GS

- omega/kappa

- Hxtx

- Hv1a Page 1 of 29

Biopesticides Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT



### GS

- omega/kappa

- Hx t x - Hv1a Pesticide Chemical (PC) Code: 006100

U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division

Dated 0 2 / 03 /14GS

- U

- ACTX

- Hv1a

- SEQ2 Page 2 of 29

Biopesticides Registration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY

................................ ................................ .............................. 4

II. ACTIVE INGREDIE NT OVERVIEW

................................ ................................ ................ 4

III. REGULATORY BACKGROUN D

................................ ................................ ................. 5

A. Applications for Pesticide Registration

................................ ................................ ................................ ................ 5

B. Food Tolerance Exemption

................................ ................................ ................................ ................................ ... 5

IV. RISK ASSESSMENT

................................ ................................ ................................ ...... 5

A. Produ ct Analysis Assessment (40 CFR § 158.2120)

................................ ................................ ....................... 6

B. Human Health Assessment (40 CFR § 158.2140)

................................ ................................ ................................ 6

C. Environmental Assessment (40 CFR § 158.2060)

................................ ................................ .............................. 11

V. ENVIRONMENTAL JU STICE

................................ ................................ .......................... 14

VI. RISK MANAGEMENT DECISION

................................ ................................ ................. 14

VII. ACTIONS REQUIR ED BY THE REGISTRANT

................................ ......................... 15

VIII. GLOSSARY OF A CRONYMS AND ABBREVIA TIONS

................................ ........... 17

IX. BIBLIOGRAPHY

................................ ................................ ................................ ................ 18

APPENDIX A. BIOCHEM ICAL/MICROBIAL PESTI CIDES DATA REQUIREME NTS

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

APPENDIX B. PESTICI DE PRODUCTS

................................ ................................ ............... 28GS

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Biopesticides Registration Action Document

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 El i s s a 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. BiologistGS

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- ACTX

- Hv1a

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Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY

The active ingredient GS

- omega/kappa

- Hx t x

- Hv1a (VersitudeTM peptide , formerly GS

- U

ACTX

- 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

- Hx t x

- 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.

The risk assessments and related regulatory documents for GS

- omega/kappa

- Hx t x

- Hv1a are available to view through either http://www.regulations.gov/ or http://www.epa.gov/pesticides/regulating/registration

- status.html

, under docket identification number EPA

- HQ

- OPP

- 2012

- 039 1

. 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 provide s 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 b e significant public interest.

A 15

- day comment period was provided, c onsistent with the policy of making registration actions more transparent , for the proposed pe sticide products containing the new active ingredient, GS

- omega kappa

- Hxtx

- Hv1a

. The allowance of the first food and first outdoor uses of GS

- omega kappa

- Hxtx

- Hv1a was also subject to comment during this 15

- day period

. During this comment period , n o comments were received.

Therefore EPA maintains t hat based upon the risk assessment and informat ion submitted in

s upport of the VST

- 006325 TGAI, and VST

- 006330 EP , it is appropriate to issue these registration s

. The basis for this 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 rate s , methods of application, formulation type s , and target pest) regarding the proposed pesticid e products containing this active ingredient.GS

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Biopesticides Registration Action Document

III. REGULATORY BACKGROUND

A. Applications for Pesticide Registration

On April 26 , 201 2

, 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) in accordance with section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). EPA an nounced 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 Register on August 14, 2012 ( 77 Federal Register (FR) 48519 ), and opened a 30

- day pu blic 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 o f December 18, 2013 (78 FR 76 613 ).

B. Food Tolerance Exemption

Concurrent with its registration application s 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 fo r residues of the pesticide active ingredient, GS

- U

- ACTX

Hv1a

- SEQ2 (now GS

- omega/kappa

- Hxtx

- Hv1a ) (Pesticide Petition (PP) 2F8014 ) in or on all food comm o dities

. 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 o f 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 nom enclature 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 i ndicat e 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 t he study is not required by 40 C FR P art 158. Both “ acceptable” and “supplemental ” studies may beGS

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Biopesticides Registration Action Document
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 he alth, toxicity or other adverse effects are based on the hazard(s) identified from mammalian toxicity and irritation studies conducted with and/or other infor mation pertaining to the active ingredient and proposed pesticide products submitted to EPA in sup port of registration. The active ingredient and formulated manufacturing and end

- use product s 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 t he acute toxicity by the oral, dermal, and inhalation routes of exposure, and their potential for dermal and eye irritatio n

. 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

or irritation

.

A. Product Analysis Assessment ( 40 CFR § 158.2120 )

The product characterization of GS

- omega/kappa

- Hxtx

- Hv1 a is provided in an EPA review ( U.S. EPA. 2013 g ). 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

- Hv1 a functions primarily as a central nervous system inhibitor for suppressi ng cabbage looper caterpillars that feed on the foliage o f labeled crops. GS

- omega/kappa

- Hxtx

- Hv1 c an be used in either the field or greenhouse for suppression of cabbage looper

.

A summary of the data requirements is located in Table s 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 compr ehensive 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 ]

Up o n c onsid era tion of r e sults of oth e r d ef initive to x i c olo g i c a l d a ta submitt e d b y the p e tition er , the E P A w a iv ed ac ute o r a l to x i c i t y /p a th o g e ni c i t y t e sti n g f

or GS

- omega/kappa

- Hxtx

- Hv1a . An

ac ute o r a l to x i c i t y s t u d y c ondu c t e d on f e m a le r a ts ( M R I

D No. 487790

- 07) d e monst ra t e d th a t GS

omega/kappa

- Hxtx

- Hv1a w as not toxic ( L D 5 0 g r ea t e r th a n 5,000 m g /k g ; To x i c i t y C a t e g o r y I V )

. 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 beenGS

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- Hv1a

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Biopesticides Registration Action Document
negative. These data indicate that this peptide would not be toxic th r o u g h the o ra l r oute of

e x posu r e a nd th a t f

u r th e r t e sti n g is not n ece ss a r y ( 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 ) : Up o n c onsid era tion of r e sults of oth e r d ef initive to x i c olo g i c a l d a ta submitt e d b y the p e tition er , the E P A w a iv ed a c ute inj ec tion to x i c it y /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 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 p rocedure) 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 LD 50 of the test substance i s 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 LD 50 of the test substance is greater than 5,0 00 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 LC 50 of the test substance is greater than 2.0 5 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 VST

006325 to cause eye irritation. Under the conditions of thi s study, the test substance is minimally irritating to the eye. This study i s classified as Acceptable /Toxicity Category IV

.
Primary D ermal 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 VST

006325 to produce irritation after a single topical application. Under the conditions of this study, the test substance is classified as modera tely irritating to the skin. This study is Acceptable /Toxicity Category III

.GS

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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 and other ingredients) may have an effect in humans or wildlife similar to an eff ect 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 ass ays 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 sys tems will proceed to the next stage of the EDSP wh ere 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 a nd 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 k nown 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 pesti cide 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 (F FDCA ) 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 resi due 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 inclu de 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,GS

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Biopesticides Registration Action Document
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 exposur e 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 mechanis m of toxicity.”

EPA performs a number of analyses to determine the risks from aggregate exposure t o pesticide residues. First, EPA determines the tox icity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and throu gh other exposures that occur as a result of pesticide use in residential settings.

Consistent with s ection 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 thi s 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 ac ute toxicity data and information discussed previously and presented in Table 5 in Appendix A , t he 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 buildin gs (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 i solated from yeast, and e x posu r e to re sidu e s of this peptide

, in

c ons u m e d f

ood is possible. GS

- omega/kappa

- Hxtx

- Hv1a may be a ppli e d foliarly to edible pl a nts, turf and ornamentals. S in c e GS

- omega/kappa

- Hxtx

- Hv1a is applied as a foliar insecticide to crops , it is possible th a t edible f ood c ommoditi e s may retain residues of GS

- omega/kappa

Hxtx

- Hv1a

. F u r th er , t rea t e d crops c ould be div er t e d f o r f ood or fee d pu rpo s e s; th eref o re , e x posu r e to GS

- omega/kappa

- Hxtx

- Hv1a in this situ a tion is a lso pl a usibl e . Although re sidu e s fr om the u s e of p e sti c id e s c ont a ini n g GS

- omega/kappa

- Hxtx

- Hv1a m a y be p r e s e nt on c e r t a in f ood c ommoditi e s, p r o c e ssing p r o c e du re s (e

. g ., p e e ling a nd w a shi n g ) m a y r e du c e su c h re sidu e s. R e g a r dl e ss of the s ce n a r io, should GS

- omega/kappa

- Hxtx

- Hv1a be p re s e nt on f ood, 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 : L ike c onsum e d f

ood, e x posu r e to re sidu e s of GS

- omega/kappa

- Hxtx

- Hv1a

, a 41 amino acid peptide , in c onsum e d d r inking w a t e r is a nti c ip a t e d to be possible but n eg l ig ibl e

. However, GS

-GS

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- ACTX

- Hv1a

- SEQ2 Page 10 of 29

Biopesticides Registration Action Document
omega/kappa

- Hxtx

- Hv1a inter acts specifically with the insect nervous system and does not interact with vertebrate systems. The submitted and reviewed acute oral data suggest GS

omega/kappa

- Hxtx

- Hv1a is not toxic via the oral route (> 5,000 mg/kg). Sub mitted 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

. A ppropriate personal protective 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 C ommon 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 GS

omega/kappa

- Hxtx

- Hv1a has a common mechanism of toxicity with other substances. For i nformation regarding EPA ’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative ef fects o f such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechani sm 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 sectio n 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 pesticid e 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 sectio n 408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of sa fety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the complet eness 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 aggregateGS

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- Hv1a

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Biopesticides Registration Action Document
exposure to the residues of GS

- omega/kappa

- Hxtx

- Hv1a

. This includes all anticipated dietary exposures and all o ther 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 conce rn, 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 risk s 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 prolonged or repeated exposure s. P otential handler expos ure 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 unreasonab le adverse effects to the U.S. population in general, and to infants and children in particu lar, will result when GS

- omega/kappa

- Hxtx

- Hv1a pesticide products are used in accordance with EPA

- approved labeling.

C. Environmental Assessment ( 40 CFR § 158.2 060 )

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 (phot odegradation 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 ad sorption/desorption), 835.6100 (terrestrial field dissipation)

, 835.1410 (volatility laboratory

– conditional, depending on chemical’s properties)

. H owever, 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 T ier I non

target organism studies

. Ecological r isk 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 non

definitive since testing concentrations were either not high enough or not l ow 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.GS

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Biopesticides Registration Action Document
Risks to Aquatic Organisms

Fish and Invertebrates

The LC 50 for freshwater fish is > 100 mg ai/L. Compared to the peak EEC of 0.044 mg ai/L, the LC 50 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 freshwat er fish and the extremely large difference between the LC 50 value and the peak EEC, it is unlikely that estuarine/marine fish would be markedly different in their sensitivity to GS

omega/kappa

- Hxtx

- Hv1a . Consequently, estuarine/marine fish are not expecte d to be at risk on an acute exposure basis.

The EC 50 for freshwater invertebrates is >1000 mg ai/L. Compared to the peak EEC of 0.044 mg ai/L, the EC 50 is at least five orders of magnitude larger. Therefore, acute risk concerns to freshwater invertebrat es 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 reaso nably 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 uncertain ties 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 th e half

- life of GS

- omega/kappa

- Hxtx

- Hv1a is only 4 days. If a similar or s horter 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

- Hxtx

Hv1a to insects, the low probability that aquatic plants have this same receptor, and the peptid e’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 LD 50 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 correspondingGS

- U

- ACTX

- Hv1a

- SEQ2 Page 13 of 29

Biopesticides Registration Action Document

L D 50 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/ka ppa

- 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 altog ether; 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 peptide molecules are made to increase the absorption. Drugs derived from the cone shell ( Conus fulmen ) are based on a pep tide 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 LD 50 is > 25 μg ai/bee for adult h oneybees. The contact EEC (converted to a dose) is 18.7 μg ai/bee, which is lower than the LD 50 . 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 ter restrial invertebrates from the proposed new pesticide. Based on the high LD 50 (> 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 expec ted, 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 re ly 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 inver tebrates).

Risk to Non

- Target Organisms Non

- target Terrestrial and Semi

- Aquatic Plants Toxicity data for terrestrial plants were available; however the solubility information for GS

omega/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.GS

- U

- ACTX

- Hv1a

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Biopesticides Registration Action Document
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 fo r food (amphibians, birds, fish, mammals, reptiles, terrestrial invertebrates) may also be at indirect risk.

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, a nd 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 th at 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, during the 15

- day public participation comment period, the EPA sought 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. The E PA received no public comments on this particular matter. For additional information regarding environmental justice issues, please visit EPA’s web site at http://www.epa.gov/com

pliance/environmentaljustice/index.html

.

V I

. 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 u sed 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 determination s above, the compositions of the pesticides ( VST

- 006325 TGAI a nd 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.GS

- U

- ACTX

- Hv1a

- SEQ2 Page 15 of 29

Biopesticides Registration Action Document
In reference to the third determination above, the Agency believes that the use of GS

omega/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 po tential risks to bee larvae. The registrant has adopt ed the following pollinator protection language for the environmental hazards section and the directions for use for the labels

.

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: D o 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. M inimization 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 unreason able 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 mat erial 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

reco gnized practice these pesticides will not generally cause unreasonable adverse effects on the environment. Therefore, the Agency believes VST

- 006325 TGAI and VST

- 006339 EP containing GS

- omega/kappa

- Hxtx

- Hv1a as a new active ingredient are eligible for r egistration under FIFRA section 3(c)(5) for the labeled uses as the label statements described in this section

were incorporated

.

V I I

. 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

.GS

- U

- ACTX

- Hv1a

- SEQ2 Page 16 of 29

Biopesticides Registration Action Document

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 summa ry 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 su spected and confirmed incidents) must be reported to EPA under the provisions of 40 CFR § 158.2140(d).GS

- U

- ACTX

- Hv1a

- SEQ2 Page 17 of 29

Biopesticides Registration Action Document

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

c fu colony

- forming unit (s) cfu/kg colony

- forming units per kilogram cfu/mL colony

- forming unit s 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 Feder al Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register g/ mL gram per milliliter LC 50 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). LD 50 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 milligram s per kilogram mg/L milligram s 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 volumeGS

- U

- ACTX

- Hv1a

- SEQ2 Page 18 of 29

Biopesticides Registration Action Document

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 De velopment 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

Pathog ens. 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: A cute 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. Unpubli shed 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 pr epared 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. Projec t

Number: 15959/12/OCR. Unpublished study prepared by Stillmeadow, Inc. 44p.GS

- U

- ACTX

- Hv1a

- SEQ2 Page 19 of 29

Biopesticides Registration Action Document

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) Sup plemental 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 Applic ation 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. 2013 b

. “ Ecological Risk Assessment fo r 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, S hade 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 Page 20 of 29

Biopesticides Registration Action Document

U.S. EPA. 2013 c

. “ 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

- AME NDMENT.” Memorandum from M. Radtke, Ph.D., and S. Sankula, Ph.D. to M. Suarez and S Cerrelli .dated September 24, 20 13.

U.S. EPA. 2013 d

. 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

– A MENDMENT 2” Memorandum from M. Radtke, Ph.D., M. Wait and S. Sankula, Ph.D. to S Cerrelli, S . B orges, 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. E PA. 2013g

. “Product characterization of VersitudeTM peptide consisting of 30% GS

omega/kappa

- Hxtx

- Hv1a

. ” Memorandum from J. Gagliardi, Ph.D. to S. Cerrelli dated September 11, 2013

.GS

- U

- ACTX

- Hv1a

- SEQ2 Page 21 of 29

Biopesticides Registration Action Document

A PPENDIX 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 § 158.2 120 ) OCSPP G uideline N umber 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

- 01GS

- U

- ACTX

- Hv1a

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Biopesticides Registration Action Document

TABLE 2 . Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient (TGAI )/MP (40 CFR § 158. 2120 )

OCSPP G uideline N umber 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

- 02GS

- U

- ACTX

- Hv1a

- SEQ2 Page 23 of 29

Biopesticides Registration Action Document

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

- 01GS

- U

- ACTX

- Hv1a

- SEQ2 Page 24 of 29

Biopesticides Registration Action Document

* 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

- 02GS

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- ACTX

- Hv1a

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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. 2 140 )

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 R eporting 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 pest icide, 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 LD 50 > 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 LD 50 > 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 LC 50 > 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 I II 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

m anufacturing product and the low potential of the inert 487790

- 12GS

- U

- ACTX

- Hv1a

- SEQ2 Page 26 of 29

Biopesticides Registration Action Document

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. 2 140 )

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

- 19GS

- omega/kappa

- Hxtx

- Hv1a Page 27 of 29

Biopesticides Registration Action Document

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. 2 06 0 ) OCSPP Guideline Number Data Requirement Results MRID No. Tier I 850.2100 Avian Acute Oral Toxicity LD 50 > 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 LC 50 > 100 mg ai/A

NOAEC = 100 mg ai/L No sub

- lethal effects 487790

- 14

850.1010 Aquatic Invertebrate Acute Toxicity EC 50 > 1000 mg ai/L

NOAEC = 1000 mg ai/L No sub

- lethal effects 487790

- 15

850.4100 Terrestrial Plant Toxicity, Seedling Emergence EC 25 > 0.8 lb ai/A NOAEC = 0.8 lb ai/A No effects 487790

- 16

850.4150 Terrestrial Plant Toxicity, Vegetative Vigor EC 25 > 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 LD 50 > 25 μg ai/bee NOAEC = 25 μg ai/bee No sub

- lethal effects 487790

- 18

OECD 213 Honey b ee acute oral toxicity
test LD 50 > 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

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 g round or aerial equipment

. As directed

on label Cabbage

looper nymphsGS

- U

- ACTX

- Hv1a

- SEQ2 Page 29 of 29

Biopesticides Registration Action Document

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