was covered with a 2 x 4 inch surgical gauze patch. After 24 hours the wrappings were removed and the application site gentl y washed with tap water. There were no mortalities following exposure, and no signs of dermal irritation at an y observation during the study
. . Acute Inhalation Toxicity (OCSPP 870.1300): Methyl jasmonate was evaluated for acute inhalation toxicity

potential in laboratory

rats (Doig, 2010). Five female and five male rats were exposed to an aerosol generated from the undiluted liquid test article at a concentration of 2.23 mg/Lfor 4 hours. No mortality occurred during the exposure or the 14 day observation period. The acute rat inhalation L C50 identified in this study was >2.23 mg/L, which is Toxicity Category I V according to the U.S. EPA criteria. Primary Ey e I rritation (OCSPP 870.2400): Methyl jasmonate was evaluated for primary ey e irritation potential in laboratory rabbits (Kuhn, 2010). In this study , undiluted methyl jasmonate (0.1 ml) was instilled in the conjunctival sac of the right ey es of three albino rabbits selected for testing. Immediately af ter the 24

- hour observation, all treated ey es were rinsed with room temperature deionized water for one minute. No effects categorized as positive were reported in the ey es at any time after treatment. Methyl jasmonate was described as minimally irritati ng to the ey es and assigned an EPA Toxicity Category I V b y the study

author.4

Primary Dermal Irritation (OCSPP 870.2500): M ethy l jasmonate was evaluated for primary dermal irritation potential in albino laboratory rabbits (Kuhn, 2010). In this study , 0. 5 ml of undiluted methy l jasmonate was applied to an intact test site on each of three rabbits and covered with a semi

- permeable dressing for four hours. Observations for potential dermal irritation were performed 1, 24, 48 and 72 hours after dressing rem oval. Meth yl jasmonate was assigned a primary irritation index of 0.0 and rated as non - irritating. Based on the irritation scores at the 72

- hour time point, methyl jasmonate was assigned to EPA Toxicity Category I V for dermal irritation. Dermal Sensit ization (OCSPP 870.2600 ): M ethyl jasmonate was evaluated for dermal sensitization potential in guinea pigs using a modification of the Buehler method (Kuhn, 2010). In this study , 15 male and 15 female guinea pigs were separated into Naïve control (5 /sex) and Test (10/sex) groups. T he Test group subjects were treated dermall y with 0.4 ml of undiluted methy l jasmonate once per week, 6 hours per day for 3 weeks. After a two

- week rest period, Test and Naïve groups were challenged with a dermal application of 0.4 ml of methy l jasmonate, applied to a virgin site. The challenge dose did not elicit a reaction in the Naïve or Test animals and study authors concluded methyl jasmonate was not a sensitizing agent in guinea pigs. The results of toxicity

testing show there is no risk to human health from exposure to methyl jasmonate. Furthermore , there is a long history of safe dietary

exposure to methy l jasmonate as it naturall y occurs in fruits that children and adults commonl y eat as well as food that methy l jasmonate is commonly added to as a flavoring agent
. International experts have even established an acceptable human dietary exposure level of 540 μg/day
. ]
D

. Aggregate Exposure 1. Dietary exposure. [ Methyl jasmonate naturall y occurs in ordinary fruits that children and adults eat routinely , including apples and strawberries. In addition, m ethy l jasmonate is common ly

used in foods as a flavoring agent . International experts specified an acceptable dietary exposure level of 540 μg/day
. The potential exposure to methyl jasmonate from use of the proposed Becker Underwood, Inc. product is well below the current estimated dietary

exposure. The results of toxicity

testing indicate there is no risk to human health or the environment from methyl jasmonate . There are no reports of ecological or human health hazards caused by methyl jasmonate
. ] i. Food. [ The proposed use pattern may result in dietary exposure with possible residues in or on agricultural commodities. However, no risk is expected for the general population, including infants and children, or animals because of the lack of demonstrated toxic ity of methyl jasmonate
. T here is a long history of safe dietary exposure to methy l jasmonate as it naturall y occurs in fruits that children and adults commonly

eat as well as food that methy l jasmonate is commonly added to as a flavoring5

agent
. The potential exposure to methyl jasmonate from use in the proposed Becker Underwood, Inc. product is well below the current estimated dietary exposure. ] ii. Drinking water
. [ Application of methyl jasmonate to pre - planted seeds through seed treatment applications is not expected to increase the levels of the biochemical in the environment above natural concentrations
. The potential exposure to methyl jasmonate from use in the proposed Becker Underwood, Inc. product is well below the current estimated dietary

exposure. E xposure to humans from residues of methyl jasmonate in potable water would be at most, insignificant
. Similarly , e x posure to surface water as well as drinking water from wells or surface water would be negligi ble. ] 2. Non

- dietary exposure
. [ The potential for non

- dietary exposure to the general population, including infants and children, is unlikely as the propos ed use sites are agricultural. The intended use of methyl jasmonate is to apply it to the seeds of agricultural crops for the purposes of stimulating the target plant’s defense sy stem
. Application of methyl jasmonate to pre - planted seeds is not expected to increase the levels of the biochemical in the environment above natural concentrations. The re sults of toxicity

testing indicate there is no risk to human health or the environment from methy l jasmonate . There are no reports of ecological or human health hazards caused b y methyl jasmonate. The absence of acute toxicity in laboratory

animals demonstrates the benign nature of this strain. Non

- dietary exposures would not be expected to pose an y quantifiable risk due to a lack of residues of toxicological concern ] E. Cumulative Effects

[ Itis not expected that, when used as proposed, methyl jasmonate would result in residues that are of toxicological concern. The intended use of methyl jasmonate is to apply

it to the seeds of agricultural crops for the purposes of stimulating the plant’s defense s ys tem
. Application of methyl jasmonate to pre - planted seeds is not expected to increase the levels of the biochemical in the environment above natural concentrations. The results of toxicity

testing indicate there is no risk to human health or the environment from methyl jasmo nate . There are no reports of ecological or human health hazards caused b y methyl jasmonate . The absence of acute toxicity in laboratory animals demonstrates the benign nature of this strain. ] F . Safety Determination 1. U.S. population. [ Acute toxicity studies have shown methyl jasmonate is not toxic or irritating to mammals. The intended use of methyl jasmonate is to apply it to the seeds of agricultural crops for th e purposes of stimulating the plant’s defense sy stem
. Application of methy l jasmonate to pre - planted seeds is not expected to increase the levels of the biochemical in the environment above natural concentrations. The results of toxicity testing indicate there is no risk to human health or the environment from methyl jasmonat e . There are no reports of ecological or human health hazards caused by methyl jasmonate . The absence of acute toxicity in laboratory

animals demonstrates th e benign6

nature of this strain. There is a reasonable certainty of no harm to the general US popul ation from exposure to this active ingredient. ] 2. Infants and children
. [ As mentioned above, it is not expected that, when used as proposed, methyl jasmonate would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infants and children from exposure to methyl jasmonate from the proposed uses .] G. Effects on the Immune and Endocrine Systems [ To date there is no evidence to suggest that methyl jasmonate functions in a manner similar to an y known hormone, or that it acts as an endocrine disrupter. ] H. Existing Tolerances [ There is no US. EPA Tolerance for methyl jasmonate .] I . International Tolerances [ Methyl jasmonate safety as a flavoring food additive was reviewed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2005). The JECFA procedure for safety evaluation of flavoring agents that was used to evaluate meth yl jasmonate integrates information on toxicity , metabolism and structure

- activity relationships to identify acceptable intakes. Data on toxicology and metabolism, and structure activit y relationships among compounds are important components of the safet y evaluation. JECFA evaluations generally emphasize that the majority of flavoring agents are metaboli zed to innocuous end

- products. Meth yl jasmonate was evaluated for safet y as one of the structural class of monocy clic and bicy clic secondary alcohols, ketones and related esters. The method used by JECFA to evaluate this group of flavoring substances is described below. The JECFA procedure for safet y evaluation of flavoring substances is based on recognized pathway s of activation and deactivation, data on toxicity , and knowledge of each substance as a component of traditional foods. The first step in the safety evaluation of a flavoring additive is to classify the substance as belonging to one of three categories, depending on chemical structure and metabolism. 1. C lass Isubstances have simple chemical structures with known metabolic pathway s and innocuous end products that suggest a low order of oral toxicity
. 2. Class II substances have chemical structures that appear less innocuous than class I, but do not contai n features that suggest toxicity
. 3. Class III substances have a chemical structure that does not allow an initial presumption of safet y and may suggest toxicity
. Methy l jasmonate was identified as a structural class II flavoring agent by JECFA, with a7

“human exposure threshold” of 540 μg/day . The human exposure threshold identified by JECFA for Category

II flavoring substances is based on the 5 th percentile animal

- based no - observed

- effect

- level (NOEL) of 0.906 mg/kg/day for this Category
. The database of toxicity studies that was used to derive this NOEL included chronic, subchronic and developmental toxicity

studies. To derive the human exposure threshold, JECFA divided the NOEL b y an uncertainty factor of 100, and assumed a bod y weight of 60 kg. The JECFA NOELof 0.906 mg/kg/day for structural Class II flavoring substances is a reasonable surrogate for a compound

- specific NOELfor developmental toxicity of methyl jasmonate because the database of surrogate data included data from developm ental toxicity

studies. ]