Document ID: EPA-HQ-OPP-2012-0389-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-07-25T04:00Z

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:

[Vestaron Corporation]

[Insert petition number]

	EPA has received a pesticide petition ([insert petition number]) from [Vestaron Corporation], [4717 Campus Drive, Ste. 1200, Kalamazoo, MI 49008] 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 to establish an exemption from the requirement of a tolerance for the biochemical pesticide [GS-U-ACTX-Hv1a-SEQ2].
	
Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, [Vestaron Corporation] has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by [Vestaron Corporation] 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. [Vestaron Corporation] Petition Summary
   
   	[Insert petition number]

A. Product Name and Proposed Use Practices

[Product Name:	VST-006325 TGAI (88847-R)
				VST-006330 EP (88847-E)

Proposed Use Practice:	VST-006325 TGAI is proposed for manufacturing use only, for further formulation into registered end-use products.

	VST-006330 EP is a biological insecticide containing the active ingredient GS-U-ACTX-Hv1a-SEQ2 for use on ornamental plants, turf and edible crops against a variety of insect pests.  VST-006330 EP functions primarily as a central nervous inhibitor for use in the control or suppression of many foliar feeding pests including caterpillars, foliage feeding coleopterans and whiteflies in infested crops.  VST-006330 EP is mixed with water and applied as a foliar spray with ground or aerial application equipment.  VST-006330 EP can be used in either the field or greenhouse for the control of any labeled pest.]

B. Product Identity/Chemistry

	1. Identity of the pesticide and corresponding residues. 

[Active Ingredient:	GS-U-ACTX-Hv1a-SEQ2 (CAS No. Not applicable).
	
	Information regarding the name, identity and chemical composition has been submitted to EPA and can be found in MRID Nos. 487790-2, 487790-3 and 87790-4.

	GS-U-ACTX-Hv1a-SEQ2, the active ingredient in VST-006325 TGAI, is a novel peptide insecticidal ingredient that is derived from peptide insect ion channel modulators produced by a family of Australian spiders, known as the funnel-web spiders.  These ion channel modulators interact with invertebrate ion channels but are inactive at vertebrate ion channels.  As a hybrid peptide, GS-U-ACTX-Hv1a-SEQ2 is active at both insect calcium channels and insect calcium activated potassium channels (MRID No. 487790-2).
                        

Mode of Action:	When used as an insecticide the active ingredient GS-U-ACTX-Hv1a-SEQ2 has a unique dual mode of action.  One mode of action that GS-U-ACTX-Hv1a-SEQ2 is inhibition of voltage-gated insect, but not vertebrate, calcium channels.  GS-U-ACTX-Hv1a-SEQ2 exhibits a concentration dependent inhibition of voltage-gated calcium channel currents in cockroach neurons with an IC50 of 500 nM.  

                        GS-U-ACTX-Hv1a-SEQ2 has a second mode of action that is inhibition of insect calcium activated potassium channels.  GS-U-ACTX-Hv1a-SEQ2 blocks insect-specific calcium activated potassium channels while having little to no activity at rat dorsal root ganglion neuronal calcium-activated potassium channels. Similar specific activity has been demonstrated for other hybrid peptide compounds (MRID Nos. 487790-2, 487790-3 and 487790-19).]

	2. Magnitude of residues at the time of harvest and method used to determine the residue. [N/A  -  Remove.]

	3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. [Magnitude of residues and method to determine:  An analytical method for residues is not applicable.  It is expected that, when used as proposed, GS-U-ACTX-Hv1a-SEQ2, would not result in residues that are of toxicological concern.]

C. Mammalian Toxicological Profile

[Toxicity of GS-U-ACTX-Hv1a-SEQ2: Studies conducted with GS-U-ACTX-Hv1a-SEQ2 and structurally similar compounds demonstrate a lack of toxicity to vertebrates.

1)	Acute Toxicity of GS-U-ACTX-Hv1a-SEQ2.  

	An acute oral study conducted on GS-U-ACTX-Hv1a-SEQ2 used the up down procedure to evaluate the potential toxicity (MRID No. 487790-07).  Three female rats received the limit dose of 5,000 mg/kg, and all appeared normal and healthy throughout the study observation period. No gross effects were identified in animals necropsied at study termination.  The oral LD50 was determined to be > 5,000 mg/kg (Toxicity Category IV).  

	An acute dermal study was conducted to support registration of GS-U-ACTX-Hv1a-SEQ2 (MRID No. 487790-08).  In this study, 5 male and 5 female rats were exposed to 5,000 mg/kg of test article moistened with distilled water and applied to the skin for 24 hours.  All animals on the study survived exposure to the test substance and gained body weight during the observation period.  The LD50 for acute dermal exposure was >5,000 mg/kg (Toxicity Category IV).  

	An acute inhalation study was conducted to support registration of GS-U-ACTX-Hv1a-SEQ2 (MRID No. 487790-09).  In this acute inhalation study, 5 male and 5 female rats were exposed to 2.05 mg/L of test article in a nose-only exposure chamber for 4 hours.  The mass median aerodynamic diameter of the particles was 3.7 μm.  All animals on the study survived exposure to the test substance and gained body weight during the 14-day observation period.  There were no gross abnormalities in any of the animals at necropsy at study termination.  The study thus concluded that the LC50 for acute inhalation exposure was >2.05 mg/L (Toxicity Category IV).  

	A primary eye irritation study was conducted to support registration of GS-U-ACTX-Hv1a-SEQ2 (MRID No. 487790-10).  In this study one-tenth of a milliliter (0.09 grams) of the test substance was instilled into the right eye of three healthy rabbits.  The left eye remained untreated and served as a control.  No corneal opacity or iritis was observed in any treated eye during the study.  All animals were free of ocular irritation by 48 hours.  The study concluded the test material was minimally irritating (Toxicity Category IV).

	A primary dermal irritation study was conducted to support registration of GS-U-ACTX-Hv1a-SEQ2 (MRID No. 487790-11).  In this study, five-tenths of a gram of test substance was moistened with distilled water and applied to the skin of three healthy rabbits for 4 hours.  All treated sites exhibited well-defined erythema and very slight edema, which cleared by Day 7.  The study concluded the test material was moderately irritating (Toxicity Category III).

	A dermal sensitization study was conducted to support registration of GS-U-ACTX-Hv1a-SEQ2 (MRID No. 487790-10).  A 75% w/w mixture of the test substance in mineral oil as topically applied to guinea pigs for a 3-week induction period.  Twenty-seven days after the first induction dose, a challenge dose of the test substance as applied.  The study concluded the test material was not a contact sensitizer.

2)	Subchronic Toxicity, Teratogenicity and Genotoxicity of GS-U-ACTX-Hv1a-SEQ2.  
  
      Vestaron Corporation has requested that the requirements for subchronic toxicity, teratogenicity and genotoxicity for GS-U-ACTX-Hv1a-SEQ2 be satisfied by existing data and information, based on the facts that: 1) the mode of GS-U-ACTX-Hv1a-SEQ2 action is specific to insects, 2) GS-U-ACTX-Hv1a-SEQ2 was not toxic in the acute toxicity studies at the limit dose, 3) data available on structurally similar surrogate compounds demonstrate a lack of toxicity, 4) data on GS-U-ACTX-Hv1a-SEQ2 and surrogate peptide compounds indicate a lack of bioavailability following exposure (MRID No. 487790-19).]

D. Aggregate Exposure

	1. Dietary exposure. 

      	i. Food. [GS-U-ACTX-Hv1a-SEQ2 has a mode of action that is specific to ion channels in the insect nervous system and that does not interact with vertebrate systems. GS-U-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye exposure to test animals, and data on structurally similar surrogate compounds demonstrate a lack of toxicity to other vertebrates. Data on surrogate peptide compounds indicate a lack of bioavailability following oral exposure, supporting the perspective that repeated exposure to GS-U-ACTX-Hv1a-SEQ2 is not of toxicological concern.  There are no reports of ecological or human health hazards caused by GS-U-ACTX-Hv1a-SEQ2.  The lack of toxicity of GS-U-ACTX-Hv1a-SEQ2 following oral exposure, and the known lack of bioavailability and toxicity of surrogate proteins supports the perspective that dietary exposures to GS-U-ACTX-Hv1a-SEQ2 EP would not be expected to pose any quantifiable risk. (MRID No. 487790-19)]
      
      	ii. Drinking water. [Similarly, exposure to humans from residues of GS-U-ACTX-Hv1a-SEQ2 in consumed drinking water would be unlikely.  Potential exposure to surface water would be unlikely and exposure to drinking water (well or ground water) would be impossible to measure. The ingredient is not applied directly to water.
      
      	GS-U-ACTX-Hv1a-SEQ2 has a mode of action that is specific to ion channels in the insect nervous system and that does not interact with vertebrate systems. GS-U-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye exposure to test animals, and data on structurally similar surrogate compounds demonstrate a lack of toxicity to other vertebrates. Data on surrogate peptide compounds indicate a lack of bioavailability following oral exposure, supporting the perspective that repeated exposure to GS-U-ACTX-Hv1a-SEQ2 is not of toxicological concern.  There are no reports of ecological or human health hazards caused by GS-U-ACTX-Hv1a-SEQ2.  The lack of toxicity of GS-U-ACTX-Hv1a-SEQ2 following exposure to vertebrates, and the known lack of bioavailability and toxicity of surrogate proteins supports the perspective that drinking water exposures to GS-U-ACTX-Hv1a-SEQ2 EP would not be expected to pose any quantifiable risk. (MRID No. 487790-19)]

	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 crops in greenhouse or field sites.  

	GS-U-ACTX-Hv1a-SEQ2 has a mode of action that is specific to ion channels in the insect nervous system and that does not interact with vertebrate systems. GS-U-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye exposure to test animals, and data on structurally similar surrogate compounds demonstrate a lack of toxicity to other vertebrates. Data on surrogate peptide compounds indicate a lack of bioavailability following oral exposure, supporting the perspective that repeated exposure to GS-U-ACTX-Hv1a-SEQ2 is not of toxicological concern.  There are no reports of ecological or human health hazards caused by GS-U-ACTX-Hv1a-SEQ2.  The lack of toxicity of GS-U-ACTX-Hv1a-SEQ2 following oral exposure, and the known lack of bioavailability and toxicity of surrogate proteins supports the perspective that non-dietary exposures to GS-U-ACTX-Hv1a-SEQ2 EP would not be expected to pose any quantifiable risk.  (MRID No. 487790-19)]

E. Cumulative Effects

[It is not expected that, when used as proposed, GS-U-ACTX-Hv1a-SEQ2 would result in residues that are of toxicological concern. GS-U-ACTX-Hv1a-SEQ2 has a mode of action that is specific to ion channels in the insect nervous system and that does not interact with vertebrate systems. GS-U-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye exposure test animals, and data on structurally similar surrogate compounds demonstrate a lack of toxicity to other vertebrates. Data on surrogate peptide compounds indicate a lack of bioavailability following oral exposure, supporting the perspective that repeated exposure to GS-U-ACTX-Hv1a-SEQ2 is not of toxicological concern.  There are no reports of ecological or human health hazards caused by GS-U-ACTX-Hv1a-SEQ2.  (MRID No. 487790-19)]

F. Safety Determination

	1. U.S. population. [GS-U-ACTX-Hv1a-SEQ2 has a mode of action that is specific to ion channels in the insect nervous system and that does not interact with vertebrate systems. GS-U-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye exposure to test animals, and data on structurally similar surrogate compounds demonstrate a lack of toxicity to other vertebrates. Data on surrogate peptide compounds indicate a lack of bioavailability following oral exposure, supporting the perspective that repeated exposure to GS-U-ACTX-Hv1a-SEQ2 is not of toxicological concern.  There are no reports of ecological or human health hazards caused by GS-U-ACTX-Hv1a-SEQ2.  (MRID No. 487790-19)

	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, GS-U-ACTX-Hv1a-SEQ2 would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infants and children from exposure to GS-U-ACTX-Hv1a-SEQ2 from the proposed uses.]

G. Effects on the Immune and Endocrine Systems

[To date there is no evidence to suggest that GS-U-ACTX-Hv1a-SEQ2 functions in a manner similar to any known hormone, or that they acts as an endocrine disrupter.]

H. Existing Tolerances

[There is no US EPA tolerance or tolerance exemption for GS-U-ACTX-Hv1a-SEQ2.]

I. International Tolerances

[A Codex Alimentarium Commission Maximum Residue Level (MRL) is not established for GS-U-ACTX-Hv1a-SEQ2.]