Registration Decision for the New Active Ingredient 

Helicoverpa armigera Nucleopolyhedrovirus strain BV-0003 

Date: 

3 Nov 20 15 
1. Background 

On October 25. 20 13, the U.S. Environmental Protection Agency (EPA) received an application 

for registration for the ne\ insecticide active ingredient Helicoverpa armigera 

Nucleopolyhedrovirus ( PV) strai n BV-0003 from SciReg, Inc., on behalf of Anderman 

Biocontrol AG, a Swiss company. SciReg subequently provided additional data on this active 

ingredient and its end-use product, Helicovex, to the EPA. After reviewing these data, the EPA 

concluded that the use o f the He/icoverpa armigera NPV strain BY -0003 pesticide end-use 

product (EP), Helicovex, will not cause any unreasonable adverse effects on the environment. 

Therefore. the Agency is registering the EP containing the new active ingredient under FIFRA 

section 3(c)(5) for the following labeled uses: tomatoes, lettuce. cucumbers, peppers, sweet corn. 

broccoli, cauliflower, cabbage, peas, beans, beets, celery, onions, garlic, leek, asparagus, okra, 

eggplant, strawberries, grapes, escarole, ornamentals, flowers, cotton, alfalfa, soybeans, peanuts, 

potatoes. corn, wheat, sweet potatoes, tobacco, sunflowers, suga r beets, sorghum, floriculture. 

and border plants. 

The active ingredient in the EP, Helicoverpa armigera NPV strain BV-0003, is a virus specific 

to Lepidopteran pests and a member of the virus family Baculoviridae, genus A lphabacu/ovirus. 

This non-genetically modi tied, naturally-occurring strain was isolated by the Institute of 

Zoology, Chinese Academy of Sciences, from several H. armigera larval cadavers infected with 

nuclear polyhcdrosis disease in a cotton field in a suburb of Beijing, China. On April 7, 2006, the 

applicant deposited a sample with the Gennan 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 NPV, whi ch was first detected in South Afri ca in 1891 in 

infected II. zea larvae. Since the two viruses, II. armigera N PV and H. zea NPV, were originally 

isolated from different hosts, they were previously classifi ed as different species. By using DNA 

restriction analysis, researchers showed that the genomes o f both viruses are very similar. This 

similarity was corroborated by genome sequencing. which demonstrated a 97% nucleotide 

identity and a 99% amino ac id identity. Because they share common host range, virulence. 

physical properties, and genome sequence, it was determined that H. zea NPV and H armigera 

NPV arc "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 (Helicove1pa zea), tobacco budworm (He/icove1pa virescens), and 

African cotton bollworm (llelicovelpa 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, there is a sub-label 

for control of the same insect pests on a subset of these food crops, flowers, and ornamentals in 

home gardens. 

2. Evaluation 

In evaluating a pesticide registration application, the EPA assesses a wide vari ety of studies to 

detennine the likelihood or adverse effects (i.e., risk) from exposures assoc iated with the use of 

the product. Risk assessments are developed to evaluate how the compound might affect a wide 

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range of nontarget organisms, including humans and ten·estrial and aquatic wildlife (plants and 

animals). 

Based on these assessments, the EPA evaluates and approves language for each pesticide label to 

ensure the directions for use and safety measures are appropriate to mitigate any potential risk. In 

this way, the pesticide's labe l helps to communicate essential limitations and mitigations that are 

necessary for public safety. In fact, the pesticide Jaw has a provision that indicates it is a 

violation to use a pesticide in a way that conflicts with the label. 

2.1 Assessment of Risk to Human Health 

In order to assess a microbial pesticide's risk to human health, the EPA initially requires a wide 

range of studies, including Tier I acute toxi city/pathogenicity (oral, pulmonary, and injection) 

data, cell culture data, reports of hypersensitivity incidents, acute toxicity (oral, dermal, and 

inhalation) data, and irritation (dermal and eye) data. Tier II and III testing (e.g., subchronic 

toxicity/pathogenicity) is triggered only when there is indication, usually through lower tier 

testing, that a microbial pesticide has unusual toxicological characteristics, such as infectivity or 

being suspected as or known to be a carcinogen. 

2.1.1 Toxicity 

For Helicoverpa armigera NPV strain BV-0003, the database of studies required to support the 

assessment of risk to human health is complete. The toxicity tests (acute oral, dermal, and 

inhalation toxicity) and irritation tests (acute eye and primary dermal irritation) that address 

potential routes of exposure to the active ingredient are all classified in Toxicity Category IV and 

reveal little to no toxicity or irritation attributed to Helicoverpa armigera NPV strain BV-0003. 

Moreover, during a typical toxicity/pathogenicity test done with microbial pesticides, 

Helicoverpa armigera NPV strain BV-0003 did not show any signs of toxicity, pathogenicity, or 

infectivity via the pulmonary route of exposure. 

The EPA waived most acute toxicity/pathogenicity studies for this active ingredient, based on 

SciReg's scientific rationale. The rationale cited to the results of other toxicological data done 

with Helicoverpa zea NPV, a literature search that yielded no human pathogenicity concerns, 

and data describing the specificity of the virus to the target insect species. Regarding cell culture 

testing, in this case, the EPA did not require these data because the applicant cited acceptable cell 

culture studies performed using Helicoverpa zea NPV. Finall y, SciReg reported that, to date, no 

hypersensitivity incidents have occurred during research, development, and testing of this insect 

virus. In light of the adequacy of the toxicological data, scientific rationale, and literature 

provided by Sci Reg and the absence of hypersensitivity incidents, the EPA did not require 

toxicological testing at higher tiers. 

2.1.2 Aggregate and Occupational 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 

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exposure through pesticide use in gardens, lawns, or buildings. 

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

armigera NPY strain BY -0003, a naturally occurring insect virus, from its use as a pesticide is 

anticipated to be negligible. Due to the ubiquitous nature of the organism and the concentrations 

of H. armigera NPY strain BV -0003 and 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 likely to be 

minimal because of the low acute oral toxicity/pathogenicity potential of Helicoverpa armigera 

NPY strain BY -0003 and any potential exposure to the virus also would be minimal. 

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

armigeraNPY strain BY-0003 in consumed drinking water is unlikely. The use patterns for 

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

by drift and runoff. Furthennore, ground water is not expected to have significant exposure to the 

virus since, like other microorganisms, this microbial pesticide would likely be filtered out by the 

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

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

wastewater treatment systems or drinking water facilities, it is likely that the virus 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 likelihood that H. armigera NPV strain 

BY -0003 is present in drinking water (e.g., water not subject to treatment systems or facilities), 

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

occur with any drinking water exposure that results from pesticide applications made in 

accordance with good agricultural practices. 

Non-occupational, Residential Risk Characterization: Given that Helicove1pa armigera NPY 

strain BV -0003 is naturally-occurring and usually not stable outside of its insect host, nonoccupational 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). 

2.1.3 Human Health Conclusion 

The EPA concludes that there is a reasonable certainty that no harm will result to the U.S. 

population, including infants and children, from aggregate exposure to residues of Helicove1pa 

annigera NPY strain BY -0003. The EPA does not expect dietary (food and drinking water) or 

other non-occupational risks from use of Helicove1pa armigera NPV strain BY-0003 as an 

active ingredient in the pesticide products. Although exposure to Helicove1pa armigera NPV 

strain BY -0003 through consumed food and drinking water is possible, the EPA anticipates these 

types of exposures may be reduced because, among other things, this insect virus is highly 

specific to target insect pests and is not persistent in the environment, and typical processing 

procedures (e.g., peeling and/or additions of sugar, salt, and other preservatives) could remove 

the microbe from commodities. Should Helicove1pa armigera NPV strain BY-0003 be present in 

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or on food, in drinking water, or in residential settings, supporting toxicological information 

indicates that human exposure to this virus would not result in adverse effects. In addition, 

He/icove1pa armigera NPV strain BY -0003 is covered by the existing exemption from the 

requirement of a tolerance for residues of Helicove1pa zea NP V in or on a ll agricultural 

commodities because H. armigera NPV is a variant of H. zea NPV. The EPA is not required to 

amend the existing tolerance exemption. 

2.2 Assessment of Ecological Exposure and Risk 

In order to assess a microbial pesticide's risk to the environment, the EPA initially requires a 

wide range of studies, including Tier I testing done on the following nontarget organisms: birds 

(ora l and inhalation), wild mammals, freshwater fish and invertebrates, estuarine/marine fish and 

invertebrates, plants, insects, and honeybees. Higher tier testing (II, Ill, and TV) generally 

encompasses definitive hazard determinations and longer term greenJ1ouse or field testing and is 

implemented onl y when unacceptable effects arc seen at the Tier I screening level. For 

Helicoverpa armigera NPV strain BV-0003, the database of studies and information required to 

support the assessment of risk to the environment is complete. 

Exposure of nontarget organisms to Helicove1pa armigera NPV strain BY -0003 is expected to 

be minimal, based on the uses as labeled. Based on data and other information provided by the 

applicant, the EPA determined that adverse effects to nontarget organisms are not anticipated 

from the uses ofHelicovex, which contains the active ingredient Helicoverpa armigera NPV 

strain BY -0003. 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. 

3. Alternatives 

The use of this microbial insecticide could reduce the use of conventional insecticides in 

commercial agriculture and residential gardening. The EP, Helicovex, has the potential to replace 

existing conventional insecticides on the market today used to control corn ea rworm, tobacco 

budworm, and African cotton bollworm. Growers and gardeners may use Helicove1pa armigera 

NPV strain BY -0003 as an alternative to conventional insecticides or in conjunction with other 

biopesticides in an Integrated Pest Management (lPM) program. Among other things, 

He/icove1pa armigera NPY strain BY -0003 will have an established exemption from the 

requirement of a tolerance (no limitations) for all food commodities. In addition, the EP has a 4-

hour Restricted Entry Interval (REI), and the EP is not classified as a restri cted-use pesticide. 

4. Benefits and Public Comments 

Biopesticides are pesticides derived from such natural materials as animals, plants, bacteria, and 

certain minerals. Microbial pesticides, a class of biopesticides, consist of a microorganism (e.g., 

bacterium, fungus, virus, or protozoan) as the active ingredient and may have the following 

benefits: 

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• Usually are inherently less harmful than conventional pesticides. 

• Generally affect only the target pest and closely related organisms, in contrast to broadspectrum conventional pesticides that may affect many different organisms (e.g., birds, 

insects, and mammals). 

• Often effective in very small quantities and often decompose quickly, thereby resulting in 

lower exposures and largely avoiding the pollution problems caused by conventional 

pesticides. 

• Can greatly decrease the use of conventional pesticides while crop yie lds remain high, 

when used as a component of integrated pest management progran1s. 

• Can offer another tool for pest management in areas where pesticide resistance, niche 

markets, environmental concerns, and organic preference limit the use of conventional 

pesticides. 

Like othe r microbial pesticides, Helicoverpa armigera NPV strain BV -0003 aligns with the 

potential benefits above as it exhibits little to no toxicity or irritation, is not pathogenic or 

infective, is specific to certain lepidopteran species, and could fill particular needs in unique 

markets. 

In the Federal Register of April 8, 2014 (79 FR 2 1919), 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 soil or 

water. The EPA anticipates no risks to nontarget insects and honeybees. While NPVs can persist 

in soil, they exist with natural populations of baculoviruses that have similar levels of persistence 

and are not expected to contribute greater exposure to human health or nontarget species. 

Because Andermatt's pesticide product application involves a new active ingredient, as well as 

this active ingredient's first food uses, the EPA opened a 15-day public comment period. The 

EPA is taking this action in accordance with a policy, first implemented in October 2009, 

designed to provide a more meaningful oppor1unity for the public to participate in major 

registration actions. No comments were received. 

5. Regulatory Decision 

The Helicoverpa armigera NPV strain BV -0003 database is comprised of studies and 

information that cover at least 33 different data requirements. The uses of Helicoverpa armigera 

NPV strain BV -0003 are well supported by this database. In considering the assessed risk to 

human health and the environment, the EPA concludes that lfelicoverpa armigera NPV strain 

BV -0003 meets the regulatory standard under the Federal Insecticide, Ftmgicide, and 

Rodenticide Act (FIFRA). Therefore, the EPA is granting the unconditional registration of the 

Helicove1pa armigera NPV strain BV-0003 pesticide product under FIFRA section 3(c)(5). 

One pesticide end-use product will be registered, Helicovex, containing the sole active ingredient 

Helicove1pa armigera NPV strain BV -0003, for control of the com earworm, tobacco bud worm, 

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and African cotton bollworm on agricultural crops (open fields and greenhouses) and in 

residential settings. Applicators and other users can apply Helicovex at a rate of 1.0 - 2.5 fl. 

oz./acre (depending on the crop or plant). 

The risk assessments supporting this decision can be found in the associated regulatory dockets 

(search for "EPA-HQ-OPP-20 14-0151" at www. regulations.gov). 

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