### BIOPESTICIDES REG I STRATION ACT IO N DOCUMENT



## H e lic overpa armigera Nucl eo polyhe droviru s strain BY-0003 Pest icide Chemica l (P C ) Code: I07310

U
. S. Environme ntal Protection Agency Office of Pe s ticide Programs Biope s ticides and Pollution Prevention Division

November 3. 20 15Heilcol'l!lpa armigera nucleopolyhcdro, · irus strain f3V-0003 11iopc sticides R egistration Ac ti on Document 

### T ABLE O F CO NTENTS Page 2 ofJO

I
. EXECUT I VE SUMMA R Y ................................................................................ .. ...................... . ... . .............. 4
I I. AC TI VE I NG R E DI ENT OVERV I EW ................................................................................. . . ... ................. 6
I l l. REGU L ATO R Y B AC K G R OUN D .............................................................................................................. 7 A. A p p l icat io n s f o r P est ic id e Pr o du c t R eg i s tr at io n .......... . ....... .. .............. .. ................ .. . ... . . .............. .. 7 B. Food T ole r ance Exe m p t ion ..................................................................... .. ....................................... 7
IV. RI SK AS S ESSMENT ................ . .............. . ... . ... . ......................... . ........................ . ... . .................................... 7 A. Produc t Ana lys is Assess m e nt (40 CF R § 1 58.2 120) ............................. . ......................................... 8 B. Hu ma n H ea lth A ss es s me n t ( .t OCF R § 1 58.2 1-t0) .................................... . ...................... . ............... 8 C. E n v ir o nm e nt a l Assess m e n t (4 0 CF R § 1 58.2 1 50)
.... .. ...... .. ... . ............... . ................. .. .. .. ....... .. ...... 1 3
V. ENV IR ONMEN T A L JUST I CE ........................................................................... . ..................................... IS
V I
. RI S K MANAG E MENT D EC IS IO N
.. .. .. .. ... . ..... .. ..................... .. ...................... . ......................... .. ... . .. . ... . .. 1 6
VII. ACT I ONS REQUIRED O F TH E R EG I S T RANT ................................................................................... t 7
V III. GLOSSA RY O F AC R ONY M S AN D A ll B R E VI AT I ONS
... .. .. .. .......... . ... . ...... . ............................. .. ........ t 8
IX. B I BL IOGRAP H Y ....................................................................................................................................... 1 9 A. St u dies S u b m itt ed t o Su p po r t t he Active I ngred i e n t, H elicoverpa a r migem nu cleo p o ly h e dr ov iru s s tr a in U V-00 0 3 a n d P es ti c id e Pr o du ct , H e li covcx , R eg is t ra ti o n ............................... .. ..... 1 9 ll
. E n v ir onmen t al Protect io n Age nc y R isk Assessme nt M e m o r anda ............................................. 20 C. Ot h er R e f e r e ncc s .............. . ....... . ................ . ....... . ....... . ... .. ............................................................... 20
A P PEN DI X A. M I C ROB I AL PES TI C ID ES DATA R EQU I R EMEN T S .................................... . ...................... 23
A PP END IX B. PEST I C ID E PR O D UC T ........................................................................................... . .................... 30Helicm •e rpa armiRera nuclcopolyhcdrovirus s train BV-0003 Bi opestieides Registration 1\ction Document



### BIOPESTICIDES REGISTRATION ACTION DOC UMENT T EAM
Office of Pesticide Program s (OPP) B i op cs ti cides a nd Pollution P re ve nti o n Di vision M icrobia l Pe s ticide s Branch

Ibrahim S. Bar so um , Ph.D. John 

### L. Kough , Ph.D. Gail T omimatsu , Ph.D. Miluti n Djurickovic, Biolo g is t 

### Science R eviews Pro du c t Analysis , Hum an Health Product Analysis, Human Health Environmental Effect s E n vironmental Effects 

### R eg ulations Pa ge 3 of30

Kimberl y Nesc i ShaRon Carlisle Shannon Bor ges Michae l Glikes Chief. Microbial Pesticides Branch D eputy C hief , M i crobial Pesticides Branc h Team Leader, Microbial Pesticides Branch Reg ul a t o r y Action Lead e rI felico,·erpa a rm igem nuclcopol yhcdro ' iru s s 1rain BV

- 0003 Bi o pes 1icidcs Rcg i s lnlli o n Ac1i o n D oc um e nt I. 

### EXECUT IVE SUMMARY Backgr ound Pag e-l of30

In October 20 1 3
. Sci Reg. Inc
. . o n be h alf o f A ndermatt Bi ocontro l AG , a Swiss company , subm itted an app lic a ti on fo r a new end- u se product (E P), Helicovex ( EPA F il e Symbo l 6955 3

- E), containing a new activ e in gre di e nt , to th e United States En v iro nmental Protection Agency (E PA ) und e r sec tion 3 of th e Fede ral In sec ticide , Fungicide , and Rodenticid e Act ( FIFRA ). The new ac tiv e ingredi e nt in the E P , 

### He li cove rpa armigera nucleopol yhedrovi ru s (N PY ) s tra in B V-0003 , is a v irus spec ifi c to Lepidoptera n pests a nd a member o f the v iru s family Bacul oviridae, ge nu s 

### Alphabaculovirus
. T hi s non-geneticall y modified, naturall y -occurring strain was i s olated b y th e In s titute of Zoo l ogy, C hinese Acad e m y of Sc iences , from seve ra l H. 

### armi ge ra la rval cadavers inf ec ted with nucl ea r po l yhedros is di sease in a cotton fi e ld in a subu rb of Beijin g , C hina. On April 7 , 2006, th e app li ca nt depo si ted a sa mple with th e German Co ll ection for Micr oo rgani s m s and Ce ll C ultures under th e access ion number BY -0003. This s train h as a si milar, i f n o t identical , h ost ran ge and v irul e nce with 

### H e liothis z e a s ingle N PY , w hi ch was fir s t d etected in in fected H. 

### zea larvae in South Africa in 1891. S in ce the two v iru ses, H. 

### armigera NPY and 

### H
. zea N PY , we re o rig in ally isolated from different ho s t s, they were previ o u s ly class ified as diff e re nt s peci es. By u s in g DN A res triction a nal ysis , resea r chers s how e d that th e ge n o mes of both vi ru ses are ve ry s imil ar. Thi s s imil a rity was corroborated by genome sequencing , w hi c h demon s trated a 97% nu cleotid e identity and a 99% amin o acid identit y . Be cause the y s hare comm o n h os t range . v irul e nce , ph ys ical propert ies , and ge n o m e seque n ce. H. 

### zea N PY a nd H. 

### armi ge ra N PY are "v ariant s of the sam e v iru s spe cies
. " Helicovex is for agricultu r a l u se in the Un i ted Sates in g ree nh o u ses and field application s to control th e com ea r wo rm 

### (llelicove lpa zea), tobacco budwo rm 

### (Helicov e rpa v ir esce n s), and Af rican cotto n boll wo m1 

### (He/icove rpa armigera) on a wide va ri e ty of food a nd non-food crops. It is for ap pl icatio n b y g ro und o r ae ri a l s pray o r by c hem iga ti o n . In add iti on , a s ub-l abe l i s for use on a s ub se t of these food c rops, flower s, a nd o mamentals in h o me garde n s . EPA sc ie nti s t s rev iewe d p ro duct a nal ysis , tox ic o logy , and n o ntar ge t o r ganism data and in formation (40 CFR 

### §§ 158.2120 , 158 .2 140 , and 158.2150 , r es pective ly) s ubmitted to s upport the re g is tra tion of the p es ti cide product. They found that , overa ll , s uch d a t a a nd inf o rm ation are adequate fo r ri sk assessment purposes_ f ulfill th e c urre nt mi c rob ial pestic ide data requirement s . and support regis trati on of the product und e r FIFRA sec ti on 3( c )(5). Product A n a l ysis For th e purposes of F I FRA sec tion 3 (c)(5) re g istration , th e prod uct anal ys i s d a ta r e quirement s for 

### HelicO\'e J pa armigera nu cleopolyhedrovirus s train BY

- 0003 and the EP. I le li covex , includin g product chemi stry and compo s iti o n , a n a l ys is of samples , physical a nd chemica l characteri s tic s were f ulfill e d by acce ptabl e g uid e line s tudi es . Tox ico logy The applicant s ubmitted a d eq uate mamm a li a n tox icolog y data a nd inf ormat io n to suppo rt th e pesticide p roduct. Acute o ral, pulmonar y , a nd inject ion toxicity / pathogenicity s tudie s s ho wed that , at a s in g le hi gh dose , 

### H e licove1pa a rmige ra N PY stra in BY -0003 is n o t tox ic and / o rH elico 1 ·erpa armigera nuclcopolyhcdrovirus s train BV- 0003 13iopes ti c id cs Registration Action D oc ument Page 5 of30 pathogenic via these routes of ex posure. Moreover, the applicant reported that no hypersensitivity incidents occurred during research, development, or testing of 

### Helicoverpa armigera NPY stra in BY-0003. In li ght of the results ofthe acute toxicity / pathogenicity data and the absence of hypersensitivit y incidents. te st ing at higher tier s (i.e
.. Tiers 

### II and Ill) was not required. To lerance Exemption Because 

### Helicovetpa zea 

### (H. zea) nucleopolyhedrovirus (N PV ) already is exempt from this requirement and s inc e 

### H. :ea NPY and 

### H. armigera PY are vari ants of the sa me virus, the applicant did not petition th e EPA for an exempt ion from the requirement of a tolerance for residues of the new strain , 

### He/icoverpa armigera nucleopolyhedrovirus strain BY-0003. In 1980 the EPA g ranted an exempt io n from the req uireme nt 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 certa in specifications related to identity. contamination control. and safety. In its app li cation to the EPA. the applican t provided data and other information to support coverage by the existin g exemption from the tolerance requirement. H ence, the E PA concludes that there is reasonable certain t y that no harm will result to the U.S. population. including infants and children, from aggregate exposure to res idu es of 

### Helicoverpa armigera NPY strain BY0003. Data and information subm itted by the app licant support the conclusion that no dietary risks are expected to occur as a result of the use of 

### Helicoverpa armigera N PY s train BY-0003 as an active ingredient in pesticide product s. The EPA concludes that there will not be significant exposure to 

### Helicoverpa armigera NPY strain BY -0003 through food and drinking water. Ba se d on the review of acute oral toxicity and pathogenicity data by E PA scientists , the Agency determined that. even if 

### 1-Jelicoverpa armigera N PY stra in BY -0003 were present on food or in drinking water , human exposure to this insect vi ru s would not r esu lt in unreasonable adverse effects. Occupational Exposure Despite the lo w toxicological profile of re sidues of the active ingredient, 

### Helicoverpa armigera NPY strain BY-0003, the EP A is requiring base lin e personal protective equ ipm ent (PPE) for handlers that , due to their occupation, may be s ubject to prolonged or repeated exposure to the active ingredient. The label on Helicovex. the end-use product , directs handler s 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 In stitut e for Occupationa l Safety and II ea lth (N IO S II ) s ta ndard s of at leas t N-95, R-95 , o r P-9. Nontanz.et Organisms The applicant submitted guideline studies and scientific rationale bridging studies previously submitted for a variant of

### fl e licoverpa armigera N PY stra in BY -0003 to support the Agency's waiving nontarget organism testing for the n ew active in g red ient (A I )
. The E P A determined that this new A I is substantiall y s imilar to the prev i ously registered A I and that previously submitted data would provide an adequate measure of ha zard for the new AI. H ence. the Agency accepted the bridging rationale and determined that the information provided is sufficient to satisfy mo s t of the Tier I nontarget organism data requirements and support a limited ecological risk assessment for this new act ive ingredient and it s uses. The risk assessment is limit ed by uncertainties assoc iated wi th baculovirus persistence and spread in the environment , which1/ e /ico l' e tpa armi gera

**nuclcopolyh~dr ovi**  **ru s**  s train BV-0003

**Biop~ ticidcs**  Regi stration Action Docum..:nt Pa ge 6 of30
include complex ecological re lationships , such as insect host

- vira l parasite, ho s t 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 app li cant, the E PA dete rm ined that adve rse effects to nontarget organisms are not anticipated from the pesticidal uses ofHelicovex, which contains the active ingredient 

### Helicov erpa armigera NPV strain BV -0003. Moreover, the EPA made a ·· No EffecC determination for direct and indirect effects to federally li sted threatened and e nd ange red spec ies a nd their designated c ri tical habitat s r es ultin g f rom these sa m e pesticid a l use s . Direct effects to indi vidua ls of listed l ep id opteran insect species cannot be precluded , n or can indirect effects to listed spec ies that depend spec i fically o n a listed lepidopteran insect. Additional analy s i s of the potential effects to these species is neces sary to make a determination for these spec ies. Public Participation On October 1 , 2009, the EPA announced a new p olicy to provide a more meaningful opportunity for the public to participate in major registrat io n decisions before they occur. According to this policy, th e E PA intends to p r ov ide a publi c comment peri od prior to makin g a r egistration deci s ion for , at minimum , the following types of applications: new active in g red ients; first food u ses: first outdoor uses; first residential uses ; o r any o th er registration actions for which the Agency believe s there may be sign ifi can t public interes t. Cons istent wi th the policy of making registration act io n s more tra n spare nt , the pest icide product containing 

### H e li coverpa armigera PV strain BV-0003 , was subject to a 15-day comment p e riod. In addition to containing a new act i ve ingredient , the regis tration of the pesticide product would re s ult in the fir s t outdoor and food u ses for H. 

### armigera NPV BV-0003. The docket id e ntification number associated w i th t hese reg istration actions , a nd accessed throu g h e ith e r 

### http :/ l wwH '
. 

### regula ! ions. gov o r 

### hit p :l l www. epa.gov /

pestic id es

l regulat i ng/registration-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 

### Helico l 'e lpa armigera PV s train BV

- 0003 Registration Actio n Docum ent ( BRAD ); (2) draft lab el for the e nd-u se pesticide product , H e li covex (EPA File Symbo l 69553-E); (3) risk assessment for product che mi stry and human health; (4) environmental ri s k assessment; and (5) draft registration decision document. E P A believes that , based upon the data and information submitted i n support of H. 

### armigera NPV stra in BY-0003 and Helicovex , it i s appropriate to is s u e the registrations. The basis for this decision can be found in the ri sk assessment fo r 

### H. arm i gera N PV stra in BV -0003 w hi c h is c h aracterized throughout thi s BRAD. No comments were received. Reg istration D ec is ion The E PA believes that the use of 

### He/icoverpa armigera NPV stra in BV -0003 pesticide products will not cause any unreasonable adverse effec t s on the environment. Therefore , the EP , Hel icovex, which contains!-/. 

### armigera N PV stra in BV-0003 as a new active ingredient , should be eligib le fo r r eg i strat ion under FIFRA section 3(c)(5) for the labe led uses. 

### II . ACTIVE INGREDIENT OVERVI E W Biolo gica l Na me: H e licovelpa armigera Nucleopolyhedrovirus strain BV0003H elicoverpa

**armi~era** nuclco po l y h

cdrO\ iru s s train £3 V

- 0003 B iopesticides R egistratio n Ac tio n Docu m e nt Page 7 of30

C ulture D e po s it:
OPP C hem i ca l Co d e: Type of Pesticide: G e rm a n Co ll ection for Microorgani s m s a nd Cell Cultures: access ion number BY-0003 107310 Microbial Pesticid e - In sec ticide Sec Append ix B for spec ifi c informati o n (e.g. , use s it e s, app li ca ti o n rate s . methods of app li cation , formulation types , and target pests) regarding the pesticide product con taining this active in g r edie nt. III. REGULATORY BACKG RO UN D A. App li catio n s for Pesticide Product Regi s tration In O c tober 2013 , SciR eg , In c . (ad dre ss: 12733 Directo rs Loop, Woodbridge. YA 22 1 92) s ubmitte d a n application o n behalf of Anderman Biocontr o l AG (address: S ta hl e rmatten 6, C ll6146 G ro s sdietw il , Sw itze rl and) to registe r an end -u se product. H e lic ovex (EPA File Symbol 69553-E )
. under FTF RA section 3
. On April 8. 2014 (79 FR 2 19 19). the EPA announce d receipt of the appl ication to regi s t e r a pesticide product containing a n e w ac ti ve ingredient for use in ag ri c ulture. Th e E PA ope ned a 30-day pub li c com m e nt period pursuan t to the provisions of FIFRA sec ti on 3(c)(4)
. Fo ll ow in g this publication , th e Agency r ece ived o ne public com m e nt ex pre ss in g co nc e rn about th e effec ts of th e prod uct on hon ey bees and it s p e rs i s t e nc e in soi l o r water. B. Foo d To l era n ce E xemption Under Fede ral Foo d , D r u g , a nd Cos m etic Act (FF DC A) sec ti on 408( d ) , the EPA in 1980 granted an exempt io n from th e r e quire m e nt of a to le ra nce fo r re s idu es of the active in g red i e nt 

### Helicove1 pa z ea N PY in or on a ll agricultural co mm o diti es (40 CF R 18 0 .1 027) as lo n g as the manufacturer meets certain s pecification s re lated to identit y . c o ntamination cont rol. and safet y . In its applica ti on to the EPA in 20 1 3 , Sci Reg
. o n behalf of the Swiss company A nd ermatt Biocontrol. prov id e d data a n d other information to support coverage of 

### He lic ove rpa armige ra N PY stra in BY -0003 by the ex i s tin g exemption f ro m th e requirement of a to le ra nce for res idu es of 

### H. zea NPY in or on a ll ag ri cu ltural commodities b ecau se 

### II. armigera N PY is a varia nt of 

### H. zeaNPY
. IV. RI SK ASSESSMENT In the F ede ral Register of Oc tobe r 26 , 2007 (72 FR 6 1 002). th e E PA i ss u ed a Fi n a l Rule on th e data requirements to s upp o rt reg i s tration of mi c ro bi a l p es ti c id es and updated th e definition for microbial pe s ti c id es. The r ul e became effec ti ve on D ecember 26. 2007
. The data and information eva luated f o r this BRAD were cons i dered in light of these requiremen t s. The EPA clas s ifi es each data sub mi ss ion wi th a n indication of the u sefu lne s s o f the information con tained in th e document s fo r ri sk assessme nt. A rating of ··acceptable" ' indi cates the s tud y is sc ientifi call y so und and i s u sef ul for ri s k asse s s m e nt. A "s uppl e m e ntal " r a tin g indi cates the d a taHelicoverpa armigera nuclcopol)hcdroviru s s train BV-00 03 Biopcs ticidc s Re gistration Action Document Page 8 of30 provide some infom1ation that can be useful for risk assessment. The studie s may ha ve certain aspects determined not to be sc ient ifically acceptabl e ("suppl e mental : upgradeable " ). If a stud y is rated as "supplemental: upgradeable , " E PA always provid es an indication o f what is lackin g or what can be provided to change the ratin g to .. acceptable."' If th e re is simply a ·· s upplemental '' ratin g . the rev iewe r w ill o ft e n state that the s tud y is not required by 40 CFR Part 158. Both ··acceptable
.. and ' · supplemental"' studies may be used in the ri s k assessment process as approp ri ate. An ''unacceptab l e" rating indicates that new data must be submitted. For the ac ute toxicity data r e quirements , Toxicity Categories are ass i gned ba sed on the hazard(s) id e ntified from s tudi es and/or other information sub mitted to the EPA in s upport of a pesticide r eg is tration. The E PA classifies th e active ingredi en t o r particular prod uct into Toxici ty Category I, II , Ill , or IV , where Toxicity Category I indicate s the highest toxicity and Toxicity Category IV indicates the lowest toxicity (see 40 CFR § 15 6
. 62). 

### A
. Product Anal ys is As s es s ment (40 CFR § 

### 158 .2120) For purpo ses of registr a ti o n under FIFRA sect ion 3(c)(5). the EPA determined that all product analysis data requirem e nt s for 

### He ficov e rpa armigera NPY s train BV-0003 hav e been fulfill ed. Refer to Tab le s 1 , 2 , 3 , and 4 in Appendix A for a su mmary of the data requirements , includin g both gene ri c and product- s pecific inform at ion. 

### B. Human Health Asse ss ment (40 CFR § 

### 158.2140) 1. 

### Toxicity A ll toxicology data require ments for 

### Heli co ve tpa armigera NPV strai n BV-0003 have been fulfilled. Acceptable Ti e r I mammalian toxicology data and information support registration of the pesticide product, ll clicovex. Furthermore , Tier II and T ie r III studies we r e not required f o r 

### Helicm· e rpa a rmig e ra PV s train BY -0 003 because of the J ac k of acute tox icity/ pathogenicity in the Ti e r I s tudies. For a summary of th e toxicology data for 

### He li coverpa armige ra NPV strai n 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 eva luat ed the identity or simila rit y between 

### He li cove rpa armige ra NPV st rain BY0003 and 

### H e licovetpa zea N PY by using DNA restriction analys is to show that the genomes of both v iru ses are very similar (Gettig and McCarthy , 1982)
. This was corroborat e d by genome sequencing. The sequence identity ofHzSNPV and HearN PY s howed a 97 % nucleotide identity and a 99 % amino acid identity (C hen et a l.. 2002). On th e basis of common h os t range and v irul ence, the common physical propertie s, and the common se quence , Chen e t al. (2002) concluded that 

### Helicov e rpa armigera NPV and 

### Helicov e rpa zea NPV are ' ·variants of the same virus species.'' Based on this conclusion , data previously submitted to s upp ort the registration of 

### He licoverpa zea NPV can be bridged to 

### J-/ e licove lpa armi gera NPV strain BY -0003. 

### Acu te Inj ec tion Toxicitv ! Pathogenicitv (Intrav e nous ) (Harm onized Guidelin e 885.3200: MRJD No 4959150?): Research e rs assessed the tox icity / infectivit y of 5 batches of the test substance o n mice by intraperitoneal (IP) in jectio n. They random ly divid e d 30 female m ice into six groups ofllelico l' erpa armigera nuckopolyhedrovirus s train BV

- 0003 Riopcsticidcs Registration Action D ocu ment Pa ge 9 of30 five mice. The y administered 5 groups one batch of the test substance by I P injection at a do se of approximately 106 Viral Occlusion Bodies (OB) per animal, and they do se d a control group wit h an equivale nt volume of s terile sal ine. Observation s for mortality and s ig ns of pharmacologic and / or toxicological effects were made twice on Day 0 and once daily through D ay 7
. Body we ig hts were record ed on Day 0 and at study termination. All mice were sacrificed on Day 7 and gross necrop s ies were performed. The researchers obse r ved no mortality or abnormalities during the s tudy. The necrop sy conducted at terminati o n of the study revealed no observab le ab n o rmalitie s . The research e r s concluded that th e tes t s ubstance is not tox ic to mice w hen administered b y intraperitoneal injection at a do se of 106 OB /mouse. The applicant submit1ed a sc ientific rationale to waive all of the other toxicity/ pathogenicity data requirements (MR ID No. 49409700): 

### Acute Oral Toxicit y

/

Pathogenicity (Harmonize d Guideline 885.3050) Acute Pulmonar y Tox i c it y/ Pathogenicit y (Harmonized Guideline 885.3 150: H

ype rsensitivit y In c id en ts (Harmonized Guid e lin e 885.3-100: Cell Cu lture (Harmoni:: ed Gu id elin e 885. 3500) A cute Oral Toxicit y (Harmonized Guide/ in e 870. I I 00: Acu te Inhalation Toxi c it y (Harmoniz ed Guid e lin e 870-1300: Ac ute Dermal Toxicity (Harmoniz ed Guideline 870.1200: Ac ute Eye Irritation Study (Harmonized Guideline 870.2 400: Ac ute Dermal Irritation S tud y (Ha rmoniz ed Guidel in e 870.2500. The EPA accepted the app lic a nt' s scientific rationale for the following rea so n s : I. Baculo v iruse s arc naturally occurring pathogens o f arthropods. and th e ir h os t range is exc lu s ivel y restricted to arthropods
. o member o f thi s v irus family i s inf ec ti ve to plants or ve rtebrates. 2
. Baculoviruses are pr ese nt in the environment and have been used for biological insect control for over I 00 years. E vidence for the safety of baculoviruses eme rges from the history of contact between baculoviruse s a nd human s without any detrimental effect. Durin g th e 1970s , the EPA es tablished " Guidance for Safety Testing of Baculoviruses ," which also became a guidel in e of b ac ulovirus safet y te s t s . 3. 

### H e licove1pa zea N PV was the first comme rcial baculovirus ins ec ticid e an d is one of the most extensively te s ted e ntom o pathogenic viruses ( l g n o ffo. I 975). Safet y te s t s o f more than 51 entomopathogenic viruses including more than 30 baculoviruses resulted in a long and complete sa fety record (exte n s ively reviewed by Ig noff o , I 973; Surges et al.l980a , I 980b; Groner , 1986). 4. No adverse effect on human health ha s been observed in any of these in vestigatio n s indicating that the use ofbaculovirus i s safe and doe s not cause any health ha zard s. 5. In the 

### He liolhis zea Rer eg i s tration Eligibilit y D oc ument. the EPA s tated th a t "d ue to the ove rall result s ofTier IIJ tox icology testing and the a dditional toxico logy data which support the negati ve response of v iral replication in mamm a ls , the Agency concludes th e re are sufficient data to sa tisfy this require m e nt without reque sting a cel l culture study." 6. Although baculovirus uptake has been observed , there has been no evidence that viral DNA1 /elicOI·erpa armigera nuclc o p o l y hcd rov iru s s tra in BV

- 0003 B io p cst icidcs R eg i s tra tio n Ac t i o n D oc um e nt P age 1 0 o f 30 replication , production of viral proteins or cytopatho lo gical effects have occurred. In vivo, th e uptake of bacu lovirus occlusion bod ies by var io u s animals did not lead to the production of baculovirus-specific anti bodies. 

### b. Ac ut e Toxicology ami Subchronic Toxicity/Pathogenicity- Tier I/ ; 

### Reprodu ctiveFer tility Effects, Ca r c inogeni city, Immunoto xicity, and Infectivit y/Pa thogenic it y 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 Federa l Food , Drug , and Cosmetic Ac t (FFDCA), the EPA has developed the Endocr in e 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 ( in cluding pesticide act i ve 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 th e Administrator may designate." FFDCA sect ion 408(p)(4) au thori zes the Administrator , by order , t o exempt from the requirements of the Endocrin e Di s rupter Screening Program a biologic substance or other substance if a detem1ination is made that the substance is anticipated to not produce an y 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 chem ic a ls, which contains 58 pesticide active ingredients and 9 inert ingredients. 

### He/icoverpa arm i gera NPV stra in BY -0003 is not among the group of 58 pesticide active in gredients on the initial list to be screened under the E DSP. The EPA be li eves that 

### H e licoverpa armige ra NPV strain BY-0003 is a substance that would not produce any effect in human s 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 exemp t 

### Helicovetpa armigera NPV strain BV-0003 from the requirements of the Section 408(p)(4) EDSP. In the eve nt the EPA does determine t o exempt this substance from the EDSP , an order will be issued. For further information on the status of the EDS P , the policies and procedures. the list of 67 chemicals, th e test guidelines and the Tier I scree nin g battery , please v i s it our website: 

### hllp :l! ll'uw.epa
. gO\ •Ie nclo /. 2. Fe deral Food, Drug, and C o s metic Act (FFDCA) Considerations Section 408(c)(2)(A)(i) ofFFOCA allows the E P A to establish an exemption from the requirem e nt for a tolerance ( the legal limit for a pesticide chemical residue in or on a food) o nl y if the EPA determines that the exempt ion is
.. safe: ' Section 408(c)(2)(A)(ii ) of FFDCA define s ··safe'· to mean that " there is a reasonable certa int y that no harm will result from aggregate exposure to th e pesticide c hem ical re sidue, including all an ti c ipated dietary exposures and a ll other exposures for which there is reliable inf o rmation. " This includes expos ure through drinking water and in residential settings , but it docs not include occupational exposure. Pur suant to section 408(c) ( 2)(B) of FFDCA , in establishing or maintaining in effect an exemption from the requirem e nt 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 g iv e special cons id eration to exposure of infants a nd children to the pesticide chemical residue in establishing a tolerance exemption , and1/ e/i co ve rpa armi ge ra nuclco p o l yhcdroviru s s train BV

- 0003 Biopc s ticidcs Re g is tration A cti o n D o cument Page II of3 0
to ..e nsure that there is a rea so nable certainty that n o harm will re s ult to inf a nt s and chi ldren from aggregate exposu r e to the pesticide chemical re s idu e .... " Additionally , section 408(b)(2)( D ) of F FD CA requires that th e E PA co n s ider " avai ! able inf o rmation concerning the c umulati ve effect s of [ a particu lar pesticid e's ]
. .. r es idu es and o th e r s ub s tance s that have a co mm o n mechani sm of tox ic ity . " The E P A perform s a numb e r of analyses to dete rmin e the ri sks from aggregate ex posure to pest icide residue s . Fi rs t , th e Agency determine s th e tox ici ty of a pe s ticide. Seco nd , the E P A examine s exposure to the pe s ticide through food. drinking wate r , and thro u g h other exposures that occ ur as a r es ult of pesticide use in res id e ntial se ttings
. Co nsistent with sec ti on 408(b)(2)(D) ofFF D CA. th e E PA ha s rev iewed th e availabl e sc i entific data a nd other r eleva nt infonnation, and con s id e r ed its va lidity , completene ss, a nd reliabilit y and the r e lat ionship of thi s information to human ri s k. Th e Age nc y also con s id e red ava ilable inf o rm a tion concernin g th e va riability of th e se n s itiviti es of m a jor id e ntifi ab le subgro up s of consumers , includin g infant s and children. Ba sed on the acute tox icity / pathogenicity data and information discussed prev i o u s ly a nd presented in Table 5 in Append ix A, the data required for a FFDC A ri sk assessment for 

### H

e/

icove rpa armigera NPV s train BV-000 3 ha ve been fulfil l ed.


### a. Aggregat e Expos ur e In exam inin g agg re gate ex posure , secti on 408 of FFD CA direct s th e E PA to consider ava il ab le information conce rnin g exposu res from th e p es ticide residue in food and all othe r nonoccupational exposures. including drinkin g wate r f rom ground water o r s urface water and ex po su re through pesticide u se in gardens. lawns. o r buildi n gs ( residential a nd o ther indoor uses)
. 

### Food Exposure and Ri sk Characterization : The E PA found that dietary expos ure to 

### Helicov erpa a rmi ge ra N PV strain BV-000 3, a natural ly occ urrin g in sect v iru s, is anticipated to be ne g li gib le. Due to th e ubiquit o u s nature o f th e o rg ani s m and th e co nc e ntration s of 

### H. 

### a rmi gera N PV s tr a in BV-0003and othe r close ly re late d v iru ses that a lready ex is t in th e env ironment. th e lik e lih ood of increased risk to human s o r a nim a ls from the u se of Helicovex is low. T he E PA conc lud ed that th e ri s k posed to adults. infant s . and children is like ly to be minimal because of the low acute ora l toxicity/ pathogenicity potential of 

### H elicove rpa a rm igera N P V st rain BV

- 0003 and any potentia l expos ure to th e v irus also wou ld be minimal. 

### Drinkin g Wa ter Exposu r e and Ri sk Cha r acte r ization : Exposure to re s idue s of 

### H el ico ve rpa a rmi ge ra NPV s tra in BV-0003in consumed drinkin g water is unlikel y. The u sc patterns for li e lico vex are so il directe d and / or so il inc o rp o rated, th e reby limitin g contact with s urface water by drift and run oti. Furth e rm o re, gro und water is n ot expec te d to have s i g nifi cant expos ure to th e v irus s ince , like other mi c ro o rganisms, thi s micr ob ia l pesticide would li ke ly be filtered o ut by th e particulate nature of many so il types . If it were to be tran sfe rred to s urf ace o r g ro und water s that arc inte nded for eventual human consumpt io n (e
. g . , throu g h spray drift o r runof t) and directed to wastewate r treatm e nt sys te m s or drinking wate r facilit ies, it likel y wo uld n o t surv i ve the conditions water is s ubj ected to in suc h sys tems or facilities, includin g ch lo rin ation , pH adjustme nts , filtrati o n , and/ or occas ionall y high tempera ture s (Ce nte rs fo r Di sease Control and Pr eve ntion 2009; U.S. E PA 2004). In th e remote like liho od that 

### H armi ge ra N PV s train BV0003 is pres e nt in drinking wa t e r (e
. g . , wa t e r not s ubject to treatm e nt sys te m s or facilities) , its1/ e/ico v e rpa armiJ!e ra nu cl c opo l yhcdro , · iru s s train BV

-0003 13 io p esti cidc s R eg istratio n Ac ti o n Doc ume n t Page 12 of30 target pest specific ity and avai lable data indicate no toxicity and/ o r pathogenicity is likel y to occur w ith any drinking water expos ure to H z ABA NPY -U that results from pesticide app li cations made in accordance w ith good ag ricultural practices (see section IY ( B )(l)(a) on pages 8

- 10 and Table 5 in Appendix A). 

### N

on-oc c upalional. Resid e ntial Risk Chara cte rization: Given that 

### Helicoverpa armigera NPY s train BY -0003 is naturally-occurring and usually not stable ou t s ide of it s insect host, the EPA determined that non-oc c up at io nal expos ure t o the bacterium is unlikely. Repeated expos ures to the microorganism from pesticida l applications do not exceed EPA's level of concern , particularly in light of available data that demonstrate that the v iru s is not toxic (acute dermal toxicity and acute pulmonary toxic it y/ pathogenicity) , non-irritating (primar y dermal irritation). and not pathogenic (acute pulmonary toxicity/ pathogenicity) (see sect ion IV(B)(l)(a) on pages 8-10 and Tab le 5 in Appendix A). 

### b
. C umul ati ve Effects f rom S u bstan ces with a Comm on Mec h an ism ofT oxicit y Section 408 (b) ( 2)(D) (v) of FFDCA require s that, when con s idering whether to establish, modify. or revoke a tolerance exemption , the EPA cons id e r '·available information concerning the c umul ative effects of [a particular pesticide ' s]
... residues a nd other s ub s tan ces that ha ve a common mechanism of toxicity
.. , 

### He lic ov e rpa armigera PV s train BY-0003 s hares a common mechanism of toxicity with s trains of 

### Heli c O\'e rpa z e a NPY b e cause the insect v iruses are variants of the same in s ect virus. The EPA concluded that the two viruses, when used as pesticides , wou ld not contribute to cumu lative effects to human health or the e nvi ronm ent. 

### flelicovelpa armigera N PY and 

### He/icoverpa zea NPY do not appear to produce a toxic metabolite against target pests. For the purposes of th e to lerance action , therefore , the EPA has assumed that 

### Helicoverpa armigera NPV strain BY

0003 doe s not have a common mechanism of toxicity with another substance because the two v iruse s ba s ically are the s ame substance. Thu s, section 408 (b) ( 2)(D) ( v) of the FFDCA does not apply. For information regarding the EPA ' s efforts to determine which chemica ls have a common mechanism of toxicity and to evaluate the cumulative effects of such c hemicals, see the EPA's website at 

### hllp :l/ www. epa.gov l pest icides /c umu/ative .


### c. Dete rm ina tion of Safety for th e U n ited States Pop ul ati o n , Infa nt s ami C hild ren In considering the establishment of a tolerance or tolerance exemption for a pesticide chemical residue , FFDCA sect ion 408(b)(2)(C) provides that the EPA s hall assess the availabl e inform ation about consumpt i o n patterns among inf ants and c hildren , specia l suscept ibility of infants and children to pesticide chem i ca l residues , and the cumulative effects on infants and children of the residues and other subs tance s with a common mechanism of toxicity. In addition , FFDCA section 408(b )(2 ) ( C ) provides that the EPA sha ll apply an additio n al tenfold (I OX) margin of exposu re (safety) for infants and children in the case of threshold effects to account for prenatal and postnatal t oxicity and the comp leteness of the database on toxicity and exposu r e unless the E PA determines that a different margin of exposu r e (safety) will be safe for infant s and children. This additiona l margin of expo s ure (safety) is commonly referred to as the Food Quality Protection Act Safety Factor. In applying this provi s ion , the EPA either retains the default v alue of 1 OX or u s e s a different additional safe ty factor whe n reliable data available to the EPA support the choice of a different factor.1/ elicoverpa armigera nuclcopo l y hcdroviru s s train BV -0003 !3iopcsticidcs Regi s tration Action Document Page 13 of30 Based on the acute toxicity and pathogenicity data/information discu ssed in section IV (B)(l)(a) (see pages 

### 8

- 1 0) and Table 5 in Appendix A. the E PA concludes that there are no threshold effects of concern to infants, children, or adults when 

### H e

/icoverpa armigera NPV strain BY0003 is used as labeled in accordance with good agricu ltural practices. As a r esu lt , the EPA concludes that no additiona l margin of exposu re (safety) i s necessary to protec t inf ants and children and that not adding any additiona l margin of exposure (safety) wi ll be sa fe for infants and children. Moreover, based o n the same dat a/information and E PA analysis as presented directly above. the Age nc y is able to conclude that there is a rea so nable certainty that no harm will re sult to the Un ited States population , including infants and children, from aggregate exposure to the residues of 

### H e/icove rpa armigera N PV strain BY-0003 when it is used

- as labeled and in accordance with good ag ri c ultural pract ices - as an insecticid e . Suc h exposure includes a ll anticipated dietary exposures and all other exposures for w hi ch the re is reliable information. The EP A has arrived at th is conclusion because, considered collect ively. the data and information ava il able on 

### He/icovetpa armigera N PV s train BV-0003 do not demonstrate toxic and/or pathogenic potential to mammals , includin g infants and children. 

### 3. O cc upati o nal Ex p os ure and Risk C h a ra cte ri zatio n The EPA does not expect handler exposure to 

### H e/i cove rpa armigera NPV s train BY -0003 to pose any undue risk. Regardless , approp r iate perso nal protective equipmen t (PPE) and precautionary statements are required on pesticide product labels to mitigate any potential risks to pesticide handlers due to prolonged or numerou s exposures. Handler s applying Helicovex in agricultural settings must wear a dust/mist filtering respirator, waterproof gloves. long-sleeved shirt, long pants. socks and s hoe s. For future products contai ning this insect virus as an active ingredient, the E P A may require additional PP E (e.g
.. protective eye wear) on a product

- spec i fic basis. 

### 4. Human Health Ri s k C har a cte rization The EPA considered human exposure to 

### H e/icov erpa armigera NPV strain BY -0003 in li ght of the stand ard for re g istra ti on in F IFRA and the relevant safety factors in FFOCA. The Agency determined that no unre aso nable adverse effects to the Un ited States population in ge neral. and to infants and children in particu lar, will result when 

### He/icoveJpa armigera NPV st rain BY

- 0003 is used in accordance with EPA-app ro ved lab e lin g. 

### C. Env ironm en t a l Assess m ent (40 CFR § 

### 158
. 2150) Data a nd other inf ormation (e.g., scientific literature) submitted a nd c ited by the applicant to s upport requests to waive nontarget organism te s ting for 

### Helicovelpa armigera NPV strain BV0003 are sufficient to fu l fill the relevant microbial pesticide data requirem e nt s and for risk assess ment purposes. Further testing of nontarg et organ i s ms at higher tier levels ( i.e ., Tiers II. Ill. and IV) is not required. The EPA pe rformed an environmental risk assessment based on data and other inform a ti on provided by the applicant. and the Agency determined that adverse effects to nontarget organisms are not anticipated from th e pesticidal uses of 

### 1/ e/icoverpa armigera N PV 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 th e ir designated critical habitats resulting from these same pesticidal use s .Heli col'erpa armigera nucleopol) hcdrovirus stra in BV - 0003 Biopcsticidc s Rcgi sLration Action Document Pa ge I-I of30

For a s umm a ry ofthe generic data require m e nt s described in se ctions I Y(C)( I ) (see pages 14

- 15) , r efer to Table 6 in Appendix A. l. 

### Eco l ogica l Ex p os u re a n d Ri s k C h aracte riz a ti o n Baculoviru s es a re ho st-spec ific within cert ain arthropod ord e rs (seve n in sec t o rd e rs, predominantly the Lepidop t e r

an and H ymenop teran in sects to date and Crustacea (Fuxa, 2004)) ; howev e r , they may persi s t in the environment (either in soil and/or su itabl e in sec t host populations) f o r several yea rs and e ve n d ecad es. The environmental safety of c urrentl y regi s te red baculovirus products to n o ntarget terre s trial and aquatic ve rtebra tes and plant s i s fai rl y welldocum e nte d ( OECD , 2002; Lapointe , et al. , 20 11 ), and the E P i\ does not know of adverse effec t s to n o nt arget organisms s u ch as honeybees. For thi s s tra in of 

### He li cove rpa annigera NPV , information from the open liter a ture to date a re sufficient to address th e m a j o rity of the n o ntarge t organism data requirements for microbial p es ticide s (40 CFR 158.21 50)
. The applicant cited older s tudi es conducted on a d ifferent N PV baculo v iru s. 

### He liothis ze a (sy nonomou s to 

### ll e licove1pa zea NPV). The cite d document ( MRID 00062584) listed seve ra l s tudies (so m e were unpublished) in which different s pecies of test organism s ( plants; insect s, including hon eybee ; fres hwate r a nd estuarine i n ve rt eb rate s and several ve rte brates) were exposed via contact , ora l or inhalation routes to 

### He lio thi s zea N PY w ithout adve rse effects. T he applicant also s ubmitted a publi s hed s tud y to s upp o rt that 

### Helicov e r pa zea N PY a nd 

### f-l elicove Jp a armi ge ra N PV are practicall y the sa m e v irus species (9 8- 99% se quenc e id e ntity) , that the host ran ge s pecificity is limite d to the Lepidopteran order of insect s (M R ID 49591500) , a nd the baculoviru s taxonomy for the microbial pe s ticide control agent (M R ID 49239301 )
.


### a. Terrestrial Animals and Pl ants Wild Mammals ( Harmonize d Gu ideline 885.-1 15 0, 

### MRJD No. -19591 5-0 2).

**Bird~ ·**  

### ( Harmonized Gu id e lin e 885. -1100), 

### Nonlarge tfn.s·ec ls (Harmonized Guid e lin e 885.43 -10
. MRID 

### No. 492393- 09), 

### Hon ey B ees (Harmonized Guide lin e 88 5.-13 80
. 

### MRID No. -192393-08) 

### and Plants (Ha rm on ize d G uid e lin e 885. -1300 ) : The a pplication s-g rou nd a nd aerial sp rays a nd s prinkl e r c hc mi gation -wou ld deposit 

### Hel icove rpa armigera N PV s train BY-000 3 o n foliar and other above g round plant surfaces. The E PA expects deposition onto these s urf aces to occur within the intended area of treatmen t , a s we ll as s urrounding areas. P ersiste nc e of th e virus in th e env ironmen t , parti cula rly in soil , i s po ss ible as l o ng as conditions are favorable , but it does not po se ri s ks to nontarget s pecies because of it s s pecificity. Bird s and mamm a ls would be exposed to 

### He licove rpa armigera NPV Strain BY

- 003 primarily thr o u gh ing es ti on of treated prey or plants. Contact w ith these surface s is not ex p ec ted to result in s i g nificant exposure, though ora l exposure may occ ur incidentall y through g r oomi ng. The submi tted data and inf o rmation are s uffici en t to conclude that 

### He li cove rpa armigera NPV St rain BV -003 i s unlikely to in fect birds or cau se adverse effects. Data with labo rator y mammal s were also s ubmitted , and co nc e rn s are not rai se d that would indic a t e p o t e ntial ri s k to v.ri ld mammal s . While birds and mammals may be expose d to 

### f-lelicove rp a a rmige ra N PV Strain BY-0 03, th e re i s sufficient ev id e nce to s h ow that this exposure will not result in adverse direct ef fects to birds and mammals. Therefo re , risk to bird s and mammals is expected to be minimal. Th e u ses of 

### He licove 1pa armige ra NPY Strain BY -003N e /i cOI•e rpa armig e ra nuclc opo lyhcdroviru s s train BV -0003 Bi o pc s ticidc s Regi s trati o n Ac ti on 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 baculovi ru ses a re not taxonom i call y related to a ny known p lant pathogens, the EPA did not require the applicant to submit data on testing 

### lf e licovetpa armigera NPV BV-003 on plants. Risk to nontarget plant s i s not anticipated as a re s ult of the uses of 

### Helicov e rpa armigera NPV 

### BY-003. b. A quati c A nimal s and Plants Freshwater Fish (Harmonized Guideline 885.-12002. Freshwater inverteb rates (Harmonized Gu id eline 885.4240), Es tuarin e /Marine Fish and In vertebrates (Harmonized Guideline 885.4280) (MR ID No. -192393-01 ) : The EPA determined that, based on the informati o n cited from the literature. risks to fresh\vater fish and invertebrate s and estuarine / marine fish and in ve rtebrates are not expected as a result of the uses of 

### Heli covetpa armigera PV st rain BV -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. Baculoviruse s have a history of safe usc as microbial pesticides , and the y generally have narrow host ranges with no adverse effec t s on nontarget organisms (OEC D 2002). Typica ll y, NPVs only infect the genus o r perhaps fami ly from which th ey were origina lly isolated. 

### 2. E nvironment a l Fate Data As the data and inf om1ation provided are sufficient to fulfill the Tier I nontarget organism data requirements and allow for nontarget organism ri sk assessment for 

### H elicove tpa armigera NPV s train BV-0003 , further testing at higher level s (Tiers II, III , and IV) is not required. 

### 3. Threatened and E ndangered Species Assessment Since the EPA has determined that no effects are ant ic ip a t ed for any nontarget spec ies exposed to 

### ff e licove!pa armigera NPV stra in BV-0003 as a result of the labeled u ses . effects to federally listed threatened and endangered species and their designated critical habitat s also are not expected. Moreove r , 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. E NVIRONM EN TAL J US TICE The EPA seeks to achieve environmental just ice - the fair treatment and meaningful involvement of all people regardless of race, color , national orig in. o r income

- w ith respec t to the development , implementation, and enforcement of environmental law s. re gu lations. and policies. Fair treatment means that no group of people , including racial, ethnic, or soc ioeconomic groups. s hould bear a disproportionate share of the negativ e environmental consequences resulting from industrial , municipal, and commercial operations or the execut i on of federal, state, local , and tribal env ironmental programs and polici es. Meaningful involvement means that 

### (I) potentiallyH elicol'e r pn nr m igera nucle o p o l y hcd ro\' irus s train BV

- 0003 Bi o pc s ti c idcs Regis trati o n 1\c ti on D oc um e nt Pag e 16 o f 30
affected comm unity residents ha ve an appropriate opportunity to participate in decisions about an activity that will affect the ir environment and / or health ; (2) the p ubli c's contribution can influence th e regulatory age ncy's decision; (3) th e concerns of all particip a nt s in vo lve d will be cons idered in the decision-making process ; and (4) the decision-makers seek out and facilitate the in volvemen t of those potentially affected. The EP A has thi s goal fo r all communi ties and persons ac ross the U nit ed S tates. To he lp ad dress potential e n v ironme ntal ju s tice iss ues , the E PA so ught information on any groups or seg m e nts of the population who, as a res ult of th e ir locat ion , cultural practices, or o th e r factors, may have atypical , unusually high exposure to 

### Helicoverpa armigera NPY strain BY

0003 compared to the general population. For additional info1mation r ega rding environmenta l ju s tic e issues, please visit th e E PA 's web s ite a t 

### http :// www.e pa .gov /c ompliance /env i ronmen talju sti c el index.html
. 

### VI. RISK MANAGEMENT DECISION Section 3(c)(5) of FIFRA permits for th e registration of a p es ti cide pro v id ed that a ll the following determinations a r e mad e : ( I ) It s composition is suc h as to wa rra nt th e clajm s fo r it ; (2) It s labe lin g and other material requi r e d to be sub mitted comp ly w ith the requirements of F IFRA ; (3) It will perform it s intended function wi th out unreasonable adverse effects on the environment; AND (4) Wh e n us e d in acco rdance with w id espread and commonly reco g ni zed practice, it will no t genera ll y cause unreason a bl e adve rse effects o n the e n vironme nt. To sat isfy crit e ri o n l, the 

### H e/icove1pa arm i gera N PY s tr ain BV-0003 product , He lico vex , has well-known properti es. The E PA has no kn ow le dge that would contradict th e c laim s made on th e l ab e l , and th e p es ticid e product is not ex p ec ted t o cause unreaso nabl e adv e rse effec t s on th e e nv ironment when u sed acco rding to labe l in s tru c tion s. Criterion 2 is sa ti sfied by the current product label. as we ll as the data and information presented in this document. T he Age ncy believes that the 

### Helicoverpa a rmi ge ra N PY st rain BY- 0003 pesticide product w ill not cause any unreasonable adve rse effects on the environment. in fact , He li covex is likely to pro v ide protect ion aga inst many inf es tations , sati sfy in g criteri on 3. C rite rion 4 is sati s fi e d in that th e 

### He li cove r pa a rmi ge ra N PY stra in BY -00 03 pesticide product is not expected t o cause unreasonable adve rse effects w he n u sed accordi ng to lab e l in s tru ct ion s. Th e r efo re, the EP , Helicovex , w hi ch contain s 

### H e lic overpa armigera N P Y s tra in B Y-0003 as a ne w act i ve in gredien t , is elig ibl e fo r reg i strat io n under F IF RA section 3(c)(5) fo r th e labeled uses.1/ e!icOI'erpa armigera nu clcopo l yh cdrovi r us s tra in 13V - 0003 13 iopcs tici d c s R egist ratio n Ac t io n D oc um e nt V II . AC TI ONS REQU I RE D O F TH E REG ISTRANT A. F in a l P ri nte d La b e lin g Pa ge 1 7 of30



### B efo r e the end-use product , Helicovex, may be r eleased for shipment , the app lic ant is required to provide appropriate final printed labeling to the EPA. B. Te rm s of R eg istr a ti o n 

### The EPA is requiring additional information on th e registration ofthe new product. Ifthe product is to be manufactured in a country other than Swit zerland. then the registrant must provide official documentation from the other country's gove rnm e nt that mi crob ia l con tam ination is not a concern and that th e water used to produc e Helicovex (e .g . , pub li c drinking wate r) is tested for pathogens s uch as Shigella 

### and Vibr io. C. R e p o rtin g o f A d ve r se Ef f e cts a nd Hy pe rse n s iti v ity I ncid e nts 

### 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 federa l registration for a pesticide product. R eports of all incid ents of adverse effects to the envi ronment must be subm itted to the EPA under the provisions stated in F fFRA 

### section 6(a)(2). Additionally, all incid e nt s of hyp ers ens iti vity (i ncludin g both suspected a nd confirmed incidents) must be reported to the EPA und er the provisions of 40 CFR § 

### 158 .2 140 (d).1/ e/ico l·erpa armigera nuclcopolyhcdrovirus strai n BV

-0003 Biopcsticides Re gistration Action Document Page 18 of 30
VI II . GLOSSARY OF AC RO N YMS AND ABBREVIAT IO NS 

### BRAD C fR eSt EDSP EP E

PA FFDCA f i FRA FR g

/mL lb/ gal LDs o
mg/kg MP MR ID o . 

### N I OSH OPP PC Code pp 

### PPE TGA I U.S
. Biopesticides Reg istration Action Doc ument Co de of Federa l Regulation s centistokes Endocrin e Disrupter Screening Pro gra m end-use pesticide product United States Environmental Protection Agency (the

-- Agency'') Federal Food, Drug , and Cosmetic Act Federa l I nsecticide, Fungicide , and Rodenticide Act Federal Register grams per milliliter pound s per ga llon median le thal dose. A statis ti cally d e r ived s ingle dose that can be ex pected to cause death in 50% of the te st a nimal s when administered by th e route indicated (oral, dermal , or inhalation). It is expressed as a weight of substance per unit weight of animal (e.g., 

### mg/kg). milligram s per kilogram manufacturing-use pesticide product Master Record Id entification Numbe r National In st itute for Occupational Safety and Health Office of Pe s ticide Programs Pesticid e C hemical Code Pe st icid e Pe tition personal protective equ ipm ent technical grade of the active ingredient United States1/ e/i co v e rpa armi ge ra nuclc o p o l y hcdro vim s strain BV -0003 Bi o pc s ticidcs Regi s tra ti o n Ac ti o n D o cument Page 19 o f3 0


### IX
. BIBLIOGRAPHY A. S tudie s S ubmitted to S upp ort the Active In g r e di e nt , 

### Heli cove rpa armigera NPV st rain BV-0003, and Pe s ticide Product Regi s tration for the E P , He lic ovex. MRIDNo. 62584

486247 1 8

4923930 1

49 23 9302
49239303

4 9239304

49239305

49239308

49 23 9309

49239310 Study Inf o rm ation Internati o n a l M in e ral s 

### & C he mi ca l Corpo rati o n (1967) Publi s hed and Un publi s hed Studies D e m o n stra tin g Spec ificity of H e li o thi s V iru s to Oth e r In sec t s. In ve rt eb rates and Vertebrates Including Hum ans. (U npubli she d study received Oct 2, 1968 und e r 8G 0697; C OL: 091209-G). Organi sa tion for Economic Co-ope rat ion a nd De ve lopm e nt (2 00 2) Consensu s Docum e nt o n Information Used in th e Assess m ent of Env iro nmental Application s In volving Baculo v iruses. S erie s o n H armonization of Reg ul a tory Oversight in Bi o tech n o logy 87p. SciReg , Inc. (20 1 3) H e licovex: Pro du c t Id e ntity , Manufacturing Process, D epos iti on of Sample in a Nati o n a ll y Recognized Cu lture Co ll ec ti o n , Di sc u ss ion of th e Fo rm a ti o n of Uni nten tion a l In g redients. Unpublished s tud y . I 04p
. Sc iR eg, Inc . (20 13) Helic ovex : Ana l ysis of Samples and Certification of Limit s . U npubli s he d study. 20p. Sc iR eg. Inc (2013) Helic ovex: S umm ary of the OPPTS 830 Se ri es Ph ysica lChemica l Properties Test Guidelines. U npubli s hed study. 5p. Ave rsa. S. (20 1 3) Ph ysica l- Chem i ca l Prope rtie s: pH , Viscosity a nd Relati ve Den s it y of Test Item Helicovex : Final R e port. Projec t N umb er: BT /1 09/13. U npubli s he d s tud y prepared b y B ioTec nologie B T S.r.l. 28 p . Walter , D
. (20 11 ) 3 Year S tora ge S tability of the Formulati o n H e licovex at 5(degrees) Ce ls iu s: Final R e port. Proj ec t Number: 2 0061 550 / 0 I/ PCTY. U npubli s hed stu dy prepared by Eurofins- GAB GmbH. 59p. Ve rge , E. (20 1 0) Ac ute Oral a nd Co nt act Toxicity to the Honey B ee Apis mel li fera 

### L. in the Lab o rato ry: Final R e p o rt. Proj ec t N umb e r : SI0 / 00139, S 10/ 00 1 39/ LJ / BLEU. Unpublished s tud y prepared by E urofi n s- GAB GmbH. 30p. Kl u g. 

### T. (20 I 0) Helicovex: Tox ic ity to the Aphid Par as ito id, Aphid iu s rhopalosiphi D e Stefan i Perez ( H yme noptera. Braconid ae) in th e Laboratory (L imit Test): Fin a l R epo rt. Pro jec t Numbe r: S 1 0/ 00142. S I 0/ 00 14 2 ! LI/NLAP. U n published study pr e par ed b y Eu rofi n s - GAB GmbH
. 28p
. Klug, 

### T. (20 I 0) Helicovex: Toxicity to the Predato r y M ite. Typ hl odrom u s pyri Sc hcute n (Aca ri , Phyto se iid ae) in the Laborato ry ( Limit Test): F in a l Report. Proj ec t N umber: 810 / 0014 3, S I0/ 00143 / L1 /NLTP. Un publi s hed s tud y prepar e d b y E uro fin s - GAB GmbH
. 28 p.He/i co 1 ·erpa armi ge ra nucleopolyhcdroviru s s train BV

-0003 Biope s ticidc s Re g istration Action Document Page 20 of30

49239311
49409700

49409701
49409702
49591501
49591502

49591503 Sc iReg , In c. (20 1 3) Helicov ex: Non target Organi s ms and Env ironmental Fate Waiver Req u ests. Unpublished study. 34p. A ndermatt Biocontrol AG (20 14) Subm is s io n of Product Chemis try and To xicity Data in Support of the Applicati on for R egistrat io n of H elicovex. Tr ansm ittal of 2 Studies. Smith , F. (20 14) Helicovex: Ana lysis of Samples. U npubli s hed s tudy prepared by SciReg , Inc. 14p
. Konrad , R. (20 14 ) Heli covex Nontarget Insect Testing. U npubli s hed study prepared by Anderman Biocontrol AG. 14p. Smith , F. (20 1 5) Helicov ex : Manufacturing Process. Unpublish e d study prepared by SciReg, In c. 8p. Murphy , V. (20 15 ) H elicovex ( Helicoverp a a rmig e ra N PV ) Intraperitoneal Acute Mouse Tox icity / In fectivity. Project Number: 1 8596/ 14. U npubli s hed study prepared by Stillmeadow , Inc. 20p. Minei, C. (20 1 5) Helicovex: !I oneybees 

### (Api s mellifera), Acute Oral Toxicity Test: Final Repo rt. Proj ect N umber: PL1 2868 / 20 14 / 28/ 0ABO/ B. 12868/ 20 14ABO. Unpublished s tudy prepared by TECAM Technologia Ambiental Ltda. 27p
.


### B. Environmental Protection Agency Ri s k Assessment Memoranda U
. S. E P A. 20 15a. Revi ew of Product Chemistry , Manufacturing Process , and Acute Toxicity Studies of the E P contain in g 

### Helicov e rpa arm i gera Nuc leopo lyhedrovirus (Hz N PV ) for sec tion 3 product reg is tration. Memorandwn from Ibra him S
. Barsoum , Ph.D
. and John 

### L. Kough , Ph.D. to Michael Glikes , dated June 10 , 2015. U.S
. EPA. 20 15b. Environmental Risk As sess ment for Section 3 Registration of an E nd- Use Product ( Helicov ex, E PA File Symbo l 69553

- E) , manufactured by Andermatt Biocontrol AG) contain in g baculovirus , 

### Helicov e 1pa zea NPV s train BY -0003 (PC Code l 0730) ; D ec ision 'o. 484373 ; DP # : 426617 ; Submission No. 965729. U .S. E PA. Registration E ligibility Deci sion ( RED ) Facts: 

### He liothis Zea PV , January 1991. 

### C. Other References Annals of the Entomological Society of America. 2004. A N e w Synonym of 

### H e licove1pa zea ( Boddie ) and Differe nti ation of Adu lt Males of 

### H zea a nd 

### H. armi ge ra ( Hubner). Vol. 97. no. 6.1/ elicOI'erpa armigera nuckop o lyhcdroviru s strain BV

- 0003 13iopc sticidcs Re gistration Action D ocu ment 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. C hen , X
. , W.J
. Zha n g, 

### .1. Wong, et al. 2002. Compa rative Analysis of the Complete Genome Sequences of ll e li coverpa zea and Helio coverpa armigera Single-Nucleocapsid NPVes
. 

### .1. Gen. Virol. 83:673-684. Hamm , J.J. 1982. Relative Susceptibility of Several Noctu id Species to a N uclear Polyhedrosi s Virus from Heliothis armige ra. J ournal oflnvertebrate P athology 39:255-256. l l ughes , P.R. , R.R. Genig, and W.J. McCarthy. 1983. Comparison of th e Time-Mortality Respon se of H e liothi s zea to 14 I so lates ofHe liothi s Nuclear Pol yhedrosis Virus. Journ al of In vertebrate Pa tholo gy 41 : 256-261. l gnoffo, C.M., A.I

- L Mcintosh, and C. Garcia. 1 983
. Susceptibi lity of Larvae of Heliothis zea , II. virescens , and II. armige ra (Lep: Noctuidae) to 3 Baculoviruses. Entomophaga 28:1-8. Jehle , 

### J.A. , M. Lange. I I. Wang , et al. 2006. Molecular ldentit"ication and Ph y logentic Analysis of Baculoviru ses of Lepidoptera. Virolog y 346:180 -196. Ogembo , J.G. , B.L. Caoi li , M. S hikata , et al. 2009. Comparative Genomic Sequence Analysis of Novel Heliocoverpa annigera NPV (NPV) Iso lated from Ken ya and Three Other Previou s ly Sequenced Helicoverpa spp . N P Vs Virus Genes. Reference not provided. Rowley , D.L. , H.J. Popham. and R.L. H arrison. 20 II. Genet ic Variation and Virulence ofNPVes Isolated Worldwide from the H eliothine P ests Helicoverpa armigera. I leliocoverpa zea. and Heliothi s virescens. 

### J. In vertebr. P athol. I 07: 11 2-126
. Williams , C. F
.. and C. C. Payne. 1984. The Susceptib ilit y of Heliothis arrnigera Larvae to Three Nuc lear Polyhedrosis Viruses. Annals of Applied Biology 104: 405-412. Z han g, C.S. , S.C. Ma. a nd Z .J
. Guo. 2005. Comparison of the Complete Genome Sequence between C 1 and G4 Isolates of the 1-Ielicoverpa armigera Single Nucleocapsid NPV
. Virology 333: 190-199. Burges, H.D
. G.Croi z ie r and J.Hub er. 1980 (?)
. A Re v iew of Safety Tests on bacu lo v iruses. Entomophaga (?) : 25:329

- 349. Portion s of the document we re ille g ible due to faded Xerox. Doyle, C..J
.. M.L. Hirst. J. S .Cory , P.F. En twi s tl e. 1990. R isk Assessment Studi es: Detailed Host Range Testing of Wild-T ype Cabbage Moth, Mame s tr a brassicae (Lep id optera: Noctu idae), Nuclear Polyhedrosis Virus. Applied and Environmental Microbiology 56:2704-2710. Fuxa. J .R. 2004. Ecology orlnsect Nucleopolyhedroviruses. Agricultu re. ecosystems and the environment. I 03:27-43. Groner , A. 1986. "Safety of nontarget invertebrates of bacu loviruses''. C hapter in book: Safety of Microbial In secticides, M.La ird , L.A.Lar ey. a nd E. W. D avidson , eds.H elicon!lpa armige ra nuckopol)hcdro, · irus strain BV- 0003

**11i p~**  **ticidc s**  Registration Action Do c ument Page 22 of30 

### Lapointe , R. D. , Thumbi and C.J.Lucarotti. 2011 (year not confinned). Recent Advances in our knowledge of Bacul ov irus Molecular Biolo gy and Its Rel evance for the Registration of Baculo v iru s-b ased Products for In sec t Pest Population Con tr ol. p.481-522, Integrated Pest Management and Pest Control

- Current and Future Tactics. Ava il able at: http: www. int echopen.com Organization f o r Econo mic Cooperation and Developme nt (OECD). 2002. Conse nsus Docume nt on Inf ormation Used in the Assessment of Environmental Applications ln volv in g Baculoviru ses . ENV / .JM / MON0(2002) I , 08 January 2002
. Availab le at: http: //www.oecd.org/science /biotrack/ 46815698.pdf. P

ossee and, R.D. , G.F. Rohrmann. 1997. Baculoviru s genome organization and evo lution. In: M ill er, L.K.(Ed). The Baculoviru ses . Plenum Press , New York , pp. 109-140. As cited in Fuxa, 2004. Ce nters for Di sease Co ntrol and Preventi o n. 2009. Drinking Water- Water Treatment. Available from htl p :ll www. cdc. gov l hea/ 1 hvwalerldri nki ng/pub/ i cl wal e r I reatmenl. him/. 

### D eFe lice 

### K , Wollenhaupt N , Buchholz D. 1 993
. Aquifers and Soil Filter Effect. Available f r om http :// exl ens ion. missouri. edu /p/ IV02-I. 

### U.S. EPA
. 2004. Primer for Municipal Wastewater Treatment Systems. EPA 832-R-04-00l. Availab le from hllp :l/ www. epa. gov /

npdes /

pubs /

primer.pdf1/ e /ico l-erpa armi ge ra nuclc o po lyhcdrovirus strain BV

-0003 Biope sticides Regi str a tion Acti o n Document Page 23 of3 0

TABLE 1. Har mo ni ze d

G ui de lin e Num b e r 885
. 1100
885. 1 200

N

/ A

885
. 1300

8 85. 1 400
885.1500

Ha rm o ni z ed

G uid e lin e Numb e r 885.1100

885.1200

N

/ A

885
. 1300

885.1400
885. 1 500 

### AP P EN DIX A
. MI C ROBIAL PES TI C ID ES DAT A RE Q UIR E M EN T S (40 CFR PART 1 5 8

- SU BPART V) Pro duc t An a l ys is D a t a Requi re me nts f o r th e A c ti ve In g r edi e n t (T G AI ) , 1-/ e/ic o ver pa armi ge ra NPV s tr a in BV- 0 0 03 (40 C FR & 158.2 12 0) D a t a Req u ire me nt Resu lt s MRID No.

Product I de n tit y Submitted data fulfill the requirement for product iden t ity and composition. 49239301 M

a nu fact ur in g S ub mitted d ata f ul fill th e r eq u i r e ment for m anufacturin g p rocess. 49239301 Process Dep os iti o n of a

Sa m p le in a Helicove1pa ar m ige r a NPV s tra in BY

- 0003 is o n d epos it w ith the Ge rman Na t iona ll y Co ll ect ion for Microorganisms and Ce ll Cultures u nder th e access ion num ber 49239301 R

ecognized Culture BY

- 0003 Collection Discussion of Format ion of Submitted data fulfil l the requi rement for preventing and detecting any 49239301 Unin tentional microbial con tam inants.

I ng r edien ts Ana l ys is of Sampl es S ubmitted d ata fu lfill th e r e quire m e nt fo r ana l ys is of sa m p l

es. 49239302 Certification of Submitted data fu lfill the requiremen t for manufacturing process. 49239302 Limits

T A BL E 2. Prod uc t A n a l ys is Dat a Req uire me nt s f o r th e En d-U s e Pe s ti c id e P r o d u c t ( E P) , He licovex (40 C FR § 158. 21 2 0 ) Da t a R equire me nt Re s u lt s MRID No.

Product I denti t y Submitted data fulfill the requirement for product ide ntity
. 4923930 1 Manufacturing P r ocess Submi tt ed data fulfi ll the requirement for manufacturing 49239301 process. 49591501 De pos iti o n of a Sa m p le in a Submi tte d d ata f ul fi ll th e require m e nt fo r depos iti o n of a sa mp l e Nati o na ll y R ecog ni ze d in a c ul ture co ll ec ti o n. N / A C ultur e Co ll ect io n Discussion of Formation of Submitted data fulfill the req uirement for preventing and 49239301 Unintentional Ingredients detecting any microbial contaminant s .

Analysis of Samples S ub mitted da t a fulfill the requirement for anal ys is of s amples 49239302 fo r p urposes of Fl FR A sectio n 3(c)(5) registration. Ce rtifi cati o n o f Limit s Li mits li s ted o n th e co nfid e nti a l s t a t

e me nt of fo rmul a are adeq uat e/ acc e ptabl e. 492393021-/elicol'erpa armigera nu cl copo l yht:drov iru s strain BV

-0003 Biopes ticidcs Regis trati on Action Document Page 2-t of30

TABLE 3. Ph ys ical a nd Chemica l Characteristics for th e Technical G rad e of th e Acti ve Ingredient (TGAI), He licoverpa armig era NPV stra in BV-0003 (40 C FR § 15 8.2 1 20) H a rm o ni zed Results 

# I Guide line Numb er Data Req uiremen t MRID No. 830.6302 Co lor Grey-brown 830.6303 Ph ysica l State Liquid 49239303 830.6304 Odor Typical o r ganic odor

- StabHity to Nonnal aL 830.6313 Elevated N / A N / A Temperature s . Metal s, and Metal Ions



### -- - 830.6317 Storage Stabi li ry S table at 5 degrees C for 36 month s 

# I 49239305 830.6319 Mi sc ibility Non emulsifiab le liquid N / A

- 

### - 830.6320 Cor rosion Non-corrosive to P ET container when stored at 5 degrees for 49239305 Charac teristics 36 months



### - - 

### --- 

### - 830.7000 pH 

# I 6.43

- 6.92 49239304 6.92 ( 1°'<> " ' "aqueous solution at 2-t
. l 0 C) 

# I on - Nc 11 10nian Ouitl
. v;soo s ;ty 

# _l__ 2863
. 7 mP als at 2.5 rpm at 20° C 8 30.7 100 690. I mPa/s at 50 rpm at 20° C 49239304 1 490.3 mP als at 2.5 rpm at 40 °C 405
.00 mPals at 50 rpm at 40° C

- Density/ Relative 830.7300 Den s ity/ Bulk Densiry 

# I 1.163 g/ mL at 20 deg ree s Ce l s iu s 49239304 (Specific Graviry) TABLE 4. Ph ys i ca l and C h emical Cha r acteristics for th e End-Use Pe stic ide Pr oduct (E P), H e li covex (40 CFR § 15 8. 212 0) H a rm on ized Data Requir e ment Re s ult s MRID No. Gu id e line N umber 8 3 0.6302 1 Co lor Grey

- brown 49239303 830.6303 1 Ph ysica l State Liquid 830 .63 04 1 Odor Typical organic odor Stabilit y to Normal and 830.6313 1 Elevated Temperatures. N/ A !A Metals. and Metal Ions 8 30.63 17 S torage Stabiliry Stable at 5 degrees C for 36 month s 49239305 8 30.63 19 Mi sc ibility Non emulsifiable liquid N/ A 830.6320 Corrosion C haracteri s tic s Non-corrosive to PET container when s tored at 5 degrees for 36 months 49239 3 05 830.7000 pH 6.43

- 6.92 6 .9 2 ( I % w/ v aqueous so lution at 24
. 1 °C) 49239304 Non-Newtonian nuid
. 2863 .7 mPals at 2
. 5 rpm at 20° C 830.7100 Viscosity 690. I m l' a/s at 50 rpm at 20 °C 49239 304 1-19 0.3 mP als at 2
.5 rpm at 40 °C 405 .00 mP als at 50 rpm at .t0 °C Density / Relative 830 .73 00 Density/ Bulk Density 1
. 16 3 g/mL at 20 degrees Ce ls iu s 49239304 (Specific Gravity)H elico ve1pa armi ge ra nuclc op olyhcdrO\' irus strain IJV -0003 Oi opc s ticidcs R egi strati on Acti o n D o

cument Page 25 ofJ O

TABLE 5. T oxico logy Data Re quir e ments f o r th e Active Ingred ient He licoverpa armigera NPV s t ra in BV -0003 a nd th e End Use P es ti cide Pro duct He li covex (40 CF R 

### &I 58.2 140) Harmoni zed

G ui de line Dat a R equirem e nt Re s ult s MRID No. Numb er Ti er I Waived based on exten s ive list of to x icology studie s on other strains 885
. 3050 Acute Oral ofN PV. 49409 7 00 Toxicity/ Pathogenicity C lass ifi ca tion : Acce pt ab le TOX I CITY CA T EGORY IV Acute Pulm onary Waived based on exte ns ive li st of toxicology s tudi es on other strains 885.3150 ofNPV. 49409700 Toxicity/ Path ogen ic it y C la ss ifi catio n : Acceptab le
Acute Inj ec ti on Submitted s tud y on intraperitoneal injection in mice demons trated no 885.3200 Toxicity/ toxicity or pathogenicity. 49591502 Pathogenicity Cla ss ific atio n : Accep t ab le The applica nt reported that no hypersensitivity incident s . including H

yperse nsi ti v ity immediate-type or delayed-type reactions of humans and domestic 885.3400 Incid ent s a nim a ls. occurred during r esea r ch, development , or t esti n g of th e 49409700 TGAI. Any Futur e hy perse ns itivity incidents must be repo rt ed to EPA (refe r to test note # 3 o f 40 CFR § 158.2 1 40(d)). Waive d due to r es ult s of toxicolo gy testin g and additional toxicology 885.3500 Cell Culture dat a which s upp o rt th e negative replication of viral rep li cation in 49409700 mammals. C l assi fic atio n : Acceo t a b le Waived based on exten s ive list of toxicolog y studie s on other strains 870.1100 Acute Oral Toxicity of PV. 49409700 C la ss ifi catio n : Accept ab le TO X IC ITY CA T EGO RY I V Waived based on ex t e ns i ve li s t of to x icolo gy s tudi e s o n ot he r s train s 870.1200 Acute Dermal Toxicity ofNPV. 49409700 C lass ifi cat ion: Acce p tab le TOXICITY CATEGORY IV Waived based on ex ten s ive li st of toxicology s tudie s on other strains 87 0
. 13 00 Acute Inh alation Toxici ty of PV. 49409 700 Classi fi ca ti on : Acce pt a bl e TOXIC IT Y CATEGO R Y I V Waived based on exten s ive lis t of toxicology studie s on o th er strains 870.2400 Acute Eye Irrit a ti on ofNPV. 49409700 C lass ifi ca tion : Acce p table TOX ICITY CA T EGORY IV Waived based on extensive li s t of toxico l ogy s tudi es o n oth e r s train s 870.2500 Primary Derma l Irrit at ion ofNPV. 49409700 C l a ss ificat io n : Acc e ptab le TOXICITY CA T EGORY I V Tiers II ami Ill Not required for Heli c 01· e rpa armi ge ra N PV strain BV -0003 ba s ed on the lack of acute toxicity /pathogenicit y in the Tier I s tudie s.lle lico l•e rpa armige ra nuclcopolyhcdrovirus strain 13V-0003 Riopc sticidcs Registration Acti o n Document Page 26 of30

TABLE 6. Non target Organi s m Toxicity a nd Environm e nt a l Fate Data Requirement s f or th e Technical Grade of the Active In g r edie nt (TGAI) , Helicoverpa armif!e ra NPV s train BV-0003 (40 C FR § 158. 21 50) Harmonized Guideline Data Req uir e ment Re s ults MRIO No. Number Ti e r 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 ci ted from the literature 49239301 (Chen et al.. 2002) provided data to support that 49591500 H

e lico verpa : ea and Helicoverpa armigera are 885.4050 Avian Oral Toxicity variants ofthe same virus species. (49591500) C la ss ifi catio n : Acceptable
. The OECD conse nsus document (OECD 2002) contains a review of information and state s that effects on birds are not expected from expos ure to 48624718 baculoviruses. C l assi fi cat ion: S uppl e m ental (acceptable f o r avia n ri sk assessme n t) 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 CF R § 885.4 1 00 Toxicity/ Pathogenicity 158 .2150(e)). S ubmitt ed rationa le cited literatu re th at was for 4923931 1 bacu loviruses in general. Classification: S upp lementa l Tests required by 40 CF R § 158.2140 are adequa te and appropriate for assessment of 49591502 hazards to wild mammals. The review of 49409700 information submi ned to fulfill those data requiremen ts does not indicate concerns for 885.4150 Wild Mammal adverse effec ts on wild mammals. T ox icity/ Path ogenicity C la ss ification: Acceptable f o r e n v ironm e n ta l ri s k a ss e ss me nt S ubmitted ra ti onale cited liter ature that was for 49239311 baculoviruses in general. Classification: S uppl e me ntal No biological response from minnow. killifish. and spot fish when exposed to 1/ e /i coverpa :ea 62584 NPV; no quanti tative information were provided 49591500 in th e study citation (62584). A study cited from 49239301 the literature (Chen er al., 2002) provided data to s up port that H e licove rpa :ea and H e licoverpa Freshwater Fish armigera a r e varia nt s of the sa me v iru s s pecies. 885.4200 Toxicity/ Pathogenicity (4959 1 500). C l as s ificati o n : Acceptabl e. A s tudy cited from the literature (Groner eta !. 1981 ) and th e OECD consensus document (OECD 2002) provide information to show that baculoviruses are generally unders tood not to be 49591500 toxic or pathogenic to fish. C lass ificati o n: Supp le mentallle lico,· e rpa armigera nu clcopolyhcd roviru s strain 13V -0003

**Biopc**

**ti cid~.:s** 
**Rc gi~tration**  Action Document Page 27 of 30
TABLE 6
. No nt arget Organi s m T oxicity a nd Environmental Fate Data Requir e me nt s f o r th e Technical Grade of the Ac ti ve In gredient (T GA I), He/icoverpa armigera NPV st rain BV

- 0003 (40 CFR § 15 8.2 15 0) Ha rm on ized Guide lin e Data Requirement Res ult s MRID No. Nu mber No biological response from grass shrimp
. brown s hrimp , or oyste r when exposed to Helico verpa =ea PV: no quanti tative information were 62584. provided in the s tud y citation (62584). A study 49239301 ci ted from the literature (Che n ct al.. 2002) 49591500 provided data to s upport that 1/ e /i corerpa = ea and H

elicove rpa armig era arc varia nt s of the sa me 885.4240 Freshwater Inve rtebrate virus spec ies. (4959 1500). Tox ic it y/ Pathoge nicity Cla ss ifi catio n : Acceptable. A st ud y c ited from th e lite rature (G ro ner et a l. 1981) and the OECD consensus document provide add iti o na l inf o rm atio n that baculoviru ses 4959 1 500 spec ific to Lep id opte ra arc not expec ted to cause adverse effects in freshwater inve rt eb rates. C lassi fi c ation: S uppl ementa l The product is not intended for direct application into estuarine or marine environments. Data are 885.4280 Es tuarine/ Marine Fish and not required since agricultural applications of 49239311 In vertebrate Testing Helicovcx are not expected to ente r these environments in sig nificant amounts. Classification: Accep t ab le Not required as the microbial pesti cide is not 885.4300 ontarget Plant Testing taxonomicall y related to any known plant /A pathogens (refer to tes t no te #7 of40 CFR § 158.2150(e)).1/ e/i co l'e rpa armige ra nuclc opo lyhcdrovirus str ain BV-0003 Bi o pc s ticidcs Regi s tration A c ti o n Document Page 28 of30

TABLE 6. N onta r ge t Orga ni s m T ox ic ity an d En v ir o nm e nt a l Fa t e Da ta Require me nts f o r th e T ec hni ca l G r a de of th e Active In g r e di e nt (T GA I), He licove r p a

**ar mi**  **~:er a**  NPV s tra in BV-0 0 0 3 (40 CF R § 158.2 1 5 0 ) H ar mo ni ze d G uid e lin e D a t a R eq uir e m ent Res ult s MRID No. Numb e r A s ubmitted s tudy conducted on para s itic wasps (Aphidiu s rhopa losiphi) indicat ed un ce 11aint y in th e tox i city a nd / or viral act i v it y because of the t e s t m ateria l o r experiment al design. R eported results were not consistent with published literature on baculovi ru s biology and pathology. There were scientific issues with the method and 49239309 duration of exposure to determine po tential baculovirus inf ec ti v ity a nd replication in parasitic wa s ps. C l ass ifi ca ti o n : Un acce pt a bl e. A s ubmitt ed s tudy conduct ed on pr edatory mit es (Ty ph lodromus pyri) indic ated un ce rt a inty in the t oxic ity a nd / o r v iral activity because of the test material o r experimental design. Reported results were not cons istent with publi s hed literature on baculovirus biology and pa t hology. The du ration of exposure to test material ma y have been too short to determine potential baculoviru s 49239310 885.4340 Nontarget In sec t Testing infectivity and replic ation in p arasi ti c wasps. C l a ss ifi ca ti o n : Un acce ptabl e. A b ioassay conducted on 3 Lepidopteran pe s t spec i es: Agrotis ipsi lon, Cydia pomonella, and Plute ll a xy los t e ll a larvae indi cated no c ro ss infectivity even a t a high dosage of ll e lic ovex. Maximum hazard dosing was no t confirmed. C lass ifi c ati o n : S uppl e me nta l. 49409702 Submitted rationale provide s a weight-of

evidence justification (based o n in fo rm ati o n a nd data fTo m th e current open literatur e) that th e re will be minima l ri s ks to th e ma j o rit y of nontar ge t in sec t populations, becau se of th e hos t spec ificity 4959 1500 ofNPV baculoviruses. s uch as l l aNP V
. llowever , the sub mitted rationale is not s uffi c ient to preclude potential adverse effec ts to li sted Lepidopteran species or to unmanaged honeybees and other pollinating insect s. C l a ss ific a ti o n : S uool e m e nt al.1/ e/icoverpa armigera nuclcopolyhcdrovirus strai n B V -0003 Biopcsticidcs Re gistra tion Action Document Pa ge 29 of30
TABLE 6. No ntar ge t Orga ni s m Tox ic ity a nd E n v iro nm e nt a l Fate D a t a Require me nt s f o r th e T ec hni c al Gr a d e of th e Ac ti ve In g r e di e nt (TC A I), H e li cover pa**armi~: a**  NPV s tr a in BV-00 03 ( 40 C FR § 158
. 2150) H ar mo ni ze d Guid e lin e Numb er

885.4380 D a t a Require me nt

Honey Bee Testing Res ult s A submitted guideline study provided an LD50 > I0 J.lL/bee (i.e
.. 2: I06 Heli coverpa armigera NPV!bee) , si nce 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 eva luated in this short test. The LD50 value is uncertain because of deficiencies with the test material , lack of appropr i ate contro ls and other is s ue s i n the experimental design and reporting of result s . Maximum hazard do s ing was not confirmed. Results of the submitted study are Inconclusive because bee mortalities did not exhibit overt symptomatology associated with baculov i rus activity. C la ss ifi c ati o n : Una cce pt a bl e du e t o in conclu s ive r es ult s . A submitted guideline s t udy provided a median oral LD50 > 2.96 x 108 OB H. armigera NPV strain BV003 / mL , in a 96-hr laboratory test. Although bee morta lities were noted in all groups, including the negative control. the differences in mortality were not significant. No s ignificant toxic effect was observed in the treatment g r oup compared >v ith the negative and inactivated control groups. However. no statistical tab l es were inc luded in the data set to confirm that no statistical differences were pre se nt between treatment and control groups. C lass ifi c ation: Unacc e ptabl e ; as bee morta lity was noted in all experimental groups and the resu l ts are inconclusive. The reported re s ults are not typical of expected baculoviru s symptomatology and may have been confounded by impure test material or experimental design flaws. Accord ing 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-ofM RID No. 49239308

49591503

evidence justification that exposures of Helicovex 49591500 to honeybee populations are not likely to cause irreversible adverse effects. becau se of the host specificity ofNPV baculoviru ses, and that baculovirus insecticides have a lim ited activi t y in the e nv ironment because of their sensitivity to sunlight and ultravio l et radiation. Cla ss ifi c ati o n: S uppl e m e nt a l. Tie r s II , Ill , and I V Not required/or H e /icov erpa armigera NPV strain BV-0003 based on the acceptabi l ity of data and other information provided for Tier I.EPA Fil e Sy mbo l

69553-E 1/e/icoverpa

**armi~era** nucle opolyhed r ovirus s train BV

- 0003 Biopcsticidc s Rc g istrat ion Action Document


### APPEND I X B. PESTICI D E PROD UC TS
Regis t ra t ion P e rce nta Formul atio n Use Si te(s) Na me ge T ype Active ln g r ed ie nt

End-u sc Agricultural ll c licovex 0.60% product



# • Page 30 of30

Method(s) o f App li cation Rate (s) Targe t Pes t App li cation

corn carworm (He li coverpa zca). Ground application tobacco budworm Aerial 1 .0

- 2.5 

### n. oz ./ acre (llclicoverpa Che mi gat i on v irescens). and Green house depe ndin g on the crop 1\ fri can colton R.: s idcntial bollworm ( Hclicovcrpa

armigcra)