BIOPESTICIDES REGISTRATION ACTION DOCUMENT 

Helicoverpa armigera Nucleopolyhedrovirus strain BY -0003 

Pesticide Chemical (PC) Code: I 07310 

U.S. Environmental Protection Agency 

Office of Pesticide Programs 

Biopesticides and Pollution Prevention Division 

November 3. 20 15 
Heilcol'l!lpa armigera nucleopolyhcdro,·irus strain f3V-0003 

11iopcsticides Registration Action Document 

TABLE OF CONTENTS 

Page 2 ofJO 

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

II. ACTIVE ING REDI ENT OVERVIEW ....................................................................................................... 6 

Ill. REGU LATORY BACKG ROUND .............................................................................................................. 7 

A. Applications for Pesticide Product Registration ............................................................................ 7 

B. Food Toler ance Exemption .............................................................................................................. 7 

IV. RISK ASSESSMENT ................................................................................................................................... 7 

A. Product Analysis Assessment (40 CFR § 158.2 120) ....................................................................... 8 

B. Human Health Assessment (.tO CFR § 158.2 1-t0) ........................................................................... 8 

C. Environmenta l Assessment (40 CFR § 158.2 150) ........................................................................ 13 

V. ENVIRONMENTAL JUSTICE ................................................................................................................. IS 

VI. RISK MANAG EMENT DECISION ......................................................................................................... 16 

VII. ACTIONS REQUIRED O F TH E REGISTRANT ................................................................................... t7 

VIII. GLOSSARY O F ACRONYMS AN D AllBREVI ATIONS ...................................................................... t8 

IX. BIBLIOGRAPHY ....................................................................................................................................... 19 

A. Studies Submitted to Support t he Active Ingredient, Helicoverpa armigem 

nucleopolyhedrov irus stra in UV-0003 and Pesticide Product, Helicovcx, Registration ...................................... 19 

ll. Environmental Protection Agency Risk Assessment Memor anda ............................................. 20 

C. Other Refer enccs ............................................................................................................................ 20 

APPENDIX A. MICROBIAL PESTIC IDES DATA REQU IREMENTS ........................................................... 23 

APPENDIX B. PESTICIDE PRO DUCT ................................................................................................................ 30 
Helicm•erpa armiRera nuclcopolyhcdrovirus strain BV-0003 

Biopestieides Registration 1\ction Document 

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM 

Office of Pesticide Programs (OPP) 

Biopcsticides and Pollution Prevention Division 

Microbial Pesticides Branch 

Ibrahim S. Barsoum, Ph.D. 

John L. Kough, Ph.D. 

Gail Tomimatsu, Ph.D. 

Milutin Djurickovic, Biologist 

Science Reviews 

Product Analysis, Human Health 

Product Analysis, Human Health 

Environmental Effects 

Environmental Effects 

Regulations 

Page 3 of30 

Kimberly Nesci 

ShaRon Carlisle 

Shannon Borges 

Michae l Glikes 

Chief. Microbial Pesticides Branch 

Deputy Chief, Microbial Pesticides Branch 

Team Leader, Microbial Pesticides Branch 

Regulatory Action Leade r 
I felico,·erpa armigem nuclcopolyhcdro' irus s1rain BV -0003 

Biopes1icidcs Rcgislnllion Ac1ion Document 

I. EXECUTIVE SUMMARY 

Background 

Page-l of30 

In October 20 13. Sci Reg. Inc .. on behalf of Andermatt Biocontrol AG, a Swiss company, 

submitted an application for a new end-use product (EP), Helicovex (EPA File Symbol 69553-

E), containing a new active ingredient, to the United States Environmental Protection Agency 

(EPA) under section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). 

The new active ingredient in the EP, Helicoverpa armigera nucleopolyhedrovirus (NPY) strain 

BV-0003 , is a virus specific to Lepidopteran pests and a member of the virus family 

Baculoviridae, genus Alphabaculovirus. This non-genetically modified, naturally-occurring 

strain was isolated by the Institute of Zoology, Chinese Academy of Sciences, from several H. 

armigera larval cadavers infected with nuclear polyhedrosis disease in a cotton field in a suburb 

of Beijing, China. On April 7, 2006, the applicant deposited a sample with the German 

Collection for Microorganisms and Cell Cultures under the accession number BY-0003. This 

strain has a similar, if not identical, host range and virulence with Heliothis zea single NPY, 

which was first detected in infected H. zea larvae in South Africa in 1891. Since the two viruses, 

H. armigera NPY and H. zea NPY, were originally isolated from different hosts, they were 

previously classified as different species. By using DNA restriction analysis, researchers showed 

that the genomes of both viruses are very similar. This similarity was corroborated by genome 

sequencing, which demonstrated a 97% nucleotide identity and a 99% amino acid identity. 

Because they share common host range. virulence, physical properties, and genome sequence. H. 

zea NPY and H. armigera NPY are "variants of the same virus species." 

Helicovex is for agricultura l use in the United Sates in greenhouses and field applications to 

control the com earworm (llelicovelpa zea), tobacco budworm (Helicoverpa virescens), and 

African cotton bollwom1 (He/icoverpa armigera) on a wide variety of food and non-food crops. 

It is for application by ground or aerial spray or by chemigation. In addition, a sub-label is for 

use on a subset of these food crops, flowers, and omamentals in home gardens. 

EPA scientists reviewed product analysis, toxicology, and nontarget organism data and 

information (40 CFR §§ 158.2120, 158.2 140, and 158.2150, respectively) submitted to support 

the registration of the pesticide product. They found that, overall, such data and information are 

adequate for risk assessment purposes_ fulfill the current microbial pesticide data requirements. 

and support registration of the product under FIFRA section 3(c)(5). 

Product Analysis 

For the purposes of FIFRA section 3(c)(5) registration, the product analysis data requirements 

for HelicO\'eJpa armigera nucleopolyhedrovirus strain BY -0003 and the EP. I lelicovex, 

including product chemistry and composition, analysis of samples, physical and chemical 

characteristics were fulfill ed by acceptable guideline studies. 

Toxicology 

The applicant submitted adequate mammalian toxicology data and information to support the 

pesticide product. Acute oral, pulmonary, and injection toxicity/pathogenicity studies showed 

that, at a single high dose, Helicove1pa armigera NPY strain BY -0003 is not toxic and/or 
Helico1·erpa armigera nuclcopolyhcdrovirus strain BV-0003 

13iopesticidcs Registration Action Document 

Page 5 of30 

pathogenic via these routes of exposure. Moreover, the applicant reported that no 

hypersensitivity incidents occurred during research, development, or testing of Helicoverpa 

armigera NPY strain BY-0003. In light of the results ofthe acute toxicity/pathogenicity data and 

the absence of hypersensitivity incidents. testing at higher tiers (i.e .. Tiers II and Ill) was not 

required. 

Tolerance Exemption 

Because Helicovetpa zea (H. zea) nucleopolyhedrovirus (NPV) already is exempt from this 

requirement and since H. :ea NPY and H. armigera PY are variants of the same virus, the 

applicant did not petition the EPA for an exemption from the requirement of a tolerance for 

residues of the new strain, He/icoverpa armigera nucleopolyhedrovirus strain BY-0003. In 1980 

the EPA granted an exemption from the requirement of a tolerance for residues of the active 

ingredient H. zea NPY in or on all agricultural commodities (7 CFR 180.1 027) as long as the 

manufacturer meets certain specifications related to identity. contamination control. and safety. 

In its application to the EPA. the applicant provided data and other information to support 

coverage by the existing exemption from the tolerance requirement. Hence, the EPA concludes 

that there is reasonable certainty that no harm will result to the U.S. population. including infants 

and children, from aggregate exposure to residues of Helicoverpa armigera NPY strain BY0003. Data and information submitted by the applicant support the conclusion that no dietary 

risks are expected to occur as a result of the use of Helicoverpa armigera N PY strain BY -0003 

as an active ingredient in pesticide products. The EPA concludes that there will not be significant 

exposure to Helicoverpa armigera NPY strain BY -0003 through food and drinking water. Based 

on the review of acute oral toxicity and pathogenicity data by EPA scientists, the Agency 

determined that. even if 1-Jelicoverpa armigera NPY strain BY -0003 were present on food or in 

drinking water, human exposure to this insect virus would not result in unreasonable adverse 

effects. 

Occupational Exposure 

Despite the low toxicological profile of residues of the active ingredient, Helicoverpa armigera 

NPY strain BY-0003, the EPA is requiring baseline personal protective equipment (PPE) for 

handlers that, due to their occupation, may be subject to prolonged or repeated exposure to the 

active ingredient. The label on Helicovex. the end-use product, directs handlers working with 

Helicoverpa armigera NPY in agricultural settings to wear a long-sleeved shirt, long pants. 

socks, shoes, and a dust/mist filtering respirator meeting Nationa l Institute for Occupational 

Safety and IIealth (NIOSII) standards of at least N-95, R-95, or P-9. 

Nontanz.et Organisms 

The applicant submitted guideline studies and scientific rationale bridging studies previously 

submitted for a variant of flelicoverpa armigera NPY strain BY -0003 to support the Agency's 

waiving nontarget organism testing for the new active ingredient (A I). The EPA determined that 

this new AI is substantially similar to the previously registered AI and that previously submitted 

data would provide an adequate measure of hazard for the new AI. Hence. the Agency accepted 

the bridging rationale and determined that the information provided is sufficient to satisfy most 

of the Tier I nontarget organism data requirements and support a limited ecological risk 

assessment for this new active ingredient and its uses. The risk assessment is limited by 

uncertainties associated with baculovirus persistence and spread in the environment, which 
1/e/icol'etpa armigera nuclcopolyh~drovirus strain BV-0003 

Biop~ ticidcs Registration Action Docum..:nt 

Page 6 of30 

include complex ecological relationships, such as insect host-viral parasite, host plant-insect 

interactions, and variable environmental factors. Further testing of nontarget organisms at higher 

tier levels (i.e., Tiers II, III, and IV) is not required. 

Based on data and other information provided by the applicant, the EPA determined that adverse 

effects to nontarget organisms are not anticipated from the pesticidal uses ofHelicovex, which 

contains the active ingredient Helicoverpa armigera NPV strain BV -0003. Moreover, the EPA 

made a ··No EffecC determination for direct and indirect effects to federally listed threatened and 

endangered species and their designated cri tical habitats resulting from these same pesticidal 

uses. Direct effects to individuals of listed lepidopteran insect species cannot be precluded, nor 

can indirect effects to listed species that depend specifically on a listed lepidopteran insect. 

Additional analysis of the potential effects to these species is necessary to make a determination 

for these species. 

Public Participation 

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

for the public to participate in major registration decisions before they occur. According to this 

policy, the EPA intends to provide a public comment period prior to making a registration 

decision for, at minimum, the following types of applications: new active ingredients; first food 

uses: first outdoor uses; first residential uses; or any other registration actions for which the 

Agency believes there may be significant public interest. 

Consistent with the policy of making registration actions more transparent, the pesticide product 

containing Helicoverpa armigera PV strain BV -0003, was subject to a 15-day comment period. 

In addition to containing a new active ingredient, the registration of the pesticide product would 

result in the first outdoor and food uses for H. armigera NPV BV-0003. The docket 

identification number associated with these registration actions, and accessed through either 

http:/ l wwH'. regula! ions. gov or hit p:llwww. epa.gov/ pest icideslregulat i ng/regist rat ion-status. ht ml, 

is EPA-HQ-OPP-20 14-0151. The following documents were made available for comment in 

EPA-HQ-OPP-20 14-0151: (I) draft Helicol'elpa armigera PV strain BV -0003 Registration 

Action Document (BRAD); (2) draft label for the end-use pesticide product, He li covex (EPA 

File Symbol 69553-E); (3) risk assessment for product chemistry and human health; (4) 

environmental risk assessment; and (5) draft registration decision document. EPA believes that, 

based upon the data and information submitted in support of H. armigera NPV strain BY -0003 

and Helicovex, it is appropriate to issue the registrations. The basis for this decision can be found 

in the risk assessment for H. armigera N PV strain BV -0003 whi ch is characterized throughout 

this BRAD. No comments were received. 

Registration Dec ision 

The EPA believes that the use of He/icoverpa armigera NPV strain BV -0003 pesticide products 

will not cause any unreasonable adverse effects on the environment. Therefore, the EP, 

Helicovex, which contains!-/. armigera NPV strain BV-0003 as a new active ingredient, should 

be eligible for registration under FIFRA section 3(c)(5) for the labeled uses. 

II. ACTIVE INGREDIENT OVERVIEW 

Biological Name: Helicovelpa armigera Nucleopolyhedrovirus strain BV0003 
Helicoverpa armi~era nuclcopolyhcdrO\ irus strain £3V -0003 

Biopesticides Registration Action Document 

Page 7 of30 

Culture Deposit: 

OPP Chemical Code: 

Type of Pesticide: 

German Collection for Microorganisms and Cell Cultures: 

accession number BY -0003 

107310 

Microbial Pesticide - Insecticide 

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

use sites, application rates. methods of application, 

formulation types, and target pests) regarding 

the pesticide product containing this 

active ingredient. 

III. REGULATORY BACKGROUND 

A. Applications for Pesticide Product Registration 

In October 2013, Sci Reg, Inc. (address: 12733 Directors Loop, Woodbridge. Y A 22 192) 

submitted an application on behalf of Anderman Biocontrol AG (address: Stahlermatten 6, Cll6146 Grossdietwil, Switzerland) to register an end-use product. Helicovex (EPA File Symbol 

69553-E). under FTFRA section 3. On April 8. 2014 (79 FR 2 19 19). the EPA announced receipt 

of the application to register a pesticide product containing a new active ingredient for use in 

agriculture. The EPA opened a 30-day public comment period pursuant to the provisions of 

FIFRA section 3(c)(4). Following this publication, the Agency received one public comment 

expressing concern about the effects of the product on honey bees and its persistence in soi l or 

water. 

B. Food Tolerance Exemption 

Under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), the EPA in 1980 granted 

an exemption from the requirement of a tolerance for residues of the active ingredient 

Helicove1pa zea NPY in or on all agricultural commodities ( 40 CFR 180.1 027) as long as the 

manufacturer meets certain specifications related to identity. contamination control. and safety. 

In its application to the EPA in 20 13, Sci Reg. on behalf of the Swiss company Andermatt 

Biocontrol. provided data and other information to support coverage of Helicoverpa armigera 

NPY strain BY -0003 by the existing exemption from the requirement of a tolerance for residues 

of H. zea NPY in or on all agri cultural commodities because II. armigera NPY is a variant of H. 

zeaNPY. 

IV. RISK ASSESSMENT 

In the Federal Register of October 26, 2007 (72 FR 6 1 002). the EPA issued a Final Rule on the 

data requirements to support registration of microbial pesticides and updated the definition for 

microbial pesticides. The rul e became effecti ve on December 26. 2007. The data and information 

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

The EPA classifies each data submission with an indication of 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 indi cates the data 
Helicoverpa armigera nuclcopol)hcdrovirus strain BV-0003 

Biopcsticidcs Registration Action Document 

Page 8 of30 

provide some infom1ation 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 will often 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 

appropri ate. An ''unacceptable" rating indicates that new data must be submitted. 

For the acute toxicity data requirements, Toxicity Categories are assigned based on the 

hazard(s) identified from studies and/or other information submitted to the EPA in support of a 

pesticide registration. The EPA classifies the active ingredient or particular product into Toxicity 

Category I, II, Ill, or IV, where Toxicity Category I indicates the highest toxicity and Toxicity 

Category IV indicates the lowest toxicity (see 40 CFR § 156.62). 

A. Product Analysis Assessment (40 CFR § 158.2120) 

For purposes of registration under FIFRA section 3(c)(5). the EPA determined that all product 

analysis data requirements for Heficoverpa armigera NPY strain BV-0003 have been fulfilled. 

Refer to Tables 1, 2, 3, and 4 in Appendix A for a summary of the data requirements, including 

both generic and product-specific information. 

B. Human Health Assessment (40 CFR § 158.2140) 

1. Toxicity 

All toxicology data requirements for Helicovetpa armigera NPV strain BV-0003 have been 

fulfilled. Acceptable Tier I mammalian toxicology data and information support registration of 

the pesticide product, llclicovex. Furthermore, Tier II and Tier III studies were not required for 

Helicm·erpa armigera PV strain BY -0003 because of the Jack of acute toxicity/ pathogenicity 

in the Tier I studies. 

For a summary of the toxicology data for Helicoverpa armigera NPV strain BY-0003 described 

in sections IV(B)(l )(a) and IY(B)(l)(b) (see pages 8- 1 0), refer to Table 5 in Appendix A. 

a. Acute Toxicity/Pathogenicity- Tier I 

The applicant evaluated the identity or similarity between Helicoverpa armigera NPV strain BY0003 and Helicovetpa zea NPY by using DNA restriction analysis to show that the genomes of 

both viruses are very similar (Gettig and McCarthy, 1982). This was corroborated by genome 

sequencing. The sequence identity ofHzSNPV and HearNPY showed a 97% nucleotide identity 

and a 99% amino acid identity (Chen et al.. 2002). On the basis of common host range and 

virulence, the common physical properties, and the common sequence, Chen et al. (2002) 

concluded that Helicoverpa armigera NPV and Helicoverpa zea NPV are '·variants of the same 

virus species.'' Based on this conclusion, data previously submitted to support the registration of 

Helicoverpa zea NPV can be bridged to J-/elicovelpa armigera NPV strain BY -0003. 

Acute Injection Toxicitv!Pathogenicitv (Intravenous) (Harmonized Guideline 885.3200: MRJD 

No 4959150?): Researchers assessed the toxicity/infectivity of 5 batches of the test substance on 

mice by intraperitoneal (IP) injection. They randomly divided 30 female mice into six groups of 
llelicol'erpa armigera nuckopolyhedrovirus strain BV -0003 

Riopcsticidcs Registration Action Document 

Page 9 of30 

five mice. They administered 5 groups one batch of the test substance by I P injection at a dose of 

approximately 106 Viral Occlusion Bodies (OB) per animal, and they dosed a control group with 

an equivalent volume of sterile saline. Observations for mortality and signs of pharmacologic 

and/or toxicological effects were made twice on Day 0 and once daily through Day 7. Body 

weights were recorded on Day 0 and at study termination. All mice were sacrificed on Day 7 and 

gross necropsies were performed. The researchers observed no mortality or abnormalities during 

the study. The necropsy conducted at termination of the study revealed no observable 

abnormalities. The researchers concluded that the test substance is not toxic to mice when 

administered by intraperitoneal injection at a dose of 106 OB/mouse. 

The applicant submit1ed a scientific rationale to waive all of the other toxicity/pathogenicity data 

requirements (MRID No. 49409700): 

Acute Oral Toxicity/Pathogenicity (Harmonized Guideline 885.3050) 

Acute Pulmonary Toxicity/Pathogenicity (Harmonized Guideline 885.3150: 

Hypersensitivity Incidents (Harmonized Guideline 885.3-100: 

Cell Culture (Harmoni::ed Guideline 885. 3500) 

A cute Oral Toxicity (Harmonized Guide/ ine 870. I I 00: 

Acute Inhalation Toxicity (Harmonized Guideline 870-1300: 

Acute Dermal Toxicity (Harmonized Guideline 870.1200: 

Acute Eye Irritation Study (Harmonized Guideline 870.2400: 

Acute Dermal Irritation Study (Harmonized Guideline 870.2500. 

The EPA accepted the applicant's scientific rationale for the following reasons: 

I. Baculoviruses arc naturally occurring pathogens of arthropods. and the ir host range is 

exclusively restricted to arthropods. o member of this virus family is infecti ve to plants or 

vertebrates. 

2. Baculoviruses are present in the environment and have been used for biological insect control 

for over I 00 years. Evidence for the safety of baculoviruses emerges from the history of contact 

between baculoviruses and humans without any detrimental effect. During the 1970s, the EPA 

established "Guidance for Safety Testing of Baculoviruses," which also became a guideline of 

baculovirus safety tests. 

3. Helicove1pa zea NPV was the first commercial baculovirus insecticide and is one of the most 

extensively tested entomopathogenic viruses (lgnoffo. I 975). Safety tests of more than 51 

entomopathogenic viruses including more than 30 baculoviruses resulted in a long and complete 

safety record (extensively reviewed by Ignoffo, I 973; Surges et al.l980a, I 980b; Groner, 1986). 

4. No adverse effect on human health has been observed in any of these investigations indicating 

that the use ofbaculovirus is safe and does not cause any health hazards. 

5. In the Heliolhis zea Reregistration Eligibility Document. the EPA stated that "due to the 

overall results ofTier IIJ toxicology testing and the additional toxicology data which support the 

negative response of viral replication in mamma ls, the Agency concludes there are sufficient data 

to satisfy this requirement without requesting a cel l culture study." 

6. Although baculovirus uptake has been observed, there has been no evidence that viral DNA 
1/elicOI·erpa armigera nuclcopolyhcdrovirus strain BV -0003 

Biopcsticidcs Registration Action Document 

Page 10 o f 30 

replication, production of viral proteins or cytopathological effects have occurred. In vivo, the 

uptake of baculovirus occlusion bodies by various animals did not lead to the production of 

baculovirus-specific anti bodies. 

b. Acute Toxicology ami Subchronic Toxicity/Pathogenicity- Tier I/; 

ReproductiveFertility Effects, Carcinogenicity, Immunotoxicity, and 

Infectivity/Pathogenicity Analysis- Tier III 

Tier II and Tier Ill studies were not required for Helicoverpa armigera NPV strain BV-0003 

based on the lack of acute toxicity/pathogenicity in the Tier I data requirements. 

c. Endocrine Disruptors 

As required by the Administrator under the Federal Food, Drug, and Cosmetic Act (FFDCA), the 

EPA has developed the Endocrine Disrupter Screening Program (EDSP) and has begun to 

implement the screening program that is to be used to test all pesticides to determine whether 

certain substances (including pesticide active 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." FFDCA section 408(p)(4) authorizes the 

Administrator, by order, to exempt from the requirements of the Endocrine Disrupter Screening 

Program a biologic substance or other substance if a detem1ination is made that the substance is 

anticipated to not produce any effect in humans similar to an effect produced by a naturally 

occun·ing estrogenic substance. Between October 2009 and February 20 I 0, EPA issued test 

orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active 

ingredients and 9 inert ingredients. He/icoverpa armigera NPV strain BY -0003 is not among the 

group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. 

The EPA believes that Helicoverpa armigera NPV strain BY -0003 is a substance that would not 

produce any effect in humans similar to an effect produced by a naturally occurring estrogenic 

substance. As such, and pursuant to Section 408(p)(4), the EPA will determine in the future 

whether it can exempt Helicovetpa armigera NPV strain BV-0003 from the requirements of the 

Section 408(p)(4) EDSP. In the event the EPA does determine to exempt this substance from the 

EDSP, an order will be issued. For further information on the status of the EDSP, the policies 

and procedures. the list of 67 chemicals, the test guidelines and the Tier I screening battery, 

please visit our website: hllp:l!ll'uw.epa.gO\•Ienclo/. 

2. Federal Food, Drug, and Cosmetic Act (FFDCA) Considerations 

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

requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) onl y 

if the 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 anti cipated dietary exposures and all 

other exposures for which there is reliable information." This includes exposure through drinking 

water and in residential settings, but it docs 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, the EPA must take into account the factors set forth in section 

408(b)(2)(C) ofFFDCA, which require the EPA to give special consideration to exposure of 

infants and children to the pesticide chemical residue in establishing a tolerance exemption, and 
1/e/icoverpa armigera nuclcopo lyhcdrovirus strain BV-0003 

Biopcsticidcs Registration Action Document 

Page II of30 

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 the EPA consider "avai !able information concerning the cumulative effects 

of [a particular pesticide's] . .. residues and other substances that have a common mechanism of 

toxicity." 

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

pesticide residues. First, the Agency determines the toxicity of a pesticide. Second, the 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. 

Consistent with section 408(b)(2)(D) ofFFDCA. the EPA has reviewed the available scientific 

data and other relevant infonnation, and considered its validity, completeness, and reliability and 

the re lationship of this information to human risk. The Agency 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/pathogenicity data and information discussed previously and 

presented in Table 5 in Appendix A, the data required for a FFDCA risk assessment for 

He/icoverpa armigera NPV strain BV-0003 have been fulfil led. 

a. Aggregate Exposure 

In examining aggregate exposure, section 408 of FFDCA directs the 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). 

Food Exposure and Risk Characterization: The EPA found that dietary exposure to Helicoverpa 

armigera NPV strain BV-0003, a naturally occurring insect virus, is anticipated to be negligible. 

Due to the ubiquitous nature of the organism and the concentrations of H. armigera NPV strain 

BV-0003and other closely related viruses that already exist in the environment. the likelihood of 

increased risk to humans or animals from the use of Helicovex is low. The EPA concluded that 

the risk posed to adults. infants. and children is like ly to be minimal because of the low acute 

oral toxicity/pathogenicity potential of Helicoverpa armigera NPV strain BV -0003 and any 

potential exposure to the virus also would be minimal. 

Drinking Water Exposure and Risk Characterization: Exposure to residues of Helicoverpa 

armigera NPV strain BV-0003in consumed drinking water is unlikel y. The usc patterns for 

lielicovex are soil directed and/or soil incorporated, thereby limiting contact with surface water 

by drift and runoti. Furthermore, ground water is not expected to have significant exposure to the 

virus since, like other mi croorganisms, this microbial pesticide would like ly be filtered out by the 

particulate nature of many soil types. If it were to be transferred to surface or ground waters that 

arc intended for eventual human consumption (e.g., through spray drift or runoft) and directed to 

wastewater treatment systems or drinking water facilities, it likely would not survive the 

conditions water is subjected to in such systems or facilities, including chlorination, pH 

adjustments, filtration, and/or occasionally high temperatures (Centers for Disease Control and 

Prevention 2009; U.S. EPA 2004). In the remote like lihood that H armigera NPV strain BV0003 is present in drinking water (e.g., water not subject to treatment systems or facilities), its 
1/e/icoverpa armiJ!era nuclcopolyhcdro,·irus strain BV -0003 

13iopesticidcs Registration Action Document 

Page 12 of30 

target pest specificity and available data indicate no toxicity and/or pathogenicity is likely to 

occur with any drinking water exposure to Hz ABA NPY -U that results from pesticide 

applications made in accordance with good agricultural practices (see section IY(B)(l)(a) on 

pages 8- 10 and Table 5 in Appendix A). 

Non-occupalional. Residential Risk Characterization: Given that Helicoverpa armigera NPY 

strain BY -0003 is naturally-occurring and usually not stable outside of its insect host, the EPA 

determined that non-occupational exposure to the bacterium is unlikely. Repeated exposures to 

the microorganism from pesticidal applications do not exceed EPA's level of concern, 

particularly in light of available data that demonstrate that the virus is not toxic (acute dermal 

toxicity and acute pulmonary toxicity/ pathogenicity), non-irritating (primary dermal irritation). 

and not pathogenic (acute pulmonary toxicity/pathogenicity) (see section IV(B)(l)(a) on pages 

8-10 and Table 5 in Appendix A). 

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, the EPA consider '·available information concerning the 

cumul ative effects of [a particular pesticide's] ... residues and other substances that have a 

common mechanism of toxicity .. , 

Helicoverpa armigera PV strain BY-0003 shares a common mechanism of toxicity with strains 

of HelicO\'erpa zea NPY because the insect viruses are variants of the same insect virus. The 

EPA concluded that the two viruses, when used as pesticides, would not contribute to cumulative 

effects to human health or the environment. flelicovelpa armigera NPY and He/icoverpa zea 

NPY do not appear to produce a toxic metabolite against target pests. For the purposes of the 

tolerance action, therefore, the EPA has assumed that Helicoverpa armigera NPV strain BY0003 does not have a common mechanism of toxicity with another substance because the two 

viruses basically are the same substance. Thus, section 408(b)(2)(D)(v) of the FFDCA does not 

apply. For information regarding the EPA's efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

EPA's website at hllp:l/www. epa.govl pest icides/cumu/ative. 

c. Determination of Safety for the United States Population, Infants ami Children 

In considering the establishment of a tolerance or tolerance exemption for a pesticide chemical 

residue, FFDCA section 408(b)(2)(C) provides that the 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 the EPA shall apply an additional tenfold (I OX) 

margin of exposure (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 the EPA determines that a different margin of exposure (safety) will be safe for infants 

and children. This additional margin of exposure (safety) is commonly referred to as the Food 

Quality Protection Act Safety Factor. In applying this provision, the EPA either retains the 

default value of 1 OX or uses a different additional safety factor when reliable data available to 

the EPA support the choice of a different factor. 
1/elicoverpa armigera nuclcopolyhcdrovirus strain BV -0003 

!3iopcsticidcs Registration Action Document 

Page 13 of30 

Based on the acute toxicity and pathogenicity data/information discussed in section IV(B)(l)(a) 

(see pages 8- 1 0) and Table 5 in Appendix A. the EPA concludes that there are no threshold 

effects of concern to infants, children, or adults when He/icoverpa armigera NPV strain BY0003 is used as labeled in accordance with good agricultural practices. As a result, the EPA 

concludes that no additional margin of exposure (safety) is necessary to protect infants and 

children and that not adding any additional margin of exposure (safety) wi ll be safe for infants 

and children. 

Moreover, based on the same data/information and EPA analysis as presented directly above. the 

Agency is able to conclude that there is a reasonable certainty that no harm will result to the 

United States population, including infants and children, from aggregate exposure to the residues 

of He/icoverpa armigera N PV strain BY -0003 when it is used- as labeled and in accordance 

with good agricultural practices - as an insecticide. Such exposure includes all anticipated 

dietary exposures and all other exposures for which there is reliable information. The EPA has 

arrived at this conclusion because, considered collectively. the data and information available on 

He/icovetpa armigera N PV strain BV-0003 do not demonstrate toxic and/or pathogenic potential 

to mammals, including infants and children. 

3. Occupational Exposure and Risk Characterization 

The EPA does not expect handler exposure to He/icoverpa armigera NPV strain BY -0003 to 

pose any undue risk. Regardless, appropriate personal protective equipment (PPE) and 

precautionary statements are required on pesticide product labels to mitigate any potential risks 

to pesticide handlers due to prolonged or numerous exposures. Handlers applying Helicovex in 

agricultural settings must wear a dust/mist filtering respirator, waterproof gloves. long-sleeved 

shirt, long pants. socks and shoes. For future products containing this insect virus as an active 

ingredient, the EPA may require additional PPE (e.g .. protective eye wear) on a product-specific 

basis. 

4. Human Health Risk Characterization 

The EPA considered human exposure to He/icoverpa armigera NPV strain BY -0003 in light of 

the standard for registration in FIFRA and the relevant safety factors in FFOCA. The Agency 

determined that no unreasonable adverse effects to the United States population in general. and 

to infants and children in particular, will result when He/icoveJpa armigera NPV strain BY -0003 

is used in accordance with EPA-approved labeling. 

C. Environmental Assessment (40 CFR § 158.2150) 

Data and other information (e.g., scientific literature) submitted and cited by the applicant to 

support requests to waive nontarget organism testing for Helicovelpa armigera NPV strain BV0003 are sufficient to fu lfill the relevant microbial pesticide data requirements and for risk 

assessment purposes. Further testing of nontarget organisms at higher tier levels (i.e., Tiers II. 

Ill. and IV) is not required. The EPA performed an environmental risk assessment based on data 

and other information provided by the applicant. and the Agency determined that adverse effects 

to nontarget organisms are not anticipated from the pesticidal uses of 1/e/icoverpa armigera 

NPV strain BY -0003. Moreover, the EPA has made a "No Effect" determination for direct and 

indirect effects to federally listed threatened and endangered species and their designated critical 

habitats resulting from these same pesticidal uses. 
Helicol'erpa armigera nucleopol) hcdrovirus strain BV -0003 

Biopcsticidcs RcgisLration Action Document 

Page I-I of30 

For a summary ofthe generic data requirements described in sections IY(C)(I) (see pages 14-

15), refer to Table 6 in Appendix A. 

l. Ecological Exposure and Risk Characterization 

Baculoviruses are host-specific within certain arthropod orders (seven insect orders, 

predominantly the Lepidopteran and Hymenopteran insects to date and Crustacea (Fuxa, 2004)); 

however, they may persist in the environment (either in soil and/or suitable insect host 

populations) for several years and even decades. The environmental safety of currently registered 

baculovirus products to nontarget terrestrial and aquatic vertebrates and plants is fairly welldocumented (OECD, 2002; Lapointe, et al., 20 11 ), and the EP i\ does not know of adverse effects 

to nontarget organisms such as honeybees. 

For this stra in of Helicoverpa annigera NPV, information from the open literature to date are 

sufficient to address the majority of the nontarget organism data requirements for microbial 

pesticides (40 CFR 158.21 50). The applicant cited older studies conducted on a different NPV 

baculovirus. Heliothis zea (synonomous to llelicove1pa zea NPV). The cited document (MRID 

00062584) listed several studies (some were unpublished) in which different species of test 

organisms (plants; insects, including honeybee; freshwater and estuarine invertebrates and 

several vertebrates) were exposed via contact, oral or inhalation routes to Heliothis zea NPY 

without adverse effects. The applicant also submitted a published study to support that 

Helicoverpa zea NPY and f-lelicoveJpa armigera NPV are practically the same virus species (98-

99% sequence identity), that the host range specificity is limited to the Lepidopteran order of 

insects (M RID 49591500), and the baculovirus taxonomy for the microbial pesticide control 

agent (M RID 49239301 ). 

a. Terrestrial Animals and Plants 

Wild Mammals (Harmonized Guideline 885.-1 150, MRJD No. -19591 5-02). Bird~· (Harmonized 

Guideline 885. -1100), Nonlargetfn.s·ecls (Harmonized Guideline 885.43-10. MRID No. 492393-

09), Honey Bees (Harmonized Guideline 885.-1380. MRID No. -192393-08) and Plants 

(Harmonized Guideline 885. -1300): 

The applications-ground and aerial sprays and sprinkler chcmigation -would deposit 

Helicoverpa armigera N PV strain BY-0003 on foliar and other above ground plant surfaces. The 

EPA expects deposition onto these surfaces to occur within the intended area of treatment, as 

well as surrounding areas. Persistence of the virus in the environment, particularly in soil, is 

possible as long as conditions are favorable, but it does not pose risks to nontarget species 

because of its specificity. Birds and mammals would be exposed to Helicoverpa armigera NPV 

Strain BY -003 primarily through ingestion of treated prey or plants. Contact with these surfaces 

is not expected to result in significant exposure, though oral exposure may occur incidentally 

through grooming. The submitted data and information are sufficient to conclude that 

Helicoverpa armigera NPV Strain BV-003 is unlikely to infect birds or cause adverse effects. 

Data with laboratory mammals were also submitted, and concerns are not raised that would 

indicate potential risk to v.ri ld mammals. While birds and mammals may be exposed to 

f-lelicoverpa armigera NPV Strain BY -003, there is sufficient evidence to show that this 

exposure will not result in adverse direct effects to birds and mammals. Therefore, risk to birds 

and mammals is expected to be minimal. The uses of Helicove1pa armigera NPY Strain BY -003 
Ne/icOI•erpa armigera nuclcopolyhcdrovirus strain BV -0003 

Biopcsticidcs Registration Action Document 

Page IS of30 

arc also not expected to significantly affect the food supply for these nontarget animals, because 

the range of species affected is expected to be narrow and widespread reductions in the majority 

of populations of nontarget, non-Lepidopteran insects and other arthropods are not anticipated. 

Since baculoviruses are not taxonomically related to any known plant pathogens, the EPA did 

not require the applicant to submit data on testing lfelicovetpa armigera NPV BV-003 on plants. 

Risk to nontarget plants is not anticipated as a result of the uses of Helicoverpa armigera NPV 

BY-003. 

b. Aquatic Animals and Plants 

Freshwater Fish (Harmonized Guideline 885.-12002. Freshwater invertebrates (Harmonized 

Guideline 885.4240), Estuarine/ Marine Fish and Invertebrates (Harmonized Guideline 

885.4280) (MRID No. -192393-01 ): 

The EPA determined that, based on the information cited from the literature. risks to fresh\vater 

fish and invertebrates and estuarine/marine fish and invertebrates are not expected as a result of 

the uses of Helicovetpa armigera PV strain B V -0003. Freshwater and estuarine/marine fish 

and invertebrates are not likely to be exposed to He/icovetpa armigera NPV BV-003 from runoff 

and drift into aquatic areas, and the virus is not pathogenic to aquatic organisms. Baculoviruses 

have a history of safe usc as microbial pesticides, and they generally have narrow host ranges 

with no adverse effects on nontarget organisms (OECD 2002). Typically, NPVs only infect the 

genus or perhaps fami ly from which they were originally isolated. 

2. Environmenta l Fate Data 

As the data and infom1ation provided are sufficient to fulfill the Tier I nontarget organism data 

requirements and allow for nontarget organism risk assessment for Helicovetpa armigera NPV 

strain BV-0003, further testing at higher levels (Tiers II, III, and IV) is not required. 

3. Threatened and Endangered Species Assessment 

Since the EPA has determined that no effects are anticipated for any nontarget species exposed 

to ffelicove!pa armigera NPV strain BV-0003 as a result of the labeled uses. effects to federally 

listed threatened and endangered species and their designated critical habitats also are not 

expected. Moreover, the EPA made a "No Effect'· determination for direct and indirect effects to 

all federally listed threatened and endangered species and their designated critical habitats 

resulting from the use of the pesticide. 

V. ENVIRONMENTAL J USTICE 

The 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 (I) potentially 
Helicol'erpn nrmigera nucleopolyhcdro\'irus strain BV -0003 

Biopcsticidcs Registration 1\ction Document 

Page 16 of 30 

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

an 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. The EPA has this goal for all communities and 

persons across the United States. 

To help address potential environmental justice issues, the EPA sought information on any 

groups or segments of the population who, as a result of the ir location, cultural practices, or other 

factors, may have atypical, unusually high exposure to Helicoverpa armigera NPY strain BY0003 compared to the general population. 

For additional info1mation regarding environmental justice issues, please visit the EPA's web 

site at http://www.epa.gov/compliance/environmentaljusticelindex.html. 

VI. RISK MANAGEMENT DECISION 

Section 3(c)(5) of FIFRA permits for the registration of a pesticide provided that all the 

following determinations are made: 

(I) Its composition is such as to warrant the clajms for it; 

(2) Its labeling and other material required to be submitted comply with the 

requirements of FIFRA; 

(3) It will perform its intended function without unreasonable adverse effects on 

the environment; AND 

(4) When used in accordance with widespread and commonly recognized 

practice, it will not generally cause unreasonable adverse effects on the 

environment. 

To satisfy criterion l, the He/icove1pa armigera NPY strain BV-0003 product, Helicovex, has 

well-known properties. The EPA has no knowledge that would contradict the claims made on the 

label, and the pesticide product is not expected to cause unreasonable adverse effects on the 

environment when used according to label instructions. Criterion 2 is satisfied by the current 

product label. as well as the data and information presented in this document. The Agency 

believes that the Helicoverpa armigera NPY strain BY-0003 pesticide product will not cause any 

unreasonable adverse effects on the environment. in fact, Helicovex is likely to provide 

protection against many infestations, satisfying criterion 3. Criterion 4 is satisfied in that the 

Helicoverpa armigera N PY strain BY -0003 pesticide product is not expected to cause 

unreasonable adverse effects when used according to label instructions. Therefore, the EP, 

Helicovex, which contains Helicoverpa armigera NPY strain BY-0003 as a new active 

ingredient, is eligible for registration under FIFRA section 3(c)(5) for the labeled uses. 
1/e!icOI'erpa armigera nuclcopolyhcdrovirus strain 13V -0003 

13iopcsticidcs Registration Action Document 

VII. ACTIONS REQU IRED OF THE REGISTRANT 

A. Final Printed Labeling 

Page 17 of30 

Before the end-use product, Helicovex, may be released for shipment, the applicant is required to 

provide appropriate final printed labeling to the EPA. 

B. Terms of Registration 

The EPA is requiring additional information on the registration ofthe new product. Ifthe product 

is to be manufactured in a country other than Switzerland. then the registrant must provide 

official documentation from the other country's government that microbial contamination is not 

a concern and that the water used to produce Helicovex (e.g., publi c drinking water) is tested for 

pathogens such as Shigella and Vibrio. 

C. Reporting of Adverse Effects and Hypersensitivity Incidents 

Notwithstanding the information stated in the previous sections. it should be clearly understood 

that certain specific data must be reported to the EPA as a requirement for maintaining the 

federal registration for a pesticide product. Reports of all incidents of adverse effects to the 

environment must be submitted to the EPA under the provisions stated in FfFRA section 6(a)(2). 

Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents) 

must be reported to the EPA under the provisions of 40 CFR § 158.2 140( d). 
1/e/icol·erpa armigera nuclcopolyhcdrovirus strain BV -0003 

Biopcsticides Registration Action Document 

Page 18 of 30 

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS 

BRAD 

CfR 

eSt 

EDSP 

EP 

EPA 

FFDCA 

f iFRA 

FR 

g/mL 

lb/gal 

LDso 

mg/kg 

MP 

MRID o. 

NIOSH 

OPP 

PC Code 

pp 

PPE 

TGAI 

U.S. 

Biopesticides Registration Action Document 

Code of Federal Regulations 

centistokes 

Endocrine Disrupter Screening Program 

end-use pesticide product 

United States Environmental Protection Agency (the --Agency'') 

Federal Food, Drug, and Cosmetic Act 

Federal Insecticide, Fungicide, and Rodenticide Act 

Federal Register 

grams per milliliter 

pounds per gallon 

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). 

milligrams per kilogram 

manufacturing-use pesticide product 

Master Record Identification Number 

National Institute for Occupational Safety and Health 

Office of Pesticide Programs 

Pesticide Chemical Code 

Pesticide Petition 

personal protective equipment 

technical grade of the active ingredient 

United States 
1/e/icoverpa armigera nuclcopolyhcdrovims strain BV -0003 

Biopcsticidcs Registration Action Document 

Page 19 of3 0 

IX. BIBLIOGRAPHY 

A. Studies Submitted to Support the Active Ingredient, Helicoverpa armigera NPV strain 

BV-0003, and Pesticide Product Registration for the EP, Helicovex. 

MRIDNo. 

62584 

486247 18 

4923930 1 

49239302 

49239303 

49239304 

49239305 

49239308 

49239309 

49239310 

Study Information 

International Minerals & Chemical Corporation (1967) Published and 

Unpublished Studies Demonstrating Specificity ofHeliothis Virus to Other 

Insects. Invertebrates and Vertebrates Including Humans. (Unpublished study 

received Oct 2, 1968 under 8G0697; COL: 091209-G). 

Organisation for Economic Co-operation and Development (2002) Consensus 

Document on Information Used in the Assessment of Environmental Applications 

Involving Baculoviruses. Series on Harmonization of Regulatory Oversight in 

Biotechnology 87p. 

SciReg, Inc. (20 13) Helicovex: Product Identity, Manufacturing Process, 

Deposition of Sample in a Nationally Recognized Culture Collection, Discussion 

of the Formation of Unintentiona l Ingredients. Unpublished study. I 04p. 

Sci Reg, Inc. (20 13) Helicovex: Analysis of Samples and Certification of Limits. 

Unpublished study. 20p. 

SciReg. Inc (2013) Helicovex: Summary of the OPPTS 830 Series PhysicalChemical Properties Test Guidelines. Unpublished study. 5p. 

Aversa. S. (20 13) Physica l-Chemical Properties: pH, Viscosity and Relative 

Density of Test Item Helicovex : Final Report. Project Number: BT/1 09/13. 

Unpublished study prepared by BioTecnologie BT S.r.l. 28p. 

Walter, D. (20 11) 3 Year Storage Stability of the Formulation He licovex at 

5( degrees) Celsius: Final Report. Project Number: 20061 550/0 I /PCTY. 

Unpublished study prepared by Eurofins- GAB GmbH. 59p. 

Verge, E. (20 1 0) Acute Oral and Contact Toxicity to the Honey Bee A pis 

mellifera L. in the Laboratory: Final Report. Project N umber: SI0/00139, 

S 10/00 139/LJ/BLEU. Unpublished study prepared by Eurofins- GAB GmbH. 

30p. 

Klug. T. (20 I 0) Helicovex: Toxicity to the Aphid Parasitoid, Aphidius 

rhopalosiphi De Stefani Perez (Hymenoptera. Braconidae) in the Laboratory 

(Limit Test): Final Report. Project Number: S 10/00142. S I 0/00 142!LI/NLAP. 

Unpublished study prepared by Eurofins - GAB GmbH. 28p. 

Klug, T. (20 I 0) Helicovex: Toxicity to the Predatory Mite. Typhlodromus pyri 

Schcuten (Acari, Phytoseiidae) in the Laboratory (Limit Test): Fina l Report. 

Project Number: 810/00143, S I0/00143/L1 /NLTP. Unpublished study prepared 

by Eurofins - GAB GmbH. 28p. 
He/ico1·erpa armigera nucleopolyhcdrovirus strain BV -0003 

Biopesticidcs Registration Action Document 

Page 20 of30 

49239311 

49409700 

49409701 

49409702 

49591501 

49591502 

49591503 

Sci Reg, Inc. (20 13) Helicovex: Nontarget Organisms and Environmental Fate 

Waiver Requests. Unpublished study. 34p. 

Andermatt Biocontrol AG (20 14) Submission of Product Chemistry and Toxicity 

Data in Support of the Application for Registration of Helicovex. Transmittal of 2 

Studies. 

Smith, F. (20 14) Helicovex: Analysis of Samples. Unpublished study prepared by 

SciReg, Inc. 14p. 

Konrad, R. (20 14) Helicovex Nontarget Insect Testing. Unpublished study 

prepared by Anderman Biocontrol AG. 14p. 

Smith, F. (20 15) Helicovex : Manufacturing Process. Unpublished study prepared 

by SciReg, Inc. 8p. 

Murphy, V. (20 15) Helicovex (Helicoverpa armigera NPV) Intraperitoneal Acute 

Mouse Toxicity/Infectivity. Project Number: 18596/ 14. Unpublished study 

prepared by Stillmeadow, Inc. 20p. 

Minei, C. (20 15) Helicovex: !Ioney bees (A pis mellifera), Acute Oral Toxicity 

Test: Final Report. Project Number: PL1 2868/20 14/28/0ABO/B. 

12868/20 14ABO. Unpublished study prepared by TECAM Technologia 

Ambiental Ltda. 27p. 

B. Environmental Protection Agency Risk Assessment Memoranda 

U.S. EPA. 20 15a. Review of Product Chemistry, Manufacturing Process, and Acute Toxicity 

Studies of the EP containing Helicoverpa armigera Nucleopolyhedrovirus (Hz NPV) for 

section 3 product registration. Memorandwn from Ibrahim S. Barsoum, Ph.D. and John 

L. Kough, Ph.D. to Michael Glikes, dated June 10, 2015. 

U.S. EPA. 20 15b. Environmental Risk Assessment for Section 3 Registration of an End-Use 

Product (Helicovex, EPA File Symbol 69553-E), manufactured by Andermatt Biocontrol 

AG) containing baculovirus, Helicove1pa zea NPV strain BY -0003 (PC Code l 0730); 

Decision 'o. 484373; DP#: 426617; Submission No. 965729. 

U.S. EPA. Registration Eligibility Decision (RED) Facts: Heliothis Zea PV, January 1991. 

C. Other References 

Annals of the Entomological Society of America. 2004. A New Synonym of Helicove1pa zea 

(Boddie) and Differentiation of Adult Males of H zea and H. armigera (Hubner). Vol. 

97. no. 6. 
1/elicOI'erpa armigera nuckopolyhcdrovirus strain BV-0003 

13iopcsticidcs Registration Action Document 

Page 21 or30 

Chen. X., I.J. Wu, R. Tarchine, et al. 2001. The Sequence of the Heliocoverpa armigera Single 

Nucleocapsid NPV Genome. J. Gen. Virol 82:241-257. 

Chen, X., W.J. Zhang, .1. Wong, et al. 2002. Comparative Analysis of the Complete Genome 

Sequences of llelicoverpa zea and Heliocoverpa armigera Single-Nucleocapsid NPVes . .1. 

Gen. Virol. 83:673-684. 

Hamm, J.J. 1982. Relative Susceptibility of Several Noctuid Species to a Nuclear Polyhedrosis 

Virus from Heliothis armigera. Journal oflnvertebrate Pathology 39:255-256. 

l lughes, P.R., R.R. Genig, and W.J. McCarthy. 1983. Comparison of the Time-Mortality 

Response of He liothis zea to 14 Isolates ofHeliothis Nuclear Polyhedrosis Virus. Journal 

of Invertebrate Pathology 41 :256-261. 

lgnoffo, C.M., A.I-L Mcintosh, and C. Garcia. 1983. Susceptibility of Larvae of Heliothis zea, II. 

virescens, and II. armigera (Lep: Noctuidae) to 3 Baculoviruses. Entomophaga 28:1-8. 

Jehle, J.A., M. Lange. I I. Wang, et al. 2006. Molecular ldentit"ication and Phylogentic Analysis 

of Baculoviruses of Lepidoptera. Virology 346:180-196. 

Ogembo, J.G., B.L. Caoi li, M. Shikata, et al. 2009. Comparative Genomic Sequence Analysis of 

Novel Heliocoverpa annigera NPV (NPV) Isolated from Kenya and Three Other 

Previously Sequenced Helicoverpa spp. NPVs Virus Genes. Reference not provided. 

Rowley, D.L., H.J. Popham. and R.L. Harrison. 20 II. Genetic Variation and Virulence ofNPVes 

Isolated Worldwide from the Heliothine Pests Helicoverpa armigera. I leliocoverpa zea. 

and Heliothis virescens. J. Invertebr. Pathol. I 07: 11 2-126. 

Williams, C. F .. and C. C. Payne. 1984. The Susceptibility of Heliothis arrnigera Larvae to Three 

Nuclear Polyhedrosis Viruses. Annals of Applied Biology 104: 405-412. 

Zhang, C.S., S.C. Ma. and Z.J. Guo. 2005. Comparison of the Complete Genome Sequence 

between C1 and G4 Isolates of the 1-Ielicoverpa armigera Single Nucleocapsid NPV. 

Virology 333: 190-199. 

Burges, H.D. G.Croizier and J.Huber. 1980(?). A Review of Safety Tests on baculoviruses. 

Entomophaga (?): 25:329-349. Portions of the document were illegible due to faded 

Xerox. 

Doyle, C..J .. M.L. Hirst. J.S.Cory, P.F.Entwistl e. 1990. Risk Assessment Studi es: 

Detailed Host Range Testing of Wild-Type Cabbage Moth, Mamestra brassicae 

(Lepidoptera: Noctuidae), Nuclear Polyhedrosis Virus. Applied and Environmental 

Microbiology 56:2704-2710. 

Fuxa. J.R. 2004. Ecology orlnsect Nucleopolyhedroviruses. Agriculture. ecosystems and the 

environment. I 03:27-43. 

Groner, A. 1986. "Safety of nontarget invertebrates of baculoviruses''. Chapter in book: Safety of 

Microbial Insecticides, M.Laird, L.A.Larey. and E. W.Davidson, eds. 
Helicon!lpa armigera nuckopol)hcdro,·irus strain BV-0003 

11i p~ ticidcs Registration Action Document 

Page 22 of30 

Lapointe, R. D., Thumbi and C.J.Lucarotti. 2011 (year not confinned). Recent Advances in our 

knowledge of Baculovirus Molecular Biology and Its Relevance for the Registration of 

Baculovirus-based Products for Insect Pest Population Control. p.481-522, Integrated 

Pest Management and Pest Control - Current and Future Tactics. Available at: http: 

www. intechopen.com 

Organization for Economic Cooperation and Development (OECD). 2002. Consensus 

Document on Information Used in the Assessment of Environmental Applications 

lnvolving Baculoviruses. ENV /.JM/MON0(2002) I, 08 January 2002. Available at: 

http://www.oecd.org/science/biotrack/46815698.pdf. 

Possee and, R.D., G.F. Rohrmann. 1997. Baculovirus genome organization and evolution. In: 

Miller, L.K.(Ed). The Baculoviruses. Plenum Press, New York, pp. 109-140. As cited in 

Fuxa, 2004. 

Centers for Disease Control and Prevention. 2009. Drinking Water- Water Treatment. Available 

from htl p:llwww. cdc. govlhea/ 1 hvwalerldri nki ng/pub/ iclwaler I reatmenl. him/. 

DeFelice K, Wollenhaupt N, Buchholz D. 1993. Aquifers and Soil Filter Effect. Available from 

http://exlension. missouri. edu/p/IV02-I. 

U.S. EPA. 2004. Primer for Municipal Wastewater Treatment Systems. EPA 832-R-04-00l. 

Available from hllp:l/www. epa. gov/npdes/ pubs/ primer. pdf 
1/e/icol-erpa armigera nuclcopolyhcdrovirus strain BV-0003 

Biopesticides Registration Action Document 

Page 23 of30 

TABLE 1. 

Harmonized 

Guideline 

Number 

885.1100 

885. 1200 

N/A 

885.1300 

885. 1400 

885.1500 

Ha rmonized 

Guideline 

Number 

885.1100 

885.1200 

N/A 

885.1300 

885.1400 

885. 1500 

APPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS 

(40 CFR PART 158 - SUBPART V) 

Product Analysis Data Requirements for the Active Ingredient (TGAI), 1-/e/icoverpa armigera NPV strain BV-0003 

(40 CFR & 158.2120) 

Data Req uirement Results MRID No. 

Product Identity Submitted data fulfill the requirement for product identity and composition. 49239301 

Manu facturing Submitted data fulfill the requirement for manufacturing process. 49239301 Process 

Deposition of a 

Sample in a Helicove1pa armigera NPV strain BY-0003 is on deposit with the German 

Nationally Collection for Microorganisms and Cell Cultures under the accession number 49239301 

Recognized Culture BY-0003 

Collection 

Discussion of 

Formation of Submitted data fulfill the requirement for preventing and detecting any 49239301 Unintentional microbial contaminants. 

Ingredients 

Analysis of Samples Submitted data fu lfill the requirement fo r analysis of samples. 49239302 

Certification of Submitted data fu lfill the requirement for manufacturing process. 49239302 Limits 

TABLE 2. Prod uct Analysis Data Requirements for the End-Use Pesticide Product (EP), Helicovex 

(40 CFR § 158.21 20) 

Data Requirement Results MRID No. 

Product Identity Submitted data fulfill the requirement for product identity. 4923930 1 

Manufacturing Process 

Submitted data fulfi ll the requirement for manufacturing 49239301 

process. 49591501 

Deposition of a Sample in a Submitted data fulfi ll the requirement fo r deposition of a samp le Nationally Recognized in a culture collection. N/A 

Culture Collection 

Discussion of Formation of Submitted data fulfill the requirement for preventing and 49239301 Unintentional Ingredients detecting any microbial contaminants. 

Analysis of Samples Submitted data fulfill the requirement for analysis of samples 49239302 

for purposes of Fl FRA section 3(c)(5) registration. 

Certification of Limits 

Limits listed on the confidential statement of fo rmula are 

adequate/acceptable. 49239302 
1-/elicol'erpa armigera nuclcopolyht:drovirus strain BV -0003 

Biopesticidcs Registration Action Document 

Page 2-t of30 

TABLE 3. Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient (TGAI), Helicoverpa armigera 

NPV stra in BV-0003 (40 CFR § 158.2 120) 

Harmonized Results I Guideline Number Data Req uirement MRID No. 

830.6302 Color Grey-brown 

830.6303 Physica l State Liquid 49239303 

830.6304 Odor Typical organic odor -

StabHity to Nonnal aL 

830.6313 Elevated N/A N/A 

Temperatures. Metals, 

and Metal Ions -- -

830.6317 Storage Stabiliry Stable at 5 degrees C for 36 months 

I 49239305 

830.6319 Miscibility Non emulsifiable liquid N/A - -

830.6320 Corrosion Non-corrosive to PET container when stored at 5 degrees for 49239305 

Characteristics 36 months - - --- - 830.7000 pH 

I 

6.43 - 6.92 49239304 

6.92 ( 1°'<> " ' "aqueous solution at 2-t.l 0

C) 

I on-Nc1110nian Ouitl. 

v;soos;ty _l__ 2863.7 mPals at 2.5 rpm at 20°C 

830.7 100 690. I mPa/s at 50 rpm at 20°C 49239304 

1490.3 mPals at 2.5 rpm at 40°C 

405.00 mPals at 50 rpm at 40°C - Density/Relative 

830.7300 Density/Bulk Densiry I 

1.163 g/mL at 20 degrees Celsius 49239304 

(Specific Graviry) 

TABLE 4. Physical and Chemical Characteristics for the End-Use Pesticide Product (EP), Helicovex (40 CFR § 158.2120) 

Harmonized Data Requirement Results MRID No. 

Guideline Number 

830.63021 Color Grey-brown 

49239303 

830.6303 1 Physical State Liquid 

830.63041 Odor Typical organic odor 

Stability to Normal and 

830.6313 1 Elevated Temperatures. N/A !A 

Metals. and Metal Ions 

830.63 17 Storage Stabiliry Stable at 5 degrees C for 36 months 49239305 

830.63 19 Misc ibility Non emulsifiable liquid N/A 

830.6320 Corrosion Characteristics 

Non-corrosive to PET container when stored at 5 degrees 

for 36 months 49239305 

830.7000 pH 6.43 - 6.92 

6.92 ( I% w/v aqueous solution at 24.1 °C) 49239304 

Non-Newtonian nuid. 

2863.7 mPals at 2.5 rpm at 20°C 

830.7100 Viscosity 690. I ml'a/s at 50 rpm at 20°C 49239304 

1-190.3 mPals at 2.5 rpm at 40°C 

405.00 mPals at 50 rpm at .t0°C 

Density/Relative 

830.7300 Density/Bulk Density 1.163 g/mL at 20 degrees Celsius 49239304 

(Specific Gravity) 
Helicove1pa armigera nuclcopolyhcdrO\'irus strain IJV -0003 

Oiopcsticidcs Registration Action Document 

Page 25 ofJO 

TABLE 5. Toxicology Data Requirements for the Active Ingredient Helicoverpa armigera NPV strain BV-0003 

and the End Use Pesticide Product Helicovex (40 CFR & I 58.2140) 

Harmonized 

Guideline Data Requirement Results MRID No. 

Number 

Tier I 

Waived based on extensive list of toxicology studies on other strains 

885.3050 Acute Oral ofNPV. 49409700 Toxicity/Pathogenicity Classification: Acceptable 

TOXICITY CATEGORY IV 

Acute Pulmonary 

Waived based on extensive list of toxicology studies on other strains 

885.3150 ofNPV. 49409700 Toxicity/Pathogenicity Classification: Acceptable 

Acute Injection Submitted study on intraperitoneal injection in mice demonstrated no 

885.3200 Toxicity/ toxicity or pathogenicity. 49591502 

Pathogenicity Classification: Acceptable 

The applicant reported that no hypersensitivity incidents. including 

Hypersensitivity immediate-type or delayed-type reactions of humans and domestic 

885.3400 Incidents 

animals. occurred during research, development, or testing of the 49409700 

TGAI. Any Future hypersensitivity incidents must be reported to EPA 

(refer to test note #3 of 40 CFR § 158.2 140(d)). 

Waived due to results of toxicology testing and additional toxicology 

885.3500 Cell Culture data which support the negative replication of viral replication in 49409700 mammals. 

Classification: Acceota ble 

Waived based on extensive list of toxicology studies on other strains 

870.1100 Acute Oral Toxicity 

of PV. 49409700 Classification: Acceptable 

TOXICITY CATEGORY IV 

Waived based on extensive list of toxicology studies on other strains 

870.1200 Acute Dermal Toxicity ofNPV. 49409700 Classification: Acceptable 

TOXICITY CATEGORY IV 

Waived based on extensive list of toxicology studies on other strains 

870.1300 Acute Inhalation Toxicity 

of PV. 49409700 Classification: Acceptable 

TOXICITY CATEGORY IV 

Waived based on extensive list of toxicology studies on other strains 

870.2400 Acute Eye Irritation 

ofNPV. 49409700 Classification: Acceptable 

TOXICITY CAT EGORY IV 

Waived based on extensive list of toxicology studies on other strains 

870.2500 Primary Dermal Irritation 

ofNPV. 49409700 Classification: Acceptable 

TOXICITY CAT EGORY IV 

Tiers II ami Ill 

Not required for Helic01·erpa armigera NPV strain BV -0003 based on the lack of acute toxicity/pathogenicity in the Tier I studies. 
llelicol•erpa armigera nuclcopolyhcdrovirus strain 13V-0003 

Riopcsticidcs Registration Action Document 

Page 26 of30 

TABLE 6. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active 

Ingredient (TGAI), Helicoverpa armif!era NPV strain BV-0003 (40 CFR § 158.21 50) 

Harmonized Guideline Data Requirement Results MRIO No. 

Number 

Tier I 

No biological response from chickens or eggs 

when exposed to Helicoverpa : ea NPV; no 

quantitative information was provided in the cited 62584 

study (62584). A srudy cited from the literature 49239301 

(Chen et al.. 2002) provided data to support that 49591500 

Helicoverpa : ea and Helicoverpa armigera are 

885.4050 Avian Oral Toxicity variants ofthe same virus species. (49591500) 

Classification: Acceptable. 

The OECD consensus document (OECD 2002) 

contains a review of information and states that 

effects on birds are not expected from exposure to 48624718 

baculoviruses. Classification: Supplemental 

(acceptable for avian risk assessment) 

Not required as the nature of the microbial 

pesticide does not indicate potential pathogenicity 

to birds or relatedness to any known bird N/A 

Avian Inhalation pathogens (refer to test note #3 of 40 CFR § 

885.4 100 Toxicity/Pathogenicity 158.2150(e)). 

Submitted rationale cited literature that was for 4923931 1 

baculoviruses in general. Classification: 

Supplemental 

Tests required by 40 CFR § 158.2140 are 

adequate and appropriate for assessment of 49591502 hazards to wild mammals. The review of 49409700 information submined to fulfill those data 

requirements does not indicate concerns for 

885.4150 Wild Mammal adverse effects on wild mammals. 

Tox icity/Pathogenicity Classification: Acceptable for environmental 

risk assessment 

Submitted rationale cited literature that was for 49239311 

baculoviruses in general. Classification: 

Supplemental 

No biological response from minnow. killifish. 

and spot fish when exposed to 1/e/icoverpa :ea 62584 NPV; no quantitative information were provided 49591500 in the study citation (62584). A study cited from 49239301 

the literature (Chen er al., 2002) provided data to 

support that Helicoverpa :ea and Helicoverpa 

Freshwater Fish armigera are variants of the same virus species. 

885.4200 Toxicity/Pathogenicity (4959 1500). Classification: Acceptable. 

A study cited from the literature (Groner eta!. 

1981 ) and the OECD consensus document 

(OECD 2002) provide information to show that 

baculoviruses are generally understood not to be 49591500 

toxic or pathogenic to fish. 

Classification: Supplemental 
llelico,·erpa armigera nuclcopolyhcdrovirus strain 13V -0003 

Biopc ti cid~.:s Rcgi~tration Action Document 

Page 27 of 30 

TABLE 6. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active 

Ingredient (TGAI), He/icoverpa armigera NPV strain BV-0003 (40 CFR § 158.2 150) 

Harmonized Guideline Data Requirement Results MRID No. 

Number 

No biological response from grass shrimp. brown 

shrimp, or oyster when exposed to Helicoverpa 

=ea PV: no quantitative information were 62584. provided in the study citation (62584). A study 49239301 cited from the literature (Chen ct al.. 2002) 49591500 provided data to support that 1/e/icorerpa =ea and 

Helicoverpa armigera arc variants of the same 

885.4240 Freshwater Invertebrate virus species. (4959 1500). 

Toxicity/Pathogenicity Classification: Acceptable. 

A study cited from the literature (Groner et al. 

1981) and the OECD consensus document 

provide additional information that baculoviruses 4959 1500 

specific to Lepidoptera arc not expected to cause 

adverse effects in freshwater invertebrates. 

Classifi cation: Supplementa l 

The product is not intended for direct application 

into estuarine or marine environments. Data are 

885.4280 Estuarine/Marine Fish and not required since agricultural applications of 49239311 Invertebrate Testing Helicovcx are not expected to enter these 

environments in significant amounts. 

Classification: Acceptable 

Not required as the microbial pesticide is not 

885.4300 ontarget Plant Testing taxonomically related to any known plant /A pathogens (refer to test note #7 of 40 CFR § 

158.2150(e)). 
1/e/icol'erpa armigera nuclcopolyhcdrovirus strain BV-0003 

Biopcsticidcs Registration Action Document 

Page 28 of30 

TABLE 6. Nonta rget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active 

Ingredient (TGAI), Helicoverpa armi~:era NPV stra in BV-0003 (40 CFR § 158.2150) 

Harmonized Guideline Data Requirement Results MRID No. 

Number 

A submitted study conducted on parasitic wasps 

(Aphidius rhopalosiphi) indicated unce11ainty in 

the tox icity and/or viral activity because of the 

test material or experimental design. Reported 

results were not consistent with published 

literature on baculovirus biology and pathology. 

There were scientific issues with the method and 49239309 

duration of exposure to determine potential 

baculovirus infectivity and replication in parasitic 

wasps. Classification: Unacceptable. 

A submitted study conducted on predatory mites 

(Typhlodromus pyri) indicated uncertainty in the 

toxicity and/or viral activity because of the test 

material or experimental design. Reported results 

were not consistent with published literature on 

baculovirus biology and pathology. The duration 

of exposure to test material may have been too 

short to determine potential baculovirus 49239310 

885.4340 Nontarget Insect Testing infectivity and replication in parasitic wasps. 

Classification: Unacceptable. 

A bioassay conducted on 3 Lepidopteran pest 

species: Agrotis ipsilon, Cydia pomonella, and 

Plutella xylostella larvae indicated no crossinfectivity even at a high dosage of llelicovex. 

Maximum hazard dosing was not confirmed. 

Classification: Supplemental. 49409702 

Submitted rationale provides a weight-ofevidence justification (based on in formation and 

data fTom the current open literature) that there 

will be minimal risks to the majority of nontarget 

insect populations, because of the host specificity 4959 1500 

ofNPV baculoviruses. such as llaNPV. 

llowever, the submitted rationale is not sufficient 

to preclude potential adverse effects to listed 

Lepidopteran species or to unmanaged honeybees 

and other pollinating insects. 

Classification: Suoolemental. 
1/e/icoverpa armigera nuclcopolyhcdrovirus strain B V -0003 

Biopcsticidcs Registration Action Document 

Page 29 of30 

TABLE 6. Nontarget Organism Tox icity and Environmental Fate Data Requirements for the Technical Grade of the Active 

Ingredient (TCAI), Helicoverpa armi~: a NPV strain BV-0003 (40 CFR § 158.2150) 

Harmonized Guidelin e 

Number 

885.4380 

Data Requirement 

Honey Bee Testing 

Results 

A submitted guideline study provided an LD50 > 

I 0 J.lL/bee (i.e .. 2: I 06 Helicoverpa armigera 

NPV!bee), since it was the highest dose tested 

and - 22% bee mortalities were reported in a 

dose-response contact exposure test for 72 hours. 

Bee mortalities were noted in the contact 

exposure test; however there were no bee 

mortalities after 48 hr of continuous oral 

exposure to Helicovex. Potential infectivity or 

pathogenicity of HaMNPV strain BV003 was not 

evaluated in this short test. The LD50 value is 

uncertain because of deficiencies with the test 

material, lack of appropriate controls and other 

issues in the experimental design and reporting of 

results. Maximum hazard dosing was not 

confirmed. Results of the submitted study are 

Inconclusive because bee mortalities did not 

exhibit overt symptomatology associated with 

baculovirus activity. Classification: 

Unacceptable due to inconclusive results. 

A submitted guideline study provided a median 

oral LD50 > 2.96 x 108 OB H. armigera NPV 

strain BV003/mL, in a 96-hr laboratory test. 

Although bee mortalities were noted in all 

groups, including the negative control. the 

differences in mortality were not significant. No 

significant toxic effect was observed in the 

treatment group compared >vith the negative and 

inactivated control groups. However. no 

statistical tables were inc luded in the data set to 

confirm that no statistical differences were 

present between treatment and control groups. 

Classification: Unacceptable; as bee mortality 

was noted in all experimental groups and the 

resu lts are inconclusive. The reported results are 

not typical of expected baculovirus 

symptomatology and may have been confounded 

by impure test material or experimental design 

flaws. According to the guidelines, testing should 

not be stopped when control mot1ality reaches 

20%. as outlined for other non-target insect 

testing. 

The submitted rationale provides a weight-ofMRID No. 

49239308 

49591503 

evidence justification that exposures of Helicovex 49591500 

to honeybee populations are not likely to cause 

irreversible adverse effects. because of the host 

specificity ofNPV baculoviruses, and that 

baculovirus insecticides have a limited activity in 

the environment because of their sensitivity to 

sunlight and ultraviolet radiation. 

Classification: Supplemental. 

Tiers II, Ill, and IV 

Not required/or He/icoverpa armigera NPV strain BV-0003 based on the acceptability of data and other information provided for Tier I. 
EPA File 

Symbol 

69553-E 

1/e/icoverpa armi~era nucleopolyhedrovirus strain BV -0003 

Biopcsticidcs Rcgistrat ion Action Document 

APPENDIX B. PESTICIDE PRODUCTS 

Registration Percenta Formulation Use Site(s) 

Name ge Type 

Active 

lngred ie 

nt 

End-usc Agricultural llclicovex 0.60% product 

• 

Page 30 of30 

Method(s) of Application Rate(s) Target Pest 

Application 

corn carworm 

(Helicoverpa zca). 

Ground application tobacco budworm 

Aerial 1.0 - 2.5 n. oz./ acre (llclicoverpa 

Chemigation virescens). and 

Greenhouse depending on the crop 1\ frican colton 

R.:sidcntial bollworm 

(Hclicovcrpa 

armigcra)