GS-omega/kappa-Hxtx-Hv1a 

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BIOPESTICIDES REGISTRATION ACTION DOCUMENT

GS-omega/kappa-Hxtx-Hv1a 

Pesticide Chemical (PC) Code: 006100

DRAFT DOCUMENT 

U.S. Environmental Protection Agency 

Office of Pesticide Programs 

Biopesticides and Pollution Prevention Division 

Dated 01/09/14 
GS-U-ACTX-Hv1a-SEQ2

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TABLE OF CONTENTS

I. EXECUTIVE SUMMARY .............................................................................................. 4

II. ACTIVE INGREDIENT OVERVIEW ................................................................................ 5

III. REGULATORY BACKGROUND ................................................................................ 5

A. Applications for Pesticide Registration ................................................................................................................ 5

B. Food Tolerance Exemption ................................................................................................................................... 6

IV. RISK ASSESSMENT ...................................................................................................... 6

A. Product Analysis Assessment (40 CFR § 158.2120) ....................................................................................... 7

B. Human Health Assessment (40 CFR § 158.2140) ................................................................................................ 7

C. Environmental Assessment (40 CFR § 158.2060) .............................................................................................. 12

V. ENVIRONMENTAL JUSTICE .......................................................................................... 15

VI. RISK MANAGEMENT DECISION ................................................................................. 15

VII. ACTIONS REQUIRED BY THE REGISTRANT ......................................................... 16

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ........................................... 17

IX. BIBLIOGRAPHY................................................................................................................ 18

APPENDIX A. BIOCHEMICAL/MICROBIAL PESTICIDES DATA REQUIREMENTS

 .........................................................................................................21

APPENDIX B. PESTICIDE PRODUCTS ............................................................................... 28
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BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM 

Office of Pesticide Programs (OPP) 

Science Reviews 

Sheryl K. Reilly, Ph.D. 

 Acute Mammalian Toxicity, Biopesticides and Pollution Prevention Division 

Elissa Reeves, Ph.D. 

 Human Health, Health Effects Division 

Joel Gagliardi, Ph.D. 

Product Analysis, Biopesticides and Pollution Prevention Division 

Meghan Radtke, Ph.D. 

Environmental Effects, Environmental Fate and Effects Division 

Regulations 

Biopesticides and Pollution Prevention Division

Kimberly Nesci Chief, Microbial Pesticides Branch 

Shannon Borges Team Leader, Microbial Pesticides Branch 

Susanne Cerrelli Regulatory Action Leader 

 Registration Division 

Deborah McCall Chief, Insecticide Branch 

Debra Rate, Ph.D. Biologist 
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I. EXECUTIVE SUMMARY 

The active ingredient GS-omega/kappa-Hxtx-Hv1a (VersitudeTM peptide, formerly GS-UACTX-Hv1a-SEQ2) acts as an insecticide against cabbage looper for use on ornamental plants 

and edible crops. The cabbage looper insect is also known by the scientific name Trichoplusia ni 

and feeds on a wide variety of cultivated plants and weeds. GS-omega/kappa-Hxtx-Hv1a 

(VersitudeTM peptide) functions primarily as a central nervous system inhibitor in insects, and is 

intended for use in the suppression of foliage feeding cabbage looper insects. The end-use 

product, VST-006330 EP, is mixed with water and applied as a pre-harvest, foliar spray with 

ground or aerial pesticide equipment, and it can be used in either the field or greenhouse to 

suppress cabbage looper. 

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for 

the public to participate in major registration decisions before they occur. Under 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 uses; first outdoor uses; first residential uses; or 

any other registration actions for which EPA believes there may be significant public interest. 

 

Consistent with the policy of making registration actions more transparent, the proposed 

pesticide products containing the new active ingredient, GS-omega/kappa-Hxtx-Hv1a, are 

subject to a 15-day comment period prior to registration of the manufacturing and end-use 

products. In addition to containing a new active ingredient, the registration of these products 

represents the first food use for GS-omega/kappa-Hxtx-Hv1a. The docket identification number 

associated with these registration actions and accessed through either 

http://www.regulations.gov/ or http://www.epa.gov/pesticides/regulating/registration-status.html, 

is EPA-HQ-OPP-2012-0391 for GS-omega/kappa-Hxtx-Hv1a. The following documents are 

available in EPA-HQ-OPP-2012-0391: 

1) Draft GS-omega/kappa-Hxtx-Hv1a Biopesticides Registration Action Document (BRAD) for 

VersitudeTM peptide, 

2) U.S. EPA. 2013a “VERSITUDETM Peptide: Summary of Hazard and Science Policy Council 

(HASPOC) Electronic Review: Recommendations on the Need for Additional Toxicity Studies” 

Memorandum from K. Rury, MPH to E. Reaves, Ph.D. dated September 18, 2013. 

3) U.S. EPA. 2013b. “Ecological Risk Assessment for the Proposed New Chemical Registration 

of GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, 

and Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial 

Flowers and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf.”

Memorandum from M. Radtke, Ph.D., F. Khan, Ph.D., E. Odenkirchen, Ph.D., and S. Sankula, 

Ph.D. dated May 30, 2013,

4) U.S. EPA. 2013c. “Ecological Risk Assessment for the Proposed New Chemical Registration 

of GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, 

and Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial 

Flowers and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf - 

AMENDMENT.” Memorandum from M. Radtke, Ph.D., and S. Sankula, Ph.D. to M. Suarez and 

S Cerrelli dated September 24, 2013.
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5) U.S. EPA. 2013d. “GS-omega/kappa-Hxtx-Hv1a: Qualitative Human Health Assessment.”

Memorandum from E . Reaves, Ph.D. and P. Shah, Ph.D. dated December 6, 2013. 

6) U.S. EPA. 2013 e. “Ecological Risk Assessment for the Proposed New Chemical Registration 

of GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, 

and Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial 

Flowers and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf – 

AMENDMENT 2” Memorandum from M. Radtke, Ph.D., M. Wait and S. Sankula, Ph.D. to S 

Cerrelli, S. Borges, and K. Nesci dated December 5, 2013.

7) VST 006325 TGAI -DRAFT Label 

8) VST-006330 EP -DRAFT Label 

While a final decision on registration is contingent upon review and consideration of public 

comments, EPA presently believes that the risk assessment and information submitted support 

registration of the VST- 006325 TGAI, and VST-006330 EP. The basis for this preliminary 

decision can be found in the risk assessment for GS-omega/kappa-Hxtx-Hv1a, which is 

characterized throughout this BRAD. 

 

II. ACTIVE INGREDIENT OVERVIEW 

Chemical Name: GS-omega/kappa-Hxtx-Hv1a 

Synonym: VersitudeTM peptide 

 OPP Chemical Code: 006100

 Type of Pesticide: Insecticide 

 See Appendix B for specific information (e.g., 

use sites, application rates, methods of application, 

formulation types, and target pest) regarding 

the proposed pesticide products containing this 

active ingredient. 

III. REGULATORY BACKGROUND

A. Applications for Pesticide Registration 

On April 26, 2012, Vestaron Corporation (address: 4717 Campus Dr., Suite 1200, Kalamazoo, 

MI 49008) submitted applications to register one end-use product, VST-006330 EP (EPA File 

Symbol 88847-E), and one manufacturing use product, VST-006325 TGAI (EPA File Symbol 

88847-R) to the U.S. Environmental Protection Agency (EPA or the Agency) to be registered in 

accordance with section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

EPA announced receipt of these applications to register pesticide products containing a new 

active ingredient, GS-U-ACTX-Hv1a-SEQ2 (now GS-omega/kappa-Hxtx-Hv1a), in the Federal 
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Register on August 14, 2012 (77 Federal Register (FR) 48519), and opened a 30-day public 

comment period pursuant to the provisions of FIFRA section 3(c)(4). No substantive comments 

were received during the comment period concerning this announcement. A correction for the 

current recognized name of the active ingredient (GS-omega/kappa-Hxtx-Hv1a ) was published 

in the Federal Register of December 18, 2013 (78 FR 76613). 

B. Food Tolerance Exemption 

Concurrent with its registration applications and under Federal Food, Drug, and Cosmetic Act 

(FFDCA) section 408(d), Vestaron Corporation submitted a petition to establish an exemption 

from the requirement of a tolerance for residues of the pesticide active ingredient, GS-U-ACTXHv1a-SEQ2 (now GS-omega/kappa-Hxtx-Hv1a) (Pesticide Petition (PP) 2F8014) in or on all 

food commodities. EPA published a Notice that Vestaron Corporation filed a petition to 

establish an exemption from the requirement of a tolerance for residues of the insecticide in the 

Federal Register of July 25, 2012 (77 FR 43562), and opened a 30-day comment period. No 

comments to the petition for GS-U-ACTX-Hv1a-SEQ2 (now GS-omega/kappa-Hxtx-Hv1a) 

tolerance exemption were received. A correction for the name of the active ingredient was 

published in the Federal Register of December 18, 2013 (78 FR 76589). The active ingredient, 

previously known as GS-U-ACTX-Hv1a-SEQ2, was revised to GS-omega/kappa-Hxtx-Hv1a, 

based on acceptable nomenclature for naming peptide toxins from spiders. 

IV. RISK ASSESSMENT 

In the Federal Register of October 26, 2007, EPA issued a Final Rule on the data requirements 

to support registration of biochemical pesticides and updated the definition for microbial 

pesticides (72 FR 61002). The rule became effective on December 26, 2007. The data and 

information evaluated for this BRAD were considered in light of these requirements. 

The classifications for each data submission are assigned by EPA science reviewers, and indicate 

the usefulness of the information contained in the documents for risk assessment. A rating of 

“acceptable” indicates the study is scientifically sound and is useful for risk assessment. A 

“supplemental” rating indicates the data provide some information that can be useful for risk 

assessment. The studies may have certain aspects determined not to be scientifically acceptable 

(“supplemental: upgradeable”). If a study is rated as “supplemental: upgradeable,” EPA always 

provides an indication of what is lacking or what can be provided to change the rating to 

“acceptable.” If there is simply a “supplemental” rating, the reviewer often will state that the 

study is not required by 40 CFR Part 158. Both “acceptable” and “supplemental” studies may be 

used in the risk assessment process as appropriate. An “unacceptable” rating indicates that new 

data need to be submitted. 

For assessing the risks to human health, toxicity or other adverse effects are based on the 

hazard(s) identified from mammalian toxicity and irritation studies conducted with and/or other 

information pertaining to the active ingredient and proposed pesticide products submitted to EPA 

in support of registration. The active ingredient and formulated manufacturing and end-use 

products are classified as Toxicity Category I, II, III, or IV according to the results of studies 

conducted with the TGAI and proposed pesticide products to determine the acute toxicity by the 

oral, dermal, and inhalation routes of exposure, and their potential for dermal and eye irritation, 

Toxicity Category I represents the highest level of toxicity or potential for eye and skin irritation 

(corrosion, permanent damage), while Toxicity Category IV indicates the lowest level of toxicity 
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or irritation. 

A. Product Analysis Assessment (40 CFR § 158.2120) 

The product characterization of GS-omega/kappa-Hxtx-Hv1a is provided in an EPA review 

(U.S. EPA. 2013g). This active ingredient is proposed for formulation in an end use product 

(EP), VST-006330, which will contain the TGAI at a concentration of 20%. The EP is proposed 

for dilution with application as a foliar spray, intended as a new broad spectrum pesticide to be 

used (pre-harvest, up to day of harvest) on various vegetable and cole crops, field crops, 

ornamentals, and nursery stock to suppress cabbage looper. GS-omega/kappa-Hxtx-Hv1a 

functions primarily as a central nervous system inhibitor for suppressing cabbage looper 

caterpillars that feed on the foliage of labeled crops. GS-omega/kappa-Hxtx-Hv1 can be used in 

either the field or greenhouse for suppression of cabbage looper. 

A summary of the data requirements is located in Tables 1-4 in Appendix A. 

B. Human Health Assessment (40 CFR § 158.2140)

1. Toxicity 

All Tier I mammalian toxicology data requirements for GS-omega/kappa-Hxtx-Hv1 were 

fulfilled. For a comprehensive summary of the toxicology data requirements described in 

sections IV(B)(1)(a) and IV(B)(1)(b), as well as additional product-specific data and other 

information submitted to support the individual registrations, refer to Table 5 in Appendix A. 

a. Acute Toxicity/Pathogenicity – Tier I

Acute Oral Toxicity/Pathogenicity [Office of Chemical Safety and Pollution Prevention (OCSPP) 

Guideline 885.3050 and Acute Pulmonary Toxicity/Pathogenicity (OCSPP Guideline 885.3150; 

Master Record Identification Number (MRID No.) 487790-19]

Upon consideration of results of other definitive toxicological data submitted by the petitioner, 

the EPA waived acute oral toxicity/pathogenicity testing for GS-omega/kappa-Hxtx-Hv1a. An 

acute oral toxicity study conducted on female rats (MRID No. 487790-07) demonstrated that GSomega/kappa-Hxtx-Hv1a was not toxic (LD50 greater than 5,000 mg/kg; Toxicity Category IV). 

In addition, the yeast used to produce the peptide is not pathogenic, the yeast is removed during 

the manufacturing process, and samples monitored for microbial contamination have been 

negative. These data indicate that this peptide would not be toxic through the oral route of 

exposure and that further testing is not necessary (U.S. EPA. 2013d). The acute oral 

toxicity/pathogenicity and acute pulmonary toxicity/pathogenicity studies were not required 

because products containing GS-omega/kappa-Hxtx-Hv1 do not contain microorganisms. 

Acute Injection Toxicity/Pathogenicity (OCSPP Guideline 885.3200; MRID No 487790-19):

Upon consideration of results of other definitive toxicological data submitted by the petitioner, 

the EPA waived acute injection toxicity/pathogenicity testing for GS-omega/kappa-Hxtx-Hv1a. 

GS-omega/kappa-Hxtx-Hv1a is low in acute toxicity. The acute oral, dermal and inhalation 

toxicity studies conducted on GS-omega/kappa-Hxtx-Hv1a all reported no deaths at the limit 

dose. In addition, the yeast used to produce the peptide is not pathogenic, the yeast is removed 
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during the manufacturing process, and samples monitored for microbial contamination have been 

negative. 

b. Hypersensitivity Incidents (OCSPP Guideline 885.3400):

Cell Culture (OCSPP Guideline 885.3500): 

This study was not required because GS-omega/kappa-Hxtx-Hv1a is not a virus (refer to test 

note #4 of 40 CFR § 158.2140(d)). 

Acute Oral Toxicity (OCSPP Guideline 870.1100; MRID No. 487790-07): An acute oral toxicity 

test (Up and Down procedure) was conducted with rats to determine the potential for VST-006325 to 

produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral 

LD50 of the test substance is greater than 5,000 mg/kg of body weight in female rats. This study is 

classified as Acceptable/Toxicity Category IV. 

Acute Dermal Toxicity (OCSPP Guideline 870.1200; MRID No. 487790-08): An acute dermal toxicity 

test was conducted with rats to determine the potential for VST-006325 to produce toxicity from a single 

topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test 

substance is greater than 5,000 mg/kg of body weight in male and female rats. This study is classified 

Acceptable/Toxicity Category IV. 

Acute Inhalation Toxicity (OCSPP Guideline 870.1300; MRID No. 487790-08): An acute inhalation 

toxicity test was conducted with rats to determine the potential for VST-006325 to produce toxicity by the 

inhalation (nose-only) exposure route. Under the conditions of this study, the single exposure acute 

inhalation LC50 of the test substance is greater than 2.05 mg/L in male and female rats. This study is 

classified as Acceptable/Toxicity Category IV. 

Acute Eye Irritation (OCSPP Guideline 870.2400; MRID No. 487790-10): A primary eye 

irritation test was conducted with New Zealand white rabbits to determine the potential for VST006325 to cause eye irritation. Under the conditions of this study, the test substance is minimally 

irritating to the eye. This study is classified as Acceptable/Toxicity Category IV. 

Primary Dermal Irritation (OCSPP Guideline 870.2500; MRID No. 487790-11: A primary skin 

irritation test was conducted with New Zealand white rabbits to determine the potential for VST006325 to produce irritation after a single topical application. Under the conditions of this 

study, the test substance is classified as moderately irritating to the skin. This study is 

Acceptable/Toxicity Category III. 

c. Acute Toxicology and Subchronic Toxicity/Pathogenicity – Tier II; 

 Reproductive Fertility Effects, Carcinogenicity, Immunotoxicity, and 

 Infectivity/Pathogenicity Analysis – Tier III 

Tier II and Tier III studies were not required for GS-omega/kappa-Hxtx-Hv1a based on the lack 

of acute toxicity in the Tier I studies.

d. Endocrine Disruptors 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 
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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 

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 quantitative 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 9 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. 

GS-omega/kappa-Hxtx-Hv1a 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), EPA must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP 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. Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations 

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement 

for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA 

determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to 

mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the 

pesticide chemical residue, including all anticipated dietary exposures and all other exposures for 

which there is reliable information.” This includes exposure through drinking water and in 

residential settings but does not include occupational exposure. Pursuant to section 408(c)(2)(B) 

of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a 

tolerance, EPA must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, 

which require EPA to give special consideration to exposure of infants and children to the 

pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable 

certainty that no harm will result to infants and children from aggregate exposure to the pesticide 

chemical residue....” Additionally, section 408(b)(2)(D) of FFDCA requires that EPA consider 

“available information concerning the cumulative effects of [a particular pesticide's] residues and 

other substances that have a common mechanism of toxicity.” 

EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide 

residues. First, EPA determines the toxicity of pesticides. Second, EPA examines exposure to the 

pesticide through food, drinking water, and through other exposures that occur as a result of 

pesticide use in residential settings. 
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Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data 

and other relevant information, and considered its validity, completeness, and reliability and the 

relationship of this information to human risk. EPA has also considered available information 

concerning the variability of the sensitivities of major identifiable subgroups of consumers, 

including infants and children. 

Based on the acute toxicity data and information discussed previously and presented in Table 5 

in Appendix A, the data required for a FQPA risk assessment for GS-omega/kappa-Hxtx-Hv1a 

have been fulfilled, and EPA has determined that there is a reasonable certainty that no harm 

will result from exposure to GS-omega/kappa-Hxtx-Hv1a residues. 

a. Aggregate Exposure 

In examining aggregate exposure, section 408 of FFDCA directs EPA to consider available 

information concerning exposures from the pesticide residue in food and all other 

nonoccupational exposures, including drinking water from ground water or surface water and 

exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor 

uses). 

Dietary Exposure and Risk Characterization: GS-omega/kappa-Hxtx-Hv1a is a 41 amino acid 

peptide derived from one of the toxicologically active components of Australian funnel spider 

(Hadronyche versuta) venom and isolated from yeast, and exposure to residues of this peptide, in 

consumed food is possible. GS-omega/kappa-Hxtx-Hv1a may be applied foliarly to edible 

plants, turf and ornamentals. Since GS-omega/kappa-Hxtx-Hv1a is applied as a foliar insecticide 

to crops, it is possible that edible food commodities may retain residues of GS-omega/kappaHxtx-Hv1a. Further, treated crops could be diverted for food or feed purposes; therefore, 

exposure to GS-omega/kappa-Hxtx-Hv1a in this situation is also plausible. Although residues 

from the use of pesticides containing GS-omega/kappa-Hxtx-Hv1a may be present on certain 

food commodities, processing procedures (e.g., peeling and washing) may reduce such residues. 

Regardless of the scenario, should GS-omega/kappa-Hxtx-Hv1a be present on food, EPA 

concludes that there is a reasonable certainty that no harm will result from exposure to such 

residues because of the lack of toxicity in the previously described toxicological studies (see 

Appendix A). 

Drinking Water Risk Characterization: 

Like consumed food, exposure to residues of GS-omega/kappa-Hxtx-Hv1a, a 41 amino acid 

peptide, in consumed drinking water is anticipated to be possible but negligible. However, GSomega/kappa-Hxtx-Hv1a interacts specifically with the insect nervous system and does not 

interact with vertebrate systems. The submitted and reviewed acute oral data suggest GSomega/kappa-Hxtx-Hv1a is not toxic via the oral route (> 5,000 mg/kg). Submitted literature 

studies on surrogate peptide compounds indicate lack of bioavailability by mammals via the oral 

route (MRID 48779019). Based on the low toxicity profile of the compound and low 

bioavailability, exposure to this compound from treated food or residues in water is not of 

concern. 

Non-occupational, Residential Risk Characterization: 

Residential exposure to GS-omega/kappa-Hxtx-Hv1a is not expected to pose any undue risk 

provided the product is used in accordance with label directions. Appropriate personal protective 
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equipment and precautionary statements are required on pesticide product labels to mitigate any 

potential risks to pesticide handlers due to prolonged or repeated exposures. 

 

b. Cumulative Effects from Substances with a Common Mechanism of Toxicity 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, 

or revoke a tolerance exemption, EPA consider “available information concerning the 

cumulative effects of [a particular pesticide’s] residues and other substances that have a common 

mechanism of toxicity.” 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for 

GS-omega/kappa-Hxtx-Hv1a. In addition, GS-omega/kappa-Hxtx-Hv1a does not convert to 

toxic metabolites resulting in other substances; therefore, EPA has not assumed that GSomega/kappa-Hxtx-Hv1a has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/. 

c. Determination of Safety for the U.S. Population, Infants and Children 

 

FFDCA section 408(b)(2)(C) provides that EPA shall assess the available information about 

consumption patterns among infants and children, special susceptibility of infants and children to 

pesticide chemical residues, and the cumulative effects on infants and children of the residues 

and other substances with a common mechanism of toxicity. In addition, FFDCA section 

408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of safety for 

infants and children in the case of threshold effects to account for prenatal and postnatal toxicity 

and the completeness of the database on toxicity and exposure unless EPA determines that a 

different margin of safety will be safe for infants and children. This additional margin of safety is 

commonly referred to as the FQPA Safety Factor. In applying this provision, EPA either retains 

the default value of 10X or uses a different additional safety factor when reliable data available 

to EPA support the choice of a different factor. 

Based on the lack of toxicity in mammals demonstrated in the studies summarized in section 

IV(B)(1)(a) and Table 5 in Appendix A, EPA concludes that there is a reasonable certainty that 

no harm will result to the U.S. population, including infants and children, from aggregate 

exposure to the residues of GS-omega/kappa-Hxtx-Hv1a. This includes all anticipated dietary 

exposures and all other exposures for which there is reliable information. EPA has arrived at this 

conclusion because the data and information available on GS-omega/kappa-Hxtx-Hv1a do not 

demonstrate toxic potential to mammals. Because there are no threshold effects of concern, the 

provision requiring an additional margin of safety does not apply. 

3. Occupational Exposure and Risk Characterization 

Occupational exposure to GS-omega/kappa-Hxtx-Hv1a is not expected to pose undue risks to 

pesticide handlers (mixer/loader/applicators), but EPA requires appropriate personal protective 

equipment and precautionary statements to mitigate any potential risks to pesticide handlers from 
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prolonged or repeated exposures. Potential handler exposure is reduced through the use of 

required personal protection equipment (PPE), including long-sleeved shirt and long pants, 

waterproof gloves and shoes plus socks. 

4. Human Health Risk Characterization 

EPA considered human exposure to GS-omega/kappa-Hxtx-Hv1a in light of the standard for 

registration in FIFRA and the relevant safety factors in FFDCA. 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 when GS-omega/kappa-Hxtx-Hv1a pesticide products are used in 

accordance with EPA-approved labeling. 

C. Environmental Assessment (40 CFR § 158.2060) 

For a comprehensive summary of the generic data requirements described in sections IV(C), 

refer to Table 6 in Appendix A. The ecological and environmental assessment (Section IX (B)) 

listed the following studies as data gaps: 835.2129 (hydrolysis), 835.2240 (photodegradation in 

water), 835.2410 (photodegradation in soil), 835.2370 (photodegradation in air – conditional, 

depending on chemical’s properties), 835.4100 (aerobic soil metabolism), 835.4200 (anaerobic 

soil metabolism), 835.4300 (aerobic aquatic metabolism), 835.4400 (anaerobic aquatic 

metabolism), 835.1230/835.1240 (leaching adsorption/desorption), 835.6100 (terrestrial field 

dissipation), 835.1410 (volatility laboratory – conditional, depending on chemical’s properties). 

However, these data are not required under 40 CFR § 158.2060 for this pesticide because no 

adverse effects were noted in the Tier I studies. These environmental fate data listed above may 

be conditionally required only when potential adverse effects are indicated in the Tier I nontarget organism studies. 

Ecological risk characterization integrates the results of the exposure and ecotoxicity data to 

evaluate the likelihood of adverse ecological effects. In some cases, toxicity is noted as nondefinitive since testing concentrations were either not high enough or not low enough and an 

exact value was not determined. Although an actual value can’t be noted, a bound can be put on 

the potential toxicity based on available information. 

No direct risk concerns were identified for the following: aquatic-phase amphibians, aquatic 

plants, birds, freshwater and estuarine/marine fish, freshwater and estuarine/marine invertebrates, 

mammals, reptiles, terrestrial-phase amphibians, terrestrial plants, or contact exposure to 

terrestrial invertebrates. 

Risks to Aquatic Organisms 

Fish and Invertebrates 

The LC50 for freshwater fish is > 100 mg ai/L. Compared to the peak EEC of 0.044 mg ai/L, the 

LC50 is at least four orders of magnitude higher. This indicates that risk concerns to freshwater 

fish on an acute exposure basis are unlikely. Acute toxicity data were not available for 

estuarine/marine fish. In lieu of this, freshwater fish are used as a surrogate. This adds some 

uncertainty to the analysis; however, given that no effects (including sub-lethal) were seen in 

freshwater fish and the extremely large difference between the LC50 value and the peak EEC, it 

is unlikely that estuarine/marine fish would be markedly different in their sensitivity to GS-
GS-U-ACTX-Hv1a-SEQ2

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omega/kappa-Hxtx-Hv1a. Consequently, estuarine/marine fish are not expected to be at risk on 

an acute exposure basis. 

The EC50 for freshwater invertebrates is >1000 mg ai/L. Compared to the peak EEC of 0.044 mg 

ai/L, the EC50 is at least five orders of magnitude larger. Therefore, acute risk concerns to 

freshwater invertebrates are unlikely. Acute toxicity data were not available for estuarine/marine 

invertebrates, thus, the freshwater invertebrate data were used as a surrogate. For the same 

reasons identified for fish, the freshwater invertebrate data are considered a reasonably protective 

surrogate for estuarine/marine invertebrates. Based on this, EPA does not have acute risk 

concerns for estuarine/marine invertebrates. 

Toxicity data were not available for chronic exposures to fish or invertebrates. One of the 

uncertainties in the acute aquatic studies was the possibility that GS-omega/kappa-Hxtx-Hv1a 

degraded very quickly and the actual exposure experienced by the test organism was far lower 

than the nominal concentration of active ingredient. Hydrolysis data for the peptide are not 

available, but it is likely that degradation rapidly occurs in water. The quaternary structure 

(protein folding) of GS-omega/kappa-Hxtx-Hv1a is very complex; conditions that even slightly 

alter the protein’s configuration (e.g., exposure to water) will interfere with its receptor binding. 

Terrestrial data indicate that the half-life of GS-omega/kappa-Hxtx-Hv1a is only 4 days. If a 

similar or shorter half-life occurs in water, aquatic organisms would not reasonably be expected 

to experience chronic exposure conditions. Therefore, risk concerns from chronic exposures are 

considered unlikely. 

Aquatic Plants 

Toxicity data were not available for aquatic vascular and non-vascular plants. At an application 

rate of 0.8 lb ai/A, terrestrial plants showed no effects. As with the aquatic invertebrate and fish 

analysis, if the 0.8 lb ai/A were sprayed directly onto a 1 ha 20,000,000 L pond, the 

concentration is expected to be 0.044 mg ai/L. Given the specificity of GS-omega/kappa-HxtxHv1a to insects, the low probability that aquatic plants have this same receptor, and the peptide’s 

predicted instability in water, EPA does not have risk concerns for aquatic plants. 

Risk to Terrestrial Organisms

Birds and Mammals 

The highest acute dose-based EEC generated for birds is 424.72 mg ai/kg-bw (20 g bird eating 

short grass). The LD50 of > 630 mg ai/kg-bw, when compared with the EEC, is approximately 

one-third higher. Thus, acute risks to birds are not expected. Similarly, the acute dose-based 

EEC for mammals is 355.56 mg ai/kg-bw (15 g mammal eating short grass). The corresponding 

LD50 is > 5000 mg ai/kg-bw, which is one order of magnitude higher than the EEC. Therefore, 

EPA does not have acute risk concerns for mammals. 

Toxicity data were not available for chronic exposures to birds and mammals. The 

bioavailability of GS-omega/kappa-Hxtx-Hv1a is expected to be low, based on the physical 

structure of the peptide. Spider venoms are designed to be injected into their prey. Oral 

ingestion is likely to result in a drastic decrease in the toxicity of the compound or eliminate it 

altogether; peptides are rapidly digested in the gut. As an example, peptide drugs that have been 

developed for human oral administration are generally limited to a bioavailability of 1-2 % 

because of their molecular size (large), hydrophilic nature, and physical stability in the digestive 

tract. Consequently, absorption enhancing agents and chemical and physical modifications to the 
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peptide molecules are made to increase the absorption. Drugs derived from the cone shell 

(Conus fulmen) are based on a peptide with the similar cystine knot of 3 disulfide bonds that is 

found in GS-omega/kappa-Hxtx-Hv1a; they also share similar physical chemical characteristics. 

The drug is delivered intrathecally (into the spinal canal) because of a lack of bioavailability 

through the oral route. The limited bioavailability and similarity of the cone shell peptide and 

GS-omega/kappa-Hxtx-Hv1a further supports the premise that the oral exposure route poses 

little chance of toxicity to vertebrates. Consequently, EPA does not have chronic risk concerns 

for birds and mammals. 

Acute Risks to Honeybees 

EECs were generated for both the oral and contact exposure pathways for honeybees. 

Toxicological data were available for the contact route; the LD50 is > 25 μg ai/bee for adult 

honeybees. The contact EEC (converted to a dose) is 18.7 μg ai/bee, which is lower than the 

LD50. Consequently, direct risks to honeybees via the contact exposure route are not considered 

likely. The insecticide is intended to be delivered to its targets through the oral route; therefore, 

risk concerns (via ingestion) are identified for honeybees (adult and larval). A study was 

submitted to complete the suite of toxicity information needed to evaluate potential risks to adult 

honeybees and non-target terrestrial invertebrates from the proposed new pesticide. Based on the 

high LD50 (> 100 μg ai/bee) and no observed sub-lethal effects, acute direct risks to terrestrial 

invertebrates, including honey bees, through the oral exposure route are no longer expected, 

based on the recently evaluated toxicity data. Direct risks to larval terrestrial invertebrates 

remain an uncertainty because no toxicity information is yet available for this life stage. Indirect 

risks may be possible for terrestrial plants that rely on larval terrestrial invertebrates for 

pollination and other ecological services. Indirect effects are also possible for taxa that rely on 

larval terrestrial invertebrates as a food source (amphibians, birds, fish, mammals, reptiles, 

terrestrial invertebrates). 

Risk to Non-Target Organisms

Non-target Terrestrial and Semi-Aquatic Plants 

Toxicity data for terrestrial plants were available; however the solubility information for GSomega/kappa-Hxtx-Hv1a needed to run the TerrPlant model was not available. The plant 

toxicity studies did not exhibit reductions in seedling emergence and vegetative vigor endpoints 

that were greater than 25%. Given that they were conducted at the highest application rate, 

effects to plants are probably unlikely for the proposed uses. Consequently, no risk concerns are 

identified for plants from the proposed application rate and uses. 

Endangered Species

Terrestrial Invertebrates 

Based on the endangered species analysis, no direct risk concerns have been identified. There is 

a potential concern for indirect effects to terrestrial plants that have obligate pollinator 

requirements or other dependencies on terrestrial invertebrates. Species that depend on 

terrestrial invertebrates for food (amphibians, birds, fish, mammals, reptiles, terrestrial 

invertebrates) may also be at indirect risk. 
GS-U-ACTX-Hv1a-SEQ2

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Biopesticides Registration Action Document - DRAFT 

V. 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. Fair 

treatment means that no group of people, including racial, ethnic, or socioeconomic groups, 

should bear a disproportionate share of the negative environmental consequences resulting from 

industrial, municipal, and commercial operations or the execution of federal, state, local, and 

tribal environmental programs and policies. Meaningful involvement means that (1) potentially 

affected community residents have an appropriate opportunity to participate in decisions about a 

proposed activity that will affect their environment and/or health; (2) the public’s contribution 

can influence the regulatory agency’s decision; (3) the concerns of all participants involved will 

be considered in the decision-making process; and (4) the decision-makers seek out and facilitate 

the involvement of those potentially affected. EPA has this goal for all communities and persons 

across the United States. 

To help address potential environmental justice issues, EPA seeks information on any groups or 

segments of the population who, as a result their location, cultural practices, or other factors, 

may have atypical, unusually high exposure to GS-omega/kappa-Hxtx-Hv1a, compared to the 

general population. Please comment if you are aware of any subpopulations that may have 

atypical, unusually high exposure compared to the general population. 

For additional information regarding environmental justice issues, please visit EPA’s web site at 

http://www.epa.gov/compliance/environmentaljustice/index.html. 

VI. RISK MANAGEMENT DECISION 

Section 3(c)(5) of FIFRA authorizes the Agency to approve the registration of a pesticide 

without condition, if the Administrator determines that (i) its composition is such as to warrant 

the proposed claims for it, (ii) its labeling and other material required to be submitted comply 

with the requirements of this Act, (iii) it will perform its intended function without unreasonable 

adverse effects on the environment, and (iv) when used in accordance with widespread and 

commonly recognized practice it will not generally cause unreasonable adverse effects on the 

environment. 

In reference to the first and second determinations above, the compositions of the pesticides 

(VST-006325 TGAI and VST-006339 EP) are such that the proposed claims are warranted and 

the Agency received satisfactory data to conduct risk assessments for the uses proposed. 

In reference to the third determination above, the Agency believes that the use of GSomega/kappa-Hxtx-Hv1a will not cause any unreasonable adverse human health or ecological 

effects. This determination is based on the findings in the Agency’s conservative human health 

and environmental risk assessments. 

The screening level assessment identified potential risks to bee larvae. The registrant has 

adopted the following pollinator protection language for the environmental hazards section and 

the directions for use for the labels. 
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Environmental Hazard: Exposure of adult bees to direct treatment or residues on 

blooming crops can lead to effects on honeybee larvae. See the "Directions for Use" 

section of this label for application instructions that minimize risk to honey bee larvae. 

Directions for Use: To minimize potential exposure to bee larvae: Do Not apply this 

product at any time between 4 days prior to bloom and until after petal fall, or if bees are 

foraging in the treatment area.

These restrictions prohibit application while bees are foraging and crops are in bloom. The 

advisory statements highlight the potential risks and exposure to bees if applied. Minimization 

of adult honey bee exposure to GS-omega/kappa-Hxtx-Hv1a residues through application 

restrictions is expected to mitigate potential risk to both adults and larvae. 

In reference to the fourth determination above, the product label that includes the mitigation 

measures described above provides adequate directions for use that when used in accordance 

with widespread and commonly recognized practice it will not generally cause unreasonable 

adverse effects on the environment. 

The Agency believes that with the revised labeling as described above, i) the composition of the 

GS-omega/kappa-Hxtx-Hv1a products are such as to warrant the proposed claims for them, (ii) 

the labeling and other material required to be submitted comply with the requirements of this 

Act, (iii) these pesticides will perform their intended function without unreasonable adverse 

effects on the environment, and (iv) when used in accordance with widespread and commonly 

recognized practice these pesticides will not generally cause unreasonable adverse effects on the 

environment. Therefore, the Agency proposes to grant these unconditional registrations and 

establish an exemption to the requirement of a tolerance for use on ornamental plants, and edible 

crops, provided that the label statements described in this section are incorporated. 

VII. ACTIONS REQUIRED BY THE REGISTRANT

A. Final Printed Labeling 

Before releasing pesticide products containing GS-omega/kappa-Hxtx-Hv1a for shipment, the 

registrant is required to provide appropriate final printed labeling to EPA. 

B. Reporting of Adverse Effects and Hypersensitivity Incidents 

Notwithstanding the information stated in the previous sections, 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 described 

below. 

Reports of all incidents of adverse effects to the environment must be submitted to EPA under 

the provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersensitivity 

(including both suspected and confirmed incidents) must be reported to EPA under the 

provisions of 40 CFR § 158.2140(d). 
GS-U-ACTX-Hv1a-SEQ2

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VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS 

ASAE American Society of Agricultural Engineers 

BPPD Biopesticides and Pollution Prevention Division 

BRAD Biopesticides Registration Action Document 

bw body weight of animal 

CFR Code of Federal Regulations 

cfu colony-forming unit(s) 

cfu/kg colony-forming units per kilogram 

cfu/mL colony-forming units per milliliter 

cP centipoise 

DSMZ Deutsche Sammlung von Mikroorganismen und Zellkulturen (the German Strain 

Collection for Microorganisms) 

EDSP Endocrine Disruptor Screening Program 

EP end-use product 

EPA Environmental Protection Agency (the “Agency”) 

FFDCA Federal Food, Drug, and Cosmetic Act 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FQPA Food Quality Protection Act 

FR Federal Register 

g/mL gram per milliliter 

LC50 median lethal concentration. A statistically derived concentration of a 

 substance that can be expected to cause death in 50% of test animals. It is 

 usually expressed as the weight of substance per weight or volume of water, 

 air, or feed (e.g., mg/L, mg/kg, or ppm).

LD50 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, dermal, or inhalation). It is expressed as a weight of 

 substance per unit weight of animal (e.g., mg/kg). 

mg/kg milligrams per kilogram 

mg/L milligrams per liter 

MP manufacturing-use product 

MRID No. Master Record Identification Number 

NIOSH National Institute for Occupational Safety and Health 

NRRL Northern Regional Research Laboratory 

OCSPP Office of Chemical Safety and Pollution Prevention 

OPP Office of Pesticide Programs 

PC Code Pesticide Chemical Code 

PP Pesticide Petition 

PPE personal protective equipment 

ppm parts per million 

TGAI technical grade of the active ingredient 

ULV ultra low volume 
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IX. BIBLIOGRAPHY 

A. Studies Submitted to Support the GS-omega/kappa-Hxtx-Hv1a Pesticide Product 

Registrations 

MRID Citation Reference 

48779000 Vestaron Corporation (2012) Submission of Product Chemistry and Toxicity Data in Support of 

the Application for Registration of VST-006325 TGAI. Transmittal of 19 Studies.

48779001 Kennedy, R. (2012) Product Chemistry for VST-006325 TGAI. Unpublished study prepared by 

Vestaron Co. 271p.

48779002

Wo, C. (2012) Physical and Chemical Characteristics: Color, Physical State, Odor, pH and 

Density/Bulk Density. Project Number: 33617/OCR, P801. Unpublished study prepared by 

Eurofins/Product Safety Laboratories. 12p.

48779003 Kennedy, R. (2012) Review of Development and Identity of VST-006325 TGAI. Project Number: 

US005763568A/OCR, 5763568. Unpublished study prepared by Vestaron Corporation. 425p.

48779004

Stoneburner, A.; Pilar, C. (2012) Evaluation of Vestaron Samples for the Detection of Foodborne 

Pathogens. Project Number: 02/06/2012/VESTARON/OCR. Unpublished study prepared by 

Micromyx, LLC. 14p.

48779005

Stoneburner, A.; Pilar, C. (2012) Evaluation of Vestaron Samples for the Detection of Vibrio 

cholera. Project Number: 03/09/2012/VESTARON2/OCR. Unpublished study prepared by 

Micromyx, LLC. 13p.

48779006 Telforrd, W.; Cavey, G. (2012) Simulated Gastric Fluid Treatment of GS-U-ACTX-Hv1a-SEQ2 

Peptide. Unpublished study prepared by Core Lab. 34p.

48779007 Durando, J. (2011) Acute Oral Toxicity Up and Down Procedure in Rats. Project Number: 

32855/OCR P320/UDP. Unpublished study prepared by Product Safety Laboratories. 15p.

48779008 Durando, J. (2011) VST-006325: Acute Dermal Toxicity Study in Rats. Project Number: 

33040/OCR, P322/RAT. Unpublished study prepared by Product Safety Laboratories. 15p.

48779009 Lowe, C. (2012) VST-006325: Acute Inhalation Toxicity Study in Rats. Project Number: 33305, 

P330/OCR. Unpublished study prepared by Product Safety Laboratories. 22p.

48779010 Durando, J. (2012) VST-006325: Primary Eye Irritation Study in Rabbits. Project Number: 33041, 

P324/OCR. Unpublished study prepared by Product Safety Laboratories. 15p.

48779011 Durando, J. (2011) VST-006325: Primary Skin Irritation Study in Rabbits. Project Number: 33042, 

P326/OCR. Unpublished study prepared by Product Safety Laboratories. 15p.

48779012

Durando, J. (2012) VST-006325: Dermal Sensitization Study in Guinea Pigs (Buehler Method). 

Project Number: 33045, P328/OCR. Unpublished study prepared by Product Safety Laboratories. 

25p.

48779013 Younger, C. (2012) VST-006325: Acute Oral Toxicity Study in Bobwhite Quail: Final Report. 

Project Number: 15676/11/OCR. Unpublished study prepared by Stillmeadow, Inc. 16p.

48779014

Mikulas, J. (2012) VST-006325: Rainbow Trout (Oncorhynchus mykiss) 96-hour Acute Toxicity 

Test: Final Report. Project Number: 15677/11/OCR. Unpublished study prepared by Stillmeadow, 

Inc. 16p.

48779015 Mikulas, J. (2012) VST-006325: Daphnia magna 48-hour Acute Toxicity Test: Final Report. 

Project Number: 15678/11/OCR. Unpublished study prepared by Stillmeadow, Inc. 19p.

48779016 Younger, C. (2012) VST-006325: Terrestrial Plant Toxicity, Seedling Emergence. Project 

Number: 15959/12/OCR. Unpublished study prepared by Stillmeadow, Inc. 44p.
GS-U-ACTX-Hv1a-SEQ2

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Biopesticides Registration Action Document - DRAFT 

48779017 Younger, C. (2012) VST-006325: Terrestrial Plant Toxicity, Vegetative Vigor: Final Report. 

Project Number: 15680/11/OCR. Unpublished study prepared by Stillmeadow, Inc. 46p.

48779018

Younger, C. (2012) VST-006325: Honey Bee, Apis mellifera, Acute Contact Toxicity Limit Test: 

Final Report. Project Number: 15681/11/OCR. Unpublished study prepared by Stillmeadow, Inc. 

12p.

48779019 Mileson, B. (2012) Response to Tier 1 Data Requirements for VST-006325 TGAI. Unpublished 

study prepared by Technology Sciences Group Inc. 463p.

49123400 Vestaron Corporation (2013) Submission of Product Chemistry Data in Support of the Application 

for Registration of VST-006325 TGAI. Transmittal of 1 Study.

49123401 Roberts, A. (2013) Supplemental Product Chemistry for VST-006325 TGAI. Unpublished study 

prepared by Technology Science Group, Inc. 55p.

49174500 Vestaron Corporation (2013) Submission of Product Chemistry Data in Support of the 

Applications for Registration of VST-006325 TGAI and VST-006330 EP. Transmittal of 1 Study.

49174501 Kennedy, R. (2013) Supplemental Product Chemistry for VST-006325 TGAI and VST-006330 

EP. Unpublished study prepared by Vestaron Corporation. 85p.

49174600 Vestaron Corporation (2013) Submission of Toxicity Data in Support of the Application for 

Registration of VST-006325 TGAI. Transmittal of 1 Study.

49123400 Vestaron Corporation (2013) Submission of Product Chemistry Data in Support of the Application 

for Registration of VST-006325 TGAI. Transmittal of 1 Study.

49174601

Sindermann, A.; Porch, J. (2013) GS-U-ACTX-HV1a-SEC2: An Acute Oral Toxicity Study with 

the Honey Bee: Final Report. Project Number: 745P/101/OCR. Unpublished study prepared by 

Wildlife International, Ltd. 33p.

49199300 Vestaron Corporation (2013) Submission of Product Chemistry Data in Support of the Application for 

Registration of VST-006325 TGAI. Transmittal of 2 Studies.

49199301 Kennedy, R. (2013) Supplemental Product Chemistry for VST-006325 TGAI and VST-006330 

EP. Unpublished study prepared by Vestaron Corporation. 28p.

49199302 Foune, C. (2013) Validation of Bioactivity of VST-006325 TGAI Lot 1234603. Unpublished study 

prepared by Vestaron Corporation. 12p.

 B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2013a “VERSITUDETM Peptide: Summary of Hazard and Science Policy Council 

(HASPOC) Electronic Review: Recommendations on the Need for Additional Toxicity Studies” 

Memorandum from Kristin Rury, MPH to Elissa Reaves, Ph.D. dated September 18, 2013. 

U.S. EPA. 2013b. “Ecological Risk Assessment for the Proposed New Chemical Registration of 

GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, and 

Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial Flowers 

and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf.” Memorandum from 

M. Radtke, Ph.D., F. Khan, Ph.D , E. Odenkirchen, Ph.D., and S. Sankula, Ph.D. dated May 30, 

2013.
GS-U-ACTX-Hv1a-SEQ2

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Biopesticides Registration Action Document - DRAFT 

U.S. EPA. 2013c. “Ecological Risk Assessment for the Proposed New Chemical Registration of 

GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, and 

Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial Flowers 

and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf - AMENDMENT.”

Memorandum from M. Radtke, Ph.D., and S. Sankula, Ph.D. to M. Suarez and S Cerrelli .dated 

September 24, 2013.

U.S. EPA. 2013d. Reaves, E. and Shah, P., “GS-omega/kappa-Hxtx-Hv1a: Qualitative Human 

Health Assessment.” Memorandum from E . Reaves, Ph.D. and P. Shah, Ph.D dated December 6, 

2013. 

U.S. EPA. 2013 e. “Ecological Risk Assessment for the Proposed New Chemical Registration of 

GS-U-ACTX-Hv1a-SEQ2 (VersutideTM peptide) on Vegetables and Cole Crops; Herbs, Spices, and 

Mints; Pasture and Hay Crops; Fruit, Nut, and Vine Crops; Field Crops; Commercial Flowers 

and Ornamental Plants; Forest, Shade Tree, and Nursery Stock; and Turf – AMENDMENT 2”

Memorandum from M. Radtke, Ph.D., M. Wait and S. Sankula, Ph.D. to S Cerrelli, S. Borges, and 

K. Nesci dated December 5, 2013. 

U.S. EPA. 2013 f. “BEAD Review of Efficacy Data for Versutide peptide (DP # 416207, MRID 

49225101)” Memorandum from D. Brassard to D. Rate, D. Walsh, D. McCall, S. Cerrelli, and K. 

Nesci. dated December 18, 2013. 

U.S. EPA. 2013g. “Product characterization of VersitudeTM peptide consisting of 30% GSomega/kappa-Hxtx-Hv1a.” Memorandum from J. Gagliardi, Ph.D. to S. Cerrelli dated September 

11, 2013.
GS-U-ACTX-Hv1a-SEQ2

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Biopesticides Registration Action Document - DRAFT 

APPENDIX A. BIOCHEMICAL/MICROBIAL PESTICIDES DATA REQUIREMENTS 

(40 CFR PART 158 – SUBPART V) 

TABLE 1. Product Analysis Data Requirements for the Technical Grade of the Active Ingredient 

 (TGAI; GS-omega/kappa-Hxtx-Hv1a) and Manufacturing Product (MP; VST-006325 TGAI) 

(40 CFR § 158.2120) 

OCSPP 

Guideline 

Number 

Data Requirement Results MRID No. 

885.1100 Product Identity Submitted data fulfill the 

requirement for product identity. 

487790-01, 487790-03, 

491745-01, 491993-01 

885.1200 Manufacturing Process Submitted data fulfill the 

requirement for manufacturing 

process. 

487790-01, 487790-04, 

487790-05 

Not 

applicable 

Deposition of a Sample in a 

Nationally Recognized Culture 

Collection 

Not applicable 

885.1300 Discussion of Formation of 

Unintentional Ingredients 

Submitted data fulfill the 

requirement for discussion of 

formation of unintentional 

ingredients 

487790-01 

885.1400 Analysis of Samples Submitted data fulfill the 

requirement for analysis of 

samples 

491745-01, 491993-01 

885.1500 Certification of Limits Acceptable CSFs dated 8/23/2013 

Additional Studies

830.1800 Enforcement Analytical Method Submitted data fulfill the 

requirement for an enforcement 

analytical method. 

491993-01 
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TABLE 2. Physical and Chemical Characteristics for the Technical Grade of the Active 

Ingredient (TGAI)/MP 

(40 CFR § 158.2120)

OCSPP Guideline 

Number Data Requirement Results MRID No. 

830.6302 Color Off-white to light tan 487790-02 

830.6303 Physical State Powder 487790-02 

830.6304 Odor Faint odor 487790-02 

830.6313 Stability to Normal 

and Elevated 

Temperatures, 

Metals, 

and Metal Ions 

The VST-006325 TGAI is stable 

after storage at 45°C for 49 days. 

The product is expected to be 

stable at normal temperatures. 

The product is not expected to 

come into contact with metal or 

metal ions during storage. 

487790-02 

830.6317 Storage Stability Preliminary data supports storage 

for 1 year, though production 

batch data is needed..

491993-01 

830.6319 Miscibility Not required per OCSPP 

830.1000(e)(2), the product is not 

an emulsifiable liquid. 

NA 

830.6320 Corrosion 

Characteristics 

Only required if MP packaged in 

metal, plastic or paper containers. 

NA 

830.7000 pH 4.89 (1% w/w) 487790-02 

830.7100 Viscosity Not applicable. NA 

830.7300 Density/Relative 

Density/Bulk 

Density 

(Specific Gravity) 

Pour density 0-.2 g/cc and tap 

density 0.4 g/cc @ 20°C 

487790-02 
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TABLE 3. Product Analysis Data Requirements for the End-Use Product (EP), VST 006330 (40 

CFR § 158.2120)

OCSPP Guideline 

Number 

Data Requirement Results MRID No. 

885.1100 Product Identity Submitted data fulfill the requirement 

for product identity. 

487791-01 

885.1200 Manufacturing 

Process 

Submitted data fulfill the requirement 

for manufacturing process. 

487791-01 

Not applicable Deposition of a 

Sample in a 

Nationally 

Recognized Culture 

Collection 

Not applicable 

885.1300 Discussion of 

Formation of 

Unintentional 

Ingredients 

Submitted data fulfill the requirement 

for discussion of formation of 

unintentional ingredients for the current 

use sites. . 

487791-01 

885.1400 Analysis of Samples Submitted data fulfill the 

requirement for analysis of samples 

487791-01 

885.1500 Certification of 

Limits 

Acceptable CSF dated 

8/23/2013 

Additional Studies

830.1800 Enforcement 

Analytical Method 

An analytical method is not required 

for enforcement purposes since the 

Agency is establishing an exemption 

from the requirement of a tolerance 

without any numerical limitation. 

491993-01
GS-U-ACTX-Hv1a-SEQ2

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*TGAI 

TABLE 4. Physical and Chemical Characteristics for the End-Use Product (EP), VST 006330 

(40 CFR § 158.2120)

OCSPP Guideline 

Number 

Data Requirement Results MRID No. 

830.6317 Storage Stability Storage Stability demonstrated for up 

to 1 year. 

491993-01, 

830.6319 Miscibility Not applicable per 40 CFR 

158.2030(e)(10) – EP is not an 

emulsifiable liquid and is not to be 

diluted with petroleum solvents. 

487791-01 

830.6320 Corrosion Characteristics Will be submitted upon completion. 487791-01 

830.7100 Viscosity Not applicable per 40 CFR 

158.2030(e)(12) – EP is a solid. 

487791-01 

 830.7300* Density/Relative 

Density/Bulk Density 

(Specific Gravity) 

Pour density 0.2 g/cc and tap density 

0.4 g/cc @ 20oC 

487790-02 
GS-U-ACTX-Hv1a-SEQ2

Page 25 of 29

Biopesticides Registration Action Document - DRAFT 

TABLE 5. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI)/ and for the 

 End-Use Product VST-006330 (40 CFR § 158.2140)

OCSPP 

Guideline 

Number

Data Requirement VST-006325 TGAI VST-006330 (EP) MRID No. 

885.3050 Acute Oral Toxicity/ 

Pathogenicity 

Not required. Only required for 

microbial pesticides. 

Not required. Only required 

for microbial pesticides. 

487790-19 

885.3150 Acute Pulmonary 

Toxicity/Pathogenicity 

Not required. Only required for 

microbial pesticides. 

Not required. Only required 

for microbial pesticides. 

487790-19 

885.3200 Acute Injection 

Toxicity/Pathogenicity 

Not required. Only required for 

microbial pesticides. 

Not required. Only required 

for microbial pesticides. 

487790-19 

885.3400 Hypersensitivity 

Incidents 

Reporting is required when incidents 

occur during testing or production of the 

pesticide, or are otherwise known or 

reported to the registrant. 

Reporting is required when 

incidents occur during testing 

or production of the pesticide, 

or are otherwise known or 

reported to the registrant. 

487790-19 

885.3500 Cell Culture Not required since the TGAI is not a 

virus 

Not required since the TGAI 

is not a virus 

870.1100 Acute Oral Toxicity Oral LD50 > 5,000 mg/kg bw 

Classification: Toxicity Category IV 

Waiver accepted, based upon 

the data submitted for the 

manufacturing product and 

the low toxicity of the inert 

ingredients. 

487790-07 

870.1200 Acute Dermal Toxicity The LD50 > 5,000 mg/kg bw. 

Classification: Toxicity Category IV 

Waiver accepted, based upon 

the data submitted for the 

manufacturing product and 

the low toxicity of the inert 

ingredients. 

487790-08 

870.1300 Acute Inhalation 

Toxicity 

The LC50 > 2.05mg/L 

Classification: Toxicity Category IV 

Waiver accepted, based upon 

the data submitted for the 

manufacturing product and 

the low toxicity of the inert 

ingredients. 

487790-09 

870.2400 Acute Eye Irritation Mildly Irritating 

Classification: Toxicity Category IV 

Eye irritation information for 

some of the inert ingredients 

in the formulation was 

insufficient to rely solely on 

the results of the TGAI. 

Provided the label includes 

Toxicity Category III 

precautionary language for 

eye irritation, a separate study 

is not required for the end 

product formulation. 

487790-10 

870.2500 Primary Dermal 

Irritation 

Moderately Irritating 

Classification: Toxicity Category III 

Skin irritation information for 

some of the inert ingredients 

in the formulation was 

insufficient to rely solely on 

the results of the TGAI. 

Provided the label includes 

Toxicity Category III 

precautionary language for 

dermal irritation, a separate 

study is not required for the 

end product formulation. 

487790-11 

870.2600 Dermal Sensitization Not a dermal sensitizer. Waiver accepted, based upon 

the data submitted for the 

manufacturing product and 

the low potential of the inert 

487790-12 
GS-U-ACTX-Hv1a-SEQ2

Page 26 of 29

Biopesticides Registration Action Document - DRAFT 

TABLE 5. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI)/ and for the 

 End-Use Product VST-006330 (40 CFR § 158.2140)

OCSPP 

Guideline 

Number

Data Requirement VST-006325 TGAI VST-006330 (EP) MRID No. 

ingredients in the formulation 

to cause dermal sensitization. 

Hypersensitivity 487790-19 

870.3100 90-day Oral - rat 

Human Health Risk analysis of available data concluded that this 

additional mammalian toxicity data was not required. 

487790-19 

870.3250 90-day Dermal - rat 487790-19 

870.3465 90-day Inhalation - rat 487790-19 

870.3700 Prenatal 

developmental – rat 

487790-19 

870.5100 Bacaterial reverse 

mutation test 

487790-19 

870.5300 

870.5375 

In vitro mammalian 

cell assay 

487790-19 
GS-omega/kappa-Hxtx-Hv1a 

Page 27 of 29

Biopesticides Registration Action Document - DRAFT 

TABLE 6. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the 

Technical Grade of the Active Ingredient (TGAI), GS-omega/kappa-Hxtx-Hv1a (40 CFR § 158.2060) 

OCSPP Guideline Number Data Requirement Results MRID No. 

Tier I

850.2100 Avian Acute Oral Toxicity LD50 > 630 mg ai/kg-bw 

NOAEC = 630 mg ai/kg-bw 

No effects 

487790-13; 

850.2200 Avian Dietary Toxicity Waiver granted. 487790-19 

850.1075 Fish Acute Toxicity, 

Freshwater 

LC50 > 100 mg ai/A 

NOAEC = 100 mg ai/L 

No sub-lethal effects 

487790-14 

850.1010 Aquatic Invertebrate Acute 

Toxicity 

EC50 > 1000 mg ai/L 

NOAEC = 1000 mg ai/L 

No sub-lethal effects 

487790-15 

850.4100 Terrestrial Plant Toxicity, 

Seedling Emergence 

EC25 > 0.8 lb ai/A 

NOAEC = 0.8 lb ai/A 

No effects 

487790-16 

850.4150 Terrestrial Plant Toxicity, 

Vegetative Vigor 

EC25 > 0.8 lb ai/A 

NOAEC = 0.8 lb ai/A 

>25% root weight decrease in 

onion and lettuce that was not 

considered reliable 

487790-17 

880.4350 Nontarget Insect Testing Contact LD50 > 25 μg ai/bee 

NOAEC = 25 μg ai/bee 

No sub-lethal effects 

487790-18 

OECD 213 Honeybee acute oral toxicity 

test 

LD50 > 100 μg ai/bee 

NOAEC = 100 μg ai/bee 

No sub-lethal effects 

49174600 

Tiers II, III, and IV 

Not required for GS-omega/kappa-Hxtx-Hv1a based on the current uses and application methods. 
GS-U-ACTX-Hv1a-SEQ2

Page 28 of 29

Biopesticides Registration Action Document - DRAFT 

APPENDIX B. PESTICIDE PRODUCTS 

EPA File 

Symbol 

Registration 

Name 

Percentage 

Active 

Ingredient 

Formulation 

Type 

Use Site(s) Methods of 

Application 

Application 

Rate 

Target 

Pest 

88847-R 

VST-006325 

TGAI 

30% TGAI Manufacturing use N/A N/A N/A 

88847-E VST-006330 

EP 

20.0% End-use 

Product 

Artichokes 

Arugula 

Asparagus 

Beans- including 

garden, dried, 

succulent, 

adzuki, fava, field, 

garbanzo, pinto, kidney, 

lentil, lima, moonbeam, 

navy, runner, snap, 

teary, wax, yard long 

Beets-including garden 

Bok Choy 

Broccoli 

Broccoli Raab 

Brussels Sprouts 

Cabbage 

Cardoni 

Carrots 

Cassava 

Cauliflower 

Cavalo 

Celeriac 

Celery 

Chayote root 

Chervil 

Chick peas 

Chicory 

China greens 

Chinese artichoke 

Chinese broccoli 

Chinese cabbage (Napa) 

Chinese mustard 

cabbage 

Collards 

Corn salad 

Cotton 

Cress 

Cucumber 

Cucurbits 

Dandelion dock 

Dry bulb onions 

Edible burdock 

Edible chrysanthemum 

Edible gourds 

Eggplant 

Escarole 

Endive 

Garlic 

Ginger 

Ginseng 

Green onions 

Greens: Beets, China, 

Dandelion, Mustard, 

Turnip, Rape 

Ground cherry 

Foliar spray 

via ground 

or aerial 

equipment. 

As directed 

on label 

Cabbage 

looper 

nymphs 
GS-U-ACTX-Hv1a-SEQ2

Page 29 of 29

Biopesticides Registration Action Document - DRAFT 

EPA File 

Symbol 

Registration 

Name 

Percentage 

Active 

Ingredient 

Formulation 

Type 

Use Site(s) Methods of 

Application 

Application 

Rate 

Target 

Pest 

Horseradish 

Jerusalem artichoke 

Kale 

Kohlrabi 

Leeks 

Lentils 

Lettuce: Head, Leaf, 

Romaine 

Lupine 

Malanga 

Melons: Cantaloupe, 

Crenshaw, Honeydew, 

Muskmelon, 

Watermelon, etc. 

Mizuna 

Mustard spinach 

Napa 

Okra 

Olives 

Onions 

Parsley 

Parsnips 

Peas-including garden, 

dried, succulent, 

blackeyed, chickpea, 

cowpea, crowder, 

edible-pod, English, 

field, green, pigeon, 

snow, sugar snap, 

Pepino 

Peppers 

Potatoes 

Pumpkins 

Purslane 

Radicchio 

Radishes 

Rhubarb 

Rutabaga 

Salsify 

Shallots 

Skirret 

Soybean foliage 

Soybean 

Spinach 

Squash 

Sugar beets 

Sweet potatoes 

Swiss chard 

Tobacco 

Tomatillo 

Tomatoes 

Turmeric 

Turnips 

Turnip-rooted chervil 

Turnip-rooted parsley 

Watercress 

Yams 

Flowers; Green house 

and field