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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 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
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[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 VST006325 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-Hv1aSEQ2 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-UACTX-Hv1a-SEQ2 has a unique dual mode of action. One 
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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 calciumactivated 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-Hv1aSEQ2 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-ACTXHv1a-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). 
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An acute inhalation study was conducted to support registration of GS-U-ACTXHv1a-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-UACTX-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-UACTX-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-UACTX-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-Hv1aSEQ2. 

 

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-UACTX-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
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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-UACTX-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-UACTX-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-UACTX-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. GSU-ACTX-Hv1a-SEQ2 was not toxic following oral, dermal, inhalation and eye 
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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-Hv1aSEQ2 following oral exposure, and the known lack of bioavailability and toxicity

of surrogate proteins supports the perspective that non-dietary exposures to GS-UACTX-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-ACTXHv1a-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
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[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.]