# Registration Decision for the N ew Acti v e Ingredient 

# Spodoptera exigua multinucleopolyhedrovirus strain BV-0004

u se nger, Director ffic e of P estic i de Pr og ram s
D a t e:



### /J. **-J.- 1~** 

### 1. Ba ck g round
On October 25,2013 , the U.S. Environmental Protection Agency (EPA) received an application for registration for the new insecticide active ingredient 

### Spodo pte ra exigua multinucleopolyhedrovirus strain BV-0004 from Sci Re g Inc. , on behalf of Andermatt Biocontrol AG, a Swiss company. Subsequently , Sci Reg provided additional data on this active ingredient and it s end-use product (EP), Spex it , to the EPA. The app li cant was not required to submit a petition for a tolerance or an exemption from th e requirement of a tolerance for residues of the active ingredient on food crops because the ne w active ingredient is covered by an existing tolerance exemptio n (40 CF R Part 

### § 180.1118) for occlus ion bodies of the n ucl ear polyhedrovirus of 

### Spodoptera exigua. After reviewing these data , the EPA concluded that the use of the pesticide EP, Spexit , will not cause any unreasonable adverse effects on the environment. On October 23,2015, EP A proposed to re g i ster the active in gredient 

### Spodoptera exigua multinucleopolyhedrovirus strain BV -0004 and afte rward s released that decision for a 15-day pub l ic comment period. EPA received no public comments on that decision.
Ther efore , the Agency is registering the EP containing the new active ingredient under FIFRA section 3(c)(5) for th e following labeled uses: tomatoes , lettuce, cucumbers , peppers , sweet corn, broccoli , cau li flower, cabbage , peas, beets , ce lery , on i o n s, asparagus, okra, strawberries, melon , eggplant , ornamental s . flowers. cotton, alfalfa , soybeans. peanuts , potatoes , corn , wheat , ri ce , sweet potatoes , tobacco , s unfl owers , sugar beets, so rghum , flax , grapes , beans, escarole, garlic, leek , floriculture, and border p lants.
The active ingredient in the EP , 

### Spodoptera exigua multinucleopolyhedrovims strain BV-0004, is a v iru s specific to 

### Spodople ra ex igua , more commonly known as the B eet armyworm , and is a member of the vi ru s family Baculoviridae. 

### Spodoptera e xigua nucleopo ly hedro v iru s strain BV0004 is a naturally-occurring, non-geneticall y modified s train originally i solated from 

### S. e xigua larvae in Ch in a. It was deposited at th e German Collection for Microorganisms and Cell Cu ltu res (DSMZ) in 2006 under the ac cess ion number BV-0004. 

### Spodopt e ra exigua multinucleopolyhedrovirus strain BV-0004 acts ve ry specificall y against larvae of the Beet armyworm. After the larva in gests it, the virus rapidly mu ltipli es w ithin the host in sect, res ulting in cell destruction and death , typically within three to seven days.
Baculoviru ses have been used as pesticides for many years without posi ng risks to human health
or the e nvironment. The species , 

### Spodoptera exigua multinucleopolyhedrovirus (SeMNPV ) , was isolated in different locat ions throughout the world. In 19 95 the EPA registered as a pesticide a strain isolated in F l orida under the trade name Spod

-X (EPA Re g . No. 70051 -4 6). After 20 years of use in the United States and around the world , there is no evidence of safety concerns for workers or of risks to human hea lth and the environment from the labeled uses of this pesticide. When researchers used DNA restriction endonuclease analysis to compare the genetic material of the strains in Spexit to the strains in Spod -X , the results showed that the pattern of Spexit is nearly ide ntical to the pattern of Spod-X. The ge nome s are estimated to be more than 93% identical. Spexit is for agricu ltural use in the United States in greenhouses and field applicat ions to control the B eet armyworm on a w i de var i ety of food and non-food crop s, and it is to be applied by Page 2 of8ground or aerial spray or by chemigation. In addition , this product in cludes a sub- l abel to contro l the same insect pest o n fruits, vege tabl es, and fl owe rs in home garden s. S ince the active ingredient in Spexit is cover e d by an exist in g tol e rance exemption , a new petition was not re quired.



### 2. Eva lu ation
In evaluating a pe s ticide reg is tration application, the EPA a ssess es a w id e var iety of stu die s to dete rmin e the lik e lih oo d of adverse effec t s ( i.e. , ri s k) from ex po s ures associated with the u se of the product. Ri sk assessments are de ve loped to evaluate how the compound might affect a wide range of nontarget organisms , includin g humans and terres tr ial and aquatic wildlife (plants and an imal s).
Based on these assessments, th e EP A evaluates and approves language for eac h p es ticide label to e nsure the d irecti ons for u se and safety measure s are appropri ate to miti gate any potential risk. 

### In t hi s way , the pes ticid e's label he lp s to co mmunica te esse ntial limitati o n s and miti gation s tha t are necessary fo r public safety. In fact, the pe s ticide law has a pro v ision that indicate s it is a vio lati on t o use a pes ti c i de in a way that conflic t s wit h the label. 

### 2.1 Assessment of Risk to Human Health
In or der to assess a microbial pes ticide ' s ri sk to hum an health , the E P A initiall y requires a w id e range of stu dies , in c ludin g T i e r I acute toxicity / pathogenicity (o ral , pulmonary , and inj ec tion) data , ce ll cu lture d ata, reports of h ypersensitivity incidents , acu te toxicity (o ral , dermal , and inhal ation) data, and irritation (de rmal and eye) data. Tier II and II I te s ting (e.g., s ubchronic tox ic i ty /pathogenicit y ) is tri gge r ed only w hen there is indicati o n , usually through lowe r ti er t es ting , tha t a microbial pe s ticid e ha s unu s ual toxi co log ical c ha racteri s ti cs, such as i nfectivity or be in g s u spected as or known to be a carcinogen.
2 .1.1 Tox i city
For Spodoptera ex i gua multinucleopolyhedroviru s s train B V-0004, th e database of s tudie s required to su pp ort the assess me nt of ri s k to hum a n hea lth is co mplet e. The toxicity test s (acute ora l , dermal , and inhalation toxic ity) and irritati on t ests (acute ey e and primary de rmal irri tation) that were cond ucted u s in g th e EP , Spexit , and add resse d potential route s of expo s ure to th e ac ti ve in g re dient are all classified in Toxicity Cat egory IV and reveal little to n o toxicity or irritation a ttributed to S podoptera ex i gua multinucl eo polyhedroviru s s train BY-000 4. Moreover , during a typical to x ic ity/path oge nicit y t es t don e w ith microbi a l pesticid es, the active ing re di e nt di d not pr oduce an y s igns of acu t e toxicit y, pathogenicity , or infectivity via the pulmonar y route of exp osure. For the other r ou tes of exposure , the applicant m e t the data requirem e nt s by c itin g e x isting studies and providin g scie ntific rationale. The rational e cited th e res ult s of othe r toxi cological data o n other spec ie s of Spodoptera. In addition , the app li cant s ubmitt ed a literature se arch that y ie lded no human pathogenicity concerns and data describin g the specificity of the viru s to the target ins ec t s pec ies.

Pa ge 3 of8The EPA also determ i ne d that there are s ufficient data to sa tisfy the requirement of cell culture test in g without requirin g the s ubmi ssio n of a study bec a u se of the sim ilarit y of the new active ingredient to other members of the baculovirus family that we re reg ist e red many years ago. Previou s ly, th e Agency had concluded in the H eliothis zea Rere g is tration Eligibili ty Document that "due to the overall results of Tier ffi toxicology te s ting and th e addit io nal toxicology data whic h s upport the negative response of viral r e pli cati o n in mammals , there are suffic ient data to
s atisfy this requirem en t without re que s tin g a cell culture st udy." S ince the Spo dopt e ra and H

eliothis genera are so close ly related, this conclusion a pplies to thi s ne w strain of Spo dopt e ra exigua

. Finall y , the applicant reported th at , to date , n o hype rsens iti v ity incidents h ave occurred durin g research , deve lopment , and testin g of thi s insect virus

. I n li ght of th e adequacy of th e toxicological data, scientific rat io nal e , a nd literature pr ov id e d b y the applicant a nd the absence of hypersensitivity incidents, the EPA did not require toxicological testing at hi g he r ti ers .
2 .1. 2 Agg r ega te a nd Oc c up a t iona l Ex po s u re
In exa mi n in g agg re gat e e xpo s ure, s ecti o n 408 of FFDCA direct s the EPA to consider available information co ncernin g exposures from the pesticide residue in foo d and all other
non occupati o nal exposures, includin g drinking wa t e r from ground water or s ur face w at er and exposure throu gh p esticide u se in gardens , lawn s, o r buildings.
Food Exposu re and Risk C h arac te ri za ti on: The EPA found th at in creased dietary expos ure to Spodoptera exigua multinucleopolyh e droviru s s train BY -0004 from its u se on food crops i s unlikely. Due to the ubiquito u s nature of this naturall y occ urrin g in sec t v iru s and th e concentrations of thi s v irus and other closely related vi ru ses that a lread y ex i st in th e environment , the likelihood of increase d risk to human s o r anima ls from the use of Spexit is low. Furthermore , because the virus degrades rapidly w hen exposed to ultra vio let l ig ht a nd durin g food harvesting and processing , expo s ur e to th e v iru s wo uld be minimal. The E P A concluded that th e risk po se d to adu lts , infants , and chi ldre n is like ly to be minimal b eca us e of the low acute
ora l toxicit y/ pathogen ic i ty p o te n tial of Spodop tera exigua multinucl eopo l yh e dro v iru s strain BV

0004. Drinking Water Exposure and Risk Characteri zation: Expos ure to residues of Spodoptera exigua multinucleop o l yhedrov iru s st ra in B V

- 0004 in cons um ed drinking water is unlikely. Th e use pattern s for Spexit are so il directed and/or soil incorporate d , thereby limit in g contact with
s ur face w at e r by drift an d run off. F urth ermo r e, ground water is no t expected to ha ve significant exposure to the v iru s s ince , like other microorganisms , this mi crobial pesticide wou ld like ly be filtere d out by the particulate nature of many s oi l types. I f it w e re to be tran sfe rre d to surface or gr ound waters that are int e nd ed fo r eve ntual human con sumption (e.g., through spray drift or runoff) and directed to wastewate r tr eatme nt syste m s or drinking water fac ilitie s , it i s unlikely that the virus would survive the conditions water is subjected to in such sys tem s or facilit ies, including chlorination , pH adju stme nt s , filtration , and/or occas io nall y hi g h temperatures. In the

r emo t e like liho o d that Spodopte ra ex i gua multinucleop o ly hedrov iru s s tr a in BV- 0004 i s prese nt in drinking water (e.g. , water not subject to treatment sys tems or facilitie s), its target pest spec i fic ity and ava ilabl e data indicate no toxicity or pathogenicity i s like ly to occur with any drinking water exposure that resu lt s from p est ic id e appli cation s made in accordance with good

a g ri c u ltura l practi ce s.

P age 4 of8

### Non-occupational. Res id ential Risk C harac te rization: Given that 

### Spodop te ra ex igua multinucleopo lyhedrov iru s s train BV -0004 is naturall y -oc c urrin g and usually n ot sta ble outside of its in sect host, non -occupationa l exposure to the v iru s is unlik e ly. Rep eated expos ures to the microorgani s m from pe st ic idal app li cat io n s do not exceed E P A ' s level of concern , particularl y in light of available d ata that demons trate that the virus is not to x ic (ac ute dermal toxicity and ac ute p ulm onary toxicity/ pathogenicity) , non-irritating (pr imar y dermal irritation) , and no t patho ge ni c (acute pulmonary toxici ty/patho ge nici ty). 

### Occupational Exposure: Th e EPA expects occu pational expos ure to 

### Spodoptera ex igua multinucl eopolyhedroviru s strain B V

- 0004 to be low, as l ong as appl ic ators follow precaution s on product labels. Th e Agric ultura l / Commercial

- Use produc t label for Spexit re qui res applicators to wear lon g s leeved s hirts and pants, water proo f g loves, s ho es plu s socks, and a N IO S H ap pro ved particulate respirator w ith a ny R or P filter w ith N IO S H approval number prefix TC-84A, or a NIOSH ap proved powe r e d a ir purifyin g res pirato r w ith an HE filter with NIOSH a pprova l number p re fix TC-21 C. Repe ated expos ure to high concentrations of microbial prot e in s can cause allergic se n s itization. These precaution s ensure th at applicator s w ill not develop an allerg ic sens iti zation to the act i ve ing re dient in the product. Furth e rm o re, even if workers are expose d to the acti ve ingredient in Spexit, toxici ty testing on thi s new strai n of th e v iru s and nearly identi cal stra in s demon s tra t e that th e re is a low ri s k to human health includin g a ll e r g i c s ensitization.
2.1.3 Human Health Conclusion
The E P A co nclude s that th e r e is a reasonable certa int y t hat no ham1 will result to the U.S. population , includin g inf ant s and c hildren , f rom aggregate ex po s ure to r es idu es of 

### Spo dopt e ra ex igua multinucleopol yh ed rov iru s strain BV-0004

. The EP A does not expect dietary (food and drinkin g wate r ) or other non-occupation a l ri sks f ro m u se of thi s v iru s as an active in g redi ent in the pe stic id e product. A lthou g h exposure to 

### Spodopte ra ex i g ua multinucleop o ly hedro v irus st r ai n BV-0004 through consumed food and drinki ng water i s po ss ible , the EPA anticipates these ty p es of expos ures m ay be red uced because , amo n g othe r t hin gs, thi s in sect virus i s h ig hl y s pec ifi c to tar ge t in sec t pes t s and is not p e rs istent in the e nvironm e nt , and typ ica l proc ess in g procedure s (e.g., pe e lin g and/or addition s of s ugar, salt , and other pre se rva tiv es) could re mo ve the microb e from commodities. Should 

### Spodop te r a exig ua multinucleopol y he drovirus s train BV-0004 be present in o r on food , in drinki ng water, or i n r es id e nti al sett in gs , s upporting toxicological informati o n indicates that human exposur e to thi s virus wo uld not result in adverse effects. In additio n , 

### S p od optera ex i gua multinucleopolyhedrovirus strai n BV -0004 is cove red by the existing exe mption from th e r e quirement of a tol erance for res idu es of 

### Spodoplera ex igua multinucl eo polyhedroviru s o n a ll agricultura l commo diti es ( 40 C FR 

### § 18 0.11 1 8). The EPA i s not require d to am e nd the existing tole rance e xe mpti o n.

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### 2 . 2 Assessment of Ecological Expos ure a nd Risk

I n order to assess a microbial pesticid e ' s risk to the e nvironment , the EPA initially requires a wide ran ge of studies , includin g Tier 

### J testing don e on the following nontarget o rganisms: bird s (oral and inhalation) , mammals , freshwater fish and invertebrates, estuari ne/ marin e fish and invertebrates , plants , insects , and honeybees. Hi ghe r tier te s ting (I I , Ill. and IV) generally
e ncompa sses definitive hazard de term inations and l o nger term greenho u se or field testing and is implemented only w h en unacc e ptable effects are see n at t he Tier I screen in g leve l. Fo r the acti ve ingredient 

### Spodopt e ra exigua multinucl eopolyhedrov irus strain BV -0004 , the database of studies and information required to support the assessme nt of risk to the environment is complete

. The EPA expects expos ure of nontarget organisms to 

### Spodoptera ex i gua multinucleopolyhedrovirus st rain BV-00 04 to be minimal. Based on data and other information provided by the applicant, the Agency determined that adverse effects to nontarget organisms are not antic ipated fro m the l abe led uses of Spexit , t he end use product contain in g t hi s acti ve ingredient. These nontarget species inc l ude mammals , birds , terrestrial and aquatic p lants , fres hwat er and marine /estuarine animals , and insects. In the case of nontarget insects , t h e app li cant su bmitted a sc ientific rationale that provide s a weight-of

- evidence ju s tification (based
on information and data from the current ope n li terature) that there will be no ri s ks to the nontarget insect popu lations because the virus is highly specific to the target insect pest. Similarly , the applicant subm itted a scie ntific rationa le providing a we i ght-of

- evidence justification that exposures of the new st rain of th e v iru s to honey b ee popu l ation s are not lik e l y to cause a d verse effects because of the viru s ' monospecific nature. In addition , baculovirus insecticides have a l imited activity in the environment becau s e oftheir se n sitiv i ty to s unli ght and
u ltraviolet radiation.
The EPA made a " No Effect" determination fo r direct and i nd i rect effects to federa ll y li sted
en dange red and threatened ( " listed") species and for their designated critica l habitats from
exposur e to 

### Spodoptera exigua mu ltinucl e opolyh e drovirus strain BV-0004. 

### Spodoptera exigua multinucleopolyhedrovirus is known to be highl y spec ifi c to its host, 

### Spodoptera e xigua larvae , as a result of a relati onsh ip that has evolved over the past 400 to 500 million years. Because it is specific to this h ost , t he virus is not go in g to infect other species , such as nontarget insects , that may b e expose d to the virus. Furthermore , exposure of nontar get o rganisms to this viru s i s expected to be minima l because it only persists on plants for a short period of time , and the virus is likely to degrade when exposed to sunlight. Hence , nontarget species will not be adversely affected by this in sec t virus from its u se as l abeled , and the virus pose s no ri sk to " li sted " spec 1e s.


### 3. Alternatives
The use of thi s microbial insecticide could reduce the use of conventional insecticides in commercia l agricu lt ure and residential gardening. The EP , Spexit, has the potentia l to repl ace many conventional ins ecticides on the market today that are used to combat th e Beet armyworm. The active ingredients in the s e conventional pesticide products are malathion , ch lorpyrifos , P age 6 of 8methomyl , diflubenzuron, profenofos , thi od icarb , and bif e nthrin. Growers and gardeners may u se 

### Spodop te ra exigua multinucl e opolyh e dro v iru s s train BV-0004 as an a lternati ve to the se co nventional insecticides or in co njuncti o n with othe r biope s ticides in an Inte grated P est Manag e m e nt ( IPM) progr am. Among other thing s, 

### Spodoptera exigua multinucleopolyhedrovirus st rain BV-0004 will have an established exe mption from the r e quirem e nt of a tol e rance (no limitation s) for all food commodities. In add ition , the EP ha s a 4- ho ur Re s tri cte d Entry Interval (RE I ), and the EP is not class ifi e d as a res tricted-u se pe s ticid e
. 

### 4. Benefits and Public Com ments
Bi o pesticides are pesticides derived from s uch natural material s as anima ls, plants , bacteria, and certa in minerals. Microbial p esticides , a cla ss of bi o pe s ticid es, consist of a microor g anism (e

. g., bacterium , fungu s, virus , or pr o to z oan) as the active ingredient a nd ma y have the followin g benefits:

• Usually are inherently le ss harm f ul than conventional pesticid es. • Generally affect only th e target pes t and closely relat ed o rgani sms, in c o ntras t to broadspec trum conve ntional pesticides that may affect man y different o rga ni s m s (e.g., birds , in sects, and mammal s)

. • Ofte n effective in very s mall quantities and ofte n d eco mpose qu ick ly, thereb y resultin g in lowe r exposures and largely avoiding th e po llution problems cause d by conve nti o n a l pesticides.
• Can g reatly d e cre ase th e use of co nve n t iona l pesticide s while c rop yie ld s re m ain hi g h , when used as a component of integrated pest man age ment pro g ra m s. • Ca n offer another tool for pest management in area s w h ere pesticide res ista nce , nich e m a rkets , environmenta l concerns, a nd organic prefer e nc e limit th e use of conventional pe s ticides.
Like other microbial pesticides , 

### Spodopte ra ex i gua multinu c leopol y hed ro v iru s stra in BV-0004 aligns with the pote ntial ben e fit s abov e as it exhibit s little to no toxicity or irritati on , is not pathogenic o r infecti ve to nonta rge t organisms, is speci fic to certain l ep id o pte ran s pecie s, and co uld fill particular needs in unique m arkets.
In the Fe de ral R eg i ste r of Apri l 8 , 2014 (79 FR 2 1 919), th e E PA announced re ceipt of the appl icati o n to register a pesticide product containing a ne w active in gred ient for use in ag ri c ulture. The EPA o pened a 30 -day public comment period pursuant to the pro v is ions of F IF RA sec tion 3(c)(4)

. Foll owi ng this publication , the Agency received one public comment, which did n o t address this microbial pe sticid e
. Becau se Andermatt 's pesticide product application involves a new active in gred ie nt , as we ll as thi s active in g redi e n t 's first fo o d use s, the EPA opened a 15-da y public comment p e riod. The E PA to ok this action in accorda nce with a policy , first impl emen ted in Oc to ber 2009, designed to provide a more m eaningful opportunity fo r the pu bli c to participate in major reg i s trat ion actions. No additiona l public co mm e nt s were s ubmitt ed.

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### 5. R eg ul a to ry D e ci s ion
The Spodoptera exigua multinucleopo ly hedrovirus strain BY -0004 database is comprised of studie s and information that meet the data requirements for and support the labeled uses of Spodopte ra exigua mu ltinucleopolyhedroviru s s train BY-0004. In co n s id eri ng the assessed risk to human health and the environment , the EPA concludes that Spodoptera exigua multinucleopolyhedrovirus st ra in BY- 0004 meets the regulatory standard under the Federal I nsecticide, Fun g icide , and Rodenticide Act ( FIFRA ). Therefore, th e EPA i s granting th e unconditional registration of the Spodoptera exigua multinucleopolyhedrovirus stra in BY-0004 pesticide product under FIFRA section 3(c)(5)

. One pesticide e nd-us e product wi ll be registered, Spexit , containing the so le active ingredient, Spodopte ra exigua multinucleopolyhedroviru s strain BY

- 0004 for control of the Beet armyworm
on agricultural crops (open fields and g reenhouses) and in residential settin gs. Applicators and other users can apply Spex it at a rate of 1.0-2.5 fl. oz ./ acre (depending on the crop or plant).

The risk assessments supporting this decision can be found in the associated regulatory dockets (searc h for " EPA-HQ-OPP-2014-0152 " at www.regulations.gov).

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