# Registration Decision for the New Active Ingredient Helicoverpa armigera Nucleopolyhedrovirus strain BV-0003

D a te :



# 3 Nov 

# 20 1 5

### 1. Background
On Oct ober 25

. 20 1 3, th e U.S. Environm e nt a l Protection Agency (E P A) rece i ved an applicati o n fo r re g i s tra ti o n for the n e \ in sec ticide active ingredient 

### H elicove rpa arm i ge ra N ucleop o ly h e dro v iru s ( PV ) strai n BV-00 03 from SciRe g, In c. , on behalf of A nderman Bioc on tr o l AG, a Swiss company. SciRe g s ub equently provided additional data o n this active in gredient a nd its end-u se p r o duct , H elicovex , to the EPA. A ft e r reviewin g th ese data , th e E P A conclud e d that the u se o f th e 

### He/icov e rpa armi ge ra N P V stra in BY -0003 pe s ticide e nd-u se product (E P ), Helicovex , w ill not cause any unreaso nabl e adverse effects on the enviro nm ent. Therefore. th e Agency i s r eg i s tering the E P co nt a inin g the new active in g redien t under F IF RA
s ection 3(c)(5) for the following labeled u ses : tomatoes , lettuce. cucumbers, peppers, sweet co rn. broccoli, cauliflow er, cabbage , p eas, bean s, beets , ce le ry , o ni o n s, garlic , leek, asparag us , okra, eggp l a nt , s trawberri es, g rapes, es carole , ornamenta ls , flow e rs, cotton , a l falfa , so ybeans, peanut s, potatoes. corn, wheat, s w ee t potatoes , tobacco, s unflower s, s u ga r beets , so rgh um , floricultur e. and border plants.
The active in g redie nt in th e E P , 

### He li cove rpa armigera N PV s train BV-000 3, i s a v iru s specific to Lepid o pte ran pests and a m e mber of th e v irus family B ac ul ov iridae, ge nu s 

### A lphabacu/ovirus. This non- ge n e ti ca ll y modi tied , naturall y -occurr in g stra in wa s iso lated by th e In st itute of Zoology, C hin ese Academy of Sciences , from severa l 

### H. a rmige ra larva l cadavers infected w ith nuclear polyhcd ro s i s di sease in a cotton fi e ld in a suburb of B e ijing, C hin a . On Apr il 7 , 2006 , the app li cant d e p os ited a sa mple with the Gennan Collect ion f o r Microorgani s m s a nd Ce ll Cu l ture s under th e access ion numb e r BY

- 0003. Thi s s train has a s imil ar , i f not id e nti cal, host range and
v irul e n ce w ith 

### Hel i o this ze a si n g le NPV , w hi c h was first detected in So uth Af ri ca in 18 91 in infected 

### II. zea larvae. Si n ce the two v iru ses, 

### II. armige ra N PV and 

### H. zea NPV, we re o ri gina ll y i so lated f r o m different h os t s, they were pr ev io u sly clas s ifi e d as diff e rent s p ec i es . By using D NA restri ct io n a nal ys is , re sea rch e rs s howed th a t the ge nom es o f both v irus es are very s imilar. Thi s similarity was corroborat ed by genome seq u e ncing. wh ic h demo n strated a 97% nucleotide identit y and a 99% amino ac id identity. B eca u se the y s h are common h ost range , vi rul e nce. ph ys ica l properties, and ge n o m e se qu e nc e, it was determin e d that 

### H. zea N PV a nd 

### H armi ge ra NPV arc "variants of the sa me viru s specie s . "
Helico vex i s for agricu ltura l u se in th e U nited Sates in g r eenhouses and field a pplications to cont ro l the com earworm 

### ( H el icove1pa zea), to bacco bud wo rm 

### ( H e/

ic o ve 1pa virescens) , a n d African co tton bollworm 

### ( ll e licove lp a armige ra) o n a wid e va riety of food a nd non - food c rops. It i s for app lic at ion by g ro und o r aeri al s pray o r by chemi gati o n. In addition , there i s a sub- labe l for contro l of the same in sec t pests on a s ub se t of these food c rops , flower s, and ornamentals in hom e g ard e n s.


### 2 . Eva lu a tion
In eva lu a tin g a pesticide reg i s tration applica ti on, the EPA assesses a w id e va ri e ty of studi es to detennine the likelih ood or adverse effects ( i. e., r i s k) from expos ures assoc i ate d with the u se of the product. Risk assessments are developed to eva lu ate how the co mp ound might affect a wide

Page 2 of 7range of nontarget organisms , inc lud ing humans and ten·estrial a nd aquatic wildlife (plant s and anima ls).
Based on these assessments, the EPA evaluates and approves language for each pest icide label to ensure the directions for u se and safety measures are appropriate to mitigate any potential ri sk. In this way , the pesticide 's labe l helps to communicate essential limitations and mitigations that are necessary for pub li c safety

. In fact, th e pesticide J aw has a p rov is i o n that ind ica t es it is a v io lation to use a pesticide in a way that conflicts with the label. 

### 2.1 Assessment of Ri s k to Human Health
In order to assess a microbial pesticide 's ri s k to human hea lth, the EPA initiall y requires a wide range of stud ies, includin g Tier I acute toxi city/pa thogenicity (o ral , pulmonary, and injection ) data, cell c ulture data , reports of hypersensitivity incidents , acute toxicity (o ra l , 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 p est icide has unusual tox ico logical characteristics, such as infectivity or being suspected as or known to be a carcinogen

. 

### 2.1.1 Toxicity
For 

### Heli coverpa armige ra NPV strain BV-0003 , the database of studies required to support the assessment of risk to human health is complete. The toxicity tests (acute ora l , dermal , and inhalation toxicity) and irritation tests (acute eye and primary dermal irritation) that address potential ro utes of exposure to th e active in g red ie nt are a ll c lass ified in Tox icity Category IV and reveal little to no toxicity or irritation attr ibuted to 

### Helicoverpa a rmi gera NPV strain BV-0003. Mo reover, during a typical toxicity / pathogenicity test done with microbial pesticides, 

### Helicoverpa armigera NPV s train BV-0003 did not show any signs of toxicity , pathogenicity , or infectivity via the pulmonary route of exposure. The EPA waived most acute toxicity/ pathogen ic i ty studies fo r this active ingredient, based on SciReg's scientific rationale. The rationale cited to the results of other toxicological data done with 

### H elicove rpa zea NPV, a literature search that y ielded no human pathogenicity concerns, and data describing the specificity of the virus to the target in sect spec ies. Regarding cell culture testing , in this case, the E PA did not require these data becaus e the applicant cited acceptable cell culture stud i es performed using 

### Helicoverpa zea NPV. Fina ll y, Sc iReg reported that, to date , no hypersensitiv ity incid en t s have occurred during researc h , deve lopment, and tes ting of th is in sect viru s. In light of the adequacy of the toxicological data , scient i fic rationa le, and literature provided by SciReg and the absence of hypersensitivity incidents , the E P A d id not require toxicological testing at higher tiers. 

### 2.1.2 Aggregate and Occup a tion a l Ex po s ure In examin in g 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 wate r or surface water and
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### exposure through pesticide use in gardens , lawns , or buildings.


### Food Exposu re and Risk Character ization: The EPA found that dietary exposure to 

### Helicov e rpa armi ge ra NPY strain BY -0 003, a naturally occurring in sec t virus, from its us e as a pesticid e is anticipated to b e negligib le. Du e to the ubiquitous nature of the organism and th e concentrations of H. 

### armigera NPY stra in BV -0003 and other closely related viruses that already exist in the
e n vi ronment, the likelihood of increased risk to hum ans or animals from the use of Helicovex is low. The EPA concluded that the risk posed to adults , infants , and ch ildren is likely to be minimal becau se of the l ow acute oral toxicity/ pathogenicity potenti a l of 

### He li cove rpa armigera NPY strain BY-0003 and any potential exposure to the v irus also would be minimal. 

### Drinking Water Exposure and Risk Characteriza tion: Exposure to residues of 

### H e licoverpa armigeraNPY s train BY-000 3 in consumed drinking water is unlike ly

. The use patterns for Helicovex are so il directed and/or soil incorporated, th ereby limitin g contact with s urface water by drift and runoff. Furthennore , gro und water is not expected to have significant exposure to the virus since, like other microorganisms, this microbial pesticide wo uld likel y be filt ered out by the particulate nature of many so il types
. If it were to be transferred to surface or g round waters that
are intended for eve ntual human consumption (e.g., through sp ray drift or runoff) and directed to wastewater treatment systems or drinking water facilities , it i s likely that the virus would not survive the conditions water is s ubject ed to in such systems or facilities, includin g chlorination , pH adjustm ents, filtration, and / or occasionally high temperatures (Centers for Di sease Control and Pr evention 2009; U.S

. EPA 2004). In the remote lik e lihood that 

### H. armigera NPV strain BY -0003 is pre se nt in drinking water (e.g. , water not subject to treatment systems or facilities) , its target p est spec ificit y a nd available data indicat e no toxicity and/or pathogenicity is likely to occur with any drinking wat e r exposure that results fro m pesticide applications made in accordance with goo d agricu ltural practices. 

### Non-occupational, Residential Risk Characterization: Given that 

### Helicove1pa arm igera NPY strain BV -0003 i s 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, particu larly in light of available data that demonstrate that the virus is not toxic (acu te dermal toxicity a nd acute pulmonary toxicity/ pathogenicity) , non-irrit ating (pri mary dermal irritation), and not pathogenic (acu te pu lm onary toxicity/ pathogenicity).
2 . 1.3 Human Health Conclusion


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

. population, includin g infants and children , from aggregate exposure to residues of 

### Helicove1pa annigera NPY strain BY-000 3. The EPA does not expect dietary (food and drink in g water) or other non-occupational risk s from use of 

### Helicove1pa a rmi gera NPV strain BY-0003 as an active ingredient in the pesticide products. Although exposure to 

### H e licove1pa 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 in sec t v iru s is highly specific to target in sect pest s and is not persistent in the envi r onment, and typica l processing procedures (e.g. , peeling and / or additions of sugar, sa lt , and other preservatives) co uld remove the microbe from commodities. Shou ld 

### H e licove1pa armigera NPV strain BY

- 0003 be present in Page 4 

### of 7or on food, in drinking wate r, or in residential se ttin gs, supporting toxico logica l in formation indicates th at hum a n exposu r e to this v iru s would n ot resu lt in adverse effects. In addition, 

### H

e /icove1pa armigera N PV stra in BY

- 0003 is covere d b y the ex i stin g exe mption from the r eq uire ment of a to le r a nce for res idu es of 

### He licove1pa zea N P V in o r o n a ll ag ricultural co mmodities b eca u se 

### H. armigera NPV i s a variant of 

### H. zea N PV. Th e E PA is not require d to ame nd th e existing tolerance exe mption. 

### 2.2 Assessment of Eco l ogical Exposure and Risk
In o rder to assess a microbial pesticide 's risk to th e env ironme nt , the E PA initi a ll y requires a w i de range of studies, including Tier I testing done on the following nontarget o rgan i s m s: birds (o r a l a nd inh a lati on), wild m a mmals , freshwater fish a nd in ve r teb rates, estua rin e/ marine fi s h and in ve rtebrates, plants , in sects, and honeybee s . Hi g her tier testing ( II , Ill , a nd TV) generall y e nco mpa sses definitiv e h azard determinations and lo n ge r term greenJ1ouse o r field t es ting and is impl eme nted o nl y w hen un accep tab le effec t s a r c see n at the Tier I scree nin g level. For 

### Helicove rpa armigera NPV s train BV-00 03, the database of studi es and information required to suppo rt the assessment of ri s k to the environmen t is complete. Exposure of nontarget organisms to 

### Helicov e 1pa armigera N P V strain BY -0003 is expected to be minimal, based on th e uses as labeled

. Based on data a nd other in for m ation provided by the app li cant , the EPA determined that adverse effec t s to n o ntarget organisms a r e not a nticipated f r om the uses ofHe li covex, w hich contain s th e act ive in g redient 

### He li coverpa a rmi gera NPV s tr a in BY -0003. Th e E P A m a de a " No Effect " d eter mination for dire ct and indirec t effects to all federally li sted threatened and endangered spec ies a nd the ir de s i g nate d criti ca l h ab ita t s r es ultin g from the use of the pest icide.


### 3. Alternatives
The use of this mi c rob ia l insecticide could reduce th e use of conventiona l insecticides in com mercial agriculture a nd res idential gardening. The E P , Helicove x, ha s the pot e ntial to replace ex i s tin g conventional in sec ticid es o n the market today u se d to control co rn ea rwo rm , tobacco budworm, and Af ri can cotto n bollworm. Growers a nd gardener s m ay use 

### H e licove 1pa armigera NPV stra in BY -0003 as an a lternat ive to convent iona l insecticides or in conjunction wi th other biopestic id es in an Int eg rated P est Management 

### (lPM) program. Among ot her things, 

### He/icove1pa armige ra N PY s train BY

- 0003 will have an established exemp ti on from the requirement of a tolerance ( no limitations) for all food co mm od iti es. In additio n , the EP h as a 4- hour Restricted Ent ry In terva l (RE I), and th e E P is not classified as a res tri c t e d-use pesticide.


### 4. Benefits and Public Comments Biopesticides are pe s ticides derived from such n atura l materials as an im a ls, plants , bacteria , and cer tain minerals. M icrobia l pesticides, a cla ss o f biopest icides, consis t of a microorganism (e.g., bac te ri um, fungu s, vi ru s, o r protozoan) as the active ingredient and may have the following benefits:
Page 5 of 7

### • Usually are inh erent ly less harmfu l than conventional pe s t ic ide s. • Gene rally affect only th e target pest and closely re la t e d organisms, in co ntrast to broadspectru m conventional pesticides that may affect many different organisms (e.g., birds , insects , and mamm als). • Often effect ive in ve ry small quantiti es and often decompose quickly , th ereby re s ultin g in lowe r expos ure s and large l y avoiding the p o lluti o n problems cau se d b y co n ventional pes ticides. • Ca n g reatl y decrease the use of c onven ti o nal pesticides whi l e crop y ie ld s remain hi g h , whe n used as a component of integrated pest man agement progran1s.
• Can offer an o th e r t ool for pest m anageme nt in areas w here pesticide resis tance , ni che
m arke t s, environ me nt a l concerns , and o rganic pr efe rence limit the use of conve nti o n a l pes ti c id es. Like o th e r microbial p est ic ide s , 

### Helicoverpa arm i gera NPV s train BV

- 0003 a li g n s with th e potential benefits abo ve as it ex hibit s littl e to no toxicity or irrit at ion , is not pathogen ic or infective , is spec ific to ce rtain lepidopteran spec ies , and could fill particular needs in unique markets.
In the Federal Registe r of Apri l 8, 2014 (79 FR 2 1919), the E PA announced r ece ipt of the application to reg ister a pes ticid e product co ntainin g a new acti ve in g redient fo r use in agriculture. The EP A opened a 30 -day public com ment period pursuant to the provisions of F IFRA sectio n 3(c)(4). Followi ng thi s publication , the Agency rece i ved o n e public comment expressing concern about the effects of th e product on hon ey bees and it s persistence in so il or water. The EPA anticipates no risks to no nt arge t insect s and ho ney bee s . While N PV s can p e rs ist in s oi l, th ey exis t w ith natura l population s of baculovirus es that hav e s imil ar leve ls of persi s te nc e and are not expected to co ntribute greate r exposure to hum an hea lth or no ntarge t spec i es.
Becau se Andermatt ' s pes ti c ide product app li cat ion involves a new active ing redie nt , as well as this active ingredient's first food u ses, the EPA ope ned a 1 5-day public comment perio d

. T he EPA i s taking this action in acco rdance with a policy, fir s t impl e me nted in O c tober 2 009 , designed t o provide a more meaningful oppo r 1unity for the public to participate in major registration ac tions. No comments were received.


### 5. Regulatory Decis ion
The 

### He licove rpa armige ra NPV strain BV-0003 databas e is comprised of s tudi es and inform at io n th at cover at least 33 different data req uirem e nt s. The u ses of 

### Helicoverpa armigera N PV s tra in BV -0003 are well su pp o rted by this database. In consider i ng the assessed ri sk to human health and the envi ronme nt , th e EPA concludes that 

### lf e licoverpa armige ra N P V strai n B V

- 0003 meets the reg ulator y stan dard under the Federal In secticide, Ftmgicide, and Rodenticid e Act (F IFRA ). Th e refore , th e E PA i s granting th e uncond itional reg is tration of th e 

### Hel icove 1pa arm i gera NPV s train BV-000 3 pesticide product under F IFRA sec tion 3(c)(5).
On e pesticide e nd-use product will be registered , Helicovex, con tain in g the sole act ive in gredient 

### Helicov e 1pa a rmigera NPV stra in B V

- 0003 , for contr o l of the co m earwor m , tobacco bud wo rm , Page 6 of 7

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

. Appl icators and other users can apply Helico vex at a rate of 1.0

- 2.5 fl. 

### oz ./ acre ( d epe ndin g on th e crop or plant). The ri sk assessments suppo rting this decision can be found in the associated regu latory dockets (search for "EPA-HQ-OPP- 20 14-0151" at 

### www. re gulations.gov).

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