Document ID: EPA-HQ-OPP-2012-0134-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-05-02T04:00Z

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 change 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 Dayton Avenue, Ames, IA 50010] requesting, 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].

	
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 by 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) Methyl Jasmonate Technical Grade (TGAI; for manufacturing use only)
      2) SCIMITAR (EP; for agricultural use)  
      
      Methyl jasmonate acts as a plant signaling molecule in stimulating the plant's own defense system 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 methyl jasmonate, as well as other jasmonic acid derivatives synthesized in the jasmonic acid biosynthesis pathway. These chemicals trigger plant responses to biotic and abiotic stresses and regulate such processes as wound responses clearly demonstrated in plants like Arabidopsis.
      Methyl 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. Methyl jasmonate signals plants to synthesize proteins that increase their resistance to temperature changes as well as attack by insects. Furthermore, these proteins can also lead to production of antifungal and/or antibacterial compounds. 
      Jasmonates induce gene expression leading to synthesis of many proteins that increase systemic resistance against biotic damage. In conifers, jasmonates act as plant elicitors, which induce a wide range of chemical and anatomical defense reactions.
	An analytical method for residues is not applicable.  It is expected 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 SCIMITAR, the formulated end-use product containing methyl 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 rates minimize the potential for exposure above the natural background levels of methyl jasmonate.]

B. Product Identity/Chemistry

	1. Identity of the pesticide and corresponding residues. [Methyl jasmonate CAS No. 1211-29-6; Cyclopentaneacetic acid, 3-oxo-2-(2-pentenyl)-, methyl 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 analytical 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):  Methyl jasmonate was categorized in Toxicity Category III 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% methyl 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 IV in an acute dermal toxicity study with an estimated rat LD50 greater than 5050 mg/kg/day (Kuhn, 2010). In this study on the TGAI (98.7% methyl 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 gently washed with tap water. There were no mortalities following exposure, and no signs of dermal irritation at any 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/L for 4 hours. No mortality occurred during the exposure or the 14 day observation period. The acute rat inhalation LC50 identified in this study was >2.23 mg/L, which is Toxicity Category IV according to the U.S. EPA criteria.
	
Primary Eye Irritation (OCSPP 870.2400): Methyl jasmonate was evaluated for primary eye 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 eyes of three albino rabbits selected for testing.  Immediately after the 24-hour observation, all treated eyes were rinsed with room temperature deionized water for one minute.  No effects categorized as positive were reported in the eyes at any time after treatment.  Methyl jasmonate was described as minimally irritating to the eyes and assigned an EPA Toxicity Category IV by the study author.  

Primary Dermal Irritation (OCSPP 870.2500): Methyl jasmonate was evaluated for primary dermal irritation potential in albino laboratory rabbits (Kuhn, 2010).  In this study, 0.5 ml of undiluted methyl 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 removal.  Methyl 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 IV for dermal irritation.  

Dermal Sensitization (OCSPP 870.2600): Methyl 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. The Test group subjects were treated dermally with 0.4 ml of undiluted methyl 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 methyl 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 methyl jasmonate as it naturally occurs in fruits that children and adults commonly eat as well as food that methyl jasmonate is commonly added to as a flavoring agent. International experts have even established an acceptable human dietary exposure level of 540 ug/day.] 

D. Aggregate Exposure

	1. Dietary exposure. [Methyl jasmonate naturally occurs in ordinary fruits that children and adults eat routinely, including apples and strawberries. In addition, methyl jasmonate is commonly used in foods as a flavoring agent. International experts specified an acceptable dietary exposure level of 540 ug/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 toxicity of methyl jasmonate. There is a long history of safe dietary exposure to methyl jasmonate as it naturally occurs in fruits that children and adults commonly eat as well as food that methyl jasmonate is commonly added to as a flavoring 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. Exposure to humans from residues of methyl jasmonate in potable water would be at most, insignificant. Similarly, exposure to surface water as well as drinking water from wells or surface water would be negligible.]

	2. Non-dietary exposure. [The potential for non-dietary exposure to the general population, including infants and children, is unlikely as the proposed 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 system.  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 jasmonate. There are no reports of ecological or human health hazards caused by 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 any quantifiable risk due to a lack of residues of toxicological concern]

E. Cumulative Effects

	[It is 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 system.  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 jasmonate. There are no reports of ecological or human health hazards caused by 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 the purposes of stimulating the plant's defense system. 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 jasmonate. There are no reports of ecological or human health hazards caused by methyl jasmonate.  The absence of acute toxicity in laboratory animals demonstrates the benign nature of this strain. There is a reasonable certainty of no harm to the general US population 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 any 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 methyl jasmonate integrates information on toxicity, metabolism and structure-activity relationships to identify acceptable intakes. Data on toxicology and metabolism, and structure activity relationships among compounds are important components of the safety evaluation.   JECFA evaluations generally emphasize that the majority of flavoring agents are metabolized to innocuous end-products. Methyl jasmonate was evaluated for safety as one of the structural class of monocyclic and bicyclic 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 safety evaluation of flavoring substances is based on recognized pathways 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. Class I substances have simple chemical structures with known metabolic pathways 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 contain features that suggest toxicity. 
      
   3. Class III substances have a chemical structure that does not allow an initial presumption of safety and may suggest toxicity. 

Methyl jasmonate was identified as a structural class II flavoring agent by JECFA, with a "human exposure threshold" of 540 ug/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 by an uncertainty factor of 100, and assumed a body weight of 60 kg.  The JECFA NOEL of 0.906 mg/kg/day for structural Class II flavoring substances is a reasonable surrogate for a compound-specific NOEL for developmental toxicity of methyl jasmonate because the database of surrogate data included data from developmental toxicity studies.]